Laccase, a member of a group of proteins collectively known as multicopper oxidases, is hypothesized to play an important role in insect cuticle sclerotization by oxidizing catechols in the cuticle to their corresponding quinones, which then catalyze protein cross-linking reactions. Laccase 2 has been proved as the gene required for beetle cuticle tanning through RNA interference (RNAi) experiments on red flour beetle Tribolium castaneum. The pine sawyer beetle, Monochamus alternatus (Coleoptero: Cerambycidae) is the insect serving as a major vector of the pinewood nematode, Bursaphelenchus xylophilus, which is the causative agent for pine wilt disease. The cDNA of MaLac2 was cloned from the insect in this study. The conceptual amino-acid sequence deduced was much conserved with other known insect laccases, particularly with the enzyme of Tribolium castaneum. Injection in hemolymph of pine sawyer larva of dsRNA targeting the laccase 2 mRNA leads to important alterations of the tanning, hardening and sclerotization of the pupal and adult cuticles. Defaults appear in a dose-dependent manner and high loads of dsRNA are lethal. The decrease of the endogenous laccase 2 mRNA affects the procuticle which is thinner and without the characteristic piling up of successive layers. The observations reinforce the role of laccase 2 as an essential phenoloxidase for making cuticle.

Background: The transcription factor HOXD9 is one of the members of the HOX family, which plays an important role in neoplastic processes. However, the role of HOXD9 in the growth and metastasis of gastric cancer (GC) remains to be elucidated. Methods:In vitro functional role of HOXD9 and RURY3 in GC cells was determined using the TMA-based immunohistochemistry, western blot, EdU incorporation, gelatin zymography, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. In vivo tumor growth and metastasis were conducted in nude mice.Results: HOXD9 is overexpressed in GC cells and tissues. The high expression of HOXD9 was correlated with poor survival in GC patients. Functionally, HOXD9 expression significantly promoted the proliferation, invasion and migration of GC cells. Mechanically, HOXD9 directly associated with the RUFY3 promoter to increase the transcriptional activity of RUFY3. Inhibition of RUFY3 attenuated the proliferation, migration and invasiveness of HOXD9-overexpressing GC cells in vitro and in vivo. Moreover, both HOXD9 and RUFY3 were highly expressed in cancer cells but not in normal gastric tissues, with their expressions being positively correlated. Conclusions:The evidence presented here suggests that the HOXD9-RUFY3 axis promotes the development and progression of human GC.

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.

BackgroundCardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated.MethodsTwenty-four rats were assigned to the normal control group (NC), sympathectomy control group (SC), and a sympathectomy plus mecobalamin group (SM). Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV) myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV), ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction.ResultsInjection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01) and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01) concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group.ConclusionsChemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves.

Gastric cancer is one of the most malignant tumor types, and its metastasis is a notable cause of mortality. Among the methods of tumor metastasis, lymphatic metastasis is the predominant one in gastric cancer. A previous study reported that the plasma oxidized low-density lipoprotein (oxLDL) is the risk factor associated with the development of tumors in patients with abnormal lipid metabolism, but the influence of plasma oxLDL in the lymphatic metastasis of gastric cancer remains unclear. In the present study, the concentration of plasma oxLDL from patients with gastric cancer was detected with an ELISA kit, and the lymphatic vessel density in gastric cancer tissues was determined by D2-40 staining. The correlation analysis of oxLDL concentration and lymphatic vessel density demonstrated that plasma oxLDL was positively correlated with lymphatic metastasis in patients with gastric cancer. Subsequently, the popliteal lymph node metastasis animal experiment with nude mice confirmed that oxLDL could promote the lymphatic metastasis of gastric cancer. Following this, the western blotting and ELISA data demonstrated that oxLDL promoted the expression and secretion of vascular endothelia growth factor (VEGF)-C in gastric cancer cell lines. Finally, blocking the lectin-like oxLDL-1 (LOX-1) receptor, a specific receptor for oxLDL, and the nuclear factor (NF)-κB signaling pathway following oxLDL (50 µg/ml) treatment in HGC-27 cells revealed that oxLDL could activate the NF-κB signaling pathway mediated by LOX-1, with subsequent upregulation of VEGF-C expression, and secretion in and from gastric cancer cells, and finally that it could promote the lymphatic metastasis of gastric cancer. These data indicate the association between the plasma oxLDL and the lymphatic metastasis of gastric cancer, and indicate that oxLDL elimination may be a potential therapeutic target for the prevention and intervention of early lymph node metastasis in gastric cancer.

No abstract

BackgroundAccumulating studies have demonstrated the abnormal expressions and prognostic values of certain members of the tripartite motif (TRIM) family in diverse cancers. However, comprehensive prognostic values of the TRIM family in hepatocellular carcinoma (HCC) are yet to be clearly defined.MethodsThe prognostic values of the TRIM family were evaluated by survival analysis and univariate Cox regression analysis based on gene expression data and clinical data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression profiles, protein–protein interaction among the TRIM family, prediction of transcription factors (TFs) or miRNAs, genetic alterations, correlations with the hallmarks of cancer and immune infiltrates, and pathway enrichment analysis were explored by multiple public databases. Further, a TRIM family gene-based signature for predicting overall survival (OS) in HCC was built by using the least absolute shrinkage and selection operator (LASSO) regression. TCGA–Liver Hepatocellular Carcinoma (LIHC) cohort was used as the training set, and GSE76427 was used for external validation. Time-dependent receiver operating characteristic (ROC) and survival analysis were used to estimate the signature. Finally, a nomogram combining the TRIM family risk score and clinical parameters was established.ResultsHigh expressions of TRIM family members including TRIM3, TRIM5, MID1, TRIM21, TRIM27, TRIM32, TRIM44, TRIM47, and TRIM72 were significantly associated with HCC patients’ poor OS. A novel TRIM family gene-based signature (including TRIM5, MID1, TRIM21, TRIM32, TRIM44, and TRIM47) was built for OS prediction in HCC. ROC curves suggested the signature’s good performance in OS prediction. HCC patients in the high-risk group had poorer OS than the low-risk patients based on the signature. A nomogram integrating the TRIM family risk score, age, and TNM stage was established. The ROC curves suggested that the signature presented better discrimination than the similar model without the TRIM family risk score.ConclusionOur study identified the potential application values of the TRIM family for outcome prediction in HCC.

AbstractsBackgroundHypertension is considered a major public health challenge. It is the most important risk factor for cardiovascular disease and is a prominent risk for China’s elderly population. However, few studies have addressed the effect of blood pressure control on elderly hypertension patients in China. In response, this study aimed to investigate the prevalence and control of hypertension in the elderly population in Shanghai’s communities.MethodsA secondary data analysis based on a government-financed health check-up program for an elderly population aged 65 and older from 2012 to 2014 was conducted in a central district of Shanghai.ResultsOf the 44,978 study participants, 20,305 (45.1%) were males and 24,673 (54.9%) were females. The participants’ median age was 72. Half of the participants were overweight or obese (BMI ≥ 24.0 kg/m2). The prevalence of hypertension was 59.9%. In the 18,032 participants without prior diagnosis of hypertension, 5530 (30.7%) had increased blood pressure. Among the 26,946 confirmed hypertension patients, the proportions of treatment and blood pressure control were 32.8% and 43.4% respectively. Multivariate analysis showed that the uncontrolled hypertension was significantly associated with older age, being overweight or obese, a lower level of education, an unbalanced dietary pattern, regular drinking and non-comorbidities.ConclusionsThe prevalence of hypertension was high in China’s elderly population. The proportion of individuals who received treatment remained low, and blood pressure control was poor among hypertension patients. These results indicate that improvement of the ability to manage and control hypertension among urban elderly residents is urgently needed.