BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

Bone morphogenetic protein 7 (BMP7) has been reported to confer renoprotective effects in acute and chronic kidney disease models, but its potential role in Type 2 diabetic nephropathy remains unknown. In cultured human proximal tubular epithelial cells (PTECs), exposure to advanced glycation end-products (AGEs) induced overexpression of intercellular adhesion molecule 1 (ICAM1), monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL-8) and interleukin 6 (IL-6), involving activation of p44/42 and p38 mitogen-activated protein kinase (MAPK) signalling. BMP7 dose-dependently attenuated AGE-induced up-regulation of ICAM1, MCP1, IL-8 and IL-6 at both mRNA and protein levels. Moreover, BMP7 suppressed AGE-induced p38 and p44/42 MAPK phosphorylation and reactive oxygen species production in PTECs. Compared with vehicle control, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3549±816.2 μg/mg compared with 8612±2037 μg/mg, P=0.036), blood urea nitrogen (33.26±1.09 mg/dl compared with 37.49±0.89 mg/dl, P=0.006), and renal cortical expression of ICAM1 and MCP1 at both gene and protein levels. In addition, BMP7-treated animals had significantly less severe tubular damage, interstitial inflammatory cell infiltration, renal cortical p38 and p44/42 phosphorylation and lipid peroxidation. Our results demonstrate that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple inflammatory signalling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation.postprin

Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-alpha, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-kappaB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and alpha-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFalpha-stimulating gene (TSG)-6 via P38 and NF-kappaB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-alpha overexpression were suppressed by recombinant HGF treatment, while the upregulation of alpha-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, alpha-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.published_or_final_versio

Quasi-Elliptic Bandpass Frequency Selective Surface Based on Coupled Stubs-Loaded Ring Resonators

© 2013 IEEE. In this paper, a novel design of frequency-selective surface (FSS) based on coupled stubs-loaded ring resonators (SLRRs) is proposed. The proposed FSS exhibits quasi-elliptic bandpass filtering characteristic at C-band. And each unit cell of the structure is composed of two SLRRs coupled by a circular aperture. A novel method of transmission line (TL) model is proposed to investigate the operating principle of a single SLRR under normal incidence plane wave. Moreover, the operating mechanism of the proposed FSS is further researched with the aid of the equivalent circuit model (ECM) analysis method. Due to the symmetric and low-profile physical structure, the FSS keeps stable frequency response under oblique incident plane wave for both transverse electric (TE) and transverse magnetic (TM) polarizations. Finally, the designed FSS is fabricated and measured. The measured results agree well with the simulated results. The measured results indicate that the proposed FSS exhibits a dual-polarized and stable bandpass frequency response with two transmission zeros (TZs) at around 5.71 and 6.87 GHz under different incident angles up to 40°

Additive-Free, Low-Temperature Crystallization of Stable α-FAPbI3 Perovskite

Formamidinium lead triiodide (FAPbI3) is attractive for photovoltaic devices due to its optimal bandgap at around 1.45 eV and improved thermal stability compared with methylammonium‐based perovskites. Crystallization of phase‐pure α‐FAPbI3 conventionally requires high‐temperature thermal annealing at 150 °C whilst the obtained α‐FAPbI3 is metastable at room temperature. Here, aerosol‐assisted crystallization (AAC) is reported, which converts yellow δ‐FAPbI3 into black α‐FAPbI3 at only 100 °C using precursor solutions containing only lead iodide and formamidinium iodide with no chemical additives. The obtained α‐FAPbI3 exhibits remarkably enhanced stability compared to the 150 °C annealed counterparts, in combination with improvements in film crystallinity and photoluminescence yield. Using X‐ray diffraction, X‐ray scattering, and density functional theory simulation, it is identified that relaxation of residual tensile strains, achieved through the lower annealing temperature and post‐crystallization crystal growth during AAC, is the key factor that facilitates the formation of phase‐stable α‐FAPbI3. This overcomes the strain‐induced lattice expansion that is known to cause the metastability of α‐FAPbI3. Accordingly, pure FAPbI3 p–i–n solar cells are reported, facilitated by the low‐temperature (≤100 °C) AAC processing, which demonstrates increases of both power conversion efficiency and operational stability compared to devices fabricated using 150 °C annealed films

Cardiovascular Outcomes in Acute Coronary Syndrome and Malnutrition: A Meta-Analysis of Nutritional Assessment Tools

Background: There is emerging evidence that malnutrition is associated with poor prognosis among patients with acute coronary syndrome (ACS). // Objectives: This study seeks to elucidate the prognostic impact of malnutrition in patients with ACS and provide a quantitative review of most commonly used nutritional assessment tools. // Methods: Medline and Embase were searched for studies reporting outcomes in patients with malnutrition and ACS. Nutritional screening tools of interest included the Prognostic Nutrition Index, Geriatric Nutritional Risk Index, and Controlling Nutritional Status. A comparative meta-analysis was used to estimate the risk of all-cause mortality and cardiovascular events based on the presence of malnutrition and stratified according to ACS type, ACS intervention, ethnicity, and income. // Results: Thirty studies comprising 37,303 patients with ACS were included, of whom 33.5% had malnutrition. In the population with malnutrition, the pooled mortality rate was 20.59% (95% CI: 14.95%-27.67%). Malnutrition was significantly associated with all-cause mortality risk after adjusting for confounders including age and left ventricular ejection fraction (adjusted HR: 2.66, 95% CI: 1.78-3.96, P = 0.004). There was excess mortality in the group with malnutrition regardless of ACS type (P = 0.132), ethnicity (P = 0.245), and income status (P = 0.058). Subgroup analysis demonstrated no statistically significant difference in mortality risk between individuals with and without malnutrition (P = 0.499) when using Controlling Nutritional Status (OR: 7.80, 95% CI: 2.17-28.07, P = 0.011), Geriatric Nutritional Risk Index (OR: 4.30, 95% CI: 2.78-6.66, P < 0.001), and Prognostic Nutrition Index (OR: 4.67, 95% CI: 2.38-9.17, P = 0.023). // Conclusions: Malnutrition was significantly associated with all-cause mortality risk following ACS, regardless of ACS type, ethnicity, and income status, underscoring the importance of screening and interventional strategies for patients with malnutrition

Genome-Wide Identification of Bcl11b Gene Targets Reveals Role in Brain-Derived Neurotrophic Factor Signaling

B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells

The effects of social connections on self-rated physical and mental health among internal migrant and local adolescents in Shanghai, China

<p>Abstract</p> <p>Background</p> <p>China is in the midst of history's largest flow of rural-urban migration in the world; a flow that includes growing numbers of children and adolescents. Their health status is an important public health issue. This study compares self-rated physical and mental health of migrant and local adolescents in China, and examines to what extent layered social connections account for health outcomes.</p> <p>Methods</p> <p>In 2010, we conducted a cross-sectional study among middle school students in Pudong New Area, Shanghai. Information about health status, social connections, and demographic factors were collected using a questionnaire survey. After controlling for sociodemographic factors, we used the <it>t-</it>test, Chi-square analysis, and a series of regression models to compare differences in health outcomes and explore the effects of social connections.</p> <p>Results</p> <p>Migrant adolescents reported significantly higher rates of good physical health. However, they also had significantly fewer social connections, lower self-esteem, and higher levels of depression than their native peers. Family cohesion was associated with depressive symptoms and low self-esteem among all adolescents; peer association and social cohesion played major roles in migrants' well-being. Gender, age, and socioeconomic (SES) factors also affected adolescents' self-rated physical and mental health.</p> <p>Conclusions</p> <p>Self-rated data suggest that migrant adolescents enjoy a physical health advantage and a mental health disadvantage. Layered social connections, such as peer association and social cohesion, may be particularly important for migrants. A public health effort is required to improve the health status of migrant youth.</p

Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel

Berberine is the major constituent of Coptis chinese and is commonly used in Chinese herbal medicine to treat patients with gastrointestinal disorders. In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines. Decreased retention of rhodamine 123 was observed in berberine-treated cells as compared to vehicle control. To examine whether the berberine modulated pgp-170 expression in cancer cells is associated with changes in drug resistance, we determined the cytotoxicity, cell cycle progression and cell morphology of Paclitaxel-treated cells. Paclitaxel (1 nM–10 μM) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 μM berberine for 24 h prior to Paclitaxel treatment resulted in increased viability as compared to that of Paclitaxel-treated cells. In addition, Paclitaxel-induced apoptosis and/or G2/M arrest in these three cancer cell lines. Pretreatment of cells with berberine prior to Paclitaxel blocked the Paclitaxel-induced cell cycle responses and morphological changes. These results together suggest that berberine modulated the expression and function of pgp-170 that leads to reduced response to Paclitaxel in digestive track cancer cells. © 1999 Cancer Research Campaig

An Intronic Variant in the GRP78, a Stress-Associated Gene, Improves Prediction for Liver Cirrhosis in Persistent HBV Carriers

Background: Our previous study indicated that a common variant (rs430397 G>A) in the intron 5 of glucose-regulated protein 78 (GRP78) gene was associated with risk and prognosis of primary hepatocellular carcinoma (HCC), including HBV- and cirrhosis-related HCC. rs430397 polymorphism may be a contributing factor or biomarker of HBV infection or HBV-related cirrhosis. Methodology/Principal Findings: 539 non-HBV-infected individuals, 205 self-limited infection and 496 persistent HBV infection were recruited between January 2001 and April 2005 from the hospitals in Southern China. Genomic DNA was genotyped for rs430397. The associations between the variation and susceptibility to liver cirrhosis (LC) in persistent HBV infection were examined. We observed that individuals carrying allele rs430397A were more likely to become HBV-related LC. When persistently infected patients were divided into four subgroups, patients with phase IV had an increased allele A and genotype AG compared with phase I and/or phase III. Decreased serum albumin and prolonged plasma prothrombin time (PT) were showed in LC patients carrying genotype AA. Furthermore, rs430397 genotype had an increased susceptibility to LC with dose-dependent manners (P-trend = 0.005), and the genotype did constitute a risk factor for the development of advanced LC (Child-Pugh classification C and B, P-trend = 0.021). Conclusions/Significance: rs430397 polymorphism may be a contributing factor to LC in persistent HBV carriers. © 2011 Zhu et al.published_or_final_versio