Objective:This study aimed to elucidate the influence of IFN-gamma(IFN-γ)in neuroblastoma(NB)cells and reveal its potential underlying molecular mechanism.Methods:The Cell Counting Kit-8,Transwell apparatus,and flow ...Objective:This study aimed to elucidate the influence of IFN-gamma(IFN-γ)in neuroblastoma(NB)cells and reveal its potential underlying molecular mechanism.Methods:The Cell Counting Kit-8,Transwell apparatus,and flow cytometry were employed to assess cellular viability,migratory capacity,invasive potential,and apoptotic rates,respectively.RNA-seq combined with bioinformatics analysis revealed differentially expressed genes(DEGs)and their possible biological functions.Protein levels were determined by western blot analysis.Results:IFN-γtreatment resulted in diminished cell viability,mitigated migratory and invasive capabilities,and augmented apoptotic activity in the SK-N-BE(2)cell line,whereas it exhibited the opposite effect in SH-SY5Y cells.Furthermore,interferon regulatory factor 1(IRF-1)was the common DEG in both IFN-γ-treated SK-N-BE(2)and SH-SY5Y cells.Additionally,we found that it was underexpressed in NB tissues.The depletion of IRF-1 promoted the progression of both SK-N-BE(2)and SH-SY5Y cells.Moreover,IRF-1 knockdown effectively counteracted the effects of IFN-γon SK-N-BE(2)cells,while exacerbating them in SH-SY5Y cells.Conclusion:This study verified that IFN-γexerted a distinct role in both N-Myc-and non-N-Myc-amplified NB cells,partially by mediating the expression of IRF-1,suggesting that it may serve as a potent agent for treating patients with NB.展开更多
Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to...Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.展开更多
BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this th...BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this threshold represent a heterogeneous group with an inadequately characterized risk profile.AIM To investigate the association between hs-TnT levels below the 99th percentile and the presence of diabetic kidney disease(DKD)in patients with diabetes mellitus.METHODS This study analyzed data from the National Health and Nutrition Examination Survey obtained between 1999 and 2004,focusing on adults with type 2 diabetes mellitus.Serum hs-TnT concentrations were evaluated.DKD was defined as impaired glomerular filtration rate(<60 mL/minute/1.73 m^(2)),proteinuria(urinary albumin-to-creatinine ratio of≥30 mg/g),or both conditions in patients with diabetes mellitus.Weighted multivariable logistic regression analysis and restricted cubic spline analyses were employed to examine the independent association between hs-TnT and DKD,with the likelihood ratio test being used to evaluate nonlinearity.RESULTS The study included 2505 patients with a mean age of 55.02(standard error:0.72)years,of whom 44.87%were females.Among the participants,909(32.34%)were diagnosed with DKD.Multivariable logistic regression analysis indicated that,compared to the lowest tertile of hs-TnT(<5.93 ng/L),tertile 2(5.94-9.79 ng/L)had an odds ratio of 1.25(95%confidence interval:0.77-2.02,P=0.350),while tertile 3(9.80-21.88 ng/L)had an odds ratio of 2.07(95%confidence interval:1.13-3.80,P=0.022),with a significant trend(P for trend=0.022).Smoothed curve fitting demonstrated a linear association between hs-TnT levels and DKD in the overall population(P=0.061 for nonlinearity)and in male(P=0.136 for nonlinearity)and female(P=0.067 for nonlinearity)subgroups.Further stratification and sensitivity analyses yielded consistent conclusions.CONCLUSION Our study findings suggest that in individuals with type 2 diabetes,detectable hs-TnT levels below the 99th percentile are associated with DKD.展开更多
基金funded by the Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities’Association(No.202101BA070001-126).
文摘Objective:This study aimed to elucidate the influence of IFN-gamma(IFN-γ)in neuroblastoma(NB)cells and reveal its potential underlying molecular mechanism.Methods:The Cell Counting Kit-8,Transwell apparatus,and flow cytometry were employed to assess cellular viability,migratory capacity,invasive potential,and apoptotic rates,respectively.RNA-seq combined with bioinformatics analysis revealed differentially expressed genes(DEGs)and their possible biological functions.Protein levels were determined by western blot analysis.Results:IFN-γtreatment resulted in diminished cell viability,mitigated migratory and invasive capabilities,and augmented apoptotic activity in the SK-N-BE(2)cell line,whereas it exhibited the opposite effect in SH-SY5Y cells.Furthermore,interferon regulatory factor 1(IRF-1)was the common DEG in both IFN-γ-treated SK-N-BE(2)and SH-SY5Y cells.Additionally,we found that it was underexpressed in NB tissues.The depletion of IRF-1 promoted the progression of both SK-N-BE(2)and SH-SY5Y cells.Moreover,IRF-1 knockdown effectively counteracted the effects of IFN-γon SK-N-BE(2)cells,while exacerbating them in SH-SY5Y cells.Conclusion:This study verified that IFN-γexerted a distinct role in both N-Myc-and non-N-Myc-amplified NB cells,partially by mediating the expression of IRF-1,suggesting that it may serve as a potent agent for treating patients with NB.
文摘Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
基金This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Gannan Medical University(approval No.EFYJ20240113007).
文摘BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this threshold represent a heterogeneous group with an inadequately characterized risk profile.AIM To investigate the association between hs-TnT levels below the 99th percentile and the presence of diabetic kidney disease(DKD)in patients with diabetes mellitus.METHODS This study analyzed data from the National Health and Nutrition Examination Survey obtained between 1999 and 2004,focusing on adults with type 2 diabetes mellitus.Serum hs-TnT concentrations were evaluated.DKD was defined as impaired glomerular filtration rate(<60 mL/minute/1.73 m^(2)),proteinuria(urinary albumin-to-creatinine ratio of≥30 mg/g),or both conditions in patients with diabetes mellitus.Weighted multivariable logistic regression analysis and restricted cubic spline analyses were employed to examine the independent association between hs-TnT and DKD,with the likelihood ratio test being used to evaluate nonlinearity.RESULTS The study included 2505 patients with a mean age of 55.02(standard error:0.72)years,of whom 44.87%were females.Among the participants,909(32.34%)were diagnosed with DKD.Multivariable logistic regression analysis indicated that,compared to the lowest tertile of hs-TnT(<5.93 ng/L),tertile 2(5.94-9.79 ng/L)had an odds ratio of 1.25(95%confidence interval:0.77-2.02,P=0.350),while tertile 3(9.80-21.88 ng/L)had an odds ratio of 2.07(95%confidence interval:1.13-3.80,P=0.022),with a significant trend(P for trend=0.022).Smoothed curve fitting demonstrated a linear association between hs-TnT levels and DKD in the overall population(P=0.061 for nonlinearity)and in male(P=0.136 for nonlinearity)and female(P=0.067 for nonlinearity)subgroups.Further stratification and sensitivity analyses yielded consistent conclusions.CONCLUSION Our study findings suggest that in individuals with type 2 diabetes,detectable hs-TnT levels below the 99th percentile are associated with DKD.
