Improved Liver Function Research Articles

Effect of Folic Acid Supplementation on the Liver Function in Chronic Schizophrenia Patients

Oxidative stress caused by free radicals and long-term antipsychotic use in chronic schizophrenic patients may result in liver cell damage and impaired liver function. Folic acid is an exogenous antioxidant that can boost the antioxidant defense mechanism (Glutathione Reductase), lowering free radicals and improving liver function. Determine the correlation between adjuvant folic acid and liver function in chronic schizophrenic patients. This was a placebo-controlled, double-blinded randomized control trial. The study sample included 36 patients in the control group and 36 patients in the treatment group. Subjects were patients who had suffered from schizophrenia for at least 2 years and received antipsychotics. Research subjects in the treatment group received folic acid supplementation. The intervention was conducted for 21 days during hospitalization. The level of AST (U/L) and ALT (U/L) was measured before and after supplementation. Following folic acid supplementation, AST levels were significantly improved (26.950 U/L compared to prior to treatment 33.09 U/L, p= <0.001). ALT levels after treatment were increased but there was no significant difference observed (p= 0.835). Folic acid supplementation improves AST levels significantly.

Urantide alleviates atherosclerosis-related liver and kidney injury via the Wnt/β-catenin signaling pathway in ApoE(-/-) mice.

To investigate the role of urantide in the prevention and treatment of atherosclerosis (AS)-related liver and kidney injury by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating the Wnt/β-catenin signaling pathway. Atherosclerotic ApoE-/- mice were treated with 20 mg/kg, 30 mg/kg, and 40 mg/kg urantide for 14days. When ApoE-/- mice developed AS, significant pathological changes occurred in the liver and kidney, and the UII/UT system in tissue was highly activated; furthermore, the Wnt/β-catenin signalling pathway was activated, and proteins related to this signalling pathway, such as GSK-3β, AXIN2, CK‑1, and APC, were significantly downregulated. After urantide treatment, the pathological damage to the liver and kidney was effectively improved, the activity of the UII/UT system was effectively inhibited, and the expression of the Wnt/β-catenin signalling pathway and related proteins was restored. Wnt/β-catenin signals were mainly localized in the cytoplasm, renal tubules, and interstitium. Urantide could improve AS-related liver and kidney injury by antagonizing the UII/UT system, and the improvements in liver and kidney function in atherosclerotic ApoE-/- mice may be related to inhibition of the Wnt/β-catenin signalling pathway.

Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials

BackgroundNonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease’s development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM.MethodsThis systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes’ certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373.ResultsFour thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD − 0.17, 95%CI − 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD − 11.72, 95%CI − 17.82 to − 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence.ConclusionsThe high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.

Preparation of pectin from fingered citron peel and its protective effect on cadmium-induced liver and kidney damage in mice

Citrus pectin has been proved for its ability to bind heavy metals from industrial wastewater. However, few studies have investigated the detoxification effect of citrus pectin on cadmium-induced damage through in vivo experiments. In this study, pectin was extracted from fingered citron peel and subjected to pH-temperature modification, and successful modification of pectin's molecular structure was confirmed by a decrease in the degree of esterification and the increase in the content of free carboxylate groups in the structure. In vitro studies suggested that the modified fingered citron peel pectin (mFCPP) showed higher cadmium removal ability compared to unmodified fingered citron peel pectin (FCPP). A 20-week study in cadmium-exposed mice suggested significant improvement in liver and kidney function with co-treatment of pectin. Co-treatment with FCPP or mFCPP ameliorated the cadmium-induced cell death and oxidative damage in the liver and kidney. Moreover, the study demonstrated that both FCPP and mFCPP were impermeable through the intestinal wall, suggesting their binding with the cadmium ions in the gastrointestinal tract, thus preventing cadmium ions absorption and entry into the systemic circulation.

Anticancer approach of zinc oxide nanocomposite prepared by gamma radiation via induction of apoptosis and PGC‐1α pathways in hepatocellular carcinoma in rats

Zinc oxide nanoparticles (ZnO NPs) are attracting the interest of researchers due to their potential applications in cancer treatment. It was recently shown that ZnO NPs specifically destroy cancer cells. However, the underlying molecular processes that drive ZnO NPs' anticancer activity are unclear. Radical polymerization was used for synthesizing zinc oxide nanoparticles using gamma radiation. Polyvinylpyrrolidone (PVP) was employed as a stabilizer in the production of zinc oxide nanoparticles using zinc nitrate. PVP@ZnO nanostructures were characterized using a number of techniques, including high‐resolution transmission electron microscopy (HRTEM) and UV–visible spectroscopy. Fourier‐transform infrared spectroscopy (FTIR) was used to study the functional groups of the produced nanostructures. Moreover, the surface morphology of prepared zinc oxide nanoparticles (ZnO NPs) and PVP@ZnO nanostructures was shown using SEM. In addition, the crystalline structure of the aforementioned samples was identified and investigated via XRD. The current work examined the anticancer effect of ZnO nanocomposite against rat hepatocellular carcinoma (HCC). The results demonstrated that ZnO nanocomposite exert distinct effects on apoptosis and PGC‐1α pathways in hepatocellular carcinoma in rats. mRNA levels of tumor suppressor gene p53 and antiapoptotic gene BCL‐2 were downregulated, while the apoptotic gene Bax was upregulated and Caspase‐3 activity increased in diethylnitrosamine (DEN) + ZnO nanocomposite‐treated rats in comparison with DEN‐treated rats. ZnO nanocomposite were also found to have an effect on liver function (ALT, AST, ALP, and GGT) and total antioxidant capacity (TAC). Treatment with DEN manifested a significant decrease in the expression of mtTFA and PGC‐1α (mtTFA: 0.54 fold and PGC‐1α: 0.31 fold in respect to the normal control), while ZnO nanocomposite treatment induced a remarkable increase in their expression. In conclusion, the present data demonstrated that ZnO nanocomposite showed anticancer activity via induction of apoptosis and PGC‐1α pathways. In addition, improvements in liver function and antioxidant capacity.

Dahuang zhechong pill ameliorates hepatic fibrosis by regulating gut microbiota and metabolites

Ethnopharmacological relevanceDHZCP is a traditional Chinese medicinal formula in “The Synopsis of Prescriptions of the Golden Chamber” that has been often used in the treatment of hepatic disorders, gynecopathy and atherosclerosis. However, its underlying mechanisms in preventing hepatic fibrosis remain incompletely understood. Aim of the studyThis study aims to explore the therapeutic efficacy and potential mechanism of DHZCP in a CCL4-induced experimental hepatic fibrosis rat model. Materials and methodsDHZCP was orally administered at doses of 0.168, 0.084 and 0.042 g⋅kg-1⋅d-1 in a CCL4-induced hepatic fibrosis model using SD rats. Histopathology, immunohistochemistry and biochemical analysis, ELISA, Flow cytometry, WB, RT-PCR, 16 S rRNA, and untargeted metabolomic analysis were used to determine the therapeutic effects and mechanisms of DHZCP in the treatment of CCL4-induced hepatic fibrosis. ResultsPharmacodynamically, DHZCP inhibited ALT and AST, improved liver function, decreased NF-κB, TNF-α and IL-6 in liver tissue, indicating its role in inhibiting CCL4-induced liver inflammation. Most importantly, it reduces the level of fibrosis in serum and liver tissue. Histological analysis also showed that DHZCP could effectively inhibit inflammatory cytokine infiltration and excessive collagen deposition. Mechanistically, DHZCP regulates gut microbiota, improves the proportion of firmicutes and bacteroidota at the phylum level, and increases the abundance of beneficial bacteria at the genus level, such as muribagulaceae unclassified, prevotella, alloprevotella, closteriales unclassified, lachnospiraceae unclassified and phascolarctobacterium. Instead, it reduced the abundance of two harmful bacteria, desulfovibrio and colidextribacter. Four types of metabolites such as hydrocarbons, organic nitrogen compounds, organic oxygen compounds, and organosulfur compounds were added. Furthermore, DHZCP was found to reduce the damage of intestinal barrier caused by changes in gut microbiota and metabolites. ConclusionDHZCP is an effective inhibitor of hepatic fibrosis by regulating gut microbiota and metabolites, improving the integrity of the intestinal barrier.

Impact of pemafibrate on lipid profile and insulin resistance in patients with statin-treated coronary artery disease with metabolic syndrome

Abstract Background Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor α, a vital modulator of lipid and glucose metabolism. We examined the effects of this drug on lipid markers and insulin resistance in patients with metabolic syndrome (MetS). Methods In the randomized, crossover PEBE study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks, followed by crossover of another 24-weeks. Forty-six of 60 patients (77%) enrolled in the PEBE study were founded to have MetS. In the present subanalysis, we compared patients with MetS (MetS group, n = 46) and those without MetS (Non-MetS group, n =14). The primary endpoints were changes from baseline in serum TG, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (Apo A-I) levels, while the secondary endpoint was change in the homeostasis model assessment of insulin resistance (HOMA-IR). Results There was a significant decrease in serum TG levels (from 266.6 mg/dL to 148.0 mg/dL in MetS group, p < 0.001; from 203.9 mg/dL to 97.6 mg/dL in Non-MetS group, p < 0.001), but %Change was not significantly different between the two groups (−44.1% vs. −51.6%, p = 0.099). Serum HDL-C and Apo A-I levels significantly increased in both groups, but no significant differences in %Change were found between the two groups (p = 0.591 in HDL-C; p = 0.432 in Apo A-I). HOMA-IR significantly decreased in MetS group (from 4.3 ± 4.0 to 3.1 ± 2.2, p = 0.011) but not in Non-MetS group (from 1.7 ± 1.0 to 1.5 ± 1.0, p = 0.553). %Change in liver enzyme levels was markedly decreased in MetS group than in Non-MetS group (alanine aminotransferase, −25.1% vs. −11.3%, p = 0.027; gamma-glutamyl transferase, −45.8% vs. −36.2%, p = 0.020). Although serum adiponectin levels did not change significantly in both groups, leptin levels significantly decreased in MetS group (from 18.5 ng/mL to 16.6 ng/mL, p = 0.004), but not in Non-MetS group (from 9.2 ng/mL to 9.0 ng/mL, p = 0.917). Conclusion Pemafibrate is as efficient in patients with MetS as in patients without MetS in improving the lipid and glucose metabolism. In addition, the use in MetS patients may be more effective in improving liver function and insulin resistance.

Abstract 15087: First Clinical Trial in China to Evaluate the Efficacy and Safety of Moyoassist® Extra-VAD System

Cardiogenic shock(CS)is associated with significant morbidity and mortality. For patients unresponsive to medicinal treatment, an alternative is a mechanical circulatory support (MCS) system. In China, common treatments using short-term MCS include IABP and VA-ECMO, both methods found their limitations. Therefore, a better strategy must be proposed to improve prognosis in CS patients, such as extracorporeal VAD (Extra VAD). Here, we reported 40 patients' data collected from a prospective, multicenter, single group clinical trial conducted from July 2021 to Feb 2023, which aims to evaluate the efficacy and safety of MoyoAssist® Extra-VAD system. MoyoAssist® is developed based on fully magnetically levitated pump technology to temporarily support the left, right, or biventricular circulation of patients with acute heart failure and cardiogenic shock of all causes. Patients were recruited for various indications, with PCCS (50%) and BTT (32.5%) being the top two causes. A combination of median sternotomy (22.5%), peripheral venous cannulation (52.5%) and mini-incision (25%) were employed to implant the device. Especially, jugular vein cannulation was a pioneering approach proposed to enable patients’ early ambulation and recovery. MoyoAssist® Extra-VAD has demonstrated stable and sufficient circulation support without severe device associated adverse events. The mean support duration was 7d16hrs, and overall survival rate at 30-day follow up was 62.5%. Hemodynamics indicated improvement with increased MAP and reduced CVP in all sub-groups. Lactate has shown a significant decrease in the PCCS-survival group (3.95 vs. 1.05, p<0.05), indicating improved reperfusion of organ tissues. While AST has shown a significant drop in the BTT-survival group (67.10 vs. 56.17, p<0.05), indicating improved liver function. During the support, 3 patients with peripheral cannulation and 2 patients with mini-incision were able to ambulate early. The types of complication seen were similar to those reported with CentriMag, but the rates of bleeding (15%) and hemolysis (0%) were much lower. In conclusion, MoyoAssist® Extra-VAD has demonstrated its safety and efficacy for short-to-mid-term support of patients with acute heart failure and cardiogenic shock.

SFgl2 gene-modified MSCs regulate the differentiation of CD4+ T cells in the treatment of autoimmune hepatitis

BackgroundAutoimmune hepatitis (AIH) is a T-cell-mediated autoimmune liver disease that can lead to liver injury and has a poor long-term prognosis. Mesenchymal stromal cells (MSCs) have immunosuppressive effects and can treat AIH. CD4+ T cells express the unique inhibitory Fcγ receptor (FcγRIIB), which is the only receptor for the immunosuppressive factor soluble fibrinogen-like protein 2 (sFgl2). This study aimed to examine the therapeutic effect of sFgl2 gene-modified MSCs (sFgl2-MSCs) on AIH.MethodsMSCs were obtained from the inguinal fat of mice and cocultured with CD4+ T cells sorted from mouse spleens. FcγRIIB expression on CD4+ T cells was determined by flow cytometry. sFgl2 expression in MSCs transfected with lentiviral vectors carrying the Fgl2 gene and a green fluorescent protein-encoding sequence was determined by enzyme-linked immunosorbent assay. The percentages of Th1 cells Th17 cells and regulatory T cells (Tregs) were determined by flow cytometry And the levels of p-SHP2 and p-SMAD2/3 were detected by Western blotting after the cells were cocultured with MSCs for 72 h. After locating MSCs by in vivo imaging Con A-induced experimental AIH mice were randomly divided into 4 groups and administered different treatments. After 24 h histopathological scores liver function and cytokine levels were examined and the proportions of CD4+ T cells CD8+ T cells Tregs Th17 cells and Th1 cells in the spleen and liver were determined by flow cytometry. In addition immunohistochemical staining was used to detect the liver infiltration of T-bet-, Foxp3- and RORγ-positive cells.ResultsFcγRIIB expression on CD4+ T cells was upregulated after coculture with MSCs. After coculture with sFgl2-MSCs, the proportion of Tregs among CD4+ T cells increased, the proportion of Th17 and Th1 cells decreased, and the levels of p-SHP2 and p-SMAD2/3 increased. In vivo, sFgl2-MSCs significantly improved liver function, decreased liver necrosis area, decreased tumor necrosis factor-α, interleukin (IL)-1β and IL-6 expression, increased IL-10 expression, reduced liver infiltration of CD4+ T and CD8+ T cells, increased the proportion of Tregs and reduced the proportions of Th17 and Th1 cells in mice.ConclusionBy promoting Tregs differentiation and inhibiting Th17 and Th1 cell differentiation, sFgl2 gene-modified MSCs have a more powerful therapeutic effect on Con A-induced experimental AIH and may represent a strategy for the clinical treatment of AIH.

Modulating intestinal barrier function by sphingosine-1-phosphate receptor 1 specific agonist SEW2871 attenuated ANIT-induced cholestatic hepatitis via the gut-liver axis

Bile acid (BA) homeostasis throughout the enterohepatic circulation system is a guarantee of liver physiological functions. BA circulation disorders is one of the characteristic clinical manifestations of cholestasis, and have a closely relationship with intestinal barrier function, especially ileum. Here, our in vivo and in vitro studies showed that intestinal tight junctions (TJs) were disrupted by α-naphthylisothiocyanate (ANIT), which also down-regulated the protein expression of sphingosine-1-phosphate receptor 1 (S1PR1) in the top of villus of mice ileum. Activating S1PR1 by specific agonist SEW2871 could improve TJs via inhibiting ERK1/2/LKB1/AMPK signaling pathway in the ileum of ANIT-treated mice and ANIT-cultured Caco-2 cells. SEW2871 not only regained ileum TJs by activating S1PR1 in the epithelial cells of ileum mucosa, but also recovered ileum barrier function, which was further verified by the recovered BA homeostasis in mice ileum (content and tissue) by using of high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS). Subsequently, the improved intestinal injury and inflammation further strengthened that SEW2871 modulated intestinal barrier function in ANIT-treated mice. Finally, our data revealed that along with the down-regulated levels of serum lipopolysaccharides (LPS), SEW2871 improved liver function and relieved hepatitis via blocking TLR4/MyD88/NF-kB signaling pathway in ANIT-treated mice. In conclusion, these results demonstrated that activating intestinal S1PR1 by SEW2871 could modulate intestinal barrier function, leading to the improvement of cholestatic hepatitis in ANIT-treated mice via the “gut-liver” axis.

Effects of curcumin/turmeric supplementation on the liver enzymes, lipid profiles, glycemic index, and anthropometric indices in non-alcoholic fatty liver patients: An umbrella meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. The evidence for curcumin's effects on patients with NAFLD is accumulating; however, meta-analyses have reported mixed results. The current umbrella meta-analysis aimed to assess the present evidence and provide an accurate estimate of the overall effects of curcumin/turmeric on NAFLD patients. The Web of Science, Scopus, PubMed, ScienceDirect, and Google Scholar databases were searched till March 2023 using MeSH terms and related keywords based on the PICO criteria. Meta-analysis studies evaluating the effects of curcumin/turmeric supplementation on NAFLD patients that reported the effect sizes (ES) and corresponding confidence intervals (CI) were eligible for inclusion in this study. All articles were screened by considering the eligibility criteria by two independent reviewers and required data were extracted from the included meta-analyses. The meta-analysis was performed utilizing a random-effects model by STATA software. Findings of 11 meta-analyses of 99 randomized controlled trials comprising 5546 participants revealed that curcumin/turmeric supplementation reduced AST (ES = -1.072, 95% CI (-1.656, -0.488), p = 0.000), ALT (ES = -0.625, 95% CI (-1.170, -0.134), p = 0.014), and TG (ES = -0.469, 95% CI (-1.057, 0.119), p = 0.128) levels, and HOMA-IR (ES = -0.291, 95% CI (-0.368, -0.214), p = 0.000), BMI (ES = -0.205, 95% CI (-0.304, -0.107), p = 0.000), and WC (ES = -1.290, 95% CI (-2.038, -0.541), p = 0.001) in comparison to the control group. However, the effects of curcumin on GGT, ALP, TC, LDL-C, HDL-C, FBS, and HbA1C levels and body weight were not significant. The findings suggest the beneficial effects of curcumin/turmeric supplementation in patients with NAFLD, such as improving liver function, decreasing serum TG levels, ameliorating insulin resistance, and reducing general and central obesity. Nevertheless, high-quality research is further required to prove these achievements.

Qijia rougan formula ameliorates ECM deposition in hepatic fibrosis by regulating the JAK1/STAT6-microRNA-23a feedback loop in macrophage M2 polarization

Hepatic fibrosis is the critical pathological stage in the progression of chronic liver disease to cirrhosis and hepatocellular carcinoma (HCC). However, no approved anti-hepatic fibrosis drugs are available currently. Qijia Rougan Formula (QRF) is a traditional Chinese medicine (TCM) with significant clinical efficacy on hepatic fibrosis. It was derived from Sanjiasan, a famous decoction documented in the Book of Treatise on the Pestilence in the Ming Dynasty of China. However, the underlying regulatory mechanisms remain elusive. This study further confirmed the therapeutic effects of QRF on hepatic fibrosis and dissected its underlying molecular mechanisms from the perspective of macrophage M2 polarization, one of the critical events in hepatic fibrosis. Experimentally, QRF significantly improved extracellular matrix (ECM) deposition and fibrosis in the liver of model rats. QRF diminished the proportion of M2 macrophages, decreased the levels of TGF-β, PDGFB and IL-10, and regulated the expression of p-JAK1, p-STAT6, JAK1 and microRNA-23a both in vitro and in vivo. Collectively, it was confirmed that QRF effectively improves liver function and hepatocyte damage, and reduces ECM deposition. QRF ameliorates hepatic fibrosis by regulating JAK1/STAT6-microRNA-23a negative feedback loop to inhibit macrophage M2 polarization and thus reduce ECM deposition. Our study illustrates the potential of QRF for hepatic fibrosis therapy, suggesting that QRF is a promising anti-hepatic fibrosis drug candidate.

Nano-curcumin ameliorates arsenic induced hepatotoxicity in female rats

Aim: To determine the protective effects of curcumin and nanocurcumin against arsenic-induced hepatotoxicity in female rats, using liver function tests and oxidative stress parameters. Methodology: Arsenic trioxide (4 mg kg-1 b.wt.), curcumin and nano curcumin (50 mg kg-1 b.wt.) were administered to healthy rats as a chronic treatment for 60 days through gavage. The liver tissue samples of exposed rats were examined for histopathological alterations, liver function tests viz. alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin (BIL) and a lipid peroxidation product-malonaldehyde (MDA). Results: Treatments with both forms of curcumin could significantly (p 0<0.05) improve liver function as indicated by serum enzyme biomarkers viz. AST, ALT, ALP and LDH. Hyper-bilirubinemia was also diminished. Fibro-proliferation caused by arsenic in the liver was also controlled by curcumin (s). Histopathological observations of liver showed significant improvement in its morphology post treatments. Interpretation: Present results suggest that curcumin and nanocurcumin both express hepatoprotective effects in arsenic treated rats. However, nanocurcumin was found to offer better protection than curcumin. Key words: Arseniasis, Fibrosis, Lipid peroxidation, Liver function, Nanocurcumin

Sericin enhances ammonia detoxification by promotes urea cycle enzyme genes and activates hepatic autophagy in relation to CARD-9/MAPK pathway

Urea cycle is an important metabolic process that initiates in liver mitochondria and converts ammonia to urea. The impairment of ammonia detoxification, both primary and secondary causes, lead to hyperammonemia, a life-threatening condition affecting to the brain. Current treatments are not enough effective. In addition, our recent proteomics study in hypercholesterolemic rat model demonstrated that sericin enhances hepatic nitrogenous waste removal through carbamoyl-phosphate synthase 1 (CPS-1), aldehyde dehydrogenase-2 (ALDH-2), and uricase proteins. However, the underlining mechanisms regard to this property is not clarified yet. Therefore, the present study aims to examine the effect of sericin on urea cycle enzyme genes (CPS-1 and ornithine transcarbamylase; OTC) and proteins (mitogen-activated protein kinase; MAPK, caspase recruitment domain-containing protein 9; CARD-9, Microtubule-associated protein light chain 3; LC-3), which relate to urea production and liver homeostasis in hepatic cell line (HepG2) and hypercholesterolemic rat treated with or without sericin. qRT-PCR, immunohistochemistry, and electron microscopy techniques were performed. In vitro study determined that high dose of sericin at 1 mg/ml increased liver detoxification enzyme (Cytochrome P450 1A2; CYP1A2 and ALDH-2) and urea cycle enzyme (CPS-1 and OTC) genes. Both in HepG2 cell and rat liver mitochondria, sericin significantly downregulated CARD-9 (apoptotic protein) expression while upregulated MAPK (hepatic homeostasis protein) and LC-3 (autophagic protein) expressions. Hence, it might be concluded that sericin promotes ammonia detoxification by both increases urea cycle enzyme genes and enhances hepatic autophagy in associated with CARD-9/MAPK pathway (as shown by their own negative relationship). This study presents another beneficial property of sericin to develop an upcoming candidate for ammonia toxicity alleviation and liver function improvement.

Human umbilical cord mesenchymal stem cells inhibit liver fibrosis via the microRNA-148a-5p/SLIT3 axis

BackgroundHuman umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have garnered considerable attention as prospective modalities of treatment for liver fibrosis (LF). The inhibition of hepatic stellate cell (HSC) activation underlies the anti-fibrotic effects of hUC-MSCs. However, the precise mechanism by which hUC-MSCs impede HSC activation remains unclarified. We aimed to elucidate the intrinsic mechanisms underlying the therapeutic effects of hUC-MSCs in LF patients. MethodsMice with liver cirrhosis induced by carbon tetrachloride (CCl4) were used as experimental models and administered hUC-MSCs via tail-vein injection. The alterations in inflammation and fibrosis were evaluated through histopathological examinations. RNA sequencing (RNA-seq) and bioinformatics analysis were then conducted to investigate the therapeutic mechanism of hUC-MSCs. Finally, an in-vitro experiment involving the co-cultivation of hUC-MSCs or hUC-MSC-derived exosomes (MSC-Exos) with LX2 cells was performed to validate the potential mechanism underlying the hepatoprotective effects of hUC-MSCs in LF patients. ResultshUC-MSC therapy significantly improved liver function and alleviated LF in CCl4-induced mice. High-throughput RNA-Seq analysis identified 1142 differentially expressed genes that were potentially involved in mediating the therapeutic effects of hUC-MSCs. These genes play an important role in regulating the extracellular matrix. miRNA expression data (GSE151098) indicated that the miR-148a-5p level was downregulated in LF samples, but restored following hUC-MSC treatment. miR-148a-5p was delivered to LX2 cells by hUC-MSCs via the exosome pathway, and the upregulated expression of miR-148a-5p significantly suppressed the expression of the activated phenotype of LX2 cells. SLIT3 was identified within the pool of potential target genes regulated by miR-148a-5p. Furthermore, hUC-MSC administration upregulated the expression of miR-148a-5p, which played a crucial role in suppressing the expression of SLIT3, thereby palliating fibrosis. ConclusionshUC-MSCs inhibit the activation of HSCs through the miR-148a-5p/SLIT3 pathway and are thus capable of alleviating LF.

Fibroblast Growth Factor 21 in Chronic Hepatitis C: A Potential Non-Invasive Biomarker of Liver Status upon Viral Eradication.

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.

Enhanced efficient micropropagation and reduced abnormal phenomena in Phyllanthus amarus plantlets cultured on medium containing silver nanoparticles

Phyllanthus amarus is a valuable medicinal plant that is used to manufacture medications that treat viral hepatitis and improve liver function. Due to excessive ethylene production, micropropagation of P. amarus frequently results in abnormal phenomena such as leaf abscission, leaf yellowing, shoot with callus and vitrification. In this study, silver nanoparticles (AgNPs) was supplemented to the shoot multiplication medium to promoted growth, reduced ethylene content and abnormal phenomena in micropropagation of P. amarus. The results indicated that 7 mg/L AgNPs in shoot multiplication medium enhanced the shoot growth consists of number of shoots (7.33 shoots), shoots higher than 3 cm in height (5.67 shoots), shoot height (5.17 cm) fresh weight (215.32 mg) and dry weight (28.36 mg) were higher than those others after 30 days of culture. Besides, 7 mg/L AgNPs derived- shoots reduced abnormal phenomena; especially, 7 mg/L AgNPs treatment reduced about 4.5-fold leaf abscission, 1.5-fold leaf yellowing, 2-fold shoot with callus and 5-fold ethylene content as compared to those in control. The subsequent growth, acclimatization and accumulation of hypophyllanthin (48.51 µg/g) and phyllanthin (213.08 µg/g) contents of AgNPs derived- plantlets were higher than those in the control.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin’s efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Effects of Dietary Acacia nilotica Fruit, Zinc Oxide Nanoparticles and Their Combination on Productive Performance, Zinc Retention, and Blood Biochemistry of Rabbits.

This study aims to examine the effects of supplementing male rabbit diets with nanoparticles of zinc oxide (Nano-ZnO) and Acacia nilotica fruit powder (ANFP) on production sustainability under hot climatic conditions. Eighty Californian male rabbits aged 40 days old (average body weight 738.5 ± 11 g) were divided into four treatment groups and administered one of the following diets: control diet, Nano-ZnO (50 mg/kg), ANFP (5 g/kg), or a combination of Nano-ZnO (50 mg/kg) and ANFP (5 g/kg) for a period of 60 days. Each of the 20 rabbits used in a treatment was regarded as a replicate. The results showed that adding Nano-ZnO and ANFP individually or in combination to rabbits' diets improved (p < 0.05) growth performance in comparison to control. In addition, zinc contents in serum or the testis tissues in the Nano-ZnO- and ANFP-treated rabbits were significantly greater (p < 0.05) than those in the control group. In addition, serum levels of creatinine, alanine aminotransferase, and aspartate aminotransferase were decreased (p < 0.05) by supplementation of Nano-ZnO, ANFP, or their combination. Carcass criteria did not differ among the treatments. Overall, the findings of the present study indicate that rabbits fed diets containing Nano-ZnO and ANFP, as well as their combination, showed improvements in growth performance, kidney and liver functions, as well as zinc retention in tissues under hot climatic conditions. The combination of Nano-ZnO and ANFP exhibited the best performance in the rabbits. More research on the synergistic effects of Nano-ZnO and ANFP in the sustainable production of rabbit meat is required.

Metabolic-Dysfunction-Associated Steatotic Liver Disease-Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population and whose prevalence is increasing worldwide due to the pandemic of obesity. Obesity, impaired glucose metabolism, high blood pressure and atherogenic dyslipidemia are risk factors for MASLD. Therefore, insulin resistance may be closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids released from adipose tissue, increase in fatty acid synthesis and reduced fatty acid oxidation in the liver and hepatic overproduction of triglyceride-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease. Considering that the development of cardiovascular diseases determines the prognosis of MASLD patients, the therapeutic interventions for MASLD should reduce body weight and improve coronary risk factors, in addition to an improving in liver function. Lifestyle modifications, such as improved diet and increased exercise, and surgical interventions, such as bariatric surgery and intragastric balloons, have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve coronary risk factors and to suppress the occurrence of cardiovascular diseases. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator pemafibrate improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs and whether such drugs and the combination therapy of such drugs could be the treatments for MASLD.