Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial.

BACKGROUND: Our previous studies showed that curcumin prevented hepatic steatosis in animal models. OBJECTIVES: This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). METHODS: In a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. RESULTS: Curcumin consumption significantly reduced CAP value compared with placebo (-17.5 dB/m; 95% confidence interval [CI]: -27.1, -7.8 dB/m; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95% CI: -4.4, -0.8 kg; P < 0.001) and BMI (-1.0 kg/m2; 95% CI: -2.0, -0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95% CI: -0.20, -0.04 mmol/L; P = 0.004), triglycerides (-0.29 mmol/L; 95% CI: -0.41, -0.14 mmol/L; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95% CI: -0.12, -0.01 mmol/L; P = 0.038), hemoglobin A1c (-0.06%; 95% CI: -0.33, -0.01%; P = 0.019), and insulin (-4.94 µU/L; 95% CI: -9.73, -0.15 µU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). CONCLUSIONS: Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn as ChiCTR2200058052.

Risk of Systemic Inflammatory Response Syndrome Following Preoperative Glucocorticoids Administration in Patients After Percutaneous Nephrolithotomy: A Retrospective Cohort Study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. METHODS: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). CONCLUSION: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.

Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

[This corrects the article DOI: 10.1371/journal.ppat.1011480.].

Anti-Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study.

HSV-1 is a common infection that can cause cold sores. In this study, the anti-HSV-1 virus activity of three series compounds A1-A9, B1-B12, C1-C22 was screened by MTT assay, qRT-PCR assay, Western blot assay and viruses' plaque assays. The results of MTT assay disclosed that phloroglucinol derivatives C2 and C3 effectively inhibited the death of HSV-1 infected vero cells with the CC50 values of C2 and C3 were 72.64 µmol/L and 32.62 µmol/L in HaCaT cells, 137.6 µmol/L and 48.55 µmol/L in Hela cells. The IC50 values of C3 in vero cells and Hela cells were 19.26 µmol/L and 22.98 µmol/L, respectively. In the qRT-PCR experiments, it showed that C2 and C3 effectively reduced the synthesis of HSV-1 early viral gene VP16 and late viral gene gD. The Western blot results showed that both C2 and C3 inhibited the expression of HSV-1 gD protein in a concentration-dependent manner. Lastly, viruses' plaque assay results showed that C2 and C3 inhibited the production of HSV-1 progeny virus in Hela cells and HaCaT cells in a concentration-dependent manner. Taken together, these results suggest that C2 and C3 are promising candidate that warrants further attention in the development of anti-HSV-1 drugs.

TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2.

Ubiquitination is an important protein modification that regulates diverse biological processes, including CD4+ T cell differentiation and functions. However, the function of most E3 ubiquitin ligases in CD4+ T cell differentiation and CD4+ T cell-mediated pathological diseases remains unclear. In this study, we find that tripartite motif-containing motif 11 (TRIM11) specifically negatively regulates regulatory T (Treg) cell differentiation in CD4+ T cells and promotes autoimmune disease development in an AIM2-dependent manner. Mechanistically, TRIM11 interacts with absent in melanoma 2 (AIM2) and promotes the selective autophagic degradation of AIM2 by inducing AIM2 ubiquitination and binding to p62 in CD4+ T cells. AIM2 attenuates AKT and FOXO1 phosphorylation, MYC signaling, and glycolysis, thereby promoting the stability of Treg cells during experimental autoimmune encephalomyelitis (EAE). Our findings suggest that TRIM11 serves as a potential target for immunotherapeutic intervention for dysregulated immune responses that lead to autoimmunity and cancers.

Microscopic dissolution process of cellulose in alkaline aqueous solvents and its application in CNFs extraction - Investigating temperature as a variable.

The target of this study is to gain a deeper understanding of the micro-dissolution process of cellulose in alkaline aqueous solutions and to develop a novel method for extracting cellulose nanofibrils (CNFs). Herein, the dissolution process of cellulose in alkaline aqueous solutions will be controlled by varying the temperature, and the undissolved cellulose will be analyzed to reveal the microscopic dissolution process of cellulose, and a novel process for extracting cellulose nanofibrils (CNFs) will be developed based on the findings. The crystalline structure of cellulose was gradually disrupted as the dissolution progressed, and the crystal form of cellulose changed gradually from cellulose I to cellulose II during the dissolution process, while all undissolved cellulose crystals remained as cellulose I. Cellulose, after its structure is disrupted during the dissolution process, will inevitably decompose into CNFs, and the microscopic dissolution process of cellulose follows a "top-down" dissolution sequence. The CNFs extraction method developed in this study can extract CNFs with high yield (>60 %) in a stable manner, as well as narrow particle size distribution, high crystallinity (>77 %), and good thermal stability. This study enhances the comprehension of the dissolution process of cellulose and paves a possible way for industrialization of CNFs production.

USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

Deubiquitinating enzymes (DUBs) regulate antiviral immune response through targeting DNA sensor signaling pathway members. As one of the DNA sensors, interferon (IFN)-γ inducible protein 16 (IFI16) play a major role in response to virus infections through activating the canonical STING/TBK-1/IRF3 signaling pathway. Only a few studies discuss the function of DUBs in IFI16-mediated antiviral response. Ubiquitin-specific protease 12 (USP12), which is one of the major members of the USP family, participates in various biological functions. However, whether USP12 regulates the nucleic acid sensor to modulate antiviral immune responses has not yet been elucidated. In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-ß, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs). Moreover, USP12 deficiency increased HSV-1 replication and host susceptibility to HSV-1 infection. Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling. Overall, our findings demonstrate an essential role of USP12 in DNA-sensing signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

Curcumin protects against high-fat diet-induced nonalcoholic simple fatty liver by inhibiting intestinal and hepatic NPC1L1 expression via down-regulation of SREBP-2/HNF1α pathway in hamsters.

Niemann-pick C1-like 1 (NPC1L1) mediates cholesterol absorption and plays a key role in the pathogenesis of nonalcoholic simple fatty liver (NASFL). Our previous study showed that curcumin reduced NPC1L1 expression and cholesterol absorption in Caco-2 cells. This study aimed to investigate whether curcumin could inhibit intestinal and hepatic NPC1L1 expression through suppressing sterol regulatory element binding protein-2 (SREBP-2) / hepatocyte nuclear factor 1α (HNF1α) pathway, then exert anti-NASFL effects. Six-week hamsters were fed high-fat diet (HFD) with or without 0.1% curcumin for 12 weeks. Curcumin supplementation lowered blood total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol levels (20.2%, 48.7%, and 36.5%), and reduced liver TC and TG contents (26.1% and 26.5%). Oil Red O staining demonstrated that curcumin significantly alleviated HFD-induced liver fat accumulation and hepatic steatosis, which was accompanied by reduced intestinal and hepatic NPC1L1, SREBP-2 and HNF1α expression (P < .05) and increased fecal neutral sterol excretion (114.5%). Furthermore, curcumin decreased cholesterol absorption in Caco-2 cells and HepG2 cells (49.2 % and 52.7 %). The inhibitory effects of curcumin on NPC1L1 expression and cholesterol absorption could be prevented by blockade of the SREBP-2 and HNF1α pathway. These findings indicated that curcumin protected against HFD-induced NASFL by inhibiting intestinal and hepatic NPC1L1 expression via down-regulation of SREBP-2/HNF1α pathway, thus reducing intestinal cholesterol absorption and hepatic biliary cholesterol reabsorption, consequently alleviating liver cholesterol accumulation and steatosis. Our study provides evidence for curcumin as a potential nutritional therapy for NASFL by regulating NPC1L1 and enterohepatic circulation of cholesterol.

Bisphenol A induced hepatic steatosis by disturbing bile acid metabolism and FXR/TGR5 signaling pathways via remodeling the gut microbiota in CD-1 mice.

Dysregulation of gut microbiota-mediated bile acid (BA) metabolism plays an important role in the pathogenesis of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our previous studies found that bisphenol A (BPA) exposure induced hepatic steatosis and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alterations were involved in BPA-induced hepatic steatosis remains unclear. Therefore, we explored the gut microbiota-related metabolic mechanisms of hepatic steatosis induced by BPA. Male CD-1 mice were exposed to low-dose BPA (50 µg/kg/day) for 6 months. Fecal microbiota transplantation (FMT) and broad-spectrum antibiotic cocktail (ABX) treatment were further adopted to test the role of gut microbiota in the adverse effects of BPA. We found that BPA induced hepatic steatosis in mice. Additionally, 16S rRNA gene sequencing showed that BPA reduced the relative abundance of Bacteroides, Parabacteroides and Akkermansia, which are associated with BA metabolism. Metabolomic analyses demonstrated that BPA significantly altered the ratio of conjugated to unconjugated BAs and increased the total level of taurine-α/ß-muricholic acid while decreasing the level of chenodeoxycholic acid, thus inhibiting the activation of special receptors, including farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), in the ileum and liver. The inhibition of FXR reduced short heterodimer partner and subsequently induced cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, which is related to hepatic BA synthesis and lipogenesis, eventually leading to liver cholestasis and steatosis. Furthermore, we found that mice that received FMT from BPA-exposed mice developed hepatic steatosis, and the influences of BPA on hepatic steatosis and FXR/TGR5 signaling pathways could be eliminated by ABX treatment, confirming the role of gut microbiota in BPA effects. Collectively, our study illustrates that suppressed microbiota-BA-FXR/TGR signaling pathways may be a potential mechanism for hepatic steatosis induced by BPA, providing a new target for the prevention of BPA-induced NAFLD.

Systematic Design and Study of Star-like Polymeric Prodrug Unimolecular Micelles ß-CD-P[CL-co-(ACL-g-DOX)-SS-MPEG]21 by DPD Simulations.

Unimolecular micelles composed of a single polymeric molecule have recently attracted significant attention in anti-cancer drug delivery due to their high thermodynamic stability and small particle sizes. Applying the prodrug strategy to unimolecular micelles may provide superior nano-drug carriers with simultaneous high stability, low drug leakage, and well-drug loading capacity. However, the formation mechanism of the unimolecular prodrug micelles, the superiority of the prodrug strategy, as well as the prodrug controlled release mechanism were scantily understood at the mesoscopic scale. In this work, dissipative particle dynamics mesoscopic simulations were employed to investigate the self-assembly behavior, formation conditions, drug distribution regularities, and the prodrug release process of the star-like polymeric prodrug unimolecular micelles formed by ß-CD-P[CL-co-(ACL-g-DOX)-SS-MPEG]21. A special bond-breaking script was used to accomplish the bond-breaking simulation of the grafted DOX bonds and the disulfide bonds. Results showed that to form well monodispersed and superior DOX-loaded unimolecular micelles, the polymer concentration should be well controlled at low volume fractions (≤10.59%), and the detailed molecular structure of the polymer was suggested as ß-cyclodextrin-P[caprolactone-co-(amino caprolactone-g-doxorubicin)-disulfide-methyl polyethylene glycol]21) (ß-CD-P[CL30-co-(ACL-g-DOX)8-SS-MPEG49]21). By comparison with the DOX physically loaded micelles, it was found that the prodrug unimolecular micelles with DOX grafted on the polymer displayed no drug leakage and superior drug loading capacity. Simulations on the prodrug release process showed that the prodrug unimolecular micelles assembled by ß-CD-P[CL30-co-(ACL-g-DOX)8-SS-MPEG49]21 would provide good dual pH/reduction-responsive DOX release performance.

USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ.

The balance between inflammatory T helper type 17 (Th17) and immunosuppressive regulatory T (Treg) cells is critical for maintaining immune homeostasis in the human body and is tightly regulated under healthy conditions. An increasing number of studies have reported that deubiquitinases (DUBs) play a vital role in regulating Th17- and Treg-cell differentiation. However, the biological functions of only a small fraction of DUBs in Th17- and Treg-cell differentiation are well defined. In this study, we identified ubiquitin-specific peptidase 1 (USP1) as a vital regulator of CD4+ T-cell differentiation. USP1 promoted Th17-cell differentiation but attenuated Treg-cell differentiation, thereby promoting the development of inflammatory diseases. Mechanistically, USP1 in CD4+ T cells enhanced the activity of RORγt but promoted the proteasomal degradation of Foxp3 through deubiquitination and stabilization of TAZ in vitro and in vivo. Notably, ML323, a specific inhibitor of the USP1/UAF1 deubiquitinase complex, inhibited Th17-cell differentiation and promoted Treg-cell differentiation in vitro and in vivo, indicating that ML323 might be a promising candidate for the treatment of diseases associated with an imbalance between Th17 and Treg cells. Our study highlights the critical role of USP1 in regulating adaptive immune responses and suggests that USP1 might be a drug target for the treatment of diseases associated with an imbalance between Th17 and Treg cells.

Hepatoprotective effect of curcumin against bisphenol A-induced hepatic steatosis via modulating gut microbiota dysbiosis and related gut-liver axis activation in CD-1 mice.

Chronic exposure to low-dose bisphenol A (BPA) has become a global problem of public health. Our previous work showed that low-dose BPA exposure caused gut microbial dysbiosis and hepatic steatosis. Curcumin, a polyphenol extracted from turmeric, has an inhibitory effect on liver lipid accumulation, whether curcumin can alleviate BPA-induced hepatic steatosis through improving intestinal flora and modulating gut-liver axis remains to be elucidated. Male CD-1 mice were fed with BPA-contaminated diet supplemented with or not with curcumin for 24 weeks. Curcumin supplementation markedly ameliorated liver fat accumulation and hepatic steatosis induced by BPA. Gut microbiota analysis via 16S rRNA sequencing revealed that the relative abundance of Proteobacteria and Firmicutes/Bacteroidetes ratio were increased in BPA-fed mice, and this alteration was reversed by curcumin treatment. Akkermansia, which was recognized as a potential probiotic, was significantly reduced after BPA exposure and was restored to the control level with curcumin addition. Furthermore, curcumin supplementation reversed the down-regulation of intestinal tight junction protein expressions (zona occludens-1 and occludin), improved increased gut permeability, reduced serum lipopolysaccharide level and suppressed the activation of hepatic toll-like receptor 4 / nuclear factor-κB (TLR4/NF-κB) pathway induced by BPA. These results indicated that the protective effect of curcumin against hepatic steatosis induced by BPA and further revealed that its mechanism might be its prebiotic effect on maintaining intestinal flora homeostasis and improving intestinal barrier function, consequently reducing serum lipopolysaccharide-triggered inflammatory response in the liver. Our work provides evidence for curcumin as a potential nutritional therapy for BPA-mediated hepatic steatosis.

Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice.

Interactions between the intestine and the liver, the so-called 'gut-liver axis', play a crucial role in the onset of hepatic steatosis and non-alcoholic fatty liver disease. However, not much is known about the impact of environmental pollutants on the gut-liver axis and consequent hepatic steatosis. Bisphenol A (BPA), a widely used plasticiser, is an important environmental contaminant that affects gut microbiota. We hypothesised that BPA induces hepatic steatosis by promoting gut microbiota dysbiosis and activating the gut-liver axis. In this study, male CD-1 mice were fed with diet containing BPA (50 µg/kg body weight/day) for 24 weeks. Dietary exposure to BPA increased lipid contents and fat accumulation in the liver. Analysis of 16 S rRNA gene sequencing revealed that the diversity of gut microbiota reduced and the composition of gut microbiota was altered in the BPA-fed mice. Further, the abundance of Proteobacteria, a marker of dysbacteria, increased, whereas the abundance of Akkermansia, a gut microbe associated with increased gut barrier function and reduced inflammation, markedly decreased. Expression levels of intestinal tight junction proteins (zona occludens-1 and occludin) also decreased drastically, leading to increased intestinal permeability and elevated levels of endotoxins. Furthermore, BPA up-regulated the expression of Toll-like receptor 4 (TLR4) and phosphorylation of nuclear factor-kappa B (NF-κB) in the liver and increased the production of inflammatory cytokines, including interleukin-1ß, interleukin-18, tumour necrosis factor-α, and interleukin-6. Take together, our work indicated that dietary intake of BPA induced hepatic steatosis, and this was closely related to dysbiosis of gut microbiota, elevated endotoxin levels, and increased liver inflammation through the TLR4/NF-κB pathway.

Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and has become a public health concern worldwide. The hallmark of NAFLD is hepatic steatosis. Therefore, there is an urgent need to develop new therapeutic strategies that are efficacious and have minimal side effects in hepatic steatosis and NAFLD treatment. The present study aimed to investigate the effect of dietary supplement of curcumin on high-fat diet (HFD)-induced hepatic steatosis and the underlying mechanism. METHODS: ApoE-/- mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with curcumin (0.1% w/w) for 16 weeks. Body and liver weight, blood biochemical.parameters, and liver lipids were measured. Intestinal permeability, hepatic steatosis and mRNA and protein expressions of TLR4-related inflammatory signaling molecule were analyzed. RESULTS: The administration of curcumin significantly prevented HFD-induced body weight gain and reduced liver weight. Curcumin attenuated hepatic steatosis along with improved serum lipid profile. Moreover, curcumin up-regulated the expression of intestinal tight junction protein zonula occluden-1 and occludin, which further improved gut barrier dysfunction and reduced circulating lipopolysaccharide levels. Curcumin also markedly down-regulated the protein expression of hepatic TLR4 and myeloid differentiation factor 88 (MyD88), inhibited p65 nuclear translocation and DNA binding activity of nuclear factor-κB (NF-κB) in the liver. In addition, the mRNA expression of hepatic tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) as well as the plasma levels of TNF-α and IL-1ß were also lowered by curcumin treatment. CONCLUSION: These results indicated that curcumin protects against HFD-induced hepatic steatosis by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. The ability of curcumin to inhibit hepatic steatosis portrayed its potential as effective dietry intervention for NAFLD prevention.

Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats.

BACKGROUND: Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats. METHODS: Male ZDF rats and Zucker lean rats aged 4-8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed. RESULTS: Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats. CONCLUSIONS: These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.

Bisphenol A exposure induces cholesterol synthesis and hepatic steatosis in C57BL/6 mice by down-regulating the DNA methylation levels of SREBP-2.

Bisphenol A (BPA), a major plasticizers that are commonly used for lining of beverage or food-storage containers, has been shown to increase cholesterol levels with molecular mechanism not clear. The present study was aimed to investigate the effects of BPA exposure on liver cholesterol synthesis and hepatic steatosis in male C57BL/6 mice and its underlying mechanisms. Male C57BL/6 mice were exposed to different doses (50, 500 and 5000 µg/kg/day) of BPA through diet for 16 weeks. Exposure to low doses (50 and 500 µg/kg/day) of BPA increased hepatic cholesterol content and the expression levels of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and sterol regulatory element binding proteins-2 (SREBP-2). DNA methylation analysis further showed that mice exposed to low-dose BPA decreased the DNA methylation levels of SREBP-2. Moreover, low doses of BPA exposure increased the expression levels of SREBP-1c and stearoyl-CoA desaturase 1 in the liver, and induced hepatic lipid synthesis and fat accumulation. Our results suggest that low-dose BPA exposure could induce hepatic cholesterol synthesis through decreasing the DNA methylation levels of SREBP-2 and subsequently up-regulating the expression of genes related to cholesterol synthesis in the liver, which causes cholesterol accumulation and further induces liver lipid synthesis and hepatic steatosis.

Nutritional Risk Screening in patients with chronic kidney disease.

Knowledge concerning nutritional status of patients with chronic kidney disease (CKD) is limited. Nutritional Risk Screening-2002 (NRS-2002) has been used to evaluate the nutritional aspects of patients according to the recommendation of European Society for Clinical Nutrition and Metabolism. Here we aim to assess the prevalence and characteristics of nutritional risk in CKD patients by using NRS-2002. NRS-2002 scores of 292 CDK patients were recorded in first 24 hours subsequent to their admission to hospital. All patients have never been on dialysis. BMI, weight and various biochemical parameters were also characterized for these patients. Possible correlations between these parameters and NRS-2002 score were investigated. The overall prevalence of nutritional risk was 44.9% (53.6% in CKD stage 4-5 patients and 38.3% in stage 1-3 patients). Statistically significant differences were found in serum Albumin, Haemoglobin B, and lymphocyte counts between patients with or without increased nutritional risk. Under the situation that attending physicians were completely unaware of NRS-2002 scores, only 35.1% of the patients at risk received nutritional support. The nutritional risk status was associated with CKD stages but independent from primary diagnosis type. More attention should be paid to the nutritional status in CKD patients (including early stage patients). We recommended using NRS-2002 for nutritional risk assessment among non-dialysis CKD patients in routine clinical practice.

A multicentre assessment of malnutrition, nutritional risk, and application of nutritional support among hospitalized patients in Guangzhou hospitals.

BACKGROUND: To assess nutritional status, the prevalence of nutritional risk, and nutritional support in hospitalized patients in Guangzhou, to determine gender or age associated differences in the prevalence of nutritional risk. METHODS: A total of 2550 patients admitted during April to December 2008 from six departments (Gastroenterology, Pulmonology, Neurology, Nephrology, General Surgery and Thoracic Surgery) of four teaching hospitals were screened using the Nutritional Risk Screening 2002 tool. RESULTS: Overall prevalence of undernutrition and nutritional risk was 17.8% and 41.5%, respectively. The department of Pulmonology had the highest prevalence of undernutrition (28.2%) and nutritional risk (55.9%). The prevalence of nutritional risk was significantly higher in patients >=70 years of age than patients <70 years (64.2% vs 32.6%, p<0.001). No gender difference in the prevalence of nutritional risk was observed in general. In total, 47.6% of "at risk" and 19.4% of "not at risk" patients received nutritional support. Parenteral nutrition accounted for 88.8% of the nutritional support. CONCLUSIONS: The present study documented the prevalence of nutritional risk defined by NRS2002 and inappropriate assignment of nutritional interventions in Guangzhou hospitals.

Soy germ isoflavones improve menopausal symptoms but have no effect on blood lipids in early postmenopausal Chinese women: a randomized placebo-controlled trial.

OBJECTIVE: Estrogen therapy is, to date, the most effective treatment of menopausal syndrome and also has a favorable effect on lipid profiles. Because of its potential adverse effects, however, a more acceptable alternative therapy needs to be identified. This study examines the effect of soy germ isoflavones on menopausal symptoms and serum lipids. METHODS: Ninety early postmenopausal Chinese women, aged 45 to 60 years, were randomly assigned to three treatment groups (30 each) receiving daily doses of 0 (placebo), 84, and 126 mg of soy germ isoflavones. Hot flush frequency, Kupperman scores, serum 17ß-estradiol, follicle-stimulating hormone, luteinizing hormone, and serum lipids, including triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and apolipoprotein B100, were assessed at baseline and at 12 and 24 weeks after treatment. RESULTS: Both the frequency of hot flushes and the Kupperman index score decreased in all three treatment groups during the intervention period, but the percentage decreases in both were significantly greater in the two isoflavone groups (44.3 ± 19.1 and 57.8 ± 37.4 [84 mg isoflavones]; 48.5 ± 27.2 and 56.7 ± 26.7 [126 mg isoflavones]) than in the placebo group (27.8 ± 15.5 and 34.6 ± 46.2; p < 0.01). There was no significant difference in the changes in estradiol, follicle-stimulating hormone, and luteinizing hormone among the three treatment groups during the study, and no significant differences were observed in the lipid components. CONCLUSIONS: A daily supplement of 84 or 126 mg soy germ isoflavones may improve menopausal symptoms, although neither dose was found to affect lipid profiles in early postmenopausal Chinese women after 24 weeks of treatment. The favorable effects are unlikely to be associated with female hormones.