Search

• The thermal and mechanical performance of the sCO2 solar cavity receiver were researched. • Large-diameter coiled tubes harm the receiver's thermal efficiency and safety. • Curvature of the coiled tube has the opposite effect on the thermal efficiency and safety of the receiver. • Cloud cover has a large influence on the temperature and stress of the solar receiver. • Solar receiver start-up early, the large flow rate produces low thermal stress. Solar thermal power systems rely on high-temperature cavity receivers. Guaranteeing the effective and secure operation of a receiver involves researching the impacts of various geometric parameters and operating conditions on its thermal performance and mechanical qualities. To examine the impacts of diameter, curvature, and various operating conditions on the thermal and mechanical performance of a receiver, a coupled thermal–mechanical model was created and assessed. The findings showed that the spiral coiled tube's thermal stress distribution is very nonuniform. Thermal efficiency declines and maximum stress rises from 74.9 MPa to 171.87 MPa as the diameter increases from 10 mm to 30 mm. The thermal efficiency rises when the curvature goes from 1/190 to 1/130, but the stress rises as well. The outlet temperature drops by 73.46 K after 5 min of cloud cover; cloud cover and startup conditions will result in rapid variations in stress and temperature on the coiled tube wall, endangering the receiver's safe function and shortening its lifespan. [ABSTRACT FROM AUTHOR]

Summary Objective To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. Methods This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months. Results Intra-abdominal fat content decreased in the GLP-1 group from baseline to 3 months (17,947 ± 5804; 13,717 ± 3628 mm 2 , P = 0.001, respectively), but was not significantly reduced in the control group (P = 0.197) and at 3 months post-treatment, it was significantly lower in the GLP-1 group than control group (P = 0.043). Glucose control, measured by HbA1c (GLP-1: 9.72 ± 1.38; 7.09 ± 0.60%, P < 0.001, 9.46 ± 1.25; 7.42 ± 0.84%, P < 0.001, respectively) and insulin resistance index LN(HOMA-IR) (GLP-1: 1.58 ± 0.40; 1.01 ± 0.33, P < 0.001, Control: 1.53 ± 0.57; 1.10 ± 0.33, P = 0.003, respectively) significantly improved in both groups with no significant difference between them. TNF-α, IL-6, and leptin were lower and adiponectin levels higher in the GLP-1 group at 3 months compared with baseline (all P < 0.05), but not significantly changed in the control group. TNF-α, IL-6 and leptin levels were similar between groups. Adiponectin level was higher in the GLP-1 group than the control group at 3 months (P = 0.025). Conclusion Combined exenatide/metformin reduced intra-abdominal fat content, and enhanced insulin resistance and inflammatory status in patients with obesity and type-2 diabetes, representing a novel treatment regimen. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study were to determine the following: the status of glycemic control in patients with type 2 diabetes mellitus (DM) at primary, secondary, and tertiary hospitals in the Jiangsu province of China; and the factors associated with achieving glyce-mic targets. Methods: This study, in which patients were enrolled from July 20 to 31, 2009, at 56 diabetes centers, used a multiple-stage, stratified sampling method to select a representative sample of the population with DM in Jiangsu. The sampling process was stratified by geographic and demographic regions, and by the outpatient numbers in the hospitals. A primary hospital was defined as a community medical institution that provided primary health services; a secondary hospital was a local medical institution that provided comprehensive health services; and a tertiary hospital was a regional medical institution that provided comprehensive and specialist health services. In primary hospitals, patients with DM were treated by general physicians; at secondary and tertiary hospitals, they were seen by specialists. Also, primary and tertiary hospitals treated patients in cities, whereas secondary hospitals treated patients from towns or rural areas. Patients with a medical history of type 2 DM for >6 months and registration at each diabetes center for ≥6 months, and who were residents of Jiangsu province, were recruited. During the patient enrollment visit, information about DM complications and comor-bidities, as well as DM management, was obtained by retrospectively reviewing medical records; basic patient data (eg, date of birth, sex, weight, height) were obtained by patient interview. Blood samples were collected for assessment of glycosylated hemoglobin (HbA1c) at a central laboratory. Results: Of 3046 sampled subjects, the analysis was performed in 2966 subjects with complete data. The mean (SD) HbA1c value for analyzed patients was 7.2% (1.6%). The proportion of patients with tight glycemic control was 40.2% (1193/2966) when a threshold of HbA1c <6.5% was used, and 56.1% (1665/2966) when a threshold of HbA1c <7.0% was used. Compared with patients who had inadequate glycemic control, those with tight control were younger (P < 0.001), had shorter duration of DM (P < 0.001), had lower body mass index (BMI) (P = 0.005 for HbA1c <6.5% and P = 0.01 for HbA1c <7.0%), had more education (P < 0.001) and income (P = 0.003 for HbA1c <6.5% and P = 0.008 for HbA1c <7.0%), were more likely to monitor their glucose (P = NS for HbA1c <6.5% and P = 0.043 for HbA1c <7.0%) and attend DM education (P = 0.027 for HbA1c <6.5% and P = 0.002 for HbA1c <7.0%) at least once a month, and were more likely to receive oral antidiabetic drugs (OADs) (P < 0.001). Age, BMI, and DM duration did not differ significantly between hospital types. Compared with primary (36.2%) and secondary hospitals (36.5%), tertiary hospitals (42.2%) had more patients with HbA1c <6.5% (P = 0.043); tertiary hospitals also had more patients with once-monthly glucose self-monitoring (P = 0.001), patients with higher income (P < 0.001) and education (P < 0.001), and those who were more likely to use ≥2 OADs or insulin with OADs (P < 0.001). Conclusion: The overall status of glycemic control was unsatisfactory during the study period, although patients at tertiary hospitals appeared to have better control than those at primary or secondary hospitals. [Copyright &y& Elsevier]

• This is the first description of circulating bile acid profiles in patients with PCOS. • Serum conjugated primary bile acids are remarkably increased in PCOS patients. • Conjugated primary bile acids are positively associated with serum total testosterone and androstenedione levels in PCOS. Polycystic ovary syndrome (PCOS) is a common metabolic disorder with hyperandrogenism as the core pathophysiologic feature. Increased bile acids and altered bile acid pool composition have been implicated in the pathogenesis of several metabolic diseases. Thus, this study aimed to clarify the specific alterations in circulating bile acids in patients with PCOS and investigate its associations with hyperandrogenism. We recruited 37 patients with PCOS and 35 age- and BMI-matched control subjects. Serum bile acids and androgen profiles were assessed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Compared with control subjects, glycine- and taurine-conjugated primary bile acids were significantly elevated in patients with PCOS (P = 0.001 and P < 0.001). In addition, these conjugated primary bile acids were significantly and positively associated with serum concentrations of total testosterone and androstenedione in the PCOS group. In conclusion, increased circulating conjugated primary bile acids are positively associated with hyperandrogenism in women with PCOS. Further studies are warranted to explore the underlying mechanism. [ABSTRACT FROM AUTHOR]

Adrenal venous sampling (AVS) is the reference standard for primary aldosteronism (PA) subtyping. Cortisol is widely used to assess the success of selective AVS, but it is not always reliable. The aim of the present study was to investigate the usefulness of adrenal androgens, compared to cortisol, in assessing the selectivity of AVS. We consecutively recruited 37 patients with PA undergoing AVS. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. We collected two baseline blood samples from 10 patients with a 15-min interval between time-15 (t-15) and time 0 (t0) to measure the variability in the levels of the tested hormones over time. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal and peripheral venous (AV and PV, respectively) samples. The selectivity index (SI) values for androstenedione and DHEA were on average 3.0- and 2.0-fold higher, respectively, than those for cortisol, respectively (P < 0.05). However, the SI for DHEAS was 5.0-fold lower than the SI for cortisol (P < 0.05). Plasma androstenedione and DHEA concentrations positively correlated with cortisol and aldosterone concentrations in AV samples (P < 0.01). Compared to cortisol, the variation ratio of AV androstenedione and DHEA decreased from t-15 to t0 (0.23 and 0.43 vs. 0.52; P = 0.001 and P = 0.061, respectively). Using receiver operating characteristic curves, an SI ≥ 3 for androstenedione or DHEA provided optimal sensitivity and specificity in AVS. Given the much larger AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors cosecreting cortisol and aldosterone. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO), besides its stimulatory effect on erythropoiesis, is beneficial to insulin resistance and obesity. However, its role in hepatic steatosis remains unexplored. Activating autophagy seems a promising mechanism for improving fatty liver disease. The present study investigated the role of EPO in alleviating hepatic steatosis and sought to determine whether its function is mediated by the activation of autophagy. Here, we show that EPO decreased hepatic lipid content significantly in vivo and in vitro . Furthermore, EPO/EPO receptor (EPOR) signalling induced autophagy activation in hepatocytes as indicated by western blot assay, transmission electron microscopy, and confocal microscopy. In addition, EPO increased the co-localization of autophagosomes and cellular lipids as shown by double labelling of the autophagy marker light chain microtubule-associated protein 3 (LC3) and lipids. Importantly, suppression of autophagy by an inhibitor or small interfering RNA (siRNA) abolished the EPO-mediated alleviation hepatic steatosis in vitro . Furthermore, EPO up-regulated sirtuin 1 (SIRT1) expression, and siRNA-mediated SIRT1 silencing abrogated the EPO-induced increases in LC3 protein and deacetylation levels, thereby preventing the alleviation of hepatic steatosis. Taken together, this study revealed a new mechanism wherein EPO alleviates hepatic steatosis by activating autophagy via SIRT1-dependent deacetylation of LC3. This finding might have therapeutic value in the treatment of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice. In vivo, male C57BL/6 mice received HFD (60% of total calories) for 12 weeks, randomized and treated orally with vehicle saline or silymarin (30 mg/kg body weight/d) for 4 weeks. In vitro, human proximal tubular epithelial cells (HK2) were exposed to 300 μM palmitic acid (PA) for 36 h followed by silymarin administration at different concentrations. The administration of silymarin significantly ameliorated HFD induced glucose metabolic disorders, oxidative stress and pathological alterations in the kidney. Silymarin significantly mitigated renal lipid accumulation, fatty acid β-oxidation and mitochondrial biogenesis in HFD mice and PA treated HK2 cells. Furthermore, silymarin partly restored mitochondrial membrane potential of HK2 cells after PA exposure. In conclusion, silymarin can improve oxidative stress and preserve mitochondrial dysfunction in the kidney, potentially via preventing accumulation of renal lipids and fatty acid β-oxidation. [ABSTRACT FROM AUTHOR]

Background Structural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated. Methods Next generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding. Results We found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated ‘functionally relevant phylotypes’. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin. Conclusion These results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats. General significance Compounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a major cause of chronic and end-stage renal disease in diabetic patients. Here, we investigated protective effects and possible mechanisms of dapagliflozin on renal injury in diabetic mice. DKD mice were established by high fat diet (HFD) feeding. Half of DKD mice were randomly assigned to receive dapagliflozin treatment (200 μg/day) for 8 weeks. Renal lipid droplets, fibrosis, oxidative and endoplasmic reticulum stress were evaluated. Glomerular injury was assessed by immunohistochemistry and transmission electron microscopy. Dapagliflozin led to marked inhibition of ROS levels and endoplasmic reticulum stress in diabetic mice. HFD-induced loss of Podocin and Nephrin, and impaired podocytes were also improved with the treatment. Importantly, overexpression of HMGB1 and suppressed autophagy in the kidney were partly reversed by dapagliflozin. Therefore, we speculate that protective effects of dapagliflozin on DKD may be associated with suppression of HMGB1 expression and restoration of autophagy in the kidney. [Display omitted] • Dapagliflozin improved renal fibrosis and urinary microalbumin in diabetic mice. • High fat diet-induced renal oxidative stress and endoplasmic reticulum stress were mitigated by Dapagliflozin. • Overexpression of renal HMGB1 and suppressed autophagy in diabetc mice were reversed with dapagliflozin treatment. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The present study aimed to investigate the pathophysiological role of SGK1 in the development of metabolic syndrome by investigating the expression and regulation of serum and glucocorticoid-inducible kinase 1 (SGK1) in adipose tissues in obesity and diabetes. Methods: SGK1 expression in adipose tissue was investigated using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. SGK1 regulation in differentiated 3T3-L1 adipocytes by metabolic-related factors was assessed using Northern blot analysis. Humans with obesity and type 2 diabetes and KKAy and db/db mice were used to evaluate SGK1 expression in the adipose tissue of subjects with obesity and diabetes using quantitative real-time PCR and Western blot analysis. Results: SGK1 was expressed in white adipose tissue as shown by mRNA and protein levels. Aldosterone and glucocorticoids stimulated SGK1 expression in a time- and dose-dependent manner, whereas PPAR-γ agonists inhibited SGK1 expression in differentiated 3T3-L1 adipocytes. Furthermore, SGK1 mRNA and protein were overexpressed in the adipose tissue of mice and humans with obesity and type 2 diabetes. Conclusion: Aldosterone, glucocorticoids and other factors contribute to excessive SGK1 expression in adipose tissue. This excessive SGK1 expression may be related to adipose tissue dysfunction, which may contribute to the development of obesity, diabetes and metabolic syndrome. [Copyright &y& Elsevier]

Abstract: Reactive oxygen species are considered to play a role in the development of type 2 diabetes mellitus (T2DM) and its complications. 8-Oxoguanine, which is one of the major oxidation base lesions produced by reactive oxygen species, may cause G:C to T:A transversion mutations because it can mispair with adenine. hMTH1 (human mutT homolog 1), hOGG1 (human 8-oxoguanine glycosylase 1) and MUTYH (human mutY homolog) genes constitute the 8-oxoG repair pathway. In this study, we screened for the polymorphism variants Val83Met (c.247G>A, rs4866) in hMTH1; c.-53G>C (rs56387615), c.-23A>G (rs1801129) and c.-18G>T (rs1801126) in the 5′-UTR of hOGG1; and AluYb8 insertion in MUTYH (AluYb8MUTYH, rs10527342) and investigated their synergistic effect on the risk of T2DM in the Chinese population. The genotypes were determined by electrophoresis, a high-resolution melting technique and sequencing of PCR products. Our results showed that the c.247G>A variant in the hMTH1 gene increased the risk of T2DM in >55years of age groups (OR=1.579; 95%CI: 1.029–2.421). The set of c.-53G>C, c.-23A>G and c.-18G>T variants detected in the 5′-UTR of the hOGG1 gene and the AluYb8 insertion in the MUTYH gene were each associated with an increased risk of T2DM (OR=1.507, 95%CI: 1.122–2.024; OR=1.229, 95%CI: 1.030–1.466, respectively). Combined analysis of the variations among the three genes suggested that the c.247G>A variant in hMTH1 combined with AluYb8MUTYH variant had a synergistic effect on increasing the risk of T2DM (OR=1.635; 95%CI: 1.147–2.330). This synergy was also observed between the variants in the 5′-UTR of the hOGG1 and the AluYb8MUTYH variant (OR=1.804; 95%CI: 1.254–2.595). Our results suggest, for the first time, the combined effects of AluYb8MUTYH with either hMTH1 c.247G>A or variants in the 5′-UTR of the hOGG1 on the risk of T2DM. [Copyright &y& Elsevier]

Abstract: Several studies have been conducted to examine the association between PPAR-γ2 Pro12Ala polymorphism and polycystic ovary syndrome (PCOS), but the results remain inconsistent. To make a more precise estimation of the relationship, a meta-analysis was performed. In the current meta-analysis, a total of 17 case–control studies, including 2176 cases and 2373 controls, were selected. Odds ratios (ORs) and 95% confidence intervals (CIs) for Pro/Ala+Ala/Ala versus Pro/Pro genotype in all population and different nationality groups, and homeostasis model assessment-insulin resistance (HOMA-IR) of different genotype were evaluated. In the overall analysis, significant association between PPAR-γ2 Pro12Ala polymorphism and reduced risk of PCOS was observed (OR=0.75; 95%CI, 0.62–0.91; p =0.003). Stratified analysis showed that significantly strong association was presented only in Europeans (OR=0.74; 95%CI, 0.60–0.90; p =0.003), but not in Asians (OR=0.86; 95%CI, 0.51–1.43; p =0.56). Additionally, carrying the Ala12 allele was not associated with HOMA-IR in PCOS patients (OR=−0.29; 95%CI, −0.82–0.24; p =0.29). This meta-analysis supported that PPAR-γ2 Pro12Ala polymorphism was capable of reducing polycystic ovary syndrome risk in Europeans, but not in Asians. [Copyright &y& Elsevier]

Abstract: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Because oxidative stress may contribute to increased diabetes risk, the common variant of the MUTYH gene (AluYb8MUTYH) was investigated for its possible role in type 2 diabetes mellitus (T2DM). A total of 565 T2DM patients and 565 healthy subjects from China were enrolled in a case-control study. The distribution of AluYb8MUTYH differed in diabetic patients from controls, with a moderately increased percentage of the mutant allele (P) (44.7% versus 40.3%, P =0.033, OR=1.199). However, this distribution was similar between the diabetic early-onset and late-onset subgroups. Another 66 T2DM patients were further evaluated for 8-hydroxy-2′deoxyguanosine (8-OHdG) levels in leukocytic DNA. The average value of 8-OHdG/106 dG was 10.4 in patients with the wild-type genotype, 15.9 in heterozygotes, and 22.3 in homozygotes with the variation (P <0.001, compared with the wild-type). Therefore, the AluYb8MUTYH polymorphism could be a novel genetic risk factor for T2DM, and accumulated 8-OHdG could contribute to this disease. [Copyright &y& Elsevier]

Abstract: hOGG1 protein excises the 8-hydroxy-2′-deoxyguanine (8-OHdG) which is associated with type 2 diabetes mellitus (T2DM). Our aim of this work is to explore whether the polymorphisms of hOGG1 gene are associated with T2DM. We screened the polymorphisms in the 5′-UTR (c.−18G>T, c.−23A>G, c.−45G>A and c.−53G>C) and c.977C>G (Ser326Cys) in exon 7 of hOGG1 gene. A case–control study indicated that c.−23A/G heterozygote was markedly associated with diabetes (P =0.004, OR=2.648, 95%CI=1.355–5.176) and with an increased level of C-peptide (705.00 versus 545.91pmol/L, P =0.044). Furthermore, a significantly increased risk of T2DM was observed in the subjects carrying heterozygous variant of c.−23A>G and homozygous mutation of Ser326Cys (OR=3.684, 95%CI=1.400–9.697). The promoter activity of the variant allele c.−23G decreased 30–40% in Hela and HEK293 cell lines. In conclusion, the variant c.−23A>G of hOGG1 gene could decrease the gene promoter activity and was a risk factor for T2DM. [Copyright &y& Elsevier]

Abstract: We describe a common mutation of the MYH gene, which is involved in the repair of oxidative damage to DNA, and its relationship to age, levels of 8-OHdG, and circulating levels of interleukin-1. We studied 1146 “healthy” and 562 unselected Chinese subjects. We observed a reverse insertion of the AluYb8 sequence (AluYb8MYH) to be homozygous in ∼25.8% of the healthy Chinese population age 20–29 years, with the incidence of homozygosity decreasing to 15.7% by age 50–59 years. Because subjects were selected on the basis of absence of disease during medical screening, this suggests that homozygosity for this gene has a marked impact on the development of age-related or chronic diseases or mortality. Because the MYH gene is involved in DNA repair we assessed whether homozygous carriage of this gene was associated with increased levels of 8-OHdG in the leukocytic DNA of carriers. The level of 8-OHdG increased from 3.8 8-OHdG/106 dG in wild-type carriers to 10.8 8-OHdG/106 dG in homozygous carriers, suggesting that the presence of the mutation was associated with impaired DNA repair. Because this mutation might be associated with the increased development of age-related or chronic disease and inflammation, we also measured plasma concentrations of interleukin-1, which increases with aging and chronic disease. We observed a highly significant increase in plasma interleukin-1 in patients homozygous for the AluYb8 insertion in the MYH gene consistent with accelerated aging or development of undiagnosed disease in homozygous subjects. Screening for this genetic variation may have predictive value in assessing potential longevity of subjects in China, as well as in the Western world. [Copyright &y& Elsevier]

Obesity-induced insulin resistance is the principal cause of type 2 diabetes worldwide. The use of natural products for the treatment of diabetes is increasingly attracting attention. Silymarin (SLM) is a flavonolignan compound that has been shown to have promise for the treatment of diabetes. In the present study, we aimed to investigate the mechanisms underlying its therapeutic effects. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and then orally administered SLM (30 mg/kg) daily for 1 month. The effects of SLM were also investigated in HepG2 cells that had been rendered insulin resistant by palmitic acid (PA) treatment. SLM ameliorated the dyslipidemia, hepatic steatosis, and insulin resistance of the HFD-fed mice. HFD-feeding and PA treatment reduced the expression of sirtuin-1 (SIRT1) in the livers of the mice and in HepG2 cells, respectively. SLM increased the phosphorylation of AKT and FOXO1, and reduced the level of FOXO1 acetylation in PA-treated cells. However, SIRT1 knockdown by RNA interference reduced these effects of SLM. Moreover, the results of molecular dynamic simulation and in vitro activity assays indicated that SLM may directly bind to SIRT1 and increase its enzymatic activity. These findings suggest that hepatic SIRT1 may be an important pharmacological target of SLM and mediate effects on insulin resistance and gluconeogenesis, which may underlie its anti-diabetic activity. [Display omitted] • Silymarin ameliorates the insulin resistance of the HFD-fed mice. • SIRT1 expression in hepatocytes is increased by silymarin administration. • Silymarin may directly bind to SIRT1 and increase its enzymatic activity. • Post-translational modifications of FOXO1 mediate the beneficial effects of silymarin. [ABSTRACT FROM AUTHOR]