To explore a scientific boundary of WHtR to evaluate central obesity and CVD risk factors in a Chinese adult population. The data are from the Prospective Urban Rural Epidemiology (PURE) China study that was conducted from 2005-2007. The final study sample consisted of 43 841 participants (18 019 men and 25 822 women) aged 35-70 years. According to the group of CVD risk factors proposed by Joint National Committee 7 version and the clustering of risk factors, some diagnosis parameters, such as sensitivity, specificity and receiver operating characteristic (ROC) curve least distance were calculated for hypertension, diabetes, high serum triglyceride (TG), high serum low density lipoprotein cholesterol (LDL-C), low serum high density lipoprotein cholesterol (HDL-C) and clustering of risk factors (number≥2) to evaluate the efficacy at each value of the WHtR cut-off point. The upper boundary value for severity was fixed on the point where the specificity was above 90%. The lower boundary value, which indicated above underweight, was determined by the percentile distribution of WHtR, specifically the 5th percentile (P5) for both males and females population. Then, based on convenience and practical use, the optimal boundary values of WHtR for underweight and obvious central obesity were determined. For the whole study population, the optimal WHtR cut-off point for the CVD risk factor cluster was 0.50. The cut-off points for severe central obesity were 0.57 in the whole population. The upper boundary values of WHtR to detect the risk factor cluster with specificity above 90% were 0.55 and 0.58 for men and women, respectively. Additionally, the cut-off points of WHtR for each of four cardiovascular risk factors with specificity above 90% in males ranged from 0.55 to 0.56, whereas in females, it ranged from 0.57 to 0.58. The P5 of WHtR, which represents the lower boundary values of WHtR that indicates above underweight, was 0.40 in the whole population. WHtR 0.50 was an optimal cut-off point for evaluating CVD risks in Chinese adults of both genders. The optimal boundaries of WHtR were 0.40 and 0.57, indicating low body weight and severe risk for CVD, respectively, in Chinese adults.

Renal fibrosis, considered to be a common consequence of progressive renal disease, involves glomerulosclerosis and/or tubulointerstitial fibrosis. Currently, research is focused on investigating potential mechanisms to prevent or reverse the damage caused by fibrosis. Under the influence of cytokines, chemokines and other signaling molecules, the cellular interactions that regulate the development of interstitial fibrosis are complex. Epithelial‑mesenchymal transition (EMT) has emerged as an important pathway leading to the generation of matrix‑producing fibroblasts and myofibroblasts in diseased kidneys. The proteomics study compared the protein profiles between the time points of podocyte EMT and tubular cell EMT in a partial unilateral ureteral obstruction (PUUO) model in rats. Proteins isolated from the PUUO group and corresponding sham rat kidney tissues were subjected to 2‑D gel electrophoresis and were then identified by mass spectrometry. In total, 43 proteins with differential expression were identified, which were reported to be involved in the regulation of the cytoskeleton and actin, glucose metabolism, cell apoptosis, mitochondrial energy metabolism, oxidative stress and endoplasmic reticulum stress. Electron transfer flavoprotein, β polypeptide was detected by immunoblot analysis and its mRNA levels were determined in renal tissues. The results demonstrate protein alterations that reflect the pathology of the obstructed kidneys, and thus may aid in understanding the pathogenesis of obstructive nephropathy.

Fibroblast growth factor (FGF) 9 is a member of the FGF family, which promotes carcinogenesis in some solid tumours. However, its biological and prognostic significance in gastric cancer (GC) is unclear. We examined FGF9 expression in 180 GC and corresponding non-tumorous gastric tissue samples by immunohistochemistry and evaluated its role in predicting tumour prognosis. Knockdown of FGF9 by siRNA inhibited cell growth and induced apoptosis in GC cell lines. Fifty of the 180 GC specimens (27.8%) had high FGF9 protein expression, whereas decreased or unchanged expression was observed in 130 cases (72.2%). High FGF9 expression was a significant predictor of poor survival (28.1 vs. 55.8 months, P < 0.001). After stratification according to AJCC stage, FGF9 remained a significant predictor of shorter survival in stage II (30.6 vs. 64.9 months, P < 0.001) and stage III GC (29.7 vs. 58.9 months, P < 0.001). Multivariate and univariate analysis showed that higher expression of FGF9 can be used as a predictor for poor prognosis (HR, 2.95; 95% CI, 1.97-4.41; P < 0.001; and HR, 2.94; 95% CI, 2.01-4.31; P < 0.001, respectively). FGF9 may provide the anti-apoptotic function and be useful as a novel independent marker for evaluating GC prognosis.

Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring's brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1α and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1α was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults.

Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice. Activation of Notch signaling with the endothelial cell (EC)-targeted soluble Dll1 Notch ligand mD1R promoted BM recovery after irradiation. mD1R treatment resulted in a significant increase in myeloid progenitors and monocytes in the BM, spleen and peripheral blood after irradiation. mD1R also enhanced hematopoiesis in mice treated with cyclophosphamide, a chemotherapeutic drug that induces BM suppression. Mechanistically, mD1R increased the proliferation and reduced the apoptosis of myeloid cells in the BM after irradiation. The β chain cytokine receptor Csf2rb2 was identified as a downstream molecule of Notch signaling in hematopoietic cells. mD1R improved hematopoietic recovery through up-regulation of the hematopoietic expression of Csf2rb2. Our findings reveal the role of Notch signaling in irradiation- and drug-induced BM suppression and establish a new potential therapy of BM- and myelo-suppression induced by radiotherapy and chemotherapy.

Epidural fibrosis is a common complication after laminectomy. It is associated with intractable lower back pain and additional complications. To date, no study has evaluated whether the local application of rapamycin (RAPA) can inhibit fibroblast proliferation and reduce epidural scar adhesion after laminectomy. The results of the present study showed that the local application of RAPA reduces epidural fibrosis after laminectomy in rats.

Hepatocellular carcinoma (HCC) is a liver cancer that could be induced by hepatitis C virus genotype 2a Japanese fulminant hepatitis-1 (JFH-1) strain. The aim of this study was to investigate the molecular mechanisms of HCC. The microarray data GSE20948 includes 14 JFH-1- and 14 mock (equal volume of medium [control])-infected Huh7 samples. The data were downloaded from the Gene Expression Omnibus. After data processing, soft cluster analyses were performed to identify co-regulated genes with similar temporal expression patterns. Functional and pathway enrichment analyses, as well as functional annotation analysis, were performed. Subsequently, combined networks of protein-protein interaction network, microRNA regulatory network, and transcriptional regulatory network were constructed. Hub nodes, modules, and five clusters of co-regulated genes were also identified. In total, 173 up and 207 down co-regulated genes were separately identified in JFH-1-infected Huh7 cells compared with those of control cells. Functional enrichment analysis indicated that up co-regulated genes were related to skeletal system morphogenesis and neuron differentiation and down co-regulated genes were related to steroid/cholesterol/sterol metabolisms. Hub genes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) were identified. Transcription factors IRF1 and Foxa1 were the targets of miR-130a, miR-17-5p, and miR-20a. PPARGC1A was targeted by miR-29 family, and MSMO1 was the target of miR-23 family. Hub nodes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) and microRNAs might be used as candidate biomarkers of JFH-1-infected HCC.

After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents.

MicroRNAs (miRNAs) play key roles in a variety of cellular processes through regulation of their target gene expression. Accumulated experimental evidence has demonstrated that infections by viruses are associated with the altered expression profile of miRNAs and their mRNA targets in the host. However, the regulatory network of miRNA-mRNA interactions during viral infection remains largely unknown. In this study, we performed small RNA (sRNA)-seq, degradome-seq and as well as a genome-wide transcriptome analysis to profile the global gene and miRNA expression in soybean following infections by three different Soybean mosaic virus (SMV) isolates, L (G2 strain), LRB (G2 strain) and G7 (G7 strain). sRNA-seq analyses revealed a total of 253 soybean miRNAs with a two-fold or greater change in abundance compared with the mock-inoculated control. 125 transcripts were identified as the potential cleavage targets of 105 miRNAs and validated by degradome-seq analyses. Genome-wide transcriptome analysis showed that total 2679 genes are differentially expressed in response to SMV infection including 71 genes predicted as involved in defense response. Finally, complex miRNA-mRNA regulatory networks were derived using the RNAseq, small RNAseq and degradome data. This work represents a comprehensive, global approach to examining virus-host interactions. Genes responsive to SMV infection are identified as are their potential miRNA regulators. Additionally, regulatory changes of the miRNAs themselves are described and the regulatory relationships were supported with degradome data. Taken together these data provide new insights into molecular SMV-soybean interactions and offer candidate miRNAs and their targets for further elucidation of the SMV infection process.

Panax notoginseng saponins (PNS) could maintain vascular smooth muscle cells (VSMCs) in stable phenotypes so as to keep blood vessel elasticity as well as prevent failing in endovascular treatment with stent. Downregulation of Notch3 expression in VSMCs could influence the phenotype of VSMCs under pathologic status. However, whether PNS is able to attenuate the Notch3 silencing induced phenotype switching of VSMCs remains poorly understood. Primary human VSMCs were transfected with a plasmid containing a small interfering RNA (siRNA) against Notch3 and then exposed to different doses of PNS. The control groups included cells not receiving any treatment and cells transfected with a control siRNA. Phenotypic switching was evaluated by observing cell morphology with confocal microscopy, as well as examining α-SM-actin, SM22α, and OPN using Western blot. Downregulated Notch3 with a siRNA induced apparent phenotype switching, as reflected by morphologic changes, decreased expression of α-SM-actin and SM22α and increased expression of OPN. These changes were inhibited by PNS in a dose-dependent manner. The phenotype switching of VSMCs induced by Notch3 knockdown could be inhibited by PNS in a dose-dependent manner. Our study provided new evidence for searching effective drug for amending stability of atherosclerotic disease.

Emerging epidemics of hand-foot-and-mouth disease (HFMD) associated with enterovirus 71 (EV71) has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6∼4.8×10⁻³ nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a). It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding.

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75-29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50-4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27-4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35-4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42-4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30-4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.

Axon guidance protein Semaphorin 3E (Sema3E) promotes tumor metastasis and suppresses tumor cell death. Here, we demonstrated that Sema3E was decreased in gastric cancer. Its levels were inversely associated with tumor progression. Levels of Sema3E were associated with low p300 and high class I histone deacetylase (class I HDAC). Ectopic expression of Sema3E inhibited proliferation and colony formation of gastric cancer cell lines in vitro and xenografts in vivo. Sema3E overexpression inhibited migration and invasion of gastric cancer cells, which was associated with induction of E-cadherin and reduction of Akt and ERK1/2 phosphorylation. We suggest that silencing of Sema3E contributes to the pathogenesis of gastric cancer.

Adenomatous polyposis coli (Apc) is a tumor suppressor that inhibits Wnt/Ctnnb1. Mutations of Apc will not only lead to familial adenomatous polyposis with associated epithelial lesions, but will also cause aggressive fibromatosis in mesenchymal cells. However, the roles of Apc in regulating mesenchymal cell biology and organogenesis during development are unknown.

Renal ischemia and reperfusion (I/R) injury, which commonly occurs in kidney transplantation, is the leading cause of acute kidney injury. Picroside II possesses a wide range of pharmacological effects, including anti-apoptosis effects. In the present study, the ability of picroside II to attenuate apoptosis in a rat model of renal I/R injury was investigated. Sprague-Dawley rats were subjected to 45 min of ischemia followed by 24 h of reperfusion. Prior to reperfusion, the rats were treated with picroside II or an equal volume of phosphate-buffered saline. It was observed that renal function was significantly improved by the treatment with picroside II. Morphological analysis indicated that picroside II markedly reduced tissue damage and the expression of cleaved caspase-3. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that the expression levels of Bax and poly(ADP-ribose) polymerase-1 (PARP-1) were upregulated in the I/R group, whereas those of Bcl-2 were downregulated. However, the treatment with picroside II inhibited these changes induced by renal I/R injury. In conclusion, picroside II has potent anti-apoptotic activity against renal I/R injury.

The Chinese white pine beetle is arguably the most destructive forest insect in the Qinling Mountains in Northern China. Little is known about the structure of the fungal communities associated with Dendroctonus armandi, even though this wood-boring insect plays important roles in ecosystem and biological invasion processes that result in huge economic losses in pine forests. The aim of this study was to investigate the fungal community structure present in the galleries and guts of D. armandi at different developmental stages using PCR-denaturing gradient gel electrophoresis (DGGE). Analysis of PCR-amplified 18S rRNA gene fragments of fungi from the guts of D. armandi revealed fungal communities of low complexity that differed according to the developmental stage. Yeast of the genus Candida and the filamentous fungi Ophiostoma predominated in D. armandi and its galleries. In particular, Candida accounted for 56% of the fungal community in the pupal stage. Characterizing the evolution and content of the intestinal microbial community structure in D. armandi may facilitate the development of new pest control strategies.

Ischemia-reperfusion is a common injury of clinical ischemic disease and surgical lesions. Ischemic postconditioning (IPO) improves the ability of organs subjected to ischemia to tolerate injury. However, renal IPO studies have been based on animal models. In order to gain insights into IPO-induced alterations at the cellular level, an in vitro model for IPO was designed using the rat proximal tubular cell line NRK-52 E. This model was established by placing NRK-52 E cells in ischemic conditions for 3 h, then exposing cells to three cycles of reperfusion for 10 min and finally to ischemic conditions for 10 min (postconditioning). The cells were cultured further in reperfusion conditions for 3, 6, 12 and 24 h. Flow cytometry and Hoechst were used to assess apoptosis. The protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, cleaved caspase-3 and caspase-8 were analyzed by western blotting. The results demonstrated that apoptosis occurred in cells subjected to ischemia/reperfusion (I/R) alone or with postconditioning following reperfusion for 24 h. Cells subjected to I/R demonstrated increased expression of Bax, cleaved caspase-3 and caspase-8 at the end of reperfusion. However, the levels of Bax, cleaved caspase-3 and caspase-8 were significantly attenuated in cells, which had undergone IPO. In conclusion, apoptosis was observed in cells subjected to 3 h of ischemia-reperfusion injury and IPO was able to inhibit this apoptosis. IPO inhibited apoptosis by inhibiting the caspase pathway thereby exerting protective effects.

Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown.