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Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.
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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.
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[This corrects the article DOI: 10.1371/journal.pone.0249704.].
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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.
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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
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.
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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
Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries by indigenous communities in Mexico and Western parts of the United States. This plant has been exploited to treat a wide variety of ailments, with reported antimicrobial and antioxidant properties, as well as cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the germination conditions of A. mexicana are described and the cytotoxic activities of different parts (seeds, leaves, inner vs. outer roots) of the plant from methanol or hexane extracts are preliminarily characterized against cells of seven unique organisms. When comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Additionally, using the MTT colorimetric assay, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC (oncogene) and APC (tumor suppressor) mRNA levels help elucidate how the A. mexicana root methanol extract may be affecting colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and subsequent nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, have been identified. The roots were found to possess both phytocompounds, while the leaf lacked chelerythrine. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial and anticancer drug discovery has plateaued.
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Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Argemone/química , Citotoxinas/farmacologia , Benzofenantridinas/farmacologia , Berberina/farmacologia , Linhagem Celular Tumoral , Humanos , México , Extratos Vegetais/farmacologia , Folhas de Planta/química , Raízes de Plantas/química , Solventes/químicaRESUMO
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.
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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
Diagnosis of colorectal cancer in patients under 45 years old should alert us to possible hereditary forms of this neoplasia. Most cases of hereditary colorectal cancer correspond to Lynch syndrome which is caused by mutations in DNA mismatch repair genes, particularly MLH1 and MSH2. The dysfunction is associated with microsatellite instability which occurs in 95% cases of this syndrome and in 15% of sporadic colorectal cancer. In sporadic colon tumors, downregulation of MLH1 is observed in cases with the BRAF V600E variant, which induces hypermetylation of the MLH1 promoter. Mutation screening for hereditary cancer has impacted the diagnosis, genetic counseling, and early tumor detection in families affected by hereditary colorectal cancer syndromes but mutation screening technologies are seldom available in public health care centers in developing countries. This study aimed to describe immunohistochemistry and microsatellite instability abnormalities in tumor samples archived in a public hospital in Mexico. Paraffin-embedded samples of patients with colorectal cancer, diagnosed at under 50 years old, were studied to analyze correlations among clinical variables, MLH1 and MSH2 protein expression (immunohistochemistry), microsatellite instability (fluorescent PCR-based assay), and BRAF V600E variant (real time PCR). Forty-seven tumor specimens from patients with TNM stage II and above were analyzed. Tumors were mainly located in the proximal colon segment and displayed histologic intestinal variety and infiltration to serosa. Twenty samples showed decreased expression of mismatch repair proteins and 10 of these presented microsatellite instability (7 high and 3 low instability patterns, respectively). There were no instances of BRAF V600E mutation found. Altered MLH1 or MSH2 expression was found in 42.5% of the samples and microsatellite instability was observed in 21.3% of the tumors. These results suggested that about a fifth of the patients were candidates for family assessment and genetic counseling.
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The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly- phenotype. Subjects with PPARG2 Ala- phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.
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Doenças Metabólicas/epidemiologia , Doenças Metabólicas/genética , Obesidade/epidemiologia , Obesidade/genética , PPAR gama/genética , Fatores de Transcrição/genética , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Estudos de Associação Genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Masculino , México/etnologia , Pessoa de Meia-Idade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
Previously, we described that acetylsalicylic acid (ASA) decreases HCV expression, but the mechanisms involved have not been clearly established. We evaluated the participation of inducible nitric oxide synthase (iNOS) in the regulation of HCV-RNA induced by ASA. Huh7 cells expressing non-structural HCV proteins were exposed to 4 mM ASA and incubated at the same times we reported HCV downregulation (24-72 h), and iNOS mRNA and protein levels were then measured by real-time PCR and Western blot, respectively. Nitric oxide levels were measured at the same time. Inhibition of iNOS mRNA by small interfering RNAs (siRNA) and activation of the iNOS gene promoter by ASA treatment were evaluated. In Huh7 replicon cells treated with ASA, we found decreased levels of iNOS mRNA, iNOS protein and nitrosylated protein levels at 48-72 h. ASA exposure also reduced the transactivation of the iNOS promoter in HCV replicon cells at 48 h, and this was partly due to the decrease in the affinity of transcription factor C/EBP-ß for its binding site in the iNOS promoter. siRNA silencing of iNOS decreased HCV-RNA expression (65 %) and potentiated the antiviral effect (80 %) of ASA compared with control cells. ASA reduces iNOS expression by downregulating promoter activity, mRNA and protein levels at the same time that it decreases HCV expression. These findings suggest that the antiviral activity of ASA is mediated partially through the modulation of iNOS.