Transcriptomes of cervical cancer provide novel insights into dysregulated pathways, potential therapeutic targets, and repurposed drugs.

Cervical cancer ranks as the fourth most prevalent gynaecological malignancy and is a significant contributor to mortality among women globally. With the exception of HPV-mediated oncogenesis, the molecular etiology of the disease is poorly understood, and there is a critical dearth of knowledge concerning cancer that is not caused by HPV. Moreover, none of the options presently accessible for the treatment of cancers specifically target cervical cancer. In context with this, this research aims to identify the critical genes, regulators, and pathways that contribute to the pathogenesis of cervical cancer, in addition to prospective pharmacological targets and repurposed therapeutic agents that can be directed against the targets. A total of eleven different global gene expression (transcriptome) datasets were subjected to analysis utilizing a variety of in silico tools. The present study reveals a previously unknown correlation between cervical cancer and five genes: SHC1, CBL, GNAQ, GNA14, and PPP2CA. Significant dysregulation was observed in four crucial transcription factors (KLF4, E2F1, FOXM1, and AR) that modulate the expression of numerous genes in cervical cancer. Furthermore, it was observed that AKT1, MAPK1, and MAPK3 ranked the highest among the regulatory genes that hold promise as therapeutic targets in the context of cervical cancer. Additional research, both in vitro and in vivo, is required to validate and establish the therapeutic potential of these crucial genes in the context of cervical cancer.

Covariates of Knowledge, Attitude, Practice, and Burdens among the Caregivers of Hypertensive Patients.

Caregivers of hypertensive patients play a significant role in ensuring adequate patient care and lowering the risk of hypertension-relatedcomplications. Caregivers are ideal study subjects for identifying gaps in hypertension management. Our study aimed to assess the knowledge, attitude, and practice (KAP) of hypertensive patients' caregivers, to identify their extent of involvement in patients' care, and to assess their care-related attributes. A descriptive cross-sectional study was conducted from August 2020 to February 2021 in the eight largest tertiary care medical college hospitals and all eight divisions of Bangladesh, with 949 caregivers enrolled. Data were collected using a pretested interviewer-administered questionnaire through snowball sampling and analyzed using a one-way ANOVA, independent-sample T-test, and chi-square test. Among the 949 interviewed caregivers, 541 (57.0%) were female, and 479 (50.5%) were aged 18 to 25 years. The percentage scores regarding overall knowledge, attitude, and practice of the caregivers were 54.83 ± 17.95, 47.95 ± 24.05, and 61.26 ± 17.50, respectively. Caregivers' education, history of hypertension, residence, age, relationship with the patient, occupation, and caregiving duration were significantly associated with the KAP scores. In addition, factors such as relationship with the patient, age, educational status, occupation, residence, and caregiving duration/day had significant correlations with all types of burden. Findings of this study suggest the necessity for awareness programs for the caregivers of hypertensive patients to diminish the gap in their KAP and improve their mental and physical health.

TTN as a candidate gene for distal arthrogryposis type 10 pathogenesis.

BACKGROUND: Arthrogryposis is a medical term used to describe congenital contractures which often affect multiple limbs. Distal arthrogryposis (DA) is one of the major categories of arthrogryposis that primarily affects the distal parts of the body, i.e., the hands and the legs. Although ten different types and several subtypes of DAs have been described, the genes associated with each of these DAs are yet to be characterized. Distal arthrogryposis type 10 (DA10) is a rare genetic disease, which is distinguished from the other arthrogryposis types by plantar flexion contractures resulting in toe-walking during infancy as well as variability in contractures of the hip, hamstring, elbow, wrist and finger joints with no ocular or neurological abnormalities. Symptoms of DA10 indicate impairment specifically in the musculoskeletal system. DA10 is still poorly studied. AIM: The objective of this study was to identify the candidate gene for DA10 by scrutinizing the protein-protein interaction (PPI) networks using in silico tools. RESULTS: Among the genes that reside within the previously reported genomic coordinates (human chromosome assembly 38 or GRCh38 coordinates 2:179,700,000-188,500,000) of the causative agent of DA10, only TTN (the gene that codes for the protein Titin or TTN) follows the expression pattern similar to the other known DA associated genes and its expression is predominant in the skeletal and heart muscles. Titin also participates in biological pathways and processes relevant to arthrogryposes. TTN-related known skeletal muscle disorders follow the autosomal-dominant pattern of inheritance, which is a common characteristic of distal arthrogryposes as well. CONCLUSION: Based on the findings of the analyses and their correlation with previous reports, TTN appears to be the candidate gene for DA10. Our attempt to discover a potential candidate gene may eventually lead to an understanding of disease mechanism and possible treatment strategies, as well as demonstrate the suitability of PPI in the search for candidate genes.