BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer...BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer（PC） remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS： The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS： EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues（P0.040）. In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION： Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.展开更多
BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is med...BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.展开更多
BACKGROUND： Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis （TWEAK） participates in brain edema. However, it is unclear whether blood-brain barrier （BBB） disruption is a...BACKGROUND： Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis （TWEAK） participates in brain edema. However, it is unclear whether blood-brain barrier （BBB） disruption is associated with TWEAK during the process of brain edema OBJECTIVE： To investigate the effects of TWEAK on BBB permeability in brain edema. DESIGN, TIME AND SETTING： An immunohistochemical observation, randomized, controlled animal experiment was performed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University ＆ Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007. MATERIALS： A total of 48 adult Wistar rats were randomly divided into three groups： normal control （n = 8）, sham-operated （n = 8）, and ischemia/reperfusion （n = 32）. Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours （n = 8）, 12 hours （n = 8）, 1 day （n = 8）, or 12 days （n = 8） of reperfusion. METHODS： Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion （MCAO） using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention. MAIN OUTCOME MEASURES： TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation. RESULTS： A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group, TWEAK-positive cells were present in the ischemic penumbra surrounding the lamellar necrotic region in the fight cerebral hemisphere at 6 hours reperfusion and increased thereafter; by 2 days reperfusion they had reached a peak level, which was significantly higher than the sham-operated and normal control groups （P 〈 0.05）. At 6 hours reperfusion, both brain water content and Evans blue extravasation showed the same tendency for change as TWEAK expression. Pearson correlation analysis results revealed that the degree of TWEAK expression was positively correlated with brain water content （r = 0.892, P 〈 0.05）. CONCLUSION： The present results confirmed that TWEAK was involved in BBB disruption and participated in brain edema following cerebral ischemia.展开更多
Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed fro...Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed from the same gene and regulates all aspects of angiogenesis and may influence the ability of tumor cells to disseminate.The aim was to analyze the relationship between miRNA-126 and EGFL7 and disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy.Methods:This study included 71 patients from a phase II study all planned for three cycles of capecitabine and oxaliplatin before surgery.Blood was sampled at baseline and right before and after the operation.Circulating miRNA-126 was analysed by RT-qPCR and a quantitative immunoassay was used for the analyses of EGFL7.Results:The rates of 5-year disease-free survival(DFS)and overall survival(OS)were 80%and 85%,respectively.The level of circulating miRNA-126 before the operation predicts recurrence,P=0.035.In patients with values below and above the median the recurrence rate was 31%and 4%,respectively.Similar results applied to EGFL7.A combined estimate identified a subgroup of patients(25 of 71)with no recurrence and a 5-year DFS and OS rate of 100%,respectively.Conclusion:MicroRNA-126 and EGFL7 are predictors for disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy and may assist in selection of adjuvant chemotherapy.展开更多
目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期...目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期糖尿病孕妇依据随机数表法分为两组。试验组61例予以门冬胰岛素皮下注射联合二甲双胍治疗,对照组61例予以地特胰岛素皮下注射联合二甲双胍治疗。比较两组治疗前后的血清VEGF、ADP、ANGPTL8表达水平、炎症因子水平及血糖水平,随访了解两组的妊娠结局。结果治疗后,试验组的血清ADP水平较对照组升高,VEGF、ANGPTL8水平较对照组降低(P<0.05);治疗后,试验组的C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平均低于对照组(P<0.05);治疗后与对照组相比,试验组的空腹血糖(FPG)、餐后1 h血糖(1 h PPG)、餐后2 h血糖(2 h PPG)均明显改善(P<0.05);相比于对照组,试验组的不良妊娠结局明显降低(P<0.05)。结论胰岛素联合二甲双胍治疗妊娠期糖尿病均具有显著的效果,但相比于地特胰岛素,门冬胰岛素皮下注射联合二甲双胍对患者血清VEGF、ADP、ANGPTL8水平及炎症因子水平的改善效果更显著,对血糖的控制效果更佳,妊娠结局更好。展开更多
BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to p...BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.展开更多
基金supported by a grant from the Research Special Fund for Public Welfare Industry of Health(201202007)
文摘BACKGROUND： Recent studies have shown the clinical significance of epidermal growth factor-like domain 7（EGFL7）in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer（PC） remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS： The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS： EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues（P0.040）. In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION： Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.
基金Supported by:the Program of the Key Laboratory of Health Department of Jilin Province, No.2006079the Fortieth National Post-Doctoral Scientific Foundation,No. 20060400893
文摘BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.
文摘BACKGROUND： Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis （TWEAK） participates in brain edema. However, it is unclear whether blood-brain barrier （BBB） disruption is associated with TWEAK during the process of brain edema OBJECTIVE： To investigate the effects of TWEAK on BBB permeability in brain edema. DESIGN, TIME AND SETTING： An immunohistochemical observation, randomized, controlled animal experiment was performed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University ＆ Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007. MATERIALS： A total of 48 adult Wistar rats were randomly divided into three groups： normal control （n = 8）, sham-operated （n = 8）, and ischemia/reperfusion （n = 32）. Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours （n = 8）, 12 hours （n = 8）, 1 day （n = 8）, or 12 days （n = 8） of reperfusion. METHODS： Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion （MCAO） using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention. MAIN OUTCOME MEASURES： TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation. RESULTS： A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group, TWEAK-positive cells were present in the ischemic penumbra surrounding the lamellar necrotic region in the fight cerebral hemisphere at 6 hours reperfusion and increased thereafter; by 2 days reperfusion they had reached a peak level, which was significantly higher than the sham-operated and normal control groups （P 〈 0.05）. At 6 hours reperfusion, both brain water content and Evans blue extravasation showed the same tendency for change as TWEAK expression. Pearson correlation analysis results revealed that the degree of TWEAK expression was positively correlated with brain water content （r = 0.892, P 〈 0.05）. CONCLUSION： The present results confirmed that TWEAK was involved in BBB disruption and participated in brain edema following cerebral ischemia.
基金This work was supported by the Cancer Foundation(no reference),the Danish Council for Independent Research(No.10-093589)Direktør Jacob Madsen&Hustru Olga Madsen’s Foundation(No.5297)the Regional Strategic Council for Research in the Region of Southern Denmark(No.14/32395).
文摘Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed from the same gene and regulates all aspects of angiogenesis and may influence the ability of tumor cells to disseminate.The aim was to analyze the relationship between miRNA-126 and EGFL7 and disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy.Methods:This study included 71 patients from a phase II study all planned for three cycles of capecitabine and oxaliplatin before surgery.Blood was sampled at baseline and right before and after the operation.Circulating miRNA-126 was analysed by RT-qPCR and a quantitative immunoassay was used for the analyses of EGFL7.Results:The rates of 5-year disease-free survival(DFS)and overall survival(OS)were 80%and 85%,respectively.The level of circulating miRNA-126 before the operation predicts recurrence,P=0.035.In patients with values below and above the median the recurrence rate was 31%and 4%,respectively.Similar results applied to EGFL7.A combined estimate identified a subgroup of patients(25 of 71)with no recurrence and a 5-year DFS and OS rate of 100%,respectively.Conclusion:MicroRNA-126 and EGFL7 are predictors for disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy and may assist in selection of adjuvant chemotherapy.
文摘目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期糖尿病孕妇依据随机数表法分为两组。试验组61例予以门冬胰岛素皮下注射联合二甲双胍治疗,对照组61例予以地特胰岛素皮下注射联合二甲双胍治疗。比较两组治疗前后的血清VEGF、ADP、ANGPTL8表达水平、炎症因子水平及血糖水平,随访了解两组的妊娠结局。结果治疗后,试验组的血清ADP水平较对照组升高,VEGF、ANGPTL8水平较对照组降低(P<0.05);治疗后,试验组的C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平均低于对照组(P<0.05);治疗后与对照组相比,试验组的空腹血糖(FPG)、餐后1 h血糖(1 h PPG)、餐后2 h血糖(2 h PPG)均明显改善(P<0.05);相比于对照组,试验组的不良妊娠结局明显降低(P<0.05)。结论胰岛素联合二甲双胍治疗妊娠期糖尿病均具有显著的效果,但相比于地特胰岛素,门冬胰岛素皮下注射联合二甲双胍对患者血清VEGF、ADP、ANGPTL8水平及炎症因子水平的改善效果更显著,对血糖的控制效果更佳,妊娠结局更好。
基金Supported by the Changzhou Science and Techology Program,No.CJ20241048Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105+1 种基金Development Foundation of the Affiliated Hospital of Xuzhou Medical University,No.XYFC202304 and No.XYFM202307The Open Project of Jiangsu Provincial Key Laboratory of Laboratory Medicine,No.JSKLM-Z-2024-002.
文摘BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.
