Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)].

Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model.

Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR?+?vehicle), a control group administered MOTILIPERM 200?mg/kg (CTR?+?M 200), a varicocele-induced control group (VC?+?vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC?+?M 100) or 200 (VC?+?M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG).

Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC?+?M 200 group compared with VC?+?vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio.

Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.     

Neuropsychiatric Disorders in Dementia: Mechanisms of Development and Approaches to Correction

Neuroscience and Behavioral Physiology - Dementia is often combined with other mental disorders which can manifest at different stages of the disease. The severity and rate of progression of these...     

The nationwide distribution and trends of hepatitis C virus genotypes in mainland China

Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical for treatment regimen selection, vaccine design, and drug development. This study aimed to understand the dynamic distribution of HCV genotypes in Mainland China. Three hundred sixty-two studies published from January 1993 to December 2017 involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors, 1509 former paid plasma donors, 160 sexually encounters, and 1992 human immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95% confidence intervals [CIs]) was estimated through the Freeman-Tukey double arcsine transformation by period, region, and risk group. A sharp decline of the subtype 1b was observed in all regions except in northwestern and central regions. The genotypes 3 and 6 showed an obvious increase in southern and southwestern regions and have already spread nationwide. After 2010, subtype 1b was the most dominant variant in all regions and risk groups, accounting for 54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second most prevalent strain in all regions except in the south and southwest, with 15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region and 3b and 3a in southwestern region had a higher proportion of infections than that in other regions. In addition, the genotypes 3 and 6 are already prevalent in almost all risk groups. The distribution of HCV genotypes were sharply shifting in China in the past three decades. The HCV subtype 1b posed a sharp decline, whereas genotypes 3 and 6 played an increasing role in the regional and populational HCV pandemic.     

MiR-19a mediates the negative regulation of the NF-κB pathway in lipopolysaccharide-induced endometritis by targeting TBK1

Objective

In both humans and animals, endometritis is severe inflammation of the uterus, and it causes great economic losses in dairy cow production. MicroRNAs have been reported to play an important role in various inflammatory diseases. However, the regulatory mechanisms of miR-19a in endometritis remain unclear. Thus, the aims of this study are to investigate the role of miR-19a in a mouse model of lipopolysaccharide (LPS)-induced endometritis and elucidate the possible mechanisms in bovine endometrial epithelial cells (bEECs).

Methods and results

Histological analysis showed that LPS induced severe pathological changes, suggesting that the endometritis mouse model was well established. The qPCR assay indicated that miR-19a expression in the uterine tissues of mice with endometritis and in bEECs with LPS stimulation was significantly reduced. The overexpression of miR-19a significantly decreased the expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the phosphorylation of NF-κB p65 and IκBα. Similar results were also obtained following the knockdown of TBK1. Furthermore, a dual luciferase reporter assay further validated that miR-19a inhibited TBK1 expression by binding directly to the 3′-UTR of TBK1.

Conclusion

We demonstrated that miR-19a has anti-inflammatory effects and mediates the negative regulation of the NF-κB Pathway in LPS-induced endometritis by targeting TBK1.

     

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

Study of the location of mandibular mental foremen in modern and neolithic adult]

37 cases of mandible of Neolithic adult that both sexes without missing teeth,alveolar bone were studied.The result showed that the location of the mental foramen below the apex of the lower second premolar was the most common(67.97%) in the modern adult,and the location of the mental foramen below between the apex of the lower second premolar and the first molar was the most common (64.86%) in the neolithic adult.     

CT辅助咽后壁瓣手术设计

目的 建立CT辅助设计咽后壁瓣的方法,以提高治疗效果。方法 应用CT测量26例腭咽闭合不全者在静止和发“i”时腭咽腔的宽度和长度,观察分析咽后壁瓣成形术所需的宽度、长度和咽后壁瓣蒂的位置和与软腭的附着位置。结果 静止时腭咽腔的宽度15.10-37.25mm,平均27.01mm,长度12.54-30.39mm,平均22.10mm;发“i”时腭咽腔的宽度为9.11-34.06mm,平均17.69mm;咽后壁瓣蒂的位置都在第一颈椎平面或以上;与软腭的附着位置大部分在软腭的中后1/3处。结论 CT作为一种定量评价腭咽闭合功能的方法,能够辅助设计咽后壁瓣手术方法。     

Heterotrophic ossification on a skin graft in a postburn scar of the chin

Some patients who have heterotrophic ossification (HO) in a postburn scar are occasionally seen in the clinic. The occurrence of HO following hip and abdominal surgery is common in males, whereas females are frequently affected following burns. The HO of skin grafts in burn scars of the superior body parts is uncommon, especially on the face. We report a recent case of a male patient in whom HO arose on skin grafts on his chin. The patient presented with a history of a painless chin mass for 48 years. Computed tomography scan suggested that the mass was located within subcutaneous tissue away from the lower jaw. The density of the mass was almost the same as the cortical bone of the lower jaw. The mass was completely resected under general anesthesia. It was a rectangular mass of 3× 0.5× 0.3 cm. Histological examination gave the diagnosis of HO, which was also confirmed by immunohistochemical stainings for vimentin. Recurrence was not found in this case by clinical and radiologic follow-up at 1 year after surgery.