医学蠕虫水通道蛋白研究进展

水通道蛋白是广泛存在于医学蠕虫中的一类可特异性介导水和其他溶质分子跨膜转运的膜内在蛋白,其在促进水跨膜转运、渗透调节、营养物质吸收、有毒代谢产物排出以及抗寄生虫药物转运过程中发挥重要作用,有望成为抗寄生虫疫苗候选分子和药物靶点。本文综述了医学蠕虫水通道蛋白的结构特征并探讨其作为抗蠕虫疫苗候选分子和药物靶点的可行性,为新型抗寄生虫疫苗或药物研发提供参考。     

日本血吸虫副肌球蛋白分子及其抗感染免疫研究进展

副肌球蛋白是最有希望的血吸虫候选疫苗之一,本文就副肌球蛋白分子的来源与分布、分子生物学、蛋白分子和核酸疫苗的免疫保护力及其免疫机制等方面的研究进展进行了综述。     

阿尔茨海默病患者皮层金属离子转运基因的生物信息学特征

目的 研究阿尔茨海默病(AD)患者皮层差异性金属离子转运基因的分子功能、生物学过程分类、分子调控网络的变化特征及关键节点，为AD的早期临床诊断和防治提供新方法和新思路。方法 从基因芯片公共数据库(GEO)中下载AD患者皮层基因芯片数据，筛选与金属离子转运相关的差异基因，采用PANTHER在线平台对差异基因进行基因本体(GO)分析，包括基因分类、分子功能、生物学过程及信号通路分析，应用STRING11.0在线分析软件对差异基因进行生物信息学调控网络分析，寻找关键节点基因，并使用Metascape在线软件分析基因功能簇间的相互作用关系，并筛选重要的基因功能簇。结果 在AD患者皮层基因中筛选出30个与金属离子转运相关的差异基因，均表达上调，其生物学功能主要与跨膜信号转导、金属离子跨膜转运、细胞内金属离子稳态、基因特异性转录调节、蛋白质结合活性调节相关，与离子型谷氨酸受体信号通路、α肾上腺素能受体信号通路密切相关。蛋白-蛋白相互作用(PPI)调控网络中的子网络分别与调节金属蛋白酶水解、调节电压依赖性钙通道及介导跨膜蛋白进入线粒体内膜密切相关，关键节点包括电压依赖性钙离子通道亚基α2/δ1(CA...     

日本血吸虫副肌球蛋白分子及其抗感染免疫研究进展

副肌球蛋白是最有希望的血吸虫候选疫苗之一，本就副肌球蛋白分子的来源与分布，分子生物学，蛋白分子和核酸疫苗的免疫保护力及其免疫机制等方面的研究进展进行了综述。     

刚地弓形虫棒状体蛋白2家族作为疫苗候选分子的研究进展

刚地弓形虫棒状体蛋白2家族(ROP2 family)是由弓形虫棒状体分泌的一类蛋白质,对弓形虫侵入宿主细胞及发挥细胞毒力起重要作用。ROP2家族成员包括ROP2、ROP4、ROP5、ROP8、ROP13、ROP16、ROP17和ROP18。近年来的研究发现,ROP2家族成员作为疫苗候选分子,可诱导宿主产生保护性免疫。本文综述了ROP2家族主要成员作为DNA疫苗或蛋白疫苗的研究进展。     

反向疫苗技术在感染性疾病疫苗研发中的应用

反向疫苗技术是指利用基因组序列信息和生物信息学技术,快速识别和鉴定疫苗候选分子的一种新型疫苗研制技术.该技术已被成功用于筛选B型脑膜炎双球菌疫苗候选抗原,且在其他重要的人体病原体疫苗候选分子的筛选中也得到了成功的应用,提示反向疫苗技术在新型疫苗研发中具有广阔的应用前景.     

斑点热疫苗研究进展

斑点热是斑点热群立克次体引起的一类重要传染病,接种疫苗仍是预防斑点热的一种重要措施. 灭活立氏立克次体接种能够刺激实验动物产生特异性体液和细胞免疫,有效对抗该立克次体的致死性攻击,但对人体免疫的保护效果并不理想. 目前已发现的斑点热群立克次体的保护性抗原主要有外膜蛋白A、外膜蛋白B、YbgF和Adr2等表面蛋白,是研发斑点热分子疫苗的潜在候选分子. 单个保护性抗原免疫虽然能够诱导动物产生良好的特异性体液和细胞免疫应答,但是不能提供完全保护. 多个保护性抗原组合或保护性抗原的T和B淋巴细胞表位组合是研发斑点热分子疫苗的有效途径.     

弓形虫棒状体颈部蛋白及棒状体蛋白研究的新进展

刚地弓形虫（Toxoplasma gondii）是一种专性细胞内寄生原虫。因其复杂的生活史和致病机理,目前尚无有效的专用药物进行治疗。近年来,关于抗弓形虫免疫及疫苗的研究逐步深入,棒状体颈部蛋白（RONs）及棒状体蛋白（ROPs）作为重要的抗弓形虫疫苗的候选抗原分子,广泛应用于新型抗弓形虫疫苗的研究中。本文总结了近几年来弓形虫棒状体颈部蛋白及棒状体蛋白的研究新进展,尤其是这些RONs及ROPs作为新型DNA疫苗分子研。宽的最新进展。     

Hepcidin在酒精性肝病发病中的作用研究进展

肝脏铁超负荷在酒精性肝病发病机制中起了重要的作用。铁调节蛋白(Hepcidin)是一种由肝脏分泌的小分子多肽,主要通过抑制肠道铁吸收和单核巨噬细胞系统铁释放来调控体内的铁稳态。近期研究发现,酒精可以影响铁调节蛋白在肝脏中的表达,导致肠道铁吸收及肝脏、单核巨噬细胞系统中铁利用再循环障碍,最终引起肝脏铁沉积。     

血吸虫疫苗候选分子的研究进展

近年来,对血吸虫病疫苗进行了广泛的研究,并取得一些进展,已鉴定、克隆和表达了近百种血吸虫病疫苗候选分子。虽然这些疫苗候选分子都没有获得如照射减毒活尾蚴疫苗那样好的免疫效果,但已有一些被WHO认为是最有希望的疫苗候选分子,它们在各种动物试验中均能诱生一定的免疫保护力。本文将血吸虫疫苗候选分子方面研究作一综述性介绍。     

Iron absorption and transport-an update

Iron is vital for all living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where heme is a significant part of the diet, most body iron is derived from dietary heme iron because heme binds few of the luminal intestinal iron chelators that inhibit absorption of non-heme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intracellularly, iron is released from heme by heme oxygenase so that iron leaves the enterocyte to enter the plasma as non-heme iron. Ferric iron is absorbed via a beta(3) integrin and mobilferrin (IMP) pathway that is not shared with other nutritional metals. Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese. Other proteins were recently described which are believed to play a role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma. The iron concentration within enterocytes reflects the total body iron and either upregulates or satiates iron-binding sites on regulatory proteins. Enterocytes of hemochromatotics are iron-depleted similarly to the absorptive cells of iron-deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorption. In non-intestinal cells most iron uptake occurs via either the classical clathrin-coated pathway utilizing transferrin receptors or the poorly defined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overload is unclear. This suggests that these pathways have intracellular functions in addition to facilitating iron uptake.     

徐州市7株猪链球菌病原学分析及分子分型研究

目的 对2020-2022年徐州市3起人感染猪链球菌疫情中分离到的7株猪链球菌进行鉴定和分型,了解本地区猪链球菌的病原学特征和流行特点。方法 采集与病例相关猪的鼻拭子和外环境等标本进行猪链球菌分离,采用飞行质谱和VITEK-2 Compact等微生物鉴定系统进行鉴定,对分离到的猪链球菌进行血清型、毒力基因的检测,并通过多位点序列分型(MLST)和脉冲场凝胶电泳(PFGE)等方法进行分子分型和溯源分析。结果 6株猪链球菌为血清2型,其中2021年人源(1株)与猪源(3株)猪链球菌荚膜多糖基因(cps2J)、溶菌酶释放蛋白基因(mrp)、细胞外蛋白因子基因(ef)和溶血素基因(sly)检测均为阳性,多位点序列分型结果为ST7型,PFGE同源性为100%,推断人可能因宰杀带菌猪时通过破损的伤口而感染;2020年和2022年临床分离株mrp基因缺失,多位点序列分型结果为ST1型。2022年外环境分离菌株不携带4种所检测的毒力基因,非数据库中已知ST型别。结论 本地区分离到的猪链球菌株携带多种毒力基因,致病菌株主要为血清2型,ST1和ST7型。     

Critical role for Streptococcus suis cell wall modifications and suilysin in resistance to complement-dependent killing by dendritic cells

Streptococcus suis is an emerging zoonotic agent of septicemia and meningitis. Knowledge on host immune responses toward S. suis and strategies used by this pathogen for subversion of these responses is scarce. Here, S. suis modulation of dendritic cell (DC) functions were assessed for the first time. Using S. suis knockout mutants in capsular polysaccharide (CPS) expression, it was shown that CPS blocks DC phagocytosis and impairs cytokine release by hindering cell wall components. Mutants impaired in D-alanylation of lipoteichoic acid (LTA) or N-deacetylation of peptidoglycan (PG) further demonstrated the importance of cell wall in modulation of DC activation. Notably, LTA/PG modifications were identified as major players in resistance to complement-dependent killing by DCs. Finally, S. suis hemolysin was partially involved in cytokine release and also contributed to bacterial escape of opsonophagocytosis. Overall, S. suis uses its arsenal of virulence factors to modulate DC functions and escape immune surveillance.     

猪链球菌BALB/c小鼠感染模型的初步建立

目的观察猪链球菌（Streptococcus suis）感染小鼠后的临床、病理变化,为将小鼠作为实验室研究猪链球菌的实验动物提供依据。方法用猪链球菌活菌经腹腔注射感染小白鼠,并做阴性对照,观察其临床症状,剖解病死小鼠,制作病理切片观察病理变化。并对病死小鼠做病原分离,通过培养特性鉴定、生化试验以及PCR鉴定确定其为猪链球菌。结果小鼠确由感染猪链球菌而致死,体内各组织、器官均产生典型的败血症病变。结论小鼠对猪链球菌易感,能够作为实验室研究猪链球菌良好的实验动物。     

Integrity of the iron transport process in mice with X-linked anaemia.

The defect in iron (Fe) absorption in X linked anaemia (sla) remains an enigma; absorption of a tracer dose of Fe is impaired in mice raised on an iron-containing cube diet but not in those raised on an iron-deficient diet. Because cobalt (Co) shares a similar intestinal transport pathway with Fe, a study was made of the effect of iron deficient diet on Co absorption. The duodenum of sla and genetically normal mice was perfused for 30 min with labelled solutions containing Co or Fe. Co uptake and transfer were similar in sla and normals fed cubes whereas Fe uptake and transfer were less in sla than in normals. The iron deficient diet caused an increase in the uptake and transfer of Co and Fe in sla and normals. When Co and Fe were perfused together in sla fed deficient diet, the uptake and transfer of each metal was less than when performed alone. The distribution of Fe and Co in subcellular mucosal fractions was determined by a differential centrifugation technique. Deficient diet resulted in a directionally similar change in the subcellular distribution of Co and Fe in sla and normals. The increase in Co as well as Fe absorption in the sla on an iron deficient diet to the same high level found in genetically normal animals, and the inhibitory effect of each metal on the absorption of the other suggests that the absorption defect in sla is unlikely to be due to a primary defect in the function of the transport carrier.     

贵州省一例人感染猪链球菌病例的病原学检测与分析

目的 对贵州省一疑似人感染猪链球菌病患者的血液来源菌株进行鉴定。方法 将患者血液分离菌株接种羊血琼脂平板,经革兰氏染色镜检、血清凝集试验和生化反应后,再用PCR技术检测猪链球菌种特异性基因(16S rRNA)和猪链球菌2型特有的荚膜多糖编码基因(cps2J)以及溶菌酶释放相关蛋白编码基因(mrp)、溶血素基因(sly)和细胞外蛋白因子编码基因(ef)。结果 传统方法和PCR技术将病例来源菌株鉴定为猪链球菌2型,PCR鉴定结果显示该菌株的毒力基因cps2J、mrp、sly和Ef均为阳性。结论 贵州省一例人感染猪链球菌疑似病例来源菌株为猪链球菌2型强毒株。     

Iron absorption and transport.

Iron is vital for living organisms because it is essential for multiple metabolic processes to include oxygen transport, DNA synthesis, and electron transport. However, iron must be bound to proteins to prevent tissue damage from free radical formation. Thus, its concentrations in body organs must be regulated carefully. Intestinal absorption is the primary mechanism regulating iron concentrations in the body. Three pathways for intestinal iron uptake have been proposed and reported. These are the mobilferrin-integrin pathway, the divalent cation transporter 1 (DCT-1) [or natural resistance-associated macrophage protein (Nramp2)] pathway, and a separate pathway for uptake of heme by absorptive cells. Each of these pathways are incompletely described. However, studies with blocking antibodies, observations in rodents with disorders of iron metabolism, and studies in tissue culture cells suggest that the DCT-1 pathway is dominant in embryonic cells and is involved with cellular uptake of ferrous iron, whereas the mobilferrin-integrin pathway facilitates absorption of dietary inorganic ferric iron. Thus, there are separate pathways for cellular uptake of ferric and ferrous inorganic iron. Body iron can enter intestinal cells from plasma via basolateral membranes containing the classical transferrin receptor pathway with a high affinity for holotransferrin. This keeps the absorptive cell informed of the state of iron repletion of the host. Intestinal mucosal cell iron seems to exit the cell via a distinct apotransferrin receptor and a newly described protein named hephaestin. Unlike the absorptive surface of intestinal cells, most other cells possess transferrin receptors on their surfaces and the vast majority of iron entering these cells is transferrin associated. There seem to be 2 distinct pathways by which transferrin iron enters nonintestinal cells. In the classical clathrin-coated pitendosome pathway, iron accompanies transferrin into the cell to enter a vesicle, which releases the iron to the cytosol with acidification (high affinity, low capacity). Under physiological conditions, a second transferrin associated pathway (low affinity, high capacity) exists which has been named the transferrin receptor independent pathway (TRIP). How the TRIP delivers iron to cells is incompletely described. In addition, tissue culture studies show that nonintestinal cells can accept iron from soluble iron salts. This occurs via the mobilferrin-integrin and probably the DCT-1 pathways. Cellular uptake of iron from iron salts probably occurs in iron overloading disorders and may be responsible for free radical damage when the iron binding capacity of plasma is exceeded. Radioiron entering the cell via the heme and transferrin associated pathways can be found in isolates of mobilferrin/paraferritin and hemoglobin. This interaction probably occurs to permit NADPH dependent ferrireduction so iron can be used for synthesis of heme proteins. Production of heme from iron delivered via these routes indicates functional specificity for the pathways.     

Purulent meningitis caused by Streptococcus suis in a pig breeder

A case of Purulent meningitis caused by Streptococcus suis type 2 is reported here. It occurred in a 58-year-old male pig breeder. A few days before presentation, the patient had experienced headache, systemic articular pain and fever (38.8 degrees C). On admission, he was stuporous and had neck stiffness and hemiparesis. Examination of cerebrospinal fluid showed purulent meningitis. The cultures identified Streptococcus suis II by PCR and specific serum. 2 months later, the patient was discharged in good clinical condition except for hearing loss. Streptococcus suis is known to be an important pathogen in the swine industry, this report is the first case of S. suis meningitis in man, in Japan.     

长春地区猪链球菌对大环内酯和林克酰胺类耐药的分子机制研究

目的　分析长春地区猪链球菌耐大环内酯类和林克酰胺类的分子机制。方法　采用微量稀释法和双纸片扩散法分别测定相关抗生素的耐药谱和红霉素耐药型 ,并以猪链球菌的染色体DNA为模板 ,PCR扩增ermB基因和mefA/E基因 ,然后将其克隆到pMD18-T载体中 ,用双脱氧链末端终止法测定DNA序列后进行序列分析。结果　 2 2株猪链球菌的临床分离菌株均扩增出ermB基因 ,而未扩增出mefA/E基因 ;对四环素、环丙沙星和大环内酯和克林霉素有高的耐药率和耐药水平 ;红霉素的耐药型以CR型为主。同源性分析显示 ,ermB基因的差异为 36 %～ 10 0 % ,与GenBank中的肺炎链球菌、粪肠球菌等的erm基因有 98%～ 10 0 %的同源性。结论　长春地区猪链球菌对MLSB 的耐药是红霉素甲基化转移酶所介导的 ,以CR型为主的耐药 ,编码该类耐药的是ermB基因 ,并与人源及动物源性的耐药基因可能存在着广泛的交换。     

An Overview of Molecular Aspects of Iron Metabolism

Iron (Fe) is an essential, but potentially noxious, metal for almost all organisms. Its precise cellular regulation is necessary to ensure synthesis of numerous iron-containing proteins required for metabolic processes yet at the same time avoiding the build-up of potentially toxic levels of iron. In humans, iron-deficiency results in anemia, while excess iron can lead to organ damage as a result of a build-up of non-transferrin-bound iron (NTBI). In recent years, the cloning of novel proteins has clarified the mechanisms of iron uptake, storage and metabolic regulation. Our current knowledge of the molecular aspects of mammalian iron metabolism and NTBI are presented in this review.