RESUMEN
Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigated the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy.
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Apoptosis , Proliferación Celular , Biología Computacional , Quercetina , Neoplasias Gástricas , Quercetina/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
The utilization of food as a therapeutic measure for various ailments has been a prevalent practice throughout history and across different cultures. This is exemplified in societies where substances like Hibiscus sabdariffa have been employed to manage health conditions like hypertension and elevated blood glucose levels. The inherent bioactive compounds found in this plant, namely, delphinidin-3-sambubioside (DS3), quercetin (QRC), and hibiscus acid (HA), have been linked to various health benefits. Despite receiving individual attention, the specific molecular targets for these compounds remain unclear. In this study, computational analysis was conducted using bioinformatics tools such as Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb to identify the molecular targets, pathways, and hub genes. Supplementary results were obtained through a thorough literature search in PubMed. DS3 analysis revealed potential genetic alterations related to the metabolism of nitrogen and glucose, inflammation, angiogenesis, and cell proliferation, particularly impacting the PI3K-AKT signaling pathway. QRC analysis demonstrated interconnected targets spanning multiple pathways, with some overlap with DS3 analysis and a particular focus on pathways related to cancer. HA analysis revealed distinct targets, especially those associated with pathways related to the nervous system. These findings emphasize the necessity for focused research on the molecular effects of DS3, QRC, and HA, thereby providing valuable insights into potential therapeutic pathways.
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Antocianinas , Citratos , Hibiscus , Quercetina , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Fosfatidilinositol 3-QuinasasRESUMEN
Rheumatoid Arthritis (RA) is characterized by joint destruction, chronic inflammation, and autoantibody production. IL-21/IL-21R plays an essential role in the immunopathology of RA. Elevated IL-21 serum levels have been associated with RA and disease activity. Here, we evaluated the association of IL-21/IL-21R polymorphisms and IL-21 serum levels with RA. The study included 275 RA patients and 280 Control subjects (CSs). Single nucleotide polymorphisms IL-21 (rs2055979 and rs2221903) and IL-21R (rs3093301) were genotyped using PCR-RFLP. Clinical activity was evaluated by DAS28-ESR; IL-21 and anti-CCP serum levels were quantified by ELISA. The IL-21 rs2055979 AA genotype was higher in RA patients than in the CS group (p = 0.0216, OR = 1.761, 95% CI = 1.085-2.859); furthermore, RA patients showed anti-CCP elevated levels compared to the CA genotype (p = 0.0296). The IL21R rs3093301 AA genotype was also higher in RA patients than in the CS group (p = 0.0122, OR = 1.965, 95% CI = 1.153-3.348). The AT haplotypes of IL-21 rs2055979 and rs2221903 were more frequent (49%) in the RA group (p = 0.006). IL-21 serum levels were significantly elevated in the RA group, but without an association with IL-21 polymorphisms. In conclusion, IL-21 rs2255979 and IL-21R rs3093301 are associated with a higher risk of RA, and could be a genetic marker. Moreover, the elevated IL-21 levels in RA suggest that IL-21/IL-21R could be a therapeutic target in RA.
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Anticuerpos Antiproteína Citrulinada , Artritis Reumatoide , Humanos , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Artritis Reumatoide/genéticaRESUMEN
Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. ß-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases. A diet-induced obesity model was performed in 16-week-old C57BL/6 mice administered with BCP [50 mg/kg]. A reduction in the expression of Claudin-1 was observed in the group with a high-fat diet (HFD), which was caused by the administration of BCP; besides BCP, the phylaAkkermansia and Bacteroidetes decreased between the groups with a standard diet (STD) vs. HFD. Nevertheless, the use of BCP in the STD increased the expression of these phyla with respect to fatty acids; a similar effect was observed, in the HFD group that had a decreasing concentration that was restored with the use of BCP. The levels of endotoxemia and serum leptin increased in the HFD group, while in the HFD + BCP group, similar values were found to those of the STD group, attributing the ability to reduce these in conditions of obesity.
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Enfermedades Gastrointestinales , Sesquiterpenos , Enfermedades de Transmisión Sexual , Animales , Claudina-1 , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/uso terapéutico , Leptina , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Enfermedades de Transmisión Sexual/complicacionesRESUMEN
INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1(83-119), D2, and B´/B epitopes. OBJECTIVES: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane. MATERIAL AND METHODS: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, IFN-γ, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with 35S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy. RESULTS: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048). CONCLUSION: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.
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Interleucina-10 , Lupus Eritematoso Sistémico/prevención & control , Vacunas de ADN , Animales , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Femenino , Interleucina-10/administración & dosificación , Interleucina-10/farmacología , Ratones , Ratones Endogámicos BALB C , Terapias en Investigación , Vacunación , Vacunas de ADN/administración & dosificación , Vacunas de ADN/farmacologíaRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. METHODOLOGY: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). RESULTS: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. CONCLUSIONS: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points ⢠IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. ⢠RF, anti-CCP, and anti-MCV had higher levels in early than established RA. ⢠IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. ⢠Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
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Artritis Reumatoide/sangre , Autoanticuerpos/sangre , Citocinas/sangre , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.
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Células de la Médula Ósea/inmunología , Células Dendríticas/inmunología , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Animales , Células de la Médula Ósea/patología , Antígenos CD40 , Daño del ADN/inmunología , Células Dendríticas/patología , Masculino , Ratones , Proteína 2 Ligando de Muerte Celular Programada 1/inmunologíaRESUMEN
Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.
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Periodontitis Crónica/genética , Periodontitis Crónica/metabolismo , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Adulto , Periodontitis Crónica/sangre , Periodontitis Crónica/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Líquido del Surco Gingival/inmunología , Líquido del Surco Gingival/metabolismo , Humanos , Oxidorreductasas Intramoleculares/química , Oxidorreductasas Intramoleculares/inmunología , Factores Inhibidores de la Migración de Macrófagos/química , Factores Inhibidores de la Migración de Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Saliva/inmunología , Saliva/metabolismoRESUMEN
BACKGROUND: Silver nanoparticles (AgNPs) have attracted considerable attention due to the variety of their applications in medicine and other sciences. AgNPs have been used in vitro for treatment of various diseases, such as hepatitis B and herpes simplex infections as well as colon, cervical, and lung cancers. In this study, we assessed the effect on proliferation, adhesion, and apoptosis in breast cancer cell lines of different molecular profiles (MCF7, HCC1954, and HCC70) exposed to AgNPs (2-9 nm). METHODS: Breast cancer cell lines were incubated in vitro; MTT assay was used to assess proliferation. Adhesion was determined by real-time analysis with the xCELLingence system. Propidium iodide and fluorescein isothiocyanate-Annexin V assay were used to measure apoptosis. The transcriptome was assessed by gene expression microarray and Probabilistic Graphical Model (PGM) analyses. RESULTS: The results showed a decreased adhesion in breast cancer cell lines and the control exposed to AgNPs was noted in 24 hours (p≤0.05). We observed a significant reduction in the proliferation of MCF7 and HCC70, but not in HCC1954. Apoptotic activity was seen in all cell lines exposed to AgNPs, with an apoptosis percentage of more than 60% in cancer cell lines and less than 60% in the control. PGM analysis confirmed, to some extent, the effects of AgNPs primarily on adhesion by changes in the extracellular matrix. CONCLUSION: Exposure to AgNPs causes an antiproliferative, apoptotic, and anti-adhesive effect in breast cancer cell lines cultured in vitro. More research is needed to evaluate the potential use of AgNPs to treat different molecular profiles of breast cancer in humans.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Nanopartículas del Metal/química , Plata/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Nanopartículas del Metal/administración & dosificación , Plata/químicaRESUMEN
Macrophage migration Inhibitory Factor (MIF) is a cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive-feedback-loop with proinflammatory cytokines and could perpetuate the inflammatory process in Systemic Lupus Erythematosus (SLE).The aim of this study was to assess the effect of recombinant-human-MIF (rhMIF) on the expression of Th1, Th2 and Th17 cytokines in Peripheral Blood Mononuclear Cells (PBMC) from Healthy Subjects (HS) and SLE patients. The PBMC were isolated from SLE patients classified according to the 1997 SLE ACR criteria and HS donors; all subjects included were women from an unrelated Mexican-Mestizo population. The PBMC isolated were stimulated with rhMIF, LPS and ISO-1 in different combinations; Th1, Th2 and Th17cytokine profiles levels were determined by MAGPIX Bio-plex assay in supernatants from cell cultures. We observed in supernatants of PBMCs from HS treated with rhMIF a predominance of Th17 cytokine profile with an increase of IL-17A, IL-17F and IL-21 versus PBMCs from SLE patients, which showed an inflammatory profile represented by increase of IL-6 cytokine. According to SLE remission/activity presented at enrollment in the study (Mex-SLEDAI index), the PBMC from active SLE patients showed higher levels of TNF-α and IL-6 versus PBMC from remission SLE patients. In conclusion, our results suggest that MIF can induce a differential inflammatory response in physiological and pathological conditions with a predominance of a Th17 cytokine profile in PBMC from HS and an increase in TNF-α and IL-6 expression in PBMC from active SLE patients.
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Interleucina-6/inmunología , Oxidorreductasas Intramoleculares/inmunología , Lupus Eritematoso Sistémico/inmunología , Factores Inhibidores de la Migración de Macrófagos/inmunología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adulto , Estudios de Casos y Controles , Citocinas/inmunología , Femenino , Humanos , Interleucina-17/inmunología , Interleucina-6/sangre , Oxidorreductasas Intramoleculares/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/sangre , Factores Inhibidores de la Migración de Macrófagos/farmacología , Persona de Mediana Edad , Cultivo Primario de Células , Proteínas Recombinantes/farmacología , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Células Th2/efectos de los fármacos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIMS: The purpose of this study was to compare the effect of naringin 100mg/kg in combination with pravastatin 10mg/kg by gavage for 6weeks compared with monotherapy over lipid profiles, glucose levels and weight in murine model of obesity. MAIN METHODS: The study design was planned with 5 groups of 6 male Wistar Albina rats: Group 1: control with balanced food and vehicle (C-); Group 2: control with Obesity and vehicle (C+); Group 3: Obesity+naringin (N); Group 4: Obesity+pravastatin (P); Group 5: Obesity+pravastatin+naringin (NP). Obesity was developed with a food model. KEY FINDINGS: The naringin groups showed a decrease in weight gain and low glucose values compared to the control group (weight NP:311.4 vs C+:348.6; glucose NP: 173.12 vs C+:235.56) (p<0.05); the group with naringin+pravastatin combination showed the total cholesterol (TC), LDL and triglycerides (TGs) to normal levels (TC NP:51.6 vs C+:83.4; LDL NP:9.32 vs C+:32.32; TGs NP:39.4 vs C+:89.4) (p<0.05); but was not statistically significant compared with monotherapy. SIGNIFICANCE: The combination of naringin and pravastatin did not appear to be better than monotherapy on lipids, but its use could generate euglycemic and antiobesogenic effects, in addition to diminishing the adverse hepatic effects of pravastatin in rats.
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Flavanonas/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Pravastatina/farmacología , Animales , Glucemia/metabolismo , HDL-Colesterol , Quimioterapia Combinada , Flavanonas/uso terapéutico , Glucosa/metabolismo , Lípidos/fisiología , Masculino , Obesidad/tratamiento farmacológico , Pravastatina/uso terapéutico , Ratas , Ratas Wistar , TriglicéridosRESUMEN
BACKGROUND: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). METHODS: The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. RESULTS: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ (721.90 vs. 8.40 pg/mL, p<0.001), IL-1ß (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70 vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43 vs. 0.92 pg/mL, p<0.001). CONCLUSION: These results highlight the potential role of MIF in the establishment of the chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in PBMC from RA and CS.
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Artritis Reumatoide/inmunología , Citocinas/inmunología , Oxidorreductasas Intramoleculares/farmacología , Factores Inhibidores de la Migración de Macrófagos/farmacología , Células TH1/inmunología , Células Th17/inmunología , Adulto , Artritis Reumatoide/patología , Femenino , Humanos , Persona de Mediana Edad , Células TH1/patología , Células Th17/patologíaRESUMEN
BACKGROUND: Human Pegivirus (HPgV) may have a beneficial effect on HIV disease progression in co-infected patients; however, the virologic characteristics of this infection are not well defined. In this study, we determined HPgV viremia prevalence in Mexico and provide new insights to understand HPgV infection and HPgV/HIV co-infection. METHODS: We analyzed and quantified 7,890 serum samples for HPgV viremia by One-Step RT-Real-Time PCR, 6,484 from healthy blood donors and 1,406 from HIV-infected patients. Data on HIV progression were obtained from patients' records. HPgV genotyping was performed in 445 samples by nested PCR of the 5'URT region. Finite Mixture Models were used to identify clustering patterns of HPgV viremia in blood donors and co-infected antiretroviral (ART)-naïve patients. RESULTS: HPgV was detected in 2.98% of blood donors and 33% of HIV patients, with a wide range of viral loads. The most prevalent genotypes were 3 (58.6%)and 2 (33.7%). HPgV viral loads from healthy blood donors and HPgV/HIV+ ART-naïve co-infected patients were clustered into two component distributions, low and high, with a cut-off point of 5.07log10 and 5.06log10, respectively. High HPgV viremia was associated with improved surrogate markers of HIV infection, independent of the estimated duration of HIV infection or HIV treatment. CONCLUSIONS: HPgV prevalence in Mexico was similar to that reported for other countries. The prevalent genotypes could be related to Mexico's geographic location and ethnicity, since genotype 2 is frequent in the United States and Europe and genotype 3 in Asia and Amerindian populations. HPgV viral load demonstrated two patterns of replication, low and high. The more pronounced beneficial response observed in co-infected patients with high HPgV viremia may explain discrepancies found between other studies. Mechanisms explaining high and low HPgV replication should be explored to determine whether the persistently elevated replication depends on host or viral factors.
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Coinfección/virología , Infecciones por Flaviviridae/diagnóstico , Flaviviridae/fisiología , Infecciones por VIH/complicaciones , Viremia/virología , Biomarcadores/análisis , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Flaviviridae/genética , Infecciones por Flaviviridae/epidemiología , Infecciones por Flaviviridae/inmunología , Genotipo , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , México/epidemiología , Prevalencia , Carga Viral , Viremia/inmunología , Replicación ViralRESUMEN
CONTEXT: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response. MATERIALS AND METHODS: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05. RESULTS: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043). DISCUSSION AND CONCLUSIONS: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Genotipo , Metotrexato/administración & dosificación , Receptores KIR2DL2/genética , Receptores KIR/genética , Adulto , Artritis Reumatoide/inmunología , Femenino , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Receptores KIR/inmunología , Receptores KIR2DL2/inmunologíaRESUMEN
Postcholecystectomy bile duct injuries (BDI) produce hepatic cholestasis and cause infection of the biliary tract. The biliary cells participate in secreting cytokines and in expression of immune response receptors. Toll-like receptors (TLRs) conduct signalling and activate the innate and adaptive inflammatory response. The objective was to determine the serum levels of TLR-2 and the expression of TLR-1 and TLR-2 and ß-defensin in liver biopsies of postcholecystectomy BDI patients. A transverse, analytical study with 2 groups was done. One group included healthy volunteers (control group) and other included 25 postcholecystectomy BDI patients with complete biliary obstruction. Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of TLR-2 were determined, and with immunofluorescence the morphologic analysis of TLR-1 and TLR-2 and ß-defensin in liver biopsies of postcholecystectomy BDI patients was performed. The average TLR-2 serum level in the control group was 0.0 pg/mL and in the BDI group, 0.023 ± 0.0045 pg/mL (P < 0.0001, bilateral Mann Whitney U). Immunofluorescence was used to determine the expression in liver biopsies, blood vessels, bile ducts, and hepatic parenchyma where 12 hepatic biopsies were positive for TLR-1 with average of 3213057.74 ± 1071019.25 µm(2); and 7 biopsies were positive for ß-defensin with an average of 730364.33 ± 210838.02 µm(2); and 6 biopsies positive for TLR-2, obtaining an average of 3354364.24 ± 838591.06 µm(2). In conclusion, TLR-1 and TLR-2 and ß-defensin play an important role in the innate antimicrobial defense of the hepatobiliary system.
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BACKGROUND AND AIMS: T. gondii is a causal agent of encephalitis in immunocompromised patients. Pyrimethamine (PYR) has been the treatment of choice for toxoplasmosis. The aim of this study was to analyze the effect of nitazoxanide and pyrimethamine on astrocytes infected with T. gondii in vitro. METHODS: Rat astrocytes were cultured and infected with T. gondii. The effect of nitazoxanide (10, 20 and 30 µg/mL) and pyrimethamine (7, 10 and 13 µg/mL) on astrocytes infected was evaluated at 24 and 48 h post-infection. Tachyzoites and astrocytes were detected by the immunocytochemical method. T. gondii viability in astrocytes infected and treated with NTZ and PYR as well as NTZ and PYR cytotoxicity on astrocytes in vitro were evaluated by the MTT assay. RESULTS: The number of parasites in astrocytes treated with the drugs was significantly reduced when compared to control (p <0.001) at 24 and 48 h. Nitazoxanide produced 97% T. gondii death in a concentration of 10 µg/mL in 48 h infected astrocytes. At 48 h, the death rate of T. gondii was higher when treated with nitazoxanide than with pyrimethamine. A higher toxicity rate in astrocyte was observed when using pyrimethamine at 40 µg/mL. CONCLUSIONS: Nitazoxanide reduced T. gondii infection more efficiently than pyrimethamine and is not cytotoxic to astrocytes at the administered dose.
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Antiparasitarios/farmacología , Astrocitos/parasitología , Pirimetamina/farmacología , Tiazoles/farmacología , Toxoplasma/efectos de los fármacos , Toxoplasmosis/tratamiento farmacológico , Animales , Antiparasitarios/toxicidad , Astrocitos/efectos de los fármacos , Supervivencia Celular , Células Cultivadas , Femenino , Antagonistas del Ácido Fólico/farmacología , Antagonistas del Ácido Fólico/toxicidad , Humanos , Ratones , Persona de Mediana Edad , Nitrocompuestos , Pirimetamina/toxicidad , Ratas , Ratas Wistar , Tiazoles/toxicidad , Toxoplasmosis/parasitologíaRESUMEN
AIM: To demonstrate that CD14⺠cells are an important source of the growth factor YKL-40 in acute and chronic liver damage. METHODS: Rats were inoculated with one dose of CCl(4) to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl(4) was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot. RESULTS: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14⺠cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14â» cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls. CONCLUSION: Hepatic CD14⺠cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated in inflammation-fibrogenesis.
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Proteínas de la Matriz Extracelular/metabolismo , Glicoproteínas/metabolismo , Hepatocitos/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Hígado/metabolismo , Hígado/patología , Adipoquinas/metabolismo , Animales , Células Cultivadas , Proteína 1 Similar a Quitinasa-3 , Proteínas de la Matriz Extracelular/genética , Glicoproteínas/genética , Sustancias de Crecimiento/metabolismo , Hepatocitos/patología , Humanos , Lectinas/metabolismo , Hígado/citología , Macrófagos Alveolares/fisiología , Masculino , Ratas , Ratas WistarRESUMEN
PROBLEM: The pregnancy and menstrual cycle (MC) are the main physiologic events linked to the human reproduction. An adequate neuroendocrine axis is mandatory for the homeostasis in both events. To analyze the distribution of NK, T, Treg cells, expression of their receptors and to associate with hormone levels in pregnant and MC in healthy women. METHOD OF STUDY: We studied two groups of healthy women: 13 pregnant women followed up at 1st, 2nd and 3rd trimesters and 11 women in the 5th and 21st day of the MC. The distribution of NK, T, Treg cells population, expression of their receptors and hormone levels were quantified. RESULTS: In pregnant women, we found an association of NK cells CD56(dim) CD16(+) with prolactin levels. This finding was also was observed for CD56(brigthCD16-) being statistical significant during 1st trimester for both subpopulations. During MC, correlation of CD56(dim) CD16(+) , CD56(bright) CD16(-) cells with prolactin in follicular and luteal phase was found. CONCLUSION: This is the first report where these cell subpopulations have been analyzed prospectively. Even we can argue the random effect for the small number of women is interesting that prolactin showed the more consistent correlation with CD56(dim) CD16(+) , CD56(brigth) CD16(-) cells during both events studied.
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Células Asesinas Naturales/inmunología , Ciclo Menstrual/sangre , Embarazo/sangre , Prolactina/sangre , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Antígeno CD56/análisis , Femenino , Citometría de Flujo , Proteínas Ligadas a GPI/análisis , Humanos , Células Asesinas Naturales/metabolismo , Ciclo Menstrual/inmunología , Embarazo/inmunología , Receptores de IgG/análisis , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
Background: During cholecystectomy, the bile duct may be injured. When this complication occurs, Kupffer cells are activated and produce tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL6) to phagocyte toxic products Aim: To measure serum levels of TNF-α and IL-6 among patients that suffered a bile duct injury after a cholecystectomy. Patients and Methods: Serum levels of TNF-α and IL-6 were measured prior to the bile-enteric derivation and after one year of follow up, in 31 patients that had a complete bile duct obstruction after open or laparoscopic cholecystectomy and in 5 healthy controls. Results: At baseline TNF-α levels in healthy subjects and patients with bile duct injury were 0 and 43.9 ± 2.9 ng/mL, respectively (p < 0.01). At one year of follow up, TNF-á became undetectable among patients. At baseline, the values for IL-6 among healthy controls and patients were 3.0 ± 2.0 and 72.0 ± 94.7 pg/mL respectively, (p < 0,004). After one year of follow up, IL-6 levels decreased to 6.4 ± 0.3 pg/mL among patients. Conclusions: TNF-α and IL-6 levels were elevated before bile-enteric derivation among patients with bile duct injury and became normal one year later.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Conductos Biliares/lesiones , Colecistectomía Laparoscópica/efectos adversos , Colestasis/etiología , /sangre , Macrófagos del Hígado/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Biomarcadores/sangre , Colestasis/sangre , Estudios TransversalesRESUMEN
Introducción: La lesión de vías biliares es un problema clínico importante, se manifiesta por activación de moléculas inflamatorias y fibrogénicas. Objetivo: Evaluar la expresión hepática y sistémica del factor de crecimiento transformante beta (TGF-ß) en la lesión de vías biliares luego de la colecistectomía. Pacientes y métodos: Grupo 1 (control), 3 sujetos sanos; grupo 2, 37 pacientes con lesión de vías biliares poscolecistectomía. Al grupo 2 se le realizó reconstrucción biliodigestiva a 8 semanas de la lesión. Se midió en suero la expresión de TGF-ß por ELISA. La biopsia hepática se sometió a análisis histopatológico e inmuhistoquímica con el anticuerpo anti-TGF-ß, se cuantificó la expresión mediante soporte digital AxioVision 4.6.3. Resultados: El promedio de los niveles séricos de TGF-ß del grupo 1 fue 904.49 ± 227.24 pg/ml contra el grupo 2 con 44 365.71 ± 20 260.61 pg/ml, 48 veces más expresión (p < 0.0001, t de Student). La actividad inflamatoria hepática fue diversa en el grupo 2, mostró grado 4 en 4 (11%); de 3, 15 (40%); de 2, 18 (49%). En el grupo 1 la actividad inflamatoria fue de grado 0. La expresión hepática del TGF-ß en el grupo 1, es de un promedio de 537.15 ± 330.96 μm2; en el grupo 2, 1 768.09 ± 1 024.50 μm2, 2.3 más expresión (p = 0.0473, t de Student). Conclusión: La expresión hepática y sistémica de TGF-ß se encontró aumentada en los pacientes con lesión de vías biliares poscolecistectomía.