RESUMO
The rapid availability of effective antiviral treatments would be beneficial during the early phases of a pandemic, as they could reduce viral loads and control serious infections until antigenic vaccines become widely available. One promising alternative therapy to combat pandemics is nanotechnology, which has the potential to inhibit a wide variety of viruses, including the influenza virus. This review summarizes the recent progress using gold, copper, silver, silicone, zinc and selenium nanoparticles, since these materials have shown remarkable antiviral capacity against influenza A virus.
RESUMO
Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.
Assuntos
Hipopigmentação , Vitiligo , Humanos , Interleucina-17/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Vitiligo/epidemiologia , Vitiligo/genética , Polimorfismo Genético , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Multidrug resistant (MDR) enteropathogenic bacteria are a growing problem within the clinical environment due to their acquired tolerance to a wide range of antibiotics, thus causing severe illnesses and a tremendous economic impact in the healthcare sector. Due to its difficult treatment, knowledge and understanding of the molecular mechanisms that confer this resistance are needed. The aim of the present review is to describe the mechanisms of antibiotic resistance from a genomic perspective observed in bacteria, including naturally acquired resistance. The present review also discusses common pharmacological and alternative treatments used in cases of infection caused by MDR bacteria, thus covering necessary information for the development of novel antimicrobials and adjuvant molecules inhibiting bacterial proliferation.
RESUMO
Abstract Background: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. Objective: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. Methods: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. Results: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). Conclusion: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.
RESUMO
BACKGROUND: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. OBJECTIVE: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. METHODS: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. RESULTS: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). CONCLUSION: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.
Assuntos
Doenças Autoimunes , Hipopigmentação , Vitiligo , Antígeno CTLA-4/genética , Estudos de Casos e Controles , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , México , Polimorfismo de Nucleotídeo Único/genética , Vitiligo/genéticaRESUMO
BACKGROUND: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. METHODS: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. CONCLUSIONS: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.
Assuntos
Doenças Metabólicas , Polimorfismo de Nucleotídeo Único , Humanos , Adolescente , Polimorfismo de Nucleotídeo Único/genética , Sobrepeso/epidemiologia , Sobrepeso/genética , México/epidemiologia , Estudos Transversais , Obesidade/epidemiologia , Obesidade/genética , Colesterol , Adiponectina/genéticaRESUMO
Cervical cancer represents a public health problem, develops resistance to traditional therapies and cost-of-treatment is high. These disadvantages have led to the search for alternative bioactive-compound-based therapies. Said bioactive compounds include phenolic compounds, flavonoids, and tannins. The present study aimed to evaluate the therapeutic effect of a P. plicata extract on the HeLa cell line. Viability and apoptosis assays were run on the two cell lines treated with the extract. The peptides, up- and down-expressed in both cell lines, were identified by PDQuest analysis software and high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Our results show that a 500 mg/L treatment deregulated cell viability, with different apoptotic morphologies observed which are associated with the presence of bio-compounds, which up- and down-regulated the peptides. In conclusion, P. plicata regulates proteins associated with apoptosis in HeLa cancer cells.
RESUMO
Resumen El objetivo del trabajo fue analizar los valores de hemoglobina glucosilada en el tercer trimestre de embarazo como predictores alternativos de la diabetes gestacional en pacientes del Noreste de México. Se trata de un estudio retrospectivo de casos y controles a partir de 121 expedientes de pacientes embarazadas, divididos en dos grupos, pacientes con diabetes gestacional (casos) y gestantes con valores glucémicos normales (controles). Se analizaron los factores de riesgo asociados a la diabetes gestacional y se obtuvo un punto de corte para la hemoglobina glucosilada. Se encontró que la obesidad materna, la edad y el antecedente del padecimiento fueron asociados significativamente con la diabetes gestacional. Valores de hemoglobina glucosilada ≥5% incrementaron el riesgo de padecer diabetes mellitus gestacional 4 veces y, aunado a un factor de riesgo, la probabilidad se incrementó 7 veces. Se concluye que los valores de hemoglobina glucosilada en el tercer trimestre de embarazo podrían emplearse como prueba diagnóstica de la diabetes gestacional en pacientes del Noreste de México. Sin embargo, aunque las diferencias encontradas fueron estadísticamente significativas, los resultados se deben interpretar con cautela y requieren su confirmación con estudios que incluyan una muestra mayor.
Abstract The objective of this study was to analise glycosylated hemoglobin values in the third trimester of pregnancy as an alternative predictor of gestational diabetes in North East Mexican cohort patients. This is a retrospective case-control study based on 121 records of pregnant patients, divided into two groups, patients with gestational diabetes (cases) and pregnant women with normal glycemic values (control). The risk factors associated with gestational diabetes were analised and a cut-off point for glycosylated hemogestaglobin was obtained. It was found that maternal obesity, age and a history of the condition were significantly associated with gestational diabetes. Values of glycosylated hemoglobin ≥5% increased the risk of suffering from gestational diabetes 4 times, and coupled with a risk factor, the risk increased 7 times. It is concluded that glycosylated hemoglobin values in the third trimester of pregnancy could be used as a diagnostic test for gestational diabetes in patients from the North East of Mexico. Although the differences found were statistically significant, our results must be interpreted with caution and require confirmation by studies with a larger sample.
Resumo O objetivo deste estudo foi analisar os valores da hemoglobina glicada no terceiro trimestre de gestação como preditores alternativos do diabetes gestacional em pacientes na região nordeste do México. Trata-se de um estudo retrospectivo de casos e controles utilizando 121 prontuários de gestantes divididas em dois grupos; pacientes com diabetes gestacional (casos) e gestantes com valores de glicemia normais (controles). Foram analisados os fatores de risco associados a diabetes gestacional obtendo-se um ponto de corte para a hemoglobina glicada. Descobriu-se que a obesidade materna, idade e antecedentes da doença foram associados significativamente ao diabetes gestacional. Valores da hemoglobina glicada ≥ 5% aumentaram o risco de padecer diabetes mellitus gestacional 4 vezes, e juntamente a um fator de risco, a probabilidade aumentou 7 vezes. Conclui-se que os valores da hemoglobina glicada no terceiro trimestre de gestação poderiam ser usados como teste diagnóstico do diabetes gestacional em pacientes da região nordeste do México. Embora as diferenças encontradas tenham sido estatisticamente significativas, os resultados devem ser interpretados com cautela e requerem confirmação através de estudos que incluam uma amostra maior.
Assuntos
Humanos , Feminino , Adulto , Terceiro Trimestre da Gravidez , Hemoglobinas Glicadas , Diabetes Gestacional/diagnóstico , Mulheres , Estudos de Casos e Controles , Probabilidade , Fatores de Risco , Técnicas e Procedimentos Diagnósticos , Corte , Gestantes , Testes Diagnósticos de Rotina , Transtornos do Metabolismo dos Lipídeos , Obesidade MaternaRESUMO
PURPOSE: Metformin has been widely used for the treatment of Type 2 Diabetes Mellitus (T2DM), hyperglycemia and polycystic ovarian syndrome. Recent studies have suggested the potential of this substance as a cancer chemopreventive agent. We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells. METHODS: mRNA levels of tumor suppressor genes AMPK, APC, and c-MYC, KRAS oncogenes were measured by qRT-PCR in RKO cells treated with 25 µM metformin alone or combined with iRNA-PFK-1, to evaluate the effect of both treatments. RESULTS: At 72 h after treatment with either 25 µM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (pË0.05), ~99.9%, (pË0.01), and ~76% (pË0.05), respectively. CONCLUSION: These in vitro results support the potential therapeutic role of metformin and PFK-1 in the treatment of colon cancer via down-modulation of the expression of several important cancer biomarkers.
Assuntos
Biomarcadores Tumorais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Metformina/administração & dosagem , Fosfofrutoquinase-1/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Combinação de Medicamentos , Humanos , Fosfofrutoquinase-1/genética , RNA , Células Tumorais CultivadasRESUMO
Vitiligo is a skin disorder characterized by depigmentation of the skin due to a lack of melanin. This condition affects men and woman of all ages and its incidence is not restricted by ethnicity or region. Vitiligo is a multifactorial disease, in which melanocytes, which serve important functions in skin pigmentation and immune processes, are impaired. There is sufficient evidence that immunological and genetic factors are primarily responsible for the destruction and dysfunction of melanocytes. Therefore, genetic DNA sequence variants that participate in skin homeostasis, pigmentation and immune response regulation, as well as altered expression patterns, may contribute to the risk of developing vitiligo. The current review presented an overview of the mechanism of pigmentation and of currently known factors involved in depigmentation, as well as the classification, epidemiology, associated comorbidities, risk factors, immunopathogenesis and several genetic and molecular changes associated with vitiligo.
RESUMO
Polyphenols may be an effective therapy for both the prevention and treatment of cancer. Previous studies have found that these compounds may inactive Hela cells, which may even be converted into a normal cells post-treatment. The present study extracted phenolic compounds from pomegranate peel, with the polyphenols then purified using different solvents and identified by means of high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS). Once the phenolic compounds had been purified, we evaluated their cytotoxic effects on both the Hela and NIH-3T3 cell lines, on which an apoptosis assay was also carried out. Additionally, apoptosis assay was carried out on Hela and NIH-3T3. Lastly, the proteome profile was analysed via two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). We isolated and then purified punicalagin and ellagic acid (EA) from pomegranate peel, with both compounds likely to have a cytotoxic effect on Hela and NIH-3T3. However, this effect depends on both concentration and exposure time. Results obtained using a Cayman commercial assay kit suggests that punicalin and EA regulate the apoptosis on the Hela and NIH-3T3 cell lines. Finally, we observed that polyphenols compounds regulate the expression of proteins related to apoptosis. In conclusion, punicalin and EA have a cytotoxic effect on Hela and, furthermore, reactive the apoptotic pathway in this cell.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ácido Elágico/farmacologia , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/farmacologia , Punica granatum , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Ácido Elágico/isolamento & purificação , Feminino , Células HeLa , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Camundongos , Células NIH 3T3 , Extratos Vegetais/isolamento & purificação , Punica granatum/química , Proteoma , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Alopecia areata is an autoimmune disease that produces non-scarring hair loss around the body. Gene variants of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a negative regulator of T-cell response, have been associated with a predisposition to autoimmune diseases in different populations; however, the involvement of these genetic variants in the development of AA is controversial. OBJECTIVE: The present study evaluated the potential association of two CTLA4 gene variants with alopecia areata in a Mexican population. METHODS: We genotyped +49AG (rs231775) and CT60 (rs3087243) variants in 50 AA patients and 100 healthy control participants through PCR-RFLP. RESULTS: No statistical difference was observed for either of the gene variants regarding allele or genotype frequencies between AA patients and the controls when the parameters of family/personal history of autoimmune diseases or gender were considered (p>0.05). STUDY LIMITATIONS: Small sample size of patients and the data were obtained from Northeast Mexico population. CONCLUSION: The genetic variants rs231775 and rs3087243 of the CTLA4 gene are not a risk factor for the development of alopecia areata in the analyzed Mexican population.
Assuntos
Alopecia em Áreas/genética , Antígeno CTLA-4/genética , Variação Genética/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto JovemRESUMO
Vitiligo is a disease characterized by skin depigmentation caused by the selective destruction of melanocytes. The melanocortin system participates as a regulator of melanogenesis and skin pigmentation. Narrowband UVB phototherapy (nb-UVB) is currently considered to be the gold standard and first choice treatment method for vitiligo vulgaris. The aim of the present study was to analyze the clinical and biochemical parameters of vitiligo, as well as to determine the expression of proopiomelanocortin (POMC), melanocortin 1 receptor (MC1R) and melanocortin 4 receptor (MC4R) genes in the skin of patients with stable vitiligo receiving nb-UVB phototherapy. Patient clinical and biochemical parameters, and the skin biopsies of 22 patients with stable vitiligo were analyzed. These biopsies were obtained before and after nb-UVB phototherapy. The genetic expression analysis of POMC, MC1R and MC4R genes was performed via RNA-Sequence analysis. A statistical evaluation of the clinical and biochemical parameters, the degree of response to treatment and the expression profiles of the melanocortin system genes were performed to identify their association with treatment response. A two-sided P≤0.05 value was considered to indicate a statistically significant difference. Alterations were observed in the expression profiles of MC1R following nb-UVB phototherapy (P≤0.05). In addition, elevated levels of triiodothyronine were associated with a poor response to nb-UVB phototherapy. In conclusion the current study revealed that nb-UVB phototherapy altered the expression profile of the MC1R gene.
RESUMO
MicroRNAs (miRNAs) are small molecules of 19-23 nucleotides of RNA that act as regulators of the expression of proteins in eukaryotic cells. Currently, the participation of miRNAs in the development of different types of cancer has been observed. To evaluate the inhibitory effect of kaempferol-3-O-glycoside on the expression of oncological biomarkers, miR31 and miR92a in a colon cancer cell line (RKO) were analyzed. Cells were cultured and treated with 1 mM kaempferol-3-O-glycoside isolated from black bean. Expression levels of miR31 and miR92a were evaluated by real-time PCR using TaqMan probes; in addition, two oncogenes (KRAS and c-MYC) and two tumor suppressors (AMP-activated protein kinase [AMPK] and adenomatous tumors of polyposis coli [APC]) were quantified to validate the biological effects; normalization of expression levels were carried out by 2-ΔΔCt. Results were analyzed by one-way ANOVA. The expression levels of miR31, miR92a, KRAS oncogene, and the c-MYC transcription factor were subexpressed upon 72 h post-treatment with kaempferol-3-O-glycoside compared with the control without treatment (P < .05); in contrast, the tumor suppressor genes AMPK (â¼4.85, P = .005) and APC (â¼2.71, P = .066) tumor suppressors genes were overexpressed. Our results showed the inhibitory effect of isolated black bean flavonoid kaempferol-3-O-glycoside on cancer biomarkers: miR31 and miR92a; based on our results, this flavonoid may have interesting nutritional, therapeutic, and/or prophylactic applications to combat colon cancer.
Assuntos
Neoplasias do Colo/genética , Glicosídeos/farmacologia , Quempferóis/farmacologia , MicroRNAs/genética , Phaseolus/química , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Extratos Vegetais/farmacologiaRESUMO
Abstract: Background: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. Objective: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. Methods: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. Results: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). Study limitations: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. Conclusion: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Terapia Ultravioleta , Vitiligo/genética , Vitiligo/radioterapia , Pigmentação da Pele/efeitos da radiação , Análise de Sequência de RNA , Biópsia , Pigmentação da Pele/genética , Resultado do Tratamento , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TranscriptomaRESUMO
BACKGROUND: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. OBJECTIVE: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. METHODS: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. RESULTS: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). STUDY LIMITATIONS: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. CONCLUSION: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.