Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection

Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Effects of TLR7 Polymorphisms on the Susceptibility and Progression of HIV-1 Infection in Chinese MSM Population

Toll-like receptor (TLR) 7 plays a key role in innate and adaptive immunity for HIV-1 infection. We evaluated the effect of TLR7 polymorphisms on disease susceptibility and progression of HIV-1 infection in Chinese MSM (men who have sex with men). Blood samples were taken from 270 patients with laboratory confirmed HIV infection, 196 male controls were tested, and three TLR7 intronic polymorphisms (rs179010-C > T, X:12884766; rs2074109-T > C, X:12885330; and rs179009-A > G, X:12885361) were analyzed by PCR-based sequencing. The frequency of TLR7 rs179010 T allele was significantly lower in MSM patients than in controls (P = 0.039). The haplotype TTA was associated with a decreased susceptibility to HIV-1 infection (P = 0.013), especially to acute HIV-1 infection (AHI) (P = 0.002), but not to chronic HIV-1 infection (CHI). Furthermore, the haplotype TTA is linked to slow disease progression in AHI patients (P = 0.002) and a lower viral load (P = 0.042). In contrast, TLR7 rs179009 allele A contributed to a higher set point in AHI patients with rapid progression, and the frequency of rs179009 minor allele G was over-presented in CHI patients. This finding supports a role for genetic variations of TLR7 in susceptibility and disease progression of an HIV-1 infection in Chinese Han population and warrants further studies on the effect of TLR7 polymorphisms on HIV-1 infection in different populations

Insufficient maintenance DNA methylation is associated with abnormal embryonic development

<p>Abstract</p> <p>Background</p> <p>Early pregnancy loss (EPL) is a frustrating clinical problem, whose mechanisms are not completely understood. DNA methylation, which includes maintenance methylation and <it>de novo </it>methylation directed by DNA methyltransferases (DNMTs), is important for embryo development. Abnormal function of these DNMTs may have serious consequences for embryonic development.</p> <p>Methods</p> <p>To evaluate the possible involvement of DNA methylation in human EPL, the expression of DNMT proteins and global methylation of DNA were assessed in villous or decidua from EPL patients. The association of maintenance methylation with embryo implantation and development was also examined.</p> <p>Results</p> <p>We found that DNMT1 and DNMT3A were both expressed in normal human villous and decidua. DNMT1 expression and DNA global methylation levels were significantly down-regulated in villous of EPL. DNMT3A expression was not significantly changed in the EPL group compared to controls in either villous or decidua. We also found that disturbance of maintenance methylation with a DNMT1 inhibitor may result in a decreased global DNA methylation level and impaired embryonic development in the mouse model, and inhibit <it>in vitro </it>embryo attachment to endometrial cells.</p> <p>Conclusions</p> <p>Our results demonstrate that defects in DNA maintenance methylation in the embryo, not in the mother, are associated with abnormal embryonic implantation and development. The findings of the current study provide new insights into the etiology of EPL.</p

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

Mesenchymal stem cell as salvage treatment for refractory chronic GVHD

Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue repair and modulating immune responses in vitro and in vivo. From April 2005 to October 2008, 19 patients with refractory cGVHD were treated with MSCs derived from the BM of volunteers. The median dose of MSCs was 0.6 × 106 cells per kg body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a CR (n=4) or a PR (n=10). The immunosuppressive agent could be tapered to less than 50% of the starting dose in 5 of 14 surviving patients, and five patients could discontinue immunosuppressive agents. The median duration between MSC administration and immunosuppressive therapy discontinuation was 324 days (range, 200–550 days). No patients experienced adverse events during or immediately after MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical improvement was accompanied by the increasing ratio of CD5+CD19+/CD5−CD19+ B cells and CD8+CD28−/CD8+CD28+ T cells. In conclusion, transfusion of MSCs expanded in vitro, irrespective of the donor, might be a safe and effective salvage therapy for patients with steroid-resistant, cGVHD

Advances in Social Media Research:Past, Present and Future

Social media comprises communication websites that facilitate relationship forming between users from diverse backgrounds, resulting in a rich social structure. User generated content encourages inquiry and decision-making. Given the relevance of social media to various stakeholders, it has received significant attention from researchers of various fields, including information systems. There exists no comprehensive review that integrates and synthesises the findings of literature on social media. This study discusses the findings of 132 papers (in selected IS journals) on social media and social networking published between 1997 and 2017. Most papers reviewed here examine the behavioural side of social media, investigate the aspect of reviews and recommendations, and study its integration for organizational purposes. Furthermore, many studies have investigated the viability of online communities/social media as a marketing medium, while others have explored various aspects of social media, including the risks associated with its use, the value that it creates, and the negative stigma attached to it within workplaces. The use of social media for information sharing during critical events as well as for seeking and/or rendering help has also been investigated in prior research. Other contexts include political and public administration, and the comparison between traditional and social media. Overall, our study identifies multiple emergent themes in the existing corpus, thereby furthering our understanding of advances in social media research. The integrated view of the extant literature that our study presents can help avoid duplication by future researchers, whilst offering fruitful lines of enquiry to help shape research for this emerging field