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Splendour of Curcuma kinds via Japan utilizing intron length polymorphism markers in genes coding diketide-CoA synthase and curcumin synthase.
While this review is based on studies with and without RUCAM, the conclusions were carefully established mainly from studies that used RUCAM. The aim of this review is to provide information on the epidemiology, risk factors, clinical presentation, diagnostic tools, and management plan based on the most recent studies of immunotherapy-induced hepatotoxicity.Interleukin (IL) 1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver. Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage, the release of inflammatory cytokines and disturbances in gut microbiota. IL1 cytokines and receptors can have pro- or anti-inflammatory roles, even dual functionalities conditioned by the microenvironment. Developing novel therapeutic strategies to block the IL1/IL1R signaling pathways seems like a reasonable option. This mode of action is now exploited by anakinra and canakinumab, which are used to treat different inflammatory illnesses, and studies in liver diseases are on the way. In this mini review, we have focused on the IL1 superfamily members, given their crucial role in liver inflammation diseases, specifically discussing their potential role in developing new treatment strategies.
The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH.
A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula
and
. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism.
The positive contribution of the Quzhi formula on NASH was confirmed
and
. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling.
The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.
The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.
Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.
Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA).
Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD 0.05, Crl 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD 0.03, Crl 0.02-0.04) and fibrosis (MD 0.01, Crl -0.12 to 0.14) compared with placebo. The luate the cardiovascular outcomes.Alcoholic liver disease is one of the most common chronic liver diseases in the world. It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea, vomiting, enlargement of the liver, and jaundice. Recent studies suggest that Kupffer cell-mediated inflammatory response is a core driver in the development of alcoholic steatohepatitis and alcoholic liver fibrosis. As a danger signal, extracellular ATP activates the assembly of NLPR3 inflammasome by acting on purine P2X7 receptor, the activated NLRP3 inflammasome prompts ASC to cleave pro-cCaspase-1 into active caspase-1in KCs. Active caspase-1 promotes the conversion of pro-IL-1β to IL-1β, which further enhances the inflammatory response. Here, we briefly review the role of the P2X7R-NLRP3 inflammasome axis in the pathogenesis of alcoholic liver disease and the evolution of alcoholic steatohepatitis and alcoholic liver fibrosis. Regulation of the inflammasome axis of P2X7R-NLRP3 may be a new approach for the treatment of alcoholic liver disease.
Liver stiffness (LS) measured by shear wave elastography (SWE) is often influenced by hepatic inflammation. The aim was to develop a dual-task convolutional neural network (DtCNN) model for the simultaneous staging of liver fibrosis and inflammation activity using 2D-SWE.
A total of 532 patients with chronic hepatitis B (CHB) were included to develop and validate the DtCNN model. An additional 180 consecutive patients between December 2019 and April 2021 were prospectively included for further validation. All patients underwent 2D-SWE examination and serum biomarker assessment. A DtCNN model containing two pathways for the staging of fibrosis and inflammation was used to improve the classification of significant fibrosis (≥F2), advanced fibrosis (≥F3) as well as cirrhosis (F4).
Both fibrosis and inflammation affected LS measurements by 2D-SWE. The proposed DtCNN performed the best among all the classification models for fibrosis stage [significant fibrosis AUC=0.89 (95% CI 0.87-0.92), advanced fibrosis AUC=0.87 (95% CI 0.84-0.90), liver cirrhosis AUC=0.85 (95% CI 0.81-0.89)]. The DtCNN-based prediction of inflammation activity achieved AUCs of 0.82 (95% CI 0.78-0.86) for grade ≥A1, 0.88 (95% CI 0.85-0.90) grade ≥A2 and 0.78 (95% CI 0.75-0.81) for grade ≥A3, which were significantly higher than the AUCs of the single-task groups. H-1152 2HCl Similar findings were observed in the prospective study.
The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.
The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.
Metabolic associated fatty liver disease (MAFLD) is a serious condition, and a simple method is needed for practitioners to identify patients with the disease and have a high risk of disease progression.
We developed and validated a nomogram for fatty liver disease and reclassified the risk factors for MAFLD. The development cohort had 335 patients who received bioelectrical impedance analysis and liver ultrasound attenuation measurements at Shenzhen People's Hospital between September 2020 and June 2021. The validation cohort had 200 patients from other hospitals who received the same evaluation. A random forest procedure and binary logistic analysis were used to screen for risk factors, establish a fatty liver disease predictive model, and forecast the risk of MAFLD. The performance of the nomogram was evaluated by measurement of discrimination, calibration, and clinical usefulness.
The nomogram provided good predictions in a model that included body mass index (BMI) and waist circumference. The areas under the curve of the nomogram were 0.793 in the development cohort and 0.774 in the validation cohort. The nomogram performed well for calibration, category-free net reclassification improvement, and integrated discrimination improvement. Decision curve analysis indicated the nomogram performed better than BMI for predicting net outcome.
The nomogram was an effective screening tool for fatty liver disease, and for those overweight individuals, may help physicians make appropriate decisions regarding treatment of MAFLD.
The nomogram was an effective screening tool for fatty liver disease, and for those overweight individuals, may help physicians make appropriate decisions regarding treatment of MAFLD.
Recognition of excessive activation of hepatic stellate cells (HSCs) in liver fibrosis prompted us to investigate the regulatory mechanisms of HSCs. We aimed to examine the role of O-GlcNAcylation modification of alanine, serine, cysteine transporter 2 (ASCT2) in HSCs and liver fibrosis.
The expression of O-GlcNAcylation modification in fibrotic mice livers and activated HSCs was analyzed by western blotting. Immunoprecipitation was used to assess the interaction of ASCT2 and O-GlcNAc transferase (OGT). In addition, ASCT2 protein stability was assayed after cycloheximide (CHX) treatment. The O-GlcNAcylation site of ASCT2 was predicted and mutated by site-directed mutagenesis. Real-time PCR, immunofluorescence, kit determinations and Seahorse assays were used to clarify the effect of ASCT2 O-GlcNAcylation on HSC glutaminolysis and HSC activation. Western blotting, immunochemistry, and immunohistofluorescence were used to analyze the effect of ASCT2 O-GlcNAcylation
.
We observed significantly increased O-GlcNAcylation modification of ASCT2. ASCT2 was found to interact with OGT to regulate ASCT2 stability. We predicted and confirmed that O-GlcNAcylation of ASCT2 at Thr122 site resulted in HSCs activation. We found Thr122 O-GlcNAcylation of ASCT2 mediated membrane trafficking of glutamine transport and attenuated HSC glutaminolysis. Finally, we validated the expression and function of ASCT2 O-GlcNAcylation after injection of AAV8-ASCT2 shRNA in CCl
-induced liver fibrosis mice
.
Thr122 O-GlcNAcylation regulation of ASCT2 resulted in stability and membrane trafficking-mediated glutaminolysis in HSCs and liver fibrosis. Further studies are required to assess its role as a putative therapeutic target.
Thr122 O-GlcNAcylation regulation of ASCT2 resulted in stability and membrane trafficking-mediated glutaminolysis in HSCs and liver fibrosis. Further studies are required to assess its role as a putative therapeutic target.
Homepage: https://www.selleckchem.com/products/h-1152-dihydrochloride.html
While this review is based on studies with and without RUCAM, the conclusions were carefully established mainly from studies that used RUCAM. The aim of this review is to provide information on the epidemiology, risk factors, clinical presentation, diagnostic tools, and management plan based on the most recent studies of immunotherapy-induced hepatotoxicity.Interleukin (IL) 1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver. Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage, the release of inflammatory cytokines and disturbances in gut microbiota. IL1 cytokines and receptors can have pro- or anti-inflammatory roles, even dual functionalities conditioned by the microenvironment. Developing novel therapeutic strategies to block the IL1/IL1R signaling pathways seems like a reasonable option. This mode of action is now exploited by anakinra and canakinumab, which are used to treat different inflammatory illnesses, and studies in liver diseases are on the way. In this mini review, we have focused on the IL1 superfamily members, given their crucial role in liver inflammation diseases, specifically discussing their potential role in developing new treatment strategies.
The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH.
A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula
and
. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism.
The positive contribution of the Quzhi formula on NASH was confirmed
and
. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling.
The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.
The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.
Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.
Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA).
Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD 0.05, Crl 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD 0.03, Crl 0.02-0.04) and fibrosis (MD 0.01, Crl -0.12 to 0.14) compared with placebo. The luate the cardiovascular outcomes.Alcoholic liver disease is one of the most common chronic liver diseases in the world. It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea, vomiting, enlargement of the liver, and jaundice. Recent studies suggest that Kupffer cell-mediated inflammatory response is a core driver in the development of alcoholic steatohepatitis and alcoholic liver fibrosis. As a danger signal, extracellular ATP activates the assembly of NLPR3 inflammasome by acting on purine P2X7 receptor, the activated NLRP3 inflammasome prompts ASC to cleave pro-cCaspase-1 into active caspase-1in KCs. Active caspase-1 promotes the conversion of pro-IL-1β to IL-1β, which further enhances the inflammatory response. Here, we briefly review the role of the P2X7R-NLRP3 inflammasome axis in the pathogenesis of alcoholic liver disease and the evolution of alcoholic steatohepatitis and alcoholic liver fibrosis. Regulation of the inflammasome axis of P2X7R-NLRP3 may be a new approach for the treatment of alcoholic liver disease.
Liver stiffness (LS) measured by shear wave elastography (SWE) is often influenced by hepatic inflammation. The aim was to develop a dual-task convolutional neural network (DtCNN) model for the simultaneous staging of liver fibrosis and inflammation activity using 2D-SWE.
A total of 532 patients with chronic hepatitis B (CHB) were included to develop and validate the DtCNN model. An additional 180 consecutive patients between December 2019 and April 2021 were prospectively included for further validation. All patients underwent 2D-SWE examination and serum biomarker assessment. A DtCNN model containing two pathways for the staging of fibrosis and inflammation was used to improve the classification of significant fibrosis (≥F2), advanced fibrosis (≥F3) as well as cirrhosis (F4).
Both fibrosis and inflammation affected LS measurements by 2D-SWE. The proposed DtCNN performed the best among all the classification models for fibrosis stage [significant fibrosis AUC=0.89 (95% CI 0.87-0.92), advanced fibrosis AUC=0.87 (95% CI 0.84-0.90), liver cirrhosis AUC=0.85 (95% CI 0.81-0.89)]. The DtCNN-based prediction of inflammation activity achieved AUCs of 0.82 (95% CI 0.78-0.86) for grade ≥A1, 0.88 (95% CI 0.85-0.90) grade ≥A2 and 0.78 (95% CI 0.75-0.81) for grade ≥A3, which were significantly higher than the AUCs of the single-task groups. H-1152 2HCl Similar findings were observed in the prospective study.
The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.
The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.
Metabolic associated fatty liver disease (MAFLD) is a serious condition, and a simple method is needed for practitioners to identify patients with the disease and have a high risk of disease progression.
We developed and validated a nomogram for fatty liver disease and reclassified the risk factors for MAFLD. The development cohort had 335 patients who received bioelectrical impedance analysis and liver ultrasound attenuation measurements at Shenzhen People's Hospital between September 2020 and June 2021. The validation cohort had 200 patients from other hospitals who received the same evaluation. A random forest procedure and binary logistic analysis were used to screen for risk factors, establish a fatty liver disease predictive model, and forecast the risk of MAFLD. The performance of the nomogram was evaluated by measurement of discrimination, calibration, and clinical usefulness.
The nomogram provided good predictions in a model that included body mass index (BMI) and waist circumference. The areas under the curve of the nomogram were 0.793 in the development cohort and 0.774 in the validation cohort. The nomogram performed well for calibration, category-free net reclassification improvement, and integrated discrimination improvement. Decision curve analysis indicated the nomogram performed better than BMI for predicting net outcome.
The nomogram was an effective screening tool for fatty liver disease, and for those overweight individuals, may help physicians make appropriate decisions regarding treatment of MAFLD.
The nomogram was an effective screening tool for fatty liver disease, and for those overweight individuals, may help physicians make appropriate decisions regarding treatment of MAFLD.
Recognition of excessive activation of hepatic stellate cells (HSCs) in liver fibrosis prompted us to investigate the regulatory mechanisms of HSCs. We aimed to examine the role of O-GlcNAcylation modification of alanine, serine, cysteine transporter 2 (ASCT2) in HSCs and liver fibrosis.
The expression of O-GlcNAcylation modification in fibrotic mice livers and activated HSCs was analyzed by western blotting. Immunoprecipitation was used to assess the interaction of ASCT2 and O-GlcNAc transferase (OGT). In addition, ASCT2 protein stability was assayed after cycloheximide (CHX) treatment. The O-GlcNAcylation site of ASCT2 was predicted and mutated by site-directed mutagenesis. Real-time PCR, immunofluorescence, kit determinations and Seahorse assays were used to clarify the effect of ASCT2 O-GlcNAcylation on HSC glutaminolysis and HSC activation. Western blotting, immunochemistry, and immunohistofluorescence were used to analyze the effect of ASCT2 O-GlcNAcylation
.
We observed significantly increased O-GlcNAcylation modification of ASCT2. ASCT2 was found to interact with OGT to regulate ASCT2 stability. We predicted and confirmed that O-GlcNAcylation of ASCT2 at Thr122 site resulted in HSCs activation. We found Thr122 O-GlcNAcylation of ASCT2 mediated membrane trafficking of glutamine transport and attenuated HSC glutaminolysis. Finally, we validated the expression and function of ASCT2 O-GlcNAcylation after injection of AAV8-ASCT2 shRNA in CCl
-induced liver fibrosis mice
.
Thr122 O-GlcNAcylation regulation of ASCT2 resulted in stability and membrane trafficking-mediated glutaminolysis in HSCs and liver fibrosis. Further studies are required to assess its role as a putative therapeutic target.
Thr122 O-GlcNAcylation regulation of ASCT2 resulted in stability and membrane trafficking-mediated glutaminolysis in HSCs and liver fibrosis. Further studies are required to assess its role as a putative therapeutic target.
Homepage: https://www.selleckchem.com/products/h-1152-dihydrochloride.html
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