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.

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.

Frequency Of Non-Diabetic Renal Disease In Type 2 Diabetes Mellitus Patients Undergoing Renal Biopsy.

BACKGROUND: Diabetes mellitus has become a major emerging health concern. Its burden, estimated to be 451 million in 2017, has been projected to rise to 693 million by 2045. This will bring a rise in the prevalence of its associated complications. There is a wide spectrum of non-diabetic renal disease (NDRD) known to be present in diabetic patients with variable prevalence. However, the majority of diabetes mellitus (DM) patients with renal disease are yet not biopsied and the diagnosis of diabetic nephropathy (DN) is presumed on clinical grounds. METHODS: It is a retrospective cross-sectional study. We selected a total of 126 cases of renal biopsies with a history of type 2 diabetes mellitus. Demographic data was collected from the medical records and pathology reports while all cases were evaluated by reviewing the archived slides. RESULTS: Patients were categorized into group 1 with isolated NDRD, group 2 showing NDRD mixed with DN and group 3 with isolated DN. Thirty-four (27%) cases had isolated NDRD (group 1), 14 (11%) had NDRD mixed with DN and 78 (62%) patients had isolated DN. NDRD, either alone or in combination with DN, was found to be present in 48 patients with an overall prevalence of 38%. CONCLUSION: Our study concludes that NDRD is frequent in type 2 diabetes mellitus patients. Renal biopsy remains the key diagnostic tool in such cases, providing crucial information for proper management of the underlying pathology.

Detection of Anti-Echinococcus granulosus Antibodies in Humans: An Update from Pakistan.

Human cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of Echinococcus granulosus sensu lato that causes economic losses by affecting livestock and also poses a public health threat worldwide. The present study is the first retrospective report on the seroprevalence of anti-E. granulosus antibodies in humans in Pakistan. The study used data from 93 blood analysis reports of patients suspected of having CE from different medical centers in Lahore, Pakistan. Out of 93 sera samples, 20 (21.5%) were seropositive, and higher seropositivity (17.2%) was recorded with the indirect hemagglutination test (IHA) than with enzyme-linked immunosorbent assay (ELISA). The findings indicated that age, gender, and year had no significant relationship with the seropositivity of CE. The current study provides directions towards the management of the disease in the near future in Pakistan.

Renal Transplant Pathology: Demographic Features and Histopathological Analysis of the Causes of Graft Dysfunction.

BACKGROUND: Renal transplant has emerged as a preferred treatment modality in cases of end-stage renal disease; however, a small percentage of cases suffer from graft dysfunction. AIM: To evaluate the renal transplant biopsies and analyze the various causes of graft dysfunction. MATERIALS AND METHODS: 163 renal transplant biopsies, reported between 2014 and 2019 and who fulfilled the inclusion criteria, were evaluated with respect to demographics, clinical, histological, and immunohistochemical features. RESULTS: Of 163 patients, 26 (16%) were females and 137 (84%) were males with a mean age of 34 ± 7 years. 53 (32.5%) cases were of rejection (ABMR and TCMR), 1 (0.6%) was borderline, 15 were of IFTA, and rest of 94 cases (57.7%) belonged to the others category. SCr (serum creatinine) in cases of rejection was 3.85 ± 0.55 mg/dl. Causes of early graft dysfunction included active ABMR (7.1 ± 4.7 months), acute TCMR (5.5 months), and acute tubular necrosis (after 6 ± 2.2 months of transplant) while the causes of late rejection were CNIT and IFTA (34 ± 4.7 and 35 ± 7.8 months, respectively). CONCLUSION: Renal graft dysfunction still remains a concerning area for both clinicians and patients. Biopsy remains the gold standard for diagnosing the exact cause of graft dysfunction and in planning further management.