Hsa_circ_0012919 regulates expression of MDA5 by miR-125a-3p in CD4+ T cells of systemic lupus erythematous.

Systemic lupus erythematous (SLE) is an autoimmune disease with production of various autoantibodies directed against various autoantigens. But the research on melanoma differentiation-associated gene 5 (MDA5) in SLE is still scarce. Here we try to elucidate the effect of hsa_circ_0012919 on MDA5 and its potential clinical value in SLE. CD4+ T cells from SLE patients and healthy control subjects were isolated. Expression of hsa_circ_0012919 and MDA5, and methylation level of MDA5 promoter were detected. Then expression and methylation level of MDA5 promoter was examined after transfection of hsa_circ_0012919-targeted siRNA and plasmids. Expression of hsa_circ_0012919 and MDA5 were further confirmed to be significantly higher in CD4+ T cells of SLE patients (p < 0.05), methylation level of MDA5 promoter was significantly lower in CD4+ T cells of SLE patients (p < 0.05), and expression of MDA5 mRNA was correlated with SLE parameters (p < 0.05). Downregulation or overexpression of hsa_circ_0012919 regulated (1) the expression of MDA5 in a dose-dependent manner and (2) the DNA methylation of MDA5 promoter in CD4+ T cells of SLE. Finally, hsa_circ_0012919 could regulate MDA5 by miR-125a-3p. Hsa_circ_0012919 regulated the expression and methylation of MDA5 in the CD4+ T cells of SLE patients, and hsa_circ_0012919 could regulate MDA5 by miR-125a-3p.

Clinicopathological Characteristics and Outcome of Cytophagic Histiocytic Panniculitis: A Single-Center, Retrospective Study.

Background: Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Purpose: To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge. Material and Methods: Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022. Results: All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal. Conclusion: The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, also may be present in hemophagocytic lymphohistiocytosis and subcutaneous panniculitis-like T-cell lymphoma. The presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders and streptococcal infections. In addition, EBV-negative CHP has a better prognosis than previously thought and provides knowledge of its prognosis in the Chinese population. With changes in the disease pedigree supported by the development of medical technology, CHP may present as a reactive process of a combined primary disease.

A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome.

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

The involvement of ERK1/2 and p38 MAPK in the premature senescence of melanocytes induced by H2O2 through a p53-independent p21 pathway.

BACKGROUND: The pathogenesis of vitiligo is still unknown and oxidative stress is an important factor that can damage or incapacitate melanocytes. OBJECTIVE: To investigate the role of oxidative stress in the premature senescence of melanocytes and their transfer of melanosomes. METHODS: Cultured human melanocytes were treated with H2O2 after which cell viability and apoptosis were assessed. We investigated whether exposure to H2O2 induces premature senescence. RNA sequencing was used to screen aging-related signaling pathways. The expression of dendritic regulatory proteins, adhesion molecules and cell cytoskeletal proteins, as well as melanosome distribution were characterized. The ROS scavenger NAC was used to study the role of ROS in cell senescence and in melanosome transfer. RESULTS: Cell viability decreased progressively and cell apoptosis increased after treatment with H2O2. H2O2 treatment tended to induce premature senescence in melanocytes through a p53-independent p21 pathway. RNA sequencing analysis showed that H2O2 treatment induced the differential expression of MAPK signaling pathway components. Western blotting and qRT-PCR confirmed that H2O2 treatment increased the phosphorylation of ERK1/2 and p38 MAPK, which are involved in inducing the senescence of melanocytes, but not JNK. The expression of cell cytoskeleton and adhesion molecules decreased after H2O2 treatment. p21 siRNA treatment reversed these changes. Treatment with NAC improved the premature senescence and the impaired melanosome transfer induced by H2O2. CONCLUSION: H2O2 increases ROS levels, which activates the ERK1/2 and p38 MAPK pathways to induce the premature senescence of melanocytes through p21 via a p53-independent pathway and consequently disrupts melanosome transfer.

Intermittent Asymptomatic Fever in a Psoriasis Patient.

Acitretin, an active metabolite of etretinate, is the most widely used systemic retinoid in the treatment of psoriasis. Several side effects of acitretin have been reported such as teratogenicity, cheilitis, xerosis, dyslipidemia, and photosensitivity. Here, we reported a case of acitretin-induced intermittent asymptomatic fever in a 79-year-old male psoriasis patient. To the best of our knowledge, only one such case has been reported in the literature so far. We report our case to draw clinical attention that acitretin may cause drug fever, which might not be a rare phenomenon.

The early repigmentation pattern of vitiligo is related to the source of melanocytes and by the choice of therapy: a retrospective cohort study.

BACKGROUND: Patients with vitiligo present with different repigmentation patterns in the early recovery stage. OBJECTIVES: To analyze the relationships between early repigmentation patterns in vitiliginous patches, their clinical characteristics, and therapeutic choices. METHODS: Patients with vitiligo seen in the Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University from 2010 to 2015, were included, and their clinical records, especially photographs and medical treatments, were reviewed. RESULTS: One hundred and sixteen patients were included in this study, and 326 lesions with different degrees of depigmentation, locations, stages, distributions, therapies, and repigmentation patterns were included and analyzed. Perifollicular repigmentation occurred more frequently in lesions with complete depigmentation (P = 0.005), in non-sun exposed areas (P < 0.001), a stable stage (P = 0.008), and lesions treated with narrow band ultraviolet B (NB-UVB) (P < 0.001, despite lesion distributions). Marginal repigmentation is more frequent in lesions with complete depigmentation (P = 0.016), lesions treated without NB-UVB (P = 0.002), and facial lesions treated with topical vitamin D analogs (TVDAs) monotherapy (P = 0.022). Diffuse repigmentation is the predominant pattern in lesions with incomplete depigmentation (P < 0.001), in sun-exposed areas (P < 0.001), progressive stage (P = 0.044), and truncal lesions treated with TVDAs (P < 0.001). CONCLUSIONS: The different repigmentation patterns of vitiligo lesions depend on the different source and status of melanocytes and their abilities to produce melanin on the choice of therapy.

Protective effect of madecassoside on H2O2-induced oxidative stress and autophagy activation in human melanocytes.

BACKGROUND: Centella asiatica (L.) Urb. is a traditional Chinese medicine that has many medical applications, including wound healing and anti-oxidation. Some traditional Chinese Medicine doctors have found that it has therapeutic effects for external use in the repigmentation of vitiligo and post-inflammatory hypopigmentation. This study was designed to evaluate the effects of madecassoside, a major bioactive component of C. asiatica, on oxidative stress in human melanocytes and its possible mechanism of action. RESULTS: In H2O2-induced oxidative conditions, madecassoside inhibited melanocyte dendrite retraction, improved MMP and reduced the accumulation of [Ca2+]i in a concentration-dependent manner. Observations by TEM showed that madecassoside attenuated the damage of mitochondria in human melanocytes caused by oxidative stress. Furthermore, autophagy activation was demonstrated by AO staining and an increased LC3-II/LC3-I ratio. MATERIALS AND METHODS: Normal human melanocytes were treated with 0.01 mM H2O2 and varying concentrations of madecassoside (0, 10, 50, 100 µg/mL). Subsequently, the retraction velocity of melanocyte dendrites was assessed. Determination of mitochondrial membrane potential (MMP, ΔΨm) was performed by flow cytometry and intracellular calcium ([Ca2+]i) level were measured. Alterations of mitochondrial ultrastructure were observed by transmission electron microscopy (TEM). Acridine orange (AO) staining was used to measure autophagy. The LC3-II/LC3-I ratio, an indicator of autophagosome formation, was analyzed by western blot. CONCLUSIONS: These results demonstrate the antioxidative effect of madecassoside on human melanocytes subjected to oxidative damage via the activation of autophagy. Moreover, madecassoside could be a promising treatment for vitiligo mainly caused by oxidative stress.

Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.

Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P < 0.001), perilesional halo nevi (P < 0.01) and the controls (P < 0.01), but not in perilesional active vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P < 0.001). The distribution and constitution of melanosomes were normal in halo nevi. Impaired melanin synthesis and melanosome transfer are involved in the pathogenesis of vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.