Lili Yang

With heart disease being the leading cause of death worldwide, cost‐effective therapies supporting healthy cardiac function are highly needed. Oxidative stress and hypercholesterolemia are risk factors in the pathogenesis of cardiac dysfunction. Many nutraceutical compositions containing Coenzyme Q ₁₀ , resveratrol, extracts of Ginkgo biloba leaf, Garlic Bulb, red rice yeast, and bovine colostrum appear to have the potential to improve cardiac function. In the present study, we aimed to evaluate whether a new combination containing the abovementioned nutraceuticals (Cardio) is protective against damage to cardiac function. In this study, C57BL/6J mice were divided into groups of control, high‐fat‐cholesterol diet fed (HFHC), and HFHC diet + Cardio (Cardio group), and fed for 16 weeks. Parameters of plasma lipid levels, inflammation, oxidative damage, and cardiac function were measured. Cardio treatment significantly inhibited hypercholesterolemia, reduced levels of cardiac damage markers including LDH and CK, improved cardiac function, and reduced HFHC diet‐induced increased levels of inflammatory cytokines including TNF‐α and IL‐1β. Our data showed that Cardio has a protective effect on cardiac dysfunction probably by ameliorating hypercholesterolemia, inflammation, and oxidative stress.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health concern. Soy protein isolate (SPI) is a plant-derived protein with high nutritional value and has shown promising effects in regulating lipid metabolism and inflammation. Objectives: This study aimed to investigate the effects of an α-subunit-deficient SPI (α-lack-SPI) on MASLD and the underlying molecular mechanisms. Methods: Rats were fed with a high-fat, high-cholesterol diet (HFD) to induce MASLD. Results: The results showed that α-lack-SPI significantly reduced the levels of hepatic TG and TC, serum ALT, AST, TC, and LDL-C, and increased serum HDL-C in rats with HFD-induced MASLD. α-lack-SPI significantly attenuated hepatic steatosis and hepatocyte ballooning revealed by histopathological analysis. Meanwhile, α-lack-SPI markedly downregulated the mRNA expressions of Srebf1, Acaca, Fasn, Pcsk9, and Hmgcr, while significantly upregulating Pparα. Additionally, α-lack-SPI treatment significantly reduced the mRNA expressions of hepatic pro-inflammatory cytokines (Tnf-α, Il-1β, Il6), chemokine (Ccl2), and inflammasome component (Nlrp3), as well as the protein expression of COX-2. Conclusions: In conclusion, α-lack-SPI alleviated MASLD in HFD-fed rats probably via improving hepatic lipid metabolism and mitigating hepatic inflammation. These findings indicate that α-lack-SPI may serve as a promising nutritional intervention for MASLD management.

Brown adipose tissue-derived eNAMPT is a key upstream driver of NLRP3 inflammasome activation in alcoholic liver injury. Dietary nicotinamide riboside is a promising nutritional intervention for alcoholic liver disease by targeting eNAMPT.

The association of niacin intake with dyslipidemia remains uncertain. The aim of this study was to explore the association between dietary niacin intake and the prevalence of dyslipidemia among adults in the United States (US). Data were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2014. The exposure variable was dietary niacin intake, measured through 24-hour dietary recall interviews and treated as both a continuous and categorical variable. Dyslipidemia, defined by diagnostic criteria, was the outcome. Logistic regression and restricted cubic spline models were applied to examine the association between niacin intake and the prevalence of dyslipidemia. Among the 19,275 individuals, the prevalence of dyslipidemia was 78.8%. Compared with individuals with lower niacin consumption Q1 (≤15.9 mg/day), the adjusted OR values for dietary niacin intake and dyslipidemia in Q3 (22.7-31.8 mg/day) and Q4 (≥31.8 mg/day) were 0.78 (95% CI: 0.64-0.94, p = 0.011) and 0.77 (95% CI: 0.61-0.98, p = 0.033), respectively. The association between niacin intake and the prevalence of dyslipidemia followed a L-shaped dose-response curve (non-linear, p = 0.009). Participants with a niacin intake of <22.3 mg/day exhibited an OR of 0.98 (95% CI: 0.96-0.99, p = 0.040) for dyslipidemia. In subgroup analyses, the inverse associations of niacin intake with the prevalence of dyslipidemia remained robust only in female. In the 2005-2014 NHANES popu-lation, higher levels of niacin intake were associated with decreased odds of dyslipidemia overall. Further studies are needed to examine the potential protective effects of niacin on dyslipidemia risk.

Introduction: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD).Materials and Methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores.Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered.Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.

Background: Targeting mitochondria and protecting the mitochondrial function of CD8⁺ T cells are crucial for enhancing the clinical efficacy of cancer immunotherapy. Objectives: In this study, our objective was to investigate the potential of nicotinamide riboside (NR) in preserving the mitochondrial function of CD8⁺ T cells and mitigating their exhaustion. Methods: We established two in vitro models to induce CD8⁺ T cell exhaustion either by tumor cell-conditioned medium (TCM) or by continuous stimulation with OVA_(257–264) peptide. CD8⁺ T cells were treated in the absence/presence of NR. Results: Our findings demonstrated that NR supplementation effectively inhibited CD8⁺ T cell exhaustion and preserved mitochondrial function in both models. Moreover, apoptosis of CD8⁺ T cells was reduced after NR treatment. Western blot data indicated that NR treatment upregulated Silent information regulator 1 (SirT1) expression. Further inhibition of Sirt1 activity using EX527 uncovered that the inhibitory effect of NR on CD8⁺ T cell exhaustion and its protective effect on mitochondria were attenuated. Conclusions: In conclusion, our results indicate that NR supplementation attenuates CD8⁺ T cell exhaustion, and its underlying mechanism is associated with increased mitochondrial function regulated by the SirT1 pathway. Our research provides evidence that NR may assist in enhancing the clinical efficacy of immunotherapy.