摘要：
Epstein-Barr virus (EBV) is closely associated with multiple human cancers. EBV-associated cancers are mainly lymphomas derived from B cells and T cells (Hodgkin lymphoma, Burkitt lymphoma, NK/T-cell lymphoma, and posttransplant lymphoproliferative disorder (PTLD)) and carcinomas derived from epithelial cells (nasopharyngeal carcinoma and gastric carcinoma). EBV can induce oncogenesis in its host cell by activating various signaling pathways, such as nuclear factor-κB (NF-κB), phosphoinositide-3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and transcription activator (JAK/STAT), mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β), and Wnt/β-catenin, which are regulated by EBV-encoded proteins and noncoding RNA. In this review, we focus on the oncogenic roles of EBV that are mediated through the aforementioned signaling pathways.
摘要：
Chronic systolic heart failure (CSHF) was a complex syndrome. Recently, vagus nerve stimulation (VNS), a novel treatment method, has emerged for the treatment of CSHF. therefore the aim of this study was to explore the possible mechanism of VNS treatment alleviating CSHF in rats. Firstly, we found after VNS treatment for 72 h, the level of B-type natriuretic peptide in VNS group was lower than that in CSHF group. In addition, VNS treatment induced the elevated left ventricular ejection fraction level, reduced left ventricular end diastolic volume and left ventricular end systolic volume level in VNS group, suggesting a mitigation of CSHF by VNS. Then we found the level of miR-183-3p in CSHF group was much lower than that in VNS group by High-throughput sequencing. The further results indicated that Bcl-2 interacting protein 3 like (BNIP3L) was identified as the target gene of miR-183-3p, and the expression of BNIP3L was notably reduced in rats of VNS group compared with CSHF group. Moreover, the down-regulated expression of miR-183-3p increased BNIP3L-mediated autophagy in rats of CSHF group compared with VNS group. Further mechanism findings demonstrated that up-regulation of miR-183-3p reduced the expression of BNIP3L, while down-regulation of miR-183-3p facilitated the expression of BNIP3L in H9c2 cells. miR-183-3p could also regulate autophagy by targeting BNIP3L in vitro, which was manifested by overexpression of miR-183-3p to inhibit BNIP3L-mediated autophagy. Our data demonstrated that VNS treatment benefited CSHF via the up-regulation of miRNA-183-3p, which reduced the BNIP3L-mediated autophagy, providing a new therapeutic direction for CSHF.
期刊：
CURRENT MOLECULAR MEDICINE,2019年19(10):719-730 ISSN：1566-5240
通讯作者：
Mo, Z.
作者机构：
[Liu, Yannan] Nursing School, Hunan University of Medicine, Huaihua 418000, China;[Huang, Qin; Yang, Zhen; Xie, Yuanjie; Mo, Zhongcheng] Clinical Anatomy & Reproductive Medicine Application Institute, Department of Histology and Embryology, Hengyang Medical school, University of South China, Hengyang 421001, China
通讯机构：
[Mo, Z.] C;Clinical Anatomy & Reproductive Medicine Application Institute, China
关键词：
Ovarian follicles;cholesterol homeostasis;fertility;lipoprotein;steroidogenesis;sterol carrier protein 2.
摘要：
<jats:sec><jats:title>:</jats:title><jats:p>Cholesterol is an important substrate for the synthesis of ovarian sex hormones and has an important influence on follicular development. The cholesterol in follicular fluid is mainly derived from plasma. High-density lipoprotein (HDL) and lowdensity lipoprotein (LDL) play important roles in ovarian cholesterol transport. The knockout of related receptors in the mammalian HDL and LDL pathways results in the reduction or absence of fertility, leading us to support the importance of cholesterol homeostasis in the ovary. However, little is known about ovarian cholesterol metabolism and the complex regulation of its homeostasis. Here, we reviewed the cholesterol metabolism in the ovary and speculated that regardless of the functioning of cholesterol metabolism in the system or the ovarian microenvironment, an imbalance in cholesterol homeostasis is likely to have an adverse effect on ovarian structure and function.</jats:p></jats:sec>
摘要：
Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.
摘要：
Stress can influence decision-making in humans from many cognitive perspectives, while the underlying neurobiological mechanism remains incompletely understood. Food-foraging is a rodent behavior involving strategic possessing of nutritional supply in social context; experimental model of this behavior could help explore the effect of stress on decision-making and the brain mechanism thereof. In the present study, the influence of stress on food-foraging behavior was assessed in rats using an open field choosing paradigm wherein food collection (standard food or sweet food) were associated with social competition (with or without a rat in the cage). Acute restraint stress (ARS) was induced by placing the rat in a plastic restrainer for 2 h before food-foraging behavioral tests, with the effect of stress also determined biochemically and immunohistochemically. Restraint stressed rats showed anxiety-like behavior and elevation of serum corticosterone (CORT) and epinephrine (EPI) relative to controls. Both restraint and control animals preferred sugared food. However, the former group tended to forage food from a cage not occupied by a conspecific rat, whereas the control rats preferred to obtain food from the cage with a social competitor. Thus, the total amount of food foraged and eaten are reduced in the restrained rats than in controls. While the restraint animals had normal social interaction with other rats, they displayed enhanced social agonistic behavior. In brain examination, ARS attenuated the increase in immunolabeling and protein levels of c-fos, p-CREB, p-ERK1/2 in the anterior cingulate cortex (ACC) observed in control animals in association with food-foraging. These results indicate that restraint stressed rats tend to forage food by taking the advantage of a less competitive opportunity. Mechanistically, this decision-making alternative appears to be mediated through a neuronal deactivation in the ACC. The current findings provide novel insights into neuronal processing of decision-making behavior under the influence of stress.
摘要：
<jats:p><jats:italic>Objective</jats:italic>. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model.<jats:italic>Methods</jats:italic>. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>5</mml:mn></mml:mrow></mml:math>per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mrow><mml:mrow><mml:mi>α</mml:mi><mml:mn>6</mml:mn></mml:mrow><mml:mo>/</mml:mo><mml:mrow><mml:mi>β</mml:mi><mml:mn>1</mml:mn></mml:mrow></mml:mrow></mml:mrow></mml:math>were measured by qRT-PCR and western blot analyses.<jats:italic>Results</jats:italic>. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:mrow></mml:math>). The expression of PI3K/AKT and integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mrow><mml:mrow><mml:mrow><mml:mi>α</mml:mi><mml:mn>6</mml:mn></mml:mrow><mml:mo>/</mml:mo><mml:mrow><mml:mi>β</mml:mi><mml:mn>1</mml:mn></mml:mrow></mml:mrow></mml:mrow></mml:math>was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:mrow></mml:math>). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms.<jats:italic>Conclusions</jats:italic>. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mrow><mml:mrow><mml:mrow><mml:mi>α</mml:mi><mml:mn>6</mml:mn></mml:mrow><mml:mo>/</mml:mo><mml:mrow><mml:mi>β</mml:mi><mml:mn>1</mml:mn></mml:mrow></mml:mrow></mml:mrow></mml:math>expression via the PI3K/AKT pathway.</jats:p>
摘要：
<jats:p><b><i>Purpose:</i></b> To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). <b><i>Methods:</i></b> The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. <b><i>Results:</i></b> A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers’ levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469–9.698, <i>p</i> = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774–8.304, <i>p</i> = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315–5.898, <i>p</i> = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017–1.577, <i>p</i> = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. <b><i>Conclusions:</i></b> The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.</jats:p>
