Structural characterization and innate immunomodulatory effect of glucomannan from Bletilla striata.

The crude polysaccharide of Bletilla striata in this study was extracted by water extraction and alcohol precipitation and further purified by gel column to yield the purified component Bletilla striata polysaccharide (BSP). Its structure and innate immune regulation activity were studied. BSP mainly comprises mannose and glucose, with a monosaccharide molar ratio of 2.9:1 and a weight-average molecular weight of 28,365 Da. It is a new low-molecular-weight water-soluble neutral glucomannan. BSP contains a â†’ 6)-ß-Manp-(1→, →4)-ß-Glcp-(1→, →4)-ß-Manp-(1 â†’ and →3)-α-Manp-(1 â†’ linear main chain, containing ß-Glcp-(1 â†’ and ß-Manp-(1 â†’ two branched chain fragments were connected to the Man residue at position 4. BSP can enhance the anti-infection ability of Caenorhabditis elegans against Pseudomonas aeruginosa, significantly improve the phagocytic ability of RAW264.7 macrophages, stimulate the secretion of NO and TNF-α, and have good innate immune regulation activity. These findings guide the use of Bletilla striata polysaccharides with immunomodulatory action.

Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging.

Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.

Ferrostatin 1 ameliorates UVB-induced damage of HaCaT cells by regulating ferroptosis.

Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer-1, 10 µM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2 ) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real-time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer-1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis-related proteins and skin barrier-related proteins, and increased levels of γ-H2AX and iron, whereas Fer-1 significantly increased their protein levels, and reduced levels of γ-H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer-1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer-1 significantly ameliorates UVB-induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R.

Identification of the role of autophagy-related TNFSF10/ hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis.

Background: Vitiligo is a common clinical disorder caused by the destruction of epidermal melanocytes, which is often associated with autoimmune mechanisms. Autophagy plays a crucial role in maintaining cellular homeostasis and exhibits close associations with various autoimmune disorders. While dysautophagy of melanocytes is associated with vitiligo pathogenesis, there is a lack of studies on autophagy-related genes (ARGs) in blood samples from individuals with vitiligo. Methods: Blood samples from individuals with vitiligo and healthy controls were compared to identify differentially expressed genes (DEGs), which were subsequently subjected to further analysis. Then, miRNAs correlated with core genes were predicted by five distinct online tools, and those miRNAs that appeared in three or more tools at the same time were chosen for further enrichment analysis. Furthermore, in vitro experiments of targeting core genes were conducted. Results: The results showed that there were a total of 30 ARGs among DEGs, with 13 up-regulated genes and 17 down-regulated genes. Based on the functional enrichment analysis of DEGs and projected miRNAs, we hypothesized that autophagy and apoptosis may synergistically contribute to the progression of vitiligo, with the TNFSF10/hsa-let-7a-5p axis potentially playing an important role that should not be ignored. In addition, epigallocatechin-3-gallate (EGCG) was found to be the common component in BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI, which were discovered to be potential in vitiligo treatment by inducing cell autophagy and apoptosis targeting TNFSF10. Conclusion: It was the first time that TNFSF/hsa-let-7a-5p was discovered to be involved in the development of vitiligo through autophagy and apoptosis. Meanwhile, we observed that BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI were promising to treat vitiligo by regulating autophagy and apoptosis via TNFSF10. These findings could lead to new directions for investigating the pathogenesis and therapy of vitiligo.

A Case of Perioral Dermatitis Successfully Treated with Abrocitinib.

Perioral dermatitis (POD) is a chronic inflammatory skin disease that primarily affects females between the ages of 16 and 45. Conventional therapies face the challenge of limited efficacy and a high recurrence rate. In this report, we present the case of a 26-year-old male patient with POD who was successfully treated using the Janus kinase (JAK) inhibitor, abrocitinib. This treatment exhibited both good efficacy and safety. Abrocitinib, as a JAK inhibitor, holds promise as a potential therapy for cases of POD that might be resistant to conventional therapies.

Current and Emerging Therapies for Atopic Dermatitis in the Elderly.

Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.

Alopecia Universalis in an Elderly Chinese Man Induced by Sacubitril/Alisartan, a Novel Angiotensin Receptor-Neprilysin Inhibitor.

Drug-induced alopecia areata is a rare adverse event wherein medications such as antimicrobials, anticonvulsants, and biologics, trigger the premature transition of actively growing hairs into the telogen phase. Herein, a unique case of alopecia universalis observed during a clinical trial involving sacubitril/alisartan, a novel angiotensin receptor-neprilysin inhibitor (ARNI) has been reported. This case contributes to the range of cutaneous reactions that might be observed in association with ARNI therapy.

Successful Treatment of Atopic Dermatitis with a Predominant Nipple Involvement by Abrocitinib During COVID-19 Pandemic: A Case Report.

Background: There is limited literature on AD with a predominant involvement of nipple among the adult male group. SARS-CoV-2 infection might have been an exacerbating factor of AD by initiating the "cytokine storm". Conventional treatment suffers from a dilemma of poor efficacy and a high recurrence. The JAK inhibitors have been clinically applied to treat the AD with a good outcome. Patients and Methods: We present a case of a 28-year-old male AD patient with a predominant nipple involvement successfully treated with JAK inhibitor abrocitinib, with no adverse affects. Results: The case shows a good clinical efficacy of JAK inhibitor abrocitinib in the treatment of AD with a predominant nipple involvement during the COVID-19 pandemic with a rapid and long-term symptomatic relief. Conclusion: JAK inhibitor abrocitinib might become a promising agent for the treatment with AD with a predominant uncommon region like nipple that might be resistant to conventional therapies during the COVID-19 pandemic.

The Value of Cell-Free Circulating DNA Profiling in Patients with Skin Diseases.

Liquid biopsy, also known as fluid biopsy or fluid-phase biopsy, is the sampling and analysis of the blood, cerebrospinal fluid, saliva, pleural fluid, ascites, and urine. Compared with tissue biopsy, liquid biopsy technology has the advantages of being noninvasive, having strong repeatability, enabling early diagnosis, dynamic monitoring, and overcoming tumor heterogeneity. However, interest in cfDNA and skin diseases has not expanded until recently. In this review, we present an overview of the literature related to the basic biology of cfDNA in the field of dermatology as a biomarker for early diagnosis, monitoring disease activity, predicting progression, and treatment response.

Cryptococcosis Inhibits the Immune Response of Dendritic Cells Through the snhg1-miR-145a-3p-Bcl2 Axis.

OBJECTIVES: Dendritic cells are one of the first host cells that cryptococcus encounters. However, the correlations among cryptococcus, dendritic cells, and long noncoding RNA remain unclear. This study was undertaken to investigate the effects of long noncoding RNAs on dendritic cells with cryptococcus infection. MATERIALS AND METHODS: We treated dendritic cells with cryptococcus and then detected expression of CD80, CD86, and major histocompatibility complex class II in dendritic cells with a real-time fluorescent quantitative polymerase chain reaction assay. We used nextgeneration sequencing and bioinformatics analysis to determine the competitive endogenous RNA mechanisms, confirmed via real-time polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation assays. RESULTS: After treatment of dendritic cells with 1 × 108 CFU/mL cryptococcus for 12 hours, dendritic cell viability was normal, whereas mRNA expression levels of CD80, CD86, and major histocompatibility complex class II in dendritic cells were substantially increased. With next-generation sequencing, we discovered 4 small nucleolar RNA host genes (snhg1, snhg3, snhg4, and snhg16) in cryptococcus-treated dendritic cells compared with wild-type dendritic cells. Bioinformatics analysis combined with real-time polymerase chain reaction led us to speculate that cryptococcus may affect the maturation and apoptosis of dendritic cells by regulating snhg1-miR-145a-3p-Bcl2. Further polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation experiments revealed that snhg1 acted as a sponge for miR145a-3p to inhibit the expression of miR-145a-3p and that miR-145a-3p promoted the expression of Bcl2 by directly targeting the 3'-UTR of Bcl2. Functional recovery experiments showed that cryptococcus promoted the maturation and apoptosis and inhibited the proliferation of dendritic cells through the snhg1-Bcl2 pathway. CONCLUSIONS: This study lays a foundation for the further understanding of the pathogenic role of snhg1-miR-145a-3p-Bcl2 axis in cryptococcosis.

The Emerging Roles of Pyroptosis, Necroptosis, and Ferroptosis in Non-Malignant Dermatoses: A Review.

Unlike apoptosis, pyroptosis, necroptosis, and ferroptosis are recently identified modes of programmed cell death (PCD) with unique molecular pathways. Increasing evidence has indicated that these PCD modes play a crucial role in the pathogenesis of various non-malignant dermatoses (a group of cutaneous disorders), including infective dermatoses, immune-related dermatoses, allergic dermatoses, benign proliferative dermatoses, etc. Moreover, their molecular mechanisms have been suggested as potential therapeutic targets for the prevention and treatment of these dermatoses. In this article, we aim to review and summarize the molecular mechanisms of pyroptosis, necroptosis, and ferroptosis and their roles in the pathogenesis of some non-malignant dermatoses.

Medical Applications of Hydrogels in Skin Infections: A Review.

Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.

Effective decolonization strategy for mupirocin-resistant Staphylococcus aureus by TPGS-modified mupirocin-silver complex.

The widespread utilization of mupirocin to treat methicillin-resistant Staphylococcus aureus (MRSA)-caused infectious diseases has led to the emergence of mupirocin-resistant Staphylococcus aureus (MuRSA), posing a serious global medical threat. In order to counteract MuRSA, we develop a d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA. The surfactivity of TPGS endows Mup-Ag with a homogeneous and small particle size (∼16 â€‹nm), which significantly enhances bacterial internalization. Silver ions are released from the mupirocin-Ag complex (Mup-Ag) to exert a synergistic antibacterial activity with mupirocin. Results manifest that our strategy reduces the concentration of mupirocin that induces 50% bacterial death from about 1000 â€‹µmol/mL to about 16 â€‹µmol/mL. In vitro bacterial infection model suggests that TPGS/Mup-Ag can not only eliminate both intracellular and inhibit bacterial adhesion, but also living cells are not affected. Results of in vivo experiments demonstrate that TPGS/Mup-Ag can effectively inhibit the progression of skin infection and accelerate wound healing, as well as alleviate systemic inflammation in both the subcutaneous infection model and the wound infection model. Furthermore, this study may contribute to the development of therapeutic agents for antibiotic-resistant bacteria and offer ideas for silver-based bactericides.

Erythema Nodosum following Nocardia Infection: A Case Report.

Cutaneous nocardiosis is a rare bacterial infection that can result in various dermatologic manifestations such as actinomycetoma, lymphocutaneous infection, superficial skin infection, and secondary infection due to hematogenous dissemination. We report on a Chinese patient with erythema nodosum-like exanthema, possibly secondary to nocardiosis. Our diagnosis for this patient was based on the clinical presentation, histopathological evidence, and microbiological findings. Given the protean manifestation of Nocardia, persistent reports on new presentations of the disease are important for early identification and treatment.

The Role of Probiotics in Skin Photoaging and Related Mechanisms: A Review.

Solar ultraviolet radiation (UVR) is the primary pathogenetic factor in skin photoaging. It can disrupt cellular homeostasis by damaging DNA, inducing an inflammatory cascade, immunosuppression, and extracellular matrix (ECM) remodeling, resulting in a variety of dermatologic conditions. The skin microbiome plays an important role in the homeostasis and maintenance of healthy skin. Emerging evidence has indicated that highly diverse gut microbiome may also have an impact on the skin health, referred to as the gut-skin axis (GSA). Oral and topical probiotics through modulating the skin microbiome and gut-skin microbial interactions could serve as potential management to prevent and treat the skin photoaging by multiple pathways including reducing oxidative stress, inhibiting ECM remodeling, inhibiting the inflammatory cascade reaction, and maintaining immune homeostasis. In this review, the effects of oral and topical probiotics in skin photoaging and related mechanisms are both described systematically and comprehensively.

Identification of Significant Genes and Pathways for the Chronic and Subacute Cutaneous Lupus Erythematosus via Bioinformatics Analysis.

Background: Chronic cutaneous lupus erythematosus (CCLE) and subacute cutaneous lupus erythematosus (SCLE) are both common variants of cutaneous lupus erythematosus (CLE) that mainly involve the skin and mucous membrane. Oral mucosal involvement is frequently observed in patients of CLE. Despite that they have different clinicopathological features, whether there is a significant difference in pathogenesis between them remains unclear. Herein, we investigated specific genes and pathways of SCLE and CCLE via bioinformatics analysis. Methods: Microarray expression datasets of GSE109248 and GSE112943 were both retrieved from the GEO database. Differentially expressed genes (DEGs) between CCLE or SCLE skin tissues and health controls were selected by GEO2R. Common DEGs were picked out via the Venn diagram software. Then, functional enrichment and PPI network analysis were conducted, and the top 10 key genes were identified via Cytohubba. Results: Totally, 176 DEGs of SCLE and 287 DEGs of CCLE were identified. The GO enrichment and KEGG analysis of DEGs of SCLE is significantly enriched in the response to virus, defense response to virus, response to IFN-gamma, cellular response to IFN-γ, type I IFN signaling pathway, chemokine activity, chemokine receptor binding, NOD-like receptor signaling pathway, etc. The GO enrichment and KEGG analysis of DEGs of CCLE is significantly enriched in the response to virus, regulation of multiorganism process, negative regulation of viral process, regulation of lymphocyte activation, chemokine receptor binding, CCR chemokine receptor binding, NOD-like receptor signaling pathway, etc. The top 10 hub genes of SCLE and CCLE, respectively, include STAT1, CXCL10, IRF7, ISG15, and RSAD2 and CXCL10, IRF7, IFIT3, CTLA4, and ISG15. Conclusion: Our finding suggests that SCLE and CCLE have the similar potential key genes and pathways and majority of them belong to IFN signatures and IFN signaling pathway. Besides, the NOD-like receptor signaling pathway might also have an essential role in the pathogenesis of SCLE and CCLE. Together, the identified genes and signaling pathways have enhanced our understanding of the mechanism underlying the occurrence and development of both SCLE and CCLE.

Pan-Cancer Analysis of BUB1B/hsa-miR-130a-3p Axis and Identification of Circulating hsa-miR-130a-3p as a Potential Biomarker for Cancer Risk Assessment.

Based on the fact that very little was found in the literature on the question of potential molecules and mechanism for high risk of cancer in patients with psoriasis, this study was designed and performed based on bioinformatics analysis including WGCNA. The most striking result to emerge from the data is that BUB1B/hsa-miR-130a-3p axis, closely related to the development of psoriasis, also plays a remarkable role in multiple cancer development. The expression patterns of hsa-miR-130a-3p were found significantly changed in multiple tumors, which was also associated with prognosis. Additionally, hsa-miR-130a-3p was downregulated in lesion skin of psoriasis, but there was no difference in blood between psoriasis patients and normal controls. Circulating has-miR-130a-3p was found to have a higher level of blood in multiple tumor patients, suggesting that hsa-miR-130a-3p has the potential to be a blood biomarker for cancer risk assessment in patients with psoriasis.

Autophagy plays an essential role in ultraviolet radiation-driven skin photoaging.

Photoaging is characterized by a chronic inflammatory response to UV light. One of the most prominent features of cutaneous photoaging is wrinkling, which is due primarily to a loss of collagen fibers and deposits of abnormal degenerative elastotic material within the dermis (actinic elastosis). These changes are thought to be mediated by inflammation, with subsequent upregulation of extracellular matrix-degrading proteases and down-regulation of collagen synthesis. Autophagy is a vital homeostatic cellular process of either clearing surplus or damaged cell components notably lipids and proteins or recycling the content of the cells' cytoplasm to promote cell survival and adaptive responses during starvation and other oxidative and/or genotoxic stress conditions. Autophagy may also become a means of supplying nutrients to maintain a high cellular proliferation rate when needed. It has been suggested that loss of autophagy leads to both photodamage and the initiation of photoaging in UV exposed skin. Moreover, UV radiation of sunlight is capable of regulating a number of autophagy-linked genes. This review will focus on the protective effect of autophagy in the skin cells damaged by UV radiation. We hope to draw attention to the significance of autophagy regulation in the prevention and treatment of skin photoaging.

Top 100 most-cited publications in hidradenitis suppurativa: An updated bibliometric analysis.

Background: Over the last several decades, our understanding of hidradenitis suppurativa (HS) has improved considerably, thereby enhancing our ability to clinically diagnose and treat the disease. Objective: The purpose of this study was to identify and analyze the top 100 most-cited publications related to HS to update bibliometric information on HS. Materials and methods: We used the Web of Science database to identify reports on hidradenitis suppurativa. Data from the 100 most-cited publications were extracted and analyzed. Results: The citation number of the top 100 most-cited articles was 89-532 (mean, 153.51), with the most productive periods being from years 2007 to 2016. Most publications originated from the British Journal of Dermatology and the Journal of the American Academy of Dermatology. The 100 articles originated from 18 countries, with Denmark being the most productive country, followed by the United States (17), England (14), and Germany (12). Jemec GB, from the University of Copenhagen, had 32 citations and was the most frequently identified author. The 100 articles encompassed several fields of research as follows: pathogenesis (18%), pathophysiology (7%), epidemiology (14%), clinical diagnosis and features (16%), treatment (25%), comorbidity (10%), and others (10%). In total, 11 reviews, three guidelines, and 86 original articles (nine randomized clinical trials) were included. Conclusion: Through this bibliometric analysis, we aimed to indicate a series of intellectual landmark publications that offer us critical reviews, guidelines, and original articles, which highlight the immense level of progress achieved in the field of HS.

Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection.

Cryptococcus neoformans is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how C. neoformans manipulates the host immune response through its pathogenic factors remains incomplete. In this study, we defined the roles of a previously uncharacterized protein, Csn1201, in cryptococcal fitness and host immunity. Use of both inhalational and intravenous mouse models demonstrated that the CSN1201 deletion significantly blocked the pulmonary infection and extrapulmonary dissemination of C. neoformans. The in vivo hypovirulent phenotype of the csn1201Δ mutant was attributed to a combination of multiple factors, including preferential dendritic cell accumulation, enhanced Th1 and Th17 immune responses, decreased intracellular survival inside macrophages, and attenuated blood-brain barrier transcytosis rather than exclusively to pathogenic fitness. The csn1201Δ mutant exhibited decreased tolerance to various stressors in vitro, along with reduced capsule production and enhanced cell wall thickness under host-relevant conditions, indicating that the CSN1201 deletion might promote the exposure of cell wall components and thus induce a protective immune response. Taken together, our results strongly support the importance of cryptococcal Csn1201 in pulmonary immune responses and disseminated infection.