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      The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases

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          Abstract

          Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.

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            Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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              Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

              The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                20 December 2020
                December 2020
                : 21
                : 24
                : 9739
                Affiliations
                Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico; gris_elda_ai91@ 123456hotmail.com (G.AC.-P.); castruitade@ 123456gmail.com (C.C.-D.l.R.); jesusm.ra94@ 123456gmail.com (J.MR.-A.); alekhandroperes@ 123456gmail.com (B.AP.-R.); guerreroajf@ 123456gmail.com (J.FG.-R.); ik.otik88@ 123456gmail.com (N.M.-A.)
                Author notes
                [* ]Correspondence: idaliagv@ 123456uaz.edu.mx (I.G.-V.); margaritamf@ 123456uaz.edu.mx (M.LM.-F.); Tel.: +52-(492)-9256690 (M.LM.-F)
                Author information
                https://orcid.org/0000-0002-6307-1696
                https://orcid.org/0000-0002-9183-2034
                https://orcid.org/0000-0003-1478-9068
                Article
                ijms-21-09739
                10.3390/ijms21249739
                7767220
                33419373
                6a60496f-2724-4808-a5e7-09f4bb1eb30e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 November 2020
                : 18 December 2020
                Categories
                Review

                Molecular biology
                matrix metalloproteinases,human diseases,metalloproteinase inhibitors
                Molecular biology
                matrix metalloproteinases, human diseases, metalloproteinase inhibitors

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