PMID:  J Ginseng Res. 2023 Apr 8. Epub 2023 Apr 8. PMID: 37362082 Abstract Title:  The potential ofnotoginseng against COVID-19 infection. Abstract:  The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years,notoginseng has been used to treat various infectious diseases. Experimental evidence ofnotoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests thatnotoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

read more

PMID:  Phytother Res. 2023 Jul 9. Epub 2023 Jul 9. PMID: 37424151 Abstract Title:  20(S)- Protopanaxadiol saponins isolated from Panax notoginseng target the binding of HMGB1 to TLR4 against inflammation in experimental ulcerative colitis. Abstract:  Ulcerative colitis (UC) has emerged as a global healthcare issue due to high prevalence and unsatisfying therapeutic measures. 20(S)- Protopanaxadiol saponins (PDS) from Panax notoginseng with anti-inflammatory properties is a potential anti-colitis agent. Herein, we explored the effects and mechanisms of PDS administration on experimental murine UC. Dextran sulfate sodium-induced murine UC model was employed to investigate anti-colitis effects of PDS, and associated mechanisms were further verified in HMGB1-exposed THP-1 macrophages. Results indicated that PDS administration exerted ameliorative effects against experimental UC. Moreover, PDS administration remarkably downregulated mRNA expressions and productions of related pro-inflammatory mediators, and reversed elevated expressions of proteins related to NLRP3 inflammasome after colitis induction. Furthermore, administration with PDS also suppressed the expression and translocation of HMGB1, interrupting the downstream TLR4/NF-B pathway. In vitro, ginsenoside CK and 20(S)-protopanaxadiol, the metabolites of PDS, exhibited greater potential in anti-inflammation, and intervened with the TLR4-binding domain of HMGB1 predictably. Expectedly, ginsenoside CK and 20(S)-protopanaxadiol administrations inhibited the activation of TLR4/NF-B/NLRP3 inflammasome pathway in HMGB1-exposed THP-1 macrophages. Summarily, PDS administration attenuated inflammatory injury in experimental colitis by blocking the binding of HMGB1 to TLR4, majorly attributed to the antagonistic efficacies of ginsenoside CK and 20(S)-protopanaxadiol.

read more

PMID:  Front Pharmacol. 2023 ;14:1143923. Epub 2023 Apr 18. PMID: 37144218 Abstract Title:  Neuroprotective effects of aa(Mart.) against diabetic retinopathy. Abstract:  Diabetes mellitus describes a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia, which induces a series of molecular events capable of leading to microvascular damage, affecting the blood vessels of the retina, causing diabetic retinopathy. Studies indicate that oxidative stress plays a central role in complications involving diabetes. Aa() has attracted much attention given its antioxidant capacity and potential associated health benefits in preventing oxidative stress, one of the causes of diabetic retinopathy. The objective of this work was to evaluate the possible protective effect of aa() on the retinal function of mice with induced diabetes, based on full field electroretinogram (ffERG).We opted for mouse models with induced diabetes by administration of a 2% alloxan aqueous solution and treatment with feed enriched with aapulp. The animals were divided into 4 groups: CTR (received commercial ration), DM (received commercial ration), DM + aa(-enriched ration) and CTR + aa(-enriched ration). The ffERG was recorded three times, 30, 45 and 60 days after diabetes induction, under scotopic and photopic conditions to access rod, mixed and cone responses, in addition to monitoring the weight and blood glucose of the animals during the study period. Statistical analysis was performed using the two-way ANOVA test with Tukey's post-test.Our work obtained satisfactory results with the ffERG responses in diabetic animals treated with aa, where it was observed that there was no significant decrease in the b wave ffERG amplitude of this group over time when compared to the results of the Diabetic group not treated with aa, which showed a significant reduction of this ffERG component.The results of the present study show, for the first time, that treatment with an aa-enriched diet is effective against the decrease in the amplitude of visual electrophysiological responses in animals with induced diabetes, which opens a new horizon for the prevention of retinal damage in diabetic individuals from treatment with aabase. However, it is worth mentioning that our findings consist of a preliminary study and further researches and clinical trials are needed to examine aapotential as an alternative therapy for diabetic retinopathy.

read more

PMID:  Antioxidants (Basel). 2022 Dec 14 ;11(12). Epub 2022 Dec 14. PMID: 36552669 Abstract Title:  Maqui Berry and Ginseng Extracts Reduce Cigarette Smoke-Induced Cell Injury in a 3D Bone Co-Culture Model. Abstract:  Cigarette smoking-induced oxidative stress has harmful effects on bone metabolism. Maqui berry extract (MBE) and ginseng extract (GE) are two naturally occurring antioxidants that have been shown to reduce oxidative stress. By using an osteoblast and osteoclast three-dimensional co-culture system, we investigated the effects of MBE and GE on bone cells exposed to cigarette smoke extract (CSE). The cell viability and function of the co-culture system were measured on day 14. Markers of bone cell differentiation and oxidative stress were evaluated at gene and protein levels on day 7. The results showed that exposure to CSE induced osteoporotic-like alterations in the co-culture system, while 1.5g/mL MBE and 50g/mL GE improved CSE-impaired osteoblast function and decreased CSE-induced osteoclast function. The molecular mechanism of MBE and GE in preventing CSE-induced bone cell damage is linked with the inhibition of the NF-B signaling pathway and the activation of the Nrf2 signaling pathway. Therefore, MBE and GE can reduce CSE-induced detrimental effects on bone cells and, thus, prevent smoking-induced alterations in bone cell homeostasis. These two antioxidants are thus suitable supplements to support bone regeneration in smokers.

read more

PMID:  Life (Basel). 2023 Apr 15 ;13(4). Epub 2023 Apr 15. PMID: 37109548 Abstract Title:  Acai Berry (sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress. Abstract:  Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry () is a potential dietary nutraceutical. The aim of this research was to investigate the neuroprotective effects of acai berry aqueous and ethanolic extracts to reduce the neurotoxicity to neuronal cells triggered by L-Glu application. L-Glu and acai berry effects on cell viability were quantified using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and effects on cellular bioenergetics were assessed via quantitation of the levels of cellular ATP, mitochondrial membrane potential (MMP), and production of reactive oxygen species (ROS) in neuroblastoma cells. Cell viability was also evaluated in human cortical neuronal progenitor cell culture after L-Glu or/and acai berry application. In isolated cells, activated currents using patch-clamping were employed to determine whether L-Glu neurotoxicity was mediated by ionotropic L-Glu-receptors (iGluRs). L-Glu caused a significant reduction in cell viability, ATP, and MMP levels and increased ROS production. The co-application of both acai berry extracts with L-Glu provided neuroprotection against L-Glu with sustained cell viability, decreased LDH production, restored ATP and MMP levels, and reduced ROS levels. Whole-cell patch-clamp recordings showed that L-Glu toxicity is not mediated by the activation of iGluRs in neuroblastoma cells. Fractionation and analysis of acai berry extracts with liquid chromatography-mass spectrometry identified several phytochemical antioxidants that may have provided neuroprotective effects. In summary, the acai berry contains nutraceuticals with antioxidant activity that may be a beneficial dietary component to limit pathological deficits triggered by excessive L-Glu accumulations.

read more

PMID:  Nutrients. 2023 Apr 7 ;15(8). Epub 2023 Apr 7. PMID: 37111027 Abstract Title:  Effects of Juara (Martius) on Health: An Overview of Clinical and Experimental Studies and Call for Action. Abstract:  BACKGROUND AND AIMS: Juara is a fruit of ecological and nutritional importance. Its fruits represent an option for the sustainable use of the plant due to its vulnerability to extinction. Thus, the aim of this review was to analyze clinical and experimental studies and highlight the literature gaps regarding the effects of supplementation with Juara on health.METHODS: For this scoping review, we consulted the Medline (PubMed), Science Direct, and Scopus databases in March, April, and May 2022. Experimental studies and clinical trials published in the last ten years (2012-2022) were analyzed. Data were synthesized and reported.RESULTS: A total of 27 studies were included, 18 of which were experimental studies. Of these, 33% evaluated inflammatory markers associated with fat accumulation. Most of these studies (83%) used pulp in lyophilized form, and the others (17%) involved juara extract mixed in water. In addition, 78% of the studies showed positive results with respect to the lipid profile, reduction of oncological lesions, inflammation, microbiota modulation, and improvement in obesity and glycemia-related metabolic complications. Nine clinical trials with results similar to those of experimental trials were found. The majority (56%) were chronic (four to six weeks into the intervention), and 44% were acute. Three offered juara supplementation in the form of juice, four used freeze-dried pulp, two used fresh pulp, and one used a 9% dilution. The dose was fixed at 5 g, but the dilution ranged from 200 to 450 mL. These trials assessed mainly healthy, physically active, and obese individual adults (19-56 years old), and cardioprotective and anti-inflammatory effects, as well as improvement in the lipid profile and prebiotic potential, were observed.CONCLUSION: Juara supplementation showed promising results with respect to its effect on health. However, further studies are needed to clarify these possible effects on health and their mechanisms of action.

read more

PMID:  Nutrients. 2023 Feb 16 ;15(4). Epub 2023 Feb 16. PMID: 36839349 Abstract Title:  Aa(Mart.) in Health and Disease: A Critical Review. Abstract:  The aapalm (Mart.), a species belonging to thefamily, has been cultivated for thousands of years in tropical Central and South America as a multipurpose dietary plant. The recent introduction of aafruit and its nutritional and healing qualities to regions outside its origin has rapidly expanded global demand for aaberry. The health-promoting and disease-preventing properties of this plant are attributed to numerous bioactive phenolic compounds present in the leaf, pulp, fruit, skin, and seeds. The purpose of this review is to present an up-to-date, comprehensive, and critical evaluation of the health benefits of aaand its phytochemicals with a special focus on cellular and molecular mechanisms of action. In vitro and in vivo studies showed that aapossesses antioxidant and anti-inflammatory properties and exerts cardioprotective, gastroprotective, hepatoprotective, neuroprotective, renoprotective, antilipidemic, antidiabetic, and antineoplastic activities. Moreover, clinical trials have suggested that aacan protect against metabolic stress induced by oxidation, inflammation, vascular abnormalities, and physical exertion. Due to its medicinal properties and the absence of undesirable effects, aashows a promising future in health promotion and disease prevention, in addition to a vast economic potential in the food and cosmetic industries.

read more

PMID:  J Biophotonics. 2023 Mar ;16(3):e202200259. Epub 2022 Dec 7. PMID: 36349809 Abstract Title:  Photodynamic therapy with acai (Euterpe oleracea) and blue light in oral cells: A spectroscopic and cytotoxicity analysis. Abstract:  OBJECTIVE: To evaluate the potential of photodynamic therapy (PDT) with blue light-emitting diode (LED) 460nm at 25, 50 and 100J/cmusing three concentrations of acai extracts (100, 40, and 10 mg/ml), in the proliferation and viability of head and neck tumor lines (SCC9).METHODS: Three groups of cells were analyzed for 3days in an in vitro assay with MTT (3- (4,5-dimethylthiazol-2-yl) -2,5, -diphenyltetrazolium bromide) and crystal violet: cells in the absence of acai extract and PDT (control group); cells in the presence of acai extract and no light; and cells in the presence of acai extract and LED blue light (PDT groups).RESULTS: When using acai as a PS combined with blue LED (460nm, 0.7466cm, 1000mW/cm) and irradiation at 25, 50, and 100J/cm, after 72h, cell viability (p

read more

PMID:  Molecules. 2022 Jul 30 ;27(15). Epub 2022 Jul 30. PMID: 35956841 Abstract Title:  A Preliminary Assessment of the Nutraceutical Potential of Acai Berry (sp.) as a Potential Natural Treatment for Alzheimer's Disease. Abstract:  Alzheimer's disease (AD) is characterised by progressive neuronal atrophy and the loss of neuronal function as a consequence of multiple pathomechanisms. Current AD treatments primarily operate at a symptomatic level to treat a cholinergic deficiency and can cause side effects. Hence, there is an unmet need for healthier lifestyles to reduce the likelihood of AD as well as improved treatments with fewer adverse reactions. Diets rich in phytochemicals may reduce neurodegenerative risk and limit disease progression. The native South American palm acai berry () is a potential source of dietary phytochemicals beneficial to health. This study aimed to screen the nutraceutical potential of the acai berry, in the form of aqueous and ethanolic extracts, for the ability to inhibit acetyl- and butyryl-cholinesterase (ChE) enzymes and scavenge free radicals via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) or 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays. In addition, this study aimed to quantify the acai berry's antioxidant potential via hydrogen peroxide or hydroxyl scavenging, nitric oxide scavenging, lipid peroxidation inhibition, and the ability to reduce ferric ions. Total polyphenol and flavonoid contents were also determined. Acai aqueous extract displayed a concentration-dependent inhibition of acetyl- and butyryl-cholinesterase enzymes. Both acai extracts displayed useful concentration-dependent free radical scavenging and antioxidant abilities, with the acai ethanolic extract being the most potent antioxidant and displaying the highest phenolic and flavonoid contents. In summary, extracts of the acai berry contain nutraceutical components with anti-cholinesterase and antioxidant capabilities and may therefore provide a beneficial dietary component that limits the pathological deficits evidenced in AD.

read more

PMID:  Vascul Pharmacol. 2023 Jun ;150:107175. Epub 2023 Apr 25. PMID: 37105373 Abstract Title:  Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction. Abstract:  AIMS: The prevalence of left ventricular (LV) diastolic and vascular dysfunction increases with age, eventually leading to heart failure with preserved ejection fraction (HFpEF). A preventive strategy is an unmet medical need. We and others reported previously on the beneficial effects of omega-3 fatty acid alpha linolenic acid (ALA) on cardiovascular disorders in animal models and translational studies. We now investigate whether long-term dietary ALA could prevent LV diastolic dysfunction and vascular aging in a murine model.METHODS AND RESULTS: Wild-type C57BL/6J mice were fed a chow or ALA diet for 12months, starting at 6months of age. Here, we show that aged (~18months) mice recapitulate major hallmarks of HFpEF, including LV diastolic dysfunction with preserved ejection fraction, impaired vascular function, cardiac fibrosis, arterial stiffening and inflammation, as well as elevated B-type natriuretic peptide (BNP). Long-term ALA supplementation upregulated the mitochondrial tricarboxylic acid enzyme Idh2 and the antioxidant enzymes SOD1 and Gpx1. It also has been associated with reduced inflammation and ECM remodeling, accompanied by a significant downregulation of fibrosis biomarkers MMP-2 and TGF-in both cardiac and vascular tissues obtained from aged mice. Our data exhibited the preventive effects of dietary ALA against LV diastolic dysfunction, impaired vasorelaxation, cardiac fibrosis, inflammation and arterial stiffening in aged mice.CONCLUSIONS: We provide evidence and a simplified mechanistic insight on how long-term ALA supplementation is a successful strategy to prevent the development of age-related diastolic and vascular dysfunction.

read more

PMID:  Sci Total Environ. 2023 Jul 15 ;882:163552. Epub 2023 Apr 23. PMID: 37094679 Abstract Title:  Dietary polyunsaturated fatty acids intake, air pollution, and the risk of lung cancer: A prospective study in UK biobank. Abstract:  BACKGROUND: Epidemiological evidence on the association between specific types of polyunsaturated fatty acids (PUFAs) intake and lung cancer risk is limited. However, whether dietary-specific PUFAs intake can modify the association between air pollutants and incident lung cancer remains unknown.METHODS: Cox proportional hazard models and restricted cubic spline regression were used to evaluate the associations of omega-3 PUFAs, omega-6 PUFAs and the ratio of omega-6 PUFAs to omega-3 PUFAs intake with lung cancer risk. Furthermore, we evaluated the associations between air pollutants and incident lung cancer, and whether dietary-specific PUFAs intake would modify the relationship using stratification analyses.RESULTS: This study found significant associations between the risk of lung cancer and omega-3 PUFAs intake (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.73-0.93; per 1g/d), and omega-6 PUFAs intake (HR, 0.98; 95% CI, 0.96-0.99; per 1g/d). We did not observe an association between the omega-6 to omega-3 PUFAs intake ratio and incident lung cancer. With regard to air pollution, omega-3 PUFAs intake attenuated the positive relationship between nitrogen oxides (NOx) pollution and lung cancer risk, and an increased incidence of lung cancer was found only in the low omega-3 PUFAs intake group (p

read more

PMID:  Front Nutr. 2023 ;10:1068343. Epub 2023 Apr 5. PMID: 37090780 Abstract Title:  The effect of omega-3 fatty acids on alcohol-induced damage. Abstract:  Alcohol is the most widely consumed psychoactive substance in the world that has a severe impact on many organs and bodily systems, particularly the liver and nervous system. Alcohol use during pregnancy roots long-lasting changes in the newborns and during adolescence has long-term detrimental effects especially on the brain. The brain contains docosahexaenoic acid (DHA), a major omega-3 (n-3) fatty acid (FA) that makes up cell membranes and influences membrane-associated protein function, cell signaling, gene expression and lipid production. N-3 is beneficial in several brain conditions like neurodegenerative diseases, ameliorating cognitive impairment, oxidative stress, neuronal death and inflammation. Because alcohol decreases the levels of n-3, it is timely to know whether n-3 supplementation positively modifies alcohol-induced injuries. The aim of this review is to summarize the state-of-the-art of the n-3 effects on certain conditions caused by alcohol intake, focusing primarily on brain damage and alcoholic liver disease.

read more

PMID:  Sci Rep. 2023 Apr 20 ;13(1):6449. Epub 2023 Apr 20. PMID: 37081029 Abstract Title:  Anti-inflammatory effect of combining fish oil and evening primrose oil supplementation on breast cancer patients undergoing chemotherapy: a randomized placebo-controlled trial. Abstract:  Breast cancer is the most common malignant tumor and one of the leading causes of cancer-related death in women throughout the world. This study is a parallel, randomized, double-blind, controlled, 12-week supplementation trial, investigating the anti-inflammatory effects of dietary intake of fish oil and evening primrose oil (EPO), in patients with breast cancer undergoing chemotherapy. The primary outcomes were changes in the nutritional status and inflammatory cytokines of patients during the study. The secondary outcomes were changes in hematological and biochemical parameters and fatty acid profile. Of the 32 eligible patients, half of them is randomly assigned to a treatment arm with fish oil and EPO (n=16), or a control arm (n=16) with mineral oil as a placebo. The intervention group was taking 2 gel capsules of fish oil and 3 gel capsules of EPO (400 mg eicosapentaenoic acid, 600 mg docosahexaenoic acid, and 351 mg gamma-linolenic acid) fish oil and evening primrose oil for 12 weeks, during their chemotherapy. The control/placebo group was taking 5 gel capsules of 1g of mineral oil. One of the patients dropped out due to discontinuation of the treatment (in the placebo group) and two did not show up at the post-treatment measurements (in the intervention group), thus, 29 women completed the study. The results showed an increase in plasma levels of docosapentaenoic acid (22:5n-3), docosahexaenoic acid (22:6n-3), total n-3PUFA, vaccenic acid (18:1n-7), and a decrease in n-6/n-3 PUFA ratio in the intervention group. An increase in the plasma level of dihomo-gamma-linolenic acid (20:3n-6) was observed in the placebo group. There was no difference in plasma levels of interleukin (IL) IL-8, IL-10, and tumor necrosis factor-alpha, while the level of IL-6 decreased in both groups and was significantly lower in the intervention group at the end of the study. In conclusion, this supplementation improved the PUFA status and decreased the level of IL-6 in breast cancer patients undergoing chemotherapy. Consequently, this treatment may help reduce cancer complications resulting from impaired lipid metabolism and inflammation. ClinicalTrials.gov Identifier: NCT03516253. Date of registration 04/05/2018.

read more

PMID:  Ultrastruct Pathol. 2023 May 4 ;47(3):188-204. Epub 2023 Mar 16. PMID: 36927382 Abstract Title:  Evening primrose oil attenuates oxidative stress, inflammation, fibrosis, apoptosis, and ultrastructural alterations induced by metanil yellow in the liver of rat: a histological, immunohistochemical, and biochemical study. Abstract:  The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5g/kg/day), Myl (200mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-B), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities.

read more

PMID:  J Diet Suppl. 2023 Apr 20:1-19. Epub 2023 Apr 20. PMID: 37078491 Abstract Title:  The Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid, and Vitamin KModulate the Gut Microbiome: A Study Using an In Vitro Shime Model. Abstract:  Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME) to excludesystemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin Kincreased alpha-diversity at 24h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the(F/B) ratio and a consistent increase inandabundances with all treatments. DHA, EPA, and vitamin Kalso modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin Kat 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x (

read more

PMID:  Front Physiol. 2023 ;14:1158140. Epub 2023 Mar 28. PMID: 37057185 Abstract Title:  High fish intake rich in n-3 polyunsaturated fatty acids reduces cardiovascular disease incidence in healthy adults: The ATTICA cohort study (2002-2022). Abstract:  The long-term effects of high fish intake rich in n-3 fatty acids for deterring cardiovascular disease (CVD) and related adverse outcomes in healthy individuals have not been yet elucidated.To evaluate the association between total seafood, as well as small fish, intake on 10- and 20-year CVD incidence and mortality in healthy adults.A prospective cohort study (n = 2,020) was conducted in healthy community dwelling adults in Athens, Greece, selected following age- and sex-based random multistage sampling (meanSD age at baseline: 45.214.0 years). Seafood (high (>2 servings/week) vs. low (2 servings/week) intake), including small fish rich in n-3 fatty acids (high (>1 serving/week) vs. low (1 serving/week) intake), consumption was evaluated by semi-quantitative food frequency questionnaire at baseline. The occurrence of non-fatal and/or fatal CVD events (ICD-10) was assessed during 10- and 20-year follow-up periods.Only 32.7% and 9.6% of participants had high seafood and small fish intakes, respectively. Participants with high seafood intake had 27% decreased 10-year CVD risk (adj. HR:0.73; 95% CI:0.55-0.98) and 74% lower attributable mortality (adj. HR:0.26; 95% CI:0.11-0.58). Participants with high seafood intake also sustained a 24% lower 20-year risk of CVD mortality (adj. HR: 0.76; 95% CI: 0.55-0.98). Moreover, participants with high small fish intake had a lower 10-year CVD risk and 76% decreased risk of 10-year CVD mortality (adj. HR:0.24; 95% CI:0.06-0.99), even among normotensive individuals (adj. HR:0.31; 95% CI:0.13-0.73). When analogous analyses focused on 20-year CVD incidence and mortality, similar but not significant associations were observed (all-values>0.10).High intake of seafood, and particularly small fish rich in n-3 fatty acids, was associated with a lower risk of 10-year fatal and non-fatal CVD. Thus, public health interventions aimed at enhancing small fish consumption may most effectively deter long-term CVD outcomes, particularly among low risk normotensive individuals.

read more

PMID:  Nutrients. 2023 Apr 7 ;15(8). Epub 2023 Apr 7. PMID: 37111029 Abstract Title:  The Prospective Associations of Egg Consumption with the Risk of Total Cerebrovascular Disease Morbidity among Chinese Adults. Abstract:  BACKGROUND: Studies investigating the relationship between egg consumption and the risk of cerebrovascular disease (CED) have yielded inconsistent results. This study evaluated the association between egg consumption and the risk of CED among Chinese adults.METHODS: Data were obtained from China Kadoorie Biobank, Qingdao. A computerised questionnaire was used to collect information regarding egg consumption frequency. CED events were tracked through linkage with the Disease Surveillance Point System and the new national health insurance databases. Cox proportional hazards regression analyses were used to evaluate associations between egg consumption and CED risk controlling for potential confounders.RESULTS: After a median follow-up of 9.2 years, 865 and 1083 CED events among men and women, respectively, were documented. More than 50% of participants consumed eggs daily with an average age of 52.0 (10.4) years at baseline. No association between egg consumption and CED were identified in the whole cohort and women. However, a 28% lower risk of CED was observed in those who consumed eggs at a higher frequency (HR = 0.72, 95% CI: 0.55-0.95) and a significant trend for the association (for trend = 0.012) in a multivariable model in men.CONCLUSION: Higher frequency of egg consumption was associated with a lower risk of total CED events among men but not women in Chinese adults. The beneficial effect on women warrants further investigations.

read more

PMID:  Nutrients. 2023 Mar 25 ;15(7). Epub 2023 Mar 25. PMID: 37049437 Abstract Title:  Consumption of Nutritionally Enriched Hen Eggs Enhances Endothelium-Dependent Vasodilation via Cyclooxygenase Metabolites in Healthy Young People-A Randomized Study. Abstract:  OBJECTIVE: The present study aimed to evaluate the effects of enriched hen egg consumption on endothelium-dependent vasodilation (EDV) and the role of cyclooxygenases in EDV in the microcirculation of young healthy individuals. This study hypothesizes that Nutri4 eggs will improve endothelial function, which will be manifested by changes in microcirculatory flow measured by a laser Doppler flowmeter (LDF) during reactive hyperemia in response to vascular occlusion, in which-3 PUFA plays an important role as well as its degradation pathway by cyclooxygenases.MATERIALS AND METHODS: Participants consumed three eggs per day for three weeks: The control group (CTRL,= 14) consumed regular hen eggs (approximately 0.330 mg of lutein, 1.785 mg of vitamin E, 0.054 mg of selenium and 438 mg of-3 PUFAs daily) and Nutri4 group (= 20) consumed enriched eggs (approximately 1.85 mg of lutein, 0.06 mg of selenium, 3.29 mg of vitamin E, and 1026 mg of-3 PUFAs daily). Skin microvascular blood flow in response to EDV (post-occlusive reactive hyperemia (PORH) and iontophoresis of acetylcholine (AChID)) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry before and after dietary protocol and in a separate group of participants who were administered perorally 100 mg of indomethacin before microvascular response assessment. Arterial blood pressure, heart rate, serum lipid, and liver enzymes, anthropometric measurements, protein expression of cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), neuronal nitric oxide synthases (nNOS), inducible nitric oxide synthases (iNOS), and endothelial nitric oxide synthases (eNOS) were measured before and after dietary protocol.RESULTS: PORH and AChID were significantly enhanced, and SNPID remained unchanged in the Nutri4 group, while none was changed in the CTRL following a respective diet. PORH decreased after administration of indomethacin in Nutri4 after dietary protocol. Protein expression of COX-2 was significantly higher in the Nutri4 group compared to the CTRL after the dietary protocol.CONCLUSION: Consumption of enriched eggs improves microvascular EDV in healthy young subjects. Results suggest an element of-3 PUFAs metabolites via the cyclooxygenases pathway in enhanced reactive hyperemia.

read more

PMID:  Int J Environ Res Public Health. 2023 Feb 25 ;20(5). Epub 2023 Feb 25. PMID: 36901143 Abstract Title:  The Global Association between Egg Intake and the Incidence and Mortality of Ischemic Heart Disease-An Ecological Study. Abstract:  The relationship between egg consumption and ischemic heart disease (IHD) remains controversial as there is still no clear answer regarding the relationship, with research limited to a few geographical regions. In the current study, we conducted a longitudinal analysis of the association between egg intake and IHD incidence (IHDi) and mortality (IHDd) using 28 years of international data from 1990 to 2018. Egg intake (g/day/capita) by country was obtained from the Global Dietary Database. Age-standard IHDi and IHDd rates per 100,000 subjects in each country were obtained from the 2019 Global Burden of Disease database. The analysis included a total of 142 countries with populations of at least one million, for which all data were available from 1990 to 2018. Eggs are consumed worldwide, and regional differences in consumption are also shown. Utilizing IHDi and IHDd as objective variables and egg intake as an explanatory variable, the analysis was conducted using linear mixed models, which controlled for inter- and intra-country variation from year to year. The results showed a significant negative association between egg intake, and IHDi (-0.2530.117,

read more

PMID:  Molecules. 2023 Mar 28 ;28(7). Epub 2023 Mar 28. PMID: 37049766 Abstract Title:  Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats. Abstract:  Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast,-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore,-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40-50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with-3 on the reported outcomes.

read more

PMID:  J Clin Med. 2023 Apr 2 ;12(7). Epub 2023 Apr 2. PMID: 37048736 Abstract Title:  Omega-3 Polyunsaturated Fatty Acids in Managing Comorbid Mood Disorders in Chronic Obstructive Pulmonary Disease (COPD): A Review. Abstract:  Chronic obstructive pulmonary disease (COPD) is the third-leading cause of mortality globally, significantly affecting people over 40 years old. COPD is often comorbid with mood disorders; however, they are frequently neglected or undiagnosed in COPD management, thus resulting in unintended treatment outcomes and higher mortality associated with the disease. Although the exact link between COPD and mood disorders remains to be ascertained, there is a broader opinion that inflammatory reactions in the lungs, blood, and inflammation-induced changes in the brain could orchestrate the onset of mood disorders in COPD. Although the current management of mood disorders such as depression in COPD involves using antidepressants, their use has been limited due to tolerability issues. On the other hand, as omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a vital role in regulating inflammatory responses, they could be promising alternatives in managing mood disorders in COPD. This review discusses comorbid mood disorders in COPD as well as their influence on the progression and management of COPD. The underlying mechanisms of comorbid mood disorders in COPD will also be discussed, along with the potential role of n-3 PUFAs in managing these conditions.

read more

PMID:  Endocrinology. 2023 Apr 17 ;164(6). PMID: 37029960 Abstract Title:  Saturated Fatty Acids and Omega-3 Polyunsaturated Fatty Acids Improve Metabolic Parameters in Ovariectomized Female Mice. Abstract:  In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks. EB treatment reversed obesity, glucose intolerance, and bone loss in ovariectomized mice. fat-1 mice fed a 1% LA diet experienced reduced weight gain and adiposity, while those fed a 22.5% LA diet exhibited increased energy expenditure and activity in EB-treated ovariectomized mice. Coconut oil SFAs and omega-3 FAs helped protect against glucose intolerance without EB treatment. Improved insulin sensitivity was observed in wild-type and fat-1 mice fed 1% LA diet with EB treatment, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. The production of short-chain fatty acids by gut microbial microbiota was linked to omega-3 FAs production and improved energy homeostasis. These findings suggest that a balanced dietary fatty acid profile containing SFAs and a lower ratio of omega-6:omega-3 FAs is more effective in alleviating metabolic disorders during E2 deficiency.

read more

PMID:  Am J Clin Nutr. 2023 Jun ;117(6):1096-1109. Epub 2023 Apr 5. PMID: 37028557 Abstract Title:  The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Abstract:  Previous data have linked omega-3 fatty acids with risk of dementia. We aimed to assess the longitudinal relationships of omega-3 polyunsaturated fatty acid intake as well as blood biomarkers with risk of Alzheimer's disease (AD), dementia, or cognitive decline. Longitudinal data were derived from 1135 participants without dementia (mean age = 73 y) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to evaluate the associations of omega-3 fatty acid supplementation and blood biomarkers with incident AD during the 6-y follow-up. A meta-analysis of published cohort studies was further conducted to test the longitudinal relationships of dietary intake of omega-3 and its peripheral markers with all-cause dementia or cognitive decline. Causal dose-response analyses were conducted using the robust error meta-regression model. In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD (hazard ratio: 0.36, 95% confidence interval: 0.18, 0.72; P = 0.004). After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by20%, especially for docosahexaenoic acid (DHA) intake (relative risk [RR]: 0.82, I= 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE4 status (RR: 0.83, I= 65%, P = 0.006). Each increment of 0.1 g/d of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8%9.9% (P

read more

PMID:  Nat Aging. 2022 Nov ;2(11):1024-1039. Epub 2022 Nov 17. PMID: 37118092 Abstract Title:  Intermittent fasting protects against Alzheimer's disease in mice by altering metabolism through remodeling of the gut microbiota. Abstract:  Alzheimer's disease (AD) is the most common form of dementia without effective clinical treatment. Here, we show that intermittent fasting (IF) improves cognitive functions and AD-like pathology in a transgenic AD mouse model (5XFAD). IF alters gut microbial composition with a significant enrichment in probiotics such as Lactobacillus. The changes in the composition of the gut microbiota affect metabolic activities and metabolite production. Metabolomic profiling analysis of cecal contents revealed IF leads to a decreased carbohydrate metabolism (for example, glucose) and an increased abundance in amino acids (for example, sarcosine and dimethylglycine). Interestingly, we found that the administration of IF-elevated sarcosine or dimethylglycine mimics the protective effects of IF in 5XFAD mice, including the amelioration of cognitive decline, amyloid-(A) burden and glial overactivation. Our findings thus demonstrate an IF regimen is a potential approach to prevent AD progression, at least through the gut-microbiota-metabolites-brain axis, and constitutes an innovative AD therapeutic avenue.

read more

PMID:  Arq Bras Cardiol. 2023 Mar ;120(5):e20220756. PMID: 37098959 Abstract Title:  Improvement in Blood Pressure After Intermittent Fasting in Hipertension: Could Renin-Angiotensin System and Autonomic Nervous System Have a Role? Abstract:  BACKGROUND: Although it has been reported that the intermittent fasting (IF) diet has positive effects on heart health and improvement in blood pressure, it has not been sufficiently clarified how it could have these positive effects yet.OBJECTIVE: We aimed to evaluate the effects of IF on the autonomic nervous system (ANS) and renin-angiotensin system (RAS), which are closely related to blood pressure.METHODS: Seventy-two hypertensive patients were included in the study, and the data of 58 patients were used. All the participants fasted for about 15-16 hours for 30 days. Participants were evaluated with 24-hour ambulatory blood pressure monitoring and Holter electrocardiography before and after IF; also, 5 ml venous blood samples were taken for assessment of Serum angiotensin I (Ang-I) and angiotensin II (Ang-II) levels and angiotensin-converting enzyme (ACE) activity. For data analysis, the p-value

read more

PMID:  Nutr Rev. 2023 Apr 12. Epub 2023 Apr 12. PMID: 37043764 Abstract Title:  Effects of intermittent fasting on cognitive health and Alzheimer's disease. Abstract:  OBJECTIVE: Caloric restriction by intermittent fasting produces several metabolic changes, such as increased insulin sensitivity and use of ketone bodies as energy sources. In humans, intermittent fasting has been studied in hypertension, diabetes, and related conditions, but, to date, not as a strategy to reduce the risk of emergent dementia. In this scoping review, the relevance of intermittent fasting as a potential preventive intervention for Alzheimer's dementia is explored.BACKGROUND: The beneficial effects of calorie restriction have been documented in animals and humans. Decreased oxidative stress damage and attenuated inflammatory responses are associated with intermittent fasting. These changes have a favorable impact on the vascular endothelium and stress-induced cellular adaptation.RESULTS: Physiological alterations associated with fasting have profound implications for pathological mechanisms associated with dementias, particularly Alzheimer's disease. Compared with ad libitum feeding, caloric restriction in animals was associated with a reduction in-amyloid accumulation, which is the cardinal pathological marker of Alzheimer's disease. Animal studies have demonstrated synaptic adaptations in the hippocampus and enhanced cognitive function after fasting, consistent with these theoretical frameworks. Furthermore, vascular dysfunction plays a crucial role in Alzheimer's disease pathology, and intermittent fasting promotes vascular health.CONCLUSIONS: These observations lead to a hypothesis that intermittent fasting over the years will potentially reverse or delay the pathological process in Alzheimer's disease.

read more

PMID:  Arq Bras Cardiol. 2023 ;120(4):e20220606. Epub 2023 Apr 7. PMID: 37042857 Abstract Title:  The Value of Intermittent Fasting and Low Carbohydrate Diet in Prediabetic Patients for the Prevention of Cardiovascular Diseases. Abstract:  BACKGROUND: Prediabetic patients are at increased risk for cardiovascular diseases and the development of microvascular and macrovascular complications. Intermittent fasting (IF) and low-carbohydrate diet (LCD) are promising dietary plans.OBJECTIVES: Our aims to analyze the benefits of IF combined with LCD on microvascular and macrovascular outcomes in prediabetic patients.METHODS: The study included 485 prediabetic patients with no history of cardiovascular diseases divided into group I: (n = 240 patients) who underwent IF (16 h IF 3-4 days per week) combined with LCD (

read more

PMID:  NPJ Biofilms Microbiomes. 2023 Apr 7 ;9(1):19. Epub 2023 Apr 7. PMID: 37029135 Abstract Title:  Intermittent fasting modulates the intestinal microbiota and improves obesity and host energy metabolism. Abstract:  Intermittent fasting (IF) is a promising paradigm for weight loss which has been shown to modulate the gut microbiota based on 16S rRNA gene amplicon sequencing. Here, 72 Chinese volunteers with a wide range of body mass index (BMI) participated in a three-week IF program during which an average loss of 3.67kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembly yielded 2934 metagenome-assembled genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and atherosclerotic cardiovascular diseases (ASCVD). MAGs enriched after the intervention showed high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.

read more

PMID:  PLoS One. 2023 ;18(3):e0282338. Epub 2023 Mar 30. PMID: 36996042 Abstract Title:  Long-term intermittent fasting improves neurological function by promoting angiogenesis after cerebral ischemia via growth differentiation factor 11 signaling activation. Abstract:  Intermittent fasting (IF), an alternative to caloric restriction, is a form of time restricted eating. IF conditioning has been suggested to have neuroprotective effects and potential long-term brain health benefits. But the mechanism underlying remains unclear. The present study focused on the cerebral angiogenesis effect of IF on ischemic rats. Using a rat middle cerebral artery occlusion model, we assessed neurological outcomes and various vascular parameters such as microvessel density (MVD), regional cerebral blood flow (rCBF), proliferation of endothelial cells (ECs), and functional vessels in the peri-infarct area. IF conditioning ameliorated the modified neurological severity score and adhesive removal test, increased MVD, and activated growth differentiation factor 11 (GDF11)/activin-like kinase 5 (ALK5) pathways in a time-dependent manner. In addition, long-term IF conditioning stimulated proliferation of ECs, promoted rCBF, and upregulated the total vessel surface area as well as the number of microvessel branch points through GDF11/ALK5 pathways. These data suggest that long-term IF conditioning improves neurological outcomes after cerebral ischemia, and that this positive effect is mediated partly by angiogenesis in the peri-infarct area and improvement of functional perfusion microvessels in part by activating the GDF11/ALK5 signaling pathway.

read more

PMID:  Adv Biol (Weinh). 2023 Mar 22:e2200337. Epub 2023 Mar 22. PMID: 36950759 Abstract Title:  Impact of Intermittent Fasting on the Gut Microbiota: A Systematic Review. Abstract:  Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.

read more

PMID:  Biomed Pharmacother. 2023 Jul ;163:114754. Epub 2023 Apr 23. PMID: 37094549 Abstract Title:  Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases. Abstract:  Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoEmice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.

read more

PMID:  Drug Des Devel Ther. 2023 ;17:1139-1151. Epub 2023 Apr 13. PMID: 37077411 Abstract Title:  Berberine Alleviates Acute Lung Injury in Septic Mice by Modulating Treg/Th17 Homeostasis and Downregulating NF-B Signaling. Abstract:  PURPOSE: A common complication of sepsis is acute lung injury (ALI), which is associated with an acute onset, rapid disease changes, and high mortality. Regulatory T (Treg) and T helper 17 (Th17) cells comprise CD4T cell subsets, which strongly influence inflammation during ALI. In this study, we investigated the effect of berberine (BBR), an antioxidant, anti-inflammatory, and immunomodulatory drug, on the inflammatory response and immune state in mice with sepsis.METHODS: A mouse model of cecal ligation and puncture (CLP) was established. The mice were intragastrically administered 50 mg/kg BBR. We used histological techniques to evaluate inflammatory tissue injury and flow cytometry for analyzing Treg/Th17 levels. We also assessed NF-B signaling pathways by Western blotting assays and immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the content of cytokines.RESULTS: Treatment with BBR considerably mitigated lung injury while improving survival, post-cecal ligation, and puncture (CLP). Treatment with BBR ameliorated pulmonary edema and hypoxemia in septic mice and inhibited the NF-B signaling pathway. BBR also increased Treg cells and decreased Th17 proportions in the spleen and lung tissue of CLP-treated mice. Blocking Treg cells weakened the protective effect of BBR on sepsis-associated lung injury.CONCLUSION: Overall, these results suggested that BBR is a potential therapeutic agent for sepsis.

read more

PMID:  Benef Microbes. 2022 Nov 16 ;13(5):407-416. Epub 2022 Oct 14. PMID: 36239668 Abstract Title:  Long-term use ofN1115 from early life alleviates high-fat-diet-induced obesity and dysmetabolism in mice. Abstract:  Obesity has become one of the most serious public health problems worldwide, and an increasing number of studies indicate that the gut microbiota can affect host metabolism. Therefore, the present study was conducted to evaluate whether long-term use of probiotics can alleviate host obesity and metabolism by altering gut microbiota. The high-fat diet (HFD) starting from weaned period led to higher levels of visceral fat and a significantly heavier liver in male mice. Moreover, HFD resulted in disorders of glucose and lipid metabolism, changes in insulin-resistance indices (IR), and an increase in serum insulin and leptin in mice. Of note, 15 weeks use ofN1115 decreased visceral fat, liver weight, serum levels of insulin and leptin, and IR and alleviated lipid dysmetabolism. HFD resulted in a significant increase in the relative abundance of,, andand may decrease the faecal short-chain fatty acid (SCFA) levels in mice; in turn, treatment with the potential probiotic strainN1115 protected mice from these negative effects. HFD significant impaired the physiology of the host especially in male mice and dramatically changed the composition of host gut microbiota. However, the use of potential probiotic strain, such asN1115, may prevent these impairments due to HFD via effecting the host gut microbiota and SCFA.

read more

PMID:  J Sci Food Agric. 2023 Apr ;103(6):2949-2959. Epub 2022 Nov 1. PMID: 36221226 Abstract Title:  Lactobacillus paracasei IMC 502 ameliorates type 2 diabetes by mediating gut microbiota-SCFA-hormone/inflammation pathway in mice. Abstract:  BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex and prevalent metabolic disease that seriously threatens human health. Numerous studies have shown that probiotics as dietary supplements have the potential to prevent and treat T2DM. However, the ability of various strains to improve diabetes symptoms and corresponding mechanisms are different. Thus, mechanistic investigation is required to validate the pharmacology of each probiotic strain for T2DM treatment. Lactobacillus paracasei IMC 502 was originally isolated from Italian elderly human feces and its probiotic attributes have been demonstrated. Here, the antidiabetic pharmacodynamics of L. paracasei IMC 502 on T2DM mice was explored.RESULTS: Lactobacillus paracasei IMC 502 significantly decreased blood glucose, HbA1c and lipid levels, improved insulin resistance and glucose intolerance, regulated the mRNA/protein expression of key hepatic enzymes associated with gluconeogenesis, de novo lipogenesis and PI3K/Akt pathway, and repaired pancreatic and hepatic tissue damage. This probiotic conferred beneficial outcomes in the gut microbiome of diabetic mice, which induced transformation of short-chain fatty acids (SCFAs) and further enhanced the secretion of downstream hormones, and ultimately ameliorated the inflammatory response.CONCLUSION: Lactobacillus paracasei IMC 502 prevents and alleviates T2DM by mediating the gut microbiota-SCFA-hormone/inflammation pathway.2022 Society of Chemical Industry.

read more

PMID:  Life (Basel). 2023 Apr 19 ;13(4). Epub 2023 Apr 19. PMID: 37109573 Abstract Title:  Fermented Vegetables and Legumes vs. Lifestyle Diseases: Microbiota and More. Abstract:  Silages may be preventive against lifestyle diseases, including obesity, diabetes mellitus, or metabolic syndrome. Fermented vegetables and legumes are characterized by pleiotropic health effects, such as probiotic or antioxidant potential. That is mainly due to the fermentation process. Despite the low viability of microorganisms in the gastrointestinal tract, their probiotic potential was confirmed. The modification of microbiota diversity caused by these food products has numerous implications. Most of them are connected to changes in the production of metabolites by bacteria, such as butyrate. Moreover, intake of fermented vegetables and legumes influences epigenetic changes, which lead to inhibition of lipogenesis and decreased appetite. Lifestyle diseases' feature is increased inflammation; thus, foods with high antioxidant potential are recommended. Silages are characterized by having a higher bioavailable antioxidants content than fresh samples. That is due to fermentative microorganisms that produce the enzyme-glucosidase, which releases these compounds from conjugated bonds with antinutrients. However, fermented vegetables and legumes are rich in salt or salt substitutes, such as potassium chloride. However, until today, silages intake has not been connected to the prevalence of hypertension or kidney failure.

read more

PMID:  Eur J Nutr. 2023 Apr 27. Epub 2023 Apr 27. PMID: 37106252 Abstract Title:  Fruit and vegetable consumption and the risk of hypertension: a systematic review and meta-analysis of prospective studies. Abstract:  PURPOSE: A high fruit and vegetable intake has been associated with reduced risk of hypertension; however, results have been inconsistent and it is unclear whether specific types of fruits and vegetables are particularly beneficial. This systematic review and meta-analysis aimed to summarize the published prospective studies on fruit and vegetable consumption and risk of hypertension.METHODS: Embase and PubMed databases were searched for relevant prospective studies up to 15th May 2022. Random effects models were used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) for the association between fruit and vegetable intake and risk of hypertension. Strength of evidence was assessed using World Cancer Research Fund (WCRF) criteria.RESULTS: Eighteen prospective studies (451 291 participants, 145 492 cases) were included. The summary RR (95% CI) of hypertension per 200 g/day was 0.97 (0.95-0.99, I=68%, n=8) for fruits and vegetables, 0.93 (0.89-0.98, I=77%, n=10) for fruits, and 1.00 (0.98-1.02, I=38%, n=10) for vegetables. Reductions in risk were observed up to 800 g/day for fruits and vegetables, and 550 g/day for fruits, and these two associations were considered probably causal using WCRF criteria. Inverse associations were observed for apples or pears, blueberries, raisins or grapes, avocado, broccoli, carrots and lettuce, while positive associations were observed for cantaloupe, Brussels sprouts, cruciferous vegetables, and total and fried potatoes (n=2-5).CONCLUSION: A high intake of fruit and vegetables combined, and total fruit was associated with reduced risk of hypertension, while results for fruit and vegetable subtypes were mixed and need further study.

read more

PMID:  Food Res Int. 2023 May ;167:112657. Epub 2023 Mar 1. PMID: 37087207 Abstract Title:  Effects of dragon fruit oligosaccharides on immunity, gut microbiome, and their metabolites in healthy adults - A randomized double-blind placebo controlled study. Abstract:  Healthy food has wide popularity and relates positively to health. Our previous studies have shown that dragon fruit oligosaccharides (DFO) have prebiotic activities, balancing the gut microbiota in a simulated human colon system, and are safe and stimulate the immune system in rats. The effects of DFO on immune stimulation gut microbe modulation and the correlation of gut microbiota and nutrients were investigated in a human trial. This clinical study was a randomized, double-blinded, placebo-controlled trial. The participants were 107 healthy adults, divided into 3 groups that received DFO in drinking waterdoses of 4 and 8 g/day, compared to the placebo group for 4 consecutive weeks. DFO consumption at 4 g/day increased IgA level (11.31 mg/dL or 10.95% from baseline) and 8 g/day outstandingly promoted the growth of Bifidobacterium spp. (8.41%) and Faecalibacterium (1.99%) and decreased harmful bacteria, especially, Escherichia coli (8.44%). The relationship between gut microbes and nutrient intake was explored and significant (p 

read more

PMID:  Front Nutr. 2023 ;10:1080825. Epub 2023 Feb 6. PMID: 36814509 Abstract Title:  Effects of kiwi fruit () polysaccharides on metabolites and gut microbiota of acrylamide-induced mice. Abstract:  INTRODUCTION: Kiwifruit () has rich nutritious and medicinal properties. It is widely consumed worldwide for the intervention of metabolism disorders, however, the underlying mechanism remains unclear. Acrylamide, a well-known toxic ingredient, mainly forms in high-temperature processed carbohydrate-rich food and causes disorders of gut microbiota and systemic metabolism.METHODS: This study explored the protective effects and underlying mechanisms of kiwifruit polysaccharides against acrylamide-induced disorders of gut microbiota and systemic metabolism by measuring the changes of gut microbiota and serum metabolites in mice.RESULTS: The results showed that kiwifruit polysaccharides remarkably alleviated acrylamide-induced toxicity in mice by improving their body features, histopathologic morphology of the liver, and decreased activities of liver function enzymes. Furthermore, the treatment restored the healthy gut microbiota of mice by improving the microbial diversity and abundance of beneficial bacteria such as. Metabolomics analysis revealed the positive effects of kiwifruit polysaccharides mainly occurred through amino and bile acid-related metabolism pathways including nicotinate and nicotinamide metabolism, primary bile acid biosynthesis, and alanine, aspartate and glutamate metabolism. Additionally, correlation analysis indicated thatexhibited a highly significant correlation with critical metabolites of bile acid metabolism.DISCUSSION: Concisely, kiwifruit polysaccharides may protect against acrylamide-induced toxicity by regulating gut microbiota and metabolism.

read more

PMID:  Nutrients. 2023 Apr 12 ;15(8). Epub 2023 Apr 12. PMID: 37111066 Abstract Title:  Association of Oral or Intravenous Vitamin C Supplementation with Mortality: A Systematic Review and Meta-Analysis. Abstract:  Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (= 0.009, RR 0.87, 95% CI 0.78 to 0.97, I= 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (= 0.005, RR 0.74, 95% CI 0.59 to 0.91, I= 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (= 0.03, RR 0.84, 95% CI 0.72 to 0.98, I= 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.

read more

PMID:  Kidney Res Clin Pract. 2023 May ;42(3):325-339. Epub 2023 Mar 22. PMID: 37098680 Abstract Title:  The flavonoid fisetin ameliorates renal fibrosis by inhibiting SMAD3 phosphorylation, oxidative damage, and inflammation in ureteral obstructed kidney in mice. Abstract:  BACKGROUND: Renal fibrosis is characterized by the accumulation of extracellular matrix and inflammatory cells and kidney dysfunction, which is a major pathway in the progression of chronic kidney disease (CKD). Accumulating evidence indicates that oxidative stress plays a critical role in the initiation and progression of CKD via proinflammatory and profibrotic signaling pathways. Fisetin (3,3',4',7-tetrahydroxyflavone) has biological activities including antioxidant, anti-inflammatory, and anti-aging effects. Therefore, we evaluated the antifibrotic effects of fisetin on unilateral ureteral obstruction (UUO)-induced kidneys.METHODS: C57BL/6 female mice were subjected to right UUO and intraperitoneally injected every other day with fisetin (25 mg/kg/ day) or vehicle from 1 hour before surgery to 7 days after surgery. Kidney samples were analyzed for renal fibrosis (-smooth muscle actin [-SMA] expression, collagen deposition, and transforming growth factor [TGF]1/SMAD3 signaling pathway), oxidative damage (4-HNE and 8-OHdG expression), inflammation (proinflammatory cytokine/chemokine, macrophage, and neutrophil infiltration), and apoptosis (TUNEL staining). Cultured human proximal tubule cells were treated with fisetin before TGF-to confirm the TGF-downstream pathway (SMAD2/3 phosphorylation).RESULTS: We found that fisetin treatment protected against renal fibrosis by inhibiting the phosphorylation of SMAD3, oxidative damage, inflammation, apoptotic cell death, and accumulation of profibrotic M2 macrophages in the obstructed kidneys. In cultured human proximal tubular cells, fisetin treatment inhibited TGF-1-induced phosphorylation of SMAD3 and SMAD2.CONCLUSION: Fisetin alleviates kidney fibrosis to protect against UUO-induced renal fibrosis, and could be a novel therapeutic drug for obstructive nephropathy.

read more

PMID:  J Orthop Surg Res. 2023 Apr 22 ;18(1):312. Epub 2023 Apr 22. PMID: 37087476 Abstract Title:  Network pharmacology identifies fisetin as a treatment for osteoporosis that activates the Wnt/-catenin signaling pathway in BMSCs. Abstract:  BACKGROUND: Although fisetin may exist widely in many natural herbs, its anti-OP mechanism is still unclear. The aim of this study is to explore the molecular anti-osteoporosis (OP) mechanism of fisetin based on network pharmacology and cell experiments.METHODS: The target of fisetin was extracted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of OP were obtained by DisGeNET, GeneCards and the Comparative Toxicogenomics Database, and the targets of fisetin in OP were screened by cross-analysis. The protein-protein interaction (PPI) network was constructed by STRING, and the core targets were obtained. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets via the Database for Annotation, Visualization and Integrated Discovery. Finally, an in vitro cell experiment was used to verify the anti-OP effect and mechanism of fisetin.RESULTS: There are 44 targets of fisetin related to the treatment of OP. The PPI results suggest that CTNNB1, CCND1, TP53, JUN, and AKT1 are the core targets. A total of 259 biological process, 57 molecular function and 26 cell component terms were obtained from GO enrichment analysis. The results of KEGG pathway enrichment analysis suggested that fisetin treatment of OP may be related to the Wnt signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway and other signaling pathways. In vitro cell experiments showed that fisetin significantly increased the expression levels of ALP, collagen I, osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) (p

read more

PMID:  J Inflamm Res. 2023 ;16:109-126. Epub 2023 Jan 10. PMID: 36647388 Abstract Title:  Theaflavin-3,3'-Digallate Ameliorates Collagen-Induced Arthritis Through Regulation of Autophagy and Macrophage Polarization. Abstract:  PURPOSE: Previous studies have presented that theaflavin-3,3'-digallate (TFDG), one of natural flavonoids, have protective effects on collagen-induced arthritis (CIA). Besides, it was reported that TFDG could affect inflammatory signaling pathways, like NF-B, JNK, and so on, to ameliorate inflammation. However, the anti-inflammatory mechanisms mentioned above are common to natural flavonoid products including TFDG. Therefore, this study aimed to further investigate the other mechanisms of TFDG against CIA.METHODS: DBA/1 mice (8-10 weeks) were intravenously injected Freund's Adjuvant (100L) at the base of tail and intraperitoneally injected PBS or different dosage of TFDG (1 mg/kg or 10 mg/kg). Then the paw and knee tissues were collected to assess the severity of joint destruction. In vitro experiments, bone marrow macrophages (BMMs) were exposed to TNF-(10ng/mL) with or without different concentrations of TFDG (0.1mol/L or 1.0mol/L). Besides, the targets of TFDG were predicted with docking software and were verified through experiment.RESULTS: TFDG treatment could reduce M1 macrophage (pro-inflammatory) and inflammatory cytokines, such as IL-1, IL- 6 and TNF-, both in vitro and in vivo. At the same time, the M2 macrophage (alternatively activated) polarization was promoted by TFDG. Animal experiments showed TFDG ameliorated joint destructions. For investigating the mechanisms, the targets of TFDG were predicted by bioinformatics tools. According to predictions, we hypothesized that TFDG could act with BCL-2 to weaken the interaction between BCL-2 and Beclin1. Beclin1 plays a central role in autophagy, and we found that the autophagy level of BMMs was recovered by TFDG. Besides, 3-MA, an autophagy inhibitor, could attenuate the therapeutic effect of TFDG.CONCLUSION: TFDG protected against collagen-induced arthritis by attenuating the inflammation and promoting anti-inflammatory M2 macrophage polarization through controlling autophagy.

read more

PMID:  Physiol Behav. 2023 Mar 15 ;261:114077. Epub 2023 Jan 11. PMID: 36638877 Abstract Title:  Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose. Abstract:  Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

read more

PMID:  Br J Nutr. 2023 Mar 23:1-8. Epub 2023 Mar 23. PMID: 36950976 Abstract Title:  Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage. Abstract:  Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidantantioxidant systems and eating habits. The study was conducted in four groups of thirty SpragueDawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.

read more

PMID:  Viruses. 2023 Apr 15 ;15(4). Epub 2023 Apr 15. PMID: 37112952 Abstract Title:  Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro. Abstract:  A limited number of effective therapies are currently available to treat human coronavirus SARS-CoV-2 and other human coronaviruses, which are responsible for nearly a third of global cases of the common cold. The possibility of new emerging coronaviruses demands powerful new antiviral strategies. Lactoferrin is a well-known protein that possesses anti-inflammatory and immunomodulatory activities, and it has previously shown antiviral activity against several viruses, including SARS-CoV-2. To increase this antiviral activity, here we present bovine liposomal lactoferrin. Liposomal encapsulation of the compound was proven to increase permeability, bioavailability, and time release. In the present work, we compare the antiviral activity of free and liposomal bovine lactoferrin against HCoV229E and SARS-CoV-2 in vitro and in human primary bronchial epithelial cells, and we demonstrated that the liposomal form exerts a more potent antiviral activity than its free form at non-cytotoxic doses.

read more

PMID:  Pathogens. 2023 Apr 14 ;12(4). Epub 2023 Apr 14. PMID: 37111484 Abstract Title:  Antimicrobial Effects of Lactoferrin againstInfection. Abstract:  ()is the primary causative agent of various gastroduodenal diseases.is an adapted microorganism that has evolved to survive in the acidic conditions of the human stomach, possessing a natural strategy for colonizing harsh environments. Despite the implementation of various eradication regimens worldwide, the eradication rate ofhas decreased to less than 80% in recent years due to the emergence of antibiotic-resistant strains. This has posed a significant challenge in treatinginfection, as antibiotic resistance and side effects have become increasingly problematic. Lactoferrin, a member of the transferrin family, is an iron-binding protein with antioxidant, antibacterial, antiviral, and anti-inflammatory properties that promote human health. The concentrations of lactoferrin in the gastric juice and mucosa significantly increase duringinfection and are strongly correlated with the severity of gastric mucosal inflammation. Numerous researchers have studied the antimicrobial properties of lactoferrin both in vitro and in vivo. In addition, recent studies have investigated the addition of oral lactoferrin supplementation toeradication therapy, even though monotherapy with lactoferrin does not eradicate the microorganism. In this article, we reviewed the survival strategy ofto evade the antimicrobial activity of human lactoferrin and explore the potential of lactoferrin ineradication therapy.

read more

PMID:  Nutrients. 2023 Mar 7 ;15(6). Epub 2023 Mar 7. PMID: 36986040 Abstract Title:  The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments. Abstract:  In order to understand how omega-3 polyunsaturated fatty acid (-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles published in the last 5 years in two databases was performed. Of the 679 articles identified, only 27 were included and examined based on five topics, taking into account: the induction type of the breast cancer used in animal models; the characteristics of the induction model by cell transplantation; the experimental design of the-3 supplementation-combined or not with a treatment antitumor drug; the fatty acids (FAs) composition used; the analysis of the studies' outcomes. There are diverse and well-established animal models of breast cancer in the literature, with very relevant histological and molecular similarities depending on the specific objective of the study, such as whether the method of tumor induction was transgenic, by cell transplantation, or by oncogenic drugs. The analyses of outcomes were mainly focused on monitoring tumor growth, body/tumor weight, and molecular, genetic, or histological analyses, and few studies evaluated latency, survival, or metastases. The best results occurred when supplementation with-3 PUFA was associated with antitumor drugs, especially in the analysis of metastases and volume/weight of tumors or when the supplementation was started early and maintained for a long time. However, the beneficial effect of-3 PUFA supplementation when not associated with an antitumor agent remains unclear.

read more

PMID:  Children (Basel). 2023 Feb 27 ;10(3). Epub 2023 Feb 27. PMID: 36980026 Abstract Title:  Vitamin D and Omega-3 (Fatty Acid) Supplementation in Pregnancy for the Primary Prevention of Food Allergy in Children-Literature Review. Abstract:  During the last decades the prevalence of food allergy (FA), an adverse immune response to a specific food antigen, has risen, with negative effects on the quality of life (QoL) of many children and their families. The pathogenesis of FA is complex, involving both genetic and environmental factors. SPINK5, STAT6, HLA and FOXP3 are some of the genes that are reported to be implicated in FA development. Regarding environmental factors, particular interest has been focused on modification of the dietary habits of pregnant women for the primary prevention of FA. Specifically, Vitamin D and omega-3 (-3) fatty acid supplementation during pregnancy may influence the development of FA in the offspring. Vitamin D is a hormone with various actions, including mediation of the immune system, reducing the production of inflammatory cytokines and promoting tolerance. Vitamin D deficiency in pregnancy suppresses T-regulatory cells in the fetus, and Vitamin D supplementation might protect against FA development. Dietary-3 fatty acids are found mainly in fish and vegetable oils. They are beneficial for human health, playing a role in the immune system as anti-inflammatory agents, and providing cell membrane stabilization with inhibition of antigen presentation. It is documented that maternal supplementation with-3 during pregnancy may protect from allergic sensitization in the children. The aim of this literature review was to explore the potential preventive role of maternal supplementation during pregnancy with Vitamin D and-3 in the development of FA in the offspring. With the prevalence of FA rising, all the possible protective mechanisms and measures for FA prevention need to be explored, starting with those that can be modified.

read more

PMID:  Int J Biol Macromol. 2023 Jun 1 ;239:124201. Epub 2023 Mar 30. PMID: 37001771 Abstract Title:  Investigation of the antitumor effect on breast cancer cells of the electrospun amygdalin-loaded poly(l-lactic acid)/poly(ethylene glycol) nanofibers. Abstract:  In this study, PLA/PEG nanofibers (NFs) loaded with amygdalin (AMG) and bitter almond kernels extract were produced by electrospinning to prevent local breast cancer recurrence, and the effect of produced NFs on the MCF-7 cell line was investigated in vitro. The electrospun NFs were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis (DSC) and tensile strength and physical analyzes were performed. Loading of AMG to nanofibers increased fiber diameters from 827.93  174.507 nm to 1855.32  291.057 m. When drug release results were analyzed, the NFs showed a controlled release profile extending up to 10 h. The encapsulation efficiency of AMG-loaded NFs was calculated at 100  0,01 %, 94  0,02 %, and 88  0,02 %. When in vitro cytotoxicity results were analyzed, showed that all NFs are effective in inducing cytotoxicity against MCF-7 breast cancer cells. Importantly, 20 mg AMG-loaded NFs displayed effectively higher cytotoxic effects against breast cancer cells relative to the other NFs. Considering all the results, AMG-loaded NFs can give sustained release of drugs at the local sites. Therefore, AMG-loaded nanofibers can reduce the risk of local recurrence of cancer after surgery and can be directly implanted into solid tumor cells for treatment.

read more

PMID:  Int Wound J. 2023 Apr 28. Epub 2023 Apr 28. PMID: 37118938 Abstract Title:  Effects of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. Abstract:  To investigate the effect of vitamin C combined with recombinant basic fibroblast growth factor (rbFGF) on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. A retrospective analysis of 98 patients with high-voltage electrical burns admitted to our hospital from January 2021 to April 2022. A total of 98 patients were divided into research group and control group, including 49 cases treated with vitamin C combined with rbFGF and 49 cases treated with only rbFGF. The disappearance time of clinical symptoms, wound healing rate, area of granulation tissue growth, level of inflammatory factors, oxygen environment were compared between two groups after one and three courses of treatment. After treatment, the disappearance time of erythema, pain, swelling, blisters, exudate symptoms, wound healing time, scab formation time, and hospitalisation time in the research group were significantly better than those in control group (P.05), while it is significantly better than those in control group after three courses of treatment (P

read more

PMID:  Antioxidants (Basel). 2023 Apr 17 ;12(4). Epub 2023 Apr 17. PMID: 37107316 Abstract Title:  Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation. Abstract:  Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (= 0.007) but did not affect the inflammatory biomarker concentrations (>0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.

read more

PMID:  Front Pharmacol. 2023 ;14:1163694. Epub 2023 Apr 5. PMID: 37089915 Abstract Title:  Vitamin C and vitamin Dalleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolismthe gut-liver axis. Abstract:  Previous studies have demonstrated that both vitamin C (VC) and vitamin D(VDhave therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acidsthe gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects.In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VDon MAFLD by using a high-fat diet (HFD)-induced obese mouse model.Treatment of mice with VC and VDefficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VDshowed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VDreshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice.Together, the results indicate that the anti-MAFLD activities of VC and VDare linked to improved gut-liver interactionsregulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.

read more

PMID:  Front Nutr. 2023 ;10:1094757. Epub 2023 Mar 24. PMID: 37051117 Abstract Title:  Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis. Abstract:  BACKGROUND: This meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.METHODS: Databases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.RESULTS: A total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97,= 0.02,= 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72,= 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74,= 0.13,= 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): -37.75 h, 404 patients) and mechanical ventilation (MD: -47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.CONCLUSION: Although intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.

read more

PMID:  Nutrients. 2023 Apr 19 ;15(8). Epub 2023 Apr 19. PMID: 37111190 Abstract Title:  The Role of a Ketogenic Diet in the Treatment of Dementia in Type 2 Diabetes Mellitus. Abstract:  Type 2 diabetes mellitus (T2DM) shares a common molecular mechanism and underlying pathology with dementia, and studies indicate that dementia is widespread in people with T2DM. Currently, T2DM-induced cognitive impairment is characterized by altered insulin and cerebral glucose metabolism, leading to a shorter life span. Increasing evidence indicates that nutritional and metabolic treatments can possibly alleviate these issues, as there is a lack of efficient preventative and treatment methods. The ketogenic diet (KD) is a very high-fat, low-carbohydrate diet that induces ketosis in the body by producing a fasting-like effect, and neurons in the aged brain are protected from damage by ketone bodies. Moreover, the creation of ketone bodies may improve brain neuronal function, decrease inflammatory expression and reactive oxygen species (ROS) production, and restore neuronal metabolism. As a result, the KD has drawn attention as a potential treatment for neurological diseases, such as T2DM-induced dementia. This review aims to examine the role of the KD in the prevention of dementia risk in T2DM patients and to outline specific aspects of the neuroprotective effects of the KD, providing a rationale for the implementation of dietary interventions as a therapeutic strategy for T2DM-induced dementia in the future.

read more

PMID:  Psychiatr Pol. 2022 Dec 31 ;56(6):1345-1363. Epub 2022 Dec 31. PMID: 37098202 Abstract Title:  Ketogenic diet in therapy of bipolar affective disorder - case report and literature review. Abstract:  Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment does not bring satisfactory results, and a certain group of patients shows resistance to treatment. Therefore, other treatment methods are sought after, including a change in diet. The most promising nutrition model is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similarly to mood stabilisers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors and blocking of AMPA receptors by medium-chain fatty acids. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate the biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. However, there is a need for carefully planned studies, with an appropriate representative group, to verify the potential benefits and risks of introducing the ketogenic diet in patients with BPAD.

read more

PMID:  Nutrition. 2023 Jun ;110:111976. Epub 2023 Feb 12. PMID: 37060636 Abstract Title:  The ketogenic diet for Dravet syndrome: A multicenter retrospective study. Abstract:  OBJECTIVE: The ketogenic diet (KD) is one of the main treatments for drug-resistant epilepsy. However, there have been few multicenter reports on the use of the KD for the treatment of Dravet syndrome (DS). The aim of this study was to analyze the efficacy and safety of this approach based on a large number of multicenter cases.METHODS: This was a retrospective, multicenter cohort study from 14 centers in China. All patients were treated with the KD. We compared the effects of KD intervention time, age, and other factors.RESULTS: From March 2014 to March 2020, we treated 114 patients with DS with the KD. The male-to-female ratio was 67:47. The KD median initiation age was 3 y and 4 mo, and the median number of antiseizure medications (ASMs) was 2.4. KD therapy was the first choice for three patients. Exactly 10.5% of the patients started KD therapy after failure of the first ASM therapy, with 35.1% after failure of the second, 44.7% after the third, and 7% after the fourth or more. After KD therapy for 1, 3, 6, and 12 mo, the seizure-free rates were 14%, 32.5%, 30.7%, and 19.3%, respectively; KD efficacy (50% reduction in seizure frequency) were 57.9%, 76.3%, 59.6%, and 43%, respectively; the retention rates were 97.4%, 93%, 71.9%, and 46.5%, respectively; and the rates of adverse events were 25.2%, 19.9%, 11%, and 5.7%, respectively.CONCLUSIONS: Real-world, multicenter data analysis showed that the KD is effective for patients with DS and has a low incidence of side effects.

read more

PMID:  J Cell Mol Med. 2023 May ;27(10):1410-1422. Epub 2023 Apr 15. PMID: 37060584 Abstract Title:  A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression. Abstract:  The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with-hydroxybutyric acid (-HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in-HB-treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE-cadherin, Ang-1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration-induced increases in vascular paracellular permeability declined after MVECs were treated by-HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of-HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically,-HB decreased PES1-facilitated ubiquitination of VE-cadherin. The KD suppressed the diabetes-induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE-cadherin in type 2 diabetic mice.

read more

PMID:  Mol Nutr Food Res. 2023 Jun ;67(11):e2200711. Epub 2023 Apr 25. PMID: 37052374 Abstract Title:  Ketogenic Diet Alleviates Hypoglycemia-Induced Neuroinflammation via Modulation the Gut Microbiota in Mice. Abstract:  SCOPE: This study aims to investigate the role of gut microbiota regulation with ketogenic diet (KD) in hypoglycemia-induced neuroinflammation.METHODS AND RESULTS: Immunofluorescence staining and western blotting show that KD alleviates blood-brain barrier injury induced by hypoglycemia by increasing Podxl and zonula occludens-1 (ZO-1) levels. KD-fed mice show reduced brain edema by decreasing aquaporin-4 (AQP4) content and maintaining its polarized expression. 16S rRNA gene amplicon sequencing results show that KD reduces the Chao 1 index of gut microbiota-diversity, and significant separation is detected in the-diversity analysis between the control and KD-fed mice. KD increases the relative abundance of Firmicutes and Proteobacteria and decreases that of Bacteroidetes. Hypoglycemia can reduce SOD and GSH-PX levels while increasing TNF-, IL-1, and IL-6 mRNA levels in the brain tissues of mice. KD alleviates hypoglycemia-induced neuroinflammation by inhibiting microglia activation and TLR4/p38MAPK/NF-B signaling pathway. Importantly, antibiotic cocktail depletion of the gut microbiota weakens anti-inflammatory and antioxidation responses in KD-fed mice.CONCLUSION: Collectively, these findings suggest that KD alleviates hypoglycemia-induced brain injury via gut microbiota modulation, which may provide novel insights into the therapy for hypoglycemia.

read more

PMID:  J Alzheimers Dis. 2023 ;92(4):1173-1198. PMID: 37038820 Abstract Title:  Ketogenic Diet as a Promising Non-Drug Intervention for Alzheimer's Disease: Mechanisms and Clinical Implications. Abstract:  Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is mainly characterized by cognitive deficits. Although many studies have been devoted to developing disease-modifying therapies, there has been no effective therapy until now. However, dietary interventions may be a potential strategy to treat AD. The ketogenic diet (KD) is a high-fat and low-carbohydrate diet with adequate protein. KD increases the levels of ketone bodies, providing an alternative energy source when there is not sufficient energy supply because of impaired glucose metabolism. Accumulating preclinical and clinical studies have shown that a KD is beneficial to AD. The potential underlying mechanisms include improved mitochondrial function, optimization of gut microbiota composition, and reduced neuroinflammation and oxidative stress. The review provides an update on clinical and preclinical research on the effects of KD or medium-chain triglyceride supplementation on symptoms and pathophysiology in AD. We also detail the potential mechanisms of KD, involving amyloid and tau proteins, neuroinflammation, gut microbiota, oxidative stress, and brain metabolism. We aimed to determine the function of the KD in AD and outline important aspects of the mechanism, providing a reference for the implementation of the KD as a potential therapeutic strategy for AD.

read more

PMID:  Front Nutr. 2023 ;10:1127845. Epub 2023 Mar 23. PMID: 37032786 Abstract Title:  Ketogenic diet alleviates renal fibrosis in mice by enhancing fatty acid oxidation through the free fatty acid receptor 3 pathway. Abstract:  INTRODUCTION: The ketogenic diet (KD), as a dietary intervention, has gained importance in the treatment of solid organ structural remodeling, but its role in renal fibrosis has not been explored.METHODS: Male C57BL/6 mice were fed a normal diet or a KD for 6 weeks prior to unilateral ureteral obstruction (UUO), a well-establishedmodel of renal fibrosis in rodents. Seven days after UUO, serum and kidney samples were collected. Serum-hydroxybutyrate (-OHB) concentrations and renal fibrosis were assessed. NRK52E cells were treated with TGF1, a fibrosis-inducing cytokine, and with or without-OHB, a ketone body metabolized by KD, to investigate the mechanism underlying renal fibrosis.RESULTS: KD significantly enhanced serum-OHB levels in mice. Histological analysis revealed that KD alleviated structural destruction and fibrosis in obstructed kidneys and reduced the expression of the fibrosis protein markers-SMA, Col1a1, and Col3a1. Expression of the rate-limiting enzymes involved in fatty acid oxidation (FAO), Cpt1a and Acox1, significantly decreased after UUO and were upregulated by KD. However, the protective effect of KD was abolished by etomoxir (a Cpt1a inhibitor). Besides, our study observed that KD significantly suppressed UUO-induced macrophage infiltration and the expression of IL-6 in the obstructive kidneys. In NRK52E cells, fibrosis-related signaling was increased by TGF1 and reduced by-OHB.-OHB treatment restored the impaired expression of Cpt1a. The effect of-OHB was blocked by siRNA targeting free fatty acid receptor 3 (FFAR3), suggesting that-OHB might function through the FFAR3-dependent pathway.DISCUSSION: Our results highlight that KD attenuates UUO-induced renal fibrosis by enhancing FAO via the FFAR3-dependent pathway, which provides a promising dietary therapy for renal fibrosis.

read more

PMID:  Pediatr Neurol. 2023 Jun ;143:79-83. Epub 2023 Mar 9. PMID: 37031571 Abstract Title:  Ketogenic Diet Attenuates Refractory Epilepsy of Harel-Yoon Syndrome With ATAD3A Variants: A Case Report and Review of Literature. Abstract:  BACKGROUND: Harel-Yoon syndrome is a disease caused by variants in the ATAD3A gene, which manifest as global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. The aim of this study is to summarize the clinical and gene mutation characteristics of a child with refractory epilepsy caused by ATAD3A gene mutation.METHODS: The whole-exome sequencing combined with copy number variation analysis could help to understand the genetic diversity and underlying disease mechanisms in ATAD3A gene mutation.RESULTS: We report a Chinese boy with Harel-Yoon syndrome presenting with refractory epilepsy, hypotonia, global developmental delay, and congenital cataract through whole-exome sequencing. Genetic analysis showed a missense mutation, c.251T>C(p.Thr84Met) in the ATAD3A gene (NM_001170535.1). Further copy number variation analysis identified a novel heterozygous deletion on chromosome1p36.33, which spans ATAD3A exon 1 and 2 regions. Multiple antiepileptic drugs failed to control his seizures. Eventually, seizure was controlled through ketogenic diet (KD).CONCLUSION: Our case shows the potential diagnostic role of whole-exome sequencing in Harel-Yoon syndrome and expands the ATAD3A gene mutation spectrum. Multiple antiepileptic drugs failed to control refractory epilepsy in Harel-Yoon syndrome. The KD therapy may be effective for patients with refractory epilepsy who carry the ATAD3A variants.

read more

PMID:  J Nutr Biochem. 2023 Aug ;118:109335. Epub 2023 Apr 5. PMID: 37023933 Abstract Title:  Ketogenic diet alleviates renal interstitial fibrosis in UUO mice by regulating macrophage proliferation. Abstract:  The ketogenic diet (KD), a high-fat and extremely low-carbohydrate dietary regimen, has long been acknowledged as a highly beneficial dietary therapy for the treatment of intractable epilepsy throughout the last decade. Because of its significant therapeutic potential for a variety of ailments, KD is increasingly attracting study interest. In renal fibrosis, KD has received little attention. This study aimed to determine whether KD protects against renal fibrosis in unilateral ureteral obstruction (UUO) models and the possible mechanisms. The ketogenic diet, according to our findings, reduces UUO-induced kidney injury and fibrosis in mice. KD dramatically decreased the number of F4/80macrophages in kidneys. Next, immunofluorescence results revealed a reduction in the number of F4/80Ki67macrophages in the KD group. Furthermore, our study evaluated the impact of-hydroxybutyric acid (-OHB) in RAW246.7 macrophages in vitro. We found that-OHB inhibits macrophage proliferation. Mechanistically,-OHB inhibits macrophage proliferation may be via the FFAR3-AKT pathway. Collectively, our study indicated that KD ameliorates UUO-induced renal fibrosis by regulating macrophage proliferation. KD may be an effective therapy method for renal fibrosis due to its protective impact against the disorder.

read more

PMID:  Endocr Connect. 2023 Jul 1 ;12(7). Epub 2023 Jun 12. PMID: 37018117 Abstract Title:  Efficacy of very low-calorie ketogenic diet with the Pronokalmethod in obese women with polycystic ovary syndrome: a 16-week randomized controlled trial. Abstract:  OBJECTIVE: The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.DESIGN: Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokalmethod (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.RESULTS: BMI decreased significantly in both groups and to a major extent in the experimental group (-13.7% vs -5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (-11.4% vs -2.9%), BIA-measured body fat (-24.0% vs -8.1%), and free testosterone (-30.4% vs -12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (-23% vs -13.2%, P>0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P>0.05) at the end of the study, respectively.CONCLUSION: In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokalmethod was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.SIGNIFICANCE STATEMENTS: To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese...

PMID:  J Taibah Univ Med Sci. 2023 Oct ;18(5):1101-1107. Epub 2023 Mar 21. PMID: 37009396 Abstract Title:  Regulatory effects of ketogenic diet on the inflammatory response in obese Saudi women. Abstract:  OBJECTIVE: In recent years, the use of a ketogenic diet (KD) against obesity has gained popularity in KSA. This study was designed to determine the impact of KD on anthropometric indices and on the abnormal regulation of inflammatory activities in obese Saudi women. Moreover, we investigated the potential of beta-hydroxybutyrate (BHB) supplementation on the inhibition of pro-inflammatory activities.METHODS: We enrolled 31 Saudi women (aged, 35.3  8.4 years) with an average BMI of 33.96  4.44 kg/munderwent an 8-week KD (8KD) from January to March 2021. Changes in anthropometric measurements were collected at baseline and after 4-8 weeks of intervention. Compliance with the dietary regimen was monitored weekly by plasma BHB level.RESULTS: Twenty-nine females commenced the diets and 23 completed the study (a 79% completion rate). In comparison to pre-intervention, the 8KD resulted in a significant increase in the levels of plasma BHB (P 

read more

PMID:  Adv Exp Med Biol. 2023 ;1411:537-554. PMID: 36949325 Abstract Title:  Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders. Abstract:  The ketogenic diet, known as a low-carbohydrate, high-protein, and high-fat diet, drastically restrains the major source of energy for the body, forcing it to burn all excess fat through a process called ketosis-the breaking down of fat into ketone bodies. First suggested as a medical treatment for children suffering from epilepsy, this diet has gained increased popularity as a rapid weight loss strategy. Over the past few years, there have been numerous studies suggesting that the ketogenic diet may provide therapeutic effects for several psychiatric conditions such as mood- and anxiety-related disorders. However, despite significant progress in research, the mechanisms underlying its therapeutic effects remain largely unexplored and are yet to be fully elucidated. This chapter provides an in-depth overview of preclinical and clinical evidence supporting the use of a ketogenic diet in the management of mood and anxiety disorders and discusses its relationship with inflammatory processes and potential mechanisms of actions for its therapeutic effects.

read more

PMID:  Geroscience. 2023 Mar 18. Epub 2023 Mar 18. PMID: 36933143 Abstract Title:  Ketogenic diets initiated in late mid-life improved measures of spatial memory in male mice. Abstract:  Studies have shown ketogenic diets (KD) started from early middle-age improved health span and longevity in mice. KDs started later in life or administered intermittently may be more feasible and promote compliance. Therefore, this study sought to test if continuous or intermittent KDs started in late-middle-aged mice would improve cognition and motor function at advanced age. Eighteen-month-old male C57BL/6JN mice were assigned to an isocaloric control (CD), KD, or intermittent ketogenic (IKD, 3-day KD/week) diet. A panel of behavior tests were performed to assess cognitive and motor functions with aging. Y-maze alternation rate was higher for both IKD and KD mice at 23 months of age and for KD mice at 26 months indicating an improved spatial working memory. Twenty-six-month-old KD mice also showed better spatial learning memory in Barnes maze when compared to the CD. Improved grid wire hang performance was observed in aged IKD and KD versus CD mice indicating better muscle endurance under isometric contraction. A reduced level of circulating proinflammatory cytokines in aged KD (IL-6 and TNF-) and IKD (IL-6) mice may contribute to the phenotypic improvements observed with these interventions. This study demonstrates that when initiated at late-middle age, the KD improved measures of spatial memory and grid wire hang performance in aged male mice, with IKD showing results intermediate to the CD and KD groups.

read more

PMID:  Cureus. 2023 Feb ;15(2):e34526. Epub 2023 Feb 1. PMID: 36879703 Abstract Title:  Alleviation of Asthma Symptoms After Ketogenic Diet: A Case Report. Abstract:  Asthma is a chronic disease that affects the quality of life of patients, and asthma exacerbations are often a reason for hospitalization and activity limitations. Obesity has been linked to asthma as a risk and exacerbating factor. Evidence suggests that weight reduction has a positive effect on asthma control. However, there is also debate on the role of the ketogenic diet in asthma control. Here we present a case of asthma who reported markedly improved asthma after starting a ketogenic diet in the absence of any other lifestyle change. Over the four months on the ketogenic diet, the patient reported losing 20 kg of weight, reduction in blood pressure (without antihypertensives), and complete alleviation of asthma symptoms. This case report is important as the control of asthma after a ketogenic diet is not studied well in humans and therefore needs to be studied extensively.

read more

PMID:  Nutrients. 2023 Feb 6 ;15(4). Epub 2023 Feb 6. PMID: 36839183 Abstract Title:  The Effects of Eight Weeks' Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity. Abstract:  Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m) (from 33.846.55 to 30.896.38,

read more

PMID:  Int J Mol Sci. 2023 Feb 4 ;24(4). Epub 2023 Feb 4. PMID: 36834515 Abstract Title:  The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line. Abstract:  The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

read more

PMID:  Maedica (Bucur). 2022 Dec ;17(4):812-819. PMID: 36818275 Abstract Title:  Anti-Tumor Effect of the Ketogenic Diet against DMH-Induced Colon Cancer in Rats. Abstract:  Colon cancer is one of the most common malignancies with significant importance. Recent theories believe that cancers are metabolic diseases. Therefore, the role of metabolism in the prevention and treatment of cancer has been considered and the ketogenic diet is one example. In the present study, we evaluated the effect of the ketogenic diet and a high carbohydrate diet on tumor size and number, histopathology, and insulin level as well as VEGF level in 1, 2 dymethylhydrazine (DMH)-induced colon cancer in rats. Forty adult male Wistar rats were divided into four groups as follows: control, colon cancer, ketogenic diet, and high carbohydrate diet groups. For induction of colon cancer, 30 mg/kg of 1,2 DMH solution was injected subcutaneously twice a week for 24 weeks. The results showed that the ketogenic diet reduced tumor size, number, and histopathological changes as well as VEGF level (P

read more

PMID:  Neurotoxicology. 2023 May ;96:37-52. Epub 2023 Mar 23. PMID: 36965781 Abstract Title:  Vinpocetine prevents rotenone-induced Parkinson disease motor and non-motor symptoms through attenuation of oxidative stress, neuroinflammation and-synuclein expressions in rats. Abstract:  Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Epidemiological reports showed a significant association between environmental toxicants-induced gut dysbiosis and PD. Neuroinflammation, mitochondrial dysfunction and decreased cerebral blood flow are hallmarks of PD. This study sought to evaluate the protective ability of vinpocetine (VIN), a neuroprotectant, on rotenone (ROT) (mitochondrial complex I inhibitor) induced PD in rats. Sixty male Sprague Dawley rats were randomly divided into six groups (n = 10) and treated orally as follows; group 1: vehicle (10 ml/kg); group 2: rotenone (10 mg/kg) + vehicle; group 3-5: vinpocetine (5, 10 or 20 mg/kg) + rotenone (10 mg/kg), respectively, or group 6: vinpocetine 20 mg/kg before behavioural assay for motor symptoms (fore-limb hanging test and open field test) and non-motor symptoms (working memory and learning capabilities in Y-maze/Morris water maze tasks, anxiety in hole board test and gut motility with intestinal transit time). Following treatment for 28 days, biochemical assays and immunostaining was performed. We examined the effect of vinpocetine on rotenone-induced oxidative stress and inflammatory markers. The pretreatment of rats with vinpocetine reversed rotenone-induced locomotor deficit, motor incoordination, cognition deficits and gut dysfunction. In addition, rotenone-induced a significant increase in the level of interleukin-6 and tumor necrotic factor-, oxidative stress markers, cholinergic signalling, gut dysfunction and haematologic dysfunctions which were attenuated by vinpocetine administration. Immunostainings showed that rotenone-induced dopamine neuron loss, microglia reactivity, astrocytes activation, toll-like receptor 4 (TLR4) and-synuclein (SNCA) expressions which were attenuated by vinpocetine administration. Findings from this study revealed a neuroprotective effect of vinpocetine on rotenone-induced PD through anti-neuroinflammatory and antioxidant mechanisms.

read more

PMID:  Metabolites. 2023 Apr 21 ;13(4). Epub 2023 Apr 21. PMID: 37110238 Abstract Title:  Thymoquinone Antifungal Activity againstOral Isolates from Patients in Intensive Care Units-An In Vitro Study. Abstract:  The number ofspp. infections and drug resistance are dramatically increasing worldwide, particularly among immunosuppressed patients, and it is urgent to find novel compounds with antifungal activity. In this work, the antifungal and antibiofilm activity of thymoquinone (TQ), a key bioactive constituent of black cumin seedL., was evaluated againsta WHO 'high-priority' pathogen. Then, its effect on the expression ofandgenes (related to biofilm adhesion and development, respectively) were analyzed. Swab samples were taken from the oral cavity of 90 hospitalized patients in ICU wards, transferred to sterile falcon tubes, and cultured on Sabouraud Dextrose Agar (SDA) and Chromagarfor presumptive identification. Next, a 21-plex PCR was carried out for the confirmation of species level.isolates underwent antifungal drug susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), amphotericin B (AMB), and TQ according to the CLSI microdilution method (M27, A3/S4). Biofilm formation was measured by an MTT assay.andgene expression was assessed by real-time PCR. From the 90 swab samples, 40 isolates were identified aswith the 21-plex PCR. Most isolates were resistant to FLZ (= 29, 72.5%), whereas 12.5% and 5% were ITZ and AMB resistant, respectively. The minimum inhibitory concentration (MIC) of TQ againstwas 50g/mL. Importantly, TQ significantly inhibited the biofilm formation ofisolates, andgene expression was reduced significantly at MICconcentration of TQ. TQ seems to have some antifungal, antibiofilm (adhesion) effect onisolates, showing that this plant secondary metabolite is a promising agent to overcomeinfections, especially oral candidiasis.

read more

PMID:  Antioxidants (Basel). 2023 Apr 1 ;12(4). Epub 2023 Apr 1. PMID: 37107234 Abstract Title:  Radical Scavenging Is Not Involved in Thymoquinone-Induced Cell Protection in Neural Oxidative Stress Models. Abstract:  Thymoquinone (TQ), an active compound fromseeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to reassess the radical scavenging properties of TQ and explore a potential mode of action. The effects of TQ were studied in models with mitochondrial impairment and oxidative stress induced by rotenone in N18TG2 neuroblastoma cells and rotenone/MPPin primary mesencephalic cells. Tyrosine hydroxylase staining revealed that TQ significantly protected dopaminergic neurons and preserved their morphology under oxidative stress conditions. Quantification of the formation of superoxide radicals via electron paramagnetic resonance showed an initial increase in the level of superoxide radicals in the cell by TQ. Measurements in both cell culture systems revealed that the mitochondrial membrane potential was tendentially lowered, while ATP production was mostly unaffected. Additionally, the total ROS levels were unaltered. In mesencephalic cell culture under oxidative stress conditions, caspase-3 activity was decreased when TQ was administered. On the contrary, TQ itself tremendously increased the caspase-3 activity in the neuroblastoma cell line. Evaluation of the glutathione level revealed an increased level of total glutathione in both cell culture systems. Therefore, the enhanced resistance against oxidative stress in primary cell culture might be a consequence of a lowered caspase-3 activity combined with an increased pool of reduced glutathione. The described anti-cancer ability of TQ might be a result of the pro-apoptotic condition in neuroblastoma cells. Our study provides evidence that TQ has no direct scavenging effect on superoxide radicals.

read more

PMID:  Carcinogenesis. 2023 Apr 27. Epub 2023 Apr 27. PMID: 37105709 Abstract Title:  Thymoquinone inhibits lung cancer stem cell properties via triggering YAP degradation. Abstract:  Due to the characteristics of high recurrence and metastasis, it is still difficult to cure lung cancer. Cancer stem cells (CSCs) are a group of tumor cells with self-renewal ability and differentiation potential, which are responsible for lung cancer recurrence. Therefore, targeting CSCs may provide a new strategy for lung cancer treatment. Thymoquinone (TQ), the main active ingredient isolated from black seed oil, has shown significant anti-cancer effects in various cancers. However, the effects of TQ on lung cancer stem cells (LCSCs) has never been clarified. In the present study, we successfully separated and enriched lung cancer tumorsphere cells. Our data showed that TQ significantly inhibited the stem-like properties of LCSCs. In addition, we found TQ promoted Yes-associated protein (YAP) phosphorylation and ubiquitination, and the inhibitory effects of TQ on LCSCs could be enhanced by silencing YAP. Taken together, these results suggest that TQ, functions by targeting YAP, may be a potential therapeutic agent against lung cancer.

read more