Search

People with comorbidities and the male sex are at a higher risk of developing severe COVID-19. In the present study, we aim to investigate the associated factors for infection, severity, and death due to COVID-19 in a population from Nuevo León, México. Epidemiological COVID-19 data were collected from 65 hospitals from December 2020 to May 2022. A total of 75,232 cases were compiled from which 25,722 cases were positive for SARS-CoV-2. Male sex, older age, diabetes, obesity, and hypertension were associated with infection. In addition to the above-mentioned factors, renal disease, cardiovascular disease, and immunosuppression were found to be associated with increased COVID-19 severity. These factors, as well as neurological diseases, are also associated with death due to COVID-19. When comparing the different variants of SARs-CoV-2, the variant B1.1.519 increased the probability of death by 2.23 times compared to the AY.20 variant. Male sex, older age, diabetes, obesity, and hypertension are associated with SARS-CoV-2 infection, severity, and death. Along with the aforementioned comorbidities, renal disease, cardiovascular disease, and immunosuppression are also associated with severity and death. Another factor associated with death is the presence of neurological disease. The SARS-CoV-2 B1.1.519 variant increases the odds of death compared to the SARS-CoV-2 AY.20 variant.

Variants of 8q24 locus have been associated with prostate cancer (PCa) susceptibility. This study aims to analyze the genetic basis of PCa susceptibility in Mexican men by analyzing SNPs in the 8q24 locus for the first time. A case-control study was performed in 875 men recruited from the Mexican Social Security Institute, 326 patients with PCa, and 549 non-PCa patients (88 with benign prostatic hyperplasia BPH and 461 healthy controls). The 8q24 locus SNPs: rs16901979, rs16983267, rs1447295, and rs7837328 were genotyped by allelic discrimination assays using TaqMan probes. Statistical analysis was performed using Epi Info statistical 7.0 and SNPstats softwares. All genotype frequencies were in Hardy-Weinberg Equilibrium. No differences were observed in genotype distribution between PCa and non-PCa patients for rs6983267. Under different inheritance models, the rs16901979, rs1447295, and rs7837328 SNPs were associated with PCa (OR = 2.8, 1.8, and 1.72, respectively; Pc

Tuberculosis drug resistance (DR) is a global problem that is not fully elucidated. Previously, overexpression of esxG and esxH genes was reported in a multidrug-resistant (MDR) Mycobacterium tuber...

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy–Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis.

Background and aims The impact of host genetic variation in susceptibility of tuberculosis is well documented. The vitamin D receptor gene (VDR) is a transacting transcription factor which mediates innate immune response by enhancing the expression of several antimicrobial peptides, including cathelicidin. An association between VDR polymorphisms with tuberculosis (TB) has been investigated in different ethnic groups; however there are contradictions and inconsistencies in the results. The aim of this study was to evaluate the association between polymorphisms of functional VDR with the susceptibility to pulmonary tuberculosis in a Mexican population. Methods A case–control study was performed in, 257 patients with pulmonary tuberculosis and 457 healthy controls recruited from: family medicine clinics of the Mexican Social Security Institute. The VDR gene polymorphisms Fok I (rs 2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were genotyped by TaqMan assays. Statistical analysis was performed using: Epi Info V-7 and SNP Stats software. Results No statistically significant associations were observed in genotype and haplotype distribution between BsmI, ApaI and TaqI polymorphisms and disease susceptibility. The CC genotype for the VDR gene FokI was significantly more frequent in patients than in controls (29.6% versus 17.5%, OR = 1.97; 95% CI = 1.37–2.8, PC = 0.0004). Moreover, TT genotype was decreased in patients as compared to the control group (24.1% versus 34.8%, OR = 0.59; 95% CI = 0.42–0.84, PC = 0.004). Conclusion To our best knowledge, this is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients. However more validation studies should be performed to prove our conclusions.

Background and aims To assess the relevance of the slow acetylator phenotype based on NAT2 genotypes, among patients with pulmonary tuberculosis (PTB) that developed hepatotoxicity after first-line tuberculosis treatment in a Northeastern Mexican population. Methods Ninety one PTB patients were included, 7 of them developed hepatotoxicity. NAT2 SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931) were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using Epi Info statistical software 7.0 and SHEsisPlus for haplotype reconstruction. The NAT2 slow non-synonymous SNP were studied by molecular dynamic analysis (MDA). Results The frequency of the haplotype associated with slow acetylation status for PTB was 58%, and for with hepatotoxicity (PTB-H) represented 42.6%. Three haplotypes, NAT2*5Q, NAT2*5U, NAT2*5Va were exclusively present in seven PTB-H patients, (P = 0.01, P = 0.0006, P = 0.01, respectively). These haplotypes include the combination of two SNPs (I114T + R197Q or I114T + G286E). The effect of the SNPs on protein structure is to disrupt the CoA binding site affecting acetylation activity. Conclusion Our study provides insight into slow acetylation NAT2 haplotypes associated with hepatotoxicity after first-line tuberculosis treatment, for first time, in a Mexican population. The molecular mechanism acts at the CoA binding site.

Tuberculosis drug resistance (DR) is a global problem that is not fully elucidated. Previously, overexpression of

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

Background Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance. Results The effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p p Conclusions LipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.

The smallest product of the Duchenne muscular dystrophy gene, dystrophin (Dp)71, is ubiquitously expressed in nonmuscle tissues. We previously showed that Dp71 expression in hepatic cells is modulated in part by stimulating factor 1 (Sp1), stimulating protein 3 (Sp3), and yin yang 1 (YY1) transcription factors, and that the polyaromatic hydrocarbon, β-naphthoflavone (β‑NF), downregulates Dp71 expression. The aim of the present study was to determine whether β‑NF represses Dp71 expression by altering mRNA stability or its promoter activity. Reverse transcription‑quantitative polymerase chain reaction was used to measure half‑life mRNA levels in β‑NF‑treated cells exposed to actinomycin D, an inhibitor of transcription, for 0, 4, 8, 12 and 16 h. Transient transfections with a plasmid carrying the Dp71 basal promoter fused to luciferase reporter gene were carried out in control and β‑NF‑treated cells. Electrophoretic mobility shift assays (EMSAs) were performed with labeled probes, corresponding to Dp71 promoter sequences, and nuclear extracts of control and β‑NF‑treated cells. To the best of our knowledge, the results demonstrated for the first time that this negative regulation takes place at the promoter level rather than the mRNA stability level. Interestingly, using EMSAs, β‑NF reduced binding of YY1, Sp1, and Sp3 to the Dp71 promoter. It also suggests that β‑NF may modulate the expression of other genes regulated by these transcription factors. In conclusion, β‑NF represses Dp71 expression in hepatic cells by altering binding of YY1, Sp1, and Sp3 to the Dp71 promoter.

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman’s rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

Mycobacterium tuberculosis has developed resistance to anti-tuberculosis first-line drugs. Multidrug-resistant strains complicate the control of tuberculosis and have converted it into a worldwide public health problem. Mutational studies of target genes have tried to envisage the resistance in clinical isolates; however, detection of these mutations in some cases is not sufficient to identify drug resistance, suggesting that other mechanisms are involved. Therefore, the identification of new markers of susceptibility or resistance to first-line drugs could contribute (1) to specifically diagnose the type of M. tuberculosis strain and prescribe an appropriate therapy, and (2) to elucidate the mechanisms of resistance in multidrug-resistant strains. In order to identify specific genes related to resistance in M. tuberculosis, we compared the gene expression profiles between the pansensitive H37Rv strain and a clinical CIBIN:UMF:15:99 multidrug-resistant isolate using microarray analysis. Quantitative real-time PCR confirmed that in the clinical multidrug-resistant isolate, the esxG, esxH, rpsA, esxI, and rpmI genes were upregulated, while the lipF, groES, and narG genes were downregulated. The modified genes could be involved in the mechanisms of resistance to first-line drugs in M. tuberculosis and could contribute to increased efficiency in molecular diagnosis approaches of infections with drug-resistant strains.

Understanding drug resistance in Mycobacterium tuberculosis requires an integrated analysis of strain lineages, mutations and gene expression. Previously, we reported the differential expression of esxG, esxH, infA, groES, rpmI, rpsA and lipF genes in a sensitive M. tuberculosis strain and in a multidrug-resistant clinical isolate. Here, we have evaluated the expression of these genes in 24 clinical isolates that belong to different lineages and have different drug resistance profiles. In vitro, growth kinetics analysis showed no difference in the growth of the clinical isolates, and thus drug resistance occurred without a fitness cost. However, a quantitative reverse transcription PCR analysis of gene expression revealed high variability among the clinical isolates, including those with similar drug resistance profiles. Due to the complexity of gene regulation pathways and the wide diversity of M. tuberculosis lineages, the use of gene expression as a molecular signature for drug resistance is not straightforward. Therefore, we recommend that the expression of M. tuberculosis genes be performed individually, and baseline expression levels should be verified among several different clinical isolates, before any further applications of these findings.

The quantification of colony forming units (cfu), turbidity, and optical density at 600 nm (OD600) measurements were used to evaluate Mycobacterium tuberculosis growth. Turbidity and OD600 measurements displayed similar growth curves, while cfu quantification showed a continuous growth curve. We determined the cfu equivalents to McFarland and OD600 units.

En este trabajo analizamos por primera vez las distancias genéticas entre grupos indígenas y mestizos mexicanos con el gen HLA-B, el más polimórfico del Complejo Principal de Histocompatibilidad (MHC). Se obtuvieron las frecuencias alélicas de 10 poblaciones indígenas reportadas en la literatura para el gen HLA-B. Además, se incluyeron las frecuencias de mestizos mexicanos (n = 102), asiáticos del noreste (n = 380), euroamericanos (n = 287) y afroamericanos (n = 396) de EUA, kurdos (n = 101), coreanos (n = 29) mandenka de Senegal (n=68) y malayos del sur de Asia (n=94) cuyos datos fueron obtenidos de la base de datos MHC Anthropology. La variación del sistema HLA en el componente amerindio muestra un patrón singular, que se caracteriza por un polimorfismo restringido y un número considerable de nuevos alelos de alta resolución dentro de ciertos linajes alélicos. Estas peculiaridades se intentan vincular a los factores más sobresalientes de la historia biológica de las poblaciones indígenas. En cuanto a los mestizos, la variación se caracteriza por la distribución de las frecuencias en un número mayor de alelos, lo cual es congruente con la diversidad de las aportaciones genéticas ancestrales a los mestizos mexicanos.