Jie Yang

Objective: Rosacea is a common chronic inflammatory skin disease with unclear pathogenesis and limited treatment options. While the therapeutic efficacy of tranilast (TR) in rosacea has been established, the molecular mechanisms underlying this effect remain to be elucidated. Given that TR is known to suppress macrophage-mediated inflammation, this study aimed to investigate the underlying macrophage-related mechanisms in the anti-rosacea action of TR. Methods: J774A.1 cells were used for in vitro experiments, whereas a cathelicidin antimicrobial peptide LL-37 induced rosacea-like dermatitis model was established for in vivo studies; all animals were randomly allocated to groups. On the final intervention day, areas of erythema on mouse skin lesions were compared. Pathological changes were assessed via hematoxylin–eosin staining. Expression of key proteins in the Toll-like receptor 4 (TLR4)-mediated and NOD-like receptor family pyrin domain-containing 3 (NLRP3) mediated inflammtory pathways was evaluated by immunofluorescence staining and Western blotting. Immunohistochemical staining was conducted to assess F4/80 expression, and Western blotting was utilized to quantify protein expression levels of cathelicidin antimicrobial peptide and vascular endothelial growth factor. Data from multiple groups were compared using one-way analysis of variance. Results: TR alleviated symptoms of rosacea-like inflammation in mice, as demonstrated by the following findings: Erythema area decreased from 20.26 ± 1.44 mm ² in the LL-37 group to 9.10 ± 1.21 mm ² in the LL37+TR group ( P < 0.001), and a significant reduction in dermal inflammatory cell infiltration was found (LL-37 group vs. LL37+TR group, 342.20 ± 35.17 vs. 130.20 ± 19.92, P < 0.001). Western blotting showed pronounced downregulation of vascular markers cathelicidin antimicrobial peptide and vascular endothelial growth factor; immunofluorescence staining indicated that TR effectively reduced the expression levels of TLR4, TNF-α, and NLRP3. Western blotting further demonstrated reduced protein expression of TLR4, MyD88, p-p65, TNF-α, NLRP3, and IL-1β, whereas immunohistochemical staining showed a significant decrease in F4/80+ macrophage infiltration (13.20 ± 1.48 vs. 1.60 ± 0.55, P < 0.001). In both LL-37– and lipopolysaccharide-stimulated J774A.1 cells, TR consistently attenuated TLR4–MyD88–NF-κB signaling and NLRP3 inflammasome activation. The TLR4 inhibitor TLR4-C34 similarly suppressed NLRP3 expression, confirming TLR4 as an upstream regulator of NLRP3. Conclusion: Our findings demonstrate that TR ameliorates rosacea-like inflammation both in cell cutures and mice models, possibly through regulation of TLR4–MyD88–NF-κB signaling and NLRP3-mediated macrophage inflammatory responses, suggesting its therapeutic potential for rosacea, however, further clinical studies are warranted to validate its efficacy and safety.

Background: It is well recognized that developing new animal models, refining the existing mouse models, and thoroughly characterizing their features are essential for gaining a deeper understanding of rosacea pathogenesis and for advancing therapeutic strategies in this direction. Accordingly, we aimed to characterize the pathological features of a long‐term LL‐37‐induced mouse model of rosacea and to compare the disease manifestations and pathophysiological characteristics between short‐term and long‐term LL‐37‐induced models. A key focus was to investigate differential gene expression and the underlying mechanisms of immune system dysregulation in these models. Methods: We comparatively assessed skin lesion manifestations, the extent of inflammatory infiltration, sebaceous gland alterations, fibrosis, and angiogenesis in both models. Assessments were performed using photographic documentation, hematoxylin–eosin (HE) staining, Van Gieson's (VG) staining, immunohistochemistry, and Western blotting. Furthermore, we employed RNA sequencing to analyze differential gene expression in mouse skin. The RNA sequencing data were validated using immunofluorescence staining and Western blotting, with a specific focus on gene variations and mechanisms related to immune system dysregulation. Results: Mice subjected to long‐term LL‐37 induction developed rosacea‐like pathological features, including angiogenesis, thickened skin tissue, and sebaceous gland hypertrophy. In the short‐term LL‐37‐induced model, immune dysregulation primarily involved the innate immune response. However, long‐term LL‐37 induction resulted in significant activation of both innate and adaptive immune responses. Conclusion: The long‐term LL‐37‐induced mouse model offers a valuable animal model for the detailed investigation of the pathological mechanisms driving moderate‐to‐severe rosacea with prolonged disease duration. Importantly, this model provides a significant experimental foundation for exploring the potential role of immune system dysregulation in rosacea pathogenesis.

Rosacea is a chronic inflammatory skin disorder that can lead to fibrosis. However, the mechanisms underlying fibrosis in the later stages of rosacea have been less thoroughly investigated. Interleukin‐17A (IL‐17A) has been implicated in both inflammation and organ fibrosis; however, the effectiveness and mechanism of IL‐17A‐neutralizing antibodies in the later stages of rosacea‐related fibrosis remain unclear. In this study, we induced rosacea‐like lesions in mice using LL‐37 and administered IL‐17A‐neutralizing antibodies. The results indicated that the IL‐17A‐neutralizing antibodies alleviated skin damage, reduced skin thickness, and decreased the secretion of inflammatory factors (TNF‐α, CAMP, TLR4, P‐NF‐kB), angiogenesis‐related factors (CD31, VEGF), and the TGF‐β1 signaling pathway, along with factors associated with epithelial–mesenchymal transition and the deposition of fibrosis‐related proteins (COL1) in the rosacea‐like mouse models. Furthermore, the IL‐17A‐neutralizing antibodies effectively diminished the expression of IL‐17, IL‐17R, CXCL5, and CXCR2 in the skin. Our findings demonstrate that IL‐17A‐neutralizing antibodies inhibit the activation of the CXCL5/CXCR2 axis in rosacea‐like skin tissue, thereby ameliorating inflammation and fibrosis associated with the condition.

Purpose: Most of the existing studies focus on the early inflammation of rosacea, with few interventions on the later development of fibrosis and the relationship between thalidomide and rosacea. The purpose of this study was to construct a long-term induction model and explore the effects of thalidomide on the later stage of inflammation and early stage of fibrosis in rosacea. Patients and Methods: BALB/c male mice were randomly divided into four groups: control group, control plus thalidomide group, LL-37 group and LL-37 plus thalidomide group, Intradermal and intraperitoneal injections were given. After repeated induction, skin changes were recorded by taking photos. The animals were sacrificed, the back skin was used for HE staining and VG staining to detect histomorphological characteristics. Immunofluorescence staining and Western blot were used to detect the expression of inflammatory and fibrosis-related factors. Results: The results were compared with the early stage of the model, wherein the skin inflammation of the 20-day mice was more obvious with a trend of fibrosis. Compared with the control group, histopathological examination showed that the inflammatory cell infiltration in the LL-37 group was significantly increased, and the skin was thickened with collagen deposition. LL-37 induction significantly increased the expression of inflammatory markers (eg, TNF-α and IL-1β) and fibrotic markers (eg, COL1, α-SMA, vimentin and N-Cadherin). Intervention with thalidomide significantly reduced erythema, inflammatory cell infiltration, collagen deposition, and down-regulate the expression of inflammation and fibrosis related factors in rosacea mice. Conclusion: The long-term continuous induction of LL-37 in mice could simulate the occurrence and development of rosacea, and thalidomide could ameliorate the rosacea induced by long-term exposure to LL-37 by regulating inflammatory infiltration, collagen deposition and fibrosis-related processes.

Background: Verruca plana is a benign proliferation of the skin caused by human papilloma virus (HPV) infection. Fresh garlic can serve as an alternative therapy, and it has shown considerable effectiveness as a topical treatment for verruca plana. However, topical garlic treatment for verruca plana triggered Koebner phenomenon (KP), which has not been previously reported.Aim: The aim of our report is to explore the possible causes of this adverse reaction.Method: We here describe a 20‐year‐old female patient who developed a beaded rash after garlic treatment for facial wart plana, known as autoinoculation or KP.Results: Garlic may have caused damage to the surrounding normal skin through primary irritation or allergic reactions. Then, the HPV virus on the primary verruca plana took the opportunity to spread to the surrounding skin injured by garlic stimulation, triggering the KP.Conclusion: When using garlic to treat verruca plana, the operator needs to precisely apply the mashed garlic to the warts, and this treatment is strictly prohibited for patients who are allergic to garlic. Avoid such adverse reactions.

Background: Local steroid hormone injections into hypertrophic scars resulted in depression of the lesion site and radiated linear depigmentation and atrophy surrounding the lesion, which is extremely rare. We reported a case.Aim: Our report was designed to explore the causes of this adverse reaction.Method: We reported a case of strange adverse reactions after steroid hormone injection for hyperplastic scars: depression of the lesion and linear‐like depigmentation and atrophy of the skin around the lesion, which did not improve after 1 year of topical drug treatment.Results: We considered that the injection was too deep. Steroid crystals are deposited in normal skin tissue and absorbed by the lymphatic vessel network responsible for removing macromolecules in the interstitial tissue, resulting in linear discoloration and atrophy along the lymphatic vessels.Conclusion: When treating hyperplastic scarring, the doctor needs to strictly grasp the depth, level, and dosage of the injection and avoid such adverse reactions.

Herpes zoster (HZ) is usually distributed on one side of the body; HZ duplex bilateralis is very rare with only 0.1% of all HZ cases. The occurrence of HZ duplex bilateralis is associated with abnormal immune function. In this report, we present a case of a 47-year-old woman who had no major health issues developed HZ duplex bilateralis after an adverse life event and extreme depression one month ago. HZ related symptoms were controlled after patient received antiviral, analgesic, and nerve-nourishing treatment in our hospital.

Skin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR‐411‐3p in bleomycin (BLM)‐induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real‐time quantitative polymerase chain reaction assess the expression levels of miR‐411‐3p, collagen (COLI) and transforming growth factor (TGF)‐β/Smad ubiquitin regulatory factor (Smurf)‐2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR‐411‐3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR‐411‐3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR‐411‐3p expression was decreased in bleomycin (BLM)‐induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)‐β signalling and collagen production. Overexpression of miR‐411‐3p inhibited the expression of collagen, F‐actin and the TGF‐β/Smad signalling pathway factors in BLM‐induced skin fibrosis and fibroblasts. In addition, miR‐411‐3p inhibited the target Smad ubiquitin regulatory factor (Smurf)‐2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF‐β/Smad signalling pathway. We demonstrated that miR‐411‐3p exerts antifibrotic effects by inhibiting the TGF‐β/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.