CXCR4-Overexpressing Umbilical Cord Mesenchymal Stem Cells Enhance Protection against Radiation-Induced Lung Injury.

Less quantity of transplanted mesenchymal stem cells (MSCs) influences the therapeutic effects on radiation-induced lung injury (RILI). Previous studies have demonstrated that MSCs overexpressing Chemokine (C-X-C motif) receptor 4 (CXCR4) could increase the quantity of transplanted cells to local tissues. In the present study, we conducted overexpressing CXCR4 human umbilical cord mesenchymal stem cell (HUMSC) therapy for RILI. C57BL mice received single dose of thoracic irradiation with 13 Gy of X-rays and then were administered saline, control HUMSCs, or CXCR4-overexpressing HUMSCs via tail vein. Transfection with CXCR4 enhanced the quantity of transplanted HUMSCs in the radiation-induced injured lung tissues. CXCR4-overexpressing HUMSCs not only improved histopathological changes but also decreased the radiation-induced expression of SDF-1, TGF-ß1, α-SMA, and collagen I and inhibited the radiation-induced decreased expression of E-cadherin. Transplanted CXCR4-overexpressing HUMSCs also could express pro-SP-C, indicated adopting the feature of ATII. These finding suggests that CXCR4-overexpressing HUMSCs enhance the protection against RILI and may be a promising strategy for RILI treatment.

Upregulation of CXCR7 Is Associated with Poor Prognosis of Prostate Cancer.

BACKGROUND Prostate cancer (PCa) is a prevalent cancer in males. CXCR7 exhibits oncogenic actions in various cancers. The aim of our study was to explore the clinical significance of CXCR7 in patients with PCa. MATERIAL AND METHODS QRT-PCR was used to detect the expression level of CXCR7 in PCa tissues. The relationship between CXCR7 expression and clinicopathologic parameters was evaluated by chi-square test. Kaplan-Meier survival curve was used for the survival analysis of patients. Cox regression analyses were performed to assess the potential of CXCR7 as a prognosis biomarker for PCa patients. We performed MTT and Transwell assays to determine the effect of CXCR7 on proliferative and migratory abilities of PCa cells, respectively. RESULTS CXCR7 was upregulated in PCa tissues (P<0.05) and was correlated with PSA (P=0.023), differentiation (P=0.022), and lymph node metastasis (P=0.018). The results of MTT and Transwell assays demonstrated that inhibition of CXCR7 suppressed PCa cells growth and migration. Additionally, high CXCR7 level predicted poor overall survival (log rank test, P=0.019). CXCR7 was a valuable prognostic biomarker for PCa patients (HR=2.271, 95%CI=1.093-4.719, P=0.028). CONCLUSIONS CXCR7 is an oncogene in PCa that can promote aggressive progression of PCa through enhancing proliferation and migration of the tumor cells. CXCR7 is an independent biomarker for the prognosis of PCa.

Evaluation of smoking cessation intervention in patients with chronic diseases in smoking cessation clinics.

This study aimed to evaluate the effects of psychological intervention and psychological plus drug intervention on smoking cessation among male smokers with single chronic diseases.A total of 509 male smokers were divided into psychological group (n = 290) and psychological plus drugs (n = 219) groups according to their will. The physicians provided free individual counseling and follow-up interviews with brief counseling for all the subjects. In addition to mental intervention, patients in psychological plus drug group also received bupropion hydrochloride or varenicline tartrate to quit smoking. Outcomes were self-reported, regarding the 7-day point prevalence on abstinence rate and continuous abstinence rates at 1-, 3-, and 6-month follow-up period. Data analyses were performed using intention-to-treat analysis and per protocol analysis.With regards to the 3 follow-up time points, 7-day point-prevalence abstinence rate in psychological plus drugs group was all higher than that in the psychological intervention group. Additionally, the 3-month continuous abstinence rate (21.4%) of the 6-month follow-up in the psychological group was not significantly higher than that (26.9%) in the psychological plus drugs group (P >.05 for all). Fagerström test score, stage of quitting smoking, perceived confidence or difficulty in quitting, and chronic disease types were independently correlated with 3-month continuous abstinence in the 6-month follow up (P <.05 for all). The results were similar between intentional analysis and protocol analysis.The psychological intervention and psychological plus drugs intervention exerted good effects on smoking cessation in a short time (1 month). Nevertheless, the advantages did not appear during long-time (6 months) follow-up.

Low-expression of miR-7 promotes cell proliferation and exhibits prognostic value in osteosarcoma patients.

AIM: MicroRNAs (miRNAs) play important roles in occurrence and development of osteosarcoma. Previous studies had verified the role of microRNA-7 (miR-7) in various diseases, especially in cancers. Our purpose in this study was to investigate the values of miR-7 in development and prognosis of osteosarcoma. METHODS: QRT-PCR was used to measure the expression of miR-7 in osteosarcoma tissues, adjacent tissues and healthy tissues as well as in osteosarcoma cell lines MG63, U2OS and normal osteoblastic cell line hFOB1.19. CCK-8 and siRNA assays were performed to estimate the effect of miR-7 in the process of cell proliferation. The Kaplan-Meier and Cox regression analysis were performed to detect the prognostic values of the miR-7 in osteosarcoma patients. RESULTS: The results demonstrated that miR-7 expression decreased in osteosarcoma tissues and cell lines compared with the controls. Proliferation assay declared that the cell proliferation was accelerated by down-regulation of miR-7. Kaplan-Meier exhibited that the overall survival time of low-miR-7 expression was shorter than those with high-miR-7 expression (P=0.001). Cox regression analysis revealed that Enneking, distant metastasis and recurrence were all prognostic factors just like low-miR-7. CONCLUSION: The expression of miR-7 was lower in osteosarcoma tissues and cell lines and miR-7 acted as a tumor suppressor. The low-expression of miR-7 was associated with clinicopathologic characteristics (age, tumor site, Enneking, therapies). Moreover, miR-7 might be an independent prognostic marker and promote cell proliferation in osteosarcoma.

Toll-Like Receptor 3 is Associated With the Risk of HCV Infection and HBV-Related Diseases.

There are inconsistent data on the association of risk of hepatitis virus infection and hepatitis virus-related diseases with the toll-like receptor 3 (TLR3) gene.Several common polymorphism sites were targeted to assess the risk of HBV infection, HCV infection, and HBV-related diseases.Meta-analysis combining data for 3547 cases and 2797 controls from 8 studies was performed in this study. Pooled ORs were calculated to measure the risk of hepatitis virus infection and hepatitis virus-related diseases. Fixed-effects pooled ORs were calculated using the Mantel-Haenszel method.The TLR3 gene was associated with a significantly increased risk of HBV-related diseases among 1355 patients and 1130 controls ([pooled OR, [95%CI]: 1.30, [1.15-1.48] for dominant; 1.77, [1.35-2.31] for recessive; 1.28 [1.16-1.41] for allele frequency). Subgroup analyses by a polymorphism site indicated an increased risk of HCV infection in relation to the TT/CT genotypes of rs3775291 (1.50 [1.11-2.01]), and a decreased risk ascribed to the T allele (0.20 [0.16-0.25]). We also noted an association between rs3775291 and significantly increased risk of HBV-related diseases (2.23 [1.55-3.21]). No significant inter-study heterogeneity or publication bias was detected in the analyses.These data suggest a likely effect on the risk to infect HCV and develop HBV-related diseases for the TLR3 gene. Large-scale studies with racially diverse populations are required to validate these findings.

MicroRNA-144 regulates proliferation, invasion, and apoptosis of cells in malignant solitary pulmonary nodule via zinc finger E-box-binding homeobox 1.

AIMS: This study was to investigate the expression of microRNA (miR)-144 in malignant solitary pulmonary nodule (SPN) tissues and peripheral blood, as well as the biological function of miR-144 in the occurrence and development of lung cancer. METHODS: In this study, 39 malignant and 30 benign SPN patients were included. The expression of miR-144 was examined using quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curve was used to identify the clinical value of miR-144 in the early diagnosis of malignant SPN. MTT assay was performed to determine A549 cell proliferation and Transwell assay was used to detect changes in A549 cell invasion and migration ability. Flow cytometry was performed to monitor cell apoptosis, while Western blotting assay was used to measure protein expression levels. At last, dual-luciferase reporter assay was employed to test whether miR-144 regulates zinc finger E-box-binding homeobox 1 (ZEB1) gene expression. RESULTS: Expression of miR-144 was reduced in patients with malignant SPN. miR-144 had diagnostic value for malignant SPN. Proliferation of A549 cells was inhibited by miR-144. Invasion ability of A549 cells was reduced by miR-144. Apoptosis of A549 cells was promoted by miR-144. miR-144 induced A549 cell apoptosis by targeting ZEB1 protein. miR-144 regulated the expression of ZEB1 by interacting with its 3'-UTR region. CONCLUSIONS: Expression of miR-144 is reduced in malignant SPN tissues and peripheral blood, being of clinical value in the diagnosis of malignant SPN. miR-144 promotes the apoptosis of lung cancer cells, and inhibits the proliferation, invasion and migration of lung cancer by regulating ZEB1 gene.

Metagenomic sequencing reveals altered metabolic pathways in the oral microbiota of sailors during a long sea voyage.

Seafaring is a difficult occupation, and sailors face higher health risks than individuals on land. Commensal microbiota participates in the host immune system and metabolism, reflecting the host's health condition. However, the interaction mechanisms between the microbiota and the host's health condition remain unclear. This study reports the influence of long sea voyages on human health by utilising a metagenomic analysis of variation in the microbiota of the buccal mucosa. Paired samples collected before and after a sea-voyage were analysed. After more than 120 days of ocean sailing, the oral microbial diversity of sailors was reduced by approximately 5 fold, and the levels of several pathogens (e.g., Streptococcus pneumonia) increased. Moreover, 69.46% of the identified microbial sequences were unclassified microbiota. Notably, several metabolic pathways were dramatically decreased, including folate biosynthesis, carbohydrate, lipid and amino acid pathways. Clinical examination of the hosts confirmed the identified metabolic changes, as demonstrated by decreased serum levels of haemoglobin and folic acid, a decreased neutrophil-to-lymphocyte ratio, and increased levels of triglycerides, cholesterol and homocysteine, which are consistent with the observed microbial variation. Our study suggests that oral mucosal bacteria may reflect host health conditions and could provide approaches for improving the health of sailors.

Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax.

Chronotype and a PERIOD3 variable number tandem repeat polymorphism in Han Chinese pilots.

An association has been determined between variable number tandem-repeat (VNTR) polymorphisms in the PERIOD3 gene (PER3, rs57875989) and chronotype. An association has been found in which the longer PER3(5) allele is correlated with diurnal preference and shorter PER3(4) allele is linked with preference for evening, respectively. In this study, we explored the genotype frequency and relationship to the chronotype of a PER3 VNTR polymorphism in Han Chinese pilots compared to other populations to further develop aviation safety research. DNA samples were genotyped with respect to the 4-repeat and 5-repeat alleles of the PER3 VNTR polymorphism. We compared and analyzed PER3 VNTR genotype frequencies of a general Han Chinese population and Han Chinese pilots. The chronotypes of our subjects were evaluated by the morningness-eveningness questionnaire (MEQ). The distribution of PER3 VNTR genotype frequencies from 240 Han Chinese was determined (PER3(4/4), 78.3%; PER3(4/5), 20.0%; PER3(5/5), 1.7%) and compared to the genotype frequencies of 126 Han Chinese pilots (PER3(4/4), 71.4%; PER3(4/5), 26.1%; PER3(5/5), 2.4%). Statistical analysis revealed no significant difference between the general Han Chinese population and Han Chinese pilots regarding the PER3 VNTR genotype and allele frequencies (x(2) = 2.170, p > 0.05). Furthermore, MEQ results showed no association between the PER3 VTNR polymorphism and chronotype. However, PER3 VNTR genotype frequencies differed significantly between Han Chinese and other ethnic groups previously reported, such as Caucasians, African Americans and Italians. These data indicate that the proposed role of the PER3 VNTR needs further clarification and the role of PER3(5) allele in sleep regulation needs to be investigated in more detail. In particular, a study of PER3 polymorphisms with a larger sample size of Han Chinese individuals and Han Chinese pilots may be required.

Influence of Per3 genotypes on circadian rhythmicity in flight cadets after militarized management.

OBJECTIVE: The purpose of this study was to explore the effect of PERIOD3 (PER3) genotypes on circadian rhythmicity in flight cadets after militarized management. METHODS: We performed a preliminary study in 146 newly enrolled male flight cadets. Venous blood samples were collected, and genotyping of PER3 (4/5) was determined by using PCR. The morningness-eveningness questionnaire (MEQ) survey was given to flight cadets upon enrollment and after militarized management for 24 months respectively. Comparison of frequency distribution of PER3 genotypes between cases and controls (120 well-matched civilians) was performed using the X(2) test. We also compared the circadian rhythmicity upon enrollment and 24 months after enrollment in flight cadets, and analyzed the connection of changes in circadian clock with PER3 genotypes. RESULTS: The frequency distribution of PER3 genotypes in flight cadets was not significantly different from that in controls subjects. MEQ survey results showed chronotype within flight cadet group varied widely at the two time-points: the moderately morning type (50%) and the neither type (41.1%) upon enrollment; the neither type (76.7%) and the moderately morning type (21.2%) 24 months after enrollment. The circadian rhythm of individuals with the PER3 (5/5) genotype showed no significant difference before and after 24 months of militarized management, whereas notable changes were found in individuals with the PER3 (4/4) genotype (n=116, X(2) =37.26, P < 0.001). CONCLUSION: In conclusion, we provide some evidence that circadian rhythm of flight cadets with the PER3 (5) allele are less likely to be affected compared to those with the PER3 (4) allele.

The cyclin D1 (CCND1) G870A polymorphism and lung cancer susceptibility: a meta-analysis.

Several studies have investigated the association between Cyclin D1 (CCND1) G870A genetic polymorphism and lung cancer susceptibility, but the results were inconclusive. The aim of this meta-analysis was to summarize available evidence for such a relationship. The reviewers made use of MEDLINE, EMBASE, and BIOSIS databases. The relevant data were independently extracted by two reviewers. The odds ratio (OR) with 95% confidence interval (CI) was selected as the principal outcome measure. The heterogeneity test, the publication bias test, and the sensitivity analysis were performed. Overall, a total of 10 case-control studies were included. Our meta-analysis indicated that CCND1 G870A genetic polymorphism was a risk factor for lung cancer under homozygote model (OR = 1.18; 95% CI = 1.02, 1.37), recessive model (OR = 1.21; 95% CI = 1.03, 1.41), and allele model (OR = 1.11; 95% CI = 1.02, 1.21). In the subgroup analysis by source of ethnicity, a statistical increase of lung cancer risk was found among Asian groups for allele model (OR = 1.11; 95% CI = 1.01-1.22). The present meta-analysis suggests that CCND1 G870A polymorphism may be a risk factor for lung cancer. Besides, allele A may contribute to increased lung cancer risk.

Potent tetravalent replicon vaccines against botulinum neurotoxins using DNA-based Semliki Forest virus replicon vectors.

Human botulism is commonly associated with botulinum neurotoxin (BoNT) serotypes A, B, E and F. This suggests that the greatest need is for a tetravalent vaccine that provides protection against all four of these serotypes. In current study, we investigated the feasibility of generating several tetravalent vaccines that protected mice against the four serotypes. Firstly, monovalent replicon vaccine against BoNT induced better antibody response and protection than that of corresponding conventional DNA vaccine. Secondly, dual-expression DNA replicon pSCARSE/FHc or replicon particle VRP-E/FHc vaccine was well resistant to the challenge of BoNT/E and BoNT/F mixture as a combination vaccine composed of two monovalent replicon vaccines. Finally, the dual-expression DNA replicon or replicon particle tetravalent vaccine could simultaneously and effectively neutralize and protect the four BoNT serotypes. Protection correlated directly with serum ELISA titers and neutralization antibody levels to BoNTs. Therefore, replicon-based DNA or particle might be effective vector to develop BoNT vaccines, which might be more desirable for use in clinical application than the conventional DNA vaccines. Our studies demonstrate the utility of combining dual-expression DNA replicon or replicon particle vaccines into multi-agent formulations as potent tetravalent vaccines for eliciting protective responses to four serotypes of BoNTs.

Enhanced potency of replicon vaccine using one vector to simultaneously co-express antigen and interleukin-4 molecular adjuvant.

We evaluated the utility of interleukin-4 (IL-4) as molecular adjuvant of replicon vaccines for botulinum neurotoxin serotype A (BoNT/A) in mouse model. In both Balb/c and C57/BL6 mice that received the plasmid DNA replicon vaccines derived from Semliki Forest virus (SFV) encoding the Hc gene of BoNT/A (AHc), the immunogenicity was significantly modulated and enhanced by co-delivery or co-express of the IL-4 molecular adjuvant. The enhanced potencies were also produced by co-delivery or co-expression of the IL-4 molecular adjuvant in mice immunized with the recombinant SFV replicon particles (VRP) vaccines. In particular, when AHc and IL-4 were co-expressed within the same replicon vaccine vector using dual-expression or bicistronic IRES, the anti-AHc antibody titers, serum neutralization titers and survival rates of immunized mice after challenged with BoNT/A were significantly increased. These results indicate IL-4 is an effective Th2-type adjuvant for the replicon vaccines in both strain mice, and the co-expression replicon vaccines described here may be an excellent candidate for further vaccine development in other animals or humans. Thus, we described a strategy to design and develop efficient vaccines against BoNT/A or other pathogens using one replicon vector to simultaneously co-express antigen and molecular adjuvant.