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Background: Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear. Methods: This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD. Results: A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD. Conclusion: This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG. [ABSTRACT FROM AUTHOR]

The multitude of obesogenic diets used in rodent studies can hardly be overviewed. Since standardization is missing and assuming that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the individual effects of three commonly used obesogenic diets, mainly differing in sugar and fat content. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research. In conclusion, we strongly recommend a careful selection of the appropriate diet in advance of a new experiment, taking into account the specific research question. [ABSTRACT FROM AUTHOR]

A conference paper about the sinusoidal endothelium and space of Disse in ageing Papio hamadrayas is presented. It examines the livers of young and old baboons to confirm that pseudocapillarization is a generalized aging change across species. Results reveal that significant age-related changes occur in the perisinusoidal region of the baboon liver.

Background: To explore the relationship between blood manganese and liver stiffness in the United States among participants with chronic obstructive pulmonary disease (COPD). Methods: All data were obtained from the 2017–2018 National Health and Nutrition Examination Survey database (NHANES). A total of 4690 participants were included in the study. All participants included complete information on COPD, liver stiffness, and blood manganese. Liver stiffness (kPa) was measured from "Examination Date" and blood manganese (ug/L) was obtained from "Laboratory Data". A multiple linear regression model was used to assess the correlation between blood manganese and liver stiffness. Results: Among the 4690 participants, blood manganese was lower in the COPD group but liver stiffness was higher (p < 0.05). There was a positive correlation between blood manganese and liver stiffness (β = 0.08, 95% CI 0.03, 0.12). This positive association was more pronounced in COPD participants (β = 0.25, 95% CI 0.08, 0.42) and there was a non-linear relationship, which was more significant when blood manganese exceeded 14.43 ug/L (β = 1.76, 95% CI 1.10, 2.41). Conclusions: The association between blood manganese and liver stiffness was positive, which was more apparent in COPD patients. [ABSTRACT FROM AUTHOR]

Background: In the late phase of production, ducks untimely cease laying, leading to a lower feed conversion. Liver plays a vital role in the synthesis and transport of yolk materials during egg formation in birds. However, the molecular mechanism of liver in ceased-laying duck is far from clear, higher resolution and deeper analysis is needed. Sing-cell RNA-sequencing of 10 × Genomics platform can help to map the liver single cell gene expression atlas of Shaoxing duck and provide new insights into the liver between egg-laying and ceased-laying ducks. Results: About 20,000 single cells were profiled and 22 clusters were identified. All the clusters were identified as 6 cell types. The dominant cell type is hepatocyte, accounted for about 60% of all the cells. Of note, the heterogeneity of cells between egg-laying duck and ceased-laying duck mainly occurred in hepatocytes. Cells of cluster 3 and 12 were the unique hepatocyte states of egg-laying ducks, while cells of cluster 0 and 15 were the unique hepatocyte states of ceased-laying ducks. The expression mode of yolk precursor transporters, lipid metabolizing enzymes and fibrinogens were different in hepatocytes between egg-laying duck and ceased-laying duck. APOV1, VTG2, VTG1, APOB, RBP, VTDB and SCD might be activated in egg-laying ducks, while APOA1, APOA4, APOC3, FGB and FGG might be activated in ceased-laying ducks. Conclusions: Our study further proofs that APOV1 and APOB play key roles in egg production, rather than APOA1 and APOA4. It is also the first to detect a correlation between the higher expression of APOC3, FGB, FGG and ceased-laying in duck. [ABSTRACT FROM AUTHOR]

Background: Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. Methods: Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. Results: We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). Conclusions: Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD. [ABSTRACT FROM AUTHOR]

Background: High caloric diet and lack of physical activity are considered main causes of NAFLD, and a change in the diet is still the only effective treatment of this disease. However, molecular mechanism of the effectiveness of diet change in treatment of NAFLD is poorly understood. We aimed to assess the involvement of epigenetic mechanisms of gene expression regulation in treatment of NAFLD. Eighteen participants with medium- to high-grade steatosis were recruited and trained to follow the Mediterranean diet modified to include fibre supplements. At three timepoints (baseline, after 30 and 60 days), we evaluated adherence to the diet and measured a number of physiological parameters such as anthropometry, blood and stool biochemistry, liver steatosis and stiffness. We also collected whole blood samples for genome-wide methylation profiling and histone acetylation assessment. Results: The diet change resulted in a decrease in liver steatosis along with statistically significant, but a minor change in BMI and weight of our study participants. The epigenetic profiling of blood cells identified significant genome-wide changes of methylation and acetylation with the former not involving regions directly regulating gene expression. Most importantly, we were able to show that identified blood methylation changes occur also in liver cells of NAFLD patients and the machine learning-based classifier that we build on those methylation changes was able to predict the stage of liver fibrosis with ROC AUC = 0.9834. Conclusion: Methylomes of blood cells from NAFLD patients display a number of changes that are most likely a consequence of unhealthy diet, and the diet change appears to reverse those epigenetic changes. Moreover, the methylation status at CpG sites undergoing diet-related methylation change in blood cells stratifies liver biopsies from NAFLD patients according to fibrosis grade. [ABSTRACT FROM AUTHOR]

Background: Postoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism. Methods and results: Rats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps < 0.05). Conclusions: This study revealed that BCAA lower blood glucose levels by reducing liver gluconeogenesis without significant elevation of plasma insulin levels. We anticipate that preoperative BCAA supplementation may be a means for preventing postoperative insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) cell culture has emerged as an alternative approach to 2D flat culture to model more accurately the phenotype of solid tissue in laboratories. Culturing cells in 3D more precisely recapitulates physiological conditions of tissues, as these cells reduce activities related to proliferation, focusing their energy consumption toward metabolism and homeostasis. Results: Here, we demonstrate that 3D liver spheroids are a suitable system to model chromatin dynamics and response to epigenetics inhibitors. To delay necrotic tissue formation despite proliferation arrest, we utilize rotating bioreactors that apply active media diffusion and low shearing forces. We demonstrate that the proteome and the metabolome of our model resemble typical liver functions. We prove that spheroids respond to sodium butyrate (NaBut) treatment, an inhibitor of histone deacetylases (HDACi), by upregulating histone acetylation and transcriptional activation. As expected, NaBut treatment impaired specific cellular functions, including the energy metabolism. More importantly, we demonstrate that spheroids reestablish their original proteome and transcriptome, including pre-treatment levels of histone acetylation, metabolism, and protein expression once the standard culture condition is restored after treatment. Given the slow replication rate (> 40 days) of cells in 3D spheroids, our model enables to monitor the recovery of approximately the same cells that underwent treatment, demonstrating that NaBut does not have long-lasting effects on histone acetylation and gene expression. These results suggest that our model system can be used to quantify molecular memory on chromatin. Conclusion: Together, we established an innovative cell culture system that can be used to model anomalously decondensing chromatin in physiological cell growth and rule out epigenetics inheritance if cells recover the original phenotype after treatment. The transient epigenetics effects demonstrated here highlight the relevance of using a 3D culture model system that could be very useful in studies requiring long-term drug treatment conditions that would not be possible using a 2D cell monolayer system. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers.Methods: One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups.Results: Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade.Conclusion: There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation. [ABSTRACT FROM AUTHOR]

Background: Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride–glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population. Methods: A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD. Results: Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03–5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders. In stratified analysis, an elevated TyG index were more remarkably associated with NAFLD in younger patients (< 65 years; OR, 2.35; 95% CI, 1.83–3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67–4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01–3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (< 1 mmol/L; OR, 2.76; 95% CI, 1.98–3.83; P < 0.001). Conclusion: The TyG index is significantly associated with NAFLD and shows superior ability for identify NAFLD risk compared with other lipid and glycemic parameters in T2DM. [ABSTRACT FROM AUTHOR]

Background: We attempted to estimate dietary vitamin A requirements based on dietary vitamin A intake in well-nourished Chinese children with adequate liver vitamin A reserves.Methods: A cross-sectional study was conducted in a kindergarten and an elementary school in Shiyan city, Hubei province of China from December 2009 to July 2010. After screening, 60 children (22 aged 4 ~ 6 y and 38 aged 7 ~ 9 y) were randomly subjected to a 3-d or 18-d deuterated-retinol-dilution (DRD) procedure to evaluate the vitamin A reserves in the body and liver. Dietary intakes of vitamin A were estimated from two (one in winter and one in summer) consecutive 3-day weighed food records and dietary recalls.Results: The dietary vitamin A intakes were significantly correlated with vitamin A stores in the body and liver, but not with the serum level of retinol. The dietary vitamin A intakes were 476.9 ± 196.7 µg retinol equivalent (RE) (or 377.7 ± 166.2 µg retinol activity equivalent (RAE)) / day for 4 ~ 6 y children and 529.1 ± 87.2 µg RE/d (or 464.0 ± 81.1 µg RAE/d) for 7 ~ 9 y children with adequate liver vitamin A reserves. The estimated liver stores of vitamin A derived from both time points (3-d and 18-d) were similar.Conclusion: Adequate dietary vitamin A intakes among the well-nourished Chinese children were estimated to be 477 µg RE/d (95%CI 385 ~ 570) or 378 µg RAE/d (95%CI 304 ~ 441) for 4 ~ 6 y children and 529 µg RE/d (95%CI 500 ~ 560) or 464 µg RAE/d (95%CI 437 ~ 491) for 7 ~ 9 y children. Although it needs to be verified in a larger population of different regions in China, our results provide important data to establish the dietary requirement of vitamin A specifically for Chinese children. [ABSTRACT FROM AUTHOR]

In their recent publication, Liu et al. leverage a novel mouse model expressing hepatic ApoE3 or ApoE4 on an Apoe knockout background to show that liver-derived E4, but not E3, has multiple pathogenic effects. Keywords: Peripheral ApoE; ApoE4; Alzheimer's disease; Cerebrovascular impairment; Blood-brain barrier; Liver EN Peripheral ApoE ApoE4 Alzheimer's disease Cerebrovascular impairment Blood-brain barrier Liver 1 4 4 10/07/22 20221004 NES 221004 Main text The 4 allele of Apolipoprotein E ( I APOE i ), which is carried by approximately one out of six individuals, remains the strongest known genetic risk factor for late-onset Alzheimer's Disease (AD). Abbreviations ApoE Apolipoprotein E AD Alzheimer's disease BBB Blood brain barrier CNS Central nervous system E3 ApoE3 E4 ApoE4 ECM Extracellular Matrix Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

Introduction: Disseminated intravascular coagulation (DIC) is a syndrome characterized by coagulopathy, microthrombus, and multiple organ failure. The complement system in DIC is overactivated, and the functions of complement and coagulation pathways are closely related. Our previous screening revealed that salvianolic acid A (SAA) has anti-complement activity. The hyper-activated complement system was involved in the lipopolysaccharide (LPS) induced DIC in rats. The effects of SAA anti-complement action on LPS-induced DIC in rats were investigated. Methods: The complement activity of the classical pathway and alternative pathway was detected through an in vitro hemolysis assay. The binding sites of SAA and complement C3b were predicted by molecular docking. LPS-induced disseminated coagulation experiments were performed on male Wistar rats to assess coagulation function, complement activity, inflammation, biochemistry, blood routine, fibrinolysis, and survival. Results: SAA had an anti-complement activity in vivo and in vitro and inhibited the complement activation in the classical and alternative pathway of complement. The infusion of LPS into the rats impaired the coagulation function, increased the plasma inflammatory cytokine level, complemented activation, reduced the clotting factor levels, fibrinogen, and platelets, damaged renal, liver, and lung functions, and led to a high mortality rate (85%). SAA treatment of rats inhibited complement activation and attenuated the significant increase in D-dimer, interleukin-6, alanine aminotransferase, and creatinine. It ameliorated the decrease in plasma levels of fibrinogen and platelets and reversed the decline in activity of protein C and antithrombin III. The treatment reduced kidney, liver, and lung damage, and significantly improved the survival rate of rats (46.2 and 78.6% for the low- and high-dose groups, respectively). Conclusion: SAA reduced LPS-induced DIC by inhibiting complement activation. It has considerable potential in DIC treatment. [ABSTRACT FROM AUTHOR]