Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy
Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVECs-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and ...
Source: Clinical Science - April 15, 2019 Category: Biomedical Science Authors: Zeng, T., Wang, X., Wang, W., Feng, Q., Lao, G., Liang, Y., Wang, C., Zhou, J., Chen, Y., Liu, J., Gao, H., Lan, B., Wu, Y., Han, Y., Liu, Y., Chen, H., Liu, L., Yang, C., Yan, L., Ren, M., Sun, K. Tags: PublishAheadOfPrint Source Type: research

Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats
In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI. (Source: Clinical Science)
Source: Clinical Science - April 12, 2019 Category: Biomedical Science Authors: Neckař, J., Hye Khan, M. A., Gross, G. J., Cyprova, M., Hrdlička, J., Kvasilova, A., Falck, J. R., Campbell, W. B., Sedlakova, L., Škutova, Šarka, Olejničkova, V., Gregorovičova, M., Sedmera, D., Kolař, F., Tags: PublishAheadOfPrint Source Type: research

Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL33/ST2 signaling axis
In conclusion, our data suggest an important role for ST2/IL-33 signaling axis in RV-induced pathological changes in COPD mice. (Source: Clinical Science)
Source: Clinical Science - April 5, 2019 Category: Biomedical Science Authors: Gimenes, J. A., Srivastava, V., Reddyvari, H., Kotnala, S., Mishra, R., Farazuddin, M., Li, W., Sajjan, U. S. Tags: PublishAheadOfPrint Source Type: research

Glutaminolysis and lipoproteins are key factors in late immune recovery in successfully treated HIV-infected patients
The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive cART. Integrated data from NMR-based lipoprotein profiles, MS-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune...
Source: Clinical Science - April 5, 2019 Category: Biomedical Science Authors: Rosado-Sanchez, I., Rodriguez-Gallego, E., Peraire, J., Vilades, C., Herrero, P., Fanjul, F., Gutierrez, F., Bernal, E., Pelazas, R., Leal, M., Veloso, S., Lopez-Dupla, M., Blanco, J., Vidal, F., Pacheco, Y. M., Rull, A. Tags: PublishAheadOfPrint Source Type: research

A pan-RAF inhibitor LY3009120 inhibits necroptosis by preventing phosphorylation of RIPK1 and alleviates dextran sulfate sodium (DSS)-induced colitis
A dramatic increase in the incidence of inflammatory bowel disease (IBD) has been observed in the past 2 decades, mainly in developed countries but also in developing regions. Necroptosis has been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), suggesting its inhibitors are promising in clinic. However, clinical drugs targeting necroptosis are seriously lacking. Through screening a clinical compound library that contains 611 inhibitors, a pan-RAF inhibitor LY3009120 was found to be promising as a necroptosis inhibitor. LY3009120 inhibited necroptosis in vitro , and its inhibition ag...
Source: Clinical Science - April 3, 2019 Category: Biomedical Science Authors: Zhang, C., Luo, Y., He, Q., Liu, S., He, A., Yan, J. Tags: PublishAheadOfPrint Source Type: research

Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities
Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5
Source: Clinical Science - April 2, 2019 Category: Biomedical Science Authors: Ko, C.-Y., Liu, Q.-Q., Su, H.-Z., Zhang, H.-P., Fan, J.-M., Yang, J.-H., Hu, A.-K., Liu, Y.-Q., Chou, D., Zeng, Y.-M. Tags: PublishAheadOfPrint Source Type: research

Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation
Conclusions: We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. This study highlights a new therapeutic strategy for early stent endothelialization. (Source: Clinical Science)
Source: Clinical Science - March 26, 2019 Category: Biomedical Science Authors: Liu, X., Zhang, R., Hou, J., Wu, J., Zhang, M., Fang, S., Wang, X., Huang, X., Tian, J., Li, H., Sun, Y., Yu, B. Tags: PublishAheadOfPrint Source Type: research

Cell-surface Translocation of Annexin A2 contributes to bleomycin-induced pulmonary fibrosis by mediating inflammatory response in mice
Bleomycin, a widely used anti-cancer drug, may give rise to pulmonary fibrosis, a serious side effect which is associated with significant morbidity and mortality. Despite the intensive efforts, the precise pathogenic mechanisms of pulmonary fibrosis still remain to be clarified. Our previous study showed that bleomycin bound directly to annexin A2 (ANXA2, or p36), leading to development of pulmonary fibrosis by impeding TFEB-induced autophagic flux. Here, we demonstrated that ANXA2 also played a critical role in bleomycin-induced inflammation, which represents another major cause of bleomycin-induced pulmonary fibrosis. W...
Source: Clinical Science - March 22, 2019 Category: Biomedical Science Authors: Lei, Y., Wang, K., Li, X., Li, Y., Feng, X., Zhou, J., Zhang, Z., Huang, C., Zhang, T. Tags: PublishAheadOfPrint Source Type: research

Use of the immunoglobulin G avidity assay to differentiate between recent Zika and past dengue virus infections
Conclusions. The IgG avidity assay accurately distinguished recent ZIKV from past DENV infections in patients who traveled to dengue endemic regions. This assay could be very useful in patients with high risk of Zika complications such as pregnant women and monitoring immune responses in vaccine trials. (Source: Clinical Science)
Source: Clinical Science - March 22, 2019 Category: Biomedical Science Authors: Furuya, A. K., Hunt, D., St. George, K., Dupuis, A. P., Kramer, L. D., Shi, P.-Y., Wong, S. Tags: PublishAheadOfPrint Source Type: research

Identification of an activated neutrophil phenotype in polymyalgia rheumatica during steroid treatment: potential involvement of immune cell cross talk
We have reported the existence of a distinct neutrophil phenotype in giant cell arteritis (GCA) patients arising at week 24 of steroid treatment. In the present study, we investigated whether longitudinal analysis of neutrophil phenotype in patients with polymyalgia rheumatica (PMR) could reveal a novel association with disease status and immune cell cross-talk. Thus, we monitored PMR patient neutrophil phenotype and plasma microvesicle profiles in blood aliquots collected pre-steroid, and then at weeks 1, 4, 12 and 24 post-steroid treatment. Using flow cytometric and flow chamber analyses we identified 12-week post-steroi...
Source: Clinical Science - March 21, 2019 Category: Biomedical Science Authors: Nadkarni, S., Lashin, H., Hollywood, J., Dasgupta, B., Mason, J. C., Perretti, M. Tags: PublishAheadOfPrint Source Type: research

Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus
Intestinal dysbiosis is implicated in Systemic lupus erythematosus (SLE). However, the evidence of gut microbiome changes in SLE is limited, and the association of changed gut microbiome with the activity of SLE, as well as its functional relevance with SLE still remains unknown. Here, we sequenced 16S rRNA amplicon on fecal samples from 40 SLE patients (19 active patients, 21 remissive patients), 20 disease controls (Rheumatoid Arthritis patients), and 22 healthy controls, and investigated the association of functional categories with taxonomic composition by Phylogenetic Investigation of Communities by Reconstruction of ...
Source: Clinical Science - March 14, 2019 Category: Biomedical Science Authors: Li, Y., Wang, H., Li, X., Li, H., Zhang, Q., Zhou, H., He, Y., Li, P., Fu, C., Zhang, X., Qiu, Y., Li, J.-L. Tags: PublishAheadOfPrint Source Type: research

Metabolomic analysis reveals metabolic characteristics of children with short stature caused by growth hormone deficiency
The diagnosis of short stature (SS) is of widespread important for later treatment. In this paper, a metabolomic method was used to analyze the metabolic characteristics of SS children caused by endocrine metabolic diseases in order to understand the underlying biochemical mechanism and provide a potential intervention strategy for SS. According to the clinical diagnosis and family investigation, all patients with SS were confirmed to be due to the endocrine disorders, especially GHD. A nuclear magnetic resonance (NMR)-based metabolomic analysis of serum was used to identify the metabolic changes of 45 SS children from the...
Source: Clinical Science - March 13, 2019 Category: Biomedical Science Authors: Xu, R., Zhu, H., Zhang, C., Shen, G., Feng, J. Tags: PublishAheadOfPrint Source Type: research

Melatonin suppresses lung cancer metastasis by inhibition of epithelial-mesenchymal transition through targeting to Twist
The epithelial-mesenchymal transition (EMT) phenotype, whereby mature epithelial cells undergo phenotype transition and differentiate into motile, invasive cells, has been indicated in tumor metastasis. The melatonin hormone secreted by the pineal gland has an antioxidant effect and protects cells against carcinogenic substances that reduce tumor progression. However, the effects of melatonin in EMT and lung cancer metastasis are largely unknown. We found that melatonin downregulated EMT by inhibiting Twist/Twist1 (twist family bHLH transcription factor 1) expression. This effect was mediated by MT1 receptor, PLC, p38/ERK ...
Source: Clinical Science - February 26, 2019 Category: Biomedical Science Authors: Chao, C.-C., Chen, P.-C., Chiou, P.-C., Hsu, C.-J., Liu, P.-Y., Yang, Y.-C., Reiter, R., Yang, S.-F., Tang, C. H. Tags: PublishAheadOfPrint Source Type: research

The serum biomarker chemerin promotes tumorigenesis and metastasis in oral squamous cell carcinoma
Chemerin, which is encoded by retinoic acid receptor responder 2 (RARRES2), has been found to be related to malignant tumours, but its role in the development of oral squamous cell carcinoma (OSCC) is largely unexplored. In the present study, a higher serum level of chemerin was evident in patients with OSCC than in healthy individuals, and this high level of chemerin significantly decreased after tumour resection. In addition, high chemerin levels were positively associated with advanced tumour stage and lymph node metastasis. The expression levels of chemerin and Chemerin Receptor 23 (ChemR23) were positiv...
Source: Clinical Science - February 25, 2019 Category: Biomedical Science Authors: Lu, Z., Liang, J., He, Q., Wan, Q., Hou, J., Lian, K., Wang, A. Tags: PublishAheadOfPrint Source Type: research

Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning mediated cardioprotection
Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection. I/R was induced either ex vivo or in vivo in male wild type (WT) and MIF knockout (MIFKO) mice with or without proceeding IPC (3 cycles of 5 min ischemia and 5 min reperfusion). Indices of myocardial injury, regional inflammation and cardiac function were determined to evaluate the exte...
Source: Clinical Science - February 25, 2019 Category: Biomedical Science Authors: Ruze, A., Chen, B.-D., Liu, F., Chen, X.-C., Gai, M.-T., Li, X.-M., Ma, Y.-T., Du, X.-J., Yang, Y.-N., Gao, X.-M. Tags: PublishAheadOfPrint Source Type: research

STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer
Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro . In pancreatic cancer cells t...
Source: Clinical Science - February 19, 2019 Category: Biomedical Science Authors: Liu, C., Shi, J., Li, Q., Li, Z., Lou, C., Zhao, Q., Zhu, Y., Zhan, F., Lian, J., Wang, B., Guan, X., Fang, L., Li, Z., Wang, Y., Zhou, B., Yao, Y., Zhang, Y. Tags: PublishAheadOfPrint Source Type: research

FNDC5/Irisin inhibits pathological cardiac hypertrophy
In conclusion, we find irisin is secreted in an ADAM family dependent manner, and irisin treatment improves cardiac function and attenuates pressure overload-induced cardiac hypertrophy and fibrosis mainly through regulating AMPK-mTOR signaling. (Source: Clinical Science)
Source: Clinical Science - February 19, 2019 Category: Biomedical Science Authors: Yu, Q., Kou, W., Xu, X., Zhou, S., Luan, P., Xu, X., Li, H., Zhuang, J., Wang, J., Zhao, Y., Xu, Y., Peng, W.-h. Tags: PublishAheadOfPrint Source Type: research

MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons
Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here we show that SPAST , which encodes a microtubule-severing protein called spastin, was a novel target gene of miR-33 in human. Actually, the miR-33 binding site in the SPAST 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of miR-33 on SPAST in mice. We demonstrated that inhibition of miR-33a, a major form o...
Source: Clinical Science - February 18, 2019 Category: Biomedical Science Authors: Nakazeki, F., Tsuge, I., Horie, T., Imamura, K., Tsukita, K., Hotta, A., Baba, O., Kuwabara, Y., Nishino, T., Nakao, T., Nishiga, M., Nishi, H., Nakashima, Y., Ide, Y., Koyama, S., Kimura, M., Tsuji, S., Naitoh, M., Suzuki, S., Izumi, Y., Kawarai, T., Kaj Tags: PublishAheadOfPrint Source Type: research

Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice.
Conclusions - Alamandine treatment prevents vascular remodelling after TAC, at least in part, through anti-fibrotic and anti-inflammatory effects. Hence, this work opens new avenues for the use of this heptapeptide also as a therapeutic target for vascular disease. (Source: Clinical Science)
Source: Clinical Science - February 8, 2019 Category: Biomedical Science Authors: Souza-Neto, F. P. d., Silva, M. M., Santuchi, M. d. C., de Alcantara-Leonidio, T. C., Motta-Santos, D., Oliveira, A., Melo, M. B., Canta, G. N., de Souza, L. E., Irigoyen, M. C., Campagnole-Santos, M. J., Guatimosim, S., Souza dos Santos, R. A., Silva, R. Tags: PublishAheadOfPrint Source Type: research

Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis
Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiate and drive the long-term progression of disease.  In particular, there are no effective therapeutics that target neutroph...
Source: Clinical Science - February 7, 2019 Category: Biomedical Science Authors: Yu, X., Seow, H. J., Wang, H., Anthony, D., Bozinovski, S., Lin, L., Ye, J.-M., Vlahos, R. Tags: PublishAheadOfPrint Source Type: research

Omeprazole prevents CDX2 and SOX9 expression by inhibiting hedgehog signaling in Barrett's esophagus cells
Activation of hedgehog(Hh) signaling contributes to the progression of Barrett's Esophagus(BE), which increases the risk of esophageal adenocarcinoma. Recent clinical studies revealed Proton-pump inhibitors (PPIs) but not H2 Receptor Antagonists (H2RAs) were associated with a decreased risk of esophageal adenocarcinoma. We would like to know whether PPIs interfere with BE progression during BE treatment. Here, we explored the role of omeprazole on Hh signaling and expression of two crucial biomarkers of BE, SOX9 and CDX2. We demonstrated that bile acids elevated expression of Hh pathway target genes, such as GLI1 and PTCH1...
Source: Clinical Science - January 31, 2019 Category: Biomedical Science Authors: Huang, J., Liu, H., Sun, T., Fang, J.-Y., Wang, J., Xiong, H. Tags: PublishAheadOfPrint Source Type: research

Activation of G protein-coupled estrogen receptor (GPER) protects intestine from ischemia/reperfusion injury in mice by protecting the crypt cell proliferation
The intestinal ischemia/reperfusion (I/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein-coupled estrogen receptor (GPER) could protect the intestine against I/R injury and explored the mechanism. Adult male C57BL/6 mice were subjected to intestinal I/R injury by clamping (45 min) of the superior mesenteric artery followed by 4 h of intestinal reperfusion. Our results revealed that the selective GPER blocker abolished t...
Source: Clinical Science - January 31, 2019 Category: Biomedical Science Authors: Chai, S., Liu, K., Feng, W., Liu, T., Wang, Q., Zhou, R., Chen, S., Wang, L., Chen, G., Ming, T., Zhao, J., Liu, C., Xue, B. Tags: PublishAheadOfPrint Source Type: research

Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury
An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during I/R injury.  Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated.  We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury.  Forty Male Wistar rats were subjected to a 30-min ischemia by coronary occlusion, foll...
Source: Clinical Science - January 31, 2019 Category: Biomedical Science Authors: Maneechote, C., Palee, S., Kerdphoo, S., Jaiwongkam, T., Chattipakorn, S., Chattipakorn, N. Tags: PublishAheadOfPrint Source Type: research

Involvement of serum amyloid A1 in the rupture of fetal membranes through induction of collagen I degradation
The de novo synthesis of serum amyloid A1 (SAA1) is augmented in human fetal membranes at parturition. However, its role in parturitionremains largely unknown. Here, we investigated whether SAA1 wasinvolved inthe rupture of fetal membranes, a crucial event in parturition accompanied with extensive degradation of collagens. Results showed that SAA1 decreased both intracellular and extracellular COL1A1 and COL1A2 abundance,the two subunits ofcollagen I, without affecting theirmRNAlevels in human amnion fibroblasts.These reductions were completely blocked only with inhibition of both matrix metalloproteases (MMPs)and autophag...
Source: Clinical Science - January 25, 2019 Category: Biomedical Science Authors: Wang, W.-s., Li, W.-j., Wang, Y.-w., Wang, L.-y., Mi, Y.-b., Lu, J.-w., Lu, Y., Zhang, C.-y., Sun, K. Tags: PublishAheadOfPrint Source Type: research

Suppression of MicroRNA Let-7i-5p Promotes Cardiomyocyte Proliferation and Repairs Heart Function Post Injury by Targeting CCND2 and E2F2.
This study was undertaken to characterize the role of let-7i-5p in the processes of cardiomyocyte cell cycle and proliferation and to reveal the mechanisms thereof. In this study, we used real-time qPCR to determine the upregulated let-7i-5p in cardiomyocytes during the postnatal switch from proliferation to terminal differentiation and further validated the role of let-7i-5p by loss- and gain-of-function of let-7i-5p in cardiomyocytes in vitro and in vivo . We found that the overexpression of let-7i-5p inhibited cardiomyocyte proliferation, whereas the suppression of let-7i-5p significantly facilitated cardiomyocyte proli...
Source: Clinical Science - January 24, 2019 Category: Biomedical Science Authors: Hu, Y., Jin, G., Li, B., Chen, Y., Zhong, L. L., Chen, G., Chen, X., Zhong, J., Liao, W., Liao, Y., Wang, Y., Bin, J. Tags: PublishAheadOfPrint Source Type: research

MTHFR C677T polymorphism Increases MTX Sensitivity via the Inhibition of S-adenosylmethionine and De Novo Purine Synthesis
Objective. Currently no guidelines are established for pharmacogenomic testing involving folate metabolic genes in long-term disease-modifying antirheumatic drugs (DMARD) therapies. We carefully investigated how common genetic variations in methylenetetrahydrofolate reductase ( MTHFR ) influence cellular metabolic kinetics in response to methotrexate (MTX). Designs. Two distinct cell models: HepG2 with stabilized MTHFR  inhibition using shRNA delivered by a Lentiviral vector; and Epstein-Barr virus transformed human lymphoblasts expressing MTHFR polymorphic allele 677C and 677T were used.  Disease activity a...
Source: Clinical Science - January 17, 2019 Category: Biomedical Science Authors: Wang, Y.-C., Wu, M.-T., Tang, F.-Y., Chen, D.-Y., Ko, H.-A., Shane, B., Huang, W.-N., Chiang, E.-P. Tags: PublishAheadOfPrint Source Type: research

Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure
Activation of the sympathetic nervous system is ahallmark of heart failure and is positively correlated with disease progression. Catecholaminergic (C1) neurons locatedin the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload heart failure (HF). However, there is no conclusiveevidence showing acontribution of RVLM-C1 neurons to the developmentof cardiac dysfunctionin the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats. A surgical art...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Andrade, D. C., Toledo, C., Diaz, H. S., Lucero, C., Arce-Alvarez, A., Oliveira, L. M., Takakura, A. C., Moreira, T. S., Schultz, H. D., Marcus, N. J., Alcayaga, J., Del Rio, R. Tags: PublishAheadOfPrint Source Type: research

NLRP3 Activation Induced by Neutrophil Extracellular Traps Sustains Inflammatory Response in the Diabetic Wound
Persistent inflammatory response in the diabetic wound impairs the healing process, resulting in significant morbidity and mortality. Mounting evidence indicates that the activation of Nod-like receptor protein (NLRP) 3 inflammasome in macrophages (M) contributes to the sustained inflammatory response and impaired wound healing associated with diabetes. However, the main trigger of NLRP3 inflammasome in the wounds is not known. Neutrophils, as sentinels of the innate immune system and key stimulators of M, are immune cells that play the main role in the early phase of healing. Neutrophils release extracellular traps (NETs)...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Liu, D., Yang, P., Gao, M., Yu, T., Shi, Y., Zhang, M., Yao, M., Liu, Y., Zhang, X. Tags: PublishAheadOfPrint Source Type: research

SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice
This study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes. (Source: Clinical Science)
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Atorrasagasti, C., Onorato, A., Gimeno, M. L., Andreone, L., Garcia, M., Malvicini, M., Fiore, E., Bayo, J., Perone, M. J., Mazzolini, G. Tags: PublishAheadOfPrint Source Type: research

ZEB1-AS1 is associated with poor prognosis in non-small-cell lung cancer and influences cell migration and apoptosis by repressing ID1
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion was determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Jin, J., Wang, H., Si, J., Ni, R., Liu, Y., Wang, J. Tags: PublishAheadOfPrint Source Type: research

Poldip2 Deficiency Protects Against Lung Edema and Vascular Inflammation in a Model of Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability, a severe inflammatory response, lung leukocyte infiltration, and resultant lung edema. Polymerase delta-interacting protein 2 (Poldip2) is a novel regulator of blood-brain barrier permeability; however, its role in regulating lung permeability and vascular inflammation is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation in a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 was found to re...
Source: Clinical Science - January 8, 2019 Category: Biomedical Science Authors: Forrester, S. J., Xu, Q., Kikuchi, D. S., Okwan-Duodu, D., Campos, A. C., Faidley, E. A., Zhang, G., Lassegue, B., Sadikot, R. T., Griendling, K. K., Hernandes, M. S. Tags: PublishAheadOfPrint Source Type: research

USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling
In conclusion, our study demonstrates that USP4 deficiency plays a detrimental role in hepatic I/R injury by promoting activation of the TAK1/JNK signalling pathways. Modulation of this axis may be a novel strategy to alleviate the pathological process of hepatic I/R injury. (Source: Clinical Science)
Source: Clinical Science - January 8, 2019 Category: Biomedical Science Authors: Zhou, J., Qiu, T., Wang, T., Chen, Z., Ma, X., Zhang, L., Zou, J. Tags: PublishAheadOfPrint Source Type: research

Sodium 4-phenylbutyrate treatment protects against renal injury in NZBWF1 mice
Systemic lupus erythematosus (SLE) is an autoimmune disease predominantly affecting women and often leading to lupus nephritis and kidney damage. Endoplasmic reticulum (ER) stress has been implicated in several forms of kidney disease, but whether ER stress contributes to renal injury in SLE is unknown. To investigate this, a small molecule chaperone, sodium 4-phenylbutyrate (4-PBA), was administered to the NZBWF1 mouse model of SLE. In a prevention study, treatment with 4-PBA from 20 weeks of age (prior to the development of renal injury) delayed the onset of albuminuria and significantly reduced additional indices of ren...
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Bonnemaison, M. L., Marks-Nelson, E. S., Boesen, E. I. Tags: PublishAheadOfPrint Source Type: research

LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma
In this study, the clinical significance, biological function and regulatory mechanisms of lncRNA DCST1-AS1 in HCC were investigated. Differential lncRNAs in HCC were identified based on The Cancer Genome Atlas (TCGA) database. The biological function and mechanism of DCST1-AS1 were studied in vitro and in vivo. LncRNA DCST1-AS1 was highly expressed in HCC tissues, and the high expression of DCST1-AS1 was significantly correlated with larger tumours and shorter survival time. Moreover, DCST1-AS1 knockout significantly inhibited proliferation, promoted apoptosis and cycle arrest of HCC cells, and inhibited tumour growth in ...
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Chen, J., Wu, D., Zhang, Y., Yang, Y., Duan, Y., An, Y. Tags: PublishAheadOfPrint Source Type: research

Neutral endopeptidase inhibitors blunt kidney fibrosis by reducing myofibroblast formation
Kidney fibrosis is the common pathophysiological mechanism in end-stage-renal-disease characterized by excessive accumulation of myofibroblast-derived extracellular matrix. Natriuretic peptides have been demonstrated to have cGMP-dependent anti-fibrotic properties likely due to interference with pro-fibrotic TGF-β signaling. However, in vivo , natriuretic peptides are rapidly degraded by neutral endopeptidases (NEP). In a unilateral urether obstruction (UUO) mouse model for kidney fibrosis we assessed the anti-fibrotic effects of SOL1, an orally-active compound that inhibits NEP and endothelin-converting enzyme (ECE)....
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Bijkerk, R., Aleksinskaya, M. A., Duijs, J. M., Veth, J., Husen, B., Reiche, D., Prehn, C., Adamski, J., Rabelink, T. J., De Mey, J. G. R., van Zonneveld, A. J. Tags: PublishAheadOfPrint Source Type: research

Rare mutations of ADAM17 from TOFs induce hypertrophy in human embryonic stem cell-derived cardiomyocytes via HB-EGF signaling
In this study, we sequenced ADAM10 and ADAM17 in a Han Chinese CHD cohort comprised of 80 TOF patients, 286 other CHD patients, and 480 matched healthy controls. Three missense variants of ADAM17 were only identified in 80 TOF patients, two of which (Y42D and L659P) are novel and not found in the ExAC database. Point mutation knock-in (KI) and ADAM17 KO human embryonic stem cells (hESCs) were generated by CRISPR/Cas9 and programmed to differentiate into cardiomyocytes (CMs). Y42D or L659P KI cells or complete KO cells all developed hypertrophy with disorganized sarcomeres. RNA-seq results showed that PI3K/Akt, which is dow...
Source: Clinical Science - January 4, 2019 Category: Biomedical Science Authors: Xie, Y., Ma, A., Wang, B., Peng, R., Jing, Y., Wang, D., Finnell, R. H., Qiao, B., Wang, Y., Wang, H., Zheng, Y. Tags: PublishAheadOfPrint Source Type: research

MTHFR C677T polymorphism Increases MTX Sensitivity via the Inhibition of S-adenosylmethionine and De Novo Purine Synthesis
Objective. Currently no guidelines are established for pharmacogenomic testing involving folate metabolic genes in long-term disease-modifying antirheumatic drugs (DMARD) therapies. We carefully investigated how common genetic variations in methylenetetrahydrofolate reductase ( MTHFR ) influence cellular metabolic kinetics in response to methotrexate (MTX). Designs. Two distinct cell models: HepG2 with stabilized MTHFR  inhibition using shRNA delivered by a Lentiviral vector; and Epstein-Barr virus transformed human lymphoblasts expressing MTHFR polymorphic allele 677C and 677T were used.  Disease activity a...
Source: Clinical Science - January 3, 2019 Category: Biomedical Science Authors: Wang, Y.-C., Wu, M.-T., Tang, F.-Y., Chen, D.-Y., Ko, H.-A., Shane, B., Huang, W.-N., Chiang, E.-P. Tags: PublishAheadOfPrint Source Type: research

The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig
Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis and when PVP is reduced, rates of liver dysfunction decrease. The aim of this study was to characterize the hemodynamic, biochemical and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects.Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80...
Source: Clinical Science - January 3, 2019 Category: Biomedical Science Authors: Hammond, J. S., Godtliebsen, F., Steigen, S., Guha, I. N., Wyatt, J., Revhaug, A., Lobo, D. N., Mortensen, K. E. Tags: PublishAheadOfPrint Source Type: research

Elafibranor Interrupts Adipose Dysfunction-mediated Gut and Liver Injury in Mice with Alcoholic Steatohepatitis
Conclusions : Altogether, these findings demonstrated that the PPARα/ agonist, elafibranor, decreased the severity of liver injury by restoration of alcohol-suppressed AT autophagy function and by decreasing the release of apoptotic markers, inflammatory cytokines and FFA, thereby reducing intestinal epithelium disruption and liver inflammation/apoptosis/steatosis in ASH mice. These data suggest that dual PPAR agonists can serve as potential therapeutic agents for the management of ASH. (Source: Clinical Science)
Source: Clinical Science - January 2, 2019 Category: Biomedical Science Authors: Li, T.-H., Yang, Y.-Y., Huang, C.-C., Liu, C.-W., Tsai, H.-C., Lin, M.-W., Tsai, C.-Y., Huang, S.-F., Wang, Y.-W., Lee, T.-Y., Huang, Y.-H., Hou, M.-C., Lin, H.-C. Tags: PublishAheadOfPrint Source Type: research

Upregulated Ferritin in Periodontitis Promotes Inflammatory Cytokine Expression in Human Periodontal Ligament Cells through Transferrin Receptor via ERK/P38 MAPK Pathways
Conclusions:Ferritin is upregulated by inflammation and exhibits cytokine-like activity in HPDLCs inducing a signaling cascade which promote expression of pro-inflammatory cytokines associated with periodontitis. (Source: Clinical Science)
Source: Clinical Science - December 14, 2018 Category: Biomedical Science Authors: Huang, W., Zhan, Y., Zheng, Y., Han, Y., Hu, W., Hou, J. Tags: PublishAheadOfPrint Source Type: research

Heme oxygenase-1 induction by hemin prevents oxidative stress-induced acute cholestasis in the rat
We previously demonstrated in in vitro and ex vivo models that physiological concentrations of unconjugated bilirubin prevent oxidative stress (OS)-induced hepatocanalicular dysfunction and cholestasis. Here, we aimed to ascertain, in the whole rat, whether a similar cholestatic OS injury can be counteracted by heme oxygenase-1 (HO-1) induction that consequently elevates endogenous bilirubin (BR) levels. This was achieved through the administration of hemin, an inducer of HO-1, the rate-limiting step in BR generation. We found that BR peaked between 6-8 h after hemin administration. During this time period, HO-1 induction ...
Source: Clinical Science - December 11, 2018 Category: Biomedical Science Authors: Martin, P. L., Ceccatto, P. L., Razori, M. V., Frances, D. E., Arriaga, S. M., Pisani, G. B., Martinez, A. I., Sanchez Pozzi, E. J., Roma, M. G., Basiglio, C. L. Tags: PublishAheadOfPrint Source Type: research

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis
In this study, we report the identification of a heterozygous nonsense PODXL mutations (Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared to those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryo...
Source: Clinical Science - December 6, 2018 Category: Biomedical Science Authors: Lin, F.-J., Yao, L., Hu, X.-Q., Bian, F., Ji, G., Jiang, G.-R., Gale, D. P., Ren, H.-Q. Tags: PublishAheadOfPrint Source Type: research

GPR120 protects lipotoxicity-induced pancreatic beta-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation
G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic beta cells remains unclear. To explore the potential link between GPR120 and beta-cell function, its agonist DHA and GSK137647AS were used in palmitic acid (PA)-induced pancreatic beats-cell dysfunction, coupled with GPR120 KD in MIN6 cells and GPR120 KO mice to identify the underlying signalling pathways. In vitro and ex vivo treatments of MIN6 cells and islets isolated from WT mice with DH and GSK restored pancreatic PDX1 expression...
Source: Clinical Science - December 6, 2018 Category: Biomedical Science Authors: Wang, Y., Xie, T., Zhang, D., Leung, P. S. Tags: PublishAheadOfPrint Source Type: research

Functional Cardiac Orexin Receptors: Role of Orexin-B/Orexin 2 Receptor in Myocardial Protection
In this study we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative RT-PCR, immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors. In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, D-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific OX1R antagonist (SB-408124) did not alter the responsiveness of OR-B. Treat...
Source: Clinical Science - November 22, 2018 Category: Biomedical Science Authors: Patel, V., Karteris, E., Chen, J., Kyrou, I., Mattu, H. S., Dimitriadis, G. K., Rodrigo, G., Antoniades, C., Antonopoulos, A., Tan, B. K., Hillhouse, E. W., Ng, A., Randeva, H. Tags: PublishAheadOfPrint Source Type: research

Type 3 innate lymphoid cell (ILC3): a new player in liver fibrosis progression
This study was designed to determine the roles of ILC3 in liver fibrosis. By flow cytometry, we documented increased frequencies of peripheral ILC3 (Lin-CD127+CD117+CD294- lymphocytes) in patients, especially at the advanced stage of hepatitis B virus (HBV)-related chronic liver diseases, and demonstrated their correlations with disease progression. The in vitro fibrogenic effects by ILC3 were determined by co-culture experiments with LX-2 [a human hepatic stellate cell (HSC) line]. The data indicate that pathogenic ILC3 can directly promote LX-2 fibrogenesis in non-contact manners by producing interleukin (IL)-17A and IL-...
Source: Clinical Science - November 20, 2018 Category: Biomedical Science Authors: Wang, S., Li, J., Wu, S.-d., Cheng, L., Shen, Y., Ma, W., She, W., Yang, C., Wang, J., Jiang, W. Tags: PublishAheadOfPrint Source Type: research

Changes in cell fate determine the regenerative and functional capacity of the developing kidney before and after release of obstruction
Congenital obstructive nephropathy is a major cause of chronic kidney disease in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud epithelium and podocytes using Foxd1Cre , Six2Cre , HoxB7Cre and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice. Persistent obstruction leads to a significant loss of tubular epithelium, rarefac...
Source: Clinical Science - November 15, 2018 Category: Biomedical Science Authors: Nagalakshmi, V. K., Li, M., Shah, S., Gigliotti, J. C., Klibanov, A. L., Epstein, F. H., Chevalier, R. L., Gomez, R. A., Sequeira Lopez, M. L. S. Tags: PublishAheadOfPrint Source Type: research

Color Spectrographic Respiratory Monitoring from the External Ear Canal
In this study we describe the use of color spectrographic analysis of breathing sounds recorded from the external ear canal as a candidate technology to meet this need. A miniature electret microphone was modified with the addition of an adapter to allow it to be placed comfortably in the external ear canal. The amplified signal was then connected to a real-time color spectrogram program running on a laptop personal computer utilizing the Windows operating system.  Based on the results obtained, we hypothesize that the real-time display of color spectrogram breathing patterns locally or at a central monitoring station...
Source: Clinical Science - November 12, 2018 Category: Biomedical Science Authors: Jafarian, K., Hassani, K., Doyle, D. J., Niakan Lahiji, M., Moradi Moghaddam, O., Saket, A., Majidi, M., Izadi, F. Tags: PublishAheadOfPrint Source Type: research

Inhibitory effects of vasostatin-1 against atherogenesis
This study provided the first evidence that vasostatin-1 may serve as a novel therapeutic target for atherosclerosis. (Source: Clinical Science)
Source: Clinical Science - November 6, 2018 Category: Biomedical Science Authors: Sato, Y., Watanabe, R., Uchiyama, N., Ozawa, N., Takahashi, Y., Shirai, R., Sato, K., Mori, Y., Matsuyama, T.-a., Ishibashi-Ueda, H., Hirano, T., Watanabe, T. Tags: PublishAheadOfPrint Source Type: research

Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes
In this study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with longstanding Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes.  Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology. (Source: Clinical Science)
Source: Clinical Science - November 6, 2018 Category: Biomedical Science Authors: Mahapatra, G., Smith, S. C., Hughes, T. M., Wagner, B., Maldjian, J. A., Freedman, B. I., Molina, A. J. A. Tags: PublishAheadOfPrint Source Type: research

Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker
Early recognition of vulnerable carotid plaques could help identifying patients at high stroke risk, who may benefit of earlier revascularization. Nowadays, different biomarkers of plaque instability have been unravelled, among these microRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two microRNAs involved in atherosclerosis progression. The goal of the...
Source: Clinical Science - November 2, 2018 Category: Biomedical Science Authors: Magenta, A., Sileno, S., D'Agostino, M., Persiani, F., Beji, S., Paolini, A., Camilli, D., Platone, A., Capogrossi, M. C., Furgiuele, S. Tags: PublishAheadOfPrint Source Type: research