Serine Proteases of Parasitic Helminths

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed.     

Prevalence of Intestinal Helminths among Inhabitants of Cambodia (2006-2011)

In order to investigate the status of intestinal helminthic infections in Cambodia, epidemiological surveys were carried out on a national scale, including 19 provinces. A total of 32,201 fecal samples were collected from schoolchildren and adults between 2006 and 2011 and examined once by the Kato-Katz thick smear technique. The overall egg positive rate of intestinal helminths was 26.2%. The prevalence of hookworms was the highest (9.6%), followed by that of Opisthorchis viverrini/minute intestinal flukes (Ov/MIF) (5.7%), Ascaris lumbricoides (4.6%), and Trichuris trichiura (4.1%). Other types of parasites detected were Enterobius vermicularis (1.1%), Taenia spp. (0.4%), and Hymenolepis spp. (0.2%). The northwestern regions such as the Siem Reap, Oddar Meanchey, and Banteay Meanchey Provinces showed higher prevalences (17.4-22.3%) of hookworms than the other localities. The southwestern areas, including Koh Kong and Preah Sihanouk Provinces showed higher prevalences of A. lumbricoides (17.5-19.2%) and T. trichiura (6.1-21.0%). Meanwhile, the central and southern areas, in particular, Takeo and Kampong Cham Provinces, showed high prevalences of Ov/MIF (23.8-24.0%). The results indicate that a considerably high prevalence of intestinal helminths has been revealed in Cambodia, and thus sustained national parasite control projects are necessary to reduce morbidity due to parasitic infections in Cambodia.     

Potential surrogate quantitative immunomodulatory potency assay for monitoring human umbilical cord-derived mesenchymal stem cells production

Mesenchymal stem cells (MSCs) play an important role as immune modulator through interaction with several immune cells, including macrophages. In this study, the immunomodulatory potency of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) was demonstrated in the in vivo middle cerebral artery occlusion (MCAo)-induced brain injury rat model and in vitro THP-1-derived macrophages model. At 24 h after induction of MCAo, hUC-MSCs was administered via tail vein as a single dose. Remarkably, hUC-MSCs could inhibit M1 polarization and promote M2 polarization of microglia in vivo after 14 days induction of MCAo. Compared with THP-1-derived macrophages which had been stimulated by lipopolysaccharide, the secretion of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ inducible protein (IP-10), were significantly reduced in the presence of hUC-MSCs. Moreover, the secretion of anti-inflammatory cytokine, interleukin-10 (IL-10), was significantly increased after cocultured with hUC-MSCs. Prostaglandins E2 (PGE2), secreted by hUC-MSCs, is one of the crucial immunomodulatory factors and could be inhibited in the presence of COX2 inhibitor, NS-398. PGE2 inhibition suppressed hUC-MSCs immunomodulatory capability, which was restored after addition of synthetic PGE2, establishing the minimum amount of PGE2 required for immunomodulation. In conclusion, our data suggested that PGE2 is a crucial potency marker involved in the therapeutic activity of hUC-MSCs through macrophages immune response modulation and cytokines regulation. This study provides the model for the development of a surrogate quantitative potency assay of immunomodulation in stem cells production.     

真菌过敏性哮喘的治疗研究进展

真菌过敏性哮喘是由环境中真菌致敏原暴露诱导的一种呼吸道慢性炎症性疾病。真菌过敏哮喘患者肺部炎症细胞、结构细胞及细胞组分间有复杂的相互作用,使得患者气道壁重塑并伴渐进性肺功能障碍,表现为喘息、胸闷、呼吸困难等症状,对患者的工作和生活造成严重影响,而目前糖皮质激素及抗菌药物等传统疗法对其治疗效果欠佳。近年来,很多研究开始致力于对真菌过敏性哮喘新的治疗方法进行积极探索,使得真菌过敏性哮喘的治疗除应用糖皮质激素等传统方法外,在抗真菌感染及其免疫学治疗控制真菌过敏性哮喘方面取得一定新进展。     

Immunomodulatory effects of mesenchymal stem cells for the treatment of cardiac allograft rejection

Heart transplantation continues to be the gold standard clinical intervention to treat patients with end-stage heart failure. However, there are major complications associated with this surgical procedure that reduce the survival prognosis of heart transplant patients, including allograft rejection, malignancies, infections, and other complications that arise from the use of broad-spectrum immunosuppression drugs. Recent studies have demonstrated the use of mesenchymal stem cells (MSCs) against allotransplantation rejection in both in vitro and in vivo settings due to their immunomodulatory properties. Therefore, utilization of MSCs provides new and exciting strategies to improve heart transplantation and potentially reduce the use of broad-spectrum immunosuppression drugs while alleviating allograft rejection. In this review, we will discuss the current research on the mechanisms of cardiac allograft rejection, the physiological and immunological characteristics of MSCs, the effects of MSCs on the immune system, and immunomodulation of heart transplantation by MSCs.     

Prevalence of Schistosomes and Soil-Transmitted Helminths among Schoolchildren in Lake Victoria Basin,Tanzania

The objectives of this study was to conduct a survey on schistosomiasis and soil-transmitted helminth (STH) infections in order to come up with feasible control strategies in Lake Victoria basin, Tanzania. Depending on the size of the school, 150-200 schoolchildren were recruited for the study. Duplicate Kato-Katz stool smears were prepared from each child and microscopically examined for Schistosoma mansoni and STHs. Urine specimens were examined for Schistosoma haematobium eggs using the filtration technique. After the survey, mass drug administration was done using praziquantel and albendazole for schistosomiasis and STHs infections, respectively. A total of 5,952 schoolchildren from 36 schools were recruited for the study and had their stool and urine specimens examined. Out of 5,952 schoolchildren, 898 (15.1%) were positive for S. mansoni, 754 (12.6%) for hookworms, 188 (3.2%) for Ascaris lumblicoides, and 5 (0.008%) for Trichuris trichiura. Out of 5,826 schoolchildren who provided urine samples, 519 (8.9%) were positive for S. haematobium eggs. The results revealed that intestinal schistosomiasis, urogenital schistosomiasis, and STH infections are highly prevalent throughought the lake basin. The high prevalence of intestinal and urogenital schistosomisiasis in the study area was a function of the distance from Lake Victoria, the former being more prevalent at localities close to the lake, whilst the latter is more so away from it. Control of schistosomiasis and STHs in the study area requires an integrated strategy that involves provision of health education to communities, regular treatments, and provision of adequate safe water supply and sanitation facilities.     

Potential canopy influences on the isotopic composition of nitrogen and sulphur in atmospheric deposition

Isotopic studies of nitrogen and sulphur inputs to plant/soil systems commonly rely on limited published data for the ¹⁵N/¹⁴N and ³⁴S/³²S ratios of nitrate, ammonium and sulphate in rainfall. For systems with well-developed plant canopies, however, inputs of these ions from dry deposition or particulates may be more important than rainfall. The manner in which isotopic fractionation between ions and gases may lead to dry deposition and particulates having ¹⁵N/¹⁴N or ³⁴S/³²S ratios different from those of rainfall is considered. Data for rainfall and throughfall in coniferous plantations are then discussed, and suggest that: (1) in line with expectations, nitrate washed from the canopy has ¹⁵N/¹⁴N ratios higher than those in rainfall; (2) the ¹⁵N/¹⁴N ratios of ammonium washed from the canopy are variable, with high ratios being found for canopies of higher pH in conditions of elevated ambient ammonia gas concentrations; and (3) in accord with expectations and previous work, ³⁴S/³²S ratios of sulphate washed from the canopy are not substantially different from those in rainfall. The study suggests that if atmospheric inputs are relevant to isotopic studies of the sources of nitrogen for canopied systems, then confident interpretation will require analysis of these inputs. Received: 3 March 1996 / Accepted: 28 September 1996     

CpG基元的免疫学进展及基因治疗策略

CpG诱发免疫反应的能力对免疫预防是一大优点 ,但在基因治疗中 ,质粒中所含的CpG基元能够阻止基因转移或导致巨大副作用 (炎症和毒性 )。本文简单综述了CpG基元的免疫学活性、主要作用和信号转导通路 ,并且针对它在基因治疗中存在的问题及可能的解决办法进行探讨。     

Targeting Ferroptosis by Ubiquitin System Enzymes: A Potential Therapeutic Strategy in Cancer

Ferroptosis is a novel type of regulated cell death driven by the excessive accumulation of iron-dependent lipid peroxidation. Therapy-resistant tumor cells, particularly those in the mesenchymal-like state and prone to metastasis, are highly susceptible to ferroptosis, suggesting that induction of ferroptosis in tumor cells is a promising strategy for cancer therapy. Although ferroptosis is regulated at various levels, ubiquitination is key to post-translational regulation of ferroptotic cell death. E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) are the most remarkable ubiquitin system enzymes, whose dysregulation accounts for the progression of multiple cancers. E3s are involved in the attachment of ubiquitin to substrates for their degradation, and this process is reversed by DUBs. Accumulating evidence has highlighted the important role of ubiquitin system enzymes in regulating the sensitivity of ferroptosis. Herein, we will portray the regulatory networks of ferroptosis mediated by E3s or DUBs and discuss opportunities and challenges for incorporating this regulation into cancer therapy.     

Prevalence of Schistosomes and Soil-Transmitted Helminths and Morbidity Associated with Schistosomiasis among Adult Population in Lake Victoria Basin,Tanzania

The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs.     

Potential diagnostic applications of biosensors: current and future directions

This review describes recent advances in biosensors of potential clinical applications. Biosensors are becoming increasingly important and practical tools in pathogen detection, molecular diagnostics, environmental monitoring, food safety control as well as in homeland defense. Electrochemical biosensors are particularly promising toward these goals arising due to several combined advantages including low-cost, operation convenience, and miniaturized devices. We review the clinical applications of electrochemical biosensors based on a few selected examples, including enzyme-based biosensors, immunological biosensors and DNA biosensors.     

寄生蠕虫的群体遗传学研究

寄生蠕虫群体遗传学研究常用的遗传标记有等位酶、线粒体DNA、随机扩增多态性DNA或扩增性片段长度多态性和微卫星DNA等。应用这些遗传标记的研究表明,大多数寄生蠕虫群体遗传结构有不同水平的变异,这些变异的产生主要与寄生虫的生活史和群体生态、宿主的地理分布和环境等因素有关,并因此提出了有关遗传变异的一些假说。本文对寄生蠕虫群体遗传学的研究作一综述。 Abstract:Genetic markers including allozyme,mtDNA,RAPD/RFLP and micro DNA have been used in the research of helminth population genetics.Available data on helminth genetic variability have shown that most helminth populations exhibit different levels of genetic variation resulting mainly from the pattern of life cycle,geographical distribution and parasite-host interaction,and several hypotheses have been proposed to explain the genetic variation.     

The promise of cognitive behavior therapy for treatment of severe mental disorders: a review of recent developments

Cognitive behavior therapy (CBT), as exemplified by the model of psychotherapy developed and refined over the past 40 years by A.T. Beck and colleagues, is one of the treatments of first choice for ambulatory depressive and anxiety disorders. Over the past several decades, there have been vigorous efforts to adapt CBT for treatment of more severe mental disorders, including schizophrenia and the more chronic and/or treatment refractory mood disorders. These efforts have primarily studied CBT as an adjunctive therapy, i.e., in combination with pharmacotherapy. Given the several limitations of state‐of‐the‐art pharmacotherapies for these severe mental disorders, demonstration of clinically meaningful additive effects for CBT would have important implications for improving public health. This paper reviews the key developments in this important area of therapeutics, providing a summary of the current state of the art and suggesting directions for future research.     

Recombinant Human Superoxide Dismutases: Production and Potential Therapeutical Uses

In many pathological situations, tissue damage is caused by cellular generation of superoxide free radicals (O₂-). These active species are generated during post-ischemic reperfusion of organs, in hyperoxic tissue, during acute and chronic inflammation and during exposure to ionizing radiation. Exogenous superoxide dismutase (SOD) was shown to significantly prevent such damage.

The genes for human cytosolic Cu/ZnSOD and mitochondrial MnSOD were cloned and introduced into an E. coli expression system. The proteins were expressed in high yields and purified to homogeneity, yielding pharmaceutical-grade materials. These enzymes were used in a variety of in vivo animal models for the demonstration of their protective effects against oxidative damage. Comparative pharmacokinetic studies in rats have revealed that the half-life of Cu/ZnSOD was 6–10min., while that of MnSOD was 5–6 hours, thus indicating that MnSOD may be superior to Cu/ZnSOD for the treatment of chronic diseases. Indeed, MnSOD was found to be erective as an anti-inflammatory agent in the rat carrageenan induced paw edema acute inflammation model. Both enzymes were also effective in ameliorating post-irradiation damage in mice exposed to whole-body or localized chest X-ray radiation.     

成体干细胞的研究及潜在应用

成体干细胞(adultstemcells)存在于人和哺乳动物的多种成体中,具有自我更新和一定的分化潜能.现已从骨髓、软骨、血液、神经、肌肉、脂肪、皮肤、角膜缘、肝脏、胰腺等许多组织中获得干细胞,并在部分成体干细胞的体外分离培养、扩增及诱导分化等研究中取得突破性进展,发现部分成体干细胞具有预想不到的分化潜能.成体干细胞不仅是发育生物学研究的理想模型,而且是细胞移植治疗、人工组织或器官构建的种子细胞和基因治疗的理想载体细胞,因此,在揭示生命的本质和规律及再生医学中有十分广阔的应用前景.     

自闭症谱系障碍的分子遗传学研究进展

自闭症谱系障碍(Autism spectrum disorder, ASD)是一类常见神经发育疾病,以社会交往障碍、刻板重复行为与狭隘的兴趣为主要临床特征。在过去40年间,ASD患病率呈不断上升趋势,因而日益受到人们关注。近年来由于大规模外显子测序的应用,发现了许多新的ASD易感基因。这些易感基因富集在几个共同的遗传信号通路中,参与突触形成和染色质重构等。最新的动物模型研究表明,ASD的发病机制包括神经突触可塑性异常和神经回路兴奋性-抑制性平衡紊乱。本文从ASD遗传病因的高度异质性、众多致病基因突变影响的共同生物学过程以及遗传诊断方法和药物研发的进展等几个方面进行了综述,以期帮助人们深入了解ASD的遗传基础和转化研究现状。