Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases.

Post-transcriptional RNA modification is an emerging epigenetic control mechanism in cells that is important in many different cellular and organismal processes. N6-methyladenosine (m6A) is one of the most prevalent, prolific, and ubiquitous internal transcriptional alterations in eukaryotic mRNAs, making it an important topic in the field of Epigenetics. m6A methylation acts as a dynamical regulatory process that regulates the activity of genes and participates in multiple physiological processes, by supporting multiple aspects of essential mRNA metabolic processes, including pre-mRNA splicing, nuclear export, translation, miRNA synthesis, and stability. Extensive research has linked aberrations in m6A modification and m6A-associated proteins to a wide range of human diseases. However, the impact of m6A on mRNA metabolism and its pathological connection between m6A and other non-communicable diseases, including cardiovascular disease, neurodegenerative disorders, liver diseases, and cancer remains in fragmentation. Here, we review the existing understanding of the overall role of mechanisms by which m6A exerts its activities and address new discoveries that highlight m6A's diverse involvement in gene expression regulation. We discuss m6A deposition on mRNA and its consequences on degradation, translation, and transcription, as well as m6A methylation of non-coding chromosomal-associated RNA species. This study could give new information about the molecular process, early detection, tailored treatment, and predictive evaluation of human non-communicable diseases like cancer. We also explore more about new data that suggests targeting m6A regulators in diseases may have therapeutic advantages.

An exploratory study of knowledge, attitudes, and practices toward HPV associated anal cancer among Pakistani population.

Background: Anal cancer, mainly attributed to human papillomavirus (HPV) infection, is rising in prevalence among the general population in Pakistan. This study aimed to examine the knowledge, attitudes, and practices (KAP) towards anal cancer screening and HPV of the general population in Pakistan. Method: We surveyed anal cancer KAP using social media and snowball sampling from December 2022 to May 2023. The questionnaire had 16 knowledge, 12 attitudes, 6 practice questions, and socio-demographic variables. We applied validity criteria for inclusion and exclusion and used cutoffs ≥50% for each KAP category. We analyzed data in R with Guttman's λ2 for reliability, did univariate and bivariate analysis, and reported frequencies, percentages, p-values, coefficients, odds ratios, and 95% confidence intervals. Results: We surveyed 1620 people and discovered low awareness of HPV and anal cancer causes prevention, and screening (11%-24%), high stigma and embarrassment for screening (54%-70%), strong moral beliefs (89%), condom nonuse (91%), and low engagement in health services and programs (9.1%-14%). Knowledge (75.23%, OR = 1.0984, p = 0.05) was shaped by socio-demographic factors, attitude, and practice, with higher education enhancing knowledge (OR = 1.0984, p = 0.05). Attitude (78.45%, OR = 6.6052, p< 0.001) was influenced by socio-demographic factors, practice, and knowledge as well. Younger females, single, unemployed, students, living with more family members, earning more income, and residing in Islamabad had a more positive attitude (ORs from 1.0115 to 6.6052, p< 0.05), while religion did not affect attitude (p = 0.51). Practice (9.16%, OR = 0.1820, p< 0.001) was determined by socio-demographic factors, knowledge, and attitude. Older males, employed teachers, living with more family members, earning less income, and residing in Islamabad had better practice (ORs from 0.1323 to 3.8431, p< 0.05), but marital status and religion did not influence practice (p > 0.05). Conclusion: Pakistani young adults need more education, awareness, health services, and programs on HPV and anal cancer, as they have low awareness, high stigma, and socio-cultural challenges. In addition, it is recommended for more research and policy initiatives are needed to address socio-cultural factors and increase anal Pap to overcome anal cancer.

An updated systemic review and meta-analysis on human papillomavirus in breast carcinogenesis.

Background: Breast Cancer (BC) stands out as the widely prevalent malignancy among all the types of cancer affecting women worldwide. There is significant evidence that the pathogenicity of BC may be altered by Human Papillomavirus (HPV) infection; however, conclusive data are not yet available. Methods: By searching five databases, including EMBASE, IBECS, PubMed, Scopus, Science Direct, Google Scholar, and Web of Science, a thorough systematic analysis was conducted on the prevalence of HPV in BC patients from 1990 to June 30, 2022. After applying extensive eligibility criteria, we selected 74 publications for further analysis based on the prevalence of HPV infections in breast tissues. All of the data were analyzed using a random-effects meta-analysis, Cochran Q test and I2 statistic were used to calculate the heterogeneity of the prevalence among these studies using subgroup analysis. Variations in the HPV prevalence estimates in different subgroups were evaluated by subgroup meta-analysis. Results: In total, 3156 studies were initially screened, resulting in 93 full-text studies reviewed, with 74 meeting inclusion criteria. Among a total of 7156 BC biopsies, the pool prevalence of HPV was 25.6% (95% CI= 0.24-0.33, τ2 = 0.0369 with significant heterogeneity between estimates (I 2 = 97% and p< 0.01). Consequently, 45 studies with available controls were further studied, and the prevalence of HPV in case-control studies was 26.2% with overall odds 5.55 (95% CI= 3.67-8.41, I 2 = 38%, τ2 = 1.4878, p< 0.01). Further subgroup analysis of HPV revealed HPV-16 had a maximum prevalence of 9.6% (95% CI= 3.06-11.86, I 2 = 0%, τ2 = 0.6111, p< 0.01). Among different geographical regions, Europe reported the maximum prevalence of HPV, i.e., 39.2% (95% CI=1.29-7.91, I 2 = 18%, τ2 = 1.2911, p< 0.01). Overall distribution showed HPV-18 was a frequent HPV subtype reported in Australia. Conclusion: Current study provides a global estimate of HPV prevalence in BC patients and demonstrates a significant association between this virus and BC etiology. Nevertheless, we recommend further investigation into the underlying mechanism is essential to validate this hypothesis.

Prevalence of Toxoplasmosis in Sheep and Goats in Pakistan: A Systematic Review and Meta-Analysis.

Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, results in congenital disorders and miscarriages among livestock and humans worldwide. This systematic review and meta-analysis were conducted to determine the prevalence of T. gondii infection in sheep and goats in Pakistan from 2000 to 2020. We searched the PubMed, Scopus, EMBASE, and Google Scholar databases and selected 17 publications that fulfilled our inclusion criteria. Eight studies were conducted in Southern Punjab, six in Khyber Pakhtunkhwa, two in Northern Punjab, and one in Central Punjab. The diagnostic tests used in the included articles to confirm toxoplasmosis were the latex agglutination test in 56% of the studies, the enzyme-linked immunosorbent assay in 38%, and the indirect hemagglutination assay in 6%. The infection rates were substantially higher among sheep > 1 year of age (37%) than among sheep ≤ 1 year old (19%). Statistically significant differences in infection rates were found between male and female sheep and goats. The overall infection rate by age was also significant among sheep and goats. Sex and age variability between sheep investigations were significant, and sex heterogeneity and age homogeneity were significant among goats. Hence, robust infection control protocols should be implemented to prevent infection in animals and humans.

Pseudogenes and Liquid Phase Separation in Epigenetic Expression.

Pseudogenes have been considered as non-functional genes. However, peptides and long non-coding RNAs produced by pseudogenes are expressed in different tumors. Moreover, the dysregulation of pseudogenes is associated with cancer, and their expressions are higher in tumors compared to normal tissues. Recent studies show that pseudogenes can influence the liquid phase condensates formation. Liquid phase separation involves regulating different epigenetic stages, including transcription, chromatin organization, 3D DNA structure, splicing, and post-transcription modifications like m6A. Several membrane-less organelles, formed through the liquid phase separate, are also involved in the epigenetic regulation, and their defects are associated with cancer development. However, the association between pseudogenes and liquid phase separation remains unrevealed. The current study sought to investigate the relationship between pseudogenes and liquid phase separation in cancer development, as well as their therapeutic implications.

Epidemiology of Toxoplasmosis among the Pakistani Population: A Systematic Review and Meta-Analysis.

Toxoplasma gondii is an intracellular obligate parasite that causes toxoplasmosis, a zoonotic infection that affects warm-blooded animals and humans worldwide. To comprehensively characterize the disease condition in Pakistan for future reference, we ascertained the prevalence of Toxoplasma infection and predisposing factors in the Pakistani population over a 20-year period. We systematically reviewed research articles published in English (2000−2020) from PubMed and Google Scholar. The search results 26 publications involving 10,924 people and 2611 seropositive cases. The toxoplasmosis seropositivity rate was higher in women (25.44%) as compared to men (21.48%) and were statistically significant (p < 0.001). Furthermore, seropositivity was high among people with direct contact with cats, who consumed uncooked meat and raw vegetables, had poor education, and lived in rural areas. The 35−65-year age group had the highest prevalence rate of T. gondii infection. Toxoplasma infection was significantly more prevalent in Khyber Pakhtunkhwa province (25.87%) than in Punjab (20.42%) (p < 0.001). This is the first comprehensive analysis of T. gondii infection epidemiology in Pakistan. It reveals a high frequency of infection among women. We strongly encourage further research to aid patient care and the development of more efficient diagnostic tests and preventative techniques.