Demographic and clinical feature disparity between progress and non-progress patients with vitiligo after COVID-19 vaccination: A cross-sectional study.

There have been several case reports regarding newly developed vitiligo following the coronavirus disease 19 (COVID-19) vaccination. However, the relationship between COVID-19 vaccine and vitiligo progression remains unclear. To explore the relationship between COVID-19 vaccine and vitiligo progression and its potential influencing factors, A cross-sectional study was conducted on 90 patients with vitiligo who received inactivated COVID-19 vaccination. Detailed information covering demographic characteristics (age and sex), vitiligo clinical features (disease subtypes, duration, stage and comorbidities) and disease activity was collected through an electronic questionnaire. Ninety patients with vitiligo included 44.4% males, with an average age of 38.1 years (standard deviation, SD = 15.0). Patients were divided into progress group (29, 32.2%) and normal group (61, 67.8%) based on whether they experienced vitiligo progression after inactivated COVID-19 vaccination. 41.3% of patients in the progress group experienced vitiligo progression within 1 week after vaccination, and disease progression mainly occurred after the first dose inoculation (20, 69.0%). Logistic regression revealed that patients aged <45 years (odds ratio (OR) was 0.87, 95% confidence interval (CI): 0.34-2.22) and male patients (OR = 0.84, 95% CI: 0.34-2.05) had lower risk for vitiligo progression, while patients with segmental vitiligo (SV) subtype (OR = 1.68, 95% CI: 0.53-5.33), with <5 years disease duration (OR = 1.32, 95% CI: 0.51-3.47) had higher risk for vitiligo progression after COVID-19 vaccination, but without statistical significance. Over 30% patients experienced vitiligo progression after inactivated COVID-19 vaccination, and female patients, elder age, shorter disease duration and SV subtype are potential risk factors for vitiligo progression.

BMP9 functions as a negative regulator in the myogenic differentiation of primary mouse myoblasts.

BMP9, a member of the TGF-ß superfamily, reveals the great translational promise for it has been shown to have the strong effect of osteogenic activity in vitro and in vivo. However, the implantation of certain BMPs (bone morphogenetic proteins) into muscular tissues induces ectopic bone formation. BMPs induce osteoblastic differentiation in skeletal muscle, suggesting that myogenic stem cells, such as myoblasts, are the potential progenitors of osteoblasts during heterotopic bone differentiation. Here, we investigate the role of BMP9 during primary mouse myoblasts differentiation. We found BMP9 enhanced cell proliferation and reduced myogenic differentiation of primary mouse myoblasts. In addition, adenovirus-mediated overexpression of BMP9 delayed muscle regeneration after BaCl2-induced injury. ALK1 knockdown reversed the inhibition of myoblast differentiation induced by BMP9. Our data indicate that BMP9 inhibits myogenic differentiation in primary mouse myoblasts and delays skeletal muscle regeneration after injury.

Integrated transcriptomic and immunological profiling reveals new diagnostic and prognostic models for cutaneous melanoma.

The mortality rate associated with cutaneous melanoma (SKCM) remains alarmingly high, highlighting the urgent need for a deeper understanding of its molecular underpinnings. In our study, we leveraged bulk transcriptome sequencing data from the SKCM cohort available in public databases such as TCGA and GEO. We utilized distinct datasets for training and validation purposes and also incorporated mutation and clinical data from TCGA, along with single-cell sequencing data from GEO. Through dimensionality reduction, we annotated cell subtypes within the single-cell data and analyzed the expression of tumor-related pathways across these subtypes. We identified differentially expressed genes (DEGs) in the training set, which were further refined using the Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm, employing tenfold cross-validation. This enabled the construction of a prognostic model, whose diagnostic efficacy we subsequently validated. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on the DEGs, and performed immunological profiling on two risk groups to elucidate the relationship between model genes and the immune responses relevant to SKCM diagnosis, treatment, and prognosis. We also knocked down the GMR6 expression level in the melanoma cells and verified its effect on cancer through multiple experiments. The results indicate that the GMR6 gene plays a role in promoting the proliferation, invasion, and migration of cancer cells in human melanoma. Our findings offer novel insights and a theoretical framework that could enhance prognosis, treatment, and drug development strategies for SKCM, potentially leading to more precise therapeutic interventions.

Chlorogenic acid attenuates deoxynivalenol-induced apoptosis and pyroptosis in human keratinocytes via activating Nrf2/HO-1 and inhibiting MAPK/NF-κB/NLRP3 pathways.

Deoxynivalenol (DON) is a common mycotoxic contaminant, frequently found in food and feed, causing a severe threat to human and animal health. Because of the widespread contamination of DON, humans involved in agricultural practices may be directly exposed to DON through the skin route. Chlorogenic acid (CGA) is a phenolic acid, which has anti-inflammatory and antioxidant properties. However, it is still unclear whether CGA can protect against DON-induced skin damage. Here, the effect of CGA on mitigating damage to human keratinocytes (HaCaT) triggered by DON, as well as its underlying mechanisms were investigated. Results demonstrated that DON exposure significantly decreased cell viability, and induced excessive mitochondrial reactive oxygen species (mtROS) generation, mitochondrial damage, oxidative stress, cell apoptosis and pyroptosis. However, CGA pretreatment for 2 h significantly increased cell viability and reversed DON-induced oxidative stress by improving antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), reducing mtROS generation and enhancing mitochondrial function through activating Nrf2/HO-1 pathway. Moreover, CGA significantly increased the Bcl-2 protein expression, decreased the protein expressions of Bax and cleaved Caspase-3, and suppressed the phosphorylated of ERK, JNK, NF-κB. Further experiments revealed that CGA could also inhibit the pyroptosis-related protein expressions including NLRP3, cleaved Caspase-1, GSDMD-N, cleaved IL-1ß and IL-18. In conclusion, our results suggest that CGA could attenuate DON-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2/HO-1 pathway and inhibiting MAPK/NF-κB/NLRP3 pathway. CGA might be a novel promising therapeutic agent for alleviating the dermal damage triggered by DON.

A mutation in CCDC91, Homo sapiens coiled-coil domain containing 91 protein, cause autosomal-dominant acrokeratoelastoidosis.

Acrokeratoelastoidosis (AKE) is a rare autosomal dominant hereditary skin disease characterized by small, round-oval, flat-topped keratotic papules on the palms, soles and dorsal aspect of hands or feet. The causative gene for AKE remains unidentified. This study aims to identify the causative gene of AKE and explore the underlying biological mechanisms. A large, three-generation Chinese family exhibiting classic AKE symptoms was identified. A genome-wide linkage analysis and whole-exome sequencing were employed to determine the causative gene. shRNA knockdown in human skin fibroblasts and CRISPR/Cas9 knockout in HEK293T cells were utilized to assess gene functions in the progression of elastic fiber biosynthesis. The linkage analysis identified a susceptibility region between rs7296765 to rs10784618 on chromosome 12. Whole-exome sequencing confirmed a splicing mutation of 1101 + 1 G > A in the CCDC91 gene, resulting in exon 11 skipping and a subsequent 59-amino-acid-residue loss (residues L309-Q367del). Further functional analysis revealed distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-HSF cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates. There are no significant changes in Fibrillin-1 microfibril assembly and lysyl oxidase activity. The findings strongly suggest that the protein product of the CCDC91 gene plays a crucial role in elastin transport. This discovery enhances our understanding of CCDC91's function and broadens the known pathogenic mechanisms of AKE.

Endoplasmic Reticulum Dysfunction: An Emerging Mechanism of Vitiligo Pathogenesis.

The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.

C3d Immunohistochemical Staining on Paraffin-Embedded Tissue for Diagnosis of Pemphigus.

CONTEXT.­: Pemphigus is an autoimmune blister disease that causes blisters on the skin and mucosal surfaces. Direct immunofluorescence (DIF) testing is critical for the clinical diagnosis of pemphigus. However, it is limited to fresh tissue specimens and fluorescence microscopy. OBJECTIVE.­: To assess the value of C3d immunohistochemistry (IHC) on paraffin-embedded skin tissue for the diagnosis of pemphigus by comparing C3d-IHC results to DIF and enzyme-linked immunosorbent assay testing in pemphigus and other blister-related skin diseases. DESIGN.­: C3d-IHC assays were retrospectively performed on paraffin-embedded skin tissue sections from 115 patients (63 with pemphigus and 52 controls). Both the case group and the control group underwent the same protocol, and cases with C3d position in the peripheral spinous layer were considered as positive samples. RESULTS.­: C3d-IHC and DIF testing had similar performance for pemphigus diagnosis, with a sensitivity of 71.0% (95% CI, 51.8%-85.1%) and 77.4% (95% CI, 58.5%-89.7%), specificity of 96.4% (95% CI, 79.8%-99.8%) and 100% (95% CI, 85.0%-100%), positive predictive value of 95.7% (95% CI, 76.0%-99.8%) and 100% (95% CI, 82.8%-100%), and a negative predictive value of 75.0% (95% CI, 57.5%-87.3%) and 80.0% (95% CI, 62.5%-90.9%), respectively. CONCLUSIONS.­: Our study indicated that C3d-IHC results for paraffin-fixed tissues were not significantly different from DIF results for the diagnosis of pemphigus. The C3d-IHC assay has the potential for routine diagnosis of pemphigus, especially in the absence of fresh-frozen tissue.

A construction and comprehensive analysis of ceRNA networks and infiltrating immune cells in papillary renal cell carcinoma.

BACKGROUND: As the second most common malignancy in adults, papillary renal cell carcinoma (PRCC) has shown an increasing trend in both incidence and mortality. Effective treatment for advanced metastatic PRCC is still lacking. In this study, we aimed to establish competitive endogenous RNA (ceRNA) networks related to PRCC tumorigenesis, and analyze the specific role of differentially expressed ceRNA components and infiltrating immune cells in tumorigenesis. METHODS: CeRNA networks were established to identify the key ceRNAs related to PRCC tumorigenesis based on the 318 samples from The Cancer Genome Atlas database (TCGA), including 285 PRCC and 33 normal control samples. The R package, "CIBERSORT," was used to evaluate the infiltration of 22 types of immune cells. Then we identified the significant ceRNAs and immune cells, based on which two nomograms were obtained for predicting the prognosis in PRCC patients. Finally, we investigated the co-expression of PRCC-specific immune cells and core ceRNAs via Pearson correlation test. RESULTS: COL1A1, H19, ITPKB, LDLR, TCF4, and WNK3 were identified as hub genes in ceRNA networks. Four prognostic-related tumor-infiltrating immune cells, including T cells CD4 memory resting, Macrophages M1, and Macrophages M2 were revealed. Pearson correlation test indicated that Macrophage M1 was negatively related with COL1A1 (p < 0.01) and LDLR (p < 0.01), while Macrophage M2 was positively related with COL1A1 (p < 0.01), TCF4 (p < 0.01), and H19 (p = 0.032). Two nomograms were conducted with favorable accuracies (area under curve of 1-year survival: 0.935 and 0.877; 3-year survival: 0.849 and 0.841; and 5-year survival: 0.818 and 0.775, respectively). CONCLUSION: The study constructed two nomograms suited for PRCC prognosis predicting. Moreover, we concluded that H19-miR-29c-3p-COL1A1 axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through Wnt signaling pathway, collaborating to promote PRCC tumorigenesis and lead to poor overall survival of PRCC patients.

Desmoplastic Melanoma: A Clinicopathological Analysis of Three Cases in the Chinese Population.

PURPOSE: To investigate the clinicopathological characteristics and immunophenotype of desmoplastic melanoma (DM) in the Chinese population. PATIENTS AND METHODS: We report three cases of DM diagnosed by the Pathology Department of Shanghai Dermatology Hospital. We describe the clinical and pathological characteristics of the three cases and examine molecular markers used in the diagnosis of DM. Finally, we summarize the current literature in the DM field. RESULTS: Clinically, lesions in the three DM patients were characterized by non-pigmented nodules or papules. Microscopically, we observed an abundance of fibrous interstitium mixed with spindle cells exhibiting various degrees of atypia. Occasionally, these structures exhibited changes in lentigo maligna at the epidermal junction, accompanied by the presence of lymphoid follicular structures and neurophilic behavior. Diagnosis of DM was confirmed by immunohistochemical staining, which revealed high expression levels of S-100 and SOX-10. Melanocyte markers were focally positive or negative. Unlike DMs from other populations, our three patients were negative for WT-1 and P53. All three cases received surgical resection, which is the preferred treatment for DM, and none of the patients experienced recurrence. CONCLUSION: DM in these Chinese patients was similar to that observed in other DM populations in terms of immunophenotype and clinical and histological features. A notable absence in p53 staining was observed in the three cases reported here, suggesting that p53 negativity should not exclude the diagnosis of DM in the Chinese population.