ABSTRACT
Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8-1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.
ABSTRACT
Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66-51% of cases) in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients.
