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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
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
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
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
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...
September 8, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Lin Song, Xin Zhou, Hong-Jun Jia, Mei Du, Jin-Ling Zhang, Liang Li
OBJECTIVE: To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. METHODS: BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection...
August 2016: Asian Pacific Journal of Tropical Medicine
Geng-Fan Ye, Shao-Wei Zhu, Shu-Gan Zhu, Feng Li, Yun-Yan Wang
Secreted protein acidic and rich in cysteine (SPARC) is widely expressed in the vascular smooth muscle cells (VSMCs) of human intracranial aneurysms (IAs), but the effect and underlying mechanism of SPARC on VSMCs during the formation and progression of IAs needs to be probed. Human umbilical arterial smooth muscle cells (HUASMCs) were treated with a gradient concentrations of SPARC in vitro for different time. Cell counting kit-8 (CCK-8) assay, cell cycle, and cell apoptosis were used to investigate the effect of SPARC on HUASMCs...
August 25, 2016: Journal of Molecular Neuroscience: MN
Desta Kassa, Leonie Ran, Wilco de Jager, Theo van den Broek, Ronald Jacobi, Muluberhan Mekonen, Tsehaynesh Messele, Mariëlle C Haks, Tom H M Ottenhoff, Debbie van Baarle
BACKGROUND: Transcriptomic host biomarkers could assist in developing effective diagnostics, vaccines and therapeutics for tuberculosis (TB). However, different biomarkers may be discriminatory in different populations depending on the host and bacillary genetics and HIV infection, and need to be addressed. METHODS: The expression levels of 45 genes that are known to be involved in or affected by TB pathogenesis were analyzed using dual color Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) assay in whole blood of 106 HIV positive individuals including active TB patients (TB(+)HIV(+), n = 29), and non TB patients that are tuberculin skin test positive (TST+) (TST(+)HIV(+), n = 26), or TST negative (TST(-)HIV(+), n = 51)...
September 2016: Tuberculosis
Zahra Nouri, Fatemeh Karami, Nadia Neyazi, Mohammad Hossein Modarressi, Roya Karimi, Mohammad Reza Khorramizadeh, Behrooz Taheri, Elahe Motevaseli
OBJECTIVE: Lactobacilli are a group of probiotics with beneficial effects on prevention of cancer. However, there is scant data in relation with the impacts of probiotics in late-stage cancer progration, especially metastasis. The present original work was aimed to evaluate the anti-metastatic and anti-proliferative activity of lactobacillus rhamnosus supernatant (LRS) and lactobacillus crispatus supernatant (LCS) on the human cervical and colon adenocarcinoma cell lines (HeLa and HT-29, respectively)...
July 2016: Cell Journal
Xiu Chen, Shan-Liang Zhong, Peng Lu, Dan-Dan Wang, Si-Ying Zhou, Su-Jin Yang, Hong-Yu Shen, Lei Zhang, Xiao-Hui Zhang, Jian-Hua Zhao, Jin-Hai Tang
PURPOSE: Chemo-resistance is the leading cause of failure in cancer therapy, however, much remains to be understood about the intrinsic mechanisms. In the present study, we discovered the novel miR-4443 that regulated malignancy of breast cancer both in vitro and in vivo. METHODS: We examined the expression of miR-4443 in MDA-MB-231/S and MDA-MB-231 Epirubicin-resistant cell lines with 76 breast cancer formalin-fixed paraffin-embedded tissues by real-time PCR. Also, we investigated the loss- and gain-functions of miR-4443 by MTT assay and flow cytometry...
2016: PloS One
John W Pickering, Zoltan H Endre
No new biomarker of acute kidney injury (AKI) has entered routine clinical practice after a decade of promise, although liver-fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipoprotein (NGAL), and the combination of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) are approved for use in some jurisdictions. Acceptance of creatinine as a surrogate of not just glomerular filtration rate (GFR) but also renal injury, changes in nephrologist workloads, failure to establish the added value of each biomarker to current clinical variables across multiple clinical settings, the lack of treatment options, and simply an insufficient passage of time, have all contributed to the lack of progress...
October 1, 2016: American Journal of Physiology. Renal Physiology
Yong-Feng Yang, Ying Ying Sun, Ted S Acott, Kate E Keller
The trabecular meshwork (TM) tissue controls drainage of aqueous humor from the anterior chamber of the eye primarily by regulating extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs). Glaucomatous TM tissue is stiffer than age-matched controls, which may be due to alterations in ECM cross-linking. In this study, we used genipin or beta-aminopropionitrile (BAPN) agents to induce or inhibit matrix cross-linking, respectively, to investigate the effects on outflow resistance and ECM remodeling...
2016: Scientific Reports
M Kurzawski, M Kaczmarek, M Kłysz, D Malinowski, A Kazienko, R Kurzawa, M Droździk
Proper function of the blood-testis barrier is pivotal to spermatogenesis. Synchronised action of matrix metalloproteinases (MMP) and their inhibitors (TIMP) is mandatory to maintain dynamic balance of the barrier. Therefore, the association of functional genetic variants of MMP-2, MMP-9 and TIMP-2 and male infertility was studied. A total of 416 infertile males and 421 healthy subjects were genotyped for 7 SNPs within MMP2, MMP9 and TIMP2 genes, along with the assessment of semen parameters (concentration, motility and morphology of spermatozoa)...
July 12, 2016: Andrologia
Wioletta Pietruszewska, Katarzyna Bojanowska-Poźniak, Józef Kobos
INTRODUCTION: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes implicated in the invasion and metastasis of many kinds of cancer because of their ability to degrade components of extracellular matrix. Specific tissue inhibitors of matrix metalloproteinases (TIMPs) regulate their activity. MMPs and TIMPs were identified in many neoplasm, including cancers of head and neck, lung, breast and colon cancer. In most researches a strong relation between MMPs and TIMPs expression and a clinical course of disease was observed, although there were many discrepancies between the authors...
June 30, 2016: Otolaryngologia Polska. the Polish Otolaryngology
Michael Heung, Luis M Ortega, Lakhmir S Chawla, Richard G Wunderink, Wesley H Self, Jay L Koyner, Jing Shi, John A Kellum
BACKGROUND: Identification of acute kidney injury (AKI) can be challenging in patients with underlying chronic disease, and biomarkers often perform poorly in this population. In this study we examined the performance characteristics of the novel biomarker panel of urinary tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 ([IGFBP7]) in patients with a variety of comorbid conditions. METHODS: We analyzed data from two multicenter studies of critically ill patients in which [TIMP2]•[IGFBP7] was validated for prediction of Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2 or 3 AKI within 12 h...
October 2016: Nephrology, Dialysis, Transplantation
Pedro Serralheiro, Elisa Cairrão, Cláudio J Maia, Marina João, Carlos M Costa Almeida, Ignacio Verde
OBJECTIVES: Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. METHODS: Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein...
June 20, 2016: Phlebology
Nicole Izykowski, Mark Kuehnel, Kais Hussein, Kristin Mitschke, Michael Gunn, Sabina Janciauskiene, Axel Haverich, Gregor Warnecke, Florian Laenger, Ulrich Maus, Danny Jonigk
BACKGROUND: Organizing pneumonia is a reaction pattern and an inflammatory response to acute lung injuries, and is characterized by intraluminal plugs of granulation tissue in distal airspaces. In contrast to other fibrotic pulmonary diseases, organizing pneumonia is generally responsive to corticosteroids. However, some patients do not respond to treatment, leading to respiratory failure and potentially death (up to 15 % of patients). In order to devise new therapeutic strategies, a better understanding of the disease's pathomechanisms is warranted...
2016: Journal of Translational Medicine
Beenish Rahat, Renuka Sharma, Rashmi Bagga, Abid Hamid, Jyotdeep Kaur
The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i...
July 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Louis El Khoury, William J Ribbans, Stuart M Raleigh
Variants within the MMP3 (rs679620) and TIMP2 (rs4789932) genes have been associated with the risk of Achilles tendon pathology (ATP) in populations from South Africa and Australia. This study aimed to determine whether these variants were associated with the risk of ATP in British Caucasians. We recruited 118 cases with ATP, including a subset of 25 individuals with Achilles tendon rupture (RUP) and 131 controls. DNA samples were isolated from saliva and genotyped using qPCR. For the TIMP2 rs4789932 variant we found a significant (p = 0...
September 2016: Meta Gene
Fu-Shun Yu, Meng-Liang Lin, Shu-Chun Hsu, Chien-Chih Yu, Yi-Ping Huang, Yueh-Hsiung Kuo, Jing-Gung Chung
4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR...
August 2016: International Journal of Oncology
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