Epigenetic mechanisms are central to the regulation of all biological processes. This manuscript reviews the current understanding of diverse epigenetic modifications and their role in the establishment and maintenance of normal skin functions. In healthy skin, these mechanisms allow for the precise control of gene expression, facilitating the dynamic balance between cell proliferation and differentiation necessary for effective barrier function.
View Article and Find Full Text PDFDrug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses.
View Article and Find Full Text PDFUnderstanding the pathophysiology of inflammatory skin diseases, including psoriasis, atopic dermatitis (AD), and prurigo nodularis (PN), has led to the development of innovative treatments. In the February issue of the Journal, we provide insight into the global epidemiology and psychosocial impact of psoriasis. We also discuss the role of tissue-resident memory T cells in disease recurrence and evaluate the effectiveness of tildrakizumab in treating difficult areas in psoriasis.
View Article and Find Full Text PDFBackground: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.
Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.
J Eur Acad Dermatol Venereol
December 2024
Introduction: This second part of the S2k guidelines is an update of the 2015 S1 European guidelines.
Objective: These guidelines aim to provide an accepted decision aid for the selection, implementation and assessment of appropriate and sufficient therapy for patients with hidradenitis suppurativa/acne inversa (HS).
Methods: The chapters have been selected after a Delphi procedure among the experts/authors.
The combinations of BRAF inhibitor-based targeted therapies with immune checkpoint inhibitors currently represent less common therapeutic approaches in advanced melanoma. The aim of this study was to assess the safety and efficacy of currently available melanoma treatments by conducting a systematic review and network meta-analysis. Four databases were systematically searched for randomized clinical studies that included patients with advanced/metastatic melanoma receiving chemotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitor therapy, or combinations thereof.
View Article and Find Full Text PDFNeglected tropical diseases (NTDs) affect over a billion individuals worldwide, predominantly in low-income countries in tropical and subtropical areas. These diseases frequently result in chronic and debilitating health conditions that significantly diminish the quality of life, often leading to social isolation. The frequent dermatological manifestations underscore the role of dermatologists in managing NTDs.
View Article and Find Full Text PDFIn the psoriatic non-lesional (PS-NL) skin, the tissue environment potentially influences the development and recurrence of lesions. Therefore, we aimed to investigate mechanisms involved in regulating tissue organization in PS-NL skin. Cytokine, chemokine, protease, and protease inhibitor levels were compared between PS-NL skin of patients with mild and severe symptoms and healthy skin.
View Article and Find Full Text PDFCells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism.
View Article and Find Full Text PDFDermatology has seen significant advancements in understanding and treating complex immune-mediated chronic inflammatory skin conditions such as psoriasis and atopic dermatitis. This editorial highlights five pivotal studies that delve into the real-world effectiveness of biological therapies and the challenges of treating pediatric patients with overlapping dermatological conditions. These studies collectively underscore the need for continued research and treatment approaches in dermatology.
View Article and Find Full Text PDFIntroduction: While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.
Methods: Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.
Vitamin D receptor (VDR) has been implicated in fatty liver pathogenesis, but its role in the regulation of organismal energy usage remains unclear. Here, we illuminate the evolutionary function of VDR by demonstrating that zebrafish Vdr coordinates hepatic and organismal energy homeostasis through antagonistic regulation of nutrient storage and tissue growth. Hepatocyte-specific Vdr impairment increases hepatic lipid storage, partially through acsl4a induction, while simultaneously diminishing fatty acid oxidation and liver growth.
View Article and Find Full Text PDFThe skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.
View Article and Find Full Text PDFPancreatic cancer (PC) poses a substantial global health challenge, ranking as the fourth leading cause of cancer-related deaths due to its high mortality rate. Late-stage diagnoses are common due to the absence of specific symptoms. Pancreatic ductal adenocarcinoma (PDAC) accounts for the majority of PC cases.
View Article and Find Full Text PDFWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.
View Article and Find Full Text PDFAdipose tissue-derived mesenchymal stem cells are promising contributors to regenerative medicine, exhibiting the ability to regenerate tissues and modulate the immune system, which is particularly beneficial for addressing chronic inflammatory ulcers and wounds. Despite their inherent capabilities, research suggests that pretreatment amplifies therapeutic effectiveness. Our experimental design exposed adipose-derived mesenchymal stem cells to six inflammatory factors for 24 h.
View Article and Find Full Text PDFUnlabelled: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem. Here we mine large scale MM proteogenomic data integrating it with MM cell line dependency screen, and drug sensitivity data to identify druggable targets and forecast treatment efficacy and resistance.
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