Caveolin-1 in skin aging – From innocent bystander to major contributor

Caveolin-1 (Cav-1) appears to be both a pathophysiological contributor and a target in different inflammatory and hyperproliferative skin conditions as well as in skin aging. Skin fibroblasts demonstrate an up-regulation of Cav-1 expression both in chronological and UV-induced aging, and such an up-regulation was observed both in vitro and in vivo. Typical alterations in aging skin involve a reduction of the dermis thickness, a significant expansion of the dermal white adipose tissue as well as modifications of the content and distribution of hyaluronan, impairment of autophagic flux, a reduction of collagen expression and an increase in tissue inflammation. All of these phenomena can be connected with changes in Cav-1 expression in the aging skin. Modified expression of Cav-1 can also significantly influence the mechanical properties of individual skin layers, thus changing the total mechanical stability of the layered composite skin/WAT, leading to typical structural modifications of the skin surface in the aging skin. Selective reduction of Cav-1 expression has the potential to exert anti-aging effects on the skin.     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

MR评价垂体腺瘤质地及与其胶原含量的关系

目的利用MR测量垂体腺瘤不同质地的信号强度,并分析其与肿瘤胶原含量间的关系。方法57例经手术证实的垂体腺瘤标本,术前均行MR检查,根据术中肿瘤硬度分为质地韧组(8例)与质地软组(49例),标本行天狼猩红染色检测其胶原含量。结果纤维化与非纤维化组T1WI瘤体/灰质信号强度比分别为1.31±0.31、1.16±0.26;T1WI瘤体/白质信号强度比分别为1.01±0.25、0.91±0.18,两组间差异无统计学意义(P(0.05);T1+WI瘤体/灰质信号强度比分别为1.83±0.28、1.84±0.51;T1+WI瘤体/白质信号强度比分别为1.56±0.24、1.46±0.37,两组间差异无统计学意义(P(0.05);T2WI瘤体/灰质信号强度比分别为1.15±0.26、1.57±0.46(P(0.05);T2WI瘤体/白质信号强度比分别为1.48±0.39、2.10±0.61,两组间有统计学意义(P(0.01);胶原含量分别为20.03%±7.99%、7.87%±4.82%,两组间有统计学意义(P<0.01);且T2WI瘤体/灰质、T2WI瘤体/白质与胶原含量呈显著负相关(r=-0.531、r=-0.726,P均(0.01)。结论术前MR可以预测垂体腺瘤的质地;其中以T2WI瘤体/白质为预测指标为最佳。胶原含量影响垂体腺瘤质地,MRI上T2WI可以反映其胶原含量的多少。     

后十字韧带重建后移植物组织学与胶原表型的变化

目的探讨采用半腱肌腱重建后十字韧带（posterior cruciate ligament,PCL）后移植物的组织学与胶原表型的变化.方法取20只成年新西兰大白兔,实验组18只切除右膝PCL后即刻用双股自体半腱肌腱重建,实验组于术后3、6、52周各处死动物2只,12、26周各处死动物6只,切取半腱肌腱移植物;对照组2只直接切取半腱肌腱和PCL.标本采用HE、甲苯胺蓝以及Ⅰ、Ⅲ型胶原免疫组化染色观察移植物的组织学与胶原表型变化,并与正常半腱肌腱和PCL进行比较.结果常规组织化学染色显示正常半腱肌腱和PCL在细胞构成上有明显的差别,PCL内可见软骨样细胞;重建后的移植物经过坏死、细胞重新长入、胶原形成和重塑阶段,52周时形成的结构类似于正常PCL,但在纤维排列上与正常PCL仍有差异.免疫组织化学染色结果显示正常PCL纤维内部仅有Ⅰ型胶原表达,重建韧带Ⅰ型胶原染色随时间延长从少到多,Ⅲ型胶原染色从多到少,52周时移植物内局部仍有表达.结论采用半腱肌腱重建PCL 52周时移植物和正常PCL结构相似,但仍有差异.     

洛沙坦对肥胖Zucker大鼠肾组织环氧化酶2表达的影响

目的 探讨血管紧张素Ⅱ(AngⅡ)1型受体拮抗剂(ARB)洛沙坦对代谢综合征(MS)肾组织环氧化酶2(COX-2)表达的影响及其机制。 方法 把7周大的MS模型肥胖Zucker大鼠随机分成洛沙坦处理组和未处理组，以瘦Zucker大鼠为对照组，连续给药4个月后观察肾组织内COX-2的表达。另外，用AngⅡ刺激6 h的系膜细胞和用从微型渗透泵灌注AngⅡ 5 d的C57BL/6小鼠肾脏提取的肾皮质，观察COX-2的表达。采用RT-PCR和Western印迹法分别检测COX-2 mRNA和蛋白的表达。 结果 洛沙坦可阻止肥胖Zucker大鼠肾组织内COX-2表达增加。AngⅡ直接刺激可以诱导系膜细胞和肾组织内COX-2表达增加。 结论 AngⅡ可以调控MS肾组织内COX-2表达增加。ARB可以通过抑制COX-2的表达保护MS肾脏，这对应用非COX-2抑制剂来保护MS肾脏具有重要的意义。     

骨胶原与骨质疏松骨密度及骨生物力学的相关性研究

目的探讨骨胶原含量在绝经后骨质疏松症的发生、发展及在骨质疏松性骨折中的作用。方法取7个月龄未交配雌性SD大鼠60只，随机分为四组，A组：对照组（sham组）；B组：切除卵巢组；C组：切除卵巢＋雌激素治疗组；D组：切除卵巢＋降钙素治疗组。除A组外，其他三组通过切除双侧卵巢法12周后制成骨质疏松模型，24周后分别行k的力学特性、右侧股骨三点弯曲试验、羟脯氨酸含量、k骨密度（BMD）测定，Masson三色染色法显示骨胶原形态。结果A、C、D组与B组在k羟脯氨酸含量、BMD、k压缩力学参数值、右侧股骨生物力学参数值、骨胶原染色含量及形态方面差异均有统计学意义（P〈0．05），而A、C、D组之间差异无统计学意义（P〉0．05）。统计学分析显示羟脯氨酸含量与BMD及骨生物力学参数值呈直线相关性。结论骨质疏松的发生与骨胶原含量下降有关。骨胶原含量的下降与BMD降低及骨生物力学改变呈相关性。应用雌激素和降钙素治疗去势后骨质疏松大鼠，不仅可以提高其BMD含量和骨生物力学性能，而且还可以提高骨胶原的含量。