Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers

Gastrointestinal (GI) cancer, including esophageal, gastric, and colorectal cancer, is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths. Despite significant advances in therapeutic strategies for GI cancers in recent decades, drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers. Accumulating evidence has demonstrated that the transforming growth factor (TGF)-β signaling pathway has crucial, complex roles in many cellular functions related to drug resistance. This review summarizes current knowledge regarding the role of the TGF-β signaling pathway in the resistance of GI cancers to conventional chemotherapy, targeted therapy, immunotherapy, and traditional medicine. Various processes, including epithelial-mesenchymal transition, cancer stem cell development, tumor microenvironment alteration, and microRNA biogenesis, are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers. Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-β signaling pathway, but this approach needs to be verified in additional clinical studies. Moreover, the identification of potential biological markers that can be used to predict the response to TGF-β signaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.     

Status of prevalence study on multimorbidity of chronic disease in China: Systematic review

It is imperative to provide a more uniform method to improve the validity of prevalence studies on multimorbidity. However, the status of prevalence studies on multimorbidity of chronic disease is still yet to be confirmed in China. The objective of the present systematic review was to evaluate the variance across prevalence studies and to explore possible explanations for variations in China. Published literature was obtained from four databases. The studies that described the prevalence of multimorbidity on chronic disease based on the general population were considered. We assessed the risk of bias by a preplanned checklist referring to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). The heterogeneity among eligible studies was estimated by I² statistic and P‐value using MetaAnalyst software. Nine studies were eligible for this systematic review. The prevalence of multimorbidity among the population aged 60 years or more ranged from 6.4% (95% CI 5.1–8.0) to 76.5% (95%CI 73.6–79.2). However, just two of nine studies could be judged as having a low risk of bias. It was shown that key items introducing the risk of bias included inconsistent sampling method, lacking of uniform measure indices and data source based on self‐report. Heterogeneity test showed I² = 50% (P < 0.001), which showed there was substantial variation among individual studies. Therefore, only a narrative summary rather than meta‐analysis was carried out. Marked methodology heterogeneity exists among prevalence studies on multimorbidity. Suggested methodological aspects that should be considered in future studies include sampling method, measure indices of multimorbidity and data source. Geriatr Gerontol Int 2015; 15: 1–10.     

Molecular chaperone Jiv promotes the RNA replication of classical swine fever virus

The nonstructural protein 2 (NS2) of classical swine fever virus (CSFV) is a self-splicing ribozyme wherein the precursor protein NS2-3 is cleaved, and the cleavage efficiency of NS2-3 is crucial to the replication of viral RNA. However, the proteolytic activity of NS2 autoprotease may be achieved through a cellular chaperone called J-domain protein interacting with viral protein (Jiv) or its fragment Jiv90, as evidence suggests that Jiv is required for the proper functioning of the NS2 protein of bovine viral diarrhea virus. Hence, the expression of Jiv may be correlated with the replication efficiency of CSFV RNA. We investigated the expression levels of Jiv and viral RNA in CSFV-infected cells and tissues using Real-time RT-PCR or Western blot analysis. The obtained results show that Jiv90 possibly plays an important role in the lifecycle of CSFV because the distribution of Jiv90 protein shows a positive correlation with the viral load of CSFV. Furthermore, the overexpression or knockdown of Jiv90 in swine cells can also significantly promote or decrease the viral load, respectively. The detection of Flow cytometry shows that the overexpression of Jiv90 prolongs the G1 phase of cell cycles but has no effect on apoptosis. These findings are likely to be of benefit in clarifying the pathogenesis of the CSFV.     

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4⁺ T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration.     

PCB77 Inducing Renal Tubular Cell Apoptosis

PCBs are a family of persistent environmental toxicants with a wide spectrum of toxic features, such as neurotoxic, hepatoxicity, immunotoxicity, endocrine disruption effects, and oncogenic effects. The kidney is the most important organ involved in the elimination of toxins and drugs. To date, little has been done to investigate the potential influence of nephrotoxicity of 3,3’,4,4’- tetrachlorobiphenyl (PCB77). By assessing cell viability and apoptotic cell death in renal tubular epithelial (NRK-52E) cells cultures, we found that PCB77 could decrease cellular viability at least at 30?μM concentration after 3?h exposure. PCB77 was demonstrated to promote DNA breakage resulting in apoptosis. Moreover, apoptotic subcellular morphological changes administration of PCB77 was observed using transmission electron microscopy. Appearance swelling of mitochondria, endoplasmic reticulum dilation and chromatin agglutinate, and other apoptosis cells morphological characteristics could be visible. Due to increased PCB77 concentration, cells viability was decreased. Collectively, our findings identified the morphological mechanism that PCB77-induced nephrotoxicity via promoting renal tubular epithelial cells apoptosis. It is suggested that using and production of PCB77 should be carefully managed to reduce public health risks.