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Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants including patients with stage 1–5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD. Accurate monitoring of chronic kidney disease (CKD) progression is essential for efficient disease management. Here Chen et al. identify five serum metabolites in patients with stage 1–5 CKD whose levels associate with disease progression, and find that 5-methoxytryptophan and its regulatory enzyme TPH-1 exert anti-fibrotic effects in mouse models of kidney injury.

ObjectiveTo evaluate the renal protective effect of Tangshenkang Granule (糖肾康颗粒) in a rat model of diabetic nephropathy (DN).MethodsForty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.ResultsCompared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).ConclusionsTangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

Vasculogenic mimicry (VM) is a new pattern of blood supplement independent of endothelial vessels, which is related with tumor invasion, metastasis and prognosis. However, the role of VM in the prognosis of cancer patients is controversial. This study aimed to perform a meta-analysis of the published data to attempt to clarify the prognostic value of VM in the digestive cancer. Relevant studies were retrieved from the PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and VIP databases published before March 29, 2018. Studies were included if they detected VM in the digestive cancer and analyzed the overall survival (OS) or disease-free survival (DFS) according to VM status. Two independent reviewers screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was performed using STATA 12.0 software. A total of 22 studies with 2411 patients were included in this meta-analysis. Meta-analysis showed that VM was related with the poor OS (HR = 2.30, 95% CI: 2.06–2.56, P < 0.001) and DFS (HR = 2.60, 95% CI: 2.07–3.27, P < 0.001) of patients with digestive cancer. Subgroup analysis showed VM was related with tumor differentiation, lymph node metastasis and TNM stage. Moreover, the present meta-analysis was reliable, and there was no obvious publication bias. This meta-analysis suggested that VM was a poor prognosis of digestive cancer patients. Further large and well-designed studies are required.

通过靶向作用于精子线粒体，抑制精子运动进行避孕是一种作用特异的、很有前景的避孕方式。AF-2364，是氯尼达明（Londidamine，LND）的类似物，其毒副作用显著降低，目前被认为是一种很有潜力的男性避孕的候选化合物。LND亦可作用于肿瘤细胞线粒体抑制能量代谢。目前尚无AF-2364对于人类精子功能作用的相关报道。在本研究中，我们探寻了AF-2364的体外杀精子作用及其初步机制。体外实验显示，AF-2364显著抑制人类精子的运动：进一步的研究发现，AF-2364可作用于精子线粒体膜通透性转换（PT）孔，降低线粒体膜电位（mitochondrial membrane potential，△ψm），抑制线粒体能量代谢，使ATP下降，从而使精子制动。我们同时检测了AF-2364作用后细胞骨架一系列蛋白调控通路在人精子中的变化及人精子蛋白组学改变，未见显著差异；AF-2364与人及小鼠其他细胞系孵育实验提示较低浓度下的AF-2364对人精子制动作用的特异性。综上，AF-2364可通过对精子线粒体PT孔的直接作用使精子制动，并可能发展为一种杀精子剂的候选成分。