To explore whether the roles of IL-1 family single nucleotide polymorphisms (SNPs) of the microRNA binding sites (miR-SNPs) in the 3' untranslated region (3'-UTR) of their target genes in the progression of gastric cancer (GC) and verify the relationship between miR-197 with chronic inflammatory gene-IL1-F5 by microRNA target prediction, a case-control study which consisted of 500 cases and 500 frequency-matched healthy controls was conducted. Single nucleotide polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR (AS-PCR). Association between SNPs and GC risk was evaluated by adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in unconditional logistic regression analyses. Quantitative real-time (qRT) PCR assay and Western Blot analyses were performed to analyze the miR-197 expression and the IL1-F5 expression. The variant homozygote and heterozygote genotype of rs9005 in IL-1RN were significantly associated with increased risks of GC (ORadjusted [95%CI]: 1.71[1.04-2.81] and ORadjusted[95%CI]: 1.36 [1.04-1.78]). Compared with the wild heterozygote genotype, the variant heterozygote genotype of rs2472188 and rs2515401 in IL-1F5 polymorphisms were significantly associated with increased GC risks (ORadjusted [95%CI]: 1.51[1.15-1.99] and ORadjusted[95%CI]: 1.36[1.04-1.76]), but no significant differences existed in other 7 IL-1 family SNPs (rs2856836 in IL-1A, rs3732131 in IL-1R1, rs1135354 and rs3771157 in IL-18RA, rs3180235, rs957201 and rs2515402 in IL-1F5) with GC. The recombinant plasmid-pGenesil-1-miR-197 could upregulate the expression of miR-197 and downregulate the expression of IL-1F5 in human gastric cancer cell lines SGC-7901 and BGC-823 cells after transfection, and the miR-197 inhibitor could facilitate the expression of IL1-F5 after transfecting the same cell lines. These results suggested that SNPs in the IL-1 family genes play important roles in the development of GC and the IL-1F5 might be the target gene of miR-197, and miR-197 might negatively regulate its expression.

Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics.

Natural killer (NK) cells and non-cytotoxic interferon-γ (IFN-γ)-producing group I innate lymphoid cells (ILC1s) produce large amounts of IFN-γ and cause activation of innate and adaptive immunity. However, how NKs and ILC1s are primed during infection remains elusive. Here we have shown that a lymphocyte subpopulation natural killer-like B (NKB) cells existed in spleen and mesenteric lymph nodes (MLNs). NKBs had unique features that differed from T and B cells, and produced interleukin-18 (IL-18) and IL-12 at an early phase of infection. NKB cells played a critical role in eradication of microbial infection via secretion of IL-18 and IL-12. Moreover, IL-18 deficiency abrogated the antibacterial effect of NKBs. Upon bacterial challenge, NKB precursors (NKBPs) rapidly differentiated to NKBs that activated NKs and ILC1s against microbial infection. Our findings suggest that NKBs might be exploited to develop effective therapies for treatment of infectious diseases.

Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome-wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3, and p300 at the Il23r, Il17a/f, and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program.

G protein-coupled receptors (GPCRs) represent the largest membrane protein family implicated in the therapeutic intervention of a variety of diseases including cancer. Exploration of biological actions of orphan GPCRs may lead to the identification of new targets for drug discovery. This study investigates potential roles of GPR160, an orphan GPCR, in the pathogenesis of prostate cancer. The transcription levels of GPR160 in the prostate cancer tissue samples and cell lines, such as PC-3, LNCaP, DU145 and 22Rv1 cells, were significantly higher than that seen in normal prostate tissue and cells. Knockdown of GPR160 by lentivirus-mediated short hairpin RNA constructs targeting human GPR160 gene (ShGPR160) resulted in prostate cancer cell apoptosis and growth arrest both in vitro and in athymic mice. Differential gene expression patterns in PC-3 cells infected with ShGPR160 or scramble lentivirus showed that 815 genes were activated and 1193 repressed. Functional annotation of differentially expressed genes (DEGs) revealed that microtubule cytoskeleton, cytokine activity, cell cycle phase and mitosis are the most evident functions enriched by the repressed genes, while regulation of programmed cell death, apoptosis and chemotaxis are enriched significantly by the activated genes. Treatment of cells with GPR160-targeting shRNA lentiviruses or duplex siRNA oligos increased the transcription of IL6 and CASP1 gene significantly. Our data suggest that the expression level of endogenous GPR160 is associated with the pathogenesis of prostate cancer.

Mesenchymal stem cells (MSCs) have great therapeutic potential due to their abilities to self-renewal and their potential for differentiating into a variety of cell lineages. However, how to improve the differentiation efficiency of MSC into osteoblast remains a big challenge in the field of bone regenerative medicine. In current study, we identified a role of CHD7 in osteogenic differentiation of MSC. We showed that CHD7 expression in MSC could be induced by BMP2 or osteogenic induction medium. Depletion of CHD7 in MSC via siRNA knockdown resulted in inhibition of key osteogenic transcription factors and impaired osteogenic capability of MSC. Complementarily, overexpression of CHD7 in MSC led to increased osteogenic ability. Mechanistically, we demonstrated that CHD7 interacted with SMAD1, downstream factor of BMP signaling. BMP2 stimulated the binding of CHD7 to the enhancer region of SP7. Finally, CHD7-silencing MSC showed comprised osteogenic ability when cultured with scaffold in vivo. Overall, our study established a new epigenetic regulation of MSC osteogenic differentiation and provided a potential target for controlling MSC osteogenesis.

Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity.

Knowledge of arsenic (As) accumulation in rice (Oryza sativa L.) is important for minimizing As transfer to the food chain. The aim of this study was to investigate the role of rice nodes in As storage and distribution. Synchrotron μX-ray fluorescence (μ-XRF) was used to map As distribution in the top node and internode of a lsi2 mutant defective in silicon/arsenite efflux carrier and its wild-type (WT) grown in soil. Lsi2 expression in different tissues during grain filling was investigated by quantitative RT-PCR. Arsenite or dimethylarsinic acid (DMA) was supplied to excised panicles to investigate the roles of Lsi2 and phytochelatins (PC) in As distribution. μ-XRF mapping revealed As storage in the phloem of different vascular bundles in the top node and internode. Soil-grown plants of lsi2 had markedly decreased As accumulation in the phloem compared with the WT. Lsi2 was strongly expressed, not only in the roots but also in the nodes. When excised panicles were exposed to As(III), the lsi2 mutant distributed more As to the node and flag leaf but less As to the grain compared with the WT, while there was no significant difference in DMA distribution. Inhibition of PC synthesis by l-buthionine-sulphoximine decreased As(III) deposition in the top node but increased As accumulation in the grain and flag leaf. The results suggest that rice nodes serve as a filter restricting As(III) distribution to the grain. Furthermore, Lsi2 plays a role in As(III) distribution in rice nodes and phytochelatins are important compounds for As(III) storage in the nodes.

CXCR4, stromal cell-derived factor-1α(SDF 1α) receptor, stimulates growth and metastasis of hepatocellular carcinoma (HCC). Alpha-fetoprotein(AFP) governs the expression of some metastasis-related genes. Here we report that AFP and CXCR4 levels correlated in HCC tissues. AFP-expressing vectors induced CXCR4. In agreement, AFP depletion by siRNA decreased CXCR4. AFP co-localized and interacted with PTEN, thus inducing CXCR4 by activating AKT(Ser473) phosphorylation. In turn, phospho-mTOR(Ser2448) entered the nucleus and bound the CXCR4 gene promoter. Thus, AFP promoted migration of HCC cells. In concusion, AFP induced CXCR4 by activating the AKT/mTOR signal pathway.

Selenium (Se) is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS) burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO) in the root of Brassica rapa under Se(IV) stress. Se(IV)-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV)-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR)- and nitric oxide synthase (NOS)-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV)-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV)-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV) stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

Colorectal cancer (CRC) is one of the most difficult cancers to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidences show that Evodiamine (EVO) exerts an inhibitory effect on cancer cell apoptosis, migration, and invasion. In this study, we investigated the effects of EVO on the metastasis of CRC cells in vitro and in vivo. In vitro, wound-healing and transwell assay showed that migration and invasion of HT-29 and HCT-116 CRC cells were inhibited significantly by EVO. Western blot and RT-PCR showed that EVO reduced the expression of matrix metalloproteinase-9 in a dose-dependent manner. In EVO-induced cells, the intracellular NAD+/NADH ratio was increased, the level of Sirt1 was increased, and acetyl-NF-κB P65 was decreased. This process was inhibited by nicotinamide, an inhibitor of Sirt1. In vivo, EVO reduced tumor metastasis markedly. These findings provide evidences that EVO suppresses the migration and invasion of CRC cells by inhibiting the acetyl-NF-κB p65 by Sirt1, resulting in suppression of metalloproteinase-9 expression in vitro and in vivo.

An apparent increase in the frequency of human adenovirus type 4 (HAdV-4) infections among general populations has been observed over the past 10 years. However, available epidemiological data that may reflect previous viral circulation and assist in predicting potential outbreaks are sparse, particularly in mainland China and Africa. In this study, a convenient neutralization assay for use in the surveillance of historical HAdV-4 infections was established based on a recombinant luciferase-expressing virus. Subsequently, the neutralizing antibodies (nAbs) of 1013 healthy adult serum samples from China and Sierra Leone were evaluated. Our results showed that over 50% of the participants from China and nearly 70% of donors from Sierra Leone had detectable nAbs against HAdV-4 despite the few infection cases officially reported in these regions. Furthermore, the prevalence of nAbs to HAdV-4 is lower than that to HAdV-5, and both varied by geographic location. In addition, the seropositive rates of both HAdV-4 and HAdV-5 nAbs increased with age. However, the nAbs stimulated by HAdV-4 remained stable at low (≤200) levels among the different age groups, whereas moderate (201-1000) or high (>1000) nAb levels were produced by HAdV-5 and tended to decrease with age. These results elucidate the human humoral immune response against HAdV-4 and revealed that this virus may be an underestimated causative agent of respiratory disease among adults in China and West Africa, demonstrating the importance of HAdV-4 surveillance and providing useful insights for the future development of HAdV-4-based vaccines.

Selenium nanoparticles (SeNPs) loaded with chemotherapeutic drugs provided a novel perspective for cancer therapy.

Evidence indicated that GATA5 may suppress hepatocellular carcinoma (HCC) cell malignant transformation, but the mechanism of how GATA5 affects cancer cell reprogramming to inhibit HCC malignant behaviour is still unclear. In this study, we report that the expression of β-catenin and reprogramming genes p-Oct4, Nanog, Klf4, c-myc and EpCAM was significantly higher in HCC tissues compared to normal liver tissues. In contrast, the expression of GATA5 was significantly lower in HCC tissues compared to normal liver tissues. Transfection of CDH-GATA5 vectors into HCC cells (HLE, Bel 7402 and PLC/PRF/5 cells) increased the GATA5 expression and decreased the expression of β-catenin and reprogramming genes p-Oct4, Nanog, Klf4, c-myc and EpCAM. Increased GATA5 expression by transfection with its expression vectors was also able to inhibit the cell growth, colony formation and capability of migration, invasion, while promoting apoptosis in HCC cells. Results revealed that GATA5 co-localization with β-catenin in the cytoplasm, preventing β-catenin from entering the nucleus. Treatment with the specific Wnt/β-catenin pathway inhibitor salinomycin was able to reduce the expression of β-catenin and reprogramming genes. Salinomycin exerted a similar influence as GATA5, and siRNA-GATA5 restored β-catenin and reprogramming gene expression. This study demonstrates that an increase in the expression of GATA5 inhibits the expression of β-catenin and reprogramming genes and suppresses tumour growth, colony formation, metastasis and invasion, while promoting apoptosis in HCC cells. The mechanism of GATA5 inhibiting the malignant behaviours of HCC cells may involve in the disruption of the Wnt/β-catenin pathway and the reduction of reprogramming gene expression.

Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways.

This study explores the therapeutic effects of Xiangshao granules in a mouse depression model and examines the potential molecular mechanisms involved. After 21 consecutive days of chronic stress challenge, all mice were divided into three groups: control group, depression group, and Xiangshao granule treatment group. On the 22nd day, rats in the Xiangshao granule treatment group received Xiangshao granules via gastrogavage for 3 consecutive weeks. Depression group mice showed a significant reduction of crossings (P < 0.01) but not rearings (P < 0.05). Serum CRH, CORT, and ACTH levels were significantly increased in depression mice compared with control (P < 0.05) and the expression levels of hippocampal BDNF and TrkB were reduced in the model group (P < 0.05). However, Xiangshao granule treatment remarkably rescued the decrease in the body weight (P < 0.05), increased crossings in the open field test (P < 0.05), upregulated the expression of hippocampal BDNF and TrkB expression, and reduced the serum CRH, CORT, and ACTH concentrations compared with the depression group (P < 0.05). Collectively, these results demonstrated that Xiangshao granule could effectively induce antidepressive effects in the depression mouse model by ameliorating the expression of hippocampal BDNF and TrkB.

Bone morphogenetic protein receptor I B (BMPR1B) is a transmembrane receptor mediating TGF-β signal transduction. Recent studies indicate a tumor suppressor role for BMPR1B in ovarian cancer. Polymorphism at BMPR1B 3'UTR within the miR-125b binding site alters its binding affinity toward the miRNA, which may result in insufficient post-transcriptional repression.

microRNAs (miRNAs) play an important regulatory role in the self-renewal and differentiation of stem cells. In this study, we examined the effects of miRNA-124 (miR-124) overexpression in bone marrow-derived mesenchymal stem cells. In particular, we focused on the effect of overexpression on the differentiation of bone marrow-derived mesenchymal stem cells into neurons. First, we used GeneChip technology to analyze the expression of miRNAs in bone marrow-derived mesenchymal stem cells, neural stem cells and neurons. miR-124 expression was substantially reduced in bone marrow-derived mesenchymal stem cells compared with the other cell types. We constructed a lentiviral vector overexpressing miR-124 and transfected it into bone marrow-derived mesenchymal stem cells. Intracellular expression levels of the neuronal early markers β-III tubulin and microtubule-associated protein-2 were significantly increased, and apoptosis induced by oxygen and glucose deprivation was reduced in transfected cells. After miR-124-transfected bone marrow-derived mesenchymal stem cells were transplanted into the injured rat spinal cord, a large number of cells positive for the neuronal marker neurofilament-200 were observed in the transplanted region. The Basso-Beattie-Bresnahan locomotion scores showed that the motor function of the hind limb of rats with spinal cord injury was substantially improved. These results suggest that miR-124 plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells into neurons. Our findings should facilitate the development of novel strategies for enhancing the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for spinal cord injury.

The analysis of complex DNA mixtures is challenging for forensic DNA testing. Accurate and sensitive methods for profiling these samples are urgently required. In this study, we developed 11 groups of mixed male DNA samples (n=297) with scientific validation of D‑value [>95% of D‑values ≤0.1 with average peak height (APH) of the active alleles ≤2,500 rfu]. A strong linear correlation was detected between the peak height (PH) and peak area (PA) in the curve fit using the least squares method (P<2e-16). The Kruskal-Wallis rank-sum test revealed significant differences in the heterozygote balance ratio (H(b)) at 16 short tandem repeat (STR) loci (P=0.0063) and 9 mixed gradients (P=0.02257). Locally weighted regression fitting of APH and Hb (inflection point at APH = 1,250 rfu) showed 92.74% of H(b) >0.6 with the APH ≥1,250. The variation of H(b) distribution in the different STR loci suggested the different forensic efficiencies of these loci. Allelic drop-out (ADO) correlated with the APH and mixed gradient. All ADOs had an APH of <1,000 rfu, and the number of ADO increased when the APH of mixed DNA profiles gradually decreased. These results strongly suggest that calibration parameters should be introduced to correct the deviation in the APH at each STR locus during the analysis of mixed DNA samples.

The growth and development of plants are sensitive to their surroundings. Although numerous studies have analyzed plant transcriptomic variation, few have quantified the effect of combinations of factors or identified factor-specific effects. In this study, we performed RNA sequencing (RNA-seq) analysis on tobacco leaves derived from 10 treatment combinations of three groups of ecological factors, i.e., climate factors (CFs), soil factors (SFs), and tillage factors (TFs). We detected 4980, 2916, and 1605 differentially expressed genes (DEGs) that were affected by CFs, SFs, and TFs, which included 2703, 768, and 507 specific and 703 common DEGs (simultaneously regulated by CFs, SFs, and TFs), respectively. GO and KEGG enrichment analyses showed that genes involved in abiotic stress responses and secondary metabolic pathways were overrepresented in the common and CF-specific DEGs. In addition, we noted enrichment in CF-specific DEGs related to the circadian rhythm, SF-specific DEGs involved in mineral nutrient absorption and transport, and SF- and TF-specific DEGs associated with photosynthesis. Based on these results, we propose a model that explains how plants adapt to various ecological factors at the transcriptomic level. Additionally, the identified DEGs lay the foundation for future investigations of stress resistance, circadian rhythm and photosynthesis in tobacco.