Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A–F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn’s disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed.     

Endothelial Dysfunction in Chronic Inflammatory Diseases

Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.     

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

Platelet‐activating factor (PAF) and its receptor (PAFr) have been implicated in a wide range of diseases and disorders that originate from the activation of inflammatory pathways. Although the exact structure of the binding site on the PAFr remains unknown, the PAFr is a well‐established therapeutic target, and an array of structurally diverse PAFr antagonists have been identified. These include compounds that are structurally similar to the natural PAF ligand, synthetic heterocycles, complex polycyclic natural products, and various metal complexes. This review provides an update on more than 20 years of progress in this area. The development and synthesis of new PAFr antagonists, structure–activity relationship studies, the biological activity of these molecules, and their therapeutic potential are discussed.     

Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis,End-Stage Renal Disease and Transplant Medicine

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.     

Stromal Cell-Derived Factor 1 Gene Polymorphism Is Associated with Susceptibility to Adverse Long-Term Allograft Outcomes in Non-Diabetic Kidney Transplant Recipients

Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs). Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157). The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p = 0.041; p = 0.0051, respectively; log rank test). Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106–6.799, p = 0.03) and 2.306-fold (95% CI. 1.254–4.24, p = 0.008) risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs.     

Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.     

骨胶原清本润肌润体露治疗皮肤瘙痒症的临床疗效和安全性研究

本研究主要评价外用蒽菲优生骨胶原清本润肌润体露产品治疗皮肤瘙痒症的临床疗效和安全性研究,采用CallegariS.P.A.SOFT5.5检测皮肤的pH、皮肤油脂含量及皮肤含水量,用问卷量表方式比较治疗前、后受试者与皮肤干燥相关的症状以及前后疗效评价等方法。     

肾移植者联合环孢素A与百令用药的年龄-血红蛋白-红细胞三维分析

研究不同年龄的肾移植患者服用环孢素A与百令胶囊的合用药时,患者年龄与体内血红蛋白、红细胞的相关三维图像,为临床合理用药提供信息,使临床血常规指标形象化显现。方法:将合用环孢素A、百令胶囊的老年、中年、青年患者的年龄与用药后的红细胞、血红蛋白指标分为三组,采用MATLAB做三维图像、分析图像特征并对比分析老年组、中年组与青年组的图像异同。结果:三维图像显示出各项指标间存在内在关系与个体差异。结论:环孢素与百令胶囊的合用对老、中、青年肾移植者的红细胞、血红蛋白指标有不同影响。     

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology.     

Human Mesenchymal Stem Cells Modulate Inflammatory Cytokines after Spinal Cord Injury in Rat

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.     

TRPA1 Role in Inflammatory Disorders: What Is Known So Far?

The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. TRPA1 expression in resident tissue cells, inflammatory, and immune cells, through the indirect modulation of a large series of intracellular pathways, orchestrates a range of cellular processes, such as cytokine production, cell differentiation, and cytotoxicity. Therefore, the TRPA1 pathway has been proposed as a protective mechanism to detect and respond to harmful agents in various pathological conditions, including several inflammatory diseases. Specific attention has been paid to TRPA1 contribution to the transition of inflammation and immune responses from an early defensive response to a chronic pathological condition. In this view, TRPA1 antagonists may be regarded as beneficial tools for the treatment of inflammatory conditions.     

老、中、青肾移植患者口服普乐可复后总胆红素、尿酸、服药天数的三维图像分析

研究分析老、中、青年肾移植患者服用普乐可复天数、总胆红素、尿酸的三维图像,使临床指标形象化显现,为预测疾病提供信息。将60岁以上老年患者、40~59岁中年患者与小于40岁青年患者分三组,采用MATLAB7.0做三维图像,分析图像特征并且对老年、中年、青年组图像进行比较。三维图像显示出各项指标间存在内在关系与个体差异。体内指标与服药天数相关,体内指标对临床预防疾病具有重要意义。     

我国苹果病害发生和防治概况

本文简要介绍了我国的苹果生产情况、苹果病害种类和苹果树腐烂病、轮纹病、炭疽病、褐斑病、斑点落叶病、白粉病、黑星病等主要病害的发生流行特点及防治现状，并就当前防治中的几个问题进行了讨论。     

保护地粉尘法施药防治番茄病害研究

保护地粉尘法施药防治番茄病害研究结果表明：５％百菌清粉尘剂在番茄感病基每隔９０－１天施药一次，全程共施粉法剂６次，对番茄晚疫病、叶霉病及早疫病防治效果７次调查平均分别为９４．４、８１．８６和８．１２％；三种病害比农户自管田推迟发病分别为１８．２４和１６天；粉地比农户自管田全程可减少施药７次，减少用药量５３．９％，节省用工９４５小时／公顷，共计减少费用２２３１．２５元／公顷，增收１６１７１．００元／     

Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition

Rosacea is a chronic cutaneous inflammatory disease that affects the facial skin. Clinically, rosacea can be categorized into papulopustular, erythematotelangiectatic, ocular, and phymatous rosacea. However, the phenotypic presentations of rosacea are more heterogeneous. Although the pathophysiology of rosacea remains to be elucidated, immunologic alterations and neurovascular dysregulation are thought to have important roles in initiating and strengthening the clinical manifestations of rosacea. In this article, we present the possible molecular mechanisms of rosacea based on recent laboratory and clinical studies. We describe the genetic predisposition for rosacea along with its associated diseases, triggering factors, and suggested management options in detail based on the underlying molecular biology. Understanding the molecular pathomechanisms of rosacea will likely aid toward better comprehending its complex pathogenesis.     

P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.     

LincRNA-p21: Implications in Human Diseases

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases.     

噬菌体展示技术及其在感染性疾病中的应用

感染性疾病是病原体与宿主相互作用的结果。了解病原体与宿主相互作用的分子基础,对于感染性疾病的预防和控制尤为重要。噬菌体展示技术不仅广泛应用于抗原表位作图和抗体工程技术,而且还可用于研究蛋白质与配体的相互作用,以揭示感染过程中蛋白与配体的相互作用机制。本文仅就噬菌体展示技术及其在感染性疾病中的应用作一综述。