Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).

Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.

Transgradient Variant of Mal De Meleda Presenting As Palmoplantar Keratoderma: A Case Report.

Mal De Meleda is a rare genetic disorder characterized by palmoplantar keratoderma, often presenting challenges in diagnosis and management. This case report discusses an 18-year-old male presenting with thickened, yellowish skin on both palms and soles, accompanied by itching and cracking. A diagnosis of the transgradiens variant of Mal De Meleda was established through clinical and histopathological examination. Treatment with oral acitretin and topical moisturizers resulted in significant improvement. This report highlights the importance of recognizing rare variants of palmoplantar keratoderma and the need for a multidisciplinary approach to diagnosis and management.

Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins-VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID-25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.

A Cross-Sectional Study of Dermoscopy and Clinical and Histopathological Study of Acquired Palmoplantar Keratodermas: A Research Protocol.

Background Acquired palmoplantar keratodermas (PPKs) pose diagnostic and therapeutic challenges due to their varied clinical presentations and overlapping features. This study aims to elucidate diagnostic criteria; assess correlations between clinical, dermoscopic, and histopathological features; and evaluate treatment outcomes for acquired PPKs, particularly palmoplantar psoriasis. Methods A prospective, cross-sectional study will be conducted at the Department of Dermatology, Venereology, and Leprosy, Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra. Patients with acquired PPKs will undergo comprehensive clinical, dermoscopic, and histopathological evaluations. Treatment outcomes for palmoplantar psoriasis will be assessed following standard therapy. Statistical analysis will include descriptive statistics, diagnostic accuracy assessments, correlation analyses, and treatment outcome evaluations. Results The study is anticipated to establish reliable diagnostic criteria for acquired PPKs, identify correlations between features, and demonstrate the effectiveness of standard therapies for palmoplantar psoriasis. The findings are expected to inform evidence-based guidelines and protocols for diagnosing and managing acquired PPKs. Conclusion This study aims to advance the understanding and management of acquired PPKs by providing insights into diagnostic accuracy, correlations between features, and treatment outcomes. The study seeks to enhance patient care and outcomes for individuals affected by acquired PPKs by improving diagnostic precision and guiding therapeutic interventions.

Shedding Light on Acne Scars: A Comprehensive Review of CO2 vs. Erbium-Doped Yttrium Aluminium Garnet (Er:YAG) Laser Therapy.

Acne scars pose a significant cosmetic concern and can have a profound impact on individuals' self-esteem and quality of life. Laser therapy has emerged as a promising treatment modality for improving the appearance of acne scars by promoting collagen remodeling and tissue regeneration. This comprehensive review compares two commonly used laser modalities, CO2 and erbium-doped yttrium aluminum garnet (Er:YAG), focusing on their mechanisms of action, efficacy, safety profiles, and patient outcomes. While CO2 lasers offer deeper tissue penetration and the potential for more significant improvement in severe acne scars, Er:YAG lasers provide a gentler approach with a lower risk of post-inflammatory hyperpigmentation. Recommendations for clinical practice include tailoring treatment approaches to individual patient characteristics, educating patients about treatment expectations and post-treatment care, considering combination therapies for enhanced outcomes, and implementing regular follow-up care. Areas for further research include long-term outcome studies, investigation of laser therapy in ethnically diverse populations, exploration of combination therapies, and evaluation of emerging laser technologies. This review aims to provide clinicians and patients with valuable insights to inform treatment decisions and optimize outcomes in managing acne scars.

A Comprehensive Review on the Efficacy of Anti-CD20 Therapies in Pemphigus Treatment.

Pemphigus, an autoimmune blistering disorder, poses significant therapeutic challenges due to dysregulated B cells and the involvement of CD20. This review assesses the efficacy of anti-CD20 therapies, including rituximab, ofatumumab, ocrelizumab, and obinutuzumab, in pemphigus treatment. Mechanisms of action, clinical studies, and safety profiles were analyzed, revealing diverse impacts on disease severity. B cell depletion emerged as a pivotal factor, disrupting the autoimmune process and reducing pathogenic antibodies. Varied efficacy and safety profiles among agents underscore the need for personalized treatment strategies guided by biomarkers. Challenges such as resistance and long-term safety concerns necessitate continued research and vigilance. In clinical practice, insights from this review inform nuanced, tailored approaches for improved pemphigus management. The dynamic landscape of emerging therapies and personalized medicine emphasizes the need for ongoing research and strategic clinical decision-making. This review is a foundation for future investigations, providing insights for clinicians and researchers in optimizing pemphigus treatment.

Painful Limb Ulcers: A Case Report on Ulcerative Discoid Lupus Erythematosus.

Lupus erythematosus is an autoimmune disorder with varied clinical features. Discoid Lupus Erythematosus (DLE) presents as erythematous, raised plaques. The patients might present with photosensitivity, arthralgia, and nail changes. However, dermoscopy, clinical features, and laboratory markers like high titers of Antinuclear antibodies (ANA) help in clenching the diagnosis. We report a patient in her mid-60s presented with non-healing ulcers oozing pus discharge associated with pain and joint stiffness. Thus, a series of investigations, treatment modifications, and the healing progression of the lesions highlight the importance of retrospective diagnosis.

The role of kisspeptin in the pathogenesis of a polycystic ovary syndrome.

Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.

Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.

Promoter-motif extraction from co-regulated genes and their relevance to co-expression using E. coli as a model.

Gene expression varies due to the intrinsic stochasticity of transcription or as a reaction to external perturbations that generate cellular mutations. Co-regulation, co-expression and functional similarity of substances have been employed for indoctrinating the process of the transcriptional paradigm. The difficult process of analysing complicated proteomes and biological switches has been made easier by technical improvements, and microarray technology has flourished as a viable platform. Therefore, this research enables Microarray to cluster genes that are co-expressed and co-regulated into specific segments. Copious search algorithms have been employed to ascertain diacritic motifs or a combination of motifs that are performing regular expression, and their relevant information corresponding to the gene patterns is also documented. The associated genes co-expression and relevant cis-elements are further explored by engaging Escherichia coli as a model organism. Various clustering algorithms have also been used to generate classes of genes with similar expression profiles. A promoter database 'EcoPromDB' has been developed by referring RegulonDB database; this promoter database is freely available at www.ecopromdb.eminentbio.com and is divided into two sub-groups, depending upon the results of co-expression and co-regulation analyses.

Adalimumab in the Treatment of Recalcitrant Livedoid Vasculopathy.

Livedoid vasculopathy is a rare condition affecting the cutaneous vasculature. Patients typically develop bilateral lower limb ulcers that tend to recur and do not heal. Edema, discomfort, and itching are linked to ulcers. The patient's quality of life is negatively impacted by this. Atrophie blanche, a stellate, porcelain-white scar, is typically left behind once these ulcers heal. Livedoid vasculitis, livedo reticularis with ulcerations, atrophie blanche, segmental hyalinizing vasculitis, and painful purpuric ulcers with a reticular pattern on the lower limbs are some of the terminologies used to describe livedoid vasculopathy. This condition has been treated using various techniques, including intravenous immunoglobulins, steroids, anticoagulants, antibiotics, immunosuppressive drugs, and antiplatelets. Here, we report the case of a 24-year-old male who presented with a red-colored, painful, and itchy lesion over his right calf for one year. He had recurring lesions over his right foot for the past 18 years. He had received multiple treatment courses over 18 years but had no relief. He was treated with eight doses of adalimumab injection (40 mg/0.8 mL) administered subcutaneously at an interval of 15 days. He had near-complete healing of the ulcer and complete remission of symptoms.

A Case Report on Senear-Usher Syndrome.

Pemphigus erythematosus is an uncommon autoimmune bullous skin disorder with clinical, histological, and serological characteristics that overlap with lupus erythematosus and pemphigus foliaceus. The autoantigens are desmoglein 3, desmoglein 1, and desmosomal adhesion proteins in keratinocytes. When these bonds are disrupted, it causes acantholysis of keratinocytes, leading to the fluid collection between layers. Hence, the patient will present clinically with small flaccid bullae with crusting and scaling, mainly on the seborrheic areas. We report the case of a 21-year-old female presenting to us with multiple hyperkeratotic plaques, mainly on the seborrheic areas, including the face, chest, and elbows. The patient was evaluated further, and based on clinical and laboratory investigations, the diagnosis of pemphigus erythematosus associated with anti-double-stranded deoxyribonucleic acid (anti-dSDNA) and anti-nuclear antibody (ANA) positivity was made. The patient was then managed using immunosuppressant therapy, and the entire course has been detailed in this case report.