Objective: To evaluate the clinical significance of high mobility group box 1 (HMGB1) expression in nephridial tissues of lupus nephritis (LN). Methods: Sixty-three patients with active LN and 15 systemic lupus erythe...Objective: To evaluate the clinical significance of high mobility group box 1 (HMGB1) expression in nephridial tissues of lupus nephritis (LN). Methods: Sixty-three patients with active LN and 15 systemic lupus erythematosus (SLE) (combined without LN) were included. Renal biopsies were performed in the two groups. The biopsies were evaluated according to the World Health Organization (WHO) classification and renal disease activity was estimated using the British Isles lupus assessment group (BILAG) index. Serum levels of HMGB1 were analyzed by western blot. HMGB1 expression in renal tissue was assessed by immunohistochemistry in the two groups. The correlation between HMGB1 and renal active index (AI), chronicity index (CI), pathological type of LN was analyzed. Results: LN biopsies showed WHO class III, IV or V and all patients had high renal disease activity (BILAG A/B). The HMGB1 expression was higher in the LN groups than the control groups (t = 9.263, P < 0.05). It showed positive correlation between HMGB1 expression and SLE DAI classification (r = 0.579, P P < 0.05) and renal tubule interstitial (TIL) classification (r = 0.815, P < 0.05), and negative correlation between HMGB1 expression and CI classification (r = 0.582, P < 0.05). In all patients, serum levels of HMGB1 increased only slightly in the patients only with SLE;however, in patients with LN WHO class IV a significant decrease was observed (P = 0.02). Immunostaining revealed a pronounced extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium. There were significant differences in HMGB1 expression between LN and control biopsies and it existed with apparent association to histopathological classification and clinical outcome. Conclusions: Renal tissue expression and serum levels of HMGB1 were elevated in LN. The unusual elevation of HMGB1 in serum and tissue in LN may reflect persistent inflammatory activity, which clearly indicates a role for HMGB1 in pathogenesis of LN.展开更多
Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target...Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.展开更多
目的 分析开放性胃肠手术患儿术后血清降钙素原(procalcitonin, PCT)、正五聚蛋白3(pentraxin 3,PTX3)、高迁移率族蛋白B1(high mobility group protein B1,HMGB-1)表达及其预测早期感染的价值。方法 2020年1月~2023年1月我院收治的开...目的 分析开放性胃肠手术患儿术后血清降钙素原(procalcitonin, PCT)、正五聚蛋白3(pentraxin 3,PTX3)、高迁移率族蛋白B1(high mobility group protein B1,HMGB-1)表达及其预测早期感染的价值。方法 2020年1月~2023年1月我院收治的开放性胃肠手术患儿206例,依据术后是否并发感染分为感染组(27例)和未感染组(179例)。比较两组一般资料及围手术期指标,比较两组术前、术后1天、3天血清PCT、PTX3、HMGB-1水平;观察术后1天、3天各血清指标单一、联合检测对开放性胃肠手术患儿术后感染的预测价值;多因素Logistic回归分析术后感染的影响因素。结果 感染组术后1天、3天血清PCT、PTX3、HMGB-1水平分别为(2.42±0.39)μg/L、(3.74±0.53)μg/L,(2.07±0.66)μg/L、(3.06±0.75)μg/L,(18.35±2.74)μg/L、(26.09±4.16)μg/L,均高于未感染组的(1.71±0.35)μg/L、(2.29±0.36)μg/L,(1.48±0.52)μg/L、(1.73±0.59)μg/L,(13.04±2.26)μg/L、(15.75±2.83)μg/L,两组比较差异有统计学意义(P<0.05);绘制受试者工作特征(receiver operating characteristic, ROC)曲线显示,术后3天血清PCT、PTX3、HMGB-1联合检测预测开放性胃肠手术患儿术后感染的曲线下面积(Area under the curve, AUC)最大,为0.989;多因素Logistic回归分析显示,年龄为患儿术后感染的独立保护因素,术中出血量、手术时间、术后1天、3天血清PCT、PTX3、HMGB-1为独立危险因素(P<0.05);感染组中重度感染患儿术后1天、3天血清PCT、PTX3、HMGB-1水平分别为(2.63±0.34)μg/L、(4.12±0.56)μg/L、(2.31±0.69)μg/L、(3.39±0.81)μg/L、(19.86±2.91)μg/L、(28.84±4.40)μg/L,均高于轻度感染患儿的(2.11±0.28)μg/L、(3.19±0.49)μg/L、(1.72±0.60)μg/L、(2.58±0.73)μg/L、(16.15±2.39)μg/L、(22.09±3.96)μg/L,差异有统计学意义(P<0.05)。结论 开放性胃肠手术患儿术后血清PCT、PTX3、HMGB-1表达显著增高,且其表达与术后早期感染及感染病情程度有关,三者联合预测价值更高。展开更多
文摘Objective: To evaluate the clinical significance of high mobility group box 1 (HMGB1) expression in nephridial tissues of lupus nephritis (LN). Methods: Sixty-three patients with active LN and 15 systemic lupus erythematosus (SLE) (combined without LN) were included. Renal biopsies were performed in the two groups. The biopsies were evaluated according to the World Health Organization (WHO) classification and renal disease activity was estimated using the British Isles lupus assessment group (BILAG) index. Serum levels of HMGB1 were analyzed by western blot. HMGB1 expression in renal tissue was assessed by immunohistochemistry in the two groups. The correlation between HMGB1 and renal active index (AI), chronicity index (CI), pathological type of LN was analyzed. Results: LN biopsies showed WHO class III, IV or V and all patients had high renal disease activity (BILAG A/B). The HMGB1 expression was higher in the LN groups than the control groups (t = 9.263, P < 0.05). It showed positive correlation between HMGB1 expression and SLE DAI classification (r = 0.579, P P < 0.05) and renal tubule interstitial (TIL) classification (r = 0.815, P < 0.05), and negative correlation between HMGB1 expression and CI classification (r = 0.582, P < 0.05). In all patients, serum levels of HMGB1 increased only slightly in the patients only with SLE;however, in patients with LN WHO class IV a significant decrease was observed (P = 0.02). Immunostaining revealed a pronounced extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium. There were significant differences in HMGB1 expression between LN and control biopsies and it existed with apparent association to histopathological classification and clinical outcome. Conclusions: Renal tissue expression and serum levels of HMGB1 were elevated in LN. The unusual elevation of HMGB1 in serum and tissue in LN may reflect persistent inflammatory activity, which clearly indicates a role for HMGB1 in pathogenesis of LN.
基金supported by the National Key Research and Development Program of China(Nos.2018YFC1002804 and 2016YFC1000600)the National Natural Science Foundation of China(Nos.81771618 and 81971356)the Fundamental Research Funds for the Central Universities(No.2042023kf0028).
文摘Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.
文摘目的 分析开放性胃肠手术患儿术后血清降钙素原(procalcitonin, PCT)、正五聚蛋白3(pentraxin 3,PTX3)、高迁移率族蛋白B1(high mobility group protein B1,HMGB-1)表达及其预测早期感染的价值。方法 2020年1月~2023年1月我院收治的开放性胃肠手术患儿206例,依据术后是否并发感染分为感染组(27例)和未感染组(179例)。比较两组一般资料及围手术期指标,比较两组术前、术后1天、3天血清PCT、PTX3、HMGB-1水平;观察术后1天、3天各血清指标单一、联合检测对开放性胃肠手术患儿术后感染的预测价值;多因素Logistic回归分析术后感染的影响因素。结果 感染组术后1天、3天血清PCT、PTX3、HMGB-1水平分别为(2.42±0.39)μg/L、(3.74±0.53)μg/L,(2.07±0.66)μg/L、(3.06±0.75)μg/L,(18.35±2.74)μg/L、(26.09±4.16)μg/L,均高于未感染组的(1.71±0.35)μg/L、(2.29±0.36)μg/L,(1.48±0.52)μg/L、(1.73±0.59)μg/L,(13.04±2.26)μg/L、(15.75±2.83)μg/L,两组比较差异有统计学意义(P<0.05);绘制受试者工作特征(receiver operating characteristic, ROC)曲线显示,术后3天血清PCT、PTX3、HMGB-1联合检测预测开放性胃肠手术患儿术后感染的曲线下面积(Area under the curve, AUC)最大,为0.989;多因素Logistic回归分析显示,年龄为患儿术后感染的独立保护因素,术中出血量、手术时间、术后1天、3天血清PCT、PTX3、HMGB-1为独立危险因素(P<0.05);感染组中重度感染患儿术后1天、3天血清PCT、PTX3、HMGB-1水平分别为(2.63±0.34)μg/L、(4.12±0.56)μg/L、(2.31±0.69)μg/L、(3.39±0.81)μg/L、(19.86±2.91)μg/L、(28.84±4.40)μg/L,均高于轻度感染患儿的(2.11±0.28)μg/L、(3.19±0.49)μg/L、(1.72±0.60)μg/L、(2.58±0.73)μg/L、(16.15±2.39)μg/L、(22.09±3.96)μg/L,差异有统计学意义(P<0.05)。结论 开放性胃肠手术患儿术后血清PCT、PTX3、HMGB-1表达显著增高,且其表达与术后早期感染及感染病情程度有关,三者联合预测价值更高。
