代谢组学及其在阿尔茨海默病研究中的应用

代谢组学〔1〕是通过考察生物体系(细胞、组织或生物体)受刺激或扰动后(如将某个特定的基因变异或环境变化后)代谢产物图谱及其动态变化,研究生物体系的代谢网络的一种技术,是继基因组学、转录组学和蛋白质组学之后发展起来的一门新兴"组学"。与其他三种组学研究的DNA、RNA和蛋白质     

代谢组学技术在糖尿病研究中的应用

糖尿病是典型的代谢性疾病,其危害主要来自高发的并发症,并最终导致高致死率和致残率.目前糖尿病确切机制仍然未知,也未见有效的根治方法,故预防成为重中之重.代谢组学作为一种能够识别和测量生物体整体代谢变化的新技术,已被广泛应用到糖尿病的相关研究中,并显现出在疾病防治中的巨大潜力.     

代谢组学及其在糖尿病研究中的应用

代谢组学是继基因组学、转录组学和蛋白质组学之后的一门新兴学科,目前已成功地运用到多学科领域,在疾病诊断、药物评价以及临床研究中发挥了重要作用.代谢组学的研究内容是生物体系中小分子代谢中间体和终产物,核磁共振和色谱-质谱的分析技术是代谢组学研究的两种主要技术手段.现综述近年来代谢组学分析技术及数据处理技术的研究进展,重点讨论代谢组学在糖尿病研究领域的应用,并对当前代谢组学研究中存在的问题及发展趋势进行探讨.     

代谢组学及其在肝脏疾病研究中的应用进展

代谢组学是继基因组学、转录组学和蛋白质组学之后兴起的又一门新的系统生物学分支,用于研究生物体系代谢网络的一种技术。近几年随着代谢组学的快速发展,其在肝脏疾病中的应用也日趋广泛。本文就近年代谢组学及其在肝脏疾病中的应用作一综述。     

代谢组学及其在心血管疾病中的研究进展

1999年英国皇家理工大学Nicholson教授及其同事首次提出代谢组学的概念[1]。代谢组学是继基因组学、转录组学和蛋白质组学之后,系统生物学的重要组成部分,是系统研究代谢产物的变化规律,解释机体生命活动代谢本质的科学。它通过高通量、高灵敏度与高精确度的现代分析技术分析细胞、组织和体     

代谢组学及其在糖尿病研究中的应用

代谢组学是继基因组学、转录组学和蛋白质组学之后的一门新兴学科,目前已成功地运用到多学科领域,在疾病诊断、药物评价以及临床研究中发挥了重要作用.代谢组学的研究内容是生物体系中小分子代谢中间体和终产物,核磁共振和色谱-质谱的分析技术是代谢组学研究的两种主要技术手段.现综述近年来代谢组学分析技术及数据处理技术的研究进展,重点讨论代谢组学在糖尿病研究领域的应用,并对当前代谢组学研究中存在的问题及发展趋势进行探讨.     

代谢组学及其在糖尿病研究中的应用

代谢组学是继基因组学、转录组学和蛋白质组学之后的一门新兴学科,目前已成功地运用到多学科领域,在疾病诊断、药物评价以及临床研究中发挥了重要作用.代谢组学的研究内容是生物体系中小分子代谢中间体和终产物,核磁共振和色谱-质谱的分析技术是代谢组学研究的两种主要技术手段.现综述近年来代谢组学分析技术及数据处理技术的研究进展,重点讨论代谢组学在糖尿病研究领域的应用,并对当前代谢组学研究中存在的问题及发展趋势进行探讨.     

代谢组学及其在肿瘤生物学研究中的应用进展

本文主要阐明了代谢组学的概念,代谢与肿瘤的关系,介绍代谢组学的研究状况及研究技术,着重讲述了其在肿瘤生物学领域研究中的应用,归纳了代谢组学在肿瘤的早期诊断、治疗和预后评估中的最新应用进展.     

代谢组学技术及其在高血压研究中的应用

代谢组学是“后基因组学”时期发展迅速的“组学”技术。基因组学、蛋白质组学和代谢组学构成了系统生物学的主体，为从基因、mRNA、蛋白质和代谢产物综合，即分别从调控生命的不同层面进行研究，探讨人类疾病的本质，逐步系统的、多维地认识疾病发生发展的规律。     

RNA干扰及其在寄生原虫研究中的应用

RNA干扰（RNAi）是由双链RNA（double stranded RNA,dsRNA）分子在mRNA水平关闭相应序列基因表达或使其沉默的过程,小分子RNA在RNAi介导的基因调节过程中发挥了重要作用。蓝氏贾第鞭毛虫中RNAi现象的发现,证明RNAi很早即已经存在于真核谱系中,抑制反转录转座子的转录可能是RNAi最古老的功能。本文就引起人类疾病的寄生原虫中的RNAi研究及应用现状进行综述。     

广东省2002～2003年人体重要寄生虫感染调查

目的了解广东省人体重要寄生虫感染现状及防治效果。方法按照2001年全国统一制定的调查方案,于2002～2003年在全省范围内按地区分层整群随机抽样的方法进行调查。以Kato-Katz法检查肠道蠕虫卵,透明胶纸肛拭法检查12岁以下儿童蛲虫卵。结果土源性线虫和华支睾吸虫感染共抽样调查17县个（市、区）51个点（村）26 363人,寄生虫总感染率为28.59%。其中男性感染率为29.99%、女性为27.20%;年龄组感染率5～9岁组最高,为37.36%,15～19岁组最低,为19.56%;渔民感染率最高,为44.00%,待业人员最低,为8.70%。人群蛔虫、钩虫、鞭虫、蛲虫和华支睾吸虫感染率分别为7.78%、6.13%、4.58%、30.38%和10.13%,其中钩虫感染率女性高于男性,蛲虫、华支睾吸虫感染率男性高于女性（P均〈0.01）。结论广东省肠道寄生虫感染率总体呈下降趋势,但华支睾吸虫、蛲虫感染率上升。     

肠道寄生虫病全民干预措施与近期效果评价

分别采取健康教育、集中供药、健康教育与集中供药相结合3种干预措施控制肠道寄生虫病,并评价其近期效果。结果表明,上述3种措施居民自愿服药率分别为8.7%、16.4%和61.3%,与对照村（1.8%）比较,差异有显著性（P〈0.05）;肠道寄生虫感染率分别下降59.7%、39.1%、85.6%和16.2%;肠道寄生虫病知识家长知晓率分别为74.2%、10.0%、60.0%和6.7%,学生知晓率分别为80.8%、15.0%、85.8%和11.7%。健康教育与集中供药相结合是防治寄生虫病有效措施。     

PCR技术应用于寄生虫分类鉴定的研究进展

PCR技术对寄生虫病原体的检测和鉴定提供了一种强有力的工具。PCR分子分类方法具有操作简便、特异性高和信息量丰富等优点,弥补了形态学分类上的不足。本文介绍了PCR-RFLP、RAPD和PCR-SSCP等技术的基本原理及用于寄生虫分类鉴定的研究进展。     

RNA干扰技术及其在血吸虫学研究中的应用

目前，血吸虫病仍然是许多国家和地区比较严重的公共卫生问题，寻找合适有效的防治方法是控制以至消灭血吸虫病工作的重点和难点。RNA干扰技术以其高效、特异、快捷地阻断特定基因的表达的优势，近年来已成为基因功能研究、基因防治和寻找药物靶点的潜在的强有力工具。本文介绍了RNA干扰技术在血吸虫学研究中的应用，包括在血吸虫生活史的不同生长发育阶段、借助不同的载体等方法实施RNA干扰进行血吸虫相关基因的功能研究，以及对其抗感染和抗病治疗的效果进行评价，以助于血吸虫生长发育及致病的一些重要基因的功能研究，为探索防治血吸虫病的新方法提供一些思路。     

Metabolomics study of blood pressure salt-sensitivity and hypertension

Background and aimsIdentify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension.Methods and resultsThe Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors.ConclusionsOur findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension.     

A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and activity are essential in parasitic Leishmania

Glycoconjugates play major roles in the infectious cycle of the trypanosomatid parasite Leishmania. While GDP-Fucose synthesis is essential, fucosylated glycoconjugates have not been reported in Leishmania major [H. Guo et al., J. Biol. Chem. 292, 10696–10708 (2017)]. Four predicted fucosyltransferases appear conventionally targeted to the secretory pathway; SCA1/2 play a role in side-chain modifications of lipophosphoglycan, while gene deletion studies here showed that FUT2 and SCAL were not essential. Unlike most eukaryotic glycosyltransferases, the predicted α 1–2 fucosyltransferase encoded by FUT1 localized to the mitochondrion. A quantitative “plasmid segregation” assay, expressing FUT1 from the multicopy episomal pXNG vector in a chromosomal null ∆fut1⁻ background, established that FUT1 is essential. Similarly, “plasmid shuffling” confirmed that both enzymatic activity and mitochondrial localization were required for viability, comparing import-blocked or catalytically inactive enzymes, respectively. Enzymatic assays of tagged proteins expressed in vivo or of purified recombinant FUT1 showed it had a broad fucosyltransferase activity including glycan and peptide substrates. Unexpectedly, a single rare ∆fut1⁻ segregant (∆fut1^s) was obtained in rich media, which showed severe growth defects accompanied by mitochondrial dysfunction and loss, all of which were restored upon FUT1 reexpression. Thus, FUT1 along with the similar Trypanosoma brucei enzyme TbFUT1 [G. Bandini et al., bioRxiv, https://www.biorxiv.org/content/10.1101/726117v2 (2021)] joins the eukaryotic O-GlcNAc transferase isoform as one of the few glycosyltransferases acting within the mitochondrion. Trypanosomatid mitochondrial FUT1s may offer a facile system for probing mitochondrial glycosylation in a simple setting, and their essentiality for normal growth and mitochondrial function renders it an attractive target for chemotherapy of these serious human pathogens.

Leishmania is a widespread human pathogen, with more than 1.7 billion people at risk, several hundred million infected, and with 12 million showing active disease ranging from mild cutaneous lesions to severe disfiguring or lethal outcomes (1–3). The Leishmania infectious cycle alternates between the extracellular promastigote in the midgut of sand flies and intracellular amastigote residing within macrophages of the mammalian host, where it survives and proliferates in highly hostile environments. These parasites have evolved specific mechanisms enabling them to endure adverse conditions, including a dense cell surface glycocalyx composed of lipophosphoglycan (LPG), glycosylphosphatidylinositol (GPI)-anchored proteins (GP63 and GP46), glycosylinositolphospholipids (GIPLs), and secreted glycoconjugates such as proteophosphoglycan (PPG) and secreted acid phosphatase (sAP) (reviewed in refs. 4–7). One prominent feature of LPG, PPGs, and sAPs is the presence of disaccharide phosphate repeating units ([6Gal(β)1,4)Man(α1)-PO₄]), also termed phosphoglycan or PG repeats.Our laboratory has focused on both forward and reverse genetic approaches to map out glycoconjugate synthesis in Leishmania, emphasizing genes impacting the glycocalyx (8, 9) as well as ether lipids and sphingolipids (10, 11). These studies have provided powerful tools leading to new insights on the requirements for LPG and related phosphoglycan-bearing molecules in both parasite stages within the mammalian and sand fly hosts (5, 6, 12–18).In several Leishmania species, modifications of the dominant PG repeats of LPG and PPG play key roles in the insect stages in mediating both the attachment and release of promastigotes and metacyclics, respectively, from the sand fly midgut via binding to midgut receptors there (19). In Leishmania major strain FV1 (LmjF), β1–3 galactosyl modifications of the PG repeating units enable replicating promastigotes to bind to the midgut lectin PpGalec, while addition of d-arabinopyranose (d-Arap) to the side-chain galactosyl residues block this interaction and allow release of parasites for subsequent transmission (19–21). We used forward genetic analysis to identify a large family of LPG side chain galactosyltransferases (SCG1-7) and d-arabinopyranosyltransferases (SCA1/2) mediating these modifications (21–26).As d-Arap is relatively uncommon in nature (27), we were motivated to explore its synthetic pathway. Previously, we identified two genes showing strong homology to the bifunctional Bacteroides protein FKP mediating synthesis of GDP-l-Fucose (GDP-Fuc) through successive kinase and pyrophosphorylase steps (28, 29). Many enzymes using l-Fucose will also accept d-Arap (which differ only by the 6-methyl group), and assays of the two recombinant Leishmania proteins showed that indeed one could synthesize both GDP-d-Arap and GDP-Fuc (AFKP; LmjF.16.0480), while the second could only synthesize GDP- Fuc [FKP; LmjF.16.0440 (28)]. These data were consistent with studies showing the presence of both GDP-Fuc and GDP-Arap in Leishmania (30). Correspondingly, genetic studies showed that knockouts of AFKP completely abrogated GDP-Arap and arabinosylated LPG synthesis, while knockouts of FKP showed little effect (28). However, we were unable to knock out both genes simultaneously, suggesting an unanticipated role for GDP-Fuc. That the essential role of A/FKPs depended on GDP-Fucose was established when GDP-Fuc but not GDP-Arap was provided through expression of the two de novo GDP-Fucose enzymes from Trypanosoma brucei, GDP-mannose 4,6-dehydratase (GMD) and GDP-Fuc synthetase, also known as GDP-4-dehydro-6-deoxy-d-mannose epimerase/reductase (GMER) (31). Similarly, the loss of de novo GDP-fucose synthesis was also lethal in T. brucei, which lacks the FKP salvage pathway (31).The essentiality of GDP-Fuc was unexpected since there are few reports of fucosylated molecules in Leishmania. One is a “fucose mannose ligand” from Leishmania donovani (32) for which a definitive structure is lacking. Several proteins were predicted to be fucosylated from mass-spectrometric (MS) proteome studies of L. donovani, albeit without experimental confirmation (33). More recently, human erythropoietin expressed in Leishmania tarentolae was shown to bear fucosylated glycans (34). While untested, it seemed unlikely that any of these putative fucosylations would be essential for growth in culture. Together, these data suggest that any putative essential Fuc-glycoconjugate predicted from genetic deletion studies must be relatively rare and/or cryptic.To better understand the fucose requirement in Leishmania, and guide efforts to identify the essential fucose conjugate, we surveyed candidate fucosyltransferases (FUTs). Unexpectedly, FUT1 localizes within the parasite mitochondrion, an uncommon observation for glycosyltransferases.     

Prevalence of intestinal parasites in rural Southern Indians

objective   To determine the prevalence of intestinal protozoal and helminthic infection in a rural population. method   Seventy-eight members of 15 families from a village were studied. Stool samples from all subjects were examined on alternate days for one month. results   The overall prevalence rate of various parasitic infections was 97.4%, with only 2 of 78 subjects not excreting parasites in any of their 15 samples. Eighteen (23.1%) persons had only one type of parasite, while 58 (74.3%) excreted multiple parasites. Giardia and Cryptosporidium were the commonest protozoan infections, affecting 42/78 (53.8%) and 31/78 (39.7%), respectively. Hookworm infestations were the commonest helminthic infections, seen in 48/78 (61.5%). Based on excretion patterns, the asymptomatic individuals could be divided into 2 groups of infrequent and frequent excretors, indicating that the host response may determine the level of parasite replication in the gut.     

The magnitude of CD4(+) T-cell activation rather than TCR diversity determines the outcome of Leishmania infection in mice

CD4(+) T cells play a critical role in determining the disease outcome in murine cutaneous leishmaniasis, and selective usage of T-cell receptor (TCR) is implied in promoting Leishmania major infection. However, little information is available on TCR usage in Leishmania-specific, IFN-γ-producing CD4(+) T cells. In this study, we investigated the TCR diversity and activation of CD4(+) T cells in a nonhealing model associated with L. amazonensis (La) infection and a self-healing model associated with L. braziliensis (Lb) infection. While marked expansion in the absolute number of several subsets was observed in Lb-infected mice, the percentages of TCR Vβ(+) CD4(+) -cell subsets were comparable in draining LN- and lesion-derived T cells in two infection models. We found that multiple TCR Vβ CD4(+) T cells contributed collectively and comparably to IFN-γ production and that the overall levels of IFN-γ production positively correlated with the control of Lb infection. Moreover, pre-infection with Lb parasites provided cross-protection against secondary La infection, owing to an enhanced magnitude of T-cell activation and IFN-γ production. Collectively, this study suggests that the magnitude of CD4(+) T-cell activation, rather than the TCR diversity, is the major determining factor for the outcome of Leishmania infection.     

益生菌在抗肠道寄生虫病感染中的作用

益生菌是一类对宿主有益的活性微生物,可以有效治疗胃肠道、呼吸道感染和过敏性疾病。虽然目前主要用于治疗细菌和病毒感染,但也有研究表明益生菌对寄生虫感染有抑制作用。因此,以益生菌制成的微生态制剂将为寄生虫防治提供一种新的途径。