Acne sequelae primarily include post-acne erythema, post-acne hyperpigmentation, and post-acne scarring. These residual cutaneous lesions persist in a substantial proportion of patients following the resolution of active acne and arise from factors such as inflammatory responses and inappropriate manipulation of lesions. Acne sequelae are highly prevalent, impose a considerable disease burden, and exert a profound negative impact on patients’ physical appearance, psychological well-being, and quality of life. Although a wide range of therapeutic modalities is currently available and new treatment technologies continue to emerge, substantial variability exists in treatment efficacy, and clinical decision-making remains highly heterogeneous. To promote standardized and evidence-based approaches to the diagnosis, prevention, and management of acne sequelae, an expert panel developed this consensus through a comprehensive review of recently published domestic and international literature, integrated with current clinical practice in China. This consensus is intended to provide practical and authoritative guidance for clinicians in the diagnosis, prevention, and treatment of acne sequelae.

OBJECTIVE:To determine how cutaneous palmitic acid (PA) modulates transient receptor potential vanilloid-1(TRPV1) in nociceptor and dorsal-root-ganglions (DRGs), and Mas-related G protein-coupled receptor B2 (MRGPRB2) in mast cells (MCs), and to investigate their associations with serum- and glucocorticoid-regulated kinase-1 (SGK1)/neural precursor cell expressed developmentally down regulated 4-like (NEDD4L) in atopic dermatitis (AD). METHODS:AD was induced in mice with nedd4l or sgk1 conditional knock-out(cKO) in nociceptor, mrgprb2, nedd4l, or sgk1 cKO in MCs. Intradermal PA, substance P(SP), or pan-palmitoylation inhibitor 2BP was administered. Isolated DRGs and mouse bone-marrow-derived-MCs (mBMMCs) were used. RESULTS:Cutaneous PA levels were increased in AD mice.PA intradermal injection promoted a TRPV1+ nociceptor-SP-MCs MRGPRB2-tryptase-AD axis. nedd4l cKO in nociceptor up-regulated cutaneous SP expression, which was further enhanced by PA. sgk1 cKO in nociceptor slightly reduced SP levels, which were further decreased by PA or 2BP. SP levels in mice with nedd4l or sgk1 cKO in MCs were increased by PA. In DRGs, supernatants from MC903-treated keratinocytes induced SGK1 and NEDD4L phosphorylation, TRPV1 S-palmitoylation, and SP production, all of which were up-regulated by PA; total and S-palmitoylated TRPV1 levels and SP production were increased following nedd4l knockdown, whereas they were slightly reduced following sgk1 knockdown and further decreased by PA. SP induced weak phosphorylation of SGK1 and NEDD4L in MCs. SP induced MRGPRB2 S-palmitoylation and tryptase release in wild-type, nedd4l or sgk1 knock-out MCs, and these effects were enhanced by PA; 2BP caused MRGPRB2 reduction in wild-type and sgk1 knock-out MCs. CONCLUSIONS:The increased cutaneous PA exacerbates AD by promoting TRPV1 S-palmitoylation and SP production in nociceptor, followed by MRGPRB2 S-palmitoylation and tryptase release in MCs. S-palmitoylation promotes TRPV1 whereas inhibits MRGPRB2 reduction via lysosome when NEDD4L and its upstream SGK1 are not phosphorylated.

Psoriasis is a chronic, immune-mediated inflammatory disorder in which neutrophils are central to pathogenesis. While recent studies have implicated the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in psoriasis, its specific role in neutrophil-mediated inflammation remains unclear. To investigate neutrophil function in psoriasis, we integrated single-cell RNA-seq from human lesions with studies in IMQ-treated mouse models (wild-type, STING-/-, PADi4-/-) and HL-60 cells. We employed transcriptomic, cytometric and functional assays to assess neutrophil recruitment, cytokine secretion and neutrophil extracellular trap (NET) formation. Our study revealed significant upregulation of STING expression in both lesional and peripheral blood neutrophils of psoriasis patients. In the IMQ-induced mouse model, STING knockout markedly alleviated disease severity, reduced neutrophil infiltration and suppressed IL-1β release. Mechanistically, STING promoted neutrophil chemotactic migration via the IRF3/NF-κB axis while directly regulating the formation of NETs in neutrophils and the release of cytotoxic mediators. Besides, distinct mouse strains exhibited significant differences in STING pathway activation, indicating genetic heterogeneity in the immunoregulatory mechanisms underlying psoriasis. Collectively, the above findings indicated that STING signalling in neutrophil-mediated psoriatic inflammation not only regulates cell recruitment but also directly drives the terminal effector function of NETs production. Furthermore, strain-specific differences suggest that the regulation of this pathway in the disease context is complex and context-dependent, potentially influencing individualised therapeutic responses. Targeting the STING pathway could serve as a therapeutic strategy to simultaneously inhibit multiple pathogenic processes mediated by neutrophils.

ObjectiveSystemic type 1 interferon (IFN1), which is regulated by intestinal homeostasis, shows potential in inhibiting the immunoglobulin E (IgE) production and Th2 response in vivo. This study aimed to determine the effect of a high-salt diet (HSD) on systemic IFN1, gut microbiota and tight junction protein zonula occludens-1 (ZO-1), intestinal serum- and glucocorticoid-inducible kinase-1 (SGK1), and epithelial sodium ion channels (ENaCs) in atopic dermatitis (AD) mice.MethodsMC903 was applied topically to establish AD in wild-type C57BL/6 mice; in mice with IFN1 receptor-1 (ifnar1) knockout, sgk1 conditional knockout (cKO) in intestinal epithelial cells (IECs), or stimulator of interferon genes (sting) cKO in dendritic cells (DCs); and in BDCA2-DTR mice with plasmacytoid DC (pDC) deletion.ResultsHSD significantly promoted AD accompanied by higher levels of serum IgE, IL-4/IL-13, ileum SGK1, phosphorylated SGK1, βENaC and γENaC, and skin sodium, but lower levels of serum IFN1, ileum ZO-1, gut Lactobacillus_murinus, and Lactobacillus_reuteri. Lactobacillus gavage alleviated AD, reduced serum IgE and IL-4/IL-13, and increased serum IFN1 and ileum ZO-1 in AD mice on HSD, which were largely counteracted by ifnar1 knockout, pDC deletion, or sting cKO in DCs, but not in IECs. cKO of sgk1 in IECs alleviated AD, slightly reduced the serum IgE and IL-4/IL-13, and significantly reduced the ileum βENaC and γENaC and the skin sodium in mice on HSD without changing the gut microbiota, ileum ZO-1, and serum IFN1 levels.ConclusionHSD promotes AD by partially impairing the systemic IFN1 production that is orchestrated by STING signaling in DCs by reducing the gut Lactobacillus and by partially increasing the sodium accumulation in skin lesions via driving the ileum SGK1 phosphorylation and βENaC and γENaC expression. Further research is necessary to assess the effect of Lactobacillus supplementation on clinical AD patients with an HSD habit.

Hidradenitis suppurativa (HS), also known as acne inversa (AI), is a chronic, recurrent inflammatory disease of the pilosebaceous unit that primarily affects intertriginous areas and is characterized by recurrent, painful, deep-seated inflammatory lesions. The pathogenesis of HS/AI is multifactorial, involving genetic susceptibility, immune dysregulation, microbial imbalance, and obesity. HS/AI remains difficult to manage, and current treatment aims to reduce the frequency and duration of flares, decrease disease severity, and improve quality of life. Treatment selection should be guided by disease severity and activity. Pharmacologic therapies include antibiotics, biologics, small-molecule agents, retinoids, and immunosuppressants, while adjunctive approaches include surgical interventions and energy-based therapies. This updated consensus aims to standardize the diagnosis and management of HS/AI in China and to improve clinical practice by providing a stepwise, multidisciplinary treatment framework in which interventions are stratified according to disease severity and recommendation strength. Recommendation strength was determined by expert voting: an agreement rate of ≥85% indicated “Should be recommended,” ≥75% to <85% indicated “Could be recommended,” ≥50% to <75% indicated “May be considered,” and <50% indicated “No consensus reached.” Key recommendations reaching the ≥85% agreement threshold included severity-based treatment selection, topical clindamycin for mild localized disease, systemic tetracyclines for mild-to-moderate HS/AI, and biologics, including adalimumab, secukinumab, and bimekizumab, for moderate-to-severe disease. The consensus has been registered on the International Practice Guidelines Registry Platform (No: PREPARE-2025CN1964).

Background Transdermal drug delivery technologies (TDDTs) enhance drug absorption and therapeutic outcomes in dermatology, yet standardized, evidence-based recommendations for their clinical application remain lacking. Objective To provide expert consensus recommendations on the clinical application of TDDTs, with a focus on fractional lasers and microneedles. Methods A multidisciplinary panel of 25 experts systematically reviewed current literature and clinical practices. The consensus was developed using the Grading of Recommendations Assessment, Development and Evaluation framework to assess evidence quality and recommendation strength and the modified Delphi method to achieve expert agreement. Results Evidence-based recommendations were formulated for the use of TDDTs in a variety of dermatological conditions, including cutaneous malignancies and precancerous lesions, viral warts, inflammatory and autoimmune skin diseases, and cosmetic indications. Conclusion Fractional lasers and microneedles are valuable transdermal delivery tools for dermatological therapy. This expert consensus provides practical, evidence-based guidance to support their safe and effective clinical use.

ABSTRACT Background Atopic dermatitis (AD) impairs quality of life due to chronic eczema and pruritus, while conventional emollients as adjunctive therapy show suboptimal treatment efficacy due to inadequate anti‐inflammatory and antipruritic activity. Objectives To evaluate the treatment efficacy and safety of HBL incorporated with CAPCS in patients with mild AD. Method In this trial, 200 AD patients were randomized (1:1) to receive either the HBL group (HBL incorporated with CAPCS) or the control group (HBL without CAPCS) three times daily for 4 weeks. The primary outcome was the proportion of patients achieving an EASI50 response at week 2. Secondary outcomes included changes from baseline in EASI, DLQI, NRS, and IGA scores at weeks 2 and 4. Results At week 2, the HBL group demonstrated significantly higher achievement in EASI score reduction than that in the control group, both for the EASI50 (37.0% vs. 19.0%) and the EASI75 (15.0% vs. 3.0%), and these differences continued into week 4. Greater reductions in EASI, DLQI, NRS, and IGA scores were observed within the HBL group. Adverse events were mild and temporary. Conclusion HBL incorporated with CAPCS demonstrates efficacy in improving skin lesions, symptoms, and quality of life in mild AD, supporting its role as an adjunctive therapy.

Background Atopic dermatitis (AD) is burdensome. AD with head, face and neck (HFN) involvement seems more strongly associated with quality-of-life impairment than other locations. Aim To investigate how HFN involvement affects the psychological and economic burden of AD in elderly population. Methods We evaluated elderly patients with AD using the eczema area and severity index (EASI), patient-oriented eczema measure (POEM), worst itch numerical rating scale (WI-NRS), dermatology life quality index (DLQI), and hospital anxiety and depression scale. Additionally, we collected data on annual direct medical costs to assess economic burden. Results A total of 3,066 elderly patients with AD were included in the study and 1375 (44.85%) patients had HFN involvement. Compared to patients without HFN involvement, patients with HFN involvement showed a greater proportion of hand, foot, breast and perianal/genital areas involvement and exhibited a higher prevalence of severe AD signs, severe AD symptoms, severe itching, moderate to severe anxiety, and moderate to severe depression, as well as annual direct medical cost. Limitations This study has several limitations; there is potential for selection and recall bias due to its reliance on data from tertiary hospitals and patient-reported outcomes, and statistical bias from using binary logistic regression rather than ordinal regression methods. Conclusion In this real-world study, HFN involvement had significant effects on clinical presentation and disease burden among elderly patients with AD. These findings could guide clinicians in formulating tailored treatment strategies and evaluating disease prognosis in elderly patients with AD.

Dermatology and Plastic Surgery Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China. Conflict of interest: All authors declare no conflicts of interest. Received 2022-12-13, Revised: 2023-1-31, Accepted: 2023-3-31 *Corresponding author: Dr. Fei Hao, Dermatology and Plastic Surgery Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China. E-mail: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Objective: IgE/antigen (Ag)-mediated systemic anaphylaxis (SA) involves alterations in type 1 interferon (IFN1), vitamin D3(VD3) and the gut microbiota. However, their interactions remain largely unknown. This study aimed to investigate the interactions between IFN1 and VD3 signalling at steady-state and their relationships with the gut microbiota underlying SA. Methods: Female adult C57BL/6 mice lacking IFN1 alpha receptor subunit 1 (Ifnar1, Ifnar1−/−), immune-related GTPase family M protein 1 (Irgm1, Irgm1−/−) or VD3 receptor (Vdr, Vdr−/−) were intravenously (IV) administered with IgE/Ag to induce passive SA (PSA) or intraperitoneally (IP) administered ovalbumin (OVA) on days 1, 15, and 29, followed by IV OVA on day 43 to induce active SA (ASA). IFNα (5000 U, 2 doses) and IFNα (3500 U, 12 doses) were IP administered in PSA and ASA models, respectively. Supplementation of VD3 (VD3-rich diet for 3 weeks) or bacteria (oral administration daily for 6 weeks) was performed. The effects of IFN1 and VD3 signalling on the activation of murine bone marrow-derived mast cells (mBMMCs) were tested in vitro. Results: Compared to wild-type (Wt) mice, both PSA and ASA were more severe in Ifnar1−/− or Vdr−/− mice (with greater severity in Ifnar1−/− than in Vdr−/− mice), but were significantly attenuated in Irgm1−/− mice. The inhibitory effects of exogenous IFNα on PSA and OVA-IgE production were partially impaired in Vdr−/− mice, while the inhibitory effects of exogenous VD3 remained intact in Ifnar1−/− mice. At steady state, the serum VD3 levels decreased in Ifnar1−/− and increased in Irgm1−/− mice, whereas the serum IFN1 levels remained unchanged in Vdr−/− mice. During IgE production, endogenous IFN1 and VD3 expressions, along with faecal Alistipes and Bacteroides, decreased. Oral supplementation with Bacteroides significantly inhibited IgE production via the IFN1/VD3 axis, whereas Alistipes moderately reduced IgE production by slightly upregulating VD3 expression independent of IFN1 modulation. Both spontaneous- and induced-degranulation were more prominent in Vdr−/− than in Ifnar1−/− mBMMCs. IgE/Ag stimulation led to a greater reduction in membrane IFNAR1 in Vdr−/− than in Wt mBMMCs. Inhibition of P38 and PKD2 kinase significantly and partially rescued membrane IFNAR1 expression in Vdr−/− mBMMCs, respectively. Exogenous VD3 could reverse the IFNAR1 reduction and thereby enhance IFNα-mediated anti-degranulation in Wt mBMMCs, an effect that was lost in Vdr−/− mBMMCs. Conclusions: These findings demonstrate that IFN1 homeostasis is more relevant for limiting SA, partially through maintaining VD3 expression. A reduction in gut Bacteroides promotes IgE production by disrupting the IFN1/VD3 axis in vivo. VD3 appears more potent than IFNα in exerting anti-degranulation effects, as it antagonises the downregulation of membrane IFNAR1 on mBMMCs in vitro.

Despite growing awareness on hand eczema (HE) in Western countries, public attention to HE in China is limited. We aimed to investigate the clinical characteristics of HE and examine its association with atopic dermatitis in the Chinese population. A multicenter cross-sectional study was conducted across 23 tertiary hospitals in China between September 2018 and November 2019. Patients with HE completed a survey covering demographics, allergic diseases, and HE-specific characteristics and underwent patch testing. Clinical severity was assessed using the Hand Eczema Severity Index. Binary logistic and linear regression models were used. In total, 2072 patients with HE were included (mean age = 39.8 years, 60.6% female). The most common HE subtype was allergic contact dermatitis, followed by irritant contact dermatitis. One third had moderate-to-very-severe HE, and at least 64.3% had chronic HE. The positive patch test rate was 50.7%. Approximately one quarter had a physician-confirmed diagnosis of atopic dermatitis that was associated with greater HE severity, longer persistence of HE, higher disease burden, and altered contact sensitization patterns in patients with HE. This study indicates that addressing both HE and atopic dermatitis might improve prognosis and QOL for affected individuals, emphasizing the need for targeted preventions and management strategies for this patient population.

Diabetic foot ulcer (DFU) is a severe diabetes complication characterized by impaired angiogenesis and chronic inflammation, leading to delayed wound healing. Exosomes (Exo) derived from hypoxic adipose-derived stem cells (H-ADSCs-Exo) show potential as therapeutic carriers. This study investigates the role of H-ADSCs-Exo carrying miR-100-5p in DFU healing. ADSCs were isolated, characterized, and their Exo analyzed via transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Transcriptome sequencing identified miR-100-5p as a key modulator of angiogenesis and inflammation. In vitro, H-ADSCs-Exo enhanced human umbilical vein endothelial cell and fibroblast proliferation, migration, and tube formation. In a rat DFU model, H-ADSCs-Exo administration reduced ulcer size, increased angiogenesis (VEGF/CD31 expression), and decreased inflammatory markers (TNF-α, IL-6). miR-100-5p overexpression further amplified these effects, demonstrating its critical role in Exo-mediated healing. These findings highlight the therapeutic potential of H-ADSCs-Exo in DFU treatment, offering insights into cell signaling mechanisms and paving the way for miRNA-based regenerative therapies.

The cGAS-STING signaling pathway is a major component of innate immunity. It is critical for identifying cytoplasmic DNA, triggering immune responses, and is linked to several diseases and malignancies. The inflammatory infiltrates and elevated cytokine expression characteristic of dermatological inflammatory disorders have drawn attention to the potential role of the cGAS-STING pathway, positioning it as an emerging focus of scientific investigation. Therapeutic strategies targeting the cGAS-STING signaling axis have been explored for the treatment of inflammatory dermatoses, with several inhibitor classes under investigation, such as cGAS inhibitors, STING palmitoylation blockers, STING trafficking suppressors, and nanoformulated inhibitors. Nevertheless, there are problems in both this pathway and drug research still left to be solved: inhibitors are not generally specific enough, drugs are not generally bioavailable enough, and there is an imbalance between the two—immunosuppression and the immune response. The several possible approaches in the future directions include combination therapy, multi-omics integration, and precision medicine approaches to treat these diseases. Given its broad immunomodulatory effects, there is high potential for clinical application of the cGAS-STING pathway modulators.

Chronic spontaneous urticaria (CSU), characterized by recurrent wheals and/or angioedema persisting for more than 6 weeks, represents a substantial clinical challenge. Although international guidelines endorse second-generation H1-antihistamines (sgAHs) as first-line therapy, up to 50% of patients remain refractory even at quadruple doses, significantly compromising quality of life and mental well-being. Notably, standardized guidelines for managing H1 antihistamine-resistant CSU are currently lacking. To address this gap, we aimed to develop an evidence-based clinical practice guideline for the diagnosis, assessment, and step-wise treatment of H1 antihistamine-resistant CSU. A multidisciplinary panel conducted a systematic literature review and through multiple rounds of group discussions, both offline and online, to draft recommendations. Evidence was graded using the Oxford CEBM 2011 system and recommendations assigned GRADE strengths. This guideline provides a standardized, personalized treatment algorithm for H1 antihistamine-resistant CSU, aiming to improve clinical efficacy, reduce socioeconomic burden, and direct future research toward validating novel agents such as JAK inhibitors and optimizing long-term outcomes.

Importance:Treatment of facial flushing and erythema for patients with erythematotelangiectatic rosacea (ETR) is challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) therapy may be beneficial for treating ETR; however, it has not been rigorously evaluated in a randomized clinical trial. Objective:To evaluate the efficacy of taVNS for ETR compared with sham stimulation (SS). Design, Setting, and Participants:Enrollment for this single-center, randomized, double-blind, sham-controlled device clinical trial was initiated in February 2024 and ended in August 2024. The follow-up period ended in February 2025, and data were analyzed in March 2025. Patients with ETR that was accompanied by a Clinician's Erythema Assessment (CEA) score of at least 2 were selected from the Department of Dermatology of Southwest Hospital in China. Interventions:Patients were allocated to the taVNS group (stimulation pulses at a frequency of 30 Hz and a pulse width of 200 μs for 30 minutes per day) or the SS group at a 1:1 ratio. Both groups received 3 weeks of treatment and 24 weeks of follow-up. Main Outcomes and Measures:The primary outcome was CEA score after 3 weeks of treatment. The secondary outcomes included improvements in erythema and facial flushing, sleep disorders, migraine, anxiety, fatigue, and depression, as measured via clinical tools. Results:Seventy-two participants (67 female individuals [93.1%]; median [IQR] age: 29.5 [24.0-36.0] years) with ETR were randomized into either the taVNS (36 [50.0%]) or SS groups (36 [50.0%]). At 3 weeks, the mean (SD) CEA score was lower in the taVNS group than the SS group (1.56 [0.84] vs 2.47 [0.81]; mean difference, -0.92; 95% CI, -1.3 to -0.53; P < .001). Moreover, taVNS also reduced the severity of anxiety (mean difference, -5.42; 95% CI, -8.11 to -2.73; P < .001) and depression (mean difference, -6.22; 95% CI, -9.69 to -2.75; P < .001). This relief persisted until the follow-up period. The effects on sleep disorders, migraine, and fatigue were consistent with the previously described indicators. Adverse events were not common for taVNS (2 of 36 [5.6%]) and SS (3 of 36 [8.3%]). Conclusions and Relevance:This randomized clinical trial demonstrated that treating ETR with taVNS concurrently ameliorated cutaneous symptoms and systemic comorbidities, and the results suggest that taVNS is a novel therapeutic option for ETR management. Trial Registration:Chinese Clinical Trial Register Identifier: ChiCTR2400080637.

Lupus nephritis causes kidney failure in systemic lupus erythematosus. We asked whether raising levels of the TAX1BP1 could slow this damage. Using mice with lupus-like disease, we delivered a gene therapy that increased TAX1BP1 in kidney tubule cells. After four weeks, treated animals showed smaller lymph nodes and spleens, lower anti-DNA antibodies and serum creatinine, and less protein in the urine. Kidney fibrosis, judged by collagen staining, was markedly reduced. Single-cell sequencing revealed that TAX1BP1 was highest in proximal tubule cells and linked to decreased Galectin-3, a known driver of fibrosis. Immunofluorescence confirmed lower Galectin-3 and fewer α-SMA + macrophages, indicating fewer cells transitioning into myofibroblasts. We conclude that boosting TAX1BP1 in proximal tubule cells limits kidney fibrosis by reducing Galectin-3 and blocking macrophage-to-myofibroblast transition, offering a potential new strategy against lupus nephritis.

This study aimed to investigate the association between serum metabolomic profiles and the gut microbiota in patients with neurogenic rosacea. We analyzed the serum metabolites and gut microbial composition in 20 patients with neurogenic rosacea and 14 healthy controls. Metabolomic analysis identified 56 differentially abundant metabolites (DAMs), with benzene and substituted derivatives, carboxylic acids and derivatives, and organophosphates being among the most enriched categories. Gut microbiota analysis revealed significant dysbiosis in patients with neurogenic rosacea, characterized by an increased abundance of Lachnospiraceae, Veillonellaceae, and Clostridiaceae, and decreased levels of Prevotellaceae and Bifidobacteriaceae. Spearman’s correlation analysis demonstrated significant relationships between specific serum metabolites and gut microbial taxa, including strong positive correlations between 3,4-dihydroxyphenylacetic acid and both Bifidobacterium (r = 0.7307, padj = 9.25e-07) and Lactobacillus (r = 0.6898, padj = 6.39e-06). These findings highlight the complex interactions between metabolic dysregulation and gut microbial imbalances in neurogenic rosacea, suggesting a potential role for the gut-skin axis in its pathophysiology. This study paves the way for future therapeutic strategies targeting both metabolic and microbial dysbiosis to manage neurogenic rosacea.

OBJECTIVES:Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterised by multi-organ involvement. The onset and progression of SLE are closely associated with the excessive release of various inflammatory factors. Integrin αvβ3, a key member of the integrin protein family, plays an essential role in inflammation. This study aimed to elucidate the molecular mechanism of the NF-κB pathway mediated by integrin αvβ3 in systemic lupus erythematosus (SLE) and further investigate its role in the pathogenesis of SLE. METHODS:We collected relevant data from 36 patients with systemic lupus erythematosus and 36 healthy control subjects using. Western blot and immunohistochemistry staining to explore the mechanisms of SE in vivo and in vitro. We used Student's t-test, ANOVA and post-hoc Kruskal-Wallis tests for data analysis. RESULTS:Our results demonstrate that elevated expression of integrin αvβ3 in the serum, skin, and renal tissues of patients with SLE contributes to the activation of NF-κB, a critical initiator of inflammatory responses in SLE. Specifically, the synthesis of NF-κB p65 and NF-κB p100 is enhanced, promoting NF-κB activation, leading to the dysregulation of TLR7 expression. This induces an increase in inflammatory factors such as TNF-α and IL-6, making organs such as the skin and kidneys more susceptible to inflammation. Moreover, our findings indicate that the administration of the integrin αvβ3 antagonist SB273005 in the MRL/lpr lupus mice model significantly reduces the synthesis of NF-κB p65/p100, suppresses NF-κB activation, decreases levels of inflammatory factors in the serum and kidneys, and alleviates organ damage in MRL/lpr lupus mice. CONCLUSIONS:This study highlights that the upregulation of integrin αvβ3 expression in SLE activates the NF-κB p65/p100 pathway, which plays a pivotal role in orchestrating inflammatory responses.

Objective:To profile spinal medium- and long- chain fatty acids (ML-CFAs) and itch-related gene expressions (IRGEs) in dorsal root ganglion (DRG), and investigate the role of spinal palmitic acid (PA) in atopic dermatitis (AD), and its relationship with DRG and spinal extracellular signal-regulated kinase (ERK). Methods:MC903 was applied topically to the nape of C57BL/6 mice to induce AD. Two doses of PA were administered intrathecally during MC903 treatment, and several antagonists were administered intrathecally one day before PA challenge. Transcriptome sequencing was performed on DRGs, and 36 ML-CFAs in the spinal cord were analyzed. Results:A global upregulation of IRGEs in DRGs and increases in major ML-CFAs including PA in the spinal cord were observed in adult AD model. MC903 resulted in less severe dermatitis with weaker IRGEs in DRGs and lower spinal ML-CFAs in senile than adult mice. In adult mice, intrathecal PA injection caused acute scratches, aggravated AD, and induced stronger IRGEs in DRGs. Intrathecal injection of transient receptor potential vanilloid-1 channel (TRPV1) antagonist capsazepine or Mas-related G protein-coupled receptor D (MRGPRD) antagonist d-Pro7-ANG-(1-7) remarkably halted PA/MC903-induced dermatitis and PA-induced scratching. Administration of histamine h4 receptor antagonist JNJ7777120 only moderately alleviated dermatitis, with no notable effect on scratches. Intrathecal pan-palmitoylation inhibitor 2-Bromopalmitate moderately alleviated MC903/PA-induced lesions and spinal ERK phosphorylation. Intrathecal lidocaine markedly suppressed both lesions and ERK phosphorylation, along with a global reduction in IRGEs in DRGs. Finally, PA-induced scratches were significantly improved by intrathecal lidocaine but not 2-Bromopalmitate. Conclusion:MC903-induced AD develops more readily in adult than senile mice, with consistent changes in IRGEs in DRG and spinal ML-CFA levels, including PA. Spinal PA promotes AD involving spinal TRPV1 and MRGPRD signaling, and IRGEs increments in DRG. Intrathecal lidocaine suppresses AD aggravated by PA via inhibiting spinal ERK phosphorylation and reducing IRGEs in DRG.