Changes and Influencing Factors of Urinary Phosphorus Excretion in Patients with Different Stages of Chronic Kidney Disease.

BACKGROUND: The aim of the study was to explore the changes and the possible influencing factors of phosphorus excretion in chronic kidney disease (CKD) patients. METHODS: A database with 204 patients who met the CKD diagnostic criteria was established. Clinical data, including 24-hour urine phosphorus excretion (24-hour UPE), were collected. The demographic and clinical characteristics of CKD patients in different stages and the changes in serum phosphorus (P) and 24-hour UPE with renal function were studied. After exploring the factors influencing 24-hour UPE by multiple linear regression analysis, the effects of gender on 24-hour UPE was assessed. RESULTS: Among 204 patients, there were significant differences in serum calcium (Ca), P, 24-hour UPE, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D [25(OH)-VD] among different CKD stages. Twenty-four-hour UPE fluctuated greatly, but serum P was relatively stable, which was > 1.46 mmol/L at an estimated glomerular filtration rate (eGFR) < 10 mL/minute/1.73 m2. Male gender (ß = 3.42, p < 0.00) and eGFR (ß = 0.06, p < 0.00) were related to 24-hour UPE, while age, body weight, albumin (ALB), iPTH, and serum P were not related to 24-hour UPE according to regression analysis. There were significant differences in 24-hour UPE and serum P between males and females. CONCLUSIONS: Urinary phosphorus excretion decreased with decreasing renal function in CKD patients. Urinary phosphorus excretion might be affected by eGFR and gender.

The effects of glucose-free and glucose-containing dialysate during dialysis in MHD patients: a prospective cross-over study.

OBJECTIVE: To investigate the effects of glucose-free and glucose-containing dialysates during dialysis in maintenance hemodialysis (MHD) patients by the prospective cross-over study, and detect glucose control methods in MHD patients. METHODS: A total of 66 MHD 18-75 years old patients in our hospital from Nov. 2019 to Mar. 2020 were recruited. All patients underwent HD with 4 hours per time, three times per week. Glucose-free dialysate (glucose-free group) and then 5.55 mmol/L glucose-containing dialysate (glucose-5.55 group) were used alternately in dialysis. The demographics and parameters of pre- and post-dialysis were recorded. RESULTS: A total of 60 patients were analyzed, and 28 patients among them had type 2 diabetes. Serum glucose pre and post dialysis were 8.64 ± 4.18 mmol/L versus 5.74 ± 1.82 mmol/L (p < 0.01) in glucose-free dialysate, and 9.31 ± 4.89 mmol/L versus 7.80 ± 2.59 mmol/L (p < 0.01) in glucose-5.55 dialysate. The post-dialysis blood glucose of glucose-free group was lower than glucose-5.55 group (5.74 ± 1.82 vs 7.80 ± 2.59, p < 0.01). About 18 (30.00%) patients in glucose-free group and 1 patient (1.67%) in glucose-5.55 group whose blood glucose was lower than 4.44 mmol/L (p < 0.01). About 29 patients (48.33%) in glucose-free group and 17 patients (28.33%; p = 0.02) in glucose-5.55 group have hunger feeling. Serum sodium level in the glucose-free group was higher than that in Glucose-5.55 group (137.92 ± 1.64 vs 136.70 ± 1.64, p < 0.01). Post-dialysis blood glucose had no significant differences between patients not using diabetes-related medication (13 patients) and patients using diabetes-related medication (15 patients) in glucose-free group (7.13 ± 1.78 mmol/L vs 6.08 ± 2.84 mmol/L, p = 0.23) and glucose-5.55 group (9.22 ± 2.59 mmol/L vs 9.35 ± 2.88 mmol/L, p = 0.90). CONCLUSIONS: Glucose-free and glucose-5.55 dialysate both decrease the blood glucose post-dialysis. Dialysates containing 5.55 mmol/L glucose can reduce the incidence of hypoglycemia and lower serum sodium, but have no effect on blood pressure during dialysis. Stopping insulin and oral anti-diabetic drugs once before dialysis may not affect the control of blood glucose.

Prevalence and influencing factors of vitamin D deficiency in chronic kidney disease: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Very few studies have investigated vitamin D deficiency of Chinese chronic kidney disease (CKD) patients. Our main aims were to measure 25(OH)D levels and to explore the possible correlated factors contributing to vitamin D deficiency. MATERIALS AND METHODS: 207 patients who came from north China and were not receiving vitamin D supplementation were included in this study from February 2013 to April 2015. We collected blood samples to determine levels of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), serum phosphate (P) and calcium (Ca), intact parathyroid hormone (iPTH), albumin (ALB), as well as urinary protein within 24 hours (24hUPr). Total 25(OH)D was measured via electrochemiluminescence immunoassay. Vitamin D deficiency should be defined as a 25(OH)D < 15 ng/mL. RESULTS: Of the 207 patients, only 20.3% had a circulating 25(OH)D level > 15 ng/mL. The concentrations of 25(OH)D were 11.73 ± 6.75 ng/mL, 10.44 ± 6.03 ng/mL, 10.05 ± 5.57 ng/mL, 9.10 ± 5.00 ng/mL, 7.13 ± 3.99 ng/mL (p < 0.001) according to estimated glomerular filtration rate (eGFR) (89 - 60, 59 - 45, 44 - 30, 29 - 15, < 15 mL/min/1.73m2). The prevalence of 25(OH)D deficiency was significantly high in each group (70.1%, 70.8%, 76.5%, 81.6%, 91.4%, p < 0.001). 25(OH)D concentration decreased with the decline of renal function. The difference of 25(OH)D levels between the 24hUPr ≥ 3.5 g group and the 24hUPr < 3.5 g group was statistically significant. Multivariate linear regression analysis showed that 25(OH)D concentration was associated with 24hUPr and serum Ca. The 25(OH)D concentration was lower, and the prevalence of 25(OH)D deficiency was higher in diabetes mellitus (DM) patients compared with patients without DM. CONCLUSION: This study shows a high prevalence of 25(OH)D deficiency in CKD patients from north China, and the deficiency is dependent on eGFR. Urinary protein and serum Ca might be associated with 25(OH)D concentration. DM patients have lower 25(OH)D concentrations than non-DM patients.

Therapeutic effect of double-filtration plasmapheresis combined with methylprednisolone to treat diffuse proliferative lupus nephritis.

OBJECTIVE: The efficacy of double-filtration plasmapheresis (DFPP), combined with methylprednisolone, to treat diffuse proliferative lupus nephritis (LN) was studied. METHODS: Twenty-four patients who were admitted to the hospital and diagnosed with diffuse proliferative LN (LN Class IV-G(A)) through renal biopsy from 2011 to 2013 were recruited as the study subjects. The patients' clinical manifestations were nephritic syndrome and/or renal insufficiency. The pathological features were glomerular diffuse proliferative lesions. The patients were divided into two groups: the treatment group and the control group, with 12 patients in each group. The patients in the treatment group were first treated with DFPP combined with methylprednisolone (0.8-1.0 mg/kg/day); subsequently, they were put on methylprednisolone therapy only. The patients in the control group were first put on methylprednisolone pulse therapy (500-1,000 mg) for 3 days; subsequently, they were treated with methylprednisolone (0.8-1.0 mg/kg/day) combined with mycophenolate mofetil (1.5 g/day). The patients were observed for 24 months. Levels of hemoglobin, platelet, albumin, serum creatinine, 24-h urinary protein, serum C3 , antinuclear antibody (ANA), anti-dsDNA, and anti-Smith were measured at 0, 3, 6, 12, and 24 months. Complete remission and recurrence standards were established. The total dosages of methylprednisolone were calculated. Repeated renal biopsy was performed on several patients. RESULTS: There was no statistical significance in the baseline conditions of the treatment and the control groups. For the treatment group, no plasmapheresis-related complications occurred. The two groups showed no significant difference in complete remission. The patients' edema and serous effusion resolved, urine volume, serum creatinine, and albumin levels returned to normal, urine protein decreased in treatment group more rapidly than the patients in the control group. The mean dose of methylprednisolone received in the treatment group was lower than in the control group. The complement C3 levels in the treatment group were significantly higher than in the control group. The recurrence rate in the treatment group was lower than in the control group. Repeated renal biopsies on several patients in the treatment group indicated that their pathology improved significantly, changing from LN (IV) to LN(II-III). CONCLUSIONS: Appropriate application of DFPP combined with glucocorticoid therapy could accelerate the remission of diffuse proliferative LN, reduce overall glucocorticoid dosage, prevent recurrence, and maintain C3 level in a higher level. J. Clin. Apheresis 31:375-380, 2016. © 2015 Wiley Periodicals, Inc.

[Hydrogen sulfide attenuates bronchial epithelial cell apoptosis by inhibiting endoplasmic reticulum stress].

OBJECTIVE: To explore the effects of hydrogen sulfide on nicotine-induced bronchial epithelial cell endoplasmic reticulum (ER) stress and apoptosis. METHODS: Nicotine was used to establish the apoptotic model in human bronchial epithelial cell line (16HBE) for mimicing the effect of cigarette smoke on apoptosis. The 16HBE cells were grouped by the concentration gradients of 0 (control), 5, 10, 20, 40, 80 µmol/L nicotine dosing. All groups were treated for 72 h. And 16HBE cells were grouped by the time gradients of 0 (control), 24, 48, 72 h of nicotine dosing. For control group, the nicotine concentration was 40 µmol/L. Then the protein expression level of CCAAT/enhancer binding protein homologous protein (CHOP) was measured by Western blot to define the effect of various concentrations of nicotine and different dosing periods of nicotine on the protein expression level of CHOP. For observing the role of hydrogen sulfide in ER stress-mediated apoptosis, 16HBE cells were divided into 6 groups of control, 40 µmol/L nicotine, 100 µmol/L sodium hydrosulfide (NaHS) + 40 µmol/L nicotine, 200 µmol/L NaHS + 40 µmol/L nicotine, 400 µmol/L NaHS + 40 µmol/L nicotine and 10 mmol/L taurine + 40 µmol/L nicotine. NaHS or taurine was pretreated for 30 min and then nicotine dosed for 72 h. The protein expression levels of GRP78 and ER stress-mediated apoptosis markers, such as cleaved caspase-12 and CHOP, were measured by Western blot. And chromatin dye Hoechst 33258 was used to detect the morphological changes of apoptotic 16HBE cells and apoptotic index calculated. RESULTS: Nicotine could concentration and time-dependently improve the expression of CHOP in 16HBE cells. The ratio of CHOP to average absorbance of glyceraldehyde phosphate dehydrogenase (GAPDH) was significantly higher in 40 µmol/L nicotine group than that in control group (1.04 ± 0.32 vs 0.30 ± 0.17, P < 0.05). The ratio of GRP78 to average absorbance of ß-actin (0.59 ± 0.19 vs 1.00 ± 0.08), cleaved caspase-12 to average absorbance of procaspase-12 (0.06 (0.01, 6.06) vs 20.30(12.79, 23.78)) and CHOP to average absorbance of ß-actin (0.18 ± 0.10 vs 0.53 ± 0.09) in 200 µmol/L NaHS + 40 µmol/L nicotine group were all significantly lower than those in 40 µmol/L nicotine group (all P < 0.05). The apoptotic index in 200 µmol/L NaHS + 40 µmol/L nicotine group (3.04 ± 1.83 vs 16.60 ± 3.32) and apoptotic index in 10 mmol/L taurine + 40 µmol/L nicotine group (4.08 ± 2.04 vs 16.60 ± 3.32) were significantly lower than those in 40 µmol/L nicotine group (all P < 0.01). CONCLUSIONS: NaHS exerts its protection against nicotine-induced bronchial epithelial cell apoptosis through suppressing ER stress. And the underlying mechanism may be through a down-regulation of ER stress-mediated apoptosis markers of cleaved caspase-12 and CHOP.

Vitamin D status and the risk of neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Previous studies have linked vitamin D deficiency with autoimmune diseases, and recent research has found low vitamin D levels in neuromyelitis optica spectrum disorder (NMOSD) patients. We aimed to determine the variances in serum 25(OH)D levels between NMOSD patients and healthy controls. METHODS: We searched English and Chinese databases (PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, WanFang Med, VIP) for observational studies related to serum 25(OH)D levels in NMOSD patients published up to August 24, 2023. We included studies with healthy controls and compared serum 25(OH)D levels between NMOSD patients and controls. We computed the mean difference (MD) and 95% confidence interval (CI) for continuous variables to evaluate serum 25(OH)D levels and combined odds ratios (ORs) and 95% CIs for dichotomized 25(OH)D data. RESULTS: Six papers were selected for meta-analysis, including 794 participants (347 in the NMOSD group and 447 in the healthy control group). Meta-analysis showed significantly lower serum 25(OH)D levels in the NMOSD group (MD: -7.83, 95 % CI: -10.99 to -4.68). The risk of 25(OH)D deficiency was 23.36 times higher in the NMOSD group (OR: 23.36, 95 % CI: 0.85 to 640.76, p = 0.06>0.05), with a 94 % occurrence rate. There was no significant difference in the risk of having sufficient 25(OH)D between the groups (p = 0.12>0.05). CONCLUSION: NMOSD patients have lower serum 25(OH)D levels than healthy controls. However, the current research results do not provide evidence for a causal relationship between serum 25(OH)D levels and the onset of NMOSD. Routine vitamin D supplementation may be advantageous for patients with NMOSD.

Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress.

Epithelial mesenchymal transition (EMT) is a contributing factor in remodeling events of chronic obstructive pulmonary disease (COPD). Hydrogen sulfide (H2S) has been implicated in the pathogenesis of COPD, but the effect of H2S in regulating EMT and the underlying mechanisms is not clear. In this study, we assessed endoplasmic reticulum (ER) stress markers, EMT markers and associated signal molecules in rat lungs, bronchial epithelial cells, and human peripheral lung tissues to investigate the effect of H2S in regulating EMT and the underlying mechanisms. We found that EMT and ER stress occurred in lung epithelial cells, especially in the bronchial epithelial cells of smokers and COPD patients. In cigarette smoke (CS)-exposed rats, intraperitoneal injection of NaHS significantly alleviated CS-induced lung tissue damage, small airway fibrosis, ER stress, and EMT, while intraperitoneal injection of propargylglycine (cystathionine-gamma-lyase inhibitor) aggravated these effects induced by CS. In the nicotine-exposed 16HBE cells, an appropriate concentration of H2S donor not only inhibited nicotine-induced ER stress, but also inhibited nicotine-induced enhancement of cell migration ability and EMT. ER stress nonspecific inhibitors taurine and 4-phenyl butyric acid also inhibited nicotine-induced enhancement of cell migration ability and EMT. Both H2S and inositol-requiring enzyme 1 (IRE1) activation inhibitor 4µ8C inhibited nicotine-induced activation of IRE1, Smad2/3 and EMT. These results suggest that H2S inhibits CS- or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The IRE1 signal pathway and Smad2/3 may be responsible for the inhibitory effect of H2S.

Relationship Between Endogenous Hydrogen Sulfide and Pulmonary Vascular Indexes on High-Resolution Computed Tomography in Patients with Chronic Obstructive Pulmonary Disease.

Objective: To explore the relationship between endogenous hydrogen sulfide (H2S) and high-resolution computed tomography (HRCT) indexes in pulmonary vascular remodeling. Methods: A total of 94 stable chronic obstructive pulmonary disease (COPD) patients were recruited for the study．Plasma H2S levels were measured using fluorescence probe. Fluorescence quantitative polymerase chain reaction was used to measure H2S synthase cystathionine-γ-lyase (CSE) mRNA and cystathionine-ß-synthesis enzyme (CBS) mRNA. The main pulmonary artery diameter (mPAD), axial diagonal mPAD, coronal mPAD, sagittal mPAD, right pulmonary artery diameter (RPAD), left pulmonary artery diameter (LPAD), and ascending aortic diameter (AAD) and the percentage of total cross-sectional area of vessels less than 5 mm2 of total lung area (%CSA <5) on HRCT were measured. Pulmonary arterial systolic pressure (PASP) of echocardiography, blood gas analysis, and routine blood tests were performed. Correlation analysis and multivariate linear regression were performed using SPSS 22.0. Results: H2S was negatively correlated with mPAD, axial diagonal mPAD, and sagittal mPAD (r = -0.25~-0.32) and positively correlated with PaO2 (r = 0.35). Relative expression of CSE mRNA was positively correlated with PASP, coronal mPAD, sagittal mPAD, white blood cell count (WBC), and neutrophil count (N) (r = 0.30~0.44). The relative expression of CBS mRNA was positively correlated with PASP, WBC, and N (r = 0.34~0.41). In separate models predicting pulmonary vascular indexes, a 1µmol/L increase in H2S predicted lower pulmonary artery diameter (for axial diagonal mPAD, 0.76mm lower; for mPAD/AAD, 0.68mm lower). All P values were less than 0.05. Conclusion: Endogenous H2S may be involved in pulmonary vascular remodeling, providing a new method for the diagnosis and treatment of COPD. The generation of H2S may be inhibited by hypoxia, inflammation, etc.

Correlation between tumor marker CA72-4 and prognosis of patients with gastric cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Gastric cancer is one of the common gastrointestinal tumors, with high recurrence and metastasis rates. Tumor marker tumor marker carbohydrate antigen 72-4 (CA72-4) has been used in the screening and diagnosis of gastric cancer, but whether it can be used as an indicator to monitor the prognosis of gastric cancer remains a great controversy. The purpose of this study was to systematically evaluate the correlation between tumor marker CA72-4 and prognosis of gastric cancer patients. METHODS: A systematic search was performed by retrieving on English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China Knowledge Network, Wanfang, Weipu (VIP Information Chinese Journal Service Platform), CBM) of clinical study on the correlation between tumor marker CA72-4 and prognosis of gastric cancer patients. The retrieval time limit was from the establishment of the database to October 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using Stata12.0 and RevMan5.3 software. CONCLUSIONS: This study will compare the correlation between tumor marker CA72-4 and prognosis of gastric cancer patients, so as to provide evidence-based basis for clinicians to select prognostic indicators of gastric cancer. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI: 10.17605 / OSF.IO / B3AMN.

Inhibition of integrin-linked kinase via a siRNA expression plasmid attenuates connective tissue growth factor-induced human proximal tubular epithelial cells to mesenchymal transition.

BACKGROUND: Increasing evidence suggests that connective tissue growth factor (CTGF) is involved in the epithelial-to-mesenchymal transition (EMT). The exact intracellular events that drive this process, however, are not fully understood. In this study, we investigated the role of integrin-linked kinase (ILK) in mediating CTGF-induced EMT. METHODS: The expression of alpha-smooth muscle actin (alpha-SMA) and E-cadherin upon the stimulation by recombinant human CTGF (rhCTGF) in cultured human tubular epithelial cell line (HK-2) was detected by real-time RT-PCR and Western blot. Subsequently, the role of ILK was determined by using ILK siRNA. RESULTS: rhCTGF increased the mRNA expression of alpha-SMA significantly in a dose- and time-dependent manner, while E-cadherin mRNA decreased in a dose- and time-dependent manner. alpha-SMA protein was up-regulated after stimulation by 5 ng/ml CTGF for 96 h, and increased further after stimulation by 50 ng/ml. An immunocytochemical study showed that alpha-SMA was initially detectable at 48 h, and increased further at 72 h, while there was almost no alpha-SMA immunostaining observed in the control group at the same time point. E-cadherin protein was also down-regulated in a dose-dependent manner. Transfection of HK-2 cells with ILK-siRNA significantly attenuated rhCTGF-induced alpha-SMA induction and E-cadherin repression. CONCLUSION: Our study suggested that ILK mediated the effect of EMT in proximal tubular epithelial cells stimulated by CTGF.

Role of ERK1/2 and PI3-K in the regulation of CTGF-induced ILK expression in HK-2 cells.

BACKGROUND: Previous studies revealed that integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase, is a critical mediator for tubular epithelial to mesenchymal transition (EMT), and likely plays an important role in the pathogenesis of chronic kidney fibrosis. However, the exact signal pathway has not been well understood. In this study, we investigated the role of extracellular regulating kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K) in the regulation of ILK expression by connective tissue growth factor (CTGF) in HK-2 cells. METHODS: Experiments were performed on transformed (human kidney cell (HKC)-clone 2) human proximal tubular epithelial cells (PTECs). Induction of ILK in response to CTGF was studied at the mRNA level by real-time PCR and protein by immunoblotting. Chemical inhibitors were used to assess the role of MEK/ERK1/2, PI3-K, and P38 MAPK signaling pathways in induction of ILK by CTGF. RESULTS: CTGF induced ILK protein expression in HK-2 cells in a time- and dose-dependent manner. There was a 5.638-fold (control: 1.000+/-0.290, 50 ng/ml: 5.638+/-1.200; *P<0.05 vs. control) and 5.740-fold (0 h: 1.000+/-0.498, 48 h: 5.740+/-1.465, *P<0.05 vs. control) increase compared to control respectively. CTGF-induced ILK expression was partially reduced by inhibiting ERK1/2 and PI3-K activation. There was no influence of ILK expression by inhibiting P38 MAPK activation when cells treated with CTGF. CONCLUSION: CTGF induces the expression of ILK protein in HK-2 cells. This induction is partially dependent on MEK/ERK1/2 and PI3-K signaling pathways. Inhibiting CTGF-induced ILK by targeting PI3-K and/or MEK/ERK1/2 signaling pathways could be of therapeutic value in renal fibrosis.

Epithelial to mesenchymal transition in the progression of tubulointerstitial fibrosis.

OBJECTIVE: To review the mechanisms of epithelial to mesenchymal transition (EMT) and its role in the progression of tubulointerstitial fibrosis. DATA SOURCES: The data used in this review were obtained mainly from the studies of EMT reported from 2000-2006. STUDY SELECTION: Relevant articles on studies of EMT in tubulointerstitial fibrosis were selected. Data were mainly extracted from the 45 articles listed in the reference section of this review. RESULTS: The process of EMT has gained wide recognition as candidate mechanism in progression of chronic fibrotic disorders. New markers were identified and facilitate the observation of EMT. EMT is regulated by many factors through activation of kinase-dependent signaling cascades. Recent findings suggest that EMT is a reversible process, which can be controlled by factors for their epithelial inducing activities. CONCLUSION: Remarkable progresses of EMT research have been made recently. Preventing or reversing EMT is a promising strategy against renal fibrosis.

MiR-22 functions as a biomarker and regulates cell proliferation, cycle, apoptosis, migration and invasion in renal cell carcinoma.

It is well known that microRNAs (miRNAs) are associated with tumor occurrence and development, and the functions of microRNA-22 (miR-22) have been investigated in numerous kinds of cancer. However, the significance of miR-22 in renal cell carcinoma (RCC) has not been fully explored. In this study, we found that miR-22 was down-regulated both in serum and tissues of RCC patients by using real time quantitative PCR (RT-qPCR) analyses. In addition, miR-22 was negatively associated with hepatic metastatic sites and lymphatic metastasis, as well as the clinical stages and prognosis. Moreover, the expression of miR-22 could be increased though surgical treatment in serum of RCC patients. Functional studies were performed to investigate the role of miR-22 in the progression of RCC. Data suggested that overexpression of miR-22 inhibited cell proliferation, migration and invasion in Caki-1 cells, whereas blockage of miR-22 could reverse these oncogenic effects. We also identified erb-b2 receptor tyrosine kinase (ERBB3) was a novel target of miR-22 in RCC cells. Consequently, our work provides evidence that the down-regulation of miR-22 expression contributed to RCC. And miR-22 may be a potential molecule biomarker for diagnose and therapy evaluation in RCC.

Hydrogen Sulfide Inhibits Cigarette Smoke-Induced Endoplasmic Reticulum Stress and Apoptosis in Bronchial Epithelial Cells.

Background: Apoptosis of lung structural cells contributes to the process of lung damage and remodeling in chronic obstructive pulmonary disease (COPD). Our previous studies demonstrated that exogenous hydrogen sulfide (H2S) can reduce the lung tissue pathology score, anti-inflammation and anti-oxidation effects in COPD, but the effect of H2S in regulating cigarette smoke (CS) induced bronchial epithelial cell apoptosis and the underlying mechanisms are not clear. Objectives: To investigate the effect of H2S on CS induced endoplasmic reticulum stress (ERS) and bronchial epithelial cell apoptosis. Methods: Male Sprague-Dawley rats randomly divided into four groups for treatment: control, CS, NaHS + CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4 months. Since the beginning of the third month, freshly prepared NaHS (14 µmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 µM) for 30 min, and then cells were exposed to 40 µmol/L nicotine for 72 h. ERS markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and human bronchial epithelial cells. The apoptotic bronchial epithelial cells were detected by Hoechst staining in vitro and TUNEL staining in vivo. Results: In CS exposed rats, peritoneal injection of NaHS significantly inhibited CS induced overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate in rat lungs, and inhibiting the endogenous H2S production by peritoneal injection of PPG exacerbated these effects. In the nicotine-exposed bronchial epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and overexpression of ERS-mediated apoptosis markers. Conclusion: H2S inhibited lung tissue damage by attenuating CS induced ERS in rat lung and exogenous H2S attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.

Role of connective tissue growth factor (CTGF) module 4 in regulating epithelial mesenchymal transition (EMT) in HK-2 cells.

BACKGROUND: Recent studies have suggested that connective tissue growth factor (CTGF) plays a key role in tissue fibrosis including renal scarring. While studies showed several forms of CTGF with 10-38 kDa in the body fluids, little is known about these small molecule species. We investigated the effect of a 10 kDa CTGF molecule consisting of module 4, on the epithelial mesenchymal transition (EMT) in human proximal tubular cell line (HK-2). METHODS: HK2 cells were cultured in DMEM medium. The response of cytokeratin (CK) and vimentin (VIM) mRNA and protein expression to the stimulation of rhCTGF(C) were observed by real-time PCR and immunocytochemistry. At the same time, the morphologic changes were observed by microscopy, and expression of alpha-smooth muscle actin (alpha-SMA) and fibronectin (FN) was detected by laser confocal microscope. These effects were compared with CTGF N-terminal [rhCTGF(N)], consisting of module 1-3, and observed in a condition with the addition of anti-CTGF antibody. RESULTS: RhCTGF(C) induced striking changes in epithelial cells, including changes in cellular morphology, loss of CK, gain VIM and alpha-SMA, and increased levels of fibronectin. Cocultured with anti-CTGF antibody could abrogate most of these effects, while cells treated with rhCTGF(N) showed no significant phenotypic changes comparing to control group. CONCLUSIONS: Our results suggest that module 4 could induce HK-2 cells EMT, whereas the residual fragment has no similar effect in spite of consisting of 3 modules of CTGF molecule.

Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on left ventricular mass index and ejection fraction in hemodialysis patients: A meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are effective therapies for left ventricular hypertrophy and heart failure. We aimed to assess the efficacy of ACEI and ARB in hemodialysis patients. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify studies published before December 2015 that investigated the use of ACEI or ARB compared with controls to determine the effect on the left ventricular mass index (LVMI) and ejection fraction (EF) in hemodialysis patients, and trial sequential analysis was also performed for outcomes. RESULTS: A total of 357 cases of patients involved in 8 clinical trials (nine comparisons) were included. Compared with controls, ACEI/ARB treatment resulted in more effective improvement of LVMI in hemodialysis patients (weighted mean difference (WMD) -14.42, 95% confidence interval (CI) -20.89 to -7.95), and the cumulative z curve crossed the trial sequential monitoring boundary for benefit in trial sequential analysis. Although ACEI/ARB and controls did not show significant differences with regards to EF (WMD: -0.84, 95% CI: -2.91 to 1.24). CONCLUSIONS: The comparison between ACEI/ARB and controls showed that the former type of drug causes a greater reduction in LVMI with hemodialysis patients, although they have no significant impact on the EF. Compared with other antihypertensive drugs or placebo, ACEI/ARB is recommended as a better choice in hemodialysis patients.

An Aqueous Rechargeable Zn//Co3 O4 Battery with High Energy Density and Good Cycling Behavior.

An aqueous rechargeable Zn//Co3 O4 battery is demonstrated with Zn@carbon fibers and Co3 O4 @Ni foam as the negative and positive electrodes, respectively, using an electrolyte of 1 m KOH and 10 × 10(-3) m Zn(Ac)2 . It can operate at a cell voltage as high as 1.78 V with an energy density of 241 W h kg(-1) and presents excellent cycling. The battery is also assembled into a flexible shape, which can be applied in flexible or wearable devices requiring high energy.

Hybrid system for rechargeable magnesium battery with high energy density.

One of the main challenges of electrical energy storage (EES) is the development of environmentally friendly battery systems with high safety and high energy density. Rechargeable Mg batteries have been long considered as one highly promising system due to the use of low cost and dendrite-free magnesium metal. The bottleneck for traditional Mg batteries is to achieve high energy density since their output voltage is below 2.0 V. Here, we report a magnesium battery using Mg in Grignard reagent-based electrolyte as the negative electrode, a lithium intercalation compound in aqueous solution as the positive electrode, and a solid electrolyte as a separator. Its average discharge voltage is 2.1 V with stable discharge platform and good cycling life. The calculated energy density based on the two electrodes is high. These findings open another door to rechargeable magnesium batteries.

Co3O4@MWCNT nanocable as cathode with superior electrochemical performance for supercapacitors.

Using a simple hydrothermal procedure, cobalt oxide (Co3O4) with preferred orientation along (220) planes is in situ prepared and coated on MWCNT. The prepared Co3O4@MWCNT nanocable shows superior electrochemical performance as cathode material for aqueous supercapacitors in 0.5 M KOH solution. Its redox peaks retain the well-defined shapes even when the scan rate increases to 200 mV/s. Its specific capacitance is high, 590 F/g at 15 A/g and 510 F/g even at 100 A/g within the potential range from -0.2 to 0.58 V (vs SCE). There is no capacitance fading after 2000 full cycles. This excellent performance is superior to the pristine and the reported Co3O4, which is ascribed to the unique nanocable structure with orientation.

Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity.

Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-ß-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.