RESUMO
Background: Improper use of over-the-counter (OTC) steroid medication has been linked to recalcitrant dermatophytosis. There is proven evidence of HPA axis suppression by the use of long-term oral steroids. This study aims to determine the prevalence and pattern of inappropriate OTC steroid use and its effects on the hypothalamus-pituitary-adrenal (HPA) axis in adults with recalcitrant dermatophytosis. Materials and Methods: This cross-sectional study of 2 months was conducted in a hospital setting and included patients of recalcitrant dermatophytosis with a history of OTC steroid use. Clinico-demographic details and basal serum cortisol levels were recorded in all and analyzed. Result: Of a total of 103 patients, 59.22% (n = 61/103) were males, and the mean duration of steroid abuse was 17.78 months. About 48.54% (n = 50/103), 3.88% (n = 4/103), and 47.57% (n = 49/103) patients reported the use of topical steroids, oral steroids, and both oral and topical steroids, respectively. Among all the topical steroid users (n = 99), clobetasol propionate 48.48% (n = 48/99), while among oral steroid users (n = 53), prednisolone 45.28% (n = 24/53) were the most commonly used agents, respectively. The morning serum cortisol levels (8-9 AM) were found to be decreased in 42.7% (n = 44/103), with a mean value of 44.28 ± 17.34 µg/dL. Conclusion: Improper OTC steroid use in recalcitrant dermatophytosis leads to HPA axis suppression. This highlights the need for intervention from apex health officials.
RESUMO
Imatinib (IM), a breakthrough in chronic myeloid leukemia (CML) treatment, is accompanied by discontinuation challenges owing to drug intolerance. Although BCR-ABL1 mutation is a key cause of CML resistance, understanding mechanisms independent of BCR-ABL1 is also important. This study investigated the sphingosine-1-phosphate (S1P) signaling-associated genes (SphK1 and S1PRs) and their role in BCR-ABL1-independent resistant CML, an area currently lacking investigation. Through comprehensive transcriptomic analysis of IM-sensitive and IM-resistant CML groups, we identified the differentially expressed genes and found a notable upregulation of SphK1, S1PR2, and S1PR5 in IM-resistant CML. Functional annotation revealed their roles in critical cellular processes such as proliferation and GPCR activity. Their network analysis uncovered significant clusters, emphasizing the interconnectedness of the S1P signaling genes. Further, we identified interactors such as BIRC3, TRAF6, and SRC genes, with potential implications for IM resistance. Additionally, receiver operator characteristic curve analysis suggested these genes' potential as biomarkers for predicting IM resistance. Network pharmacology analysis identified six herbal compounds-ampelopsin, ellagic acid, colchicine, epigallocatechin-3-gallate, cucurbitacin B, and evodin-as potential drug candidates targeting the S1P signaling genes. In summary, this study contributes to efforts to better understand the molecular mechanisms underlying BCR-ABL1-independent CML resistance. Moreover, the S1P signaling genes are promising therapeutic targets and plausible new innovation avenues to combat IM resistance in cancer clinical care in the future.