KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

2,4-Diamino-6-methyl-1,3,5-triazin-1-ium nitrate

In the title salt, C4H8N5 +·NO3 −, a ring N atom of 2,6-diamino-4-methyl­triazine is protonated. Each anion is connected to three neighbouring cations by multiple N—H⋯O hydrogen bonds which, together with N—H⋯N contacts, generate a layer structure

Granulocyte colony-stimulating factor affects the distribution and clonality of TRGV and TRDV repertoire of T cells and graft-versus-host disease

<p>Abstract</p> <p>Background</p> <p>The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Recent data indicated that gamma delta⁺T cells might participate in mediating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. However, whether G-CSF could influence the T cell receptors (TCR) of gamma delta⁺T cells (<it>TRGV </it>and <it>TRDV </it>repertoire) remains unclear. To further characterize this feature, we compared the distribution and clonality of <it>TRGV </it>and <it>TRDV </it>repertoire of T cells before and after G-CSF mobilization and investigated the association between the changes of TCR repertoire and GVHD in patients undergoing G-CSF mobilized allo-PBSCT.</p> <p>Methods</p> <p>The complementarity-determining region 3 (CDR3) sizes of three <it>TRGV </it>and eight <it>TRDV </it>subfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using RT-PCR and genescan technique. To determine the expression levels of <it>TRGV </it>subfamily genes, we performed quantitative analysis of <it>TRGV</it>I~III subfamilies by real-time PCR.</p> <p>Results</p> <p>The expression levels of three <it>TRGV </it>subfamilies were significantly decreased after G-CSF mobilization (<it>P </it>= 0.015, 0.009 and 0.006, respectively). The pattern of <it>TRGV </it>subfamily expression levels was <it>TRGV</it>II ><it>TRGV </it>I ><it>TRGV </it>III before mobilization, and changed to <it>TRGV </it>I ><it>TRGV </it>II ><it>TRGV </it>III after G-CSF mobilization. The expression frequencies of <it>TRGV </it>and <it>TRDV </it>subfamilies changed at different levels after G-CSF mobilization. Most <it>TRGV </it>and <it>TRDV </it>subfamilies revealed polyclonality from pre-G-CSF-mobilized and G-CSF-mobilized samples. Oligoclonality was detected in <it>TRGV </it>and <it>TRDV </it>subfamilies in 3 donors before mobilization and in another 4 donors after G-CSF mobilization, distributed in <it>TRGV</it>II, <it>TRDV</it>1, <it>TRDV</it>3 and <it>TRDV</it>6, respectively. Significant positive association was observed between the invariable clonality of <it>TRDV</it>1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (<it>P </it>= 0.015, <it>OR </it>= 0.047).</p> <p>Conclusions</p> <p>G-CSF mobilization not only influences the distribution and expression levels of <it>TRGV </it>and <it>TRDV </it>repertoire, but also changes the clonality of gamma delta⁺T cells. This alteration of <it>TRGV </it>and <it>TRDV </it>repertoire might play a role in mediating GVHD in G-CSF mobilized allo-PBSCT.</p

Alcohol Consumption and Ankle-to-Brachial Index: Results from the Cardiovascular Risk Survey

BACKGROUND AND METHODOLOGY: A low ankle-to-brachial index (ABI) is a strong correlate of cardiovascular disease and subsequent mortality. The relationship between ABI and alcohol consumption remains unclear. Data are from the Cardiovascular Risk Survey (CRS), a multiple-ethnic, community-based, cross-sectional study of 14,618 Chinese people (5757 Hans, 4767 Uygurs, and 4094 Kazakhs) aged 35 years and over at baseline from Oct. 2007 to March 2010. The relationship between alcohol intake and ABI was determined by use of analysis of covariance and multivariable regressions. PRINCIPAL FINDINGS: In men, alcohol consumption was significantly associated with ABI (P<0.001). After adjusted for the confounding factors, such as age, sex, ethnicity, body mass index, smoking, work stress, diabetes, and fasting blood glucose, the difference remained significant (P<0.001); either the unadjusted or multivariate-adjusted odds ratio (OR) for peripheral artery disease (PAD) was significantly higher in men who consumed >60.0 g/d [OR = 3.857, (95% CI: 2.555-5.824); OR = 2.797, (95% CI: 1.106-3.129); OR = 2.878, (95% CI: 1.215-4.018); respectively] and was significantly lower in men who consumed 20.1-40.0 g/d [OR= 0.330, (95% CI: 0.181-0.599); OR = 0.484, (95% CI: 0.065-0.894); OR = 0.478, (95% CI: 0.243-1.534); respectively] and 40.1-60.0 g/d [OR= 0.306, (95% CI: 0.096-0.969); OR = 0.267, (95% CI: 0.087-0.886); OR = 0.203, (95% CI: 0.113-0.754); respectively] compared with never drinking, respectively (all P<0.01). Neither in unadjusted nor in multivariate-adjusted model was the association between ABI and alcohol consumption significant (all P>0.05) in women. Similarly, PAD was not correlated with alcohol intake in women (all P>0.05). CONCLUSIONS/SIGNIFICANCE: Our results indicated that in Chinese men, alcohol consumption was associated with peripheral artery disease, and consumption of less than 60 g/d had an inverse association with peripheral atherosclerosis whereas consumption of 60 g/d or more had a positive association

Proteomics study of serum exosomes in Kawasaki disease patients with coronary artery aneurysms

Background: To study the protein profile of the serum exosomes of patients with coronary artery aneurysms (CAA) caused by Kawasaki disease (KD). Methods: Two-dimensional electrophoresis (2-DE) was used to identify proteins from the exosomes of serum obtained from children with CAA caused by KD, as well as healthy controls. Differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight/timeof-flight mass spectrometry (MALDI-TOF/TOF MS) analysis. Results: Thirty two differentially expressed proteins were identified (18 up-regulated and 14 downregulated) from serum exosomes of children with CAA and were compared to healthy controls. The expression levels of 4 proteins (TN, RBP4, LRG1, and APOA4) were validated using Western blotting. Classification analysis and protein–protein network analysis showed that they are associated with multiple functional groups, including host immune response, inflammation, apoptotic process, developmental process, and biological adhesion process. Conclusions: These findings establish a comprehensive proteomic profile of serum exosomes from children with CAA caused by KD, and provide additional insights into the mechanisms of CAA caused by KD

Symptom clusters after chemoradiotherapy in discharged nasopharyngeal carcinoma patients

ObjectiveTo investigate the incidence of complications and types of chemoradiotherepy induces symptom clusters in patients with nasopharyngeal carcinoma (NPC) who were first diagnosed after treatment and discharged from hospital.MethodsAfter their discharge home, 130 NPC patients who had been treated with chemoradiotherapy were asked to complete a modified Chinese version of the Quality of Life Questionnaire–Head and Neck Module developed by the European Organization for the Research and Treatment of Cancer in the Head and Neck. Symptom clusters in patients were identified through exploratory factor analysis.ResultsThe most serious symptoms for discharged NPC patients who had received chemoradiotherapy were dental problems, a sense of obstruction while swallowing, embarrassment in physical contact with family members and friends, difficulty in speaking with others, and embarrassment in public. The six symptom clusters identified through exploratory factor analysis were (1) painful eating, (2) social difficulties, (3) psychological disorders, (4) symptomatic shame, (5) teeth/throat injuries, and (6) sensory abnormalities. The total contribution rate of variance was 65.73%.ConclusionNPC patients who are treated with chemoradiotherapy can experience adverse symptom clusters that continue after discharge. Nurses should evaluate the patients’ symptoms before discharge and provide targeted health education services which would reduce the patients’ complications and improve the quality of life at home. Besides, medical staff should evaluate the complications in a timely and comprehensive manner and provide individualized health education for the affected patients to help them manage chemoradiotherapy side effects

Levels of Inflammatory Cytokines in Type 2 Diabetes Patients with Different Urinary Albumin Excretion Rates and Their Correlation with Clinical Variables

Although the pathogenetic mechanism of DN has not been elucidated, an inflammatory mechanism has been suggested as a potential contributor. This study was designed to explore the relationship between low-grade inflammation and renal microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three groups according to UAE: a normal albuminuria group, a microalbuminuria group, and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP, TNF-, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were measured in all subjects. Compared with the normal controls, levels of hs-CRP, TNF-, uMCP-1, and SAA in T2DM patients were significantly higher. They were also elevated in the normal albuminuria group, &lt; 0.05. Compared with the normal albuminuria group, levels of these inflammatory cytokines were significantly higher in the microalbuminuria and macroalbuminuria group, &lt; 0.01. The macroalbuminuria group also showed higher levels than the microalbuminuria group, &lt; 0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC. We noted no significance correlated with course, TG, or HDL-C. Only TNF-; was positively correlated with HbA1c. This study revealed the importance of these inflammatory cytokines in DN pathogenesis. Further studies are needed to fully establish the potential of these cytokines as additional biomarkers for the development of DN

PROKINETIC AND LAXATIVE EFFECTS OF XIAO'ER QIXINGCHA, A HOUSEHOLD PEDIATRIC HERBAL FORMULA

Background: Xiao'er Qixingcha, a household Chinese Medicinal formula, has been extensively applied in pediatric clinic for dyspepsia and constipation for hundreds of years. The present study firstly inspected whether the extract of Xiao'er Qixingcha (EXQ) has in vivo and in vitro prokinetic and laxative effects, and evaluated its acute toxicity. Materials and methods: In the in vivo study, small intestinal transit rates and fecal output characters (number and fecal weight) were measured on normal and two models of constipated mice (induced by diphenoxylate and by water-fasting respectively). In the in vivo study, the contraction rates of ileum smooth muscle were examined with EXQ treatment. Moreover, in acute toxicity study, EXQ was administered orally for 14 days to juvenile SD rats, and clinical signs, viscera lesion and body weight were monitored daily. Results: EXQ at all doses significantly increased the small intestinal transit rates, and ameliorated the fecal output characters of normal mice. In diphenoxylate-induced constipated mice, EXQ dose-dependently improved the small intestinal transit rates and fecal output. In water-fasting-induced constipated mice, EXQ dose-dependently improved the small intestinal transit rates, and significantly ameliorated the fecal output characters at 2.92 and 6.75 g/kg. Furthermore, in the in vitro study, EXQ dose-dependently raised the contraction rates of the isolated rabbit ileum smooth muscle. Finally, the acute toxicity study indicated that no toxicological effect was observed in terms of clinical signs, viscera lesion or change of body weight. Conclusions: Taken together, EXQ exhibited prominent prokinetic and laxative activities, promising it as a safe and effective alternative pharmaceutical therapy for constipation