肠道菌群代谢产物短链脂肪酸在慢性肾脏病中的研究进展

近年来研究发现肾脏与肠道微生态间存在密切的联系,称为"肠-肾轴"。慢性肾脏病患者(CKD)由于各种因素往往导致肠道生态失调,表现为肠道菌群种类的相对丰度、组成及其代谢产物发生改变。肠道菌群代谢产物短链脂肪酸(SCFAs)是联系宿主和肠道菌群的重要中介物质,具有生物学效应。研究发现SCFAs主要通过与G蛋白偶联受体结合,抑制组蛋白去乙酰化酶调节RAS系统、炎症反应和细胞自噬等,起到延缓肾脏炎症和纤维化的作用。基于SCFAs与肾脏之间的紧密联系,SCFAs可能成为慢性肾脏病治疗的新靶点。外源性补充SCFAs能延缓CKD发生和发展的作用逐渐受到认可。因此,进一步研究SCFAs在肾脏方面的具体作用机制尤为重要。     

肠道菌群失调与高尿酸血症关系的研究进展

高尿酸血症（hyperuricemia,HUA）是一种涉及肝、肾、肠等多个器官的代谢性疾病，因尿酸代谢异常而引起代谢障碍。尿酸在肝脏和肾脏中的代谢途径目前已经被阐明，但在肠道内的代谢途径尚未完全清晰。肠道菌群在人体肠道中定植，与宿主存在互惠共生的关系，在宿主的代谢和免疫调节中起着至关重要的作用。肠道菌群结构的变化可能引起代谢紊乱，肠道菌群参与嘌呤代谢酶的合成和炎症因子的释放，与HUA的发生发展密切相关。肠道菌群作为探讨HUA发病机制的切入点，已成为新的研究热点。本综述主要阐述HUA与肠道菌群之间的关系，探讨肠道菌群抗HUA的机制，如肠道菌群促进嘌呤和尿酸分解代谢，影响尿酸排泄，以及HUA引起的肠道炎症反应等，以期为通过调节肠道菌群来治疗HUA提供一定的依据。     

衰弱症干预的新角度：营养-肠道菌群-衰弱轴

在全球人口老龄化背景下,衰弱症作为老年医学重要的多维概念,其早期诊断和干预已成为研究者关注的主要方向。能量和营养的低摄入在推动衰弱症进展中的作用不容忽视。肠道菌群通过双向调节宿主和肠菌的营养代谢、信号传导,以及对宿主多种器官的直接生物化学作用,不仅参与代谢疾病的发病机制,而且帮助营养策略发挥干预作用。本综述从骨骼肌和免疫角度总结了肠道菌群和食源性代谢物参与营养-衰弱相互作用的文献进展。现有文献提示短链脂肪酸和氨基酸等食源性肠道菌群代谢物作为宿主受体的配体参与调节肌肉、认知和免疫功能,进而影响宿主的衰弱进程,即支持“营养-肠道菌群-衰弱轴”的存在。随着肠道菌谱分析和代谢组学等技术在该领域的深入应用,营养-肠道菌群将为衰弱症的早期发现和干预提供新颖、经济和有效的个体化手段。     

基于无菌动物研究肠道微生物与类风湿关节炎发病相关性

肠道微生物与宿主的生长发育、免疫、代谢等方面均密切相关,但肠道菌群与宿主之间复杂的相互作用在很大程度上仍然是未知的。目前无菌动物已成为探索肠道微生物与宿主相互作用的重要工具,多项研究使用无菌动物模型探讨肠道菌群在宿主代谢、机体免疫系统的发育和成熟等方面的作用,其中包括肠道菌群在自身免疫性疾病发病及预后中的作用。研究发现,肠道菌群作为环境因素之一可能参与类风湿关节炎(rheumatoid arthritis,RA)发病,然而其因果关系未明。本文将对使用无菌动物探讨肠道微生物参与类风湿关节炎发病的相关性研究作一综述,为进一步深入研究肠道菌群在RA发病中的作用及机制研究提供理论依据。     

胆汁酸和肠道菌群相互作用对非酒精性脂肪性肝病的影响

近年来,大量研究发现胆汁酸与肠道菌群相互作用对非酒精性脂肪性肝病的发生和发展有重要影响。胆汁酸主要在肝脏中合成,分泌进入肠道后不仅可以促进脂类物质的消化和吸收,还具有重要的生理信号和代谢调节作用,其能通过参与能量代谢和炎症反应影响非酒精性脂肪性肝病的进程。肠道菌群的代谢产物(如胆汁酸、短链脂肪酸、内生性乙醇和三甲胺等)对宿主的代谢表型、免疫稳态、炎症反应和病程进展等都有重要调节作用。本文主要综述了胆汁酸的合成、转运代谢与肠道菌群结构变化之间的互相作用和对话交流机制,揭示了肠道菌群结构紊乱和胆汁酸代谢异常对非酒精性脂肪性肝病的推动作用,以期为临床上治疗非酒精性脂肪性肝病提供全新的策略和方法。     

肠道菌群与宿主关系解析及肠道菌群调控/合成研究进展

肠道菌群和宿主健康之间有着密切的关系,其与宿主之间存在着复杂的相互作用,如菌群及其代谢产物与免疫系统的互作、脑-肠轴、肺-肠轴等.肠道菌群紊乱与多种疾病的发生和发展存在相关性,且部分微生物菌株与一些疾病的发生存在着因果关系.肠道菌群还会影响药物代谢,个体差异的肠道菌群使得不同个体对于同种药物的代谢具有很大差别;解析个体肠道菌群的状态及其与宿主之间的关系是实施个性化精准诊疗的重要环节.肠道菌群具有可塑性,通过饮食调控、益生菌/益生元/合生元补充、粪菌移植等干预手段可以使肠道菌群处于健康状态,应用肠道菌群编辑和合成肠道微生物组等新技术调控、合成肠道菌群的研究已有报道.目前,利用合成生物学等方法调控肠道菌群已成为改善和治疗疾病的有效方法之一.本文综述了肠道菌群与人体等宿主的相互作用、肠道菌群与部分疾病的相关性和因果性,以及通过肠道菌群调控改善人体健康状态的策略,展望了微生物组学和合成生物学在肠道菌群调控与合成方面的应用.     

益生菌及益生元调节骨代谢的研究进展

骨质疏松症已成为威胁中老年人健康的主要疾病之一,越来越多的人受到该病症的危害.肠道菌群是定殖在机体肠道内,与宿主形成共生关系的微生物,对宿主的免疫及代谢等产生重要影响,研究发现,肠道菌群与骨代谢之间存在密切关系,本文从肠道菌群与免疫、骨代谢与免疫、肠道菌群与骨代谢、益生菌及益生元调节骨代谢等几个方面阐述,肠道菌群有望成为骨质疏松症治疗的一个新靶点,通过益生菌或益生元来干预肠道菌群组成,进而调节免疫系统状态,抑制促炎因子的生成,从而降低骨吸收作用,达到预防和治疗骨质疏松症的目的.     

运动与肠道菌群的相关性

肠道菌群与人体互相依存,与机体的感染、营养、免疫及代谢密不可分,在某些疾病的预防和治疗中有着非常重要的作用。肠道菌群具有易变性,它的种类和数量是由遗传和环境因素共同决定的,环境因素主要包括宿主健康状态和生活方式等。近来发现,生活方式与代谢性疾病的发生发展密切相关,而这些代谢性疾病的发生发展都与肠道菌群的改变有关。本研究就机体不同代谢状态下肠道菌群的变化以及运动这种生活方式直接对肠道菌群的影响进行综述。     

膳食营养与肠道微生物组

膳食营养是影响肠道菌群结构和功能最为重要,也较为迅速的因素,并由此影响宿主的代谢状况。高脂等不健康饮食习惯会引起肠道菌群的失调,使肠道通透性增加,形成全身的慢性、低水平炎症,进一步破坏胰岛素的信号转导通路,最终导致包括胰岛素抵抗、肥胖、糖尿病等在内的代谢综合征的发生。高纤维饮食可能通过富集短链脂肪酸(SCFAs)产生菌,增加肠道内SCFAs浓度,降低内毒素产生菌水平,进而减少脂多糖(LPS)入血引起的组织器官炎症。这类饮食还能抑制某些能产生有害物质,如三甲胺(TMA)和吲哚的有害菌,从而改善宿主的代谢状况。益生元能减少宿主的脂肪积累,降低宿主的炎症水平并增加胰岛素敏感性,同时还伴随着食欲因子、胃肠肽水平和肠道中某些益生菌丰度的增加。此外,蔬菜、水果、奶制品等食物也能通过调节肠道菌群进而改善宿主的代谢状况。虽然越来越多的研究表明,肠道菌群可能在调节宿主的代谢状况中存在着因果关系,但是在食物-肠道菌群-代谢这条通路中到底存在着一种怎样的机制,有待进一步研究。     

褐藻膳食纤维对机体代谢及其肠道菌群调节作用的研究进展

褐藻膳食纤维（海藻酸盐,Alg）是存在于海洋食用藻类中的一种酸性多糖,具有多种生物活性作用。研究表明,褐藻膳食纤维可有效地改善肠道菌群的组成结构,通过菌群代谢膳食纤维发酵产物调节宿主机体的代谢水平,从而改善肥胖、糖尿病等代谢相关性疾病。从作为食品添加剂的角度出发,对褐藻膳食纤维作用于人和动物模型体重、血糖、脂代谢以及肠道菌群的效果加以综述,并探讨其潜在机制,为海洋功能性产品的开发和应用提供科学依据。     

人正常软骨和软骨肉瘤蛋白多糖的比较研究

取三例一般型一级的软骨肉瘤及不同年令正常人股骨头关节软骨,经4mol/L盐酸胍提取和氯化铯平衡等密度梯度离心,分析蛋白多糖组份的化学组成,并用Sepharose CL-2B层析分析蛋白多糖分子大小。初步结果,两例软骨肉瘤蛋白多糖的化学组成和分子大小与新生儿接近,另一例软骨肉瘤蛋白多糖的化学组成和分子大小与成年人相似。此结果说明软骨肉瘤生物学行为的多变性及其蛋白多糖的异质性。     

Chondroitin and keratan sulphate in the epidermal club cells of teleosts

Club cells in the epidermis of the catfish, Corydoras aeneus and the loaches, Acanthophthalmus semicinctus and Botia horae contain chondroitin and keratan sulphate as demonstrated by immunocytochemistry using monoclonal antibodies. Their release from club cells might contribute to the physical support of the epithelium and could help seal damaged tissue.     

Drowning-out crystallisation of sodium sulphate using aqueous two-phase systems

A novel method to obtain crystals of pure, anhydrous salt, using aqueous two-phase systems was studied. A concentrated salt solution is mixed with polyethylene glycol (PEG), upon which three phases are formed: salt crystals, a PEG-rich liquid and a salt-rich liquid. After removal of the solid salt, a two-phase system is obtained. Both liquid phases are recycled, allowing the design of a continuous process, which could be exploited industrially. The phase diagram of the system water–Na₂SO₄–PEG 3350 at 28°C was used. Several process alternatives are proposed and their economic potential is discussed. The process steps needed to produce sodium sulphate crystals include mixing, crystallisation, settling and, optionally, evaporation of water. The yield of sodium sulphate increases dramatically if an evaporation step is used.     

Autoactivation of prolegumain is accelerated by glycosaminoglycans

The cysteine protease legumain participates in several biological and pathological processes including tumour invasion and metastasis. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform in order to reach an enzymatically active form. Here we demonstrate that the naturally occurring polyanionic glycosaminoglycans (GAGs) chondroitin 4-sulphate (C4S), chondroitin 6-sulphate (C6S), chondroitin 4,6-sulphate (C4,6S), heparin, heparan sulphate (HS) as well as chondroitin sulphate (CS)-derived decasaccharides accelerated the autocatalytic activation of prolegumain through ionic interactions in a concentration-, size- and time-dependent manner at pH 4.0. In contrast, at pH 5.0 only C4S and C4,6S were able to promote prolegumain activation, while CS-derived decasaccharides, C6S, heparin and HS lost their effect at this pH.     

Cholesterol sulphate sulphohydrolase from human placenta microsomes--purification and properties of the dephosphorylated form of enzyme

The procedure for purification of cholesterol sulphate sulphohydrolase (ChS-ase) from human placenta microsomes was elaborated. The highy purified enzyme preparation (specific activity 2000 nmol×min⁻¹×mg protein⁻¹) exhibited optimal activity at pH 9.0. The K_m value was established to be 1.5±0.85×10⁻⁵ M. The high molecular weight form (200 kDa) and the low molecular weight form (20 kDa) of the enzyme were separated. The interconversion of the high molecular weight variant into the low one occurs under the influence of dephosphorylation. Both forms exhibited typical Michaelis–Menten saturation kinetics. The effect of different compounds on the enzyme activity was tested.     

Developmental response of zygotes exposed to similar mutagens

Exposure of mouse zygotes to ethylene oxide (EtO) or ethyl methanesulfonate (EMS) led to high incidences of fetal death and of certain classes of fetal malformations (Generoso et al., 1987, 1988; Rutledge and Generoso, 1989). These effects were not associated with induced chromosomal aberrations (Katoh et al., 1989) nor are they likely to be caused by gene mutations (Generoso et al., 1990). Nevertheless, the anomalies observed in these studies resemble the large class of stillbirths and sporadic defects in humans that are of unknown etiology, such as cleft palate, omphalocoel, clubfoot, hydrops and stillbirths (Czeizel, 1985; Oakley, 1986). Therefore, we continue to study the possible mechanisms relating to induction of these types of zygote-derived anomalies in mice. Effects of zygote exposure to the compounds methyl methanesulfonate (MMS), dimethyl sulfate (DMS), and diethyl sulfate (DES), which have similar DNA-binding properties as EtO and EMS, were studied. DMS and DES, but not MMS, induced effects that are similar to those induced by EtO and EMS. Thus, no site-specific alkylation product was identifiable as the critical target for these zygote-derived anomalies. We speculate that the developmental anomalies arose as a result of altered programming of gene expression during embryogenesis.     

Effect of pretreatment chemicals on xylose fermentation by Pichia stipitis

Pretreatment of biomass with dilute H₂SO₄ results in residual acid which is neutralized with alkalis such as Ca(OH)₂, NaOH and NH₄OH. The salt produced after neutralization has an effect on the fermentation of Pichia stipitis. Synthetic media of xylose (60 g total sugar/l) was fermented to ethanol in the presence and absence of the salts using P. stipitis CBS 6054. CaSO₄ enhanced growth and xylitol production, but produced the lowest ethanol concentration and yield after 140 h. Na₂SO₄ inhibited xylitol production, slightly enhanced growth towards the end of fermentation but had no significant effect on xylose consumption and ethanol concentration. (NH₄)₂SO₄ inhibited growth, had no effect on xylitol production, and enhanced xylose consumption and ethanol production.     

Gene 68, a new bacteriophage T4 gene which codes for the 17K prohead core protein is involved in head size determination

We have identified the gene for a major component of the prohead core of bacteriophage T4, the 17K protein. The gene, which we call gene 68, lies between genes 67 and 21 in the major cluster of T4 head genes. All of the genes in this region of the T4 genome have overlapping initiation and termination codons with the sequence T-A-A-T-G. We present the DNA sequence of the gene and show that it codes for a protein containing 141 amino acids with an acidic amino-terminal half and a basic carboxyl terminus. Antibodies prepared against the 17K protein were used to show that it is cleaved by the phage-coded gp21 protease during head maturation and that most of the protein leaves the head after cleavage. A frameshift mutation of the gene was constructed in vitro and recombined back into the phage genome. The mutated phages had a drastically reduced burst size and about half of the particles produced were morphologically abnormal, having isometric rather than prolate heads. Thus, the 17K protein is involved in head shape determination but is only semi-essential for T4 growth.