Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl‐CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment.     

输尿管支架管结壳患者尿液菌群的分布特点

目的探讨输尿管支架管结壳患者尿液菌群的分布特点。方法选取2018年10月至2019年3月在山东省立第三医院、山东大学齐鲁医院、济南市中心医院和济南市济钢医院就诊的35例输尿管支架管置入术后患者。纳入标准:年龄18~65岁;输尿管镜碎石术后留置内支架管4周。排除标准:尿液细菌培养阳性;严重肉眼血尿;近期口服抗生素;存在明显残石患者。本研究采用横断面研究方法(临床研究注册号为ChiCTR1800020025),根据有无支架管结壳将患者分为结壳组23例和无结壳组12例。收集拔管当日患者尿液行细菌16s DNA检测。使用UPARSE、UCHIME和RDP calssifier等软件分析两组患者尿液菌群分布特点,明确两组患者尿液中细菌种类总数、细菌丰度,以及丰度占比较大的细菌类别,比较两组患者尿液细菌种类、数量及细菌丰度的差异,明确结壳组患者尿液中丰度占比较大的细菌菌属。结果两组患者的年龄、性别、体质指数、置管侧别、内支架管型号及结石成分差异均无统计学意义(P>0.05)。16s DNA检测结果显示,结壳组丰度占比>1%的菌属数量为11个,丰度占比>0.01%的菌属数量为74个;无结壳组丰度占比>1%的菌属数量为7个,丰度占比>0.01%的菌属数量为11个,两组丰度占比>1%的菌属数量比较差异有统计学意义(t=5.12,P=0.000)。结壳组中菌属丰度占比前3位分别为乳杆菌属(23.1%)、拟杆菌属(18.8%)和未分级拟杆菌属(17.1%),非结壳组中菌属丰度占比前3位分别是为埃希菌-志贺菌属(32.2%)、肠球菌属(24.9%)和假单胞菌属(18.2%)。两组间差异最大的3种细菌是乳杆菌属(P=0.010),拟杆菌属(P=0.004)和未分级拟杆菌属(P=0.004)。结论支架管结壳患者尿液中细菌种类和数量都明显多于非支架管结壳患者。拟杆菌属细菌在支架管结壳患者尿液中的细菌种类丰度较大。     

The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid‐1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)‐induced lung injury in mice. For this, adult mice pre‐treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS‐challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre‐treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre‐treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.     

Sonodynamic Therapy: Advances and Challenges in Clinical Translation

Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them.     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

肠道菌群与恶性肿瘤的研究进展

人类微生物群是由寄生在人体上皮屏障的细菌和其他微生物组成的，其中大部分位于肠道内，与宿主之间形成共生的关系。机体肠道微生物的组成虽然受到年龄、饮食、生活方式等因素的影响，但在正常生理情况下是相对稳定的。近年来，肠道菌群与恶性肿瘤的关系越来越受到重视。肠道菌群不但能够维持局部稳态，还能调节机体代谢、炎症和免疫等生理过程。有研究表明，微生物群，特别是肠道菌群能够显著调节机体对癌症治疗的反应性以及机体对毒副反应的敏感性。检查肠道菌群中各菌种之间的比例可作为筛查恶性肿瘤的新方法。本文将综述微生物群具有影响肿瘤的发生发展、抗肿瘤治疗疗效以及药物不良反应的证据，以及其中所涉及的微生物种类，从而为恶性肿瘤精准治疗提供证据。