Adipokine vaspin maintains angiogenesis and neurological function during cerebral ischemia-reperfusion via suppressing endoplasmic reticulum stress.

INTRODUCTION: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine. It has been reported that decreased serum vaspin levels are significantly associated with stroke severity and prognosis. PURPOSE: This article aims to explore the theoretical feasibility of vaspin supplementation for cerebral ischemia-reperfusion (I/R) injury. METHODS: The I/R mouse models were constructed by the middle cerebral artery occlusion (MCAO) method, and the effects of vaspin on cerebral infarction, neurological function, angiogenesis and endoplasmic reticulum (ER) stress were explored. To verify the mediation of ER stress in the regulation of vaspin, human brain microvascular endothelial cells (HBMECs) were subjected to ER stress agonist tunicamycin in vitro. The impacts of vaspin and tunicamycin on oxygen glucose deprivation/ recovery (OGD/R)-induced cell viability, apoptosis, and angiogenesis were examined. RESULTS: Vaspin inhibited blood-brain barrier breakdown and infarction occurred in the brain tissue of the I/R mice. Vaspin also enhanced cerebral neovascularization and reduced the apoptosis. Additional tunicamycin increased the apoptosis of HBMECs and inhibited angiogenesis, reversing the protective effect of vaspin on cells. CONCLUSION: Together, this study reveals that vaspin supplementation reduces cerebral infarction and works against neurological dysfunction. It maintains the survival and angiogenesis capacity of HBMECs by inhibiting ER stress.

Clinical and Microbiological Characteristics of Klebsiella pneumoniae Bloodstream Infection in a Chinese Hospital: Hypervirulent and Multiclonal.

Purpose: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging globally and can cause various infections. This study aimed to investigate the clinical and microbiological characteristics of bloodstream infection (BSI) caused by hvKP. Patients and Methods: The clinical data of hospitalized patients with K. pneumoniae BSI were retrospectively analyzed. The K. pneumoniae strains were collected and re-identified, and antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular serotypes and virulence genes were detected using polymerase chain reaction, and hvKP was defined as aerobactin positive. Molecular typing was done by multilocus sequence typing. The hvKP and classic K. pneumoniae (cKP) subgroups were compared. Results: Of the 66 nonrepetitive BSI K. pneumoniae strains included, 29 (43.9%) were hvKP. In these BSI hvKP strains, salmochelin and yersiniabactin accounted for 86.2% and 72.4%, respectively. The prevalence of rmpA, iroBCD cluster, ybtS, clbA, and allS was 89.7%, 86.2%, 72.4%, 51.7%, and 41.4%, respectively, which were all significantly different between the hvKP and cKP subgroups. Serotypes K1 and K2 were strongly associated with hypervirulence (P < 0.05). Nineteen sequence types were scattered in the 29 hvKP strains, and the most common was ST23 (24.1%). None of the hvKP strains were carbapenem resistant. Compared with cKP, hvKP was more capable of developing a liver abscess. However, the 30-day mortality rate was lower (13.8% vs 21.6%) in the hvKP subgroup than in the cKP subgroup. Conclusion: This study demonstrated a high proportion of hvKP in BSI K. pneumoniae, most of which were RmpA and siderophore producing, and of multiclonal origin.

Angiotensin-(1-7) protects against sepsis-associated left ventricular dysfunction induced by lipopolysaccharide.

Sepsis-induced myocardial dysfunction is a major cause of death. The present study explored whether angiotensin (Ang)-(1-7), an important biologically active peptide of the renin-angiotensin system, could improve cardiac dysfunction and attenuate inflammation and apoptosis. Experiments were carried out in mice and in neonatal rat cardiomyocytes (NRCMs) treated with lipopolysaccharide (LPS) or Ang-(1-7). Angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and Mas receptor (MasR) expressions were reduced in the mouse left ventricular and NRCM treated with LPS. Ang-(1-7) increased the ejection fraction and fractional shortening of left ventricular, which were reduced upon LPS injection in mice. Ang-(1-7) pre-treatment reversed LPS-induced decreases of α-myosin heavy chain (MHC) and ß-MHC, and increases of S100 calcium binding protein A8 (S100A8) and S100A9 in the mouse left ventricular. The LPS-induced increases of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the mouse left ventricular and NRCMs were inhibited by Ang-(1-7) administration. Ang-(1-7) treatment reversed the increases of cleaved-caspase 3, cleaved-caspase 8 and Bax, and the decrease of Bcl2 induced by LPS in the mouse left ventricular and NRCMs. The increases of MAPKs pathway induced by LPS in NRCMs were inhibited by Ang-(1-7). These results indicate that Ang-(1-7) protects against sepsis-associated left ventricular dysfunction induced by LPS, and increases cardiac contractility via attenuating inflammation and apoptosis.

Association between ACR1 gene product expression and cardiomyopathy in children.

Cardiomyopathy is a heterogeneous heart disease. Although morbidity of pediatric cardiomyopathy has been on the increase, effective treatments have not been identified. The aim of the study was to examine the expression of ACR1 gene products in association with cardiomyopathy in children. In total, 73 patients and 76 healthy subjects were enrolled in the study, from April, 2013 to April, 2015. The relative expression of ACR1 mRNA and protein were quantified in all cases, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), ELISA and western blot analysis. Immunohistochemistry was used to stain cardiac tissue samples to reveal differences between the patients and the control group. The results showed that the level of ACR1 mRNA by RT-qPCR was not different between the two study groups. However, ELISA and western blot analysis showed a significant difference, with patients expressing lower levels of ACR1. Additionally, immunohistochemistry revealed the levels of ACR1 were reduced in patients as the time course of disease increased. Thus, there is an association between the inhibition of ACR1 expression and the development of the disease. These findings are useful in the elucidation of the pathogenesis of pediatric cardiomyopathy, a severe disease with few effective treatment options available.

Role of the PTEN/PI3K/VEGF pathway in the development of Kawasaki disease.

Kawasaki disease (KD) is a disease of unknown etiology and the leading cause of childhood acquired heart disease. In this study, the significance of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/vascular endothelial growth factor (VEGF) pathway in the development of KD was investigated in a rabbit model. Rabbits were divided into the control group, which received saline injection, and the experimental group, which was treated with bovine serum albumin to induce arthritis and KD. After 1, 7 and 30 days the animals were sacrificed, and the white blood cell count, serum VEGF, and serum creatine kinase (CK) levels were measured. The coronary artery was examined histologically as well as immunohistochemically for PTEN and PI3K. After the induction of arthritis, coronary artery of the rabbits showed endothelial cell swelling, osteoporosis, necrosis and inflammatory cell infiltration. PTEN expression in these rabbits increased with the increasing number of modeling days. The expression of PI3K showed a decreasing trend. The number of white blood cells in rabbits after KD modeling were significantly higher than those in the controls. One day and 7 days after modeling the serum VEGF level in KD rabbits was significantly higher than that in the control group after 1 and 7 days followed by a decrease by 30 days. There was no significant change in serum CK on the day after the modeling, and the serum CK level was significantly higher after 7 and 30 days. In conclusion, the expression of PTEN/PI3K was altered at different stages of KD. PTEN expression gradually increased with the disease progression, while the expression of PI3K gradually decreased. Serum markers indicated that the PTEN/PI3K/VEGF signaling pathway is important in the vascular injury in KD.

Therapeutic effect comparison of hepatocyte-like cells and bone marrow mesenchymal stem cells in acute liver failure of rats.

GOALS: To evaluate the therapeutic efficacy of rat bone marrow mesenchymal stem cells (BMSCs) induced into hepatocyte-like cells and of un-induced BMSCs in acute liver failure rats. METHODS: BMSCs in highly homogenous passage 3 were cultured using the whole bone marrow adherent culture method. Hepatic-related characters were confirmed with morphology, RT-PCR analysis, glycogen staining and albumin (ALB) immunofluorescence assay. Carbon tetrachloride (CCl4) was injected intraperitoneally to establish an acute rat liver failure model. Hepatocyte-like cells or un-induced BMSCs were respectively injected into the models to examine rats' appearance, liver function assay and liver tissue pathology. RESULTS: Hepatocyte-like morphology, higher expression of cytokeratin 18 (CK18) mRNA and ALB protein, and glycogen accumulation were confirmed in the induced BMSCs. The transplanted DAPI-labeled BMSCs were localized in the liver tissue 3-14 days after transplantation. The levels of liver function indicators (AST, ALT, ALP, and TBIL) from transplanted rats were significant decreased and pathology was improved, indicating the recovery of liver function. However, the differences were statistically insignificant. CONCLUSION: Both hepatocyte-like cells and un-induced BMSCs had a similarly positively therapeutic efficacy on liver regeneration in rat liver failure model.

Polyphenols in Regulation of Redox Signaling and Inflammation During Cardiovascular Diseases.

Cardiovascular diseases remain one of the major health problems worldwide. The worldwide research against cardiovascular diseases as well as genome wide association studies were successful in indentifying the loci associated with this prominent life-threatening disease but still a substantial amount of casualty remains unexplained. Over the last decade, the thorough understanding of molecular and biochemical mechanisms of cardiac disorders lead to the knowledge of various mechanisms of action of polyphenols to target inflammation during cardiac disorders. The present review article summarizes major mechanisms of polyphenols against cardiovascular diseases.

Bone marrow-derived mesenchymal stem cells promote hepatic regeneration after partial hepatectomy in rats.

OBJECTIVES: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. METHODS: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4',6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2'-deoxyuridine. RESULTS: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4',6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2'-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. CONCLUSION: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.

[Autologous transplantation of bone marrow stem cells versus peripheral blood stem cells for treatment of decompensate liver cirrhosis: a comparative study of 30 cases].

Not Abstract.