Epigenetics is the study of nucleotide modifications that are heritable and act as regulatory mechanisms without changing the nucleotide sequence of the genome. Exogenous cues such as environment, lifestyle, nutrition, stress, and psychological factors affect epigenetic mechanisms. This mechanism is in concordance with the genetic information that plays an important role during prenatal and postnatal life of an individual. Recent epigenetic studies have revealed the potential of epigenetics in elucidating the mechanisms of different diseases. In this review, we discuss basic epigenetic mechanisms and their roles in health and disease. In addition, reported aberrations in epigenetic regulation for some common human diseases are described. Finally, we address some epigenetic approaches that have shown potential for targeted treatment of diseases.

In recent years, nanotechnology has achieved a remarkable status in shaping the future of biological applications, especially in combating fungal diseases. Owing to excellence in nanotechnology, iron nanoparticles (Fe NPs) have gained enormous attention in recent years. In this review, we have provided a comprehensive overview of Fe NPs covering key synthesis approaches and underlying working principles, the factors that influence their properties, essential characterization techniques, and the optimization of their antifungal potential. In addition, the diverse kinds of Fe NP delivery platforms that command highly effective release, with fewer toxic effects on patients, are of great significance in the medical field. The issues of biocompatibility, toxicity profiles, and applications of optimized Fe NPs in the field of biomedicine have also been described because these are the most significant factors determining their inclusion in clinical use. Besides this, the difficulties and regulations that exist in the transition from laboratory to experimental clinical studies (toxicity, specific standards, and safety concerns) of Fe NPs-based antifungal agents have been also summarized.

Introduction: Hypospadias [MIM: 300633] is one of the most frequent congenital malformations of male external genitalia. The spectrum of genetic variants causing hypospadias is varied, with studies commonly implicating genes critical in the fetal steroidogenic pathway. This is the first genetic study on hypospadias from the Yemen ethnicity and the second to report HSD3B2 mutations in more than one affected individual from the same family.Material and methods: Surgical hypospadias repair was performed on two hypospadias-affected siblings from a consanguineous family. Whole-exome sequencing (WES) was performed to identify the potential pathogenic variant for hypospadias, which was later confirmed by Sanger sequencing. The identified variant was further analyzed for its pathogenicity by using in silico tools such as SIFT, PolyPhen-2, MutationAssessor, MutationTaster, FATHMM, and ConSurf.Results: We identified a novel missense mutation (Chr1:119964631T>A, c.507T>A, p. N169K) in 3β-hydroxysteroid 2-dehydrogenase (HSD3B2) gene by WES. Sanger sequencing confirmed that the variant segregated the disease in the family between the affected and non-affected individuals. Both patients are homozygous, while parents and two unaffected siblings are heterozygous carriers, indicating an autosomal recessive pattern of inheritance. The in silico analysis by all six in silico tools (SIFT, PolyPhen-2, MutationAssessor, MutationTaster, FATHMM, and ConSurf) predicted the variant to be pathogenic/deleterious.Discussion: An abnormal fetal steroidogenic pathway due to genetic influences may affect the development of the male genital tract, including the urethral tract closure and morphogenesis of male genitalia. Furthermore, the pathogenicity of the observed variant in this study, confirmed by multiple in silico tools, characterizes the influence HSD3B2 gene variants may have in the etiology of hypospadias.Conclusion: Understanding of pathogenic manifestation and inheritance of confounding genetic variants in hypospadias is a matter of great concern, especially in familial cases.

Background: Intellectual disability (ID) is characterized by impairments in cognitive functioning and adaptive behavior. Globally, it affects 1-3% of the general population, with an increased prevalence in consanguineous families. It is a clinically heterogeneous disorder that can manifest as a variable phenotype. Intellectual developmental disorder and retinitis pigmentosa (IDDRP) is a rare syndrome in which patients present with both ID and retinitis pigmentosa. Aims and Objectives: This study examined a consanguineous family to identify disease-associated pathogenic mutations and elucidate their potential functional impact in patients with IDDRP. Methodology: Clinical assessment of the patients revealed characteristics consistent with both intellectual disability (ID) and retinitis pigmentosa. Individuals affected by IDDRP were subjected to whole exome sequencing (WES), and the identified candidate pathogenic variants were validated by Sanger sequencing. Computational analyses were conducted to evaluate the impact of these mutations on the protein structure and function. Results: WES identified a protein-truncating variant, c.2605A>T (p.Lys869Ter), in the Sphase cyclin A-associated protein in the endoplasmic reticulum (SCAPER) gene. SCAPER has previously been reported to cause IDDRP. In silico analyses revealed structural and interactional alterations in the SCAPER protein. This variant is novel in the Pakistani population and has not been previously reported. This variant exhibits an autosomal recessive mode of inheritance and segregates among the investigated affected and unaffected family members. Conclusion: The present study expands the spectrum of disease-causing variants in SCAPER and will contribute to a better understanding of the genetic etiology of IDDRP.

Objectives: To characterize the potential role of Y-chromosome microdeletion (YCM) as a genetic cause for infertility in the Arab population from the Al Madinah Al Munawarah. Methods: We screened 97 infertile men from Al Madinah Al Munawarah, from February 2022 to March 2024. Genomic blood DNA was analyzed for 8 sequence tagged site (STS) markers of Y chromosome by multiplex polymerase chain reaction. Results: We found microdeletions in 3 infertile men, indicating a prevalence of 3.1%. The STS markers sY254 and sY255 corresponding to AZFc regions were deleted in these men. No deletion was observed in any other STS markers investigated in this study. Conclusion: Our findings for prevalence in Arab population of Al Madinah Al Munawarah is comparable to other studies from Saudi Arabia. However, large variance in the prevalence of YCM in the Arab population of other Middle Eastern countries is reportedly observed. The YCM has significant prognostic value, since it indicates the spermatogenic profile, the success probability of assisted reproduction technique (ART) procedures as testicular sperm extraction and apprise of potential risk of vertical transmission of microdeletion from father to son in patients opting for ART. With these considerations, we re-emphasize the need for genetic screening of YCM in azoo- and oligozoospermic infertile men.