The role of botulinum neurotoxin BoNT-A in the management of oily skin and acne vulgaris: A comprehensive review.

Oily skin and acne vulgaris are prevalent dermatological conditions with a significant impact on both physical and emotional well-being. Despite numerous available treatments, there is a pressing need for effective, long-term solutions. Botulinum Neurotoxin (BoNT-A) has emerged as a potential therapeutic option. However, existing reviews in this area are often limited. This review aims to comprehensively assess the use of BoNT-A in managing oily skin and acne vulgaris while addressing gaps in previous publications. It integrates the latest research, clinical trials, and case studies to provide an up-to-date analysis of BoNT-A mechanisms of action, efficacy, safety, and long-term outcomes. The review systematically analyzes existing evidence, critically evaluates study strengths and limitations, and explores potential synergies with other treatments. It also examines the safety profile of BoNT-A and its potential long-term effects. This review uncovers promising insights into how BoNT-A affects oily skin and acne vulgaris, including its ability to regulate sebum production, reduce inflammation, and potentially shrink pore size. It provides a comprehensive overview of relevant studies and clinical trials, detailing their methodologies, protocols, measures, and results. Collectively, these studies show significant reductions in sebum production, increased patient satisfaction, and smaller pores following BoNT-A treatment. In conclusion, this review addresses knowledge gaps and provides a comprehensive analysis of BoNT-A as a therapeutic option for oily skin and acne vulgaris. By consolidating evidence and highlighting areas for further investigation, it guides clinicians and researchers toward more effective, personalized treatments for individuals with these dermatological challenges.

In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor.

Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. Materials and methods: Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes. Results and discussion: We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.

Botulinum Toxin A for Hair Loss Treatment: A Systematic Review of Efficacy, Safety, and Future Directions.

Background: Hair loss is a common condition with significant impact globally, yet its treatment efficacy and safety remain debated. Botulinum toxin A (BoNT-A) has emerged as a potential therapeutic option, but a comprehensive review on this topic is lacking. Objective: This review critically evaluates the current evidence on BoNT-A for hair loss treatment, highlighting the gaps in previous reviews and providing a comprehensive analysis of its efficacy, safety, and future prospects. Methods: A systematic search of electronic databases identified relevant studies published up to September 2022. Results: Prior reviews primarily focused on androgenetic alopecia and lacked the evaluation of other alopecia types and underlying mechanisms. Our review addresses this gap, incorporating a broader spectrum of hair loss conditions. Mechanisms of BoNT-A in hair growth modulation, potential side effects, and future research directions are discussed. Conclusion: This review adds to the existing body of knowledge by providing a comprehensive evaluation of BoNT-A in hair loss treatment. The findings will serve as a foundation for further research and guide clinicians in making informed decisions, ultimately improving the outcomes and quality of life for individuals suffering from hair loss.

Prospective study of the effects of isotretinoin and vitamin D levels on severe acne vulgaris.

Background/aim: Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous hypersecretion and Cutibacterium acnes colonization. Vitamin D plays a crucial role in the pathogenesis of various inflammatory skin disorders, including AV, due to its immunomodulatory effects and involvement in keratinocyte growth and maturity. However, adequate sun exposure is required for optimal vitamin D synthesis. Isotretinoin (IOS), a vitamin A derivative, is a commonly used medication for severe acne, acting by binding to retinoid receptors. It can also form heterodimers with vitamin D receptors, potentially increasing vitamin D catabolism. Previous studies examining the impact of oral IOS on serum vitamin D levels have yielded inconsistent results. Therefore, this study aimed to assess changes in 25-hydroxy (OH) vitamin D serum levels in individuals with severe AV before and after IOS treatment. Materials and methods: One hundred patients with severe AV were enrolled, each receiving 0.75 mg/kg IOS treatment daily for 4 months. Serum 25 OH vitamin D levels were measured before, during, and after treatment. Results: This study found a significant increase in serum 25 OH vitamin D levels among patients with severe AV following IOS treatment (p < 0.001). Conclusion: This study suggests that AV may negatively impact vitamin D synthesis, but IOS treatment appears to raise vitamin D serum levels in individuals with severe AV. Further research is needed to confirm the potential relationship between AV and vitamin D levels.

Ameliorative inhibition of sirtuin 6 by imidazole derivative triggers oxidative stress-mediated apoptosis associated with Nrf2/Keap1 signaling in non-small cell lung cancer cell lines.

Background: Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. A high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics, and rapid proliferation, framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD + dependent deacetylase activity that have a remarkable impact on antioxidant and redox signaling (ARS) linked with Nrf2 deacetylation thereby increasing its transcription by epigenetic modifications which has been identified as a crucial event in cancer progression under the influence of oxidative stress in various transformed cells. SIRT6 plays an important role in the cytoprotective effect of multiple diseases, including cancer. This study aimed to inhibit SIRT6 using an imidazole derivative, Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate, to assess its impact on Nrf2/Keap1 signaling in A549 and NCI-H460 cell lines. Method: Half maximal inhibitory concentration (IC50) of Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate was fixed by cell viability assay. The changes in the gene expression of important regulators involved in this study were examined using quantitative real-time PCR (qRT-PCR) and protein expression changes were confirmed by Western blotting. The changes in the antioxidant molecules are determined by biochemical assays. Further, morphological studies were performed to observe the generation of reactive oxygen species, mitochondrial damage, and apoptosis. Results: We inhibited SIRT6 using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate and demonstrated that SIRT6 inhibition impacts the modulation of antioxidant and redox signaling. The level of antioxidant enzymes and percentage of reactive oxygen species scavenging activity were depleted. The morphological studies showed ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptotic factors confirmed apoptotic cell death. Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. Conclusion: The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.