Cutaneous T-cell lymphomas (CTCL) are a group of rare hematological malignancies characterized by infiltration of malignant T-cells into the skin. Two main types of CTCL constitute of Mycosis Fungoides (MF), a more indolent form of the disease, and Sézary syndrome (SS), the aggressive and leukemic variant with blood involvement. Sézary syndrome presents a significant clinical challenge due to its very aggressive nature, poor prognosis, and treatment resistance, and to date, the disease remains incurable. Histone deacetylase inhibitors have gained attention in CTCL treatment with promising results, but they expose limited specificity and strong side effects. Recent genomic studies underscore the role of epigenetic modifiers in CTCL pathogenesis, prompting an investigation into HDAC10, a member of class IIb HDACs, in SS. HDAC10 was investigated in different cancers, revealing its involvement in cell cycle regulation, apoptosis, and autophagy, but its role in CTCL is unknown. In this study we aimed to determine the role of HDAC10 in SS, focusing on its cellular localization, role in cell growth, and therapeutic potential. We indicated that HDAC10 is overexpressed in SS patients and located mainly in the cytoplasm. Its overexpression leads to an inhibitory effect on apoptosis progression when exposed to the pro-apoptotic compound Camptothecin (CPT). Knockdown of HDAC10 resulted in reduced cell growth and induction of apoptosis and autophagy, highlighting its potential importance in CTCL pathogenesis. Whole transcriptome analysis indicated that HDAC10 is associated with crucial cancer-related pathways, for example, hematopoietic cell lineage, PI3K-Akt signaling pathway, Ras signaling pathway, MAPK signaling pathway or JAK-STAT signaling pathway, which are critical for the survival and proliferation of malignant T cells. Inhibition of HDAC10 with selective HDAC10i increased the sensitivity of Sézary cells to the pro-apoptotic CPT. Our findings demonstrate that HDAC10 plays a key role in the molecular background of Sézary syndrome, highlighting its importance in the cellular mechanisms of the disease.
Senescence is accompanied by numerous processes that lead to alterations in cell metabolism, cell cycle arrest, and, increased production and secretion of senescence-associated secretory phenotype (SASP). Consequently, signaling pathways cascades are activated, leading to inflammation that can trigger multiple disorders, including cancer. Recently, a novel therapeutic approach was proposed based on targeting senescent cells using senolytics. This group of biologically active compounds includes fisetin, quercetin, dasatinib, and others. These compounds were shown to affect laboratory animals (rodents) by improving the quality of life and significantly increasing the length of life by reducing senescent cells pool in different organs. Based on these findings, we decided to evaluate the potential of these compounds in targeting senescent cells in human skin using in vitro model based on human-derived keratinocytes (HEKa) and fibroblasts (HDFa). Cytotoxicity assay revealed that the activity of the compounds was time- and dose-dependent as well as cell-type dependent. Further studies were performed to reveal the mechanistic aspect of these observations including assessment of the senescence marker, namely p16. However, it requires clarification before entering clinical trials to provide not only efficient but, first of all, safe application of senolytics to human skin.
Objectives: Actinic keratoses (AKs) are one of the most common reasons for consultation in the elderly population. This study aimed to assess the efficacy of 5-ALA PDT in AK treatment using high-frequency ultrasonography (HFUS) to evaluate skin layer changes during therapy. Methods: In our study, we included 44 AK patients aged 53 to 89 years. All patients had lesions clinically evaluated with the Olsen and AKASI scale. HFUS imaging was performed on seemingly healthy skin and lesions before and at 4, 8, and 12 weeks of therapy. Ultrasound markers such as skin thickness, echogenicity, and pixel intensity were measured. 5-ALA was applied under occlusion for 3 h. After removing the occlusive dressing, 5-ALA was removed with a saline solution and a directed therapy with a BF-200 lamp. Full follow-ups of 56 markers of suitable quality were selected. Results: The thickness of SLEB significantly decreased in the following weeks compared to the pre-therapy results, reaching its lowest values after 12 weeks. The average pixel intensity significantly increased in each skin layer after therapy (p < 0.01). For SLEB, there were statistically significant differences in LEP, MEP and contrast. The AKASI score before and after treatment was determined for the 39 patients who underwent follow-up at week 12. The median AKASI score was 3.2 (1.2–8.6) before treatment and 0.6 (0–2.8) after. Conclusions: According to the literature data, this is the first study describing the ALA-PDT treatment efficacy in different AK severities evaluated in HFUS. HFUS provides a valuable non-invasive tool for monitoring the efficacy of PDT in AK treatment, showing significant improvements in skin texture and structure.
Abstract Despite the growing interest by researchers into cellular senescence, a hallmark of cellular aging, its role in human skin remains equivocal. The skin is the largest and most accessible human organ, reacting to the external and internal environment. Hence, it is an organ of choice to investigate cellular senescence and to target root‐cause aging processes using senolytic and senomorphic agents, including naturally occurring plant‐based derivatives. This review presents different aspects of skin cellular senescence, from physiology to pathology and signaling pathways. Cellular senescence can have both beneficial and detrimental effects on the skin, indicating that both prosenescent and antisenescent therapies may be desirable, based on the context. Knowledge of molecular mechanisms involved in skin cellular senescence may provide meaningful insights for developing effective therapeutics for senescence‐related skin disorders, such as wound healing and cosmetic skin aging changes.
Transdermal therapeutic systems (TTS) belong to the widely used methods of drug administration, which allow rate-controlled drug delivery and avoidance of first-pass metabolism in the liver Beside scopolamine, nitroglycerin (glyceryl trinitrate), nicotine, clonidine and fentanyl, also transdermal delivery of sex steroids for hormone replacement therapy and contraception is a well-known and popular method in daily clinical practice. It is estimated that approximately 20% of patients using transdermal estradiol may complain of adverse cutaneous side effects. Most of those reactions are mild or moderate, usually limited to the area of drug application. However, prolonged use may increase the chance of developing sensitization. The purpose of this review is to provide up-to date information on the spectrum of cutaneous reactions caused by TTS and the characteristics of potential contact allergens, including sex hormones. Proper management and prophylactic measures were also included.
Acne vulgaris is one of the most common dermatological disease which may present with disturbed epidermal barrier function, exacerbated by drugs used to treat acne, both general and local. The instructing patients with acne in the selection of appropriate cosmetic products, significantly improves their quality of life. The aim of the study was to gain the knowledge of acne patients about the skin care principles. The study involved 80 patients suffering from acne vulgaris and showed the need to conduct education in the field of proper care of the acne skin.
Actinic keratosis (AK) is a common disorder, presented with scaly, erythematous lesions associated with chronic exposure to ultraviolet (UV) radiation and possible transforming into an invasive squamous cell carcinoma. Photodynamic Therapy (PDT) is one of non-invasive methods of treatment AK. We report the case of a 61-year-old female patient with AK treated with PDT in whom erythema and pustules with concomitant elevated body temperature were observed, what might indicate on reactivation of herpes simplex virus (HSV) infection.
'%3e%3cg id='e'%3e%3cg id='c' fill='none' stroke='%23fff' stroke-width='2'%3e%3cpath id='b' d='M0 1h26M1 10V5h8v4h8V5h-5M4 9h2m20 0h-5V5h8m0-5v9h8V0m-4 0v9' transform='scale(1.4)'/%3e%3cpath id='a' d='M0 7h9m1 0h9' transform='scale(2.8)'/%3e%3cuse xlink:href='%23a' y='120'/%3e%3cuse xlink:href='%23b' y='145.2'/%3e%3c/g%3e%3cg id='d'%3e%3cuse xlink:href='%23c' x='56'/%3e%3cuse xlink:href='%23c' x='112'/%3e%3cuse xlink:href='%23c' x='168'/%3e%3c/g%3e%3c/g%3e%3cuse xlink:href='%23d' x='168'/%3e%3cuse xlink:href='%23e' x='392'/%3e%3c/g%3e%3cg fill='%23da0000' transform='matrix(45 0 0 45 315 180)'%3e%3cg id='f'%3e%3cpath d='M-.548.836A.912.912 0 0 0 .329-.722 1 1 0 0 1-.548.836'/%3e%3cpath d='M.618.661A.764.764 0 0 0 .422-.74 1 1 0 0 1 .618.661M0 1l-.05-1L0-.787a.31.31 0 0 0 .118.099V-.1l-.04.993zM-.02-.85 0-.831a.144.144 0 0 0 .252-.137A.136.136 0 0 1 0-.925'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='scale(-1 1)'/%3e%3c/g%3e%3c/svg%3e)
