Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective To investigate the risk factors for ligamentum flavum hypertrophy(LFH)and its correlation with clinical symptoms in patients with degenerative lumbar spinal stenosis(DLSS).Methods The clinical and imaging data of 79 patients with DLSS were collected.Patients were divided into four groups based on LFH severity.Quantitative parameters,including lumbar lordosis(LL),sacral slope(SS),facet tropism,facet joint effusion,intervertebral height index,dural sac cross-sectional area(CSA),epidural fat area,and fat infiltration rate(FIR)of the paraspinal muscle were measured on imaging.One-way analysis of variance was used to compare the differences in these parameters among groups.Multiple linear regression analysis was performed to identify the risk fac-tors for LFH,and the correlation between LFH severity and clinical manifestations was analyzed.Results The results of one-way analy-sis of variance showed that there were statistically significant differences among the four groups of patients in terms of sex,body mass index(BMI),LL,epidural fat area and FIR of the multifidus(MF).Multiple linear regression analysis identified that BMI,LL,and epidural fat area as independent risk factors for LFH.Correlation analysis indicated a weak positive association between LFH and dis-ease duration(r=-0.231,P=0.041).Conclusion In DLSS patients,LFH is weakly correlated with disease duration,while BMI,LL,and epidural fat area are risk factors for LFH.

OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.

Cardiovascular diseases have the very high morbidity and mortality in the world.In recent years,the pharmacological effect and mechanism of Ganoderma lucidum has become the focus of research.Ganoderma lucidum,a traditional Chinese medicine,has broad development prospects and resource reserves.However,the mechanism of Ganoderma lucidum prevention and treatment of cardiovascular diseases is still lack of a complete review.In this paper,several domestic and foreign databases including CNKI and PubMed were searched to summarize the research progress of Ganoderma lucidum in anti-atherosclerosis,lowering blood lipids and lowering blood pressure in recent ten years.The main pharmacological mechanisms of Ganoderma lucidum in preventing and treating cardiovascular diseases include anti-inflammation,anti-oxidative stress,regulation of mitochondrial function,inhibition of calcium overload,regulation of intestinal flora and maintenance of cholesterol balance.On this basis.In addition,the paper also proposes to strengthen the in-depth study of Ganoderma lucidum in preventing and treating cardiovascular diseases,and pointed out the shortcomings of the existing research on Ganoderma lucidum,which provided some reference and guidance for promoting the in-depth study of its mechanism of action and clinical transformation of drugs.

Objective To investigate the relationship between kinase insert domain receptor(KDR)rs2305948 polymorphism and clopidogrel resistance(CR)in patients with acute coronary syndrome after receiving percutaneous coronary intervention(PCI).Methods A total of 468 patients with acute coronary syndrome,who were admitted to the Zhangjiakou Municipal First Hospital of China from September 2022 to September 2023,were selected as the subjects of study.All patients received PCI treatment and took medication of clopidogrel after the treatment.The occurrence of CR was recorded.The factors influencing the occurrence of CR were analyzed.The clinical significance of KDR rs2305948 polymorphism in predicting CR in patients with acute coronary syndrome after receiving PCI was evaluated.Results Of 468 patients with acute coronary syndrome,116(24.79％)developed CR.Logistic multivariate regression analysis indicated that low-density lipoprotein cholesterol(LDL-C,95％CI=1.420-8.390,OR=3.452),type 2 vascular endothelial growth factor receptor(VEGFR-2,95％CI=1.374-8.118,OR=3.340),KDR rs2305948 T/T genotype(95％CI=1.677-9.905,OR=4.076),and T allele(95％CI=1.390-8.207,OR=3.377)were the independent factors influencing the occurrence of CR inpatients with acute coronary syndrome after receiving PCI(all P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity,specificity,and area under ROC curve(AUC)of the T/T genotype of KDR rs2305948 in predicting CR in patients with acute coronary syndrome after receiving PCI were 75.86％,70.45％,and 0.773(95％CI=0.666-0.880)respectively.Conclusion In patients with acute coronary syndrome after receiving PCI,the risk of developing CR is higher.The KDR rs2305948 polymorphism is correlated with CR in patients with acute coronary syndrome after receiving PCI,and it has a certain predictive value for CR.

Objective To investigate the risk factors for ligamentum flavum hypertrophy(LFH)and its correlation with clinical symptoms in patients with degenerative lumbar spinal stenosis(DLSS).Methods The clinical and imaging data of 79 patients with DLSS were collected.Patients were divided into four groups based on LFH severity.Quantitative parameters,including lumbar lordosis(LL),sacral slope(SS),facet tropism,facet joint effusion,intervertebral height index,dural sac cross-sectional area(CSA),epidural fat area,and fat infiltration rate(FIR)of the paraspinal muscle were measured on imaging.One-way analysis of variance was used to compare the differences in these parameters among groups.Multiple linear regression analysis was performed to identify the risk fac-tors for LFH,and the correlation between LFH severity and clinical manifestations was analyzed.Results The results of one-way analy-sis of variance showed that there were statistically significant differences among the four groups of patients in terms of sex,body mass index(BMI),LL,epidural fat area and FIR of the multifidus(MF).Multiple linear regression analysis identified that BMI,LL,and epidural fat area as independent risk factors for LFH.Correlation analysis indicated a weak positive association between LFH and dis-ease duration(r=-0.231,P=0.041).Conclusion In DLSS patients,LFH is weakly correlated with disease duration,while BMI,LL,and epidural fat area are risk factors for LFH.

OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.

Cardiovascular diseases have the very high morbidity and mortality in the world.In recent years,the pharmacological effect and mechanism of Ganoderma lucidum has become the focus of research.Ganoderma lucidum,a traditional Chinese medicine,has broad development prospects and resource reserves.However,the mechanism of Ganoderma lucidum prevention and treatment of cardiovascular diseases is still lack of a complete review.In this paper,several domestic and foreign databases including CNKI and PubMed were searched to summarize the research progress of Ganoderma lucidum in anti-atherosclerosis,lowering blood lipids and lowering blood pressure in recent ten years.The main pharmacological mechanisms of Ganoderma lucidum in preventing and treating cardiovascular diseases include anti-inflammation,anti-oxidative stress,regulation of mitochondrial function,inhibition of calcium overload,regulation of intestinal flora and maintenance of cholesterol balance.On this basis.In addition,the paper also proposes to strengthen the in-depth study of Ganoderma lucidum in preventing and treating cardiovascular diseases,and pointed out the shortcomings of the existing research on Ganoderma lucidum,which provided some reference and guidance for promoting the in-depth study of its mechanism of action and clinical transformation of drugs.

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals