Zhaowei Teng

Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies.

Objective To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies. Methods Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates. Results Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed. Conclusions This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.

Restrictive blood transfusion strategies and associated infection in orthopedic patients: a meta-analysis of 8 randomized controlled trials

This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47–0.91; p = 0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.

Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNF

Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) has been used to treat spinal cord injury (SCI) to enhance tissue repair and neural cell regeneration. Glial cell line derived neurotrophic factor (GDNF) is an identified neural growth and survival factor. Here, we examined whether modification of GDNF levels in MSCs may further increase the potential of MSCs in promoting neural cell regeneration and subsequently the therapeutic outcome. Methods: We examined the mRNA and protein levels of GDNF in human MSCs by RT-qPCR and Western blot, respectively. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target GDNF in MSCs. The functional binding of miRNAs to GDNF mRNA was examined by a dual luciferase reporter assay. MSCs were transduced with adeno-associated virus (AAV) carrying null or antisense for miR-383 (as-miR-383), which were transplanted into nude rats that underwent SCI. The intact tissue, cavity volume, and recovery of locomotor activity were assessed. Results: MSCs expressed very low GDNF protein, but surprisingly high levels of GDNF mRNA. Bioinformatics analyses showed that miR-383 inhibited protein translation of GDNF, through binding to the 3’-UTR of the GDNF mRNA. MSCs transduced with AAV-as-miR-383 further increased the intact tissue percentage, decreased cavity volume, and enhanced the recovery of locomotor activity in nude rats that underwent SCI, compared to MSCs. Conclusions: Suppression of miR-383 may increase the therapeutic potential of human bone-marrow-derived MSCs in treating SCI via augmentation of GDNF protein levels.

Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies

Objective This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. Methods The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. Results The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08–1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07–1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89–1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11–1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11–1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11–1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05–1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03–1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. Conclusions This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed.

Promotion of cell growth and adhesion of a peptide hydrogel scaffold via mTOR/cadherin signaling

Understanding neurite outgrowth, orientation, and migration is important for the design of biomaterials that interface with the neural tissue. However, the molecular signaling alternations have not been well elucidated to explain the impact of hydrogels on cell morphology. In our previous studies, a silk fibroin peptide (SF16) hydrogel was found to be an effective matrix for the viability, morphology, and proliferation of PC12 rat pheocrhomocytoma cells. We found that PC12 cells in the peptide hydrogel exhibited adhesive morphology compared to those cultured in agarose or collagen. Moreover, we identified that cell adhesion molecules (E‐ and N‐cadherin) controlled by mTOR signaling were highly induced in PC12 cells cultured in the SF16 peptide hydrogel. Our findings suggest that the SF16 peptide might be suitable to be a cell‐adhesion material in cell culture or tissue engineering, and mTOR/cadherin signaling is required for the cell adhesion in the SF16‐peptide hydrogel.

Correction: Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies

[This corrects the article DOI: 10.1371/journal.pone.0181852.].

SEMA3B-AS1-inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis: ZHANG et al.

Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair‐related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B‐AS1 regulating hMSCs osteogenesis. SEMA3B‐AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B‐AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B‐AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix–receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B‐AS1 is a target for controlling osteogenesis of hMSCs.

miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration

Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT-PCR. Using a dual-luciferase reporter assay, we found that miR-142-5p can bind to and decrease expression of VCAM-1 mRNA. Such reduction was prohibited when the miR-142-5p binding site in VCAM-1 3′UTR was deleted, and Western blotting analyses validated the fact that miR-142-5p inhibited the expression of VCAM-1 protein. Bone marrow-derived mesenchymal stem cells (BMMSCs) transfected with miR-142-5p showed a significantly decreased migration ability in a Transwell migration assay. Collectively, these data indicated the important role of miR-142-5p in osteoporosis development involving targeting VCAM-1 and inhibiting BMMSC migration.

Association of carotid atherosclerosis and recurrent cerebral infarction in the Chinese population: a meta-analysis

Stroke, when poor blood flow to the brain results in cell death, is the third leading cause of disability and mortality worldwide, and appears as an unequal distribution in the global population. The cumulative risk of recurrence varies greatly up to 10 years after the first stroke. Carotid atherosclerosis is a major risk factor for stroke. The aim of this study was to investigate and estimate the relationship between carotid atherosclerosis and risk of stroke recurrence in the Chinese population. We performed a systematic review and meta-analysis of randomized controlled trials published from 2000 to 2013, using the following databases: PubMed, Embase, Medline, Wanfang, and the China National Knowledge Infrastructure. The odds ratios with 95% confidence intervals were calculated to examine this strength. A total of 22 studies, including 3,912 patients, 2,506 first-ever cases, and 1,406 recurrent cases, were pooled in this meta-analysis. Our results showed that the frequency of carotid atherosclerosis is higher in recurrent cases than that in the first-ever controls (78.88% vs 59.38%), and the statistical analysis demonstrated significant positive association between carotid atherosclerosis and recurrent cerebral infarction (odds ratio: 2.87; 95% confidence interval: 2.42–3.37; P<0.00001) in a fixed-effect model. No significant heterogeneity was observed across all studies. In conclusion, our results showed that carotid atherosclerosis was associated with increased risk of recurrent stroke. However, further well-designed research with large sample sizes is still needed to identify the clear mechanism.