The regulation of matrix metalloproteinases and their inhibitors

The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available

Novel Porin genes and modes of Porin regulation in <em>Salmonella typhi</em>

[no abstract available

Tissue inhibitor of metalloproteinase-3 is up-regulated by transforming growth factor-beta1 in vitro and expressed in fibroblastic foci in vivo in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and extracellular matrix accumulation. However, the mechanisms involved in matrix remodeling have not been elucidated. In this study, the authors aimed to evaluate the expression of the tissue inhibitors of matrix metalloproteinases (TIMPs) in human fibroblasts and whole tissues from IPF and normal lungs. They also determined the role of mitogen-activated protein kinase (MAPK) in TIMP3 expression. TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts. Transforming growth factor (TGF)-beta 1, a profibrotic mediator, induced strong up-regulation of TIMP3 at the mRNA and protein levels. The authors examined whether the MAPK pathway was involved in TGF-beta 1-induced TIMP3 expression. TGF-beta 1 induced the phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2. Biochemical blockade of p38 by SB203580, but not of the ERK MAPK pathway, inhibited the effect of this factor. The effect was also blocked by the tyrosine kinase inhibitor genistein and by antagonizing TGF-beta 1 receptor type I (activin-linked kinase [ALK5]). In IPF tissues TIMP3 gene expression was significantly increased and the protein was localized to fibroblastic foci and extracellular matrix. Our findings suggest that TGF-beta 1-induced TIMP3 may be an important mediator in lung fibrogenesis

Knowledge, Attitudes, and Practices about Zika among a University Community Located in an Endemic Zone in Mexico

To assess the knowledge, attitudes, and practices about the Zika virus in both students and workers at the University of Veracruz, an online survey was conducted. The participants were divided into two groups: one according to sex, the other according to whether they were workers or students. Their answers were classified into knowledge, attitudes, and practices and they were rated as low, medium, and high. The results showed that knowledge about Zika prevailing among the university population is considered as medium in 79.4% of the study population. Most respondents know that the mosquito spreads the Zika virus (98.8%) and the clinical characteristics, while sexual transmission by the virus is little known (36.85%). Both the univariate analysis (OR (CI5) 0.227 (0.070&#8315;0.735), p = 0.013] and multivariate analysis (OR (CI95) 0.234 (0.071&#8315;778), p = 0.018] showed that belonging to the health sciences area is related to having a greater knowledge about Zika. Despite the existing knowledge, a low level of prevention practices prevails in the whole community (55%). A medium level of knowledge about Zika prevailed, while proper implementation of preventive measures for Zika is low, despite the fact that the state of Veracruz&#8212;the place where the University is located&#8212;is an endemic area

Evaluation of Anomalies and Neurodevelopment in Children Exposed to ZIKV during Pregnancy

Zika virus (ZIKV) infection in pregnancy is associated with birth and developmental alterations in infants. In this study, clinical records of 47 infants whose mothers had Zika during pregnancy or clinical manifestations compatible with Zika were reviewed. A description of the infants&rsquo; anomalies was established, and a neurodevelopmental assessment was performed on 18 infants, using the Evaluation of Infant Development (EDI for its initialism in Spanish) and DDST-II (Denver Developmental Screening Test II) tests. From his sample, 74.5% of the infants evaluated had major anomalies and 51.9% had minor anomalies. The incidence of major anomalies, related to trimester of pregnancy, was 84.2% for the first trimester, 77.8% for the second trimester, and 37.5% in the third trimester. A similar trend was observed in the frequency of infants without anomalies and was less evident in the incidence of minor anomalies (p = 0.016). Through neurodevelopmental assessments, EDI identified 27.8% of infants as having normal development, while 55.5% of affected infants had developmental delay, and 16.7% were at risk for developmental delay. The DDSST-II showed that 77.7% infants had delay in the gross motor and language area, 88.8% in the fine-adaptative motor area, and 72.2% in the personal&ndash;social area. In this work, children of mothers with ZIKV infection during pregnancy may have major or minor anomalies regardless of the trimester of pregnancy in which the infection occurred. The neurodevelopmental assessment shows that ZIKV can cause a developmental delay in infants with the fine-adaptative motor area being the most affected