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https://www.readbyqxmd.com/read/28811488/deregulation-of-zpr1-causes-respiratory-failure-in-spinal-muscular-atrophy
#1
Naresh K Genabai, Annapoorna Kannan, Saif Ahmad, Xiaoting Jiang, Kanchan Bhatia, Laxman Gangwani
Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810592/protective-effect-and-mechanism-of-estrogen-receptor-%C3%AE-on-myocardial-infarction-in-mice
#2
Jun-Biao Zhang, Chang-Lei Guo
The protective effect and the mechanism of estrogen receptor β (ERβ) on myocardial infarction (MI) in mice were explored. A total of 12 female Tg-ERβ transgenic mice and 12 non-transgenic littermate control (NLC) wild-type C57 mice were used for the present study. Both transgenic and wild-type mice had similar baseline data such as age, sex, and weight. The mouse model of MI was established by coronary artery ligation method, and the cardiac structure and function changes of the mouse were observed by ultrasonic echocardiography on days 1, 3 and 7 after the operation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#3
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808223/metastasis-associated-protein-1-deficiency-results-in-compromised-pulmonary-alveolar-capillary-angiogenesis-in-mice
#4
Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang
BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry...
August 15, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28805947/penile-neurovascular-structure-revisited-immunohistochemical-studies-with-three-dimensional-reconstruction
#5
G N Yin, S-H Park, M-J Choi, A Limanjaya, K Ghatak, N N Minh, J Ock, K-M Song, J-K Ryu, J-K Suh
Penile erection is a neurovascular phenomenon that requires well coordinated and functional interaction between penile vascular and nervous systems. In order to provide a useful tool to examine pathologic changes in the erectile tissue, mainly focusing on penile neurovascular dysfunction, we established the technique to determine the differential distribution of endothelial cells, smooth muscle cells, pericytes, and nerve fibers in the mouse penis using immunohistochemical staining with three-dimensional reconstruction...
August 14, 2017: Andrology
https://www.readbyqxmd.com/read/28801561/inflammation-mediated-sod-2-upregulation-contributes-to-epithelial-mesenchymal-transition-and-migration-of-tumor-cells-in-aflatoxin-g1-induced-lung-adenocarcinoma
#6
Li Yi, Haitao Shen, Mei Zhao, Peilu Shao, Chunping Liu, Jinfeng Cui, Juan Wang, Can Wang, Ningfei Guo, Lifei Kang, Ping Lv, Lingxiao Xing, Xianghong Zhang
Tumor-associated inflammation plays a critical role in facilitating tumor growth, invasion and metastasis. Our previous study showed Aflatoxin G1 (AFG1) could induce lung adenocarcinoma in mice. Chronic lung inflammation associated with superoxide dismutase (SOD)-2 upregulation was found in the lung carcinogenesis. However, it is unclear whether tumor-associated inflammation mediates SOD-2 to contribute to cell invasion in AFG1-induced lung adenocarcinoma. Here, we found increased SOD-2 expression associated with vimentin, α-SMA, Twist1, and MMP upregulation in AFG1-induced lung adenocarcinoma...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799578/nusinersen-antisense-oligonucleotide-to-increase-smn-protein-production-in-spinal-muscular-atrophy
#7
D M Paton
Patients with spinal muscular atrophy (SMA) have an autosomal recessive disease that limits their ability to produce survival motor neuron (SMN) protein in the CNS resulting in progressive wasting of voluntary muscles. Detailed studies over several years have demonstrated that phosphorothioate and 2'-O-methoxyethyl- modified antisense oligonucleotides (ASOs) targeting the ISS-N1 site increase SMN2 exon 7 inclusion, thus increasing levels of SMN protein in a dose- and time-dependent manner in liver, kidney and skeletal muscle, and CNS tissues only when administered intrathecally...
June 2017: Drugs of Today
https://www.readbyqxmd.com/read/28798084/a-small-population-of-liver-endothelial-cells-undergoes-endothelial-to-mesenchymal-transition-in-response-to-chronic-liver-injury
#8
Jordi Ribera, Montse Pauta, Pedro Melgar-Lesmes, Bernat Cordoba, Anna Bosch, Maria Calvo, Daniel Rodrigo-Torres, Pau Sancho-Bru, Aurea Mira, Wladimiro Jimenez, Manuel Morales-Ruiz
BACKGROUND AND AIMS: Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. METHODS: Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28797711/identification-of-a-myofibroblast-specific-expression-signature-in-skin-wounds
#9
Vera Bergmeier, Julia Etich, Lena Pitzler, Christian Frie, Manuel Koch, Matthias Fischer, Gunter Rappl, Hinrich Abken, James J Tomasek, Bent Brachvogel
After skin injury fibroblasts migrate into the wound and transform into contractile, extracellular matrix-producing myofibroblasts to promote skin repair. Persistent activation of myofibroblasts can cause excessive fibrotic reactions, but the underlying mechanisms are not fully understood. We used SMA-GFP transgenic mice to study myofibroblast recruitment and activation in skin wounds. Myofibroblasts were initially recruited to wounds three days post injury, their number reached a maximum after seven days and subsequently declined...
August 7, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28782260/mmp-13-deletion-decreases-profibrogenic-molecules-and-attenuates-n-nitrosodimethylamine-induced-liver-injury-and-fibrosis-in-mice
#10
Joseph George, Mikihiro Tsutsumi, Mutsumi Tsuchishima
Connective tissue growth factor (CTGF) is involved in inflammation, pathogenesis and progression of liver fibrosis. Matrix metalloproteinase-13 (MMP-13) cleaves CTGF and releases several fragments, which are more potent than the parent molecule to induce fibrosis. The current study was aimed to elucidate the significance of MMP-13 and CTGF and their downstream effects in liver injury and fibrosis. Hepatic fibrosis was induced using intraperitoneal injections of N-nitrosodimethylamine (NDMA) in doses of 10 μg/g body weight on three consecutive days of each week over a period of 4 weeks in both wild-type (WT) and MMP-13 knockout mice...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28780788/-therapeutic-effect-of-mir-489-in-a-mouse-model-of-silica-induced-matured-pulmonary-fibrosis
#11
S X Jin, Q Y Wu, W W Yan, C H Ni
Objective: To explore the potential therapeutic role of miR-489 in silica-induced pulmonary fibrosis mouse models. Methods: A total of 32 C57BL/6 male mice were randomly divided into four groups: saline, silica, silica plus miRNA control and silica plus miR-489 agomir (n=8 in each group) . The mice were instilled with silica particles suspended in saline or sterile saline intratracheally. Subsequently, miR-489 agomir or miRNA control was injected via the tail vein into each mouse at days 28, 35, 42 and 49, the miR-489 levels, histological examination, collagen deposition, fibrotic biomarkers (E-cadherin, α-SMA, Vimentin, Fibronectin) and transforming growth factor-β(1) (TGF-β(1)) protein levels in mouse lung tissues were measured...
May 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28780584/platelet-derived-growth-factor-alpha-pdgfr%C3%AE-induces-the-activation-of-cardiac-fibroblasts-by-activating-c-kit
#12
Lexun Wang, Yuan Yue, Xiao Yang, Tian Fan, Bo Mei, Jian Hou, Mengya Liang, Guangxian Chen, Zhongkai Wu
BACKGROUND Enhanced platelet-derived growth factor receptor a (PDGFRα) signaling pathway activity leads to cardiac fibrosis. However, because of the pleiotropic effects of PDGFR signaling, its role in mediating the cardiac fibrotic response remains poorly understood. This study aimed to investigate the regulatory effect of c-Kit in cardiac fibroblasts activated by PDGFRa signaling. MATERIAL AND METHODS A cardiac fibrosis mice model was induced using isoproterenol, and the heart tissues of mice were tested through western blotting and real-time quantitative PCR (RT-qPCR)...
August 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28775379/tia1-is-a-gender-specific-disease-modifier-of-a-mild-mouse-model-of-spinal-muscular-atrophy
#13
Matthew D Howell, Eric W Ottesen, Natalia N Singh, Rachel L Anderson, Joonbae Seo, Senthilkumar Sivanesan, Elizabeth M Whitley, Ravindra N Singh
Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C (+/+)) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774593/inhibiton-of-fkbp10-attenuates-hypertrophic-scarring-through-suppressing-fibroblast-activity-and-extracellualr-matrix-deposition
#14
Xiao Liang, Bangda Chai, Ran Duan, Yiwen Zhou, Xiaolu Huang, Qingfeng Li
Hypertrophic scar (HS) is a pathogenic form of scar formation with no recognized treatment to date. Its molecular mechanism is related to the abnormal proliferation and transition of fibroblasts and overproduction of extracellular matrix (ECM). FK506-binding protein 10 (FKBP10) is a molecular chaperone able of regulating α-SMA expression and pro-collagen maturation in fibroblasts. However, no research has investigated the biological function of FKBP10 in scar formation to date. In this study, we aim to assess the expression and function of FKBP10 in hypertrophic scarring...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28770956/investigation-into-the-correlations-of-expressions-of-cav-3-and-smad3-with-pathogenesis-and-prognosis-of-viral-myocarditis
#15
Ch-L Jia, J Liu
OBJECTIVE: To investigate the correlations of expressions of Caveolae-3 (Cav-3) and sma and mad homologue (Smad3) with the pathogenesis and prognosis of viral myocarditis (VMC). MATERIALS AND METHODS: VMC animal models were prepared and divided into the control group, the virus group and the Shenmai group. We detected the levels of creatine kinase isoenzyme (CK-MB) in the serum that was associated with the myocardial injuries, investigated the pathological features of VMC in BALB/C mice via hematoxylin-eosin (HE) staining, measured the mRNA expressions of Cav-3 and Smad3 via Real-time polymerase chain reaction (RT-PCR) and determined the protein expressions of Cav-3 and Smad3 through Western blotting method...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28770521/styrene-maleic-acid-encapsulated-raloxifene-micelles-for-management-of-inflammatory-bowel-disease
#16
Khaled Greish, Safa Taha, Anfal Jasim, Sara Abd Elghany, Ameera Sultan, Ali AlKhateeb, Manal Othman, Fang Jun, Sebastien Taurin, Moiz Bakhiet
BACKGROUND: Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28766848/microrna-30a-ameliorates-hepatic-fibrosis-by-inhibiting-beclin1-mediated-autophagy
#17
Jianliang Chen, Yue Yu, Shu Li, Yuting Liu, Shu Zhou, Shouji Cao, Jie Yin, Guoqiang Li
We explored the role of microRNA-30a (miR-30a) and the mechanism involved in hepatic fibrosis. MiR-30a overexpression was achieved by miR-30a mimics transfection in hepatic stellate cells (HSCs) (HSC-T6, LX-2), and miR-30a agomir (ago-miR-30a) treatment in mice. MiR-30a levels were measured using TaqMan miRNA assay system, and the localization of miR-30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR-30a and Beclin1 was confirmed by dual-luciferase reporter assay. Autophagic flux was analysed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy and Western blot of LC3-II/I ratio...
August 1, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28763748/the-therapeutic-effects-of-yongdamsagan-tang-on-autoimmune-hepatitis-models
#18
Jiyoung Park, Hayeon Kim, In-Seung Lee, Kang-Hoon Kim, Yumi Kim, Yun-Cheol Na, Jang-Hoon Lee, Hyeung-Jin Jang
Autoimmune hepatitis (AIH) is an immunity disorder that is the result of antibodies in the liver tissue of the patient that are attacked by activated immune cells due to an unknown cause. In this study, we aimed to investigate the anti-inflammatory effect of Yongdamsagan-tang (YST) extracts and confirm effects on autoimmune hepatitis models as the therapeutic agent using the YST extracted by various solvents. YST, a mixture of 11 herbal extracts, is known in traditional Korean medicine as a widely used treatment for inflammatory diseases...
July 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28761179/soluble-epoxide-hydrolase-inhibition-protected-against-angiotensin-ii-induced-adventitial-remodeling
#19
Chi Zhou, Jin Huang, Qing Li, Jiali Nie, Xizhen Xu, Dao Wen Wang
Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761146/how-gastrin-releasing-peptide-receptor-grpr-and-%C3%AE-v%C3%AE-3-integrin-expression-reflect-reorganization-features-of-tumors-after-hyperthermia-treatments
#20
Sandra Hallasch, Sindy Frick, Maximilian Jung, Ingrid Hilger
The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and αvβ3 integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 °C) or low dose (42 °C) water hyperthermia for 60 min. Changes of GRPR and αvβ3 integrin expression were assessed via multiplexed optical imaging...
July 31, 2017: Scientific Reports
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