Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial.

BACKGROUND: Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. OBJECTIVES: The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. METHODS: We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well-established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator-controlled, observer-blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. RESULTS: In laboratory investigations, CAP time-dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty-nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p = 0.456) or in the GAIS responder rates (p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. CONCLUSION: CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

Characteristics of fish community structure and environmental driving factors in Taihu Lake during the first year of fishing ban.

Taihu Lake has officially implemented the full fishing ban policy since October 1, 2020. We investigated fish community of Taihu Lake in the four seasons of 2020. A total of 42 fish species were collected, belonging to 6 orders, 7 families, and 33 genera. The first five dominant species ranked by the index of relative importance were Coilia nasus, Toxabramis swinhonis, Hypophthalmichthys molitrix, Hypophthalmichthys nobilis, and Salangichthys tangkahkeii. The number of C. nasus accounted for 85.1% of the total number of catches. According to the distributional characteristics of cyanobacterial blooms and aquatic plants, Taihu Lake could be divided into the northern, central, and eastern regions. There was no significant difference in catch per unit effort (CPUE) among different lake regions, but Shannon diversity index and Pielou evenness index in the eastern region was greater than in the other two regions. The CPUE, Shannon diversity index, and Pielou evenness index were significantly different among the four seasons, with the lowest CPUE in autumn and higher diversity in autumn and winter than in spring and summer. Electrical conductivity, water depth, chloride, and transparency were the main environmental factors driving the seasonal variations of fish community in Taihu Lake, while electrical conductivity, dissolved oxygen, total alkalinity, and transparency were key variables driving the spatial patterns. The results could be used as the baseline data for fish community studies in Taihu Lake after the fishing ban.

Deficiency of Pink1 promotes the differentiation of Th1 cells.

Previous studies have found that Pink1 is crucial for T cell activation and the function of Treg cells. However, the effect of Pink1 on inflammatory Th1 cells is largely unknown. In the process of Th1 differentiation from human naïve T cells, we found a reduction of Pink1 and Parkin. We then focused our attention on the Pink1 KO mice. Although there was no difference in the baseline of the T cell subset of Pink1 KO mice, Th1 differentiation from Pink1 KO naïve T cells in vitro showed a significant increase. Subsequently, we transferred naïve CD4+ T cells into Rag2 KO mice to establish a T-cell colitis mouse model and found that CD4+ T cells in mesentery lymph nodes of mice receiving Pink1 KO cells increased significantly, especially Th1 cells. Intestinal IHC staining also showed that the transcription factor T-bet of Th1 increased. Treatment of CD4+ T cells from lupus-like mice with mitophagy agonist urolithin A, a reduction of Th1 cells was observed, suggesting the clinical value of using mitophagy agonists to suppress Th1-dominated disease in the future.

Exacerbation of psoriasis induced by Nivolumab in a patient with stage IIIc gastric adenocarcinoma: A case report and literature review.

Nivolumab, the programmed cell death 1 inhibitor, is a kind of immune checkpoint inhibitor commonly used to treat advanced cancers. Unfortunately, such drugs often induce various immune-related adverse events involving different body systems, with psoriasis being one of the skin toxicities. We report the clinical features of an exacerbated psoriasis induced by using nivolumab after three days in a patient with stage IIIc gastric adenocarcinoma. At the same time, we searched 27 case reports published from 2015 to 2021 over the world and systematically summarized the clinical manifestation of a total of 44 cases with psoriasis caused or exacerbated by Nivolumab. Commonly traditional treatment could be useful, and small molecule drugs such as apremilast are effective among some patients. However, more studies are needed to evaluate the efficacy and safety of biologics or small molecule drugs in treating psoriasis induced by nivolumab.

An update on epigenetic regulation in autoimmune diseases.

Autoimmune diseases (AIDs) generally manifest as chronic immune disorders characterized by significant heterogeneity and complex symptoms. The discordant incidence of AIDs between monozygotic twins guided people to attach importance to environmental factors. Epigenetics is one of the major ways to be influenced, some of them can even occur years before clinical diagnosis. With the advent of high-throughput omics times, the mysterious veil of epigenetic modification in AIDs has been gradually unraveled, and some progress has been made in utilizing it as indicators of diagnosis and disease activity. For example, the hypomethylated IFI44L promoter in diagnosing systematic lupus erythematosus (SLE). More recently, newly identified noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are also believed to be involved in the etiology of AIDs while the initial factor behind those epigenetic alterations can be diverse from metabolism to microbiota. Update and comprehensive insights into epigenetics in AIDs can help us understand the pathogenesis and further orchestrate it to benefit patients in the future. Therefore, we reviewed the latest epigenetic findings in SLE, rheumatoid arthritis (RA), Type 1 diabetes (T1D), systemic sclerosis (SSc) primarily from cellular levels.

Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus.

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Here we show single-cell RNA sequencing data of cutaneous lesions from DLE and SLE patients and skin tissues from healthy controls (HCs). We find significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20+ keratinocyte, CXCL1+ fibroblast, ISGhiCD4/CD8 T cell, ISGhi plasma cell, pDC, and NK subclusters are identified in DLE and SLE compared to HC. In addition, we observe higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. In summary, we clarify the heterogeneous characteristics in cutaneous lesions between DLE and SLE, and discover some specific cell subtypes and ligand-receptor pairs that indicate possible therapeutic targets of lupus erythematosus.

Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.

Background: The familial clustering phenomenon together with environmental influences indicates the presence of a genetic and epigenetic predisposition to systematic lupus erythematosus (SLE). Interestingly, regarding lupus nephritis (LN), the worst complication of SLE, mortality, and morbidity were not consistent with SLE in relation to sexuality and ethnicity. Summary: Genetic and epigenetic alterations in LN include genes and noncoding RNAs that are involved in antigen-presenting, complements, immune cell infiltration, interferon pathways, and so on. Once genetic or epigenetic change occurs alone or simultaneously, they will promote the formation of immune complexes with autoantibodies that target various autoantigens, which results in inflammatory cytokines and autoreactive immune cells colonizing renal tissues and contributing to LN. Key Messages: Making additional checks for immunopathology-related heredity and epigenetic factors may lead to a more holistic perspective of LN.

Soluble Receptor for Advanced Glycation End Product Is Involved in the Inflammatory Response of Human Adenovirus-Infected Patients.

Human adenovirus (HAdV) infection causes excessive inflammation associated with severe tissue injury, such as pneumonia. The molecules involved in the underlying inflammatory mechanisms remain to be elucidated. Receptor for advanced glycation end product (RAGE) is mainly expressed on immune cells and lung tissues, and it is a key factor in the initiation and development of inflammation. RAGE can be cleaved by metalloprotease 9 (MMP9) to release the extracellular segment, which is named soluble RAGE (sRAGE), into the intercellular space, where it can bind to RAGE ligands and block RAGE activation and subsequent inflammation. In our study, we enrolled HAdV-infected patients and their contacts to examine the relationship between sRAGE and inflammation induced by HAdV infection. The results showed that HAdV infection stimulated inflammatory cytokine secretion, increased such as high mobility group box 1 (HMGB1) levels, and suppressed sRAGE expression. sRAGE levels were significantly different between patients with or without pneumonia. We also found that MMP9 was significantly lower in patients with pneumonia, and it was positively correlated with sRAGE levels over 7 days after disease onset. The mitogen-activated protein kinase (MAPK) pathway is an important immune activation signaling pathway that is regulated by RAGE. We observed the activation of the MAPK pathway in the peripheral blood mononuclear cells (PBMCs) of patients. Negative correlations between sRAGE and phosphorylated JNK and p38 were observed. These results suggest that sRAGE is involved in HAdV-induced inflammatory responses, and might be a potential therapeutic target to alleviate the HAdV-induced excessive inflammation.