Progressive decay of Ca2+ homeostasis in the development of diabetic cardiomyopathy

BACKGROUND: Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca(2+) homeostasis. This study investigated the effects of alterations in Ca(2+) homeostasis and sarcoplasmic reticulum Ca(2+)-associated proteins on cardiac function in the development of diabetic cardiomyopathy. METHODS: Sprague–Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca(2+) spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca(2+)-associated proteins were assessed by Western blotting. RESULTS: Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca(2+) spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca(2+) spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+)-2ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX1) were decreased, together with quantitative alterations in Ca(2+)regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. CONCLUSIONS: Ca(2+) sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca(2+)-associated proteins

Detection of differentially expressed genes between Erhualian and Large White placentas on day 75 and 90 of gestation

<p>Abstract</p> <p>Background</p> <p>Placental efficiency is strongly associated with litter size, fetal weight and prenatal mortality. Together with its rapid growth during late gestation, the Large White pig breed shows a significant increase in placental size and weight, but this does not occur in the highly prolific Chinese pig breeds. To understand the molecular basis of placental development during late gestation in Chinese indigenous and Western breeds with different placental efficiency, female placental samples were collected from six pregnant Erhualian gilts at gestation day 75 (E75) and day 90 (E90) and from six pregnant Large White gilts at gestation day 75 (L75) and day 90 (L90). Two female placentas from one sow were used to extract RNA and then pooled in equal volumes. Twelve pooled samples were hybridized to the porcine Affymetrix GeneChip.</p> <p>Results</p> <p>A total of 226 and 577 transcripts were detected that were differentially expressed between E75 and L75 and between E90 and L90 (p < 0.01, q < 0.2), respectively. Gene Ontology (GO) analysis revealed that these genes belong to the class of genes that participate in angiogenesis and development. Real-time RT-PCR confirmed the differential expression of eight selected genes. Significant differential expression of five genes in the <it>VEGF </it>pathway was also detected between the breeds. A search of chromosomal location revealed that 44 differentially expressed genes located to QTL regions related to reproduction. Differential expression of six candidate imprinted genes was also confirmed. Three of the six genes (<it>PLAGL1</it>, <it>DIRAS3</it>, and <it>SLC38A4</it>) showed monoallelic expression in the porcine placenta.</p> <p>Conclusion</p> <p>Our study detected many genes that showed differential expression between placentas of two divergent breed of pigs, and confirmed the imprinting of three genes. These findings help to elucidate the genetic control of placental efficiency and improve the understanding of placental development.</p

Malaria incidence from 2005–2013 and its associations with meteorological factors in Guangdong, China

Background: The temporal variation of malaria incidence has been linked to meteorological factors in many studies, but key factors observed and corresponding effect estimates were not consistent. Furthermore, the potential effect modification by individual characteristics is not well documented. This study intends to examine the delayed effects of meteorological factors and the sub-population's susceptibility in Guangdong, China. Methods: The Granger causality Wald test and Spearman correlation analysis were employed to select climatic variables influencing malaria. The distributed lag non-linear model (DLNM) was used to estimate the non-linear and delayed effects of weekly temperature, duration of sunshine, and precipitation on the weekly number of malaria cases after controlling for other confounders. Stratified analyses were conducted to identify the sub-population's susceptibility to meteorological effects by malaria type, gender, and age group. Results: An incidence rate of 1.1 cases per 1,000,000 people was detected in Guangdong from 2005-2013. High temperature was associated with an observed increase in malaria incidence, with the effect lasting for four weeks and a maximum relative risk (RR) of 1.57 (95% confidence interval (CI): 1.06-2.33) by comparing 30°C to the median temperature. The effect of sunshine duration peaked at lag five and the maximum RR was 1.36 (95% CI: 1.08-1.72) by comparing 24 hours/week to 0 hours/week. A J-shaped relationship was found between malaria incidence and precipitation with a threshold of 150 mm/week. Over the threshold, precipitation increased malaria incidence after four weeks with the effect lasting for 15 weeks, and the maximum RR of 1.55 (95% CI: 1.18-2.03) occurring at lag eight by comparing 225 mm/week to 0 mm/week. Plasmodium falciparum was more sensitive to temperature and precipitation than Plasmodium vivax. Females had a higher susceptibility to the effects of sunshine and precipitation, and children and the elderly were more sensitive to the change of temperature, sunshine duration, and precipitation. Conclusion: Temperature, duration of sunshine and precipitation played important roles in malaria incidence with effects delayed and varied across lags. Climatic effects were distinct among sub-groups. This study provided helpful information for predicting malaria incidence and developing the future warning system.School of Nursin

Enhancement of cisplatin sensitivity in lewis lung carcinoma by liposome-mediated delivery of a survivin mutant

<p>Abstract</p> <p>Background</p> <p>A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant could enhance the anti-tumor activity of CDDP.</p> <p>Methods</p> <p>A plasmid encoding the phosphorylation-defective dominant-negative mouse survivin threonine 34→alanine mutant (survivin T34A) complexed to a DOTAP-chol liposome (Lip-mS) was administered with or without CDDP in Lewis Lung Carcinoma (LLC) cells and in mice bearing LLC tumors, and the effects on apoptosis, tumor growth and angiogenesis were assessed. Data were analyzed using one-way analysis of variance(ANOVA), and a value of <it>P </it>< 0.05 was considered to be statistically significant.</p> <p>Results</p> <p>LLC cells treated with a combination of Lip-mS and CDDP displayed increased apoptosis compared with those treated with Lip-mS or CDDP alone. In mice bearing LLC tumors and treated with intravenous injections of Lip-mS and/or CDDP, combination treatment significantly reduced the mean tumor volume compared with either treatment alone. Moreover, the antitumor effect of Lip-mS combined with CDDP was greater than their anticipated additive effects.</p> <p>Conclusion</p> <p>These data suggest that the dominant-negative survivin mutant, survivin T34A, sensitized LLC cells to chemotherapy of CDDP. The synergistic antitumor activity of the combination treatment may in part result from an increase in the apoptosis of tumor cells, inhibition of tumor angiogenesis and induction of a tumor-protective immune response.</p

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p

Physics perspectives of heavy-ion collisions at very high energy

Heavy-ion collisions at very high colliding energies are expected to produce a quark-gluon plasma (QGP) at the highest temperature obtainable in a laboratory setting. Experimental studies of these reactions can provide an unprecedented range of information on properties of the QGP at high temperatures. We report theoretical investigations of the physics perspectives of heavy-ion collisions at a future high-energy collider. These include initial parton production, collective expansion of the dense medium, jet quenching, heavy-quark transport, dissociation and regeneration of quarkonia, photon and dilepton production. We illustrate the potential of future experimental studies of the initial particle production and formation of QGP at the highest temperature to provide constraints on properties of strongly interaction matter.Comment: 35 pages in Latex, 29 figure

A new, feasible, and convenient method based on semantic segmentation and deep learning for hemoglobin monitoring

ObjectiveNon-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input.MethodsSurgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE).ResultsA total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499–0.507), 0.518 (95% CI, 0.515–0.522) and 1.6 g/dL (95% CI, 1.6–1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL).ConclusionWe developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on