First identification of Kruppel-like factor 2 mutation in heritable pulmonary arterial hypertension
Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenic protein receptor 2 gene and/or genes of its signalling pathway in about 85% of patients. We clinically and genetically analysed a HPAH family without mutations in previously described PAH genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterisation in case of suspected disease. Genetic diagnostics were performed using a PAH-specific gene panel including all known 12 PAH genes an...
Source: Clinical Science - February 10, 2017 Category: Biomedical Science Authors: Eichstaedt, C. A., Song, J., Rodriguez Viales, R., Pan, Z., Benjamin, N., Fischer, C., Hoeper, M., Ulrich, S., Hinderhofer, K., Grunig, E. Tags: PublishAheadOfPrint Source Type: research

VMP1-Related autophagy induced by fructose rich diet in {beta}-cells: It's prevention by incretins
Conclusions : VMP1-related autophagy is a reactive process against F-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge could help to use autophagy as potential target for preventing progression from IGT to T2DM. (Source: Clinical Science)
Source: Clinical Science - February 10, 2017 Category: Biomedical Science Authors: Maiztegui, B., Boggio, V., Roman, C. L., Flores, L. E., Del Zotto, H., Ropolo, A., Grasso, D., Vaccaro, M. I., Gagliardino, J. J. Tags: PublishAheadOfPrint Source Type: research

Annexin II-binding Immunoglobulins in Patients with Lupus Nephritis and their Correlation with Disease Manifestations
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in NZBWF1/J mice. Annexin II-binding immunoglobulins in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis was ...
Source: Clinical Science - February 9, 2017 Category: Biomedical Science Authors: Cheung, K. F., Yung, S., Chau, M. K., Yap, D. Y., Chan, K. W., Lee, C. K., Tang, C. S., Chan, T. M. Tags: PublishAheadOfPrint Source Type: research

Activation of TRPV4 by dietary apigenin antagonizes renal fibrosis in deoxycorticosterone acetate (DOCA) salt-induced hypertension
In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks. Apigenin significantly attenuated the DOCA-salt-induced structural and functional damage to the kidney, which was accompanied by reduced expression of transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway and extracellular matrix proteins. Immunochemistry, cell-attached patch clamp and fluorescent Ca2+ imaging results indicated that TRPV4 was expressed and activated by apigenin in both the kidney and renal cells. Importantly, k...
Source: Clinical Science - January 31, 2017 Category: Biomedical Science Authors: Wei, X., Gao, P., Pu, Y., Li, Q., Yang, T., Zhang, H., Xiong, S., Cui, Y., Li, L., Ma, X., Liu, D., Zhu, Z. Tags: PublishAheadOfPrint Source Type: research

Genome-wide methylation profiles in coronary artery ectasia
In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE. (Source: Clinical Science)
Source: Clinical Science - January 31, 2017 Category: Biomedical Science Authors: Lu, T.-P., Chuang, N.-C., Cheng, C.-Y., Hsu, C.-A., Wang, Y.-C., Lin, Y.-H., Lee, J.-K., Wu, C.-K., Hwang, J.-J., Lin, L.-Y., Yeh, S.-F. S., Chien, K.-L., Juang, J.-M. J. Tags: PublishAheadOfPrint Source Type: research

Oxytocin: its role in the benign prostatic hyperplasia (BPH) via the ERK pathway
Conclusions: Oxytocin is highly expressed in the serum and prostate tissue of BPH patients. Additionally, oxytocin aggravates BPH and the oxytocin-induced proliferative effect on prostatic cells is mediated through MEK-ERK-RSK pathway, at least partly. Thus, hypothalamic regulation may be involved in BPH development, which may open a novel door for more medications for BPH in the future. (Source: Clinical Science)
Source: Clinical Science - January 27, 2017 Category: Biomedical Science Authors: Xu, H., Fu, S., Chen, Y., Chen, Q., Gu, M., Liu, C., Qiao, Z., Zhou, J., Wang, Z. Tags: PublishAheadOfPrint Source Type: research

Allergic environment enhances airway epithelial pro-inflammatory responses to rhinovirus infection
We examined the effect of an allergic cytokine environment on the response of AEC to rhinovirus, the most common trigger of acute exacerbations of asthma. Calu-3 cells, a well-differentiated human AEC line, were cultured with or without the T-helper type 2 cytokines IL-4 and IL-13, then stimulated with a toll-like receptor (TLR) 3 agonist (poly I:C, dsRNA) or a TLR7 agonist (imiquimod), or infected with rhinovirus 16. Expression of pro-inflammatory and anti-viral mediators, and of viral pattern-recognition molecules, was assessed using nCounter assays, quantitative real-time PCR, and protein immunoassays. Both dsRNA and im...
Source: Clinical Science - January 23, 2017 Category: Biomedical Science Authors: Herbert, C., Do, K., Chiu, V., Garthwaite, L., Chen, Y., Young, P. M., Traini, D., Kumar, R. K. Tags: PublishAheadOfPrint Source Type: research

BAY 11-7082 inhibits the NF-kB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis.
BAY 11-7082 antagonizes I-B kinase-β preventing nuclear translocation of NF-B; it also inhibits NLRP3 inflammasome activation.NF-B is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20 mg/kg/i.p.) or its vehicle (...
Source: Clinical Science - January 17, 2017 Category: Biomedical Science Authors: Irrera, N., Vaccaro, M., Bitto, A., Pallio, G., Pizzino, G., Lentini, M., Arcoraci, V., Minutoli, L., Scuruchi, M., Cutroneo, G., Anastasi, G. P., Ettari, R., squadrito, F., Altavilla, D. Tags: PublishAheadOfPrint Source Type: research

Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer
Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli (E. coli) could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway which leads to microsatellite instability (MSI). This work, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells. Moreover, we demonstrated that colibactin-producing E....
Source: Clinical Science - January 16, 2017 Category: Biomedical Science Authors: Gagniere, J., Bonnin, V., Jarrousse, A.-S., Cardamone, E., Agus, A., Uhrhammer, N., Sauvanet, P., Dechelotte, P., Barnich, N., Bonnet, R., Pezet, D., Bonnet, M. Tags: PublishAheadOfPrint Source Type: research

HMGB1-induced autophagy: a new pathway to maintain Treg cell function during chronic hepatitis B virus infection
High-mobility group box-1 protein (HMGB1), as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly-conserved self-digestive process in response to environmental stress. Recent mouse studies indicate autophagy is highly active in regulatory T cells (Treg). Here, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autop...
Source: Clinical Science - January 12, 2017 Category: Biomedical Science Authors: Cheng, L.-s., Li, J., Liu, Y., Wang, F.-p., Wang, S.-q., She, W.-m., Wu, S.-d., Qi, X.-l., Zhou, Y.-p., Jiang, W. Tags: PublishAheadOfPrint Source Type: research

MicroRNA-378 reduces mesangial hypertrophy and kidney tubular fibrosis via MAPK signaling
Aims: To determine the regulatory role of a novel miRNA, miR-378, in the development of fibrosis through repression of the MAPK1 (ERK2) pathway. Methods: miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E, and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor. NRK52E cells were co-transfected with the SMAD3 CAGA reporter and miR-378 in the presence of TGF-β1 was assessed.R...
Source: Clinical Science - January 4, 2017 Category: Biomedical Science Authors: Wang, B., Yao, K., Wise, A. F., Lau, R., Shen, H.-H., Tesch, G. H., Ricardo, S. D. Tags: PublishAheadOfPrint Source Type: research

GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction
This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8). Assessments included clinical characteristics and repeated subcutaneous abdominal AT biopsies. Liraglutide resulted in weight loss in most participants (-3.12±1.72kg, p=0.007) and significant reduction in visceral AT. It was more effecti...
Source: Clinical Science - January 3, 2017 Category: Biomedical Science Authors: Pastel, E., McCulloch, L. J., Ward, R., Joshi, S., Gooding, K. M., Shore, A. C., Kos, K. Tags: PublishAheadOfPrint Source Type: research

Dual effects of fructose on ChREBP and FoxO1/3{alpha} are responsible for AldoB upregulation and vascular remodeling
Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodeling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced upregulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms have been unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively. C57Bl/6 mice were fed with control or fructose-enriched diet for 3 months and ultr...
Source: Clinical Science - December 22, 2016 Category: Biomedical Science Authors: Cao, W., Chang, T., Li, X.-q., Wang, R., Wu, L. Tags: PublishAheadOfPrint Source Type: research

Insulinotropic effects of GPR120 agonists are altered in obese non-diabetic and diabetic states
This study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states. GPR120 expression was detected in rodent islet β cells. Docosahexaenoic acid (DHA) and synthetic GPR120 agonist GSK137647 (GSK) augmented insulin release from rat/mouse islets and INS-1E; DHA effects were partially mediated by GPR40. GPR120 knockdown and overexpression attenuated and enhanced DHA effects in INS-1E, respectively. DHA and GSK improved postprandial hyperglycemia of diabetic mice. Inhibition of calcium signalin...
Source: Clinical Science - December 15, 2016 Category: Biomedical Science Authors: Zhang, D., So, W. Y., Wang, Y., Wu, S. Y., Cheng, Q., Leung, P. S. Tags: PublishAheadOfPrint Source Type: research

Decreased circulating BMP-9 levels in patients with type 2 diabetes is a signature of IR
The objective of this study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analyzed by ELISA in 280 well-characterized individuals. 2-h oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a GLP-1 receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulatin...
Source: Clinical Science - December 9, 2016 Category: Biomedical Science Authors: Luo, Y., Li, L., Xu, X., Wu, T., Yang, M., Zhang, C., Mou, H., Zhou, T., Jia, Y., Cai, C., Liu, H., Yang, G., Zhang, X. Tags: PublishAheadOfPrint Source Type: research

The ligands of translocator protein inhibit human Th1 responses and the rejection of murine skin allografts
The translocator protein (TSPO) ligands impacted inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the current study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose- dependent manner by purified human CD4+ T cells from PBMCs after stimulation. TSPO ligands inhibited the production of IFN- by memory CD4+ T cells and the differentiation of naïve CD4+ T cells into Th1 cells via  suppressing the activity of the corresponding transcription factors as indicated by reduced expression ...
Source: Clinical Science - December 6, 2016 Category: Biomedical Science Authors: Zhang, Y., Yu, S., Li, X., Yang, B., Wu, C. Tags: PublishAheadOfPrint Source Type: research

TrpC5 regulates differentiation through the Ca2+-Wnt5a signal pathway in colorectal cancer
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca2+ channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca2+]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading...
Source: Clinical Science - November 28, 2016 Category: Biomedical Science Authors: Chen, Z., Tang, C., Zhu, Y., Xie, M., He, D., Pan, Q., Zhang, P., Hua, D., Wang, T., Jin, L., Qi, X., Zhu, Y., Yao, X., Jin, J., Ma, X. Tags: PublishAheadOfPrint Source Type: research

Enhanced protective responses to a serotype independent pneumococcal vaccine when combined with an inactivated influenza vaccine
In this study we co-immunised C57BL/6 mice intranasally with a mixture of -PN (whole inactivated cells) and -FLU (whole inactivated virions) and examined protective efficacy. Co-immunisation enhanced -PN vaccine efficacy against virulent pneumococcal challenge, which was dependent on CD4+ T cell responses. In contrast to vaccination with -PN alone, co-immunisation enhanced pneumococcal-specific effector Th17 and Th1 memory cells, promoted development of CD4+ tissue-resident memory cells, and enhanced pneumococcus-specific antibody responses. Furthermore, co-immunisation elicited significant protection against lethal influe...
Source: Clinical Science - November 24, 2016 Category: Biomedical Science Authors: Babb, R., Chen, A., Ogunniyi, A. D., Hirst, T. R., Kara, E. E., McColl, S. R., Alsharifi, M., Paton, J. C. Tags: PublishAheadOfPrint Source Type: research

CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome
In this study, male Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were setup for 2 weeks of treatment: Sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + TNF-α antagonist PTX, and CBDL + normal saline groups. Liver and lung tissues were collected after mean arterial pressure (MAP) and portal venous pressure (PVP) measurements. Hematoxylin and Eosin staining (lung) and Masson staining (liver) were performed for pathological analyses. Finally, pulmonary tissue RNA and total protein were assessed for target effectors. The mRNA a...
Source: Clinical Science - November 22, 2016 Category: Biomedical Science Authors: li, X., Chen, Y., Chang, Y., LI, S., Zhao, Z., Zhang, H. Tags: PublishAheadOfPrint Source Type: research

Intact initiation of autophagy and mitochondrial fission by acute exercise in skeletal muscle of patientswith type 2 diabetes
Conclusions: Our results demonstrate that initiation of autophagy and mitochondrial fission is activated by exercise in human skeletal muscle, and that these responses are intact in T2D. The exercise-induced decrease in LC3B-II could be due to increased autophagic turnover. (Source: Clinical Science)
Source: Clinical Science - November 11, 2016 Category: Biomedical Science Authors: Kruse, R., Pedersen, A. J. T., Kristensen, J. M., Petersson, S. J., Wojtaszewski, J. F. P., Hojlund, K. Tags: PublishAheadOfPrint Source Type: research

Strong antineoplastic effects of metformin in preclinical models of liver carcinogenesis
Conclusions The potent antitumoral effects of metformin in multiple preclinical models implicating several molecular mechanisms provide strong rationale for clinical trials including combination studies in hepatocellular carcinoma patients. (Source: Clinical Science)
Source: Clinical Science - November 1, 2016 Category: Biomedical Science Authors: Cauchy, F., Mebarki, M., Leporq, B., Laouirem, S., Albuquerque, M., Lambert, S., Bourgoin, P., Soubrane, O., van Beers, B., Faivre, S., Bedossa, P., Paradis, V. Tags: PublishAheadOfPrint Source Type: research

Homocysteine deteriorates intrahepatic derangement and portal-systemic collaterals in cirrhotic rats
In conclusion, homocysteine is harmful to vascular derangements and liver fibrosis in cirrhosis. (Source: Clinical Science)
Source: Clinical Science - November 1, 2016 Category: Biomedical Science Authors: Tung, H.-C., Hsu, S.-J., Tsai, M.-H., Lin, T.-Y., Hsin, I.-F., Huo, T.-I., Lee, F.-Y., Huang, H.-C., Ho, H.-L., Lin, H.-C., Lee, S.-D. Tags: PublishAheadOfPrint Source Type: research

Defective adaptive thermogenesis contributes to metabolic syndrome and liver steatosis in obese mice
Fatty liver diseases are complications of the metabolic syndrome associated with obesity, insulin resistance and low grade inflammation. Our aim was to uncover mechanisms contributing to hepatic complications in this setting. We used foz/foz mice prone to obesity, insulin resistance and progressive fibrosing NASH. Foz/foz mice are hyperphagic but WT-matched calorie intake failed to protect against obesity, adipose inflammation and glucose intolerance. Obese foz/foz mice had similar physical activity level but reduced energy expenditure. Thermogenic adaptation to high-fat diet or to a cold exposure was severely impaired in ...
Source: Clinical Science - November 1, 2016 Category: Biomedical Science Authors: Poekes, L., Legry, V., Schakman, O., Detrembleur, C., Bol, A., Horsmans, Y., Farrell, G. C., Leclercq, I. A. Tags: PublishAheadOfPrint Source Type: research

Binding of Anti-dsDNA Antibodies to Proximal Tubular Epithelial Cells Contributes to Renal Tubulo-interstitial Inflammation
We examined the effect of human polyclonal anti-dsDNA antibodies on inflammatory processes in cultured proximal renal tubular epithelial cells (HK-2 cells) and their association with serum levels of IL-6, IL-8 and MCP-1 in patients. Binding of anti-dsDNA antibodies to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry. IL-6, IL-8 and MCP-1 secretion, MAPK activation and the effect of mycophenolic acid (MPA) were investigated by ELISAs and Western blot analysis. NZBWF1/J mice with active nephritis were randomized to receive either MMF (100 mg/kg/day) or vehicle for up to 12 weeks to study...
Source: Clinical Science - October 25, 2016 Category: Biomedical Science Authors: Yung, S., Ng, C. Y., Au, K. Y., Cheung, K. F., Zhang, Q., Zhang, C., Yap, D. Y., Chau, M. K., Chan, T. M. Tags: PublishAheadOfPrint Source Type: research

Genetic analysis of rare coding mutations in CELSR1-3 in Chinese Congenital Heart and Neural Tube Defects
The planar cell polarity (PCP) pathway is critical for proper embryonic development of the neural tube and heart. Mutations in these genes have previously been implicated in the pathogenesis of neural tube defects (NTDs), but not in congenital heart defects (CHDs) in humans. We systematically identified the mutation patterns of CELSR1-3 , one family of the core PCP genes, in human cohorts composed of 352 NTD cases, 412 CHD cases, and matched controls. A total of 72 disease-specific rare novel coding mutations were identified, of which 37 were identified in CHD cases, and 36 were identified in NTD patients. Most of these mu...
Source: Clinical Science - October 18, 2016 Category: Biomedical Science Authors: Qiao, X., Liu, Y., Li, P., Chen, Z., Li, H., Yang, X., Finnell, R. H., Yang, Z., Zhang, T., Qiao, B., Zheng, Y., Wang, H. Tags: PublishAheadOfPrint Source Type: research

Mas receptor contributes to pregnancy-induced cardiac remodeling
In conclusion, these data show that while Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of the cardiac function through Mas-independent mechanism. (Source: Clinical Science)
Source: Clinical Science - October 7, 2016 Category: Biomedical Science Authors: Carmos-Silva, C., Almeida, J. F. Q. d., Macedo, L. M., Melo, M. B. B., Pedrino, G. R., Santos, F. F. C. A., Biancardi, M. F., Santos, R. A. S. d. A. S., Carvalho, A. A., Mendes, E. P., Colugnati, D. B., Mazaro-Costa, R., Castro, C. H. d. Tags: PublishAheadOfPrint Source Type: research

mPGES-1 deletion affects platelet functions in mice
Microsomal prostaglandin E2 synthase-1 (mPGES-1) constitutes an essential player of inflammation and is involved in the pathogenesis of rheumatoid arthritis (RA). Platelets participate in the regulation of inflammatory processes by the release of pro-inflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE2 pathway on platelet functions has not been investigated. Here we report a significant impact of mPGES-1 on platelet functions during inflammation. Wild-type (WT) and mPGES-1-/- (KO) mice were stimulated with lipopolysaccharide (LPS) for 24 hours. Platelet cou...
Source: Clinical Science - October 7, 2016 Category: Biomedical Science Authors: Raouf, J., Mobarrez, F., Larsson, K., Jakobsson, P.-J., Korotkova, M. Tags: PublishAheadOfPrint Source Type: research

Novel role of Vav1-Rac1 pathway in actin cytoskeleton regulation in Interleukin-13-induced minimal change-like nephropathy
In conclusion, we have demonstrated the role of Vav1-Rac1 pathway characterised by phosphorylation of Vav1, activation of Rac1 and the subsequent actin cytoskeleton rearrangement in IL-13 induced podocyte injury, possibly explaining the podocyte foot process effacement seen in our IL-13 overexpression rat model. (Source: Clinical Science)
Source: Clinical Science - October 5, 2016 Category: Biomedical Science Authors: Chan, C.-Y., Ng, K.-H., Chen, J., Lu, J., Lee, C. G.-L., Tan, P.-H., Jordan, S. C., Yang, H. H., Yap, H.-K. Tags: PublishAheadOfPrint Source Type: research

Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload
Conclusions DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through JNK inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. (Source: Clinical Science)
Source: Clinical Science - October 4, 2016 Category: Biomedical Science Authors: Li, W.-m., Zhao, Y.-f., Zhu, G.-f., Peng, W.-h., Zhu, M.-y., Yu, X.-j., Chen, W., Xu, D.-c., Xu, Y.-w. Tags: PublishAheadOfPrint Source Type: research

cTnI Exacerbates Myocardial Ischemia/Reperfusion Injury by Inducing Adhesion of Monocytes to VECs via TLR4/NF-{kappa}B-dependent Pathway
Cardiac troponin I (cTnI), a biomarker for myocardial damage and risk stratification, may be involved in the pathogenesis of cardiovascular diseases, which was ascribed to the effect of cTnI auto-antibodies. Whether or not cTnI itself has a direct impact on acute myocardial injury is unknown. To exclude the influence of cTnI antibody on the cardiac infarct size, we studied the effect of cTnI shortly after myocardial ischemia-reperfusion (I/R) injury when cTnI antibodies were not elevated. Pretreatment with cTnI augmented the myocardial infarct size caused by&...
Source: Clinical Science - September 28, 2016 Category: Biomedical Science Authors: Han, Y., Liao, X., Gao, Z., Yang, S., Chen, C., Liu, Y., Wang, W. E., Wu, G., Chen, X., Jose, P. A., Zhang, Y., Zeng, C. Tags: PublishAheadOfPrint Source Type: research

Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulants Dicumarol
In this study, we analyzed the gene expression profiles of preoperative samples from ER-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signaling pathways of these genes. Inhibiting the PSG1 can effectively reduce chemoresistance via transforming growth factor-β (TGF-β)-related pathway in ER-negative breast cancer cells. Drug screening then identified dicumarol (DCM) to target the PSG1 and inhibited chemoresistan...
Source: Clinical Science - September 21, 2016 Category: Biomedical Science Authors: He, D.-x., Gu, F., Wu, J., Gu, X.-T., Lu, C.-x., Mao, A.-q., Zhang, G.-y., Ding, Z.-y., Wang, J.-k., Hao, J.-j., Fu, L., Ma, X. Tags: PublishAheadOfPrint Source Type: research

Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airways disease
This study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone (intranasally (i.n)-administered with 1x106 cells once weekly), RLX alone (i.n-administered with 0.8mg/ml daily) or a combination of MSCs or AECs and RLX from weeks ...
Source: Clinical Science - September 19, 2016 Category: Biomedical Science Authors: Royce, S. G., Tominaga, A. M., Shen, M., Patel, K. P., Huuskes, B. M., Lim, R., Ricardo, S. D., Samuel, C. S. Tags: PublishAheadOfPrint Source Type: research

Shifts in Lachnospira and Clostridium sp. in the 3-month stool microbiome are associated with preschool-age asthma
Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in one-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n = 39) or matched healthy controls (n...
Source: Clinical Science - September 15, 2016 Category: Biomedical Science Authors: Stiemsma, L., Arrieta, M.-C., Dimitriu, P., Cheng, J., Thorson, L., Lefebvre, D., Azad, M. B., Subbarao, P., Mandhane, P., Becker, A., Sears, M., Kollmann, T., Mohn, W., Finlay, B., Turvey, S. Tags: PublishAheadOfPrint Source Type: research

Apple peel polyphenols: A key player in the prevention and treatment of experimental inflammatory bowel disease
In conclusions, DAPP exhibit powerful anti-oxidant and anti-inflammatory actions in the intestine and are associated with the regulation of cellular signaling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases. (Source: Clinical Science)
Source: Clinical Science - September 14, 2016 Category: Biomedical Science Authors: Denis, M. C., Roy, D., Yeganeh, P. R., Desjardins, Y., Varin, T., Haddad, N., Amre, D., Sane, A. T., Garofalo, C., Furtos, A., Patey, N., Delvin, E., Tremblay, E., Marette, A., Beaulieu, J. F., Levy, E. Tags: PublishAheadOfPrint Source Type: research

Mas receptor contributes to pregnancy-induced cardiace remodeling
In conclusion, these data show that while Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of the cardiac function through Mas-independent mechanism. (Source: Clinical Science)
Source: Clinical Science - September 13, 2016 Category: Biomedical Science Authors: Carmos-Silva, C., Almeida, J., Macedo, L., Melo, M. B., Pedrino, G., Santos, F., Biancardi, M., Santos, R. A. S., Carvalho, A., Mendes, E., Colugnati, D., Mazaro-Costa, R., Castro, C. Tags: PublishAheadOfPrint Source Type: research

Potential role of microRNA-10b down-regulation in cardiomyocyte apoptosis in aortic stenosis patients
MicroRNAs have been associated with cardiomyocyte apoptosis, a process involved in myocardial remodelling in aortic valve (Av) stenosis (AS). Our aim was to analyse whether the dysregulation of myocardial microRNAs was related to cardiomyocyte apoptosis in AS patients. Endomyocardial biopsies were obtained from 28 patients with severe AS (based on pressure gradients and Av area) referred to Av replacement and from necropsies of 10 cardiovascular disease-free control subjects. AS patients showed an increased ( P 0.08%; n=12). Group 2 patients presented lower cardiomyocyte density ( P
Source: Clinical Science - September 13, 2016 Category: Biomedical Science Authors: Gallego, I., Beaumont, J., Lopez, B., Ravassa, S., Jose Gomez-Doblas, J. J., Moreno, M. U. U., Valencia, F., de Teresa, E., Diez, J., Gonzalez, A. Tags: PublishAheadOfPrint Source Type: research

Mesenchymal Stem Cells-Conditioned Media Ameliorates Diabetic Endothelial dysfunction by Improving Mitochondrial Bioenergetics via the Sirt1/AMPK/PGC-1{alpha} Pathway
Vasculopathy is a major complication of diabetes. Impaired mitochondrial bioenergetics and biogenesis due to oxidative stress is a critical causal factor for diabetic endothelial dysfunction. Sirt1, a NAD+-dependent enzyme, is known to play an important protective role through deacetylation of many substrates involved in oxidative phosphorylation and reactive oxygen species (ROS) generation. Conditioned medium from mesenchymal stem cells (MSCs-CM) has emerged as a promising cell-free therapy due to the trophic actions of MSCs secreted molecules. Here, we investigated the therapeutic potential of MSCs-CM on diabetic endothe...
Source: Clinical Science - September 9, 2016 Category: Biomedical Science Authors: Yuan, Y., Shi, M., Li, L., Liu, J., Chen, B., Chen, Y., An, X., Liu, S., Luo, R., Long, D., Zhang, W., Newsholme, P., Cheng, J., Lu, Y. Tags: PublishAheadOfPrint Source Type: research

APOA5 genetic and epigenetic variability jointly regulate circulating triglyceride levels.
In conclusion, CGI methylation in exon 3 of APOA5 acts, in combination with -1131T>C, S19W and 724C>G polymorphisms, in the individual's predisposition to high circulating TG levels. This serves as an example that combined analysis of SNPs and methylation applied to a larger set of genes would improve our understanding of predisposition to hypertriglyceridemia. (Source: Clinical Science)
Source: Clinical Science - September 9, 2016 Category: Biomedical Science Authors: Oliva, I., Guardiola, M., Vallve, J. C., Ibarretxe, D., Plana, N., Masana, L., Monk, D., Ribalta, J. Tags: PublishAheadOfPrint Source Type: research

Identification of genetic defects in pulmonary arterial hypertension by a new panel diagnostic
Conclusions:The new PAH-specific gene panel developed in this study allowed for the first time the assessment of all known PAH genes and further candidates at once and markedly reduced overall sequencing time and costs. Sensitivity and specificity reached 100% when Sanger sequencing was additionally applied. Thus, this technique will potentially change the routine diagnostic genetic testing in PAH patients. (Source: Clinical Science)
Source: Clinical Science - September 9, 2016 Category: Biomedical Science Authors: Song, J., Eichstaedt, C. A., Rodriguez Viales, R., Benjamin, N., Harutyunova, S., Fischer, C., Grunig, E., Hinderhofer, K. Tags: PublishAheadOfPrint Source Type: research

Ultrasound-targeted Microbubble Destruction Enhances Delayed BMC Delivery and Attenuates Post-infarction Cardiac Remodeling by Inducing Engraftment Signals
Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. Here, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs, and subsequently attenuate post-infarction cardiac remodeling. A myocardial ischemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligati...
Source: Clinical Science - September 8, 2016 Category: Biomedical Science Authors: Chen, Y., Zhang, C., Shen, S., Guo, S., Zhong, L., Li, X., Chen, G., Chen, G., He, X., Huang, C., He, N., Liao, W., Liao, Y., Bin, j. Tags: PublishAheadOfPrint Source Type: research

Vasopressin Type 1A Receptor Deletion Enhances Cardiac Contractility, {beta}-Adrenergic Receptor Sensitivity and Acute Cardiac Injury-induced Dysfunction
V1AR expression is elevated in chronic human heart failure and contributes to cardiac dysfunction in animal models, in part via reduced βAR responsiveness.  While cardiac V1AR overexpression and V1AR stimulation are each sufficient to decrease βAR activity, it is unknown whether V1AR inhibition conversely augments βAR responsiveness.  Further, although V1AR has been shown to contribute to chronic progression of heart failure, its impact on cardiac function following acute ischemic injury has not been reported.  Using V1AR KO mice we assessed the impact of V1AR deletion on cardiac contractility...
Source: Clinical Science - September 2, 2016 Category: Biomedical Science Authors: Wasilewski, M. A., Grisanti, L. A., Song, J., Carter, R. L., Repas, A. A., Myers, V. D., Gao, E., Koch, W. J., Cheung, J. Y., Feldman, A. M., Tilley, D. Tags: PublishAheadOfPrint Source Type: research

OX40 Regulates pressure overload induced cardiac hypertrophy and remodelling Via CD4+ T Cells
In this study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In this study, cardiac hypertrophy was induced by aortic banding in OX40 knockout (KO) mice and wild-type mice. After 8 weeks, the OX40 KO mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation as well as preserved cardiac function compared with the wild-type mice. Follow-up in vitro studies suggested that CD4+ T lymphocyte proliferation and pro-inflammatory cytokine release were significantly decreased, while anti-inflammatory cytokine release was considerably increased in OX40 KO m...
Source: Clinical Science - August 31, 2016 Category: Biomedical Science Authors: Wu, Q. Q., Yuan, Y., Jiang, X. H., Xiao, Y., Yang, Z., Ma, Z. G., Liao, H. H., Liu, Y., Chang, W., Bian, Z. Y., Tang, Q. Z. Tags: PublishAheadOfPrint Source Type: research

Influence of Gestational Diabetes Mellitus on Human Umbilical Vein Endothelial Cell microRNA
To identify microRNAs (miRNAs) whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) impacts both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes.A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycemic controls. miRNAs were ide...
Source: Clinical Science - August 25, 2016 Category: Biomedical Science Authors: Tryggestad, J. B., Vishwanath, A., Jiang, S., Mallappa, A., Teague, A. M., Takahashi, Y., Thompson, D. M., Chernausek, S. D. Tags: PublishAheadOfPrint Source Type: research

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury
Eph-Ephrin signaling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homeostasis, and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signaling are unknown. Here, we evaluated the role of EphA2 signaling from mice with LPS-induced lung injury. Acute LPS exposure significantly upregulated EphA2 and EphrinA1 expression. Compared with LPS + IgG mice (IgG instillation after LPS exposure), LPS+ E...
Source: Clinical Science - August 22, 2016 Category: Biomedical Science Authors: Hong, J. Y., Shin, M. H., Douglas, I. S., Chung, K. S., Kim, E. Y., Jung, J. Y., Kang, Y. A., Kim, S. K., Chang, J., Kim, Y. S., Park, M. S. Tags: PublishAheadOfPrint Source Type: research

Glufosinate aerogenic exposure induces glutamate and IL-1 receptors dependent lung inflammation.
In conclusion, GLA aerosol exposure causes glutamate signaling and IL-1R dependent pulmonary inflammation with airway hyperreactivity in mice. (Source: Clinical Science)
Source: Clinical Science - August 22, 2016 Category: Biomedical Science Authors: MAILLET, I., PERCHE, O., PARIS, A., RICHARD, O., GOMBAULT, A., HERZINE, A., PICHON, J., HUAUX, F., MORTAUD, S., RYFFEL, B., QUESNIAUX, V., Montecot-Dubourg, C. Tags: PublishAheadOfPrint Source Type: research

Angiotensin-(1-7) decreases the expression of collagen I via TGF-{beta}1/Smad2/3 and subsequently inhibits fibroblast-myofibroblast transition
Previous studies have shown that renin-angiotensin system (RAS) might participate in airway remodeling in asthma. As a main component in RAS, Angiotensin-(1-7) [Ang-(1-7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signaling pathways of Ang-(1-7) have not been well illustrated. In the present study, we analyzed the effect of Ang-(1-7) on Angiotensin II (AngII)-induced human lung fibroblast (HLF)-myofibroblast (MF) transition by detecting collagen type I (Col-I), transforming growth factor-beta 1(TGF-β1) and α-smooth muscle actins (&alpha...
Source: Clinical Science - August 19, 2016 Category: Biomedical Science Authors: Zhou, J. P., Tang, W., Feng, Y., Li, N., Gu, C. J., Li, Q. Y., Wan, H. Y. Tags: PublishAheadOfPrint Source Type: research

Lung function and respiratory symptoms in a randomized smoking cessation trial of electronic cigarettes
Quitting smoking is the most important step smokers can take to improve their health. Nonetheless, there is little information on long-term improvements in lung function and/or respiratory symptoms after smoking cessation. Here we illustrate long-term changes in spirometric indices as well as in respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to electronic cigarettes. Prospective evaluation of cigarette consumption, spirometry and symptoms was performed in a 1-year randomized controlled trial of smokers receiving electronic cigarette containing 2.4%, 1.8%, or 0% nicotine. ...
Source: Clinical Science - August 19, 2016 Category: Biomedical Science Authors: Cibella, F., Campagna, D., Caponnetto, P., Amaradio, M. D., Caruso, M., Russo, C., Cockcroft, D. W., Polosa, R. Tags: PublishAheadOfPrint Source Type: research

Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity
We previously developed cardiac ventricle-specific choline acetyltransferase ( ChAT ) gene-overexpressing transgenic mice ( ChAT tgm), i.e., an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous report, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the WT mice brains; in contrast, the ChAT tgm h...
Source: Clinical Science - August 15, 2016 Category: Biomedical Science Authors: Oikawa, S., Kai, Y., Tsuda, M., Ohata, H., Mano, A., Mizoguchi, N., Sugama, S., Nemoto, T., Suzuki, K., Kurabayashi, A., Muramoto, K., Kaneda, M., Kakinuma, Y. Tags: PublishAheadOfPrint Source Type: research

Dual Actions of Netrin-1 on Islet Insulin Secretion and Immune Modulation
Conclusions: We propose here a dual action of Netrin-1 in islets during pathophysiological hyperglycaemia: by maintaining insulin secretion while attenuating inflammation. (Source: Clinical Science)
Source: Clinical Science - August 12, 2016 Category: Biomedical Science Authors: Gao, S., Zhang, X., Qin, Y., Xu, S., Zhang, J., Wang, Z., Wang, W., Kong, D., Li, C. Tags: PublishAheadOfPrint Source Type: research

Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis
Background: Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of HDL has been observed. Although the actual players are unknown, anti-HDL were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario. Methods: IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC), and 54 subjects with traditional CV r...
Source: Clinical Science - August 12, 2016 Category: Biomedical Science Authors: Rodriguez-Carrio, J., Alperi-Lopez, M., Lopez-Mejias, R., Lopez, P., Ballina-Garcia, F. J., Abal, F., Gonzalez-Gay, M. A., Suarez, A. Tags: PublishAheadOfPrint Source Type: research