Hemorrhoids are a prevalent medical condition that necessitates effective treatment options. The current options for treatment consist of oral medications, topical applications, or surgery, yet a scarcity of highly effective drugs still exists. Genetic markers provide promising avenues for investigating the treatment of hemorrhoids, as they may reveal intricate biological mechanisms and targeted drug therapies, ultimately enhancing more precise treatment tailored to the patient. This study aims to identify new drug candidates for treating hemorrhoids through a meticulous bioinformatics approach and integrated with genomic network analysis. After extracting 21 druggable target genes using DrugBank from 293 genes connected to hemorrhoids, 87 possible drugs were selected. Three of these drugs (ketamine, methylene blue, and fulvestrant) hold potential in addressing issues associated with hemorrhoids and have been supported by clinical or preclinical studies. Eighty-four compounds present new therapeutic possibilities for managing hemorrhoids. We highlight that our findings indicate that NOX1 and NOS3 genes are promising biomarkers, with NOS3 gaining significance owing to its robust systemic functional annotations. Sapropterin, an existing drug, is closely associated with NOS3, providing a clear target for biomarker-driven interventions. This study illustrates the potential of combining genomic network analysis with bioinformatics to repurpose drugs for treating hemorrhoids. Subsequent research will explore the mechanisms for utilizing NOS3 targeting in the treatment of hemorrhoids.

Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC.

Background/Aim: Leukaemia is a malignant disease of blood cells found in the bone marrow, which can be divided into acute lymphocytic leukaemia and myelocytic leukaemia. Current management of acute leukaemia still uses chemo therapy as the main therapy but has many side effects, therefore a new approach is needed to identify genetic factors involved in leukaemia. The aim of this study was to investigate gene variations that have potential pathogenic properties in leukaemia. Methods: This study used genome-wide association study (GWAS) data obtained from the National Human Genome Research Institute (NHGRI) to search for genomic variants associated with leukaemia. The data was then screened using SNPnexus to detect potentially protein-damaging variants. Furthermore, the gene expression of these variants was analysed using the GTEx portal. Results: Of the 2115 genomic variants found, four were deleterious, namely rs12140153, rs140386498, rs757110 and rs2066827, representing four different genes, namely PATJ, MINDY1, ABCC8 and CDKN1B. Alterations in the expression of PATJ, MINDY1, CDKN1B and ABCC8 genes affect the brain and leukaemia development. PATJ maintains brain cell integrity, MINDY1 regulates gene expression, CDKN1B controls the cell cycle and ABCC8 regulates glucose levels. Their deregulation is associated with neurological dysfunction and leukaemia. Variation in allele frequencies showed differences between continents, with rs757110 and rs2066827 having higher expression than rs12140153 and rs140386498. Variant gene expression also varied between tissues, with rs757110 and rs2066827 showing higher expression than rs12140153 and rs140386498. Conclusion: This study successfully identified four genomic variants by harnessing a genomic and bioinformatic database, which are associated with leukemia and demonstrated variations in gene distribution and expression across different populations and tissues.

The most common type of liver cancer is hepatocellular carcinoma (HCC), accounting for 75–85% of cases. Despite its associated side effects, sorafenib remains the standard treatment for HCC. Given the critical need to improve therapeutic efficacy while minimizing adverse effects, alternative drugs must be thoroughly investigated. Numerous studies indicate that combining sorafenib with metformin results in a more favorable treatment profile. The aim of this study was to employ bioinformatics methodologies to elucidate the molecular pathways and genetic underpinnings of metformin's efficacy in HCC treatment. Genes associated with metformin and its action against HCC (Huh-7 and HepG2 cells) were acquired from the NCBI-GEO data collection by utilizing pre-determined keywords. Subsequently, pathways implicated in metformin-mediated HCC treatment were analyzed through the Kyoto Encyclopedia of Genes and Genomes (KEGG). Our analysis revealed the involvement of multiple pathways, with metabolic pathways implicated in 80% of the total cases. Neurodegenerative pathways were involved in only around 60% of the total cases. These findings align with the multifaceted mechanisms of metformin’s action, encompassing adenosine monophosphate-activated protein kinase activation, apoptosis induction, insulin regulation, anti-inflammatory responses, and modulation of cell proliferation. This comprehensive investigation sheds light on the intricate molecular landscape underpinning metformin's therapeutic efficacy in HCC, thereby informing potential avenues for optimizing treatment strategies.

Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatological emergencies characterised by widespread epidermal necrolysis and sloughing. SJS is defined as the shedding of skin on less than 10 % of the body surface area, whereas TEN involves the shedding of skin on more than 30 %. The pathogenesis of SJS is identified by the occurrence of apoptosis of keratinocytes, which is spread throughout the body. The binding of the molecule to the human leukocyte antigen (HLA) peptide is one of the basic triggering mechanisms for SJS due to an autoimmune reaction. This study aims to predict genetic predictive markers for the prevention and pharmacological treatments of SJS/TEN. The PharmGKB website was used to gather information regarding the relationship among drugs, genes and the SJS condition. Results revealed notable gene variants (eg HLA-A, HLA-B, HLA-B, HLA-C, CYP2B6) predisposing individuals to a toxic response, instigating the SJS reaction. Implicated drugs included allopurinol, antiepileptics such as carbamazepine, lamotrigine, oxcarbazepine and phenytoin, as well as methazolamide and nevirapine, identified as potential risk factors. As a result, this study can provide information and facilitate precision medicine, which focuses on individual genetic variations as a means of prevention and treatment, enabling early prognosis and optimising patient care in preventing SJS/TEN.