Fecal microbiota transplantation for the treatment of chronic inflammatory skin diseases.

The regulation of immune functions and the maintenance of homeostasis in the internal environment are both integral to human gut microbiota (GM). If GM is disturbed, it can result in a range of autoimmune diseases, including chronic inflammatory skin conditions. Chronic inflammatory skin diseases driven by T or B-cell-mediated immune reactions are complex, including the most prevalent diseases and some rare diseases. Expanding knowledge of GM dysbiosis in chronic inflammatory skin diseases has emerged. The GM has some causal roles in the pathogenesis of these skin conditions. Targeting microbiota treatment, particularly fecal microbiota transplantation (FMT), is considered to be a promising strategy. FMT was commonly used in intestinal diseases by reshaping and balancing GM, serving as a reasonable administration in these skin inflammatory diseases. This paper summarizes the existing knowledge of GM dysbiosis in chronic inflammatory skin diseases and the research data on FMT treatment for such conditions.

Systemic comparison of molecular characteristics in different skin fibroblast senescent models.

BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS: Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.

HSP90-regulated mitophagy can alleviate heat stress damage by inhibiting pyroptosis in the hepatocytes of Wenchang chickens.

Heat shock protein 90 (HSP90) has a recognized anti-heat stress injury effect, but its function and corresponding molecular mechanism in heat-stressed hepatocytes are not fully understood, especially in tropical animals. In the present study, we identified several key factors affecting resistance to injury liver tissues from heat-stressed Wenchang chickens (a typical tropical species), such as HSP90, cellular pyroptosis and mitophagy. Heat stress upregulated the NLRP3/Caspase-1/GSDMD-N-mediated cellular pyroptosis pathway and the Pink1/Parkin-mediated mitophagy pathway in chicken hepatocytes, accompanied by the upregulation of HSP90. We also found that HSP90 overexpression significantly reduced heat stress-induced hepatocyte pyroptosis and enhanced mitophagy in primary hepatocytes from Wenchang chickens (PHWCs). HSP90 knockdown significantly increased heat stress-induced hepatocyte pyroptosis and decreased mitophagy in PHWCs. Interestingly, we performed immunoprecipitation and immunofluorescence colocalization and found that HSP90 and Pink1 can interact and directly regulate the level of mitophagy in PHWCs. Our results suggest that HSP90, which regulates Pink1, is an important factor in mitophagy that attenuates heat stress injury by inhibiting cellular pyroptosis.

The synthesis and bioactivity of apigenin derivatives.

BACKGROUND: Apigenin, a naturally occurring compound with a flavone core structure, is known for its diverse bioactivities, including anti-inflammation, anti-toxicant, anti-cancer and so on. There has been significant interest in the medicinal chemistry community. To address these challenges, researchers have developed various derivatives of apigenin to address challenges such as poor water-solubility and low intestinal absorption, aiming to enhance the pharmacological activities and pharmacokinetic properties of this compound. OBJECTIVE: In recent years, there has been a proliferation of apigenin derivatives with enhanced bioactivity. However, there is a lack of comprehensive reviews on the function-based modification of these derivatives. In this paper, we provide an overview of the apigenin derivatives with varying bioactivities and explored their structure activity relationships. And the functions of different groups of apigenin derivatives were also analyzed. CONCLUSION: This review summarized the current achievements that could provide some clues for further study of apigenin-based drugs.

Proteomics analysis for key molecules in adrenal glands of Wenchang chickens for their resistance to heat stress.

Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.

Dye-doped cellulose nanocrystals as novel dusting powders for visualizing latent fingerprints.

Powder-dusting method based on the visual contrast between the background surface and powder-covered ridges of a fingerprint is widely used to develop the invisible latent fingerprints (LFPs) left at crime scenes. Recently, the development of nano-sized powders with excellent optical performances has been extensively explored. In this work, we employed environmentally friendly and low-toxicity cellulose nanocrystals as the novel support. Using dye-doped cellulose nanocrystals as novel dusting powders, two dyes (phenylfluorone and curcumin) were adsorbed on the cellulose nanocrystals by a simple batch adsorption method. The dye-doped cellulose nanocrystals (namely, phenylfluorone-doped cellulose nanocrystals (PDCN) and curcumin-doped cellulose nanocrystals (CDCN)) containing 2% of the loaded mass of both the dyes with bright green fluorescence were developed to visualize LFPs on the surfaces of various substrates (such as glass slide, printing paper, orange plastic card, tile, stainless steel, compact disc, red plastic packing, copper foil and aluminum foil). Images of the LFPs can been obtained by both the dye-doped cellulose nanocrystals with sufficient affinity to the ridges of LFPs. High-quality ridge details with features at the second and third level can be detected by CDCN, whereas PDCN only display the secondary-level features of ridge details. Compared with PDCN, CDCN illustrate higher sensitivity, higher selectivity, and better contrast, especially for detecting fresh and non-fresh LFPs on porous and non-porous substrates, and has the potential for practical use in forensic science.

A double-blind pilot study of oral baricitinib in adult patients with lupus erythematosus panniculitis.

Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well-being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]-active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI-A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active-(CLASI-A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI-A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI-A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.

Langerhans cells and skin immune diseases.

Langerhans cells (LCs) are the key antigen-presenting cells in the epidermis in normal conditions and respond differentially to environmental and/or endogenous stimuli, exerting either proinflammatory or anti-inflammatory effects. Current knowledge about LCs mainly originates from studies utilizing mouse models, whereas with the development of single-cell techniques, there has been significant progress for human LCs, which has updated our understanding of the phenotype, ontogeny, differentiation regulation, and function of LCs. In this review, we delineated the progress of human LCs and summarized LCs' function in inflammatory skin diseases, providing new ideas for precise regulation of LC function in the prevention and treatment of skin diseases.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.