Hydrogen sulfide (H2S), a colorless, water soluble, flammable gas with a characteristic smell of rotten eggs, has been known as a highly toxic gas for several years. However, much like carbon ...monoxide (CO) and nitric oxide (NO), the initial negative perception of H2S has developed with the discovery that H2S is generated enzymatically in animals under normal conditions. With the result of this discovery, much more work is needed to elucidate the biologic effects of H2S. In recent years, its cytoprotective properties have been recognized in multiple organs and tissues. In particular, H2S plays important roles in combating oxidative species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) and protect the body from oxidative stress. Therefore, this review discusses the biologic effect of H2S and how it protects cells in various diseases by acting as an antioxidant that reduces excessive amounts of ROS and RNS.
Ethical approval and informed consent are not required, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care.
H2S has been found to be cytoprotective in oxidative stress in a wide range of physiologic and pathologic conditions, an increasing number of therapeutic potentials of H2S also have been revealed. However, there is still much debate on the clear mechanism of action of H2S, so that the mechanisms of cell signaling that promote cellular survival and organ protection need to be further investigated to provide better H2S-based therapeutics.
Loss of melanocytes (MCs) is the most notable feature of vitiligo. Hence, it is critical to clarify the mechanisms of MC destruction in vitiligo. Apoptosis is most widely studied cell death pathways ...in vitiligo. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis of vitiligo. Anoikis is likely to be connected with the death of detached MCs, which is provoked specifically by loss of anchorage. Primary phagocytosis, later called phagoptosis can execute death of viable cells, probably partly responsible for the loss of MCs in vitiligo. In this review, we aim to summarize the latest insights into various forms of MC death in vitiligo and discuss the corresponding mechanisms.
Inherited epidermolysis bullosa is a heterogeneous group of hereditary skin diseases characterized by skin (mucosa) fragility, which leads to blistering. Junctional epidermolysis bullosa is ...associated with mutations in genes expressing proteins of the dermo-epidermal junction. Dupilumab, an antibody that directly targets interleukin (IL)-4 receptor alpha, may be an effective treatment for dystrophic epidermolysis bullosa. We describe a case of junctional epidermolysis bullosa that improved with dupilumab.
Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in ...the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. We demonstrated that ATG7-dependent autophagy could affect melanin content of melanocytes by regulating melanogenesis. Moreover, suppression of ATG7-dependent autophagy inhibits proliferation and promotes oxidative stress-induced apoptosis of melanocytes, whereas enhancement of ATG7-dependent autophagy protects melanocytes from oxidative stress-induced apoptosis. Meanwhile, deficiency of ATG7-dependent autophagy results in premature senescence of melanocytes under oxidative stress. Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.
Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates ...in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.
Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions ...about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin‐lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064‐nm Q‐Switched Nd: YAG laser, 755‐nm PicoWay laser, nonablative 1927‐nm fractional thulium fiber laser, new pulsed‐type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized.
Riehl's melanosis is an acquired pigmentation disorder that is possibly caused by type IV hypersensitivity response, genetic, ultraviolet radiation, and autoimmune factors. The current methods to help diagnose Riehl's melanosis include clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system. Topical skin‐lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies have been proved effectiveness in treatment. Latest researches of Riehl's melanosis have demonstrated several potential biomarkers and the comorbidity with autoimmune disorders.
•Serum levels of CCL20 could be a novel biomarker to monitor disease activity and to guide treatment of progressive vitiligo.•Increased proportions of Th1/17 and Tc1/17 cells were found in active ...vitiligo, accompanied by increased levels of CCR6 and CCL20 in PBMCs.•A profound skewing of CCR6 and CCL20 was observed in vitiligous lesions.
Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.
To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo.
One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry.
The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells.
CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo.
Highlights • The comparison of microRNA profile of human dermis from young and aged donors revealed 40 miRNAs differentially expressed in aged dermis. • The constructed microRNA-gene-network analysis ...revealed the dominant regulatory roles of miR-29 and miR-34 family in skin aging. • Similar alteration of miRNAs was observed in senescent fibroblasts in vitro, and they might interact with p16 pathway to regulate the senescence of fibroblasts. • MiR-34 in HDFs can modulate the cell function and the expression of MMP-1, COL1A1 and elastin.
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