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https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#1
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636071/the-role-of-homocysteine-in-seminal-vesicles-remodeling-in-rat
#2
Adel Ghoul, Elara Moudilou, Mohamed El Hadi Cherifi, Fouzia Zerrouk, Billel Chaouad, Anissa Moulahoum, Souhila Aouichat-Bouguerra, Khira Othmani, Jean-Marie Exbrayat, Yasmina Benazzoug
INTRODUCTION: Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM...
June 21, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#3
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634868/occurrence-removal-and-health-risk-assessment-of-phthalate-esters-in-the-process-streams-of-two-different-wastewater-treatment-plants-in-lagos-and-ogun-states-nigeria
#4
O O Olujimi, O A Aroyeun, T F Akinhanmi, T A Arowolo
Phthalate esters (PEs) are one of the environmentally active organic pollutants capable of causing endocrine disruption. The levels of PE congeners were determined in the influent and effluent from Covenant Oxidation Pond (COP) and Ikeja Wastewater Treatment Plant (IWWTP). Standard methods were adopted for determining the physical and chemical parameters of the water samples. The water samples for PE congener's determination were collected, acidified and stored at 4 °C prior to liquid-liquid extraction and analysis by gas chromatograph...
July 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#5
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28634392/the-traditional-chinese-medicine-achyranthes-bidentata-and-our-de-novo-conception-of-its-metastatic-chemoprevention-from-phytochemistry-to-pharmacology
#6
Zhou Jiang, Jun Qian, Haiyan Dong, Jingyi Yang, Xiaobo Yu, Jianzhong Chen, Hongning Chen, Qing Shi, Lee Jia
Our recent biosystems analysis revealed similarities between embryonic implantation and cancer cell adhesion, which suggests that abortifacients may be good for safe and effective metastatic chemoprevention targeting circulating tumor cells (CTC). Here we test the hypothesis by using the well-known abortion herb Achyranthes bidentata Blume (A. bidentata). Five compounds were separated from the herb root. Among them, ginsenoside Ro was the most potent in inhibiting embryonic implantation within non-cytotoxic concentrations...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634370/microbial-antigens-stimulate-metalloprotease-7-secretion-in-human-b-lymphocytes-using-mtor-dependent-and-independent-pathways
#7
Mohamed F Ali, Harika Dasari, Virginia P Van Keulen, Divi Cornec, George Vasmatzis, Tobias Peikert, Eva M Carmona
Metalloproteinases (MMPs) contribute to tissue remodeling and acute inflammation not only by degrading extracellular matrix proteins but also by controlling the influx of chemokines through the regulation and shedding of syndecans. B-lymphocytes, in addition to their well-known function as antibody producing cells, participate in the innate immune response by secreting inflammatory cytokines and chemokines. However, there is little information about the role of B-lymphocytes in the regulation of MMPs; consequently, herein we investigated whether activated human circulating B-lymphocytes contributed to the secretion of MMPs...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634008/aging-associated-modifications-of-collagen-affect-its-degradation-by-matrix-metalloproteinases
#8
Preety Panwar, Georgina S Butler, Andrew Jamroz, Pouya Azizi, Christopher M Overall, Dieter Brömme
The natural aging process and various pathologies correlate with alterations in the composition and the structural and mechanical integrity of the connective tissue. Collagens represent the most abundant matrix proteins and provide for the overall stiffness and resilience of tissues. The structural changes of collagens and their susceptibility to degradation are associated with skin wrinkling, bone and cartilage deterioration, as well as cardiovascular and respiratory malfunctions. Here, matrix metalloproteinases (MMPs) are major contributors to tissue remodeling and collagen degradation...
June 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28633995/quantitative-mri-study-of-the-permeability-of-peritumoral-brain-edema-in-lung-cancer-patients-with-brain-metastases
#9
Dan Wang, Ming-Liang Wang, Yue-Hua Li
PURPOSE: To use Ktrans to evaluate the aggressiveness and vascular permeability of peritumoral edema in cases of lung cancer brain metastases. MATERIALS AND METHODS: A total of 68 lung cancer patients with 92 metastatic brain lesions were enrolled (20 metastatic lesions only in the gray matter -group 1; and 72 metastatic lesions located in the gray and white matter junction -group 2). All patients underwent MRI examination, which involved a dual angle (2° and 15°) enhanced T1W-VIBE (volume interpolated breath-hold examination) sequence to calculate the T1 parameter map...
June 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28633927/dencichine-ameliorates-kidney-injury-in-induced-type-ii-diabetic-nephropathy-via-the-tgf-%C3%AE-smad-signalling-pathway
#10
Li Jie, Qiu Pengcheng, He Qiaoyan, Bi Linlin, Zhang Meng, Wang Fang, Jia Min, Yan Li, Zhang Ya, Yang Qian, Wang Siwang
Diabetic nephropathy (DN), a common complication associated with both type I and type II diabetes mellitus (DM), is a major cause of chronic nephropathy and a common cause of end-stage renal diseases (ESRD) throughout the world. This study is aimed to determine whether dencichine (De) can ameliorate renal damage in high-glucose-and-fat diet combined STZ (streptozocin) induced DN in type II DM rats and to investigate the potential underlying mechanisms. Markers of metabolism, diabetes, and renal function, and levels of extracellular matrix (ECM) collagen I (Col I), collagen IV (Col IV), fibronectin (FN) and laminin (LN), and of proteins in the TGF-β/Smad pathway were analysed through RT-PCR, western blot, immunofluorescence and immunohistochemistry...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#11
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28631819/protective-effects-of-tannic-acid-on-pressure-overload-induced-cardiac-hypertrophy-and-underlying-mechanisms-in-rats
#12
Li Chu, Pinya Li, Tao Song, Xue Han, Xuan Zhang, Qiongtao Song, Tao Liu, Yuanyuan Zhang, Jianping Zhang
OBJECTIVES: The aim of this study was to examine the cardioprotective effects and latent mechanism of tannic acid (TA) on cardiac hypertrophy. METHODS: Abdominal aortic banding (AAB) was used to induce pressure overload-induced cardiac hypertrophy in male Wistar rats, sham-operated rats served as controls. AAB rats were treated with TA (20 and 40 mg/kg) or captoril. KEY FINDINGS: Abdominal aortic banding rats that received TA showed ameliorated pathological changes in cardiac morphology and coefficients, decreased cardiac hypertrophy and apoptosis, a reduction in over expressions of angiotensin type 1 receptor (AT1 R), angiotensin type 2 receptor (AT2 R), phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β (TGF-β) mRNA, and modified expression of matrix metal proteinase-9 (MMP-9) mRNA in AAB rat hearts...
June 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28631286/knockdown-of-mediator-subunit-med19-suppresses-bladder-cancer-cell-proliferation-and-migration-by-downregulating-wnt-%C3%AE-catenin-signalling-pathway
#13
Hejia Yuan, Shengqiang Yu, Yuanshan Cui, Changping Men, Diandong Yang, Zhenli Gao, Zhe Zhu, Jitao Wu
Mediator complex subunit 19 (Med19), a RNA polymerase II-embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real-time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin-embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630860/regulation-of-matrix-metalloproteinase-2-secretion-from-scleral-fibroblasts-and-retinal-pigment-epithelial-cells-by-mir-29a
#14
Yingjie Zhang, Dan-Ning Hu, Yi Zhu, Hao Sun, Ping Gu, Dongqing Zhu, Jibo Zhou
PURPOSE: To identify an effective method to prevent myopia progression by characterizing the regulation of matrix metalloproteinase- (MMP-) 2 expression and its secretion from scleral fibroblasts and retinal pigment epithelium (RPE) cells by miR-29a. METHODS: The effects of miR-29a on the growth of scleral fibroblasts and RPE cells were assessed using the cell counting kit-8. The changes in MMP-2 mRNA levels in scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor were measured by quantitative PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28630659/homocysteine-induces-apoptosis-of-human-umbilical-vein-endothelial-cells-via-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress
#15
Zhimin Zhang, Congying Wei, Yanfen Zhou, Tao Yan, Zhengqiang Wang, Wei Li, Lianyou Zhao
Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28630410/investigating-the-life-expectancy-and-proteolytic-degradation-of-engineered-skeletal-muscle-biological-machines
#16
Caroline Cvetkovic, Meghan C Ferrall-Fairbanks, Eunkyung Ko, Lauren Grant, Hyunjoon Kong, Manu O Platt, Rashid Bashir
A combination of techniques from 3D printing, tissue engineering and biomaterials has yielded a new class of engineered biological robots that could be reliably controlled via applied signals. These machines are powered by a muscle strip composed of differentiated skeletal myofibers in a matrix of natural proteins, including fibrin, that provide physical support and cues to the cells as an engineered basement membrane. However, maintaining consistent results becomes challenging when sustaining a living system in vitro...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630135/inhibition-of-the-cardiac-fibroblast-enriched-lncrna-meg3-prevents-cardiac-fibrosis-and-diastolic-dysfunction
#17
Maria-Teresa Piccoli, Shashi Gupta, Janika Viereck, Ariana Foinquinos, Sabine Samolovac, Freya Kramer, Ankita Garg, Janet Remke, Karina Zimmer, Sandor Batkai, Thomas Thum
Rationale: Cardiac fibroblasts (CFs) drive extracellular matrix (ECM) remodeling following pressure overload, leading to fibrosis and diastolic dysfunction. Recent studies described the role of long noncoding RNAs (lncRNAs) in cardiac pathologies. Nevertheless, detailed reports on lncRNAs regulating CF biology and describing their implication in cardiac remodeling are still missing. Objective: Here, we aimed at characterizing lncRNA expression in murine CFs following chronic pressure overload, in order to identify CF-enriched lncRNAs and investigate their function and contribution to cardiac fibrosis and diastolic dysfunction...
June 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28629818/corydalis-hendersonii-hemsl-protects-against-myocardial-injury-by-attenuating-inflammation-and-fibrosis-via-nf-%C3%AE%C2%BAb-and-jak2-stat3-signaling-pathways
#18
Ruifeng Bai, Xu Yin, Xiao Feng, Yuan Cao, Yan Wu, Zhixiang Zhu, Chun Li, Pengfei Tu, Xingyun Chai
ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury...
June 16, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28628905/a-ros-mediated-mitochondrial-pathway-and-nrf2-pathway-activation-are-involved-in-bde-47-induced-apoptosis-in-neuro-2a-cells
#19
Hongmei Chen, Xuexi Tang, Bin Zhou, Zhongyuan Zhou, Ningning Xu, You Wang
Our previous study showed that 2,2'-,4,4'-tetrabromodiphenyl ether (BDE-47) is cytotoxic and induces apoptosis in Neuro-2a cells. In the present study, we aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcriptional regulator of oxidative stress and apoptosis, is involved in this process. The results of toxicological experiments showed that BDE-47 decreased the cellular mitochondrial membrane potential (MMP) and increased cytochrome c release to the cytoplasm, followed by an increase in intracellular caspase-9 and caspase-3 activity, suggesting that a mitochondrial pathway was involved in the apoptotic process...
June 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28628116/cadherin-composition-and-multicellular-aggregate-invasion-in-organotypic-models-of-epithelial-ovarian-cancer-intraperitoneal-metastasis
#20
Y Klymenko, O Kim, E Loughran, J Yang, R Lombard, M Alber, M S Stack
During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood...
June 19, 2017: Oncogene
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