Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

L158,809和西拉普利对体外培养系膜细胞TGF-β1表达和细胞外基质蛋白分泌的影响

目的：观察血管紧张素受体拮抗剂(ARBs)L158，809和血管紧张素转换酶(ACE)抑制剂西拉普利对体外培养人肾小球系膜细胞转化生成因子(TGF—β1)表达和纤维连接蛋白、层粘连蛋白和Ⅳ型胶原分泌的影响。方法：分别在不同葡萄糖浓度(5.6mmol／L和30mmol／L)和药物浓度(1、10、100和500μmol／L)下体外培养人肾小球系膜细胞，分别于24、48和72h后测定细胞增殖。然后将系膜细胞分为低糖(5．6mmol／L)对照组(LG)、高糖(30mmol／L)对照组(HG)、L158，809(10μmol／L)组和西拉普利(10μmmol／L)组，48h后，分别用RT-PCR法测定TGF-β1表达，ELISA和放射免疫法测定细胞上清液中TGF-β1、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度。结果：与低糖对照组相比，高糖对照组系膜细胞过度增殖，细胞上清液中TGF-βl、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度明显升高，TGF-βlmRNA表达也显升高；而L158，809组和西拉普利组TGF-β1和细胞外基质(ECM)蛋白水平明显低于高糖对照组，且TGF-β1mRNA水平亦表达明显降低。结论：高糖可刺激体外培养系膜细胞过度增殖，TGF-β1表达增高，ECM蛋白分泌明显增加，而L158，809和西拉普利均可抑制高糖环境下上述现象。     

阿托伐他汀对系膜增殖性肾炎大鼠肾组织细胞外基质和纤溶酶原激活剂抑制物-1表达的影响

目的：观察阿托伐他汀对系膜增殖性肾炎（MsPGN）大鼠肾组织细胞外基质（ECM）和纤溶酶原激活剂抑制物-1（PAI-1）表达的影响，探讨其肾脏保护作用的机制。方法：采用抗胸腺细胞血清诱发的MsPGN大鼠模型，将SD大鼠随机分为正常对照组、肾炎模型组、小剂量阿托伐他汀治疗组（8mg·kg^-1·d^-1）和大剂量阿托伐他汀治疗组（16mg·kg^-1·d^-1）。治疗12d后。检测各组大鼠血总胆固醇（CHOL）、甘油三酯（TG）、血肌酐（Scr）和24h尿蛋白，以及肾组织Ⅳ型胶原（Col Ⅳ）、纤维结合蛋白（FN）和PAI-1的表达。结果：阿托伐他汀治疗组大鼠24h尿蛋白、肾组织Col Ⅳ、FN和PAI-1 mRNA的表达明显下降。肾组织病理改变明显改善，与模型组相比有统计学差异（P〈0．05），且呈剂量依赖关系。其中肾炎模型组尿蛋白（30．34±0．62）mg／d。阿托伐他汀小剂量治疗组（21．17±0．79）mg／d，大剂量治疗组（9．77±0．54）mg／d。同时，各组血脂水平无明显差异（P〉0．05）。结论：阿托伐他汀可显著改善MsPGN大鼠肾脏病变，抑制肾组织ECM成分和PAI-1的表达。     

FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro.

Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/TGF-beta signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Hospital Frailty Risk Score Outperforms Current Risk Stratification Models in Primary Total Hip and Knee Arthroplasty

BackgroundModels for risk stratification and prediction of outcome, such as the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Method (ECM), the 5-factor modified Frailty Index (mFI-5), and the Hospital Frailty Risk Score (HFRS) have been validated in orthopedic surgery. The aim of this study is to compare the predictive power of these models in total hip and knee replacement.MethodsIn a retrospective analysis of 8250 patients who had undergone total joint replacement between 2011 and 2019, CCI, ECM, mFI-5, and HFRS were calculated for each patient. Receiver operating characteristic curve plots were generated and the area under the curve (AUC) was compared between each score with regard to adverse events such as transfusion, surgical, medical, and other complications. Multivariate logistic regression models were used to assess the relationship among risk stratification models, demographic factors, and postoperative adverse events.ResultsIn prediction of surgical complications, HFRS performed best (AUC: 0.719, P < .001), followed by ECM (AUC: 0.578, P < .001), mFI-5 (AUC: 0.564, P = .003), and CCI (AUC: 0.555, P = .012). With regard to medical complications, other complications, and transfusion, HFRS also was superior to ECM, mFI-5, and CCI. Multivariate logistic regression analyses revealed HFRS as an independent risk stratification model associated with all captured adverse events (P ≤ .001).ConclusionThe HFRS is superior to current risk stratification models in the context of total joint replacement. As the HRFS derives from routinely collected administrative data, healthcare providers can identify at-risk patients without additional effort or expense.     

Selected conditions associated with an increased incidence of incisional hernia: A review of molecular biology

BackgroundIncisional hernias (IH) following a laparotomy, on average, occur in 10–20% of patients, however, little is known about its molecular basis. Thus, a better understanding of the molecular mechanisms could lead to the identification of key target(s) to intervene pre-and post-operatively.MethodsWe examined the current literature describing the molecular mechanisms of IH and overlap these factors with smoking, abdominal aortic aneurysm, obesity, diabetes mellitus, and diverticulitis.ResultsThe expression levels of collagen I and III, matrix metalloproteinases, and tissue inhibitors of metalloproteases are abnormal in the extracellular matrix (ECM) of IH patients and ECM disorganization has an overlap with these comorbid conditions.ConclusionUnderstanding the pathophysiology of IH development and associated risk factors will allow physicians to identify patients that may be at increased risk for IH and to possibly act preemptively to decrease the incidence of IH.     

Neuropsin regulates an early phase of schaffer-collateral long-term potentiation in the murine hippocampus

We found that neuropsin, an extracellular matrix serine protease, has a regulatory effect on Schaffer-collateral long-term potentiation (LTP) in the mouse hippocampus. Bath application of 1-170 nM recombinant neuropsin modulated early phase LTP in the Schaffer-collateral pathway with a 'bell-shape' dose-response curve. The maximum enhancing activity (134% of control LTP) was found at approximately 2.5 nM. Bath application of a neutralizing antibody against neuropsin in the hippocampal slice resulted in a marked inhibition of the tetanus-induced early phase of LTP. The in vivo continuous intraventricular infusion of an antisense oligonucleotide against neuropsin significantly reduced the amplitude of the tetanus-induced early phase of LTP in vitro. Neuropsin did not directly change the N-methyl D-aspartate (NMDA) current. Thus, neuropsin appears to act as a regulatory molecule in the early phase of LTP via its proteolytic function on extracellular matrix rather than affecting NMDA receptor-mediated calcium increase.     

2005年龙岩市部分健康人群流脑带菌状况和免疫水平调查

[目的]了解龙岩市健康人群流脑带菌状况与免疫水平，以确定高危人群，预测、预报流脑疫情。[方法]2005年3月，对龙岩市部分健康人群进行了流脑的带菌状况与血清抗体水平调查。[结果]调查168人，检出3株A群脑膜炎奈瑟菌，带菌率为1．49%；血清A群与C群流脑抗体阳性率分别为54．76％、29．76％，GMT分别为1：0．49、1：0．19，各年龄组均〈1：1．00。[结论]龙岩市健康人群有低水平的脑膜炎奈瑟菌携带率和流脑免疫水平，尚未发现C群菌的带菌者。     

MiR-486-3p targeting ECM1 represses cell proliferation and metastasis in cervical cancer

MicroRNAs (miRNAs) regulate gene expression and are involved in cervical cancer. But the molecular mechanism is still unclear. Here, miRNA profile of cervical cancer was performed and demonstrated that miR-486-3p decreased in specimens of cervical cancer patients. In addition, our clinical data show that decreased miR-486-3p was associated with metastasis in cervical cancer patients. ECM1 was predicted and velified as a target gene of miR-486-3p. Overexpression of miR-486-3p inhibited cell growth and metastasis by targeting ECM1. In a conclusion, these findings suggest that miR-486-3p is a tumor suppressor miRNA and induction of miR-486-3p is a potential strategy to inhibit cervical cancer progression.