Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis

BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular carcinoma.The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis.Therefore,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic fibrosis.AIM To explore the effect of taurine on aHSC proliferation and the mechanisms involved.METHODS Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated group.Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs.Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron concen-tration.Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs.Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,ATG5,Beclin 1,PTGS2,SLC7A11,and p62.RESULTS Taurine promoted the death of aHSCs and reduced the deposition of the ECM.Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulating LC3B and Beclin 1 protein expression,and upregulating p62 protein expression.Meanwhile,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload,lipid ROS accumu-lation,glutathione depletion,and lipid peroxidation.Furthermore,bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4,exhibiting the best average binding affinity of-20.99 kcal/mol.CONCLUSION Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

The effect of traditional Chinese medicine rehabilitation exercise(pulmonary Daoyin)in patients with chronic obstructive pulmonary disease:A systematic review and meta-analysis

Objective:Previous research has demonstrated that pulmonary Daoyin could be an efficacious way to ameliorate the physical and psychological state of sufferers with chronic obstructive pulmonary disease(COPD)and bolster the quality of life.However,the results are not consistent.Thus,the objective of this research is to assess the impacts of pulmonary Daoyin in individuals with COPD.Methods:Relevant articles were searched in Web of Science,Cochrane Library,PubMed,EMBASE,SinoMed,CNKI,Wanfang,and VIP from database inception to January 2024.Results:There were a total of 15 randomized controlled trials(RCTs)included in this meta-analysis involving 1732 patients,of which 864 participated in the intervention group and 868 in the control group.When comparing with the control group,the COPD patients practicing pulmonary Daoyin demonstrated a significant improvement in 6 min walking distance(mean difference[MD]=24.53,95%confidence interval[CI][18.55,30.52],P<0.00001),forced expiratory volume in the 1 s(FEV_(1))(MD=0.39,95%CI[0.18,0.59],P=0.0002),percentage of FEV_(1)to the predicted value(FEV_(1)%)(MD=5.35,95%CI[3.22,7.48],P<0.0001),the forced vital capacity(FVC)(MD=0.39,95%CI[0.06,0.73],P=0.02),percentage of FVC to the predicted value(FVC%)(MD=7.52,95%CI[4.91,10.13],P<0.00001),the ratio of FEV_(1)/FVC(MD=4.95,95%CI[0.91,8.99],P=0.02),peak expiratory flow rate(standardized MD=0.98,95%CI[0.74,1.22],P<0.00001),modified Medical Research Council(mMRC)scale(MD=-0.47,95%CI[-0.89,-0.04],P=0.03),and Borg scale(MD=-0.65,95%CI[-0.75,-0.55],P<0.00001).Conclusions:Our findings may illuminate the influence of pulmonary Daoyin on exercise ability,breathlessness,and pulmonary function in COPD patients.More rigorous RCTs with larger samples and longer-term interventions will be required moving forward.

Study on the mechanism of effect of Daodi Tongguan Decoction on rats with premature ovarian failure

Objective:To investigate the mechanism of the effect of Daodi Tongguan Decoction on ovarian function in rats with premature ovarian failure.Methods:Forty SD female rats with regular estrous cycle were randomly divided into the blank group,the model group,the positive group(Bujiale 0.099 mg/kg),the Daodigitongguan decoction high-dose group(1.4 g/100 g)and the Daodigitongguan decoction medium-dose group(0.7 g/100 g).The model group,positive group,Daodi Tongguan Decoction high-dose group and Daodi Tongguan decoction medium-dose group were given Tripterygium wilfordii polyglycoside tablets suspension(50 mg/kg)by continuous gavage for 14 days to establish a rat model of premature ovarian failure.After the modeling,each group was given the corresponding intervention agent for 28 consecutive days.After the intervention,serum and ovarian tissue were collected from rats in each group.The morphological structure of rat ovarian tissue was observed after HE staining.Serum AMH level was determined by ELISA.The expressions of Bcl-2,Bax and VEGF in ovarian tissue were detected by IHC.The apoptosis of granulosa cells in ovary was observed by TUNEL.Results:Compared to the normal group,the growth follicles in the model group were reduced and the atretic follicles were increased.Serum AMH level was significantly decreased(P<0.01).The expression of Bax protein in ovarian tissue was increased(P<0.01).The protein expressions of Bcl-2 and VEGF were decreased(P<0.01,P<0.05),and the apoptosis rate of follicular granulosa cells in ovarian tissue was increased(P<0.01).Compared to the molding group,the serum AMH level in the TCM dose groups was increased to varying degrees,and the change of the AMH in high-dose group was the most significant(P<0.05).The expression of Bax protein in ovarian tissue decreased(P<0.05),while the expression of Bcl-2 and VEGF protein increased(P<0.05,P<0.05).The apoptosis rate of follicular granulosa cells in ovarian tissue was decreased in the high dose group(P<0.05).Conclusion:Daodi Tongguan Decoction can improve the histological morphology of ovary and relieve ovarian injury,and its mechanism may be related to improving the sex hormone level of POF model rats,reducing the expression level of Bax protein in ovarian tissue,increasing the expression level of Bcl-2 and VEGF protein in ovarian tissue,and reducing the apoptosis rate of follicular granulosa cells in ovarian tissue.

Application status of artificial neural network in related research of liver cancer

The overcoming of liver cancer is a major problem urgently to be solved by the World Health Organization.The emergence of precision medicine brings hope to improving the level of diagnosis and treatment of liver cancer,but it is difficult for clinicians to effectively analyze and integrate a large amount of data from multiple dimensions and angles of precision medicine,so it is difficult totthem to provide the best treatment plan for liver cancer patients.Artificial neural networks have powerful integration,analysis and autonomous learning capabilities,which can effectively improve the accuracy of diagnosis,staging,prognosis and treatment of liver cancer patients,and are of great significance to the development of precision medicine for liver cancer.Therefore,this article reviews the application status of Artificial neural networks in the field of liver cancer.

Pulmonary nocardiosis with bloodstream infection diagnosed by metagenomic next-generation sequencing in a kidney transplant recipient:A case report

BACKGROUND Pulmonary nocardiosis is difficult to diagnose by culture and other conventional testing,and is often associated with lethal disseminated infections.This difficulty poses a great challenge to the timeliness and accuracy of clinical detection,especially in susceptible immunosuppressed individuals.Metagenomic nextgeneration sequencing(mNGS)has transformed the conventional diagnosis pattern by providing a rapid and precise method to assess all microorganisms in a sample.CASE SUMMARY A 45-year-old male was hospitalized for cough,chest tightness and fatigue for 3 consecutive days.He had received a kidney transplant 42 d prior to admission.No pathogens were detected at admission.Chest computed tomography showed nodules,streak shadows and fiber lesions in both lung lobes as well as right pleural effusion.Pulmonary tuberculosis with pleural effusion was highly suspected based on the symptoms,imaging and residence in a high tuberculosisburden area.However,anti-tuberculosis treatment was ineffective,showing no improvement in computed tomography imaging.Pleural effusion and blood samples were subsequently sent for mNGS.The results indicated Nocardia farcinica as the major pathogen.After switching to sulphamethoxazole combined with minocycline for antinocardiosis treatment,the patient gradually improved and was finally discharged.CONCLUSION A case of pulmonary nocardiosis with an accompanying bloodstream infection was diagnosed and promptly treated before the dissemination of the infection.This report emphasizes the value of mNGS in the diagnosis of nocardiosis.mNGS may be an effective method for facilitating early diagnosis and prompt treatment in infectious diseases,which overcomes the shortcomings of conventional testing.

The role of microRNA-200a in the occurrence and development of liver disease

microRNA(miRNA)is a type of small non-coding RNA that can participate in cell proliferation and apoptosis by regulating gene expression.More and more evidences indicate that miRNA-200a is involved in the occurrence and development of non-alcoholic fatty liver disease,alcoholic liver disease,drug-induced liver injury,liver fibrosis,and hepatocellular carcinoma.Downstream target genes of serotonin,regulating related signal pathways and playing different roles in the progression of a variety of liver diseases,provide a reference for exploring the mechanism of a variety of chronic liver diseases.

Integrating serum pharmacochemistry,network pharmacology and metabolomics analysis to explore the possible mechanism of Qingjiehuagong decoction in the treatment of acute pancreatitis

Background:The Qingjiehuagong decoction(QJHGD),which has been used in clinical trials to treat acute pancreatitis(AP),has demonstrated encouraging results.Methods:In this particular investigation,we used both metabolomics and network pharmacology to investigate the fundamental processes and targets that QJHGFD employs to cure AP.Results:Using a cerulein-induced rat model of AP,we showed that QJHGD effectively improved pancreatic tissue damage and reduced serum levels of AMY,LPS,IL-1β,IL-6,IL-8 and TNF-α.In total,28 blood entry compounds derived from QJHGD were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology.The intersecting target genes of 108 genes associated with identified compounds in QJHGD and AP disease genes were identified using a network pharmacology approach.The protein interaction network revealed AKT1,TNF-α,IL-6,VEGFA,and TP53 as important targets.Gene ontology analysis showed that response to stimulus,molecular function regulator and organelle part were the main functions,and Kyoto Encyclopedia of Genes and Genomes analysis showed that 20 pathways such as AGE-RAGE signaling pathway in diabetic complications and the IL-17 signaling pathway were the main pathways involved in the anti-AP effects of QJHGD.Thirty-two potential metabolic markers and 13 possible metabolic pathways were identified by metabolomics analysis.Combined network pharmacological analysis revealed that QJHGD affects four metabolic pathways(tryptophan metabolism;glycolysis and gluconeogenesis metabolism;valine,leucine and isoleucine degradation metabolism;the urea cycle and metabolism of arginine,proline,glutamate,aspartate and asparagine),five metabolites(indole-3-acetate,pyruvate,methylmalonate,L-citrulline,N-acetyl-l-glutamate)and four related targets(AKT1,ALDH2,NOS2,NOS3)to combat inflammation.The strong affinity of QJHGD’s interactions with its primary targets was established by molecular docking and molecular dynamics simulations.Conclusion:This research investigate the critical targets and mechanisms of QJHGFD for treating AP.The results of this investigation provide novel tactics and complementary techniques for the clinical treatment of AP.

The role of microRNA-155 in the development and diagnosis of liver disease

microRNA(miRNA)is a type of single-stranded small molecule non-coding RNA that interacts with the 3'untranslated region of the target gene to achieve negative regulation of the target gene and participate in multiple links of cell proliferation and apoptosis.At present,there is evidence that miRNA-155 is involved in the occurrence and development of a variety of liver diseases.By consulting relevant literature reports,this article summarizes the effects of miRNA-155 in non-alcoholic fatty liver disease,alcoholic liver disease,viral hepatitis,acute liver failure,and liver disease.The research progress of fibrosis and liver cancer in a variety of liver diseases,and the potential of miRNA-155 as a non-invasive biomarker is analyzed to provide a reference for exploring the diagnosis and treatment of liver diseases.

Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

AIM: To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients. METHODS: We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals. Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis. A new fibrosis index [globulin/platelet (GP) model] was developed, including globulin (GLOB) and platelet count (PLT). GP model = GLOB (g/mL) × 100/PLT (× 109/L). We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models. RESULTS: Thirteen clinical biochemical and hematological variables [sex, age, PLT, alanine aminotransferase, aspartate aminotransferase (AST), albumin, GLOB, total bilirubin (T.bil), direct bilirubin (D.bil), glutamyltransferase, alkaline phosphatase, HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1, F2-F3 and F4). Bivariate Spearman's rank correlation analysis showed that six variables, including age, PLT, T.bil, D.bil, GLOB and PT, were correlated with the three fibrosis stages (FS). Correlation coefficients were 0.23, -0.412, 0.208, 0.220, 0.314 and 0.212; and P value was 0.014, < 0.001, 0.026, 0.018, 0.001 and 0.024, respectively. Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT: F = 11.772, P < 0.001; GLOB: F = 6.612, P = 0.002). Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R 2 = 0.237). By Spearman's rank correlation analysis, GP model was significantly correlated with the three FS (r = 0.466, P < 0.001). The median values in F0-F1, F2-F3 and F4 were 1.461, 1.720 and 2.634. Compared with the six available models (fibrosis index, AST-platelet ratio, FIB-4, fibrosis-cirrhosis index and age-AST model and age-PLT ratio), GP model showed a highest correlation coefficient. The sensitivity and positive predictive value at a cutoff value < 1.68 for predicting minimal fibrosis F0-F1 were 72.4% and 71.2%, respectively. The specificity and negative predictive value at a cutoff value < 2.53 for the prediction of cirrhosis were 84.5% and 96.7%. The area under the curve (AUC) of GP model for predicting minimal fibrosis and cirrhosis was 0.762 [95% confidence interval (CI): 0.676-0.848] and 0.781 (95% CI: 0.638-0.924). Although the differences were not statistically significant between GP model and the other models (P all > 0.05), the AUC of GP model was the largest among the seven models. CONCLUSION: By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.

Therapeutic effect and apoptosis mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis

Objective:To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis,and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation.Methods:A total of 60 C57BL/6J male rats were included in the study.The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation.About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each:blank control group,cisplatin group,low dose group,medium dose group and high dose group.The blank control group was treated with normal saline,and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses.The volume change in transplanted tumor,tumor inhibition rate,apoptosis rate,and expression of Bc1-2,Bax.cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared.Results:The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group.The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction,and the difference in growth of tumor volume among groups was statistically significant(P<0.05).The cisplatin group showed the highest tumor inhibition rate,with dose-dependent increase(P<0.05).The apoptosis rate in low dose group was higher than blank control group but lower than high dose group(P<0.05).The apoptosis rate in medium dose group was significantly higher man blank control group(P).05).The apoptosis rate in high dose group was significantly higher than control group(P<0.05).The positive expression rates of Bel-2 and Bax in all groups showed statistically significant difference(P<0.05),while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different,with dose-dependent increase(P<0.05).Conclusions:The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis,probably with good clinical therapeutic effect.

Integrated network analysis of transcriptomic and protein-protein interaction data in taurine-treated hepatic stellate cells

BACKGROUND Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells(HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use "omics" methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis.AIM To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.METHODS We used microarrays, bioinformatics, protein-protein interaction(PPI) network,and sub-modules to investigate taurine-induced changes in gene expression in human HSCs(LX-2). Subsequently, all of the differentially expressed genes(DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software.RESULTS A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1(ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway,estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including MMP2, MMP9, MMP21,TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were identified in the PPI network analysis.CONCLUSION Taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.

The active principle region of Buyang Huanwu decoction induced differentiation of bone marrow-derived mesenchymal stem cells into neural-like cells Superior effects over original formula of Buyang Huanwu decoction

The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction （active principle region of decoction for invigorating yang for recuperation）. After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula.

Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

AIM:To investigate the inhibitory effect of natural taurine(NTau)on portal hypertension(PHT)in rats with experimentally-induced liver cirrhosis(LC). METHODS:Experimentally-induced LC Wistar rats(20 rats/group)were treated with either oral saline or oral NTau for 6 consecutive weeks.Evaluation parameters included portal venous pressure(PVP),portal venous resistance(PVR),portal venous flow(PVF),splanchnic vascular resistance(SVR)and mean arterial pressure (MAP).Vasoactive substance levels including nitric oxide(NO),nitric oxide synthase(NOS)and cyclic guanosine monophosphate(cGMP)were also measured. Histological investigation of typeⅠandⅢcollagen (COLⅠandⅢ)and transforming growth factor-β1 (TGF-β1)was also performed. RESULTS:Treatment with NTau(1)significantly decreased PVP,PVR and PVF,and increased MAP and SVP;(2)markedly increased the vascular compliance and reduced the zero-stress of the portal vein;(3) markedly decreased the amount of NO and cGMP and activity of NOS;and(4)improved the pathological sta-tus of the liver tissue and reduced the expression of COLⅠ,COLⅢand TGF-β1. CONCLUSION:NTau inhibited the LC-induced PHT by improving hyperdynamic circulation,morphology of liver and biomechanical properties of the portal vein in experimentally-induced LC rats.

MicroRNA-34a promoting apoptosis of human lens epithelial cells through down-regulation of B-cell lymphoma-2 and silent information regulator

AIM： To investigate the role of micro RNA-34a（mi R-34a） in the induction of apoptosis of human lens epithelial（HLE-B3） cells. METHODS： The apoptosis of HLE-B3 cells was detected by Annexin V-PE apoptosis detection kit after the treatment with 200 μmol/L H2O2 for 24h and lentiviral mi R-34 a vector transfection. The expression of mi R-34 a in the cells was quantified by quantitative real time polymerase chain reaction（q RT-PCR） in response to H2O2 exposure and the vector transfection. The effects of overexpression of mi R-34 a on the expression of B-cell lymphoma-2（Bcl-2） and silent information regulator 1（SIRT1） was determined by q RT-PCR and Western blot. RESULTS： The expression of mi R-34 a was up-regulated by the treatment of H2O2 in HLE-B3 cells. The increased expression of mi R-34 a is accompanied with the cell apoptosis. Consistence with the H2O2 exposure,ectopic overexpression of mi R-34 a in HLE-B3 cells promoted cells apoptosis. Importantly the anti-apoptosis factors Bcl-2 and SIRT1 were reduced significantly by up-regulation of mi R-34 a in HLE-B3 cells.CONCLUSION： Mi R-34 a promotes the apoptosis of HLE-B3 cells by down-regulating Bcl-2 and SIRT1,suggesting that mi R-34 a may involve in the pathogenesis of cataract formation and targeting mi R-34 a may be a potentially therapeutic approach for treatment of cataract.

Metabolomic profiling for identification of metabolites and relevant pathways for taurine in hepatic stellate cells

AIM To develop a reliable and simple method to identify important biological metabolites and relevant pathways for taurine in hepatic stellate cells(HSCs), in order to provide more data for taurine therapy.METHODS All the biological samples were analyzed by using highperformance liquid chromatography-time electrospray ionization/quadrupole-time of flight mass spectrometry. Principal component analysis and partial least squares discriminant analysis were used to identify statistically different metabolites for taurine in HSCs, and metabolomic pathway analysis was used to do pathway analysis for taurine in HSCs. The chemical structure of the related metabolites and pathways was identified by comparing the m/z ratio and ion mode with the data obtained from free online databases.RESULTS A total of 32 significant differential endogenous metabolites were identified, which may be related to the mechanism of action of taurine in HSCs. Among the seven relevant pathways identified, sphingolipid metabolism pathway, glutathione metabolism pathway and thiamine metabolism pathway were found to be the most important metabolic pathways for taurine in HSCs.CONCLUSION This study showed that there were distinct changes in biological metabolites of taurine in HSCs and three differential metabolic pathways including sphingolipid pathway, glutathione pathway and thiamine metabolism pathway might be of key importance in mediating the mechanism of action of taurine in HSCs.

Electroacupuncture exerts neuroprotective effects on ischemia/reperfusion injury in JNK knockout mice：the underlying mechanism

Simple regulation of c-Jun N-terminal kinase（JNK） or p38 mitogen-activated protein kinase（MAPK） pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway（JNK/p38 MAPK） together with inhibition of the growth factor activated extracellular signal-regulated kinase（ERK） pathway can promote cell apoptosis.We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury.To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice,mouse models of cerebral ischemia/reperfusion injury were established by Longa’s method.Electroacupuncture was conducted at acupoints Chize（LU5）,Hegu（LI4）,Sanyinjiao（SP6） and Zusanli（ST36） 1.5 hours after ischemia/reperfusion injury for 20 minutes,once a day.The neurological function was evaluated using neurological deficit scores.The expression of phospho-extracellular signal-regulated kinase（p-ERK） and phospho-p38（p-p38） in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay.The m RNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction.Electroacupuncture improved neurological function,increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side.Electroacupuncture increased m RNA expression of ERK,but decreased that of p38 in the cerebral cortex and hippocampus on the injured side.In conclusion,electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway,thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.

Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively, mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.

An experimental research of Weining granule in treating gastric precancerous lesions

目的将在胃的癌症前期的损害的治疗调查 Weining 小粒的潜在的治疗学的效果和机制。六十只老鼠随机被分到一个空白的组或一个模型组或到的方法收到酸或高的 retinoic -- ，中等 -- 或低 -- Weining 的剂量小粒。动物的一般条件在治疗前后被遵守。在胃的 mucosal pathohistology， telomerase 活动，增长索引(PI ) 和 apoptosis 索引(AI ) 的变化被测量。结果将军调节，包括活动并且吃，与肠的组织变形(IM ) ，不正常的增生(ATP ) 或是比在模型的那些显著地低的积极 telomerase 活动组织的老鼠有的数字在所有 Weining-granule-treated 组被改进(P 【 0.05 或 P 【 0.01 ) 。与模型组相比， Weining 小粒的所有剂量显著地减少了 PI (P 【 0.01 ) 并且增加的 AI (P 【 0.05 ) 。结论 Weining 小粒可以由禁止 telomerase 活动和胃的癌症房间并且由加速他们的 apoptosis 的增长为胃的癌症前期的损害的治疗提供一个治疗学的好处。

Intercellular adhesion molecule-5 protects PAJU cells during in vitro ischemia following cerebral infarction

BACKGROUND： Intercellular adhesion molecule-5 （ICAM-5） relieves the damage of beta-amyloid protein to PAJU cells, However, little is known about how ICAM-5 works as a neurotrophic factor, or whether ICAM-5 lessens neuronal damage under ischemic conditions following cerebral infarction. OBJECTIVE： To investigate the effects of ICAM-5 on PAJU cells growth in serum-free medium under ischemic conditions following cerebral infarction. DESIGN, TIME AND SETTING： The cytological in vitro study was performed at the Central Laboratory, Second Xiangya Hospital, Central South University, China, in June 2009. MATERIALS： Human ICAM-5 gene transfected into PAJU-TLN cells was supplied by the Life Science College, Helsinki University, Finland. Empty vector transfected PAJU-NEO cells were established by the Gene Center, Second Xiangya Hospital, Central South University, China. METHODS： PAJU-TLN cells transfected with human ICAM-5 or empty vector were incubated in serum-free medium. MAIN OUTCOME MEASURES： Phase contrast microscopy was used to observe changes in PAJU cell morphology. 3-（4, 5-dimethylthiazolzyl）-2, 5-diphenyltetrazolium bromide was used to determine cell viability. Hoechst 33258 was used to stain cell nuclei. Flow cytometry was utilized to measure the apoptosis rate of both PAJU-TLN and PAJU-NEO cells. RESULTS： Both PAJU-TLN and PAJU-NEO cells were injured by cultivating in serum-free medium, but the survival rate of PAJU-TLN cells was significantly higher. CONCLUSION： ICAM-5 protects PAJU-TLN cells from serum deprivation-induced apoptosis, induces the outgrowth of PAJU cells, and diminishes their morphologic impairment.