Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673757

RESUMO

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.


Assuntos
Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Linfócitos T , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia Adotiva/métodos , Microambiente Tumoral/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo
2.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175995

RESUMO

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/metabolismo , Síndrome de COVID-19 Pós-Aguda , Peptidil Dipeptidase A/metabolismo , Interações entre Hospedeiro e Microrganismos
3.
Mar Drugs ; 18(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019517

RESUMO

Ciguatera is a food intoxication caused by the consumption of primarily coral fish; these species exist in large numbers in the seas that surround the Colombian territory. The underreported diagnosis of this clinical entity has been widely highlighted due to multiple factors, such as, among others, ignorance by the primary care practitioner consulted for this condition as well as clinical similarity to secondary gastroenteric symptoms and common food poisonings of bacterial, parasitic or viral etiology. Eventually, it was found that people affected by ciguatoxins had trips to coastal areas hours before the onset of symptoms. Thanks to multiple studies over the years, it has been possible to identify the relation between toxigenic dinoflagellates and seagrasses, as well as its incorporation into the food chain, starting by fish primarily inhabiting reef ecosystems and culminating in the intake of these by humans. Identifying the epidemiological link, its cardinal symptoms and affected systems, such as gastrointestinal, the peripheral nervous system and, fortunately with a low frequency, the cardiovascular system, leads to a purely clinical diagnostic impression without necessitating further complementary studies; in addition, what would also help fight ciguatera poisoning is performing an adequate treatment of the symptoms right from the start, without underestimating or overlooking any associated complications.


Assuntos
Ciguatera/epidemiologia , Animais , Região do Caribe/epidemiologia , Colômbia/epidemiologia , Dinoflagellida , Peixes , Humanos
4.
BMC Med Ethics ; 21(1): 122, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239017

RESUMO

BACKGROUND: Informed consent is an important factor in a child's moral structure from which different types of doctor-patient relationships arise. Children's autonomy is currently under discussion in terms of their decent treatment, beyond what doctors and researchers perceive. To describe the influential practices that exist among clinicians and researchers toward children with chronic diseases during the process of obtaining informed consent. METHODS: This was a cross-sectional, qualitative study via a subjective and interpretivist approach. The study was performed by conducting semi-structured interviews of 21 clinicians and researchers. Data analysis was performed using the SPSS version 21® and Atlas Ti version 7.0® programs. RESULTS: The deliberative and paternalistic models were influential practices in the physician-patient relationship. In the deliberative model, the child is expected to have a moral awareness of their care. The paternalistic model determined that submission was a way of structuring the child because he or she is considered to be a subject of extreme care. CONCLUSIONS: The differentiated objectification [educational] process recognizes the internal and external elements of the child. Informed consent proved to be an appropriate means for strengthening moral and structuring the child.


Assuntos
Consentimento Livre e Esclarecido , Princípios Morais , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Paternalismo , Relações Médico-Paciente
5.
Int J Mol Sci ; 20(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766160

RESUMO

The complex physiology of eukaryotic cells is regulated through numerous mechanisms, including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the differential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology.


Assuntos
Epigênese Genética , Lúpus Eritematoso Sistêmico/genética , Processamento de Proteína Pós-Traducional , Acetilação , Animais , Glicosilação , Humanos , Hidroxilação , Lúpus Eritematoso Sistêmico/metabolismo , Fosforilação
6.
Sci Rep ; 14(1): 9555, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664528

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.


Assuntos
Biomarcadores , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Metabolômica , Humanos , Feminino , Lúpus Eritematoso Sistêmico/urina , Lúpus Eritematoso Sistêmico/metabolismo , Adulto , Metabolômica/métodos , Biomarcadores/urina , Masculino , Colômbia , Nefrite Lúpica/urina , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/metabolismo , Metaboloma , Pessoa de Meia-Idade , Estudos de Coortes , Estudos de Casos e Controles , Cromatografia Gasosa-Espectrometria de Massas , Adulto Jovem
7.
Front Genet ; 15: 1327243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304339

RESUMO

Background: Cancer genomics, as an interdisciplinary research area within the Global Cancer Research agenda, genomics and precision medicine, its important in research and clinical practice in Latin America. To date, there has been no study investigating evolution of this area in this region. The aim of this study was to evaluate for first time, the historical evolution of cancer genomics research in Latin America. Methods: Bibliometric cross-sectional study of documents on cancer genomics published by Latin American authors until 2023 in Scopus was performed. Statistical and visual analysis was performed with R programming language. Results: A total of 1534 documents were obtained. The first document of cancer genomics research was published in 1997, marking the inception of a 26-year evaluation period that extended until 2023. Among the documents, 74.3% (n = 1140) constituted original articles, followed by 22.7% (n = 349) classified as reviews. International collaboration was observed in 6.5% (n = 100) of the articles. Within the compilation of the ten most prolific authors in this region, 90% of them are from Brazil. This observed pattern extends to affiliations as well, wherein the Universidade de São Paulo emerges as the most active institution (n = 255 documents). This arrangement firmly establishes Brazil's prominence as the preeminent country in the region concerning cancer genomics research, showcasing robust collaboration networks both regionally and intercontinentally. An important transition in the studied hot topics over the last 20 years was identified, from the exploration of the human genome and the characterization of genomic and proteomic cancer profiles (1997-2010) to an in-depth investigation of cancer stem cells and personalized medicine (2011-2023). Among the array of cancer types under study, predominant attention has been directed towards breast, lung, prostate, and leukemia. Conclusion: Over the course of the past 26 years, a favorable and notable evolution has characterized cancer genomics research within Latin America, with Brazil leading the way, which possess a robust network of regional and intercontinental collaboration. Furthermore, the lines of research and hot topics have change in harmony with the region's objectives, strategies, and requisites.

8.
Pharmaceuticals (Basel) ; 16(8)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37630978

RESUMO

The growing emergence of microbes resistant to commercially available antibiotic therapies poses a threat to healthcare systems worldwide. Multiple factors have been associated with the increasing incidence of hospital-acquired infections caused by antibiotic-resistant pathogens, including the indiscriminate use of broad-spectrum antibiotics, the massive application of antibiotics in hospitals as a prophylactic measure, self-medication, and nonadherence to pharmacological therapies by patients. In this study, we developed a novel treatment to mitigate the impact of microbial resistance. We synthesized a benzoporphyrin derivative, 5,10,15,20-tetrakis (4-ethylphenyl) porphyrin (TEtPP), with a reaction yield close to 50%. TEtPP exhibited excellent photophysical properties (Φf = 0.12 ± 0.04 and ΦΔ = 0.81 ± 0.23) and was thereby assessed as a potential agent for antibacterial photodynamic therapy. The photophysical properties of the synthesized porphyrin derivative were correlated with the assayed antimicrobial activity. TEtPP showed higher activity against the MRSA strain under irradiation than in the absence of irradiation (minimum inhibitory concentration (MIC) = 69.42 µg/mL vs. MIC = 109.30 µg/mL, p < 0.0001). Similar behavior was observed against P. aeruginosa (irradiated MIC = 54.71 µg/mL vs. nonirradiated MIC = 402.90 µg/mL, p < 0.0001). TEtPP exhibited high activity against S. aureus in both the irradiated and nonirradiated assays (MIC = 67.68 µg/mL vs. MIC = 58.26 µg/mL, p = 0.87).

9.
Front Psychiatry ; 14: 1222972, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645639

RESUMO

Suicide is a complex and multifaceted public health issue that affects individuals from all walks of life, including healthcare professionals such as physicians. According to research, physicians have a higher risk of suicide compared to the general population, with an estimated suicide rate that is two to three times greater than that of the general population. Suicide in physicians can have devastating consequences, not only for the individual but also for their patients and colleagues. The factors contributing to suicide in physicians are numerous and often interrelated. Physicians are exposed to numerous stressors in their daily lives, including long work hours, high workload, burnout, and exposure to traumatic events. These stressors can lead to mental health problems such as depression, anxiety, and substance use disorders, which in turn can increase the risk of suicide. In addition to work-related stressors, personal factors such as relationship problems, financial stress, and a history of mental health problems can also contribute to suicide risk in physicians. Stigma and shame around seeking help for mental health issues may also prevent physicians from seeking treatment, exacerbating the problem. Understanding the complex factors that contribute to suicide in physicians is crucial for developing effective prevention strategies. For this reason, it is necessary to know the behavior of this phenomenon and the factors associated with a higher risk of suicide in this population. However, taking into account that different regions of the world vary in socioeconomic, cultural, professional, occupational, and health attributes, it is to be expected that the behavior of these risk factors will also be heterogeneous. At present, it is presumed that there is a significant gap in the evidence, due to a predominance of evidence on this topic from high-income countries. Considering the importance of having a comprehensive understanding of the risk factors for suicide in the medical population and possible strategies to mitigate this condition, the aim of this review is to analyze the most recent evidence on these factors, and to assess the quality of the evidence and gaps that need to be studied further.

10.
Saudi J Kidney Dis Transpl ; 33(Supplement): S18-S29, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37102521

RESUMO

Our study aimed to describe the glomerular diseases, both primary glomerular disease (PGD) and secondary glomerular disease (SGD) in the Colombian Caribbean based on the first regional Colombian Nephropathy Registry (NEFRORED®). A descriptive and retrospective study of adult patients with glomerular diseases from the Colombian Caribbean region was made. All diagnoses by renal biopsy with light microscopy and immunofluorescence obtained between January 2008 and June 2018 were recorded. Eight hundred and seventy-one renal biopsies were obtained. The main clinical indication for biopsy was nephritic syndrome (36%). SGD was more frequent than PGD (55% vs. 45%). Within SGD group, lupus nephritis (LN) was the most frequent etiology (83%). Within PGD group, membranous nephropathy (33%) and focal segmental glomerulosclerosis (FSGS) (19%) were the most common glomerular diseases. At a 24-month follow-up, the patients with FSGS and paraproteinemia-mediated glomerular disease had the worst renal survival prognosis. This is the first Colombian Nephropathy Registry in a Caribbean population, demonstrating a high predominance of SGD due to LN.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefropatias , Nefrite Lúpica , Região do Caribe/epidemiologia , Colômbia , Estudos Retrospectivos , Sistema de Registros , Rim/patologia , Biópsia , Glomerulosclerose Segmentar e Focal/epidemiologia , Nefrite Lúpica/epidemiologia , Nefropatias/epidemiologia
11.
Diagnostics (Basel) ; 12(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36428942

RESUMO

We developed and standardized an efficient and cost-effective in-house RT-PCR method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, and other statistical parameters by different RT-qPCR methods including triplex, duplex, and simplex assays adapted from the initial World Health Organization- (WHO) recommended protocol. This protocol included the identification of the E envelope gene (E gene; specific to the Sarvecovirus genus), RdRp gene of the RNA-dependent RNA polymerase (specific for SARS-CoV-2), and RNase P gene as endogenous control. The detection limit of the E and the RdRp genes were 3.8 copies and 33.8 copies per 1 µL of RNA, respectively, in both triplex and duplex reactions. The sensitivity for the RdRp gene in the triplex and duplex RT-qPCR tests were 98.3% and 83.1%, respectively. We showed a decrease in sensitivity for the RdRp gene by 60% when the E gene acquired Ct values > 31 in the diagnostic tests. This is associated with the specific detection limit of each gene and possible interferences in the protocol. Hence, developing efficient and cost-effective methodologies that can be adapted to various health emergency scenarios is important, especially in developing countries or settings where resources are limited.

12.
Clin Epigenetics ; 13(1): 39, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602320

RESUMO

BACKGROUND: In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. METHODS: We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. RESULTS: We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. CONCLUSION: The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.


Assuntos
Doença de Crohn/enzimologia , Doença de Crohn/genética , MicroRNAs/genética , Linfócitos T CD4-Positivos/metabolismo , Montagem e Desmontagem da Cromatina/genética , Ilhas de CpG , Doença de Crohn/fisiopatologia , Metilação de DNA , Epigênese Genética , Regulação da Expressão Gênica , Humanos , Imunidade/genética , Mapas de Interação de Proteínas/genética , Processamento de Proteína Pós-Traducional/genética
14.
PLoS One ; 14(6): e0218116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237906

RESUMO

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p.


Assuntos
Epigênese Genética , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Bases de Dados Genéticas , Ontologia Genética , Redes Reguladoras de Genes , Estudos de Associação Genética , Humanos , MicroRNAs/metabolismo , Processamento de Proteína Pós-Traducional
15.
Cells ; 7(7)2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30011912

RESUMO

The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to different types of cells of the central nervous system (CNS). A strict temporal space control of the NSC differentiation is necessary, because its alterations are associated with neurological dysfunctions and, in some cases, death. This work reviews the current state of the molecular mechanisms that regulate the transcription in NSCs, organized according to whether the origin of the stimulus that triggers the molecular cascade in the CNS is internal (intrinsic factors) or whether it is the result of the microenvironment that surrounds the CNS (extrinsic factors).

16.
PLoS One ; 12(11): e0187973, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29136041

RESUMO

Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.


Assuntos
Nefrite Lúpica/sangue , MicroRNAs/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Colômbia , Feminino , Humanos , Nefrite Lúpica/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Br J Pharmacol ; 174(14): 2373-2392, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28476069

RESUMO

BACKGROUND AND PURPOSE: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation. EXPERIMENTAL APPROACH: We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo. KEY RESULTS: The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group. CONCLUSIONS AND IMPLICATIONS: We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included.


Assuntos
Diterpenos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Proteína Quinase C beta/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Camundongos , Conformação Molecular , Relação Estrutura-Atividade
18.
PLoS One ; 11(11): e0166202, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27835701

RESUMO

Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.


Assuntos
Biomarcadores/sangue , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , MicroRNAs/sangue , Adulto , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Componente Principal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
19.
Rev. colomb. nefrol. (En línea) ; 7(supl.2): 249-258, jul.-dic. 2020. graf
Artigo em Espanhol | COLNAL, LILACS | ID: biblio-1251588

RESUMO

Resumen La educación en ciencias biológicas juega un papel importante a la hora de entender los sistemas vivos y ecosistemas que nos rodea en contexto de una epidemia de tipo zoonótico como SARS-CoV-2 y cumple un papel importante para el autocuidado en pacientes con enfermedad renal que son una población en alto riesgo según datos epidemiológicos. El presente trabajo pretende describir la asociación entre la educación en ciencia biológica y la epidemia por COVID-19. La educación en ciencias biológicas es un componente importante supeditado al autocuidado para que muchos pacientes con enfermedad renal puedan entender la importancia de tener una mejor adherencia al régimen terapéutico y el régimen alimenticio, y en el caso puntual de la epidemia por COVID-19 puede permitir que ellos tomen las medidas preventivas que eviten su exposición al patógeno.


Abstract Biologic education plays an important role in understanding the living systems and ecosystems that it does not surround in the context of a zoonotic-like epidemic such as SARS-CoV-2 may have an important role for self-care in patients with kidney disease that they are a population at high risk according to epidemiological data. That is why the present work aims to describe the association between education in biological science in patients with kidney disease in the context of a covid-19 epidemic. Biological science education is an important component subject to self-care so that many patients with kidney disease allowing them to understand, the importance of having a better adhere to the therapeutic regimen, dietary regimen and in the specific case of the epidemic by COVID-19 may allow them to take preventive measures to avoid their exposure to the pathogen.


Assuntos
Humanos , Masculino , Feminino , Disciplinas das Ciências Biológicas , COVID-19 , Pacientes , Autocuidado , Educação de Pacientes como Assunto , Colômbia , Educação , Nefropatias
20.
Rev. colomb. nefrol. (En línea) ; 7(supl.2): 259-272, jul.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1251589

RESUMO

Resumen La infección por el síndrome respiratorio agudo severo (SARS-CoV-2) ha causado una de las emergencias epidemiológicas más grandes de los últimos 10 años y sus efectos patológicos son aún estudiados. Por lo anterior, resulta importante describir los mecanismos asociados al compromiso renal y digestivo en la infección por SARS-CoV-2. Los mecanismos patológicos en tejido renal y en intestino causados por la infección por SARS-CoV-2 son propios del tropismo viral por células de estos sistemas y de los mecanismos citopáticos de etapa lítica de la infección, con una liberación continua de viriones que favorece la generación de un entorno inflamatorio con la consecuente secreción descontrolada de citoquinas proinflamatorias que conducen a la infección entérica del intestino y a las alteraciones en el riñón.


Abstract Infection with Severe Acute Respiratory Syndrome (SARS-CoV-2) has caused one of the largest epidemiological emergencies in the last 10 years and its pathological effects are still studied. Due to the aforementioned, it is important to describe the mechanisms associated with renal and digestive compromise in SARS-CoV-2 infection. The pathological mechanisms in kidney tissue and in the intestine caused by SARS-CoV-2 infection are characteristic of the viral tropism by cells of these systems and of the lymphocytic mechanisms of the lytic stage of the infection, with a continuous release of virions that favors the generation of an inflammatory environment with the consequent uncontrolled secretion of proinflammatory cytokines that lead to enteric infection of the intestine and alterations in the kidney.


Assuntos
Humanos , Masculino , Feminino , Gastroenteropatias , Nefropatias , Tecidos , Colômbia , Infecções por Coronavirus , Tropismo Viral , COVID-19
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA