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https://www.readbyqxmd.com/read/28087697/development-of-high-affinity-and-high-specificity-inhibitors-of-metalloproteinase-14-through-computational-design-and-directed-evolution
#1
Valeria Arkadash, Gal Yosef, Jason Shirian, Itay Cohen, Yuval Horev, Moran Grossman, Irit Sagi, Evette S Radisky, Julia M Shifman, Niv Papo
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as three decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28081267/single-nucleotide-variants-of-candidate-genes-in-aggrecan-metabolic-pathway-are-associated-with-lumbar-disc-degeneration-and-modic-changes
#2
Romain Shanil Perera, Poruwalage Harsha Dissanayake, Upul Senarath, Lalith Sirimevan Wijayaratne, Aranjan Lional Karunanayake, Vajira Harshadeva Weerabaddana Dissanayake
INTRODUCTION: Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. OBJECTIVES: The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed...
2017: PloS One
https://www.readbyqxmd.com/read/28045061/feature-selection-and-classification-of-urinary-mrna-microarray-data-by-iterative-random-forest-to-diagnose-renal-fibrosis-a-two-stage-study
#3
Le-Ting Zhou, Yu-Han Cao, Lin-Li Lv, Kun-Ling Ma, Ping-Sheng Chen, Hai-Feng Ni, Xiang-Dong Lei, Bi-Cheng Liu
Renal fibrosis is a common pathological pathway of progressive chronic kidney disease (CKD). However, kidney function parameters are suboptimal for detecting early fibrosis, and therefore, novel biomarkers are urgently needed. We designed a 2-stage study and constructed a targeted microarray to detect urinary mRNAs of CKD patients with renal biopsy and healthy participants. We analysed the microarray data by an iterative random forest method to select candidate biomarkers and produce a more accurate classifier of renal fibrosis...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035415/mirna-301a-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-by-directly-targeting-timp2-erk1-2-and-akt-pathways
#4
Xianbao Huang, Ling Qi, Wei Lu, Gangping Yang, Yan Chen, Rongyan Zhang, Jia Rao, Dexiang Ji, Ruibin Huang, Guoan Chen
We investigated the biological functions and mechanism of miRNA‑301a on apoptosis in chronic myelogenous leukemia (CML). The expression of miRNA‑301a in patient with CML cells was higher than the expression of normal patients. Overall survival (OS) of chronic granulocytic leukemia cell patient with low miRNA‑301 expression was superior to that of CML patient with high miRNA‑301 expression. Moreover, the upregulation of miRNA‑301a increased cell proliferation, inhibited apoptosis and caspase-3 and -9 activity of K562 cells...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28012239/secretion-of-pro-inflammatory-cytokines-and-chemokines-and-loss-of-regulatory-signals-by-fibroblast-like-synoviocytes-in-juvenile-idiopathic-arthritis
#5
AnneMarie C Brescia, Megan M Simonds, Kathleen E Sullivan, Carlos D Rose
OBJECTIVE: The goal was to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins. METHODS: Expression of 89 cytokines and chemokines was determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls were also examined for protein expression...
December 23, 2016: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28011057/the-ischemic-nephrotoxic-acute-kidney-injury-and-the-use-of-renal-biomarkers-in-clinical-practice
#6
REVIEW
Michele Andreucci, Teresa Faga, Antonio Pisani, Maria Perticone, Ashour Michael
The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy...
December 21, 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/27997075/vascular-canals-in-permanent-hyaline-cartilage-development-corrosion-of-non-mineralized-cartilage-matrix-and-removal-of-matrix-degradation-products
#7
Simone Gabner, Gabriele Häusler, Peter Böck
Core areas in voluminous pieces of permanent cartilage are metabolically supplied via vascular canals (VCs). We studied cartilage corrosion and removal of matrix degradation products during the development of VCs in nose and rib cartilage of piglets. Conventional staining methods were used for glycosaminoglycans, immunohistochemistry was performed to demonstrate collagens types I and II, laminin, Ki-67, von Willebrand factor, VEGF, macrophage marker MAC387, S-100 protein, MMPs -2,-9,-13,-14, and their inhibitors TIMP1 and TIMP2...
December 20, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27923447/amelioration-of-non-alcoholic-fatty-liver-disease-with-npc1l1-targeted-igy-or-n-3-polyunsaturated-fatty-acids-in-mice
#8
Jin-Sik Bae, Jong-Min Park, Junghoon Lee, Byung-Chul Oh, Sang-Ho Jang, Yun Bin Lee, Young-Min Han, Chan-Young Ock, Ji-Young Cha, Ki-Baik Hahm
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice...
January 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27922684/excess-mechanical-stress-and-hydrogen-peroxide-remodel-extracellular-matrix-of-cultured-human-uterosacral-ligament-fibroblasts-by-disturbing-the-balance-of-mmps-timps-via-the-regulation-of-tgf%C3%A2-%C3%AE-1-signaling-pathway
#9
Qifan Zhang, Cheng Liu, Shasha Hong, Jie Min, Qing Yang, Ming Hu, Yang Zhao, Li Hong
The regulation of the extracellular matrix (ECM) by mechanical stress is of interest as the ECM is essential in the development of pelvic organ prolapse. In the present study, the effect of overexposure to mechanical stress on the ECM, and the probable underlying mechanisms in cultured human uterosacral ligament fibroblasts (hUSLFs), was explored. Mechanical stress has an effect on oxidation‑antioxidation products in parametrial ligament fibroblasts. Thus, hUSLFs were incubated with different concentrations of hydrogen peroxide to elucidate any potential interactions...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27894112/association-of-mbl2-gene-polymorphism-with-dental-caries-in-saudi-children
#10
Yousef M Alyousef, J Francis Borgio, Sayed AbdulAzeez, Naif Al-Masoud, Ali A Al-Ali, Emad Al-Shwaimi, Amein K Al-Ali
The high prevalence of dental caries in children worldwide is a major oral health problem which requires early intervention. Dental caries is mainly caused by the action of acids produced by bacteria in addition to many other factors. Recent genetic studies have reported that a number of genes are associated with the susceptibility to dental caries. The majority of these genes are associated with inflammation, increased susceptibility to infection, and dentine matrix formation. Using the TaqMan assay and direct DNA sequencing, the prevalence of 6 single-nucleotide polymorphisms (SNPs) in MMP9, MBL2, MMP2, and TIMP2 genes was determined in 102 children with caries and in 100 age-matched caries-free controls...
November 29, 2016: Caries Research
https://www.readbyqxmd.com/read/27882817/h2s-improves-renal-fibrosis-in-stz-induced-diabetic-rats-by-ameliorating-tgf-%C3%AE-1-expression
#11
Yan Li, Lin Li, Ou Zeng, Jun Mao Liu, Jun Yang
Nephropathy develops in many patients with type 1 diabetes mellitus (T1DM). However, the specific mechanisms and therapies remain unclear. For this purpose we investigated the effects of hydrogen sulfide (H2S) on renal fibrosis in streptozotocin (STZ) induced diabetic rats and its underlying mechanisms. Experimental rats were randomly divided into four groups: Control group (normal rats), DM group (diabetes rats), DM + NaHS group [diabetes rats treated with sodium hydrosulfide (NaHS)], and NaHS group (normal rats treated with NaHS)...
November 24, 2016: Renal Failure
https://www.readbyqxmd.com/read/27850944/1308-accuracy-of-timp2-igfbp7-in-diagnosis-and-prognosis-of-acute-kidney-injury-a-systematic-review
#12
Ying Feng, Xiao Yang, Hui Zhou, Zhifeng Li, Zhiyong Peng, Jianguo Li
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27834627/promotion-of-astrocytoma-cell-invasion-by-micro-rna-22-targeting-of-tissue-inhibitor-of-matrix-metalloproteinase-2
#13
Yu-Ichiro Ohnishi, Koichi Iwatsuki, Masahiro Ishihara, Toshika Ohkawa, Manabu Kinoshita, Koei Shinzawa, Yasunori Fujimoto, Toshiki Yoshimine
OBJECTIVE Diffuse astrocytomas (DAs) have a high recurrence rate due to diffuse infiltration into the brain and spinal cord. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been reported that miRNA-22 (miR-22) is involved in the invasion of some cancer cell lines. The aim of this study was to identify the biological effects of miR-22 in regard to the invasion of human DAs. METHODS The authors evaluated whether the level of miR-22 is elevated in human spinal DAs by using miRNA chips...
November 11, 2016: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/27829417/administration-of-jte013-abrogates-experimental-asthma-by-regulating-proinflammatory-cytokine-production-from-bronchial-epithelial-cells
#14
Tomomi Terashita, Kazuyuki Kobayashi, Tatsuya Nagano, Yoshitaka Kawa, Daisuke Tamura, Kyosuke Nakata, Masatsugu Yamamoto, Motoko Tachihara, Hiroshi Kamiryo, Yoshihiro Nishimura
BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine the contribution of the signaling of S1P and S1PRs expressed in airway epithelial cells (ECs) to asthma responses in mice...
November 9, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27810779/intravenous-transfusion-of-endothelial-progenitor-cells-that-overexpress-vitamin-d-receptor-inhibits-atherosclerosis-in-apoe-deficient-mice
#15
Wei Xiang, Zhi-Lan Hu, Xiao-Jie He, Xi-Qiang Dang
Endothelial progenitor cells (EPCs) are widely used for angiogenic therapies, as well as predictive biomarkers to assess cardiovascular disease risk. However, it is unknown that whether overexpressed vitamin D receptor (VDR) in EPCs could help EPCs counteracting atherosclerotic risks. Here, we study intravenous transplantation of genetically modified EPCs over-expressing VDR in regulating endothelial dysfunction and spontaneously arising atherosclerotic plaques of ApoE-deficient mice. Firstly, we found that over-expression of VDR in EPCs could reduce atherosclerotic plaque formation in transplanted ApoE-/- mice...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27768799/altered-protein-composition-and-gene-expression-in-strabismic-human-extraocular-muscles-and-tendons
#16
Andrea B Agarwal, Cheng-Yuan Feng, Amy L Altick, David R Quilici, Dan Wen, L Alan Johnson, Christopher S von Bartheld
Purpose: To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods: Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27742777/pnpla3-overexpression-results-in-reduction-of-proteins-predisposing-to-fibrosis
#17
Piero Pingitore, Paola Dongiovanni, Benedetta Maria Motta, Marica Meroni, Saverio Massimo Lepore, Rosellina Margherita Mancina, Serena Pelusi, Cristina Russo, Andrea Caddeo, Giorgio Rossi, Tiziana Montalcini, Arturo Pujia, Olov Wiklund, Luca Valenti, Stefano Romeo
Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown. We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis.Here, we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs...
October 13, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27633774/novel-insights-into-vascularization-patterns-and-angiogenic-factors-in-glioblastoma-subclasses
#18
Siobhan Conroy, Michiel Wagemakers, Annemiek M E Walenkamp, Frank A E Kruyt, Wilfred F A den Dunnen
Glioblastoma (GBM) is a highly vascularized and aggressive type of primary brain tumor in adults with dismal survival. Molecular subtypes of GBM have been identified that are related to clinical outcome and response to therapy. Although the mesenchymal type has been ascribed higher angiogenic activity, extensive characterization of the vascular component in GBM subtypes has not been performed. Therefore, we aimed to investigate the differential vascular status and angiogenic signaling levels in molecular subtypes...
September 15, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27632538/an-evaluation-of-the-stemness-paracrine-and-tumorigenic-characteristics-of-highly-expanded-minimally-passaged-adipose-derived-stem-cells
#19
Oula El Atat, Diane Antonios, George Hilal, Nabil Hokayem, Joelle Abou-Ghoch, Hussein Hashim, Rim Serhal, Clara Hebbo, Mayssam Moussa, Nada Alaaeddine
The use of adipose-derived stem cells (ADSC) in regenerative medicine is rising due to their plasticity, capacity of differentiation and paracrine and trophic effects. Despite the large number of cells obtained from adipose tissue, it is usually not enough for therapeutic purposes for many diseases or cosmetic procedures. Thus, there is the need for culturing and expanding cells in-vitro for several weeks remain. Our aim is to investigate if long- term proliferation with minimal passaging will affect the stemness, paracrine secretions and carcinogenesis markers of ADSC...
2016: PloS One
https://www.readbyqxmd.com/read/27631965/linc00312-inhibits-the-migration-and-invasion-of-bladder-cancer-cells-by-targeting-mir-197-3p
#20
Yun-Yan Wang, Zi-Yu Wu, Gong-Cheng Wang, Kun Liu, Xiao-Bing Niu, Shuo Gu, Jun-Song Meng
To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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