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Lymphoma is a disease that affects countless lives each year. In order to combat this disease, researchers have been exploring the potential of DNMTi and HDACi drugs. These drugs target the cellular processes that contribute to lymphomagenesis and treatment resistance. Our research evaluated the effectiveness of a combination of two such drugs, hydralazine (DNMTi) and valproate (HDACi), in B-cell and T-cell lymphoma cell lines. Here we show that the combination of hydralazine and valproate decreased the viability of cells over time, leading to the arrest of cell-cycle and apoptosis in both B and T-cells. This combination of drugs proved to be synergistic, with each drug showing significant growth inhibition individually. Microarray analyses of HuT 78 and Raji cells showed that the combination of hydralazine and valproate resulted in the up-regulation of 562 and 850 genes, respectively, while down-regulating 152 and 650 genes. Several proapoptotic and cell cycle-related genes were found to be up-regulated. Notably, three and five of the ten most up-regulated genes in HuT 78 and Raji cells, respectively, were related to immune function. In summary, our study suggests that the combination of hydralazine and valproate is an effective treatment option for both B- and T-lymphomas. These findings are highly encouraging, and we urge further clinical evaluation to validate our research and potentially improve lymphoma treatment.

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INTRODUCTION: Many Mexicans face barriers to receive delivery care from qualified professionals, especially indigenous and poor sectors of the population, which represent most of the population in the state of Chiapas. When access to institutional delivery care is an option, experiences with childbirth care are often poor. This underscores the need for evidence to improve the quality of services from the user's perspective. The present study was conceived with the objective of understanding how non-clinical aspects of care shape women's birthing experiences in public health institutions in Chiapas. METHODS: We conducted an exploratory qualitative study. Data collection consisted in 20 semi-structured interviews to women who had delivered in a public health facility in Chiapas during the last six months prior to the interview. For the design of the interview guide we used the WHO health system responsiveness framework, which focus on the performance of the health system in terms of the extent to which it delivers services according to the "universally legitimate expectations of individuals" and focuses on the non-financial and non-clinical qualities of care. The resulting data were analyzed using thematic analysis methodology. RESULTS: We identified a total of 16 themes from the data, framed in eight categories which followed the eight domains of the WHO health systems responsiveness framework: Choice of the provider and the facility, prompt attention, quality of basic amenities, access to social support, respectful treatment, privacy, involvement in decisions, and communication. We shed light on the barriers women face in receiving prompt care, aspects of health facilities that impact women's comfort, the relevance of being provided with adequate food and drink during institutional delivery, how accompaniment contributes positively to the birthing experience, the aspects of childbirth that women find important to decide on, and how providers' interpersonal behaviors affect the birthing experience. CONCLUSIONS: We have identified non-clinical aspects of childbirth care that are important to the user experience and that are not being satisfactorily addressed by public health institutions in Chiapas. This evidence constitutes a necessary first step towards the design of strategies to improve the responsiveness of the Chiapas health system in childbirth care.

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BACKGROUND: Mexico is one of the countries with the greatest excess death due to COVID-19. Chiapas, the poorest state in the country, has been particularly affected. Faced with an exacerbated shortage of health professionals, medical supplies, and infrastructure to respond to the pandemic, the non-governmental organization Compañeros En Salud (CES) implemented a COVID-19 infection prevention and control program to limit the impact of the pandemic in the region. We evaluated CES's implementation of a community health worker (CHW)-led contact tracing intervention in eight rural communities in Chiapas. METHODS: Our retrospective observational study used operational data collected during the contract tracing intervention from March 2020 to December 2021. We evaluated three outcomes: contact tracing coverage, defined as the proportion of named contacts that were located by CHWs, successful completion of contact tracing, and incidence of suspected COVID-19 among contacts. We described how these outcomes changed over time as the intervention evolved. In addition, we assessed associations between these three main outcomes and demographic characteristics of contacts and intervention period (pre vs. post March 2021) using univariate and multivariate logistic regression. RESULTS: From a roster of 2,177 named contacts, 1,187 (54.5%) received at least one home visit by a CHW and 560 (25.7%) had successful completion of contact tracing according to intervention guidelines. Of 560 contacts with complete contact tracing, 93 (16.6%) became suspected COVID-19 cases. We observed significant associations between sex and coverage (p = 0.006), sex and complete contact tracing (p = 0.049), community of residence and both coverage and complete contact tracing (p < 0.001), and intervention period and both coverage and complete contact tracing (p < 0.001). CONCLUSIONS: Our analysis highlights the promises and the challenges of implementing CHW-led COVID-19 contact tracing programs. To optimize implementation, we recommend using digital tools for data collection with a human-centered design, conducting regular data quality assessments, providing CHWs with sufficient technical knowledge of the data collection system, supervising CHWs to ensure contact tracing guidelines are followed, involving communities in the design and implementation of the intervention, and addressing community member needs and concerns surrounding stigmatization arising from lack of privacy.

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The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model.

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COVID-19, caused by SARS-CoV-2, is a primarily pulmonary disease that can affect several organs, directly or indirectly. To date, there are many questions about the different pathological mechanisms. Here, we generate an approach to identify the cellular-level tropism of SARS-CoV-2 using human proteomics, virus-host interactions, and enrichment analysis. Through a network-based approach, the molecular context was visualized and analyzed. This procedure was also performed for SARS-CoV-1. We obtained proteomes and interactomes from 145 different cells corresponding to 57 different tissues. We discarded the cells without the proteins known for interacting with the virus, such as ACE2 or TMPRSS2. Of the remaining cells, a gradient of susceptibility to infection was observed. In addition, we identified proteins associated with the coagulation cascade that can be directly or indirectly affected by viral proteins. As a whole we identified 55 cells that could be potentially controlled by the virus, with different susceptibilities, mainly being pneumocytes, heart, kidney, liver, or small intestine cells. These results help to explain the molecular context and provide elements for possible treatments in the current situation. This strategy may be useful for other viruses, especially those with limited reported PPI, such as a new virus.

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Introducción El ácido tranexámico (TXA) es uno de los métodos farmacológicos más efectivos para disminución de pérdida de sangre en reemplazos articulares. El objetivo fue evaluar los efectos de la administración de TXA en infiltración periarticular combinado con vía intraarticular comparado con TXA tópico en la pérdida sanguínea en remplazo total de rodilla (RTC). Materiales & Métodos Estudio observacional retrospectivo. Se incluyeron pacientes sometidos a RTC. Se recolectó valores de hematocrito y hemoglobina pre y posquirúrgica en pacientes operados entre marzo de 2016 y marzo de 2018. Al primer grupo se les realizó infiltración periarticular con mezcla de bupivacaina con epinefrina 150mg, ketorolaco 30mg, morfina 0.1mg/kg y 2g. de TXA intraarticular; al segundo grupo administró el mismo protocolo anterior más 1g. de TXA en la mezcla infiltrada. Resultados 174 pacientes [Grupo 1: 174 (65.9%) y Grupo 2: 90 (34.1%)]. Del grupo 1, el porcentaje de transfusión fue del 0,57% (1 paciente). La disminución promedio del hematocrito fue del 7,03% (-1.4 a 18.3) y la disminución de la hemoglobina de 2,51 (-0.5 a -5.7) g/dl. En el grupo 2 sin transfusiones. Disminución media del hematocrito fue del 7,05 (-0.3 a 15.1) y la disminución de la hemoglobina de 2,56 (0.0-5.2) g/dl. Discusión Los resultados de nuestro estudio son similares a reportes de estudios previos. La utilización de TXA en la mezcla de infiltración periarticular adicional a su uso tópico no genera beneficio en el control de pérdida sanguínea en el remplazo total de rodilla.

Introduction The tranexamic acid is currently one of the most effective pharmacological methods for blood lose in articular replacements. The study aimed to evaluate the effects of TXA administration in periarticular infiltration combined with intraarticular administration compared to topical TXA in blood lose in total knee arthoplasty. Methods Retrospective observational study. Patients undergoing total primary knee arthoplasty were included. Hematocrit and pre-surgical and post-surgical hemoglobin values ??were collected in patients operated between March 2016 and March 2018. The first group underwent peripheral joint infiltration with bupivacaine mixture with epinephrine 150mg, ketorolac 30mg, morphine 0.1mg / kg and 2g. of intraarticular TXA; the second group administered the same previous protocol plus 1g. of TXA in the infiltrated mixture. Outcomes 174 patients [Group 1: 174 (65.9%) and Group 2: 90 (34.1%)]. From group 1, the percentage of transfusion was 0.57% (1 patient). The average decrease in hematocrit was 7.03% (-1.4 to 18.3) and the decrease in hemoglobin from 2.51 (-0.5 to -5.7) g / dl. In group 2 there were no transfusions. The average decrease in hematocrit was 7.05 (-0.3 to 15.1) and the decrease in hemoglobin of 2.56 (0.0-5.2) g / dl. Discussion The results of our study are similar to reports from previous studies. The use of TXA in the mixture of periarticular infiltration in addition to its topical use does not generate benefit in the control of blood loss in the total knee arthroplasty.

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Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.

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Epidemiological information and animal models have shown various Mycobacterium tuberculosis phenotypes ranging from hyper- to hypovirulent forms. Recent genomic and proteomic studies suggest that the outcome of infection depends on the M. tuberculosis fitness, which is a direct consequence of its phenotype. However, little is known about the molecular and cellular mechanisms used by mycobacteria to survive, replicate and persist during infection. The aim of this study was to perform a comprehensive proteomic analysis of culture filtrate from hypo- (CPT23) and hypervirulent (CPT31) M. tuberculosis isolates. Using two-dimensional electrophoresis we observed that 70 proteins were unique, or more abundant in culture filtrate of CPT31, and 15 of these were identified by mass spectrometry. Our analysis of protein expression showed that most of the proteins identified are involved in lipid metabolism (FadA3, FbpB and EchA3), detoxification and adaptation (GroEL2, SodB and HspX) and cell wall processes (LprA, Tig and EsxB). These results suggest that overrepresented proteins in M. tuberculosis CPT31 secretome could facilitate mycobacterial infection and persistence.

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Se realizó un estudio descriptivo y transversal de 20 niños de 0 a 5 años de edad con metabolopatías congénitas (fenilcetonuria, galactosemia, deficiencia de biotinidasa, hiperplasia suprarrenal congénita e hipotiroidismo congénito), quienes habían sido diagnosticados a través de la pesquisa neonatal, procedentes de todos los municipios de Santiago de Cuba, y fueron atendidos en el Centro Provincial de Genética Médica desde el 2006 hasta el 2011, a fin de caracterizarles según algunas variables clínicas y epidemiológicas. En la provincia de Santiago de Cuba se obtuvo una baja tasa de incidencia de los trastornos metabólicos congénitos detectados en la pesquisa neonatal, con una mayor frecuencia del hipotiroidismo congénito (55,0 %). De igual manera, los pacientes mostraban escasas manifestaciones clínicas, las cuales, además, eran leves. Los resultados de la serie reflejaron la presencia de un diagnóstico y tratamiento oportunos, unidos a una adecuada atención pediátrica.

A descriptive and cross sectional study was conducted in 20 children from 0 to 5 years of age with inborn errors of metabolism (phenylketonuria, galactosemia, biotinidase deficiency, congenital adrenal hyperplasia and congenital hypothyroidism), coming from all the municipalities of Santiago de Cuba, who were diagnosed through neonatal screening and attended in the Provincial Center of Medical Genetics from 2006 to 2011, in order to characterize them according to some clinical and epidemiological variables. In Santiago de Cuba province a low rate of incidence of congenital metabolic disorders diagnosed in neonatal screening was obtained, with a higher frequency of congenital hypothyroidism (55.0%). Similarly, patients had a few clinical manifestations, which also were mild. The results of the series revealed the presence of an early diagnosis and treatment, with adequate pediatric care.

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