细胞间线粒体转运的研究进展

线粒体是真核生物能量代谢的重要细胞器,是细胞进行氧化磷酸化生成ATP的主要场所.他参与完成细胞能量代谢、维持离子浓度梯度、传递细胞凋亡信号等生理功能.阿尔茨海默病、帕金森病、心肌梗塞等疾病与线粒体功能异常相关.近年来发现,由创伤或炎症造成脑、心脏、肺缺氧时在细胞间会发生线粒体转移.线粒体转移,作为一种进化上保守的现象可能与神经降解、心血管疾病等相关.     

微生态制剂防治儿童感染性腹泻的有效性评价

目的对微生态制剂防治儿童感染性腹泻的有效性和安全性进行分析研究。方法选取2017年3月到2018年3月间我院收治的132例感染性腹泻患儿为研究对象,依据随机数字表法分为对照组(n=66)与观察组(n=66)。对照组患儿施以常规药物防治,观察组患儿应用益生菌进行防治。对两组患儿的治疗效果、腹泻持续时间、治疗后病情、血常规与肝功能情况进行比较分析。结果观察组患儿治疗总有效率(96.97%)明显高于对照组(86.36%)。观察组患儿腹泻持续时间为(2.41±1.08)d,明显少于对照组的(3.67±1.89)d。观察组患儿治疗3 d后腹泻频率≤2次/d的发生率为24.24%,低于对照组的60.61%。观察组患儿治疗后脱水发生率为3.03%,低于对照组的22.73%。观察组患儿血常规与肝功能水平明显高于对照组,差异均有统计学意义(P0.05)。结论在儿童感染性腹泻中应用微生态制剂有助于提高治疗效果,缩短腹泻持续时间,促进大便恢复正常,且具有较高的安全性,可有效促进患儿康复。     

微生态制剂在胃肠道疾病中的临床应用

微生态制剂(microbial ecological agents, MEA)是利用益生菌及其代谢产物而制成的一种药物制剂。MEA主要是通过补充有益的微生物来重建人体肠道内的菌群平衡,以治疗多种胃肠道疾病。现就近年来MEA在胃肠道中的作用机制,以及在防治炎症性肠病、与抗生素相关的腹泻、幽门螺杆菌感染和慢性肝病等疾病中的临床应用作一概述,为更好地开发和利用MEA治疗疾病奠定基础。     

The genetic association study of TP53 polymorphisms in Saudi obese patients

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.     

Metabonomics of mice intestine in Codonopsis foetens induced apoptosis of intestine cancer cells

Intestinal cancer is a disease with high morbidity and high mortality in China. Previous studies have shown that Codonopsis foetens can inhibit cellular autophagy and promote the apoptosis of intestine cancer cells. Based on metabolomics method coupled with liquid chromatography-mass spectrometry (LC-MS) technology, we aimed to analyze intestinal small molecule metabolites in the intestinal cancer model group and the Codonopsis foetens treated group. Principal component analysis (PCA) and Partial Least Squares (PLS-DA) were used to identify the pattern of the data. And the metabolic characteristics of the cancer model group were explored based on the metabolic differences between the groups. Multivariate statistical analysis revealed that metabolites presented with differences included: Acetamide, Phosphoric acid, Hydrogen sulfite, Pyruvic acid, Cytosine, 2-Hydroxypyridine, Phosphoric acid, Uracil, Gamma-Aminobutyric acid, Glycerol alpha-monochlorohydrin, Thiosulfic acid, L-Valine, Cysteamine, Taurine, Creatine, Homocysteine, Hypoxanthine, Se-Methylselenocysteine, 5-Hydroxymethyluracil, Oxoglutaric acid, LysoPC(20:0), LysoPC(22:4(7Z,10Z,13Z,16Z)), LysoPC(18:2(9Z,12Z)), LysoPC(16:1(9Z)), LysoPE(0:0/16:0), LysoPE(0:0/18:2(9Z,12Z)), LysoPE(18:0/0:0), LysoPE(20:1(11Z)/0:0), etc. Combined with metabolic pathway analysis, pathways presented with differences included: Citrate cycle (TCA cycle), ABC transporters, 2-Oxocarboxylic acid metabolism, Taurine and hypotaurine metabolism, Butanoate metabolism), Phenylalanine, tyrosine and tryptophan biosynthesis, Biosynthesis of amino acids, Protein digestion and absorption, Aminoacyl-tRNA biosynthesis, C5-Branched dibasic acid metabolism, GABAergic synapse, Proximal tubule bicarbonate reclamation, Mineral absorption, Phenylalanine metabolism. The results showed that the proliferation of intestinal cancer cells caused cell metabolism disorders, manifesting as changes in metabolic pathways and resulting in changes in metabolites.     

Impact of deforestation on the abundance,diversity, and richness of Culex mosquitoes in a southwest Cameroon tropical rainforest

Deforestation is a major threat to biodiversity but little data exist on how deforestation in real‐time affects the overall mosquito species community despite its known role in the transmission of diseases. We compared the abundance and diversity of Culex mosquitoes before and after deforestation along a gradient of three different anthropogenic disturbance levels in a tropical rainforest in southwestern Cameroon. The collections were conducted in unlogged forest (January, 2016), selectively logged forest (January, 2017), and within a young palm plantation (October, 2017) using net traps, sweep nets, resting traps, and dipping for immature stages in water bodies. Mosquitoes were morphologically identified to subspecies, groups, and species. A total of 2,556 mosquitoes was collected of which 1,663 (65.06%) belong to the genus Culex, (n=427 (25.68%) in the unlogged forest; n=900 (54.12%) in the selectively logged forest; and n=336 (20.2%) in the young palm plantation) with a significant difference among the habitats. Diversity and richness of mosquitoes varied significantly among habitats with the highest values found in the selectively logged forest (H=2.4; DS=0.87; S=33) and the lowest value in the unlogged forest (H=1.37; DS=0.68; S=13). The results of this study showed that deforestation affects the abundance and diversity of Culex mosquitoes and favors the invasion of anthropophilic mosquitoes. Higher mosquito abundance and diversity in the selectively logged forest than in the pristine forest is notable and some explanations for these differences are discussed.     

Progranulin: A conductor of receptors orchestra,a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases

Progranulin (PGRN), a widely expressed glycoprotein with pleiotropic function, has been linked to a host of physiological processes and diverse pathological states. A series of contemporary preclinical disease models and clinical trials have evaluated various therapeutic strategies targeting PGRN, highlighting PGRN as a promising therapeutic target. Herein we summarize available knowledge of PGRN targeting in various kinds of diseases, including common neurological diseases, inflammatory autoimmune diseases, cancer, tissue repair, and rare lysosomal storage diseases, with a focus on the functional domain-oriented drug development strategies. In particular, we emphasize the role of extracellular PGRN as a non-conventional, extracellular matrix bound, growth factor-like conductor orchestrating multiple membrane receptors and intracellular PGRN as a chaperone/co-chaperone that mediates the folding and traffic of its various binding partners.     

脐带血干细胞移植治疗非恶性血液病进展

异基因造血干细胞移植（allo-HSCT）是治愈多种非恶性病的有效方法。脐带血干细胞（UCB）具有免疫原性低、人类白细胞抗原不合耐受性好、移植物抗宿主反应发生率低以及获取相对快捷等特点,可作为非恶性血液疾病患者allo-HSCT的来源。本文简要综述脐血干细胞移植在原发性免疫缺陷病、遗传性骨髓衰竭、遗传代谢病以及自身免疫性疾病等非恶性血液疾病的治疗效果。     

Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc

The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated “Fc-one/kappa” (Fc1κ) is based on interspersed constant Ig domains substituting the CH3 domains of a γ1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CLκ domains and contain sequence stretches of an IgG1 CH3 domain, destined to enable interaction with the neonatal Fc receptor, and thus promote extended serum half-life. The resulting monovalent Fv-Fc1κ fusion protein (Atrosimab) retained strong binding to TNFR1 as determined by enzyme-linked immunosorbent assay and quartz crystal microbalance, and potently inhibited TNF-induced activation of TNFR1. Atrosimab lacks agonistic activity for TNFR1 on its own and in the presence of anti-human IgG antibodies and displays clearly improved pharmacokinetic properties.     

BMP-9与骨代谢及糖代谢关系研究进展

骨形成蛋白-9(BMP-9)是从胚胎鼠的肝脏c DNA文库中克隆得到的新型细胞因子,属于转化生长因子β超家族的成员,由肝脏非实质细胞合成分泌,在体内以类激素的形式发挥广泛的生物学作用。BMP-9不仅具有强烈的骨诱导活性,促进成骨细胞分化,还可通过调控糖代谢过程中关键酶的表达、促进胰岛素合成及分泌、增加胰岛素敏感性等方式调节体内葡萄糖平衡。本文主要对BMP-9与骨代谢及糖代谢的关系进行综述,为深入认识糖尿病、代谢性骨病及糖尿病性骨质疏松的发生机理提供理论依据,为糖尿病和骨骼疾病的防治提供新的思路。