原发性醛固酮增多症的分子机制研究进展

原发性醛固酮增多症(PA)是最常见的继发性高血压。近年来随着对PA病例的研究,关于不同基因如何导致疾病发生的分子遗传学机制已取得重大进展,PA的分子机制研究具有重要意义。本研究主要从原发性醛固酮增多症的发病机制及分子机制两个方面进行综述,以期为更深入的诊断和治疗提供新思路。     

脊髓损伤的治疗进展

脊髓损伤分为原发性损伤与继发性损伤。原发性损伤包括机械压迫、出血；继发性损伤包括水肿、炎症反应、局部缺血、谷氨酸受体过度激活、脂质过氧化作用、钙离子超载等；疾病最终导致脊髓灰白质缺血、变形、坏死。继发性损伤在原发性损伤后较长一段时间内起作用，是一种细胞和分子水平的主动调节过程，具有可逆性。继发性损伤可加重原发损伤，造成脊髓功能障碍，致机体全瘫或不全瘫。如能阻断此连锁反应中的某一环节，则可明显减轻继发损伤，促进脊髓功能的恢复。到目前为止，对原发性脊髓损伤尚无有效的治疗方法，仅依靠外科手术是不够的；对继发性损伤进行积极的药物控制和基因治疗，     

脊髓损伤的治疗进展

脊髓损伤分为原发性损伤与继发性损伤。原发性损伤包括机械压迫、出血;继发性损伤包括水肿、炎症反应、局部缺血、谷氨酸受体过度激活、脂质过氧化作用[1]、钙离子超载[2]等;疾病最终导致脊髓灰白质缺血、变形、坏死。继发性损伤在原发性损伤后较长一段时间内起作用,是一种细胞和分子水平的主动调节过程,具有可逆性。继发性损伤可加重原发损伤,造成脊髓功能障碍,致机体全瘫或不全瘫[3]。如能阻断此连锁反应中的某一环节,则可明显减轻继发损伤,促进脊髓功能的恢复。到目前为止,对原发性脊髓损伤尚无有效的治疗方法,仅依靠外科手术是不够的;对…     

T细胞在骨关节炎发病机制中的作用

T细胞在骨关节炎（OA）发病和进展中的作用日益受到重视。近年研究发现在OA滑膜中T细胞浸润、T细胞激活抗原、Th1细胞因子的产生和寡克隆T细胞的出现以及滑膜中CD3-ζ链表达减少、MNC浸润等在软骨破坏中起了重要作用。本文综述了T细胞在原发性骨性关节炎免疫学发病机制中的研究进展。     

长链的非编码 RNA生长停滞特异性转录本 5在骨关节炎中的研究进展

骨关节炎( OA)是一种以软骨退变、骨重建为主要病理特点的慢性关节疾病。目前没有可治愈该疾病的药物及手段,疗策略有限的根本原因是对其潜在发病机制的认识不足。长链的非编码 RNA(LncRNAs)被认为是许多疾病中的一类新的调治控因子,是目前研究 OA发病机制的一个重要切入点。 LncRNA生长停滞特异性转录本 5(Cas5)参与调控细胞的增殖、分化及凋亡,是一种在软骨细胞中特异性高表达的 LncRNA。然而,由于 LncRNA Cas5作用机制复杂,其与 OA相关具体分子机制目前仍不明确。该文针对 LncRNA Cas5在 OA中的软骨细胞凋亡、软骨基质代谢成骨分化及治疗方面的作用进行综述。     

三叉神经痛的分子发病机制的研究进展

三叉神经痛(trigeminal neuralgia,TN)是指三叉神经的一支或几支分布区的反复性、阵发性剧痛,对病人的生活质量影响较大的一种较难完全治愈的疾病,临床一般分为原发性和继发性TN。关于原发性TN的病因和发病机制目前尚不明确。现在,随着分子生物学研究的进展,已经发现多种神经类物质和TN有着密切的联系。该文从分子方面对TN的发病机制研究进展情况作一综述,旨在为TN的治疗提供理论依据。     

脊髓损伤的治疗现状及进展

脊髓损伤(SCI)由于损伤机制的不同,分为原发性、继发性损伤。原发性损伤是直接损伤,多为创伤性的,具有不可逆性。继发性损伤为创伤后的病理生理过程,包括神经细胞的坏死和凋亡等,具有可逆性。既往有不少学者在阻止或减少继发性损伤的治疗方面做了很多研究,取得了一定的成果;近年来有不少新的行之有效的方法涌现,现就脊髓损伤的治疗现状及进展作一综述,以期为研究人员或医务工作者提供有价值的参考。     

caspase家族与冠心病研究现状及其进展

冠状动脉粥样硬化性心脏病因冠状动脉血管发生动脉粥样硬化等病变而引起血管腔狭窄或者阻塞,造成心肌缺血、缺氧或坏死而导致的心脏病,常称为"冠心病"。在欧美等发达国家已成为第一杀手。冠心病的发病机制很复杂,给治疗和预防带来很大的挑战。近年来,随着细胞分子生物技术的发展,使冠心病发病机制的研究进入了细胞分子水平。细胞凋亡是冠心病发生发展过程中的重要环节,而与细胞凋亡相关的分子,就是半胱氨酸天冬氨酸特异性蛋白酶(caspase)家族。研     

微波治疗毛细血管扩张症25例分析

毛细血管扩张症是近皮肤和粘膜表面的细静脉、毛细血管和细动脉呈持久性丝状、星状或网状扩张,压之褪色,任何年龄均可发生。血管内皮细胞及其支持组织病变可能与发病有关。可分原发性和继发性两大类,原发性:血管痣、血管角化瘤、遗传性出血性毛细血管扩张症等。继发性:酒渣鼻、     

足细胞损伤与膜性肾病的研究进展

膜性肾病是常见的原发性肾小球疾病,是以肾小球脏层上皮细胞下免疫复合物弥漫性沉积、基底膜增厚伴钉突形成为其病理学特征。其发病机制复杂,近年来,随着对足细胞的一些标志分子的深入研究,证实足细胞的异常与蛋白尿的产生密切相关。在此对足细胞的异常与膜性肾病的发生发展等相关进展作简单综述。     

New molecular targets for the treatment of osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Current treatments are focused on symptomatic relief but they lack efficacy to control the progression of this disease which is a leading cause of disability. Therefore, the development of effective disease-modifying drugs is urgently needed. Different initiatives are in progress to define the molecular mechanisms involved in the initiation and progression of OA. These studies support the therapeutic potential of pathways relevant in joint metabolism such as Wnt/β-catenin, discoidin domain receptor 2 or proteinase-activated receptor 2. The dysregulation in cartilage catabolism and subchondral bone remodeling could be improved by selective inhibitors of matrix metalloproteinases, aggrecanases and other proteases. Another approach would favor the activity of anabolic processes by using growth factors or regulatory molecules. Recent studies have also revealed the role of oxidative stress and synovitis in the progression of this disease, supporting the development of a number of inhibitory strategies. Novel targets in OA are represented by genes involved in OA pathophysiology discovered using gene network, epigenetic and microRNA approaches. Further insights into the molecular mechanisms involved in OA initiation and progression may lead to the development of new therapies able to control joint destruction and repair.     

Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review

Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians' complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the above mentioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.     

Increased expression levels of apolipoprotein J/clusterin during primary osteoarthritis

Osteoarthritis (OA) is a slowly progressive degenerative joint disease that is associated with joint space narrowing, osteophyte formation and subchondral sclerosis. Despite extensive effort actual breakthroughs in the field of genetic or biochemical biomarkers of OA are limited. As secretory apolipoprotein J/clusterin (sCLU) has been implicated in both inflammatory and apoptotic molecular processes which contribute to the OA phenotype, the sCLU concentration in human serum and synovial fluid during advanced primary knee and hip OA was analysed. Elevated sCLU protein levels were shown in these two biological fluids. sCLU mRNA expression was also studied in normal cartilage and in advanced primary knee and hip OA samples. A significant up-regulation of sCLU mRNA expression (~25-fold) was found in samples collected from the tibial bone that was osteotomized during total knee arthroplasty in patients with primary knee OA, as compared to healthy tissue samples collected from the femoral head of macroscopically normal cartilage during the surgical treatment of subcapital fractures. By studying sCLU mRNA expression levels in samples collected during total hip arthroplasty in patients with advanced primary hip OA, an additional up-regulation of the sCLU mRNA expression (~4-fold), as compared to advanced primary knee OA, was found. Taken together, these observations indicate that the sCLU protein or mRNA expression level may be of a significant diagnostic and/or prognostic value during OA progression.     

miRNA-140在骨性关节炎中的研究进展

骨性关节炎(OA)是伴随疼痛和关节运动障碍的一种以关节软骨退变和关节周围形成骨质增生为病理特征的慢性进行性骨关节病。临床治疗往往不能令人满意。在OA治疗新进展中基因网络得到广泛研究,尤其是MicroRNA在OA的发病机制过程中有所表达并具有调控降解和修复等作用。该文通过miRNA结构功能;miRNA-140在OA的发病中调控机制、作用靶点以及miRNA-140在骨生长板的作用机制结合近几年的国内外研究做一综述。     

Treatment decisions,side-effect liability and cost-effectiveness in osteoarthritis

Cost-benefit ratios emphasize benefits as much as they do risks but the consequences of not treating also figure in the equation. For osteoarthritis (OA), most drugs designed to alter the progression have either been found wanting or have been withdrawn. That leaves palliation of symptoms as the search for pharmacological intervention to replace the very effective surgery continues. Guidelines to aid in the search succeed in defining alternatives to amelioration but less satisfactority define disease modifiers. Much of this derives from a misunderstanding: OA is not a disease, though it often provokes symptoms, but rather is the final common pathway of all events at a joint. Treatment can therefore be offered only when OA produces symptoms, and that is too late to reverse the process. If prediction were possible, more effective prophylaxis might be developed. The interferences with life content, life space and life span lead to the therapeutic decisions and their cost-effectiveness. Because symptoms in OA often result from secondary inflammation, anti-inflammatory drugs remain appropriate choices, even though simple analgesics suffice in the short term for pain relief alone. That inflammation may also underlie the inception of the process that leads to OA is self-evident and more effective initial treatment might slow the progression, but the symptoms of established OA are a secondary event, long after the historically elusive primary insult, and warrant careful appraisal of cost-effectivness of interventions as part of risk assessment.     

Patient and physician satisfaction with rofecoxib in osteoarthritis: results of the EVA (experience with VIOXX in arthritis) survey.

A nationwide survey was undertaken among 74,192 patients with osteoarthritis (OA) and 5986 physicians (including 5265 general practitioners [GPs]) in Belgium to evaluate satisfaction with the selective cyclo-oxygenase-2 inhibitor rofecoxib (12.5 or 25 mg, given once a day for an average of 30 days). Rofecoxib was considered by patients to be a very effective treatment for OA, with satisfaction scores of good or very good in the domains of pain, mobility and general satisfaction. More than 80% of GP-treated patients expressed a wish to continue rofecoxib therapy. Preference for rofecoxib was especially strong in patients (n = 45,453) who had previously been treated with conventional non-steroldal anti-inflammatory drugs (NSAIDs), notably patients who had used diclofenac, ibuprofen and nimesulide. Physicians also expressed high satisfaction with rofecoxib, with more than 80% of surveyed physicians indicating a wish to continue prescribing the drug. The results of this large survey demonstrate a clear preference for rofecoxib over conventional NSAIDs in a substantial majority of OA patients. The satisfactory pain relief and excellent gastrointestinal safety profile of rofecoxib demonstrated in earlier controlled trials are likely to have been factors in patients' preferences for rofecoxib over NSAIDs.     

Leptin – A Link between Obesity and Osteoarthritis. Applications for Prevention and Treatment

Osteoarthritis (OA) is the most common cause of musculoskeletal disability and pain in the world. The current drug treatment for OA is symptom relieving, and there is an urgent need for treatments that could retard, prevent or repair cartilage destruction in OA. Obesity is a major risk factor for OA. Traditionally, it has been thought to contribute to the development of OA by increasing the load on weight‐bearing joints. However, this appears to be an over‐simplification, because obesity is also linked to OA in the hand and finger joints. Recent studies have shown that adipocytokine leptin is a possible link between obesity and OA: Leptin levels in synovial fluid are increased in obese patients, leptin receptor (Ob‐R) is expressed in cartilage, and leptin induces the production of matrix metalloproteinases (MMPs), pro‐inflammatory mediators and nitric oxide (NO) in chondrocytes. Furthermore, according to the very recent findings, not only leptin levels in the joint but also leptin sensitivity in the cartilage are enhanced in obese OA patients. The findings supporting leptin as a causative link between obesity and OA offer leptin as a potential target to the development of disease‐modifying drugs for osteoarthritis (DMOAD), especially for obese patients.     

Proliferating effect of orotic acid through mTORC1 activation mediated by negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells

Orotic acid (OA) is a tumor promoter of experimental liver carcinogenesis initiated by DNA reactive carcinogens, the molecular mechanisms of which have not been fully elucidated. OA increases cell proliferation and decreases apoptosis in serum-starved SK-Hep1 hepatocellular carcinoma cells, which may ascribe to the inhibition of AMP-activated protein kinase (AMPK) phosphorylation and thus activation of mammalian target of rapamycin complex 1 (mTORC1). The effects of OA on mTORC1 activation, cell proliferation, and cell-cycle progression to S and G2/M phases were completely reversed by rapamycin. Activation of AMPK by a constitutively active mutant or aminoimidazole carboxamide ribonucleotide (AICAR) rescued the effects of OA. In conclusion, OA increases the proliferation and decreases the starvation-induced apoptosis of SK-Hep1 cells via mTORC1 activation mediated by negative regulation of AMPK.