Tuning Fe3O4 for sustainable cathodic heterogeneous electro-Fenton catalysis by acetylated chitosan.

Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.

Sodium oxamate reduces lactate production to improve the glucose homeostasis of Micropterus salmoides fed high-carbohydrate diets.

The study was performed to evaluate the effects of the reduced lactate production by sodium oxamate (SO) on growth performance, lactate and glucose and lipid metabolism, and glucose tolerance of Micropterus salmoides fed high-carbohydrate (CHO) diets. In in vitro study, primary hepatocytes were incubated for 48 h in a control medium (5.5 mM glucose), a high-glucose medium (25 mM glucose, HG), or a SO-containing high-glucose medium (25 mM glucose + 50 mM SO, HG-SO). Results indicated lactate and triglyceride (TG) levels, and lactate dehydrogenase a (LDH-a) expression in the HG-SO group were remarkably lower than those of the HG group. In in vivo study, M. salmoides (5.23 ± 0.03 g) were fed four diets containing a control diet (10% CHO, C) and three SO contents [0 (HC), 100 (HC-SO1), and 200 (HC-SO2) mg·kg-1, respectively] of high-CHO diets (20% CHO) for 11 wk. High-CHO diets significantly reduced weight gain rate (WGR), specific growth rate (SGR), p-AMPK-to-t-AMPK ratio, and expression of insulin receptor substrate 1 (IRS1), insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), fructose-1,6-biphosphatase (FBPase), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase 1α (CPT1α) compared with the C group, whereas the opposite was true for plasma levels of glucose, TG, lactate, tissue glycogen, and lipid contents, and expression of LDH-a, monocarboxylate transporter 1 and 4 (MCT1 and MCT4), insulin, glucokinase (GK), pyruvate dehydrogenase E1 subunit (PDH), sterol-regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). The HC-SO2 diets remarkably increased WGR, SGR, p-AMPK-to-t-AMPK ratio, and expression of IRS1, IGF-I, IGF-IR, GK, PDHα, PDHß, FAS, acetyl-CoA carboxylase 1 (ACC1), PPARα, and CPT1α compared with the HC group. Besides, HC-SO2 diets also enhanced glucose tolerance of fish after a glucose loading. Overall, the reduced lactate production by SO benefits growth performance and glucose homeostasis of high-CHO-fed M. salmoides through the enhancement of glycolysis, lipogenesis, and fatty acid ß-oxidation coupled with the suppression of glycogenesis and gluconeogenesis.

Identification of novel rare copy number variants associated with sporadic tetralogy of Fallot and clinical implications.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.

Functional significance of novel variants of the MEF2C gene promoter in congenital ventricular septal defects.

Ventricular septal defect (VSD) is the most common congenital heart disease. Although the coding region of MEF2C is highly relevant to cardiac malformations, the role of MEF2C gene promoter variants in VSD patients has not been genetically investigated. We investigated the role of MEF2C gene promoter variants in 400 Han Chinese subjects (200 patients with isolated and sporadic VSD and 200 healthy controls). The promoter region of the MEF2C gene was sequenced that identified 10 variants. Expression vectors encompassing the variants and the firefly luciferase reporter gene plasmid (pGL3-basic) were constructed and subsequently transfected into HEK-293 cells. The luciferase activities were measured by Dual-luciferase reporter assay system. MEF2C gene promoter transcriptional activity was significantly reduced in 4 of the 10 variants in HEK-293 cells (P < 0.05). In addition, the JASPAR database was used to perform bioinformatics analysis, which showed that these variants disrupt the putative binding sites of transcription factors and affected the expression of MEF2C protein. This study for the first time identified the variants in the promoter of the MEF2C gene in Han Chinese population and revealed the role of these variants in the formation of VSD.

Effect of CPB glucose levels on inflammatory response after pediatric cardiac surgery.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a common complication after cardiac surgery. There are no definite optimal glycemic threshold for pediatric patients receiving open-heart surgery with CPB. The study aimed to investigate the optimal cardiopulmonary bypass (CPB) glucose in patients undergoing cardiac surgery. METHODS: We enrolled children with congenital heart disease who underwent surgical repair between June 2012 and December 2020. We included only patients who underwent cardiac surgery with CPB. The primary outcome was severe SIRS. A two-piece-wise regression model was applied to examine threshold effect of CPB glucose on severe SIRS. RESULTS: A total of 7350 patients were enrolled in the present study, of whom 3895 (52.99%) are female. After potential confounders were adjusted, non-linear relationship was detected between CPB glucose and severe SIRS, whose turning point was 8.1. With CPB glucose < 8.1 mmol/L, the estimated dose-response curve was consistent with a horizontal line. However, the prevalence of severe SIRS increased with increasing glucose up to the turning point (Glucose > 8.1 mmol/L); the odds ratio (OR) of the Glucose was 1.35 (95% CI 1.21, 1.50). CONCLUSIONS: The present study indicates the association of CPB glucose with inflammatory response after pediatric cardiac surgery. The patients might have the best outcomes with the optimal CPB glucose no more than 8.1 mmol/L.

Risk factors for development of acute renal failure in 5077 coronary artery bypass grafting patients in the current era.

BACKGROUND: Acute renal failure (ARF) is one of the major complications after coronary artery bypass grafting (CABG) surgery. The risk factors are changing along with the technical evolution. The aim of this study was to identify the risk factors for ARF requiring dialysis after CABG surgery in the current era. METHODS: Between April 2012 and November 2019, 5077 consecutive patients who underwent CABG were analyzed retrospectively. The patients were divided into ARF group and non-ARF group according to whether ARF occurred and dialysis was required after operation. Univariate analysis was performed to find possible factors associated with ARF. Any variables that had trends to be associated with ARF were included in stepwise multiple logistic regression analysis. RESULTS: Of the 5077 patients who underwent CABG, 53 (1.04%) developed ARF requiring dialysis whereas 5024 (98.96%) were in non-ARF group. Cardiopulmonary bypass (CPB) time (odds ratio [OR], 1.009; 95% confidence interval [CI], 1.003-1.016; p = .006), insertion of intra-aortic balloon pump (IABP; OR, 19.294; 95% CI, 5.49-67.808; p = .000), and low ejection fraction (EF; OR, 0.943; 95% CI, 0.894-0.994; p = .030) were independent risk factors for development of ARF requiring dialysis in patients undergoing CABG surgery. CONCLUSION: Our study identified prolonged CPB time, insertion of IABP, and low EF as independent risk factors for developing ARF requiring dialysis after CABG. The results suggest that shortening of CPB time and protection of cardiac function are important factors to prevent ARF and that special care should be taken to protect the renal function when the patient need insertion of IABP.

Identification of variants of ISL1 gene promoter and cellular functions in isolated ventricular septal defects.

Ventricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Studies have documented that ISL1 has a crucial impact on cardiac growth, but the role of variants in the ISL1 gene promoter in patients with VSD has not been explored. In 400 subjects (200 patients with isolated and sporadic VSDs: 200 healthy controls), we investigated the ISL1 gene promoter variant and performed cellular functional experiments by using the dual-luciferase reporter assay to verify the impact on gene expression. In the ISL1 promoter, five variants were found only in patients with VSD by sequencing. Cellular functional experiments demonstrated that three variants decreased the transcriptional activity of the ISL1 promoter (P < 0.05). Further analysis with the online JASPAR database demonstrated that a cluster of putative binding sites for transcription factors may be altered by these variants, possibly resulting in change of ISL1 protein expression and VSD formation. Our study has, for the first time, identified novel variants in the ISL1 gene promoter region in the Han Chinese patients with isolated and sporadic VSD. In addition, the cellular functional experiments, electrophoretic mobility shift assay, and bioinformatic analysis have demonstrated that these variants significantly alter the expression of the ISL1 gene and affect the binding of transcription factors, likely resulting in VSD. Therefore, this study may provide new insights into the role of the gene promoter region for a better understanding of genetic basis of the formation of CHDs and may promote further investigations on mechanism of the formation of CHDs.

Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects.

Ventricular septal defect (VSD) is the most common congenital heart defect. Previous studies have reported genetic variations in the encoding region of CITED2 highly associated with cardiac malformation but the role of CITED2 gene promoter variations in VSD patients has not yet been explored. We investigated the variation of CITED2 gene promoter and its impacts on gene promoter activity in the DNA of paediatric VSD patients. A total of seven variations were identified by Sanger sequencing in the CITED2 gene promoter region in 400 subjects, including 200 isolated and sporadic VSD patients and 200 healthy controls. Using dual-luciferase reporter assay, we found four of the 7 variations identified significantly decreased the transcriptional activity of the CITED2 gene promoter in HEK-293 cells (P < .05). Further, a bioinformatic analysis with the JASPAR databases was performed and a cluster of putative binding sites for transcription factors was created or disrupted by these variations, leading to low expression of CITED2 protein and development of VSD. Our study for the first time demonstrates genetic variations in the CITED2 gene promoter in the Han Chinese population and the role of these variations in the development of VSD, providing new insights into the aetiology of CHD.

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest.

Neurological dysfunction commonly occurs after cardiac surgery with deep hypothermic circulatory arrest (DHCA). The mechanisms underlying DHCA-associated brain injury remain poorly understood. This study determined the changes in expression profiles of circular RNAs (circRNAs) in the hippocampus in rats that underwent DHCA, with an attempt to explore the potential role of circRNAs in the brain injury associated with DHCA. Adult male Sprague Dawley rats were subjected to cardiopulmonary bypass with DHCA. Brain injury was evaluated by neurological severity scores and histological as well as transmission electron microscope examinations. The expression profiles of circRNAs in the hippocampal tissues were screened by microarray. Quantitative real-time PCR (RT-qPCR) was used to validate the reliability of the microarray results. Bioinformatic algorithms were applied to construct a competing endogenous RNA (ceRNA) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential biological roles of the circRNAs. Out of 14 145 circRNAs screened, 56 were differentially expressed in the hippocampus between the DHCA and sham-operated rats, including 30 upregulated and 26 downregulated circRNAs. The expression changes of six selected circRNAs (upregulated: rno_circRNA_011190, rno_circRNA_012988, rno_circRNA_000544; downregulated: rno_circRNA_010393, rno_circRNA_012043, rno_circRNA_015149) were further confirmed by RT-qPCR. Bioinformatics analysis showed the enrichment of these confirmed circRNAs and their potential target mRNAs in several KEGG pathways including histidine metabolism, adipocytokine signaling, and cAMP signaling. By revealing the change expression profiles of circRNAs in the brain after DHCA, this study indicates possible involvements of these dysregulated circRNAs in brain injury and suggests a potential of targeting circRNAs for prevention and treatment of neurological dysfunction associated with DHCA.

Loop isolation-based uploading preconditioning to protect heart from damage: a proof-of-concept study.

BACKGROUND: Little is known on the role of indirect clamp releasing in coronary artery bypass grafting (CABG). Loop isolation-based uploading preconditioning (LiuPhD) was modified to protect the heart from damage and the question of whether this can attenuate reperfusion injury after global myocardial ischemia was examined. METHODS: A post-hoc comparative analysis was conducted of a prospective single-arm trial on the use of the LiuPhD strategy for 60 multivessel-disease patients undergoing isolated first-time elective on-pump CABG versus 1:1 propensity score-matched patients from the historical database of the same center. RESULTS: A total of 120 matched patients had a median age of 62.0 (interquartile range [IQR] 55.8-69.0) years, 27 (22.5%) women, 35 (29.2%) with left main disease, and median follow-up of 18.5 (10.9-35.4) months. The LiuPhD group had shorter post-bypass times than conventional controls (10 [6-13] vs 14 [10-19] mins; p = 0.003). The LiuPhD group had similar needs in terms of composite cardiac-specific interventions (38/60 vs 44/60; p = 0.29). At follow-up of safety, the risk for composite major adverse cardiac and cerebrovascular events was similar between groups (event-free survival: 82.3% vs 73.8%; hazard ratio 1.00 [0.39, 2.54], p log-rank test = 0.99). CONCLUSION: The LiuPhD strategy is associated with short post-bypass times, comparable risk of myocardial injury, and similar safety compared with conventional direct clamp releasing.

Cathode-Introduced Atomic H* for Fe(II)-Complex Regeneration to Effective Electro-Fenton Process at a Natural pH.

Promotion of iron solubility using ligands is the preliminary step in the homogeneous electro-Fenton (EF) process at a mild pH, but the chelate efficiencies of most organic ligands are unsatisfactory, resulting in insufficient Fe(II) availability. In this study, atomic H* was, for the first time, introduced to the EF process to accelerate the regeneration of the Fe(II)-complex at a mild pH using a Ni-deposited carbon felt (Ni-CF) cathode. The introduction of atomic H* significantly elevated total organic carbon (TOC) abatement of ciprofloxacin (CIP) from 42% (CF) to 81% (Ni-CF) at a natural pH. In the presence of humic acids (HAs), atomic H* introduced via Ni-CF enhanced the CIP degradation rate to 10 times that of the CF at a mild pH. The electron spin resonance (ESR), density functional theory (DFT) calculations, electrochemical characterization, and in situ electrochemical Raman study clearly demonstrated that the atomic H* generated from the Ni-CF cathode was highly efficient at reducing Fe(III)-complexes at a natural pH. Additionally, the Ni-CF could generate atomic H* without significant nickel leaching. Thus, the atomic H* could continuously facilitate iron cycling and, consequently, enhance pollutant mineralization via the homogeneous EF process at a mild pH in an environmentally friendly manner.

Tetramethylpyrazine suppresses angiotensin II-induced soluble epoxide hydrolase expression in coronary endothelium via anti-ER stress mechanism.

Activation of soluble epoxide hydrolase (sEH) is associated with endothelial dysfunction in hypertension, though the underlying mechanisms are inadequately understood and the role of endoplasmic reticulum (ER) stress is yet to be studied in detail. Tetramethylpyrazine (TMP), a major bioactive ingredient of Chinese herb Chuanxiong, is well-known for its cardiovascular benefits. Nevertheless, whether TMP may protect vascular endothelium from ER stress and whether regulation of sEH is involved remain unknown. This study aimed at investigating the role of ER stress in angiotensin-II (Ang-II)-induced sEH dysregulation and elucidating the significance of ER stress regulation in the vasoprotective effect of TMP. Porcine primary coronary artery endothelial cells (PCECs) were used for western blot, ELISA, and reverse-transcription PCR analysis. Porcine coronary arteries were assessed in a myograph for endothelial dilator function. Ang-II induced expression of ER stress molecules in PCECs meanwhile enhanced sEH expression and decreased 11,12-EET. Exposure of PCECs to the chemical ER stress inducer tunicamycin also increased sEH expression. Inhibition of ER stress suppressed sEH upregulation, resulting in an increase of 11,12-EET. The impairment of endothelium-dependent vasorelaxation induced by Ang-II or tunicamycin was ameliorated by inhibitors of ER stress or sEH. TMP showed comparable inhibitory effect to ER stress inhibitors on the expression of ER stress molecules, the dysregulation of sEH/EET, and the impairment of endothelial dilator function. We demonstrated that ER stress mediates Ang-II-induced sEH upregulation in coronary endothelium. TMP has potent anti-ER stress capacity through which TMP normalizes sEH expression and confers protective effect against Ang-II on endothelial function of coronary arteries.

Accuracy of Multi-Slice Spiral Computed Tomography for Preoperative Tumor Node Metastasis (TNM) Staging of Colorectal Carcinoma.

BACKGROUND With the advances in imaging technologies, multi-slice spiral computed tomography (MSCT) has demonstrated superiority in the diagnosis and staging of colorectal carcinoma. In the current study, preoperative TNM staging of colorectal carcinoma by using MSCT was conducted and compared with the corresponding postoperative pathological examination findings, in order to evaluate the accuracy of preoperative MSCT for TNM staging. MATERIAL AND METHODS Combinations of biphasic or triphasic enhanced-phase MSCT scans were obtained for 76 patients with colorectal carcinoma, and the TNM stage was determined based on imaging reconstruction from various angles and perspectives to display the size, location, and affected range of tumors. The preoperative TNM stage was compared with the postoperative pathological stage, and the consistency between the 2 methods was tested by the k test using SPSS 17.0 software. RESULTS Among the different combinations of enhanced-phase MSCT scanning, triphasic MSCT imaging, comprising the arterial, portal venous, and delayed phases, showed the highest accuracy rates, at 81.6% (62/76), 82.89% (63/76), and 96.1% (73/76) for T, N, and M staging, respectively, with k values of 0.72, 0.65, and 0.56, respectively, indicating consistency with the postoperative pathological staging. CONCLUSIONS Combined MSCT scanning comprising the arterial phase, portal venous phase, and delayed phase showed satisfying consistency with the postoperative pathological analysis results for TNM staging of colorectal carcinoma. Thus, MSCT is an important clinical value for improving the accuracy of TNM staging and for planning the appropriate colorectal cancer treatment.

Downregulation of p38 MAPK involved in inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin.

Curcumin, as a main pharmacological component in the traditional Chinese medicine-turmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein (LDL) and different concentrations of curcumin (0, 6.25, 12.5, 25.0 µmol/L) or p38 MAPK inhibitor, SB203580 (10 µmol/L). Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species (ROS) generation was increased and p38 MAPK was activated significantly (P<0.05). When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 µmol/L, LDL-induced proliferation of mesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated (P<0.05). In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS production and p38 MAPK.

Inhibition of the Activating Transcription Factor 6 Branch of Endoplasmic Reticulum Stress Ameliorates Brain Injury after Deep Hypothermic Circulatory Arrest.

Neurological dysfunction is a common complication of deep hypothermic circulatory arrest (DHCA). Endoplasmic reticulum (ER) stress plays a role in neuronal ischemia-reperfusion injury; however, it is unknown whether it contributes to DHCA-induced brain injury. Here, we aimed to investigate the role of ER stress in a rat DHCA model and cell hypothermic oxygen-glucose deprivation reoxygenation (OGD/R) model. ER stress and apoptosis-related protein expression were identified using Western blot analysis. Cell counting assay-8 and flow cytometry were used to determine cell viability and apoptosis, respectively. Brain injury was evaluated using modified neurological severity scores, whereas brain injury markers were detected through histological examinations and immunoassays. We observed significant ER stress molecule upregulation in the DHCA rat hippocampus and in hypothermic OGD/R PC-12 cells. In vivo and in vitro experiments showed that ER stress or activating transcription factor 6 (ATF6) inhibition alleviated rat DHCA-induced brain injury, increased cell viability, and decreased apoptosis accompanied by C/EBP homologous protein (CHOP). ER stress is involved in DHCA-induced brain injury, and the inhibition of the ATF6 branch of ER stress may ameliorate this injury by inhibiting CHOP-mediated apoptosis. This study establishes a scientific foundation for identifying new therapeutic targets for perioperative brain protection in clinical DHCA.

Cannabinoid Receptor Agonist WIN55, 212-2 Attenuates Injury in the Hippocampus of Rats after Deep Hypothermic Circulatory Arrest.

OBJECTIVES: Postoperative neurological deficits remain a challenge in cardiac surgery employing deep hypothermic circulatory arrest (DHCA). This study aimed to investigate the effect of WIN55, 212-2, a cannabinoid agonist, on brain injury in a rat model of DHCA. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into three groups: a control group (which underwent cardiopulmonary bypass (CPB) only), a DHCA group (CPB with DHCA), and a WIN group (WIN55, 212-2 pretreatment before CPB with DHCA). Histopathological changes in the brain were evaluated by hematoxylin-eosin staining. Plasma levels of superoxide dismutase (SOD) and proinflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-a) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression of SOD in the hippocampus was detected by Western blot and immunofluorescence staining. Levels of apoptotic-related protein caspase-3 and type 1 cannabinoid receptor (CB1R) in the hippocampus were evaluated by Western blot. RESULTS: WIN55, 212-2 administration attenuated histopathological injury of the hippocampus in rats undergoing DHCA, associated with lowered levels of IL-1ß, IL-6, and TNF-α (p < 0.05, p < 0.001, and p < 0.01, vs. DHCA, respectively) and an increased level of SOD (p < 0.05 vs. DHCA). WIN55, 212-2 treatment also increased the content of SOD in the hippocampus. The protein expression of caspase-3 was downregulated and the expression of CB1R was upregulated in the hippocampus by WIN55, 212-2. CONCLUSIONS: the administration of WIN55, 212-2 alleviates hippocampal injury induced by DHCA in rats by regulating intrinsic inflammatory and oxidative stress responses through a CB1R-dependent mechanism.

Mechanisms of the protective effects of BMSCs promoted by TMDR with heparinized bFGF-incorporated stent in pig model of acute myocardial ischemia.

This study investigates the mechanism by which transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor incorporated degradable stent implantation (TMDRSI) enhanced effects of bone marrow mesenchymal stem cells (BMSCs) transplantation against acute ischemic myocardial injury. After the mid-third of left anterior descending artery was ligated, miniswine were divided into none-treatment group (control, n = 6), BMSCs implantation group (C, n = 6), TMDRSI group (TS, n = 6) and TMDRSI and BMSCs implantation group (TSC, n = 6). Two channels of 3.5 mm diameter were established by a self-made drill in the ischemic region, into which a stent was implanted for the TS and TSC groups. Autologous BMSCs were transplanted into the ischemic region in C group or around the channels in TSC group. Expression of von Willebrand factor, vascular endothelial growth factor, interleukin-1ß, transforming growth factor-ß(3) , cell proliferation and apoptosis, histological and morphological analyses, myocardial remodelling and cardiac function were evaluated at different time-points. Six weeks after the operation, the above indices were significantly improved in TSC group compared with others (P < 0.05), though C and TS groups also showed better results than the control group (P < 0.05). The new method was shown to have activated paracrine pathway of transplanted BMSCs, increased survival and differentiation of such cells, and enhanced effects of BMSCs transplantation on myocardial remodelling, which may provide a new strategy for cell therapies against acute ischemic myocardial injury.

Reversal by growth hormone of homocysteine-induced epithelial-to-mesenchymal transition through membrane raft-redox signaling in podocytes.

Epithelial-to-Mesenchymal Transition (EMT) is an important pathogenic mechanism mediating glomerular injury or sclerosis in a variety of renal and systemic diseases such as hyperhomocysteinemia (hHcys). The present study was designed to test whether Hcys-induced EMT in podocytes is reversed by growth hormone (GH), a hormone regulating cell differentiation and growth and to explore the cellular and molecular mechanism mediating its action. It was found that Hcys induced significant EMT in podocytes, as shown by marked decreases in slit diaphragm-associated protein P-cadherin and zonula occludens-1 as epithelial markers and by dramatic increases in the expression of mesenchymal markers, fibroblast specific protein-1 and α-smooth muscle actin, which were detected by all examinations via immunocytochemistry, real time RT-PCR and Western blot analysis. When podocytes were treated with GH at 25 ng/mL, however, Hcys failed to induce podocyte EMT. Using electromagnetic spin resonance spectrometry, Hcys-induced superoxide (O(2).(-)) production via NADPH oxidase was found to be significantly inhibited by GH (66%). Functionally, GH was shown to substantially inhibit Hcys-induced increases in the permeability of podocyte monolayers and to block the decrease in podocin expression in these cells. In addition, NADPH oxidase subunit, gp91(phox) and GH receptors aggregated in membrane raft clusters, which produced O(2).(-) in response to Hcys and could be blocked by GH, membrane raft disruptors filipin and MCD or NADPH oxidase inhibitor, apocynin. It is concluded that Hcys-induced podocyte EMT is associated with transmembrane membrane raft-redox signaling and that GH reverses this Hcys-induced EMT protecting podocytes from functional disturbance.

[Differences in nitric oxide release and endothelium-derived hyperpolarizing factor-mediated hyperpolarization between human radial artery and saphenous vein].

OBJECTIVE: To compare the differences in nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization between human radial artery (RA) and saphenous vein (SV) through direct measurement of NO and membrane potential. METHODS: RA (n = 8), SV (n = 23), and surgical prepared SV (PV, n = 9, dilatation with normal saline solution at a pressure of 100 - 600 mmHg, 1 mmHg = 0.133 kPa) segments (5 mm long) taken from patients undergoing coronary artery bypass grafting were placed in an organ chamber. The NO-sensitive electrode and intracellular glass microelectrode was used to directly measure the NO release and the membrane potential changes in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with NG-nitro-L-arginine, indomethacin, and oxyhemoglobin. RESULTS: The basal release of NO in RA [(11.9 ± 1.8) nmol/L] was significantly greater than that in SV [(9.9 ± 2.8) nmol/L, P = 0.041]. BK-induced NO release in RA was lower than that in SV [for BK 10(-7) mol/L: (25.8 ± 3.6) nmol/L vs. (43.7 ± 8.2) nmol/L, P = 0.006]. Both basal and ACh- or BK-induced NO release in PV were significantly reduced [basal release: PV (3.4 ± 1.4) nmol/L; P = 0.006 vs. RA; P = 0.002 vs. SV; stimulated release: for ACh 10(-5) mol/L: PV (4.8 ± 3.2) nmol/L; vs. RA (28.6 ± 7.9) nmol/L, P = 0.005; vs. SV (27.4 ± 3.7) nmol/L, P = 0.003; for BK 10(-7) mol/L: PV (7.0 ± 3.6) nmol/L; vs. RA (25.8 ± 3.6) nmol/L, P = 0.016; vs. SV (43.7 ± 8.2) nmol/L, P = 0.004]. EDHF-mediated hyperpolarization was greater in RA than that in SV [ACh 10(-5) mol/L: (-9.7 ± 1.9) mV vs. (-4.5 ± 1.1) mV, n = 17, P = 0.002]. CONCLUSIONS: RA is superior to SV in terms of NO basal release and EDHF-mediated endothelial function. Surgical preparation and pressure dilatation may severely impair the NO-mediated endothelial function of SV, which may contribute to the poor long-term patency of SV coronary graft.

[Coronary artery lumen diameter and bifurcation angle derived from CT coronary angiographic image in healthy people].

OBJECTIVE: To observe the coronary vessel lumen diameter and bifurcation angle in subjects with normal CT coronary angiography (CTCA) imaging. METHODS: 64-row CT coronary angiography imaging from 526 adult people with excellent image quality and normal vascular image were analyzed in this study. The lumen diameter from the origin to distal with 2 mm lumen of left main coronary artery (LM), anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA) was measured at 1 cm interval in CPR image. The vascular tapered ratio was calculated. The bifurcation angle in the diagonal branch, obtuse marginal branch, posterior descending branch, acute marginal branch as well as the origin diameter was also measured in VR image. RESULTS: The LAD average length was 13 cm and lumen diameter was 3.92 mm at origin and 2.10 mm at distal. The average decremented ratio of LAD was 7.7% (male 7.0%, female 8.4%). The maximal decremented ratio 8.0% - 10.0% occurred at 3 - 5 cm apart from the origin of LAD. The LCX average length was 13 cm and lumen diameter was 3.57 mm at origin and 2.10 mm at distal. The average decremented ratio of LCX was 9.7% (male 9.6%, female 9.7%). Lumen decremented ratio was less than 3.0% between origin and proximal 3 cm and 8.3% - 10.7% in the rest portion of the LCX. The RCA average length was 18 cm and lumen diameter was 3.97 mm at origin and 2.15 mm at distal. The average decremented ratio of RCA was 5.1% (male 4.9%, female 5.3%). The decremented ratio of RCR was less than 4.0% between origin and proximal 10 cm and 6.1% - 15.2% in the rest portion. The bifurcation angle was 50, 55, 66 and 76 degree for LAD with diagonal branch, LCX with obtuse marginal branch, RCA with posterior descending branch and RCA with obtuse marginal branch respectively. CONCLUSION: Coronary artery length, lumen diameter and decremented ratio as well as bifurcation angel could be identified in 64 row CTCA image in vivo. This information could help us to understand the in vivo coronary artery anatomy.