MicroRNA-1 and Circulating Microvesicles Mediate the Protective Effects of Dantonic in Acute Myocardial Infarction Rat Models

Aim: To investigate the protective effect of dantonic in ischemic myocardial damage by evaluating the expression of circulating microvesicles (MVs) and microRNA-1 (miR-1) in two animal models.Methods: Two animal models of myocardial ischemia were established that were isoproterenol-induced myocardial ischemia (ISO-AMI) rat model and the acute myocardial infarction rat model induced by ligation of the left anterior descending coronary artery (LAD-AMI) of rat. To investigate the protective effect of dantonic, we observed the myocardial infarction size, creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) activities, cardiac troponin I (cTnI) level in serum, and the plasma levels of miR-1 and MVs.Results: The results showed that pretreatment with dantonic significantly attenuated the LAD-AMI induced myocardial damage by decreasing the size of myocardial infarction, CK, LDH, AST activities, and cTnI level in serum. High dose dantonic treatment could significantly abrogate the increased plasma levels of miR-1 and MVs as compared to the LAD rat model. In addition, pretreatment with dantonic also showed a significant myocardial protective effect through reducing the expression levels of CK, LDH, and AST as compared to the ISO-AMI model. Whereas the cTnI level was no significant difference between model group and control group, suggesting that the model caused less myocardial damage. In the ISO-induced myocardial ischemia model, there is no significant difference between the model group with the control group of MVs and miR-1 levels. This may be that miR-1 is reported as a biomarker of acute myocardial infarction. The pathological changes of IOS-induced acute myocardial ischemia model are also different from those of acute myocardial infarction.Conclusion: Dantonic showed the protective effect in these two ischemic myocardial injury rat models, whereas the circulating miR-1 and MVs levels were only ameliorated in the LAD rat model

A case report of neuralgic amyotrophy

Neuralgic muscular atrophy is not uncommon in clinical practice. Due to the different branches of brachial plexus involved in the lesion, the clinical symptoms are different, and there is a lack of clear imaging diagnostic criteria, so the diagnosis of this disease brings great challenges to clinicians. We have certain experience in the diagnosis and treatment of this disease, and hereby select a representative case of neuralgic muscular atrophy to share its diagnosis and treatment process, focusing on analyzing the characteristic symptoms of this disease, valuable imaging data and targeted treatment, so as to enable clinicians to better understand this disease

G protein-coupled receptor-mediated calcium signaling in astrocytes

Astrocytes express a large variety of G~protein-coupled receptors (GPCRs) which mediate the transduction of extracellular signals into intracellular calcium responses. This transduction is provided by a complex network of biochemical reactions which mobilizes a wealth of possible calcium-mobilizing second messenger molecules. Inositol 1,4,5-trisphosphate is probably the best known of these molecules whose enzymes for its production and degradation are nonetheless calcium-dependent. We present a biophysical modeling approach based on the assumption of Michaelis-Menten enzyme kinetics, to effectively describe GPCR-mediated astrocytic calcium signals. Our model is then used to study different mechanisms at play in stimulus encoding by shape and frequency of calcium oscillations in astrocytes.Comment: 35 pages, 6 figures, 1 table, 3 appendices (book chapter

Initialized Decadal Predictions by LASG/IAP Climate System Model FGOALS-s2: Evaluations of Strengths and Weaknesses

Decadal prediction experiments are conducted by using the coupled global climate model FGOALS-s2, following the CMIP 5 protocol. The paper documents the initialization procedures for the decadal prediction experiments and summarizes the predictive skills of the experiments, which are assessed through indicators adopted by the IPCC AR5. The observational anomalies of surface and subsurface ocean temperature and salinity are assimilated through a modified incremental analysis update (IAU) scheme. Three sets of 10-year-long hindcast and forecast runs were started every five years in the period of 1960–2005, with the initial conditions taken from the assimilation runs. The decadal prediction experiment by FGOALS-s2 shows significant high predictive skills in the Indian Ocean, tropical western Pacific, and Atlantic, similar to the results of the CMIP5 multimodel ensemble. The predictive skills in the Indian Ocean and tropical western Pacific are primarily attributed to the model response to the external radiative forcing associated with the change of atmospheric compositions. In contrast, the high skills in the Atlantic are attributed, at least partly, to the improvements in the prediction of the Atlantic multidecadal variability coming from the initialization

Pancreatic stone protein/regenerating protein (PSP/reg): a novel secreted protein up-regulated in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) has insulin resistance (IR) or reduced β-cell mass, partially due to an increased β-cell apoptosis rate. Pancreatic stone protein/regenerating protein (PSP/reg) is a secretory protein produced in the pancreas and up-regulated dramatically during pancreatic disease. Recent studies revealed that β-cells undergoing apoptosis induce PSP/reg expression in surviving neighboring cells. Further experiments demonstrated that PSP/reg was elevated during disease progression in type 1 diabetes mellitus (T1DM). However, the association between PSP/reg and T2DM patients is unknown. The aim of this pilot study was to investigate PSP/reg in different clinical stages of T2DM and evaluate its correlation with chronic complications of diabetes. A total of 1,121 participants (479 males, 642 females; age range 23-80 years) were enrolled in this study. PSP/reg serum values were measured by a newly developed enzyme-linked immunosorbent assay (ELISA). We analyzed its correlation with clinical and biochemical parameters in subjects with T2DM at different clinical phases. Statistical analyses were conducted using SPSS 17.0 software. Correlations of PSP/reg and clinical parameters were performed using Spearman's rank correlation coefficient. Differences between groups were determined by Nemenyi test. PSP/reg was elevated in high-risk and impaired glucose regulation (IGR) patients (p < 0.05). PSP/reg was significantly up-regulated in newly diagnosed T2DM patients and long-term diabetes patients with complications (p < 0.001). PSP/reg levels correlated with the duration of diabetes (p < 0.001). The area under the curve (AUC) for presence of diabetes-onset and its chronic complications was 0.640 and 0.754, respectively. PSP/reg is significantly up-regulated in T2DM patients, and PSP/reg levels are related to the duration of diabetes. Therefore, PSP/reg might be useful as a predictor of T2DM and disease progression

High Glucose Aggravates the Detrimental Effects of Pancreatic Stellate Cells on Beta-Cell Function

Background and Aims. We here assess the effects of PSCs on β-cell function and apoptosis in vivo and in vitro. Materials and Methods. PSCs were transplanted into Wistar and Goto-Kakizaki (GK) rats. Sixteen weeks after transplantation, β-cell function, apoptosis, and islet fibrosis were assessed. In vitro the effects of PSCs conditioned medium (PSCs-CM) and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endoplasmic reticulum stress (ER stress) associated CHOP expression. Results. PSCs transplantation exacerbated the impaired β-cell function in GK rats, but had no significant effects in Wistar rats. In vitro, PSCs-CM caused impaired INS-1 cell viability and insulin secretion and increased apoptosis, which were more pronounced in the presence of high glucose. Conclusion. Our study demonstrates that PSCs induce β-cell failure in vitro and in vivo

Pancreatic stone protein/regenerating protein (PSP/reg): a novel secreted protein up-regulated in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) has insulin resistance (IR) or reduced β-cell mass, partially due to an increased β-cell apoptosis rate. Pancreatic stone protein/regenerating protein (PSP/reg) is a secretory protein produced in the pancreas and up-regulated dramatically during pancreatic disease. Recent studies revealed that β-cells undergoing apoptosis induce PSP/reg expression in surviving neighboring cells. Further experiments demonstrated that PSP/reg was elevated during disease progression in type 1 diabetes mellitus (T1DM). However, the association between PSP/reg and T2DM patients is unknown. The aim of this pilot study was to investigate PSP/reg in different clinical stages of T2DM and evaluate its correlation with chronic complications of diabetes. A total of 1,121 participants (479 males, 642 females; age range 23-80years) were enrolled in this study. PSP/reg serum values were measured by a newly developed enzyme-linked immunosorbent assay (ELISA). We analyzed its correlation with clinical and biochemical parameters in subjects with T2DM at different clinical phases. Statistical analyses were conducted using SPSS 17.0 software. Correlations of PSP/reg and clinical parameters were performed using Spearman's rank correlation coefficient. Differences between groups were determined by Nemenyi test. PSP/reg was elevated in high-risk and impaired glucose regulation (IGR) patients (p<0.05). PSP/reg was significantly up-regulated in newly diagnosed T2DM patients and long-term diabetes patients with complications (p<0.001). PSP/reg levels correlated with the duration of diabetes (p<0.001). The area under the curve (AUC) for presence of diabetes-onset and its chronic complications was 0.640 and 0.754, respectively. PSP/reg is significantly up-regulated in T2DM patients, and PSP/reg levels are related to the duration of diabetes. Therefore, PSP/reg might be useful as a predictor of T2DM and disease progression

Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape

Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the STOML3+ cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants