From inadequate prior antidepressants that targeted monoamine neurotransmitter systems emerged the discovery of alternative drugs for depression. For instance, drugs targeted interleukin 6 receptor (IL6R) in inflammatory system. Genomic analysis-based drug repurposing using single nucleotide polymorphism (SNP) inclined a promising method for several diseases. However, none of the diseases was depression. Thus, we aimed to identify drug repurposing candidates for depression treatment by adopting a genomic-analysis-based approach. The 5885 SNPs obtained from the machine learning approach were annotated using HaploReg v4.1. Five sets of functional annotations were applied to determine the depression risk genes. The STRING database was used to expand the target genes and identify drug candidates from the DrugBank database. We validated the findings using the ClinicalTrial.gov and PubMed databases. Seven genes were observed to be strongly associated with depression (functional annotation score = 4). Interestingly, IL6R was auspicious as a target gene according to the validation outcome. We identified 20 drugs that were undergoing preclinical studies or clinical trials for depression. In addition, we identified sarilumab and satralizumab as drugs that exhibit strong potential for use in the treatment of depression. Our findings indicate that a genomic-analysis-based approach can facilitate the discovery of drugs that can be repurposed for treating depression.
Biopsychosocial factors, including family history, influence the development of breast cancer. Malignancies in women with a family history of breast cancer may be detectable based on DNA methylation and microRNA. Objectives: The present study extended an integrative analysis of DNA methylation and microRNA to identify genes associated with biopsychosocial factors. Methods: We identified 3060 healthy women from the Taiwan Biobank and included 32 blood plasma samples for analysis of biopsychosocial factors and epigenetic changes. GEO databases and bioinformatics approaches were used for the identification and validation of potential genes. Results: Our integrative analysis revealed GNPDA1 and SLC25A16 as potential genes. Age, a family history of cancer, and alcohol consumption were associated with GNPDA1 and SLC25A16 based on the current data set and the GEO data set. GNPDA1 and SLC25A16 exhibited significant expression in breast cancer tissues based on UALCAN analysis, where they were overexpressed and underexpressed, respectively. Through a MethSurv analysis, GNPDA1 hypomethylation and SLC25A16 hypermethylation were associated with poor prognoses in terms of overall survival in breast cancer. Moreover, through a MetaCore functional enrichment analysis, GNPDA1 and SLC25A16 were associated with the BRCA1, BRCA2, and pro-oncogenic actions of the androgen receptor in breast cancer. Further, GNPDA1 and SLC25A16 were enriched in known targets of approved cancer drugs as potential genes associated with breast cancer. Conclusions: These two genes might serve as biomarkers for the early detection of breast cancer, especially for women with a family history of breast cancer.
Background: The Diabetes Obstacles Questionnaire-Short Version is a tool for measuring the quality of life in patients with diabetes mellitus. However, the validity and reliability of this tool has never been tested in Indonesia. Purpose: This study was designed to adapt and validate a Bahasa Indonesia version of the Diabetes Obstacles Questionnaire-Short Version for Indonesians with type 2 diabetes mellitus. Methods: This was a cross-sectional study. Data were collected from July to November 2023, and accidental sampling was used to recruit and enroll 1,116 participants. Convergence testing used the Diabetes Quality of Life questionnaire. The validity test used construct and convergent validities with significant Pearson correlations, and construct validity included exploratory factor analysis and confirmatory factor analysis. Reliability testing used Cronbach’s alpha, composite reliability, and average variance extracted. Results: The results of the exploratory factor analysis showed nine factors with a factor loading per item of >.45, a Kaiser-Meyer-Olkin test score of .915, and significant Bartlett’s test of sphericity results. The Cronbach’s alpha value for all items was .930, and those of individual factors ranged from .730 to .848. The test-retest results with interclass correlation coefficients ranged from .910 to .973. The results of the confirmatory factor analysis indicate that this instrument has an acceptable model fit. Conclusions/Implications for Practice: The Bahasa Indonesia Diabetes Obstacles Questionnaire-Short Version produces valid and reliable results for measuring quality of life in people with type 2 diabetes mellitus in Indonesia. The sufficient but small number of items allows the questionnaire to be completed relatively quickly, making it useful in clinical settings. The subscales in this instrument may be used simultaneously or separately based on individual needs.