肠道菌群调控慢性疼痛机制的研究进展

近年来, 肠道菌群与肠-脑轴的相互作用逐渐被认识, 肠道菌群参与调控神经系统相关疾病的机制也日益被关注, 其中肠道菌群可参与调控多种慢性疼痛, 包括内脏痛、炎性痛、神经病理性疼痛和头痛等。肠道菌群本身的成分以及其代谢产物和副产物会通过调控多种细胞信号通路及神经递质干预慢性疼痛的发生和发展。本文对已发表的肠道菌群调控慢性疼痛的相关研究进行了广泛检索及总结, 并在此基础上综述肠道菌群参与慢性疼痛的机制, 以期为研发通过调控肠道菌群而发挥镇痛作用的靶点药物提供理论基础。

     

慢性肝病与肠道菌群的研究进展

肝脏与肠道微生态可谓息息相关,互为影响。慢性肝病患者均存在不同程度的菌群失调,而菌群失调与血内毒素水平升高相关,且可诱发肝性脑病、二重感染的发生。肠道菌群失调促进了慢性肝病并发症的发生、发展,增加了患者的死亡率,且菌群失调与肝功能损害程度成正比。微生态制剂可通过恢复肠道菌群平衡,维持肠道屏障的完整性,抑制产生内毒素的G-数量,减少肠氨的产生,辅助治疗慢性肝病。     

肠道菌群在慢性肝脏疾病中作用的研究进展

随着肠—肝轴机制研究的不断深入,肠道菌群与多种慢性肝脏疾病如非酒精性脂肪性肝病、酒精性肝病、肝硬化等相关性研究日益增多。肠道菌群通过肠道菌群失调、物质能量代谢改变及免疫反应激活等机制在多种肝脏疾病发生发展中发挥重要作用。本文对肠道菌群与慢性肝脏疾病关系的研究进展进行综述。     

创伤性脑损伤与肠道菌群关系研究进展

创伤性脑损伤是一种高致死率的疾病，严重危害人类生命健康。肠脑轴是大脑和胃肠道系统之间主要的双向通讯途径。近年来，创伤性脑损伤与肠道菌群的相互作用关系逐渐被揭示。肠道菌群通过肠脑轴参与了创伤性脑损伤后急性病理损伤的调节过程并发挥重要作用。本文综述了创伤性脑损伤的发生、对人类健康的巨大影响，肠脑轴的含义及其在颅脑损伤中的病理调节机制，并在此基础上提出可能的治疗手段，包括粪便微生物菌群移植、使用益生菌、刺激迷走神经、摄入多酚类物质以及靶向免疫调节策略，以期为临床治疗创伤性脑损伤提供新的思路。     

肠道菌群功能与成瘾机制的研究进展

烟酒成瘾、药物滥用和停药反应的增多,对社会和家庭造成巨大的经济损失,同时也产生了一系列的健康问题,其中神经系统是成瘾的关键。近年来,越来越多的资料证明脑-肠轴的联系,人们发现肠道微生物的扰动对神经系统的调节有至关重要的作用。综述了烟酒和药物的成瘾机制,脑-肠轴影响宿主的代谢和对神经功能的调节,益生元和益生菌的摄入能引起肠道菌群的改变。深入分析脑-肠轴和肠道菌群代谢,通过益生菌,益生元改变菌群结构治疗成瘾成为今后研究的重点方向。     

肠道菌群影响非酒精性脂肪性肝病的机制及应对策略

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的发病率逐年升高,已成为最常见的肝脏疾病之一。目前其发病机制未被完全阐明,尚无有效治疗药物。肠道菌群与人体共生,作为人体的“第二基因组”,其在消化、吸收及代谢中发挥重要作用。新近研究表明,肠道菌群已成为影响NAFLD发生、进展的重要因素,肠道菌群失调和肠肝轴紊乱与非酒精性单纯性脂肪肝(nonalcoholic fatty liver,NAFL)发展为非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)、肝纤维化和肝细胞癌(hepatocellular carcinoma,HCC)密切相关。因此,肠道微生态干预有望成为预防或治疗NAFLD的新手段。本综述主要探讨肠道菌群异常对NAFLD/NASH发病过程、机制的影响及干预措施。     

肠道菌群与胆汁酸代谢在代谢相关脂肪性肝病的发生发展中的作用CSCD

代谢相关脂肪性肝病(metabolic-dysfunction-associated fatty liver disease,MAFLD)已成为我国慢性肝病的主要病因之一,其发病率呈逐年上升趋势。MAFLD是代谢综合征累及肝脏的表现,其发生发展与肠道菌群失调和代谢功能障碍等密切相关。由于发病机制尚不明确,目前依旧缺乏有效的药物治疗方法。肠道菌群与胆汁酸代谢密切相关,胆汁酸可靶向法尼醇X受体(farnesoid X receptor,FXR)信号通路负反馈调控肠道菌群,同时肠道菌群通过一系列复杂的生化反应影响胆汁酸代谢。大量研究发现MAFLD的免疫应答受损及全身低度慢性炎症可导致胆汁酸代谢紊乱。此外,MAFLD常伴随肠道菌群失调。本文就肠道菌群与胆汁酸代谢在MAFLD发生发展中的作用作一综述,以期探寻治疗MAFLD潜在的新的靶点。     

肠道菌群与精神分裂症的研究进展

精神分裂症是一种精神障碍疾病。除了遗传因素外,一些环境因素也参与了精神分裂症的发生,肠道微生物群是近年来发现的主要影响因素之一。研究表明,精神分裂症患者肠道菌群普遍发生了紊乱,肠道菌群通过肠-脑轴影响神经功能和疾病。肠道菌群可以通过影响神经系统发育、免疫和代谢功能来诱导精神分裂症的发生,肠道菌群可能是精神分裂症防治的有效靶点,调节肠道菌群可能是防治精神分裂症的一种潜在方法。本文就精神分裂症的易感因素、肠道菌群在精神分裂症中的作用、机制以及防治策略等方面的研究进展进行综述。     

肠道菌群与病毒性肺炎关系的研究进展

在21世纪头20年里,呼吸道病毒造成的地区性乃至世界性的流行已经发生多次,而疫情的暴发严重威胁人类健康与生存,但临床上,仍缺乏针对病毒的特异性治疗手段。随着肠道微生态相关研究的广泛开展,肠道菌群在哮喘,纤维化及细菌性感染等多种肺部疾病的发病及防治中发挥着重要作用,成为"肠-肺轴"的关键枢纽。病毒性肺炎与肠道微生态间也存在着紧密的相互联系,通过改善肠道菌群,对呼吸病毒感染具有较好的防治作用。其内在机制主要涉及到:通过增强肠道黏膜屏障功能、减少继发性细菌的感染;通过菌体成分或者代谢产物如短链脂肪酸,色氨酸代谢产物等提高固有样淋巴细胞(Innate lymphoid cells,ILC)、单核-巨噬细胞、树突状细胞、自然杀伤细胞(Natural killer,NK)、粒细胞等固有免疫细胞的抗病毒免疫功能及调节Th17/Treg平衡抑制过度的炎症反应等。本文将系统回顾已发表的文章,对肠道菌群在病毒性肺炎方面的研究作系统的阐述,以求为研究者在病毒性肺炎的机制探究和防治方面提供帮助。     

肠-肝轴与非酒精性脂肪性肝病

肠道菌群组成和数量的改变影响宿主的能量代谢、免疫应答和炎症反应状态。非酒精性脂肪性肝病患者常伴有小肠细菌过度生长或某些菌群种类和数量的改变,以及肠道黏膜通透性增加。肠道细菌通过增强肝脏脂肪合成、诱导机体胰岛素抵抗、激活天然免疫系统相关分子模式等机制,诱发肝脏炎症反应,启动纤维化进程,促进单纯性脂肪变向脂肪性肝炎发展。鉴定影响机体能量代谢和炎症反应的肠道菌群及其产物将为阐明肠-肝轴对肝脏炎症发生、发展所起的作用奠定基础,为揭示非酒精性脂肪性肝病发生、发展的机制开辟新思路,为该病的防治探索新策略。     

分子探针定量和定位分析种子吸涨早期活性氧的生成

借助活性氧发光分子探针,利用荧光光谱和激光共聚焦扫描显微技术,在不同年份的玉米种子吸胀早期,对其胚、淀粉和糊粉层细胞活性氧生成进行了定量和亚细胞定位分析.结果表明:胚细胞产生的活性氧最多,糊粉层细胞次之,淀粉细胞几乎不产生活性氧;而且胚细胞产生的活性氧主要定位在细胞内,细胞膜上不产生:糊粉层细胞产生的活性氧主要定位在细胞膜.这一种子吸涨早期活性氧生成机制的揭示,为化学发光检测种子活力提供了生理依据.     

超微粒TiO2对U937细胞光杀伤效应及机理研究

超微粒TiO₂经光催化氧化后对U937白血病细胞有明显的杀伤作用,DNA琼脂糖凝胶电泳图证明了光激发TiO₂能够损伤细胞内的DNA,从而导致细胞死亡,提出了一种杀伤癌细胞的新思路.     

Dual oxidase in the intestinal epithelium of zebrafish larvae has anti-bacterial properties

Reactive oxygen species (ROS) function in a range of physiological processes such as growth, metabolism and signaling, and also have a pathological role. Recent research highlighted the requirement for ROS generated by dual oxidase (DUOX) in host-defence responses in innate immunity and inflammatory disorders such as inflammatory bowel disease (IBD), but in vivo evidence to support this has, to date, been lacking. In order to investigate the involvement of Duox in gut immunity, we characterized the zebrafish ortholog of the human DUOX genes. Zebrafish duox is highly expressed in intestinal epithelial cells. Knockdown of Duox impaired larval capacity to control enteric Salmonella infection.     

In vitro propagation of the medicinal plant Ziziphora tenuior L. and evaluation of its antioxidant activity

Ziziphora tenuior L. (Lamiaceae) is an aromatic herb used for its medicinal values against fungi, bacteria. Micropropagation can be used for large-scale multiplication of essential oil producing plants thus avoiding an overexploitation of natural resources. This work aims to develop a reliable protocol for the in vitro propagation of Z. tenuior, and to compare the antioxidant activity between in vitro propagated and wild plants.The explants were sterilized and cultured on MS medium containing different concentrations of growth regulators naphthalene acetic acid (NAA) or indole-3-butyric acid (IBA) with 0.5 mg/L of kinetin (Kin) callus formation was 70.2% after 45 days of incubation in dark on medium supplemented with 1.5 mg/L of NAA. After one month of callus culture on medium supplemented with 2 mg/L BA the shoot number was 5.12 and for the multiplication stage. The shoot number was 4.21 and length was 6.17 cm on medium supplemented with 1 mg/L Kin + 0.1 mg/L NAA.DPPH• reagent was used to test the antioxidant activity. The aqueous and methanol extracts of in vitro plants which were treated with 1.5 and 1 mg/L of kin plus 0.1 mg/L of NAA showed a strong DPPH• scavenging activity where IC₅₀ was 0.307 and 0.369 mg/ml, respectively, while the IC₅₀ of aqueous and methanol extracts of wild plants was 0.516 and 9.229 mg/ml, respectively. Our results suggested that plant growth regulators and in vitro culture conditions increased the antioxidant activity.     

Molecular evolution and structure--function relationships of the superoxide dismutase gene families in angiosperms and their relationship to other eukaryotic and prokaryotic superoxide dismutases

This study assesses whether the phylogenetic relationships between SODs from different organisms could assist in elucidating the functional relationships among these enzymes from evolutionarily distinct species. Phylogenetic trees and intron positions were compared to determine the relationships among these enzymes. Alignment of Cu/ZnSOD amino acid sequences indicates high homology among plant sequences, with some features that distinguish chloroplastic from cytosolic Cu/ZnSODs. Among eukaryotes, the plant SODs group together. Alignment of the Mn and FeSOD amino acid sequences indicates a higher degree of homology within the group of MnSODs (>70%) than within FeSODs (approximately 60%). Tree topologies are similar and reflect the taxonomic classification of the corresponding species. Intron number and position in the Cu/Zn Sod genes are highly conserved in plants. Genes encoding cytosolic SODs have seven introns and genes encoding chloroplastic SODs have eight introns, except the chloroplastic maize Sod1, which has seven. In Mn Sod genes the number and position of introns are highly conserved among plant species, but not among nonplant species. The link between the phylogenetic relationships and SOD functions remains unclear. Our findings suggest that the 5' region of these genes played a pivotal role in the evolution of function of these enzymes. Nevertheless, the system of SODs is highly structured and it is critical to understand the physiological differences between the SODs in response to different stresses in order to compare their functions and evolutionary history.     

Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt

Cepharanthine (CEP), a biscoclaurine alkaloid, has been reported to induce cell death, however, the molecular mechanism of this phenomenon remains unclear. We herein report that CEP induced apoptosis in HuH-7 cells through nuclear fragmentation, DNA ladder formation, cytochrome c release, caspase-3 activation and poly-(ADP-ribose)-polymerase cleavage. CEP triggered the generation of reactive oxygen intermediates, the activation of mitogen activated protein kinase (MAPK) p38, JNK1/2 and p44/42, and the downregulation of protein kinase B/Akt. Antioxidants and SP600125, an inhibitor of JNK1/2, but not inhibitors of p38 MAPK and MEK1/2, significantly prevented cell death, thus implying that reactive oxygen species and JNK1/2 play crucial roles in the CEP-induced apoptosis of HuH-7 cells.     

Mechanism of hydrogen peroxide-induced keratinocyte migration in a scratch-wound model

Recent studies have shown that low concentrations of H₂O₂ are produced endogenously by nonphagocytes after wounding. We observed that H₂O₂ at such concentrations can stimulate proliferation as well as migration of keratinocytes in a scratch-wound assay. Both wounding and H₂O₂ can induce phosphorylation of ERK1/2 via EGFR, but the activation of ERK1/2 by H₂O₂ is more sustained and can last more than 8 h. Sustained ERK1/2 activation is required for the increased proliferation and migration induced by H₂O₂. The p38 MAPK was also found to be phosphorylated upon treatment with H₂O₂ but it was not required for H₂O₂-induced migration or proliferation. Furthermore, it was observed that there is a cross talk between the ERK1/2 and the p38 pathways whereby inhibition of either pathway can lead to activation of the other. As a result, the motogenic effects of H₂O₂ were further enhanced when p38 was inhibited. Our data are consistent with the view that H₂O₂ may play an important signaling role in wound healing.     

Involvement of Ceramide in the Mechanism of Cr(VI)-induced Apoptosis of CHO Cells

Mitochondria reduce Cr(VI) to Cr(V) with concomitant generation of reactive oxygen species, thereby exhibiting cytotoxic effects leading to apoptosis in various types of cells. To clarify the mechanism by which Cr(VI) induces apoptosis, we examined the effect of Cr(VI) on Chinese hamster ovary (CHO) cells. Cr(VI) increased cellular levels of ceramide by activating acid sphingomyelinase (ASMase) and inhibiting the phosphorylation of pleckstrin homology domain-containing protein kinase B (Akt). Cr(VI) also induced cyclosporin A- and trifluoperazine-sensitive depolarization of mitochondria and activated caspase-3, 8 and 9, thereby causing fragmentation of cellular DNA. The presence of desipramine, an inhibitor of ASMase, and membrane permeable pCPT-cAMP suppressed the Cr(VI)-induced activation of caspases and DNA fragmentation. These results suggested that accumulation of ceramide play an important role in the Cr(VI)-induced apoptosis of CHO cells through activation of mitochondrial membrane permeability transition.     

Promising effects of the 4HPR-BSO combination in neuroblastoma monolayers and spheroids

To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10 μM, 24 h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100 μM, 24 h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capacity of each cell line and the increase in cytotoxicity induced by 4HPR-BSO compared to 4HPR. No significant correlation between baseline antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids, 4HPR-BSO induced a strong synergistic growth retardation and induction of apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in neuroblastoma monolayers and spheroids in ROS-producing cell lines. This indicates that the 4HPR-BSO combination might be a promising new strategy in the treatment of neuroblastoma.