RESUMEN
Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.
Asunto(s)
COVID-19 , Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/genética , COVID-19/genética , SARS-CoV-2 , Riñón , Expresión GénicaRESUMEN
The first cases of unexplained pneumonia were reported in Wuhan, China, in December of 2019. Later, a novel coronavirus (SARS-CoV-2) was identified as the causal agent of pneumonia. This virus has since spread to more than 180 countries and has been declared a pandemic by the World Health Organization. Herein, we aimed to determine the epidemiological and clinical characteristics of symptomatic patients with coronavirus disease 2019 (COVID-19) and the relationship between the influenza vaccine with a lower risk of severe COVID-19 infection in the state of Sinaloa. We collected demographic and clinical data of 4,040 patients with acute respiratory infections across Sinaloa state hospitals from February 28 to May 15, 2020. The prevalence of COVID-19 among hospitalized patients with respiratory symptoms in Sinaloa showed 45.2% of men were more affected than women (p < 0.001), and people aged 40-49 years were the most affected. The main symptoms of COVID-19 infection were cough and fever (p < 0.001), while hypertension, obesity, and type 2 diabetes were the chronic diseases associated with COVID-19 than non-COVID-19 (p < 0.003). Healthcare workers were most likely to be infected compared to other occupations (p < 0.001). The general lethality rate was 14.1%, and males >62 years were the ones who had a higher lethality rate (p < 0.001); the aforementioned chronic diseases were related to higher lethality of COVID-19 (p < 0.001). Likewise, higher lethality was seen in housewives and patient retirees/pensioners compared with other occupations (p < 0.001). Finally, we found there was a relationship between influenza vaccination and a lower risk of severe COVID-19 infection and mortality (p < 0.001). These findings showed that healthcare workers, men >62 years with chronic diseases, and retired people were most affected. Furthermore, the influenza vaccine could decrease the severeness of COVID-19 cases.
Asunto(s)
COVID-19/epidemiología , Vacunas contra la Influenza/administración & dosificación , Adulto , COVID-19/mortalidad , Comorbilidad , Tos/virología , Diabetes Mellitus Tipo 2 , Femenino , Fiebre/virología , Humanos , Hipertensión , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiology. Genetic variation within different major histocompatibility complex (MHC) loci contributes to the susceptibility to IPF. The effect of 70 kDa heat shock proteins (HSP70) gene polymorphisms in the susceptibility to IPF is unknown. The aim of this study was to explore the association between HSP70 polymorphisms and IPF susceptibility in the Mexican population. METHODS: Four HSP70 single nucleotide polymorphisms (SNPs) were evaluated using real time PCR assays in 168 IPF patients and 205 controls: +2763 C>T of HSPA1L (rs2075800), +2437 of HSP HSPA1L A>G (rs2227956), +190 of HSPA1A G>C (rs1043618) and +1267 of HSPA1B G>A (rs1061581). RESULTS: The analysis of the recessive model revealed a significant decrease in the frequency of the genotype HSPA1B AA (rs1061581) in IPF patients (OR = 0.27, 95 % CI = 0.13-0.57, Pc = 0.0003) when compared to controls. Using a multivariate logistic regression analysis in a codominant model the HSPA1B (rs1061581) GA and AA genotypes were associated with a lower risk of IPF compared with GG (OR = 0.22, 95 % CI = 0.07-0.65; p = 0.006 and OR = 0.17, 95 % CI = 0.07-0.41; p = <0.001). Similarly, HSPA1L (rs2227956) AG genotype (OR = 0.34, 95 % CI = 0.12-0.99; p = 0.04) and the dominant model AG + GG genotypes were also associated with a lower risk of IPF (OR = 0.24, 95 % CI = 0.08-0.67; p = 0.007). In contrast, the HSPA1L (rs2075800) TT genotype was associated with susceptibility to IPF (OR = 2.52, 95 % CI = 1.32-4.81; p = 0.005). CONCLUSION: Our findings indicate that HSPA1B (rs1061581), HSPA1L (rs2227956) and HSPA1 (rs1043618) polymorphisms are associated with a decreased risk of IPF.
Asunto(s)
Proteínas HSP70 de Choque Térmico/genética , Fibrosis Pulmonar Idiopática/genética , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Modelos Logísticos , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS: Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS: Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION: High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection.
Asunto(s)
Lesión Renal Aguda/virología , Gripe Humana/complicaciones , Obesidad/complicaciones , Síndrome de Dificultad Respiratoria/virología , Lesión Renal Aguda/metabolismo , Adulto , Enfermedad Crítica , Femenino , Humanos , Inflamación/metabolismo , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/metabolismo , Masculino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/metabolismoRESUMEN
Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death.
Asunto(s)
Lesión Renal Aguda/metabolismo , Proteínas Angiogénicas/metabolismo , Inflamación/metabolismo , Gripe Humana/metabolismo , Neovascularización Patológica/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/virología , Adulto , Biomarcadores/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CXCL10/metabolismo , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/complicaciones , Gripe Humana/mortalidad , Masculino , México/epidemiología , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/virología , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by an influx of activated T cells to the lung, in which the CD28/B7 costimulatory signals are essential for the T cell activation and the outcome of the inflammatory response. In this study, we investigated the effect of the CD28/B7 antagonist, CTLA-4Ig, on the lung inflammation and the T cell subset profile in experimental Saccharopolyspora recivirgula (SR)-induced HP. C57BL/6 mice were treated with SR or saline during two and three weeks and in addition of CTLA-4Ig was administrated after either the second or third week and mice were sacrificed seven days later. The extent of the lung inflammation was quantified by histopathology and the lung T cell subsets (Treg, Th17, γδT and NKT) were analyzed by flow cytometry. Mice treated with CTLA-4Ig showed a significant decrease in the extent of lung damage (p<0.05), and exhibited a decreased number of inflammatory cells in the bronchoalveolar lavage (BAL) with diminished CD4/CD8 T cell ratio. Also, a significant increase in the percentage of lung γδT (p<0.01) and NKT (p<0.05) cells was observed in two weeks SR-treated mice with the administration of CTLA-4Ig/SR. At 3 weeks, SR-treated mice showed an increased percentage of regulatory T cells but no significantly differences were found in the percentage of Th17 cells when compared with CTLA-4Ig/SR-treated mice. Our findings suggest that the treatment with CTLA-4Ig affects the HP progression and the lung T cell subset kinetics in mice.
Asunto(s)
Alveolitis Alérgica Extrínseca , Antígenos B7/antagonistas & inhibidores , Antígenos CD28/antagonistas & inhibidores , Inmunoconjugados/farmacología , Subgrupos de Linfocitos T , Abatacept , Alveolitis Alérgica Extrínseca/tratamiento farmacológico , Alveolitis Alérgica Extrínseca/inmunología , Animales , Antígenos B7/inmunología , Antígenos CD28/inmunología , Progresión de la Enfermedad , Femenino , Inmunofenotipificación , Inmunosupresores/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Ratones , Ratones Endogámicos C57BL , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunologíaRESUMEN
The Galß1,3GalNAc-specific lectin from Amaranthus leucocarpus (ALL) shows a differential binding pattern on murine thymocytes, peripheral and activated CD4(+) and CD8(+) T cells. Although ALL detects activation-related changes in T cell surface carbohydrate moieties, no study has been performed to examine the effect of ALL on T cell activation. In this study, we analyzed the anti-CD3-dependent activation of murine T cells in the presence of ALL by measuring proliferation, surface activation marker expression, and IL-2 secretion using total cells from the lymph node. The results showed that ALL did not significantly induce T cell activation but did enhance anti-CD3-dependent activation of both CD4(+) and CD8(+) T cells. In addition, ALL protected T cells from spontaneous apoptosis and increased cell survival in serum-free culture conditions. Our findings indicate that ALL alone does not affect T cell activation, but do suggest that ALL has an anti-CD3-dependent co-stimulatory-like effect on T cell activation. Moreover, ALL promotes cell survival in regular and serum-free culture conditions. This study is the first report of a non-mitogenic T cell-binding lectin that can induce a possible costimulatory-like effect and provides a new tool for understanding how glycosylation impacts the T cell response.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Complejo CD3/inmunología , Glicoproteínas/farmacología , Activación de Linfocitos/efectos de los fármacos , Lectinas de Plantas/farmacología , Linfocitos T/efectos de los fármacos , Animales , Anticuerpos Monoclonales/inmunología , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/metabolismo , Apoptosis/efectos de los fármacos , Carbohidratos/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate gene expression at the posttranscriptional level by blocking translation or inducing degradation of messenger RNA targets. It has been shown that miRNAs participate in a wide spectrum of essential biologic processes including cell cycle, differentiation, development, apoptosis and hematopoiesis, revealing one of the major regulators of human gene expression. Recent studies have shown evidences of abnormal expression of miRNAs in solid and hematological tumors, as well as the association of altered miRNAs with oncogenic or tumor suppressor functions, suggesting a key role of miRNAs in carcinogenesis. Moreover, unique profiles of altered miRNAs expression seem to allow distinction from normal tissue, prediction of disease outcomes, and evaluation of tumor aggressiveness in several types of cancer, including lung cancer. These unique and highly stable miRNAs patterns seems not to depend of age and race, and these characteristics highlight their potential diagnostic and prognosis utility. These findings are particularly promising for lung cancer, a worldwide leading cause of cancer-related deaths with a poor survival rate, despite the discovery of novel therapies. This review describes the potential of miRNAs as biomarkers for diagnosis, cancer classification and estimation of prognosis in lung cancer; and the approaches used to detect and quantify these miRNAs; including the current information about circulating miRNAs as potential biomarkers in lung cancer. This review also provides a description of miRNAs biogenesis, nomenclature and available database for miRNA sequences.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs , Biomarcadores/análisis , Humanos , MicroARNs/análisis , PronósticoRESUMEN
Activation of CD4(+) T cells plays a main role in adaptive immune response by regulating cellular and humoral immunity via processes associated with changes in cell surface oligosaccharide receptors. Lectins are glycoproteins that specifically recognize oligosaccharides and have been used to characterize changes in oligosaccharides present on T cell surface and their effects on activation. A lectin from Amaranthus leucocarpus seeds (ALL) is specific for glycoprotein structures containing galactose-N-acetylgalactosamine and is able to bind to human and murine CD4(+) T cells, however, its effect on activation remains unclear. We examined the effect of ALL on the activation of peripheral blood human CD4(+) T cells and analyzed cell proliferation, expression of the activation-associated molecule CD25, secretion of the activation-dependent cytokine interleukin (IL)-2 and intracellular calcium influx changes using flow cytometry. CD4(+) T cells were stimulated with anti-CD3 antibodies that provided the first activation signal in the presence or absence of ALL. ALL alone did not induce CD4(+) T cell activation but when also stimulated with anti-CD3 antibodies, ALL up-regulated CD25 expression, cell proliferation, IL-2 secretion and an intracellular calcium influx in a dose-dependent manner. In addition, ALL recognized CD4(+) T cells expressing the CD69 and Ki67 molecules expressed only by activated T cells and induced production of the TH1-type cytokine interferon-gamma. Our findings indicate that ALL binds to human activated CD4(+) T cells and enhances the degree of activation of CD4(+) T cells that are stimulated with anti-CD3 antibodies. ALL provides a new tool for analyzing T cell activation mechanisms.
Asunto(s)
Anticuerpos/inmunología , Complejo CD3/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Glicoproteínas/farmacología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Lectinas de Plantas/farmacología , Anticuerpos/farmacología , Linfocitos T CD4-Positivos/citología , Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Humanos , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Amaranthus leucocarpus lectin (ALL) is specific for GalNAc, and recognizes human T cells. The receptor for ALL was purified from T cells using biotin-labeled lectin and avidin-agarose as affinity matrix. It is a 70-kDa glycoprotein, constituted mainly by serine, glycine, and glutamic acid; its glycosidic portion contains mainly GalNAc; galactose, sialic acid, mannose, and GlcNAc were identified at a lower proportion. By ionic strength chromatography, as well as double dimension electrophoresis, we identified four isoforms of the ALL-receptor. N-terminal amino acid was blocked both in the ALL-receptor and its isoforms, therefore, tryptic peptides of ALL-receptor, analyzed through MALDI-TOF, were compared with the relative values obtained from the NCBInr (ProFound 2004/06/01) database. Our results indicated that the tryptic peptides obtained showed 54% homology with a DnaK-core molecular chaperone, 47% with human KIAA protein, and 44% with heat shock protein 8. The most frequent phenotype of the CD4 or CD8 ALL+ T cells was CD45RA+ CD27+; 26% of ALL+ T cells were CD25+ and 13% were CD69+, indicating that the glycoprotein recognized by ALL is present mainly on naive or quiescent T cells.