Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

[Objective] To establish a real-time fluorescence quantitative PCR nucleic acid detection method of human parvovirus B19 and validate the method systematically. [Methods] Specific primers and probes for the highly conserved regions of the three genotypes of B19 virus were designed, and B19 quantitative amplification standard curves were established. The accuracy, precision (repeatability and intermediate precision), linear range, quantification limit, detection limit, specificity, anti cross contamination, genotyping and anti-interference ability of this method were verified. [Results] When the quantitative reference range for B19 virus was 2.0×10¹ to 1.0×10⁸ IU/mL, a double logarithmic regression analysis was performed between the measured values and the theoretical values, and the regression equation R²≥0.98 showed good linear correlation. The quantification limit was 20 IU/mL, with a detection rate of 100%. The detection limit was 10 IU/mL, and the detection rate is 95.23%. Three genotypes of B19 virus samples can be effectively detected. The plasma of seven non B19 pathogens, including hepatitis A virus, hepatitis B virus, hepatitis C virus, human immuno-deficiency virus, human cytomegalovirus, hepatitis E virus and Treponema pallidum, was non reactive and has good species specificity. Simultaneously, in the presence of seven other concurrent pathogens, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. When the hemoglobin concentration was 431 mg/dL, triglycerides (1 269 turbidity) and unconjugated bilirubin concentration was 20 mg/dL, this method was non reactive for all three common plasma interfering substances. In the presence of three common plasma interfering substances, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. The deviation between the detection values of standard substances at two concentration levels of S1 (E5 IU/mL) and S2 (E4 IU/mL) and the target values were≤±0.5 log value. The CV values of positive sample 1 (concentration level E5 IU/mL) and positive sample 2 (concentration level E4 IU/mL) for daily precision confirmation and continuous 5-day intra-day precision confirmation were both≤5%. [Conclusion] This method has strong specificity, high sensitivity, wide linear range, stability, reliability and high accuracy, and can be used for the detection of human parvovirus B19 nucleic acid in plasma.

Objective To explore the role of Panax notoginseng saponins(PNS)in regulating the expression of sortilin and ATP-binding cassette transporter A1(ABCA1)in macrophages,and the effect of PNS on inhibiting formation of foam cells and the potential mechanism of PNS adjusting sortilin expression and cholesterol metabolism.Methods The macrophages were divided into five groups as follows:group A(only added with cell culture),group B(transfected with negative control lentivirus),group C(transfected with lentivirus-mediated sortilin overexpression),group D(transfected with lentivirus-mediated sortilin overexpression+60 μg·mL-1PNS),group E(transfected with lentivirus-mediated sortilin overexpression+10 μmol·L-1 mitogen-activated protein kinase kinase(MEK)inhibitor PD98059+60 μg·mL-1 PNS).The protein contents of sortilin,ABCA1,extracellular signal-regulated kinase(ERK)and phosphorylated-ERK(p-ERK)were evaluated with Western blot.All the cells in five groups were cultured with 50 μg·mL-1ox-LDL to form foam cells.The lipid in macrophages was investigated with red O assay.Results The relative expression levels of sortilin protein were 1.00±0.08,0.91±0.15,2.28±0.13,1.62±0.09 and 2.01±0.08;the relative expression levels of ABCA1 protein were 1.00±0.01,0.92±0.07,0.29±0.04,0.66±0.09 and 0.44±0.07;the ratios of p-ERK/ERK protein were 1.00±0.09,0.92±0.05,1.03±0.12,2.00±0.12 and 1.64±0.14;the contents of lipid in macrophages were(4.82±2.19)％,(6.70±0.88)％,(44.56±4.15)％,(27.66±3.25)％and(41.67±5.45)％.Except the ratios of p-ERK/ERK,the other parameters between group C and group A were statistically significant difference(all P＜0.01).Meanwhile,there were also statistically significant difference between group D and group C as well as group D and group E(P＜0.05,P＜0.01).Conclusion PNS inhibits the lipid accumulation in macrophages through upregulating ABCA1 and downregulating sortilin,and ERK signaling pathway may be as one of important mechanisms influencing the expression of sortilin and ABCA1 mediated by PNS.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.