Mexican Institute for Social Security

Mexican, Mexico

Mexican Institute for Social Security

Mexican, Mexico

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Schnoor M.,CINVESTAV | Garcia Ponce A.,CINVESTAV | Vadillo E.,CINVESTAV | Pelayo R.,Mexican Institute for Social Security | And 2 more authors.
Cellular and Molecular Life Sciences | Year: 2017

Sepsis is a leading cause of death worldwide. Increased vascular permeability is a major hallmark of sepsis. Dynamic alterations in actin fiber formation play an important role in the regulation of endothelial barrier functions and thus vascular permeability. Endothelial integrity requires a delicate balance between the formation of cortical actin filaments that maintain endothelial cell contact stability and the formation of actin stress fibers that generate pulling forces, and thus compromise endothelial cell contact stability. Current research has revealed multiple molecular pathways that regulate actin dynamics and endothelial barrier dysfunction during sepsis. These include intracellular signaling proteins of the small GTPases family (e.g., Rap1, RhoA and Rac1) as well as the molecules that are directly acting on the actomyosin cytoskeleton such as myosin light chain kinase and Rho kinases. Another hallmark of sepsis is an excessive recruitment of neutrophils that also involves changes in the actin cytoskeleton in both endothelial cells and neutrophils. This review focuses on the available evidence about molecules that control actin dynamics and regulate endothelial barrier functions and neutrophil recruitment. We also discuss treatment strategies using pharmaceutical enzyme inhibitors to target excessive vascular permeability and leukocyte recruitment in septic patients. © 2016 Springer International Publishing


Rivas-Santiago B.,Mexican Institute for Social Security | Rivas-Santiago C.,Rutgers University | Rivas-Santiago C.,Instituto Nacional Of Ciencias Medicas Y Nutricion Sz | Hernandez-Pando R.,Instituto Nacional Of Ciencias Medicas Y Nutricion Sz
Immunotherapy | Year: 2015

Aim: Patients with pulmonary tuberculosis (TB) are the most important source for TB infection, being the risk of infection determined by the source case infectiousness and the contact closeness. Currently, the administration of isoniazid is used to prevent the infection to some extent in household contacts. At experimental level, defensins are efficient molecules for the treatment of TB and other infectious diseases. Materials & methods: In this work, we used a model of Mycobacterium tuberculosis transmission by long cohabitation of infected and noninfected mice, and treated the latter group with antimicrobial peptides in order to determine the potential capacity of defensins to prevent the infection. Results: Our results showed that the intratracheal administration of human neutrophil peptide-1, human β-defensin-2 alone or in combination and the use of L-isoleucine significantly prevents bacterial transmission, diminishing pulmonary lesions and bacterial loads. Conclusion: Data suggest the potential use of L-isoleucine as prophylactic for TB household contacts. © 2015 Future Medicine Ltd.


PubMed | Autonomous University of Zacatecas and Mexican Institute for Social Security
Type: Journal Article | Journal: Immunological investigations | Year: 2016

Aging is a major health issue due to the increased susceptibility of elderly people to infectious, autoimmune, and cardiovascular diseases. Innate immunity is an important mechanism to avoid primary infections; therefore, decreasing of its activity may lead to development of infections. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can eliminate microbial invaders. The role that cytokines play in the regulation of these innate immune mechanisms needs to be explored. Serum determinations of Th1, Th2, and Th17 cytokines were performed in order to evaluate their association with AMPs human beta-defensin (HBD)-2 and LL-37 in young adults, elder adults, and elder adults with recurrent infections. Our results showed differences in interleukin (IL)-10 and IL-6 among the different groups. Inverse correlations in serum cytokine levels and HBD-2 production were identified for IL-10, IL-2, IL-4, tumor necrosis factor-, and IL-6. Also inverse correlations were identified for IL-10, IL-4, and cathelicidin (LL-37). Such results could impact the development of immunomodulators that promote AMP production to prevent and/or contain infectious diseases in this population.


PubMed | CINVESTAV, Oncology Hospital, e-Security, Villa Coapa General Hospital and Mexican Institute for Social Security
Type: Journal Article | Journal: Cell cycle (Georgetown, Tex.) | Year: 2016

Chronic Myeloid Leukemia (CML) is sustained by a small population of cells with stem cell characteristics known as Leukemic Stem Cells that are positive to BCR-ABL fusion protein, involved with several abnormalities in cell proliferation, expansion, apoptosis and cell cycle regulation. Current treatment options for CML involve the use of Tirosine Kinase Inhibitor (Imatinib, Nilotinib and Dasatinib), that efficiently reduce proliferation proliferative cells but do not kill non proliferating CML primitive cells that remain and contributes to the persistence of the disease. In order to understand the role of Cyclin Dependent Kinase Inhibitors in CML LSC permanence after TKI treatment, in this study we analyzed cell cycle status, the levels of several CDKIs and the subcellular localization of such molecules in different CML cell lines, as well as primary CD34(+)CD38(-)lin(-) LSC and HSC. Our results demonstrate that cellular location of p18(INK4c) and p57(Kip2) seems to be implicated in the antiproliferative activity of Imatinib and Dasatinib in CML cells and also suggest that the permanence of quiescent stem cells after TKI treatment could be associated with a decrease in p18(INK4c) and p57(Kip2) nuclear location. The differences in p18(INK4c)and p57(Kip2)activities in CML and normal stem cells suggest a different cell cycle regulation and provide a platform that could be considered in the development of new therapeutic options to eliminate LSC.


PubMed | CINVESTAV, Oncology Hospital, Federico Gomez Childrens Hospital, Autonomous University of Mexico City and Mexican Institute for Social Security
Type: | Journal: BioMed research international | Year: 2015

B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNF, IL-1, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13(+)CD33(+) population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.


Enciso J.,Mexican Institute for Social Security | Enciso J.,National Autonomous University of Mexico | Mayani H.,Mexican Institute for Social Security | Mendoza L.,National Autonomous University of Mexico | Pelayo R.,Mexican Institute for Social Security
Frontiers in Physiology | Year: 2016

Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells. © 2016 Enciso, Mayani, Mendoza and Pelayo.


PubMed | Mexican Institute for Social Security
Type: Journal Article | Journal: Microbes and infection | Year: 2014

The increasing number of people with type 2 diabetes (DM2) is alarming and if it is taken into account that the relative odds of developing tuberculosis in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients, thus in developing countries where these two diseases are encountering face to face, there is a need for prophylaxis strategies. The role of vitamin D has been widely implicated in growth control of Mycobacterium tuberculosis (Mtb) during primary infection mainly through the induction of certain antimicrobial peptides (AMPs). In this study we evaluated the vitamin D serum levels, CYP27B1-hydroxylase enzyme, vitamin D receptor (VDR) and AMPs gene expression in Healthy donors, DM2 and TB patients. Results showed that DM2 group has lower VDR and AMPs expression levels. When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis. This preliminary study suggests the use of vitamin D as prophylaxis for tuberculosis in high DM2 endemic countries.


PubMed | Mexican Institute for Social Security
Type: | Journal: Microbial pathogenesis | Year: 2016

Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non-infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients.


PubMed | Mexican Institute for Social Security
Type: Controlled Clinical Trial | Journal: Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy | Year: 2014

LigaSure was developed as an alternative to suture ligatures, hemoclips and staplers for ligating vessels and tissue bundles. The aim of the present study was to determine whether LigaSure can be used as a welding instrument in the performance of laparoscopic sleeve gastrectomy.Gastric specimens were assigned into four groups. Group 1 - specimens remained with the staple line intact. Group 2 - the staple line was oversewn. Group 3 - the staple line was resected with LigaSure. Group 4 - staple line was resected with LigaSure and the seal was oversewn. In all specimens the pressure tolerance was assessed using a portable sensor.In group 1 the leak pressure was 34.7 11.7 whereas in group 2 specimens the pressure increased three-fold (101.9 21.4). The LigaSure seal alone (group 3) achieved a mean pressure of 13.7 mmHg. However, in group 4 there was an exponential increase on their burst strength up to 142 mmHg (p = 0.0005).According to our results, LigaSure could be used to perform laparoscopic sleeve gastrectomy with reduction of staple-line bleeding and, when reinforced with a running suture, it achieves a strength that approaches that of staples plus oversewing.


PubMed | Mexican Institute for Social Security
Type: Journal Article | Journal: Immunotherapy | Year: 2015

Patients with pulmonary tuberculosis (TB) are the most important source for TB infection, being the risk of infection determined by the source case infectiousness and the contact closeness. Currently, the administration of isoniazid is used to prevent the infection to some extent in household contacts. At experimental level, defensins are efficient molecules for the treatment of TB and other infectious diseases.In this work, we used a model of Mycobacterium tuberculosis transmission by long cohabitation of infected and noninfected mice, and treated the latter group with antimicrobial peptides in order to determine the potential capacity of defensins to prevent the infection.Our results showed that the intratracheal administration of human neutrophil peptide-1, human -defensin-2 alone or in combination and the use of L-isoleucine significantly prevents bacterial transmission, diminishing pulmonary lesions and bacterial loads.Data suggest the potential use of L-isoleucine as prophylactic for TB household contacts.

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