Mast Cell Infiltration Research Articles

Anti-Pruritic and Immunomodulatory Effects of Coix [Coix lacryma-jobi L. var. ma-yuen (Rom. Caill.) Stapf.] Sprouts Extract

This study explored the anti-pruritic and immunomodulatory effects of Coix sprouts extract, focusing on histamine release and IL-31 cytokine production in HMC-1 cells. The extract significantly inhibited both factors, indicating its potential for pruritus relief. In a pruritus induction mouse model, Coix sprouts extract outperformed prednisolone in anti-pruritus effectiveness, also improving skin lesions and inhibiting mast cell infiltration. The extract suppressed tryptase expression, reduced release, inhibited mast cell proliferation, and lowered nitric oxide production, suggesting anti-inflammatory properties. Coix sprouts extract shows promise in suppressing inflammation and pruritus, making it a valuable candidate for clinical use. Additionally, the analysis of coixol content in Coix sprouts revealed variations in growth time, indicating their potential as functional materials with anti-pruritus and immune-enhancing applications.

Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.

Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD. AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ. ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade. ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.

A Novel Gene Signature Based on Immune Cell Infiltration Landscape Predicts Prognosis in Lung Adenocarcinoma Patients.

The tumor microenvironment (TME) is created by the tumor and dominated by tumor-induced interactions. Long-term survival of lung adenocarcinoma (LUAD) patients is strongly influenced by immune cell infiltration in TME. The current article intends to construct a gene signature from LUAD ICI for predicting patient outcomes. For the initial phase of the study, the TCGA-LUAD dataset was chosen as the training group for dataset selection. We found two datasets named GSE72094 and GSE68465 in the Gene Expression Omnibus (GEO) database for model validation. Unsupervised clustering was performed on the training cohort patients using the ICI profiles. We employed Kaplan-Meier estimators and univariate Cox proportional-hazard models to identify prognostic differentially expressed genes in immune cell infiltration (ICI) clusters. These prognostic genes are then used to develop a LASSO Cox model that generates a prognostic gene signature. Validation was performed using Kaplan-Meier estimation, Cox, and ROC analysis. Our signature and vital immune-relevant signatures were analyzed. Finally, we performed gene set enrichment analysis (GSEA) and immune infiltration analysis on our finding gene signature to further examine the functional mechanisms and immune cellular interactions. Our study found a sixteen-gene signature (EREG, HPGDS, TSPAN32, ACSM5, SFTPD, SCN7A, CCR2, S100P, KLK12, MS4A1, INHA, HOXB9, CYP4B1, SPOCK1, STAP1, and ACAP1) to be prognostic based on data from the training cohort. This prognostic signature was certified by Kaplan-Meier, Cox proportional-hazards, and ROC curves. 11/15 immune-relevant signatures were related to our signature. The GSEA results indicated our gene signature strongly correlates with immune-related pathways. Based on the immune infiltration analysis findings, it can be deduced that a significant portion of the prognostic significance of the signature can be attributed to resting mast cells. We used bioinformatics to determine a new, robust sixteen-gene signature. We also found that this signature's prognostic ability was closely related to the resting mast cell infiltration of LUAD patients.

Osteoporosis in Systemic Mastocytosis: A Scoping Review

Background: Mastocytosis (MS) is a rare disease that can involve various organs, including the bone. Given the incidence of the disease in the global population, MS poses a challenge for physicians, and early therapeutic intervention in the initial stages could significantly impact the quality of life of affected patients. Objective: The aim of this scoping review was to provide an overview of secondary osteoporosis in systemic mastocytosis (SM), focusing on the heterogeneity of its manifestations, the benefits of early diagnosis, and appropriate pharmacological treatment. Design: A technical expert panel (TEP) consisting of 8 physicians with expertise in metabolic bone diseases conducted the review following the PRISMA-ScR model. A strength of this study is that it provides various therapeutic approaches for patients with bone involvement in SM, although the limited available literature on the topic constituted a limitation. The TEP sought evidence regarding the following diagnostic and therapeutic modalities in the management of SM: “bisphosphonate therapy”, “zoledronic acid therapy”, “denosumab therapy”, “IFN-alpha therapy”, and “IFN-alpha therapy in combination with pamidronate”. Results: Clinical data showed a correlation between densitometric outcomes, serum tryptase levels, and mast cell infiltration in the bone marrow, between increased bone mineral density and the presence of osteosclerosis in cases of advanced SM, between the severity of osteoporosis and hypertryptasemia, and also provided results on the long-term effects of bisphosphonate therapy, the therapeutic efficacy of zoledronic acid administration, the positive effect of denosumab on the reduction of serum tryptase levels (even if is proved in a limited numbers of cases) and the prevention of new fractures, and the effect of IFN-alpha in more severe cases of SM, either alone or in combination with pamidronate. Conclusions: Studies have demonstrated the effectiveness of various treatments depending on the form of mastocytosis, whether indolent systemic or advanced systemic, in the prognosis of the disease. However, this role should be further investigated in additional clinical studies, considering the limited data on the use of these interventions.

Cutaneous mastocytosis: diagnostic challenges and dietary influences in a prolonged case report

Cutaneous mastocytosis is a rare condition characterized by abnormal mast cell proliferation in the skin. We present the case of a 65-year-old man with recurrent urticaria-like rashes persisting for more than eight years. Despite multiple misdiagnoses as insect bites, examination and biopsy revealed mast cell infiltration. The patient's unique lifestyle, particularly his frequent seafood consumption, adds an intriguing dimension to the case. Treatment with systemic antihistamines and corticosteroids provided symptomatic relief, but long-term follow-up showed the persistence of clinical lesions, indicating that the treatment did not adequately address the underlying cause of the disease. A notable improvement in disease control was observed when the patient's diet was adjusted, suggesting a potential link between food and cutaneous mastocytosis. To our knowledge, this is the first documented case of maculopapular cutaneous mastocytosis in Syria.

Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

Plasma-Activated AVC Hydrogel for Reactive Oxygen and Nitrogen Species Delivery to Treat Allergic Contact Dermatitis.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease that accounts for approximately 20% of all occupational skin diseases. As an adverse and recurrent inflammatory dermatological agent, ACD shows insufficient response to current therapies largely owing to abnormal inflammatory activation and accompanying bacterial infection in lesions. Cold atmospheric plasma is a noninvasive fledgling reactive oxygen and nitrogen species (RONS)-based therapeutic technique for ACD treatment; however, its clinical adoption has been hindered due to the risk of electrical burns and insufficient delivery of the plasma-generated RONS. To address these limitations, we constructed plasma-activated AVC (PA-AVC) hydrogels loaded with plasma-generated RONS for ACD treatment as an alternative to the common direct plasma irradiation treatment. The proposed PA-AVC hydrogels were produced on a biodegradable acryloyldimethylammonium taurate/VP copolymer (AVC) with the aid of a novel air discharge plasma without the involvement of any catalyst. In vitro data showed that abundant RONS were produced and incorporated into the PA-AVC hydrogels via complex gas-liquid reactions between the air discharge plasma and hydrosolvent; additionally, the PA-AVC hydrogels exhibited excellent storage, slow release and transdermal delivery of RONS as well as good antibacterial effects. Moreover, in vivo experiments demonstrated that PA-AVC hydrogels effectively alleviated the ACD symptoms, such as skin redness and swelling, reduced epidermal thickening and inhibited mast cell infiltration and IL-9, TNF-α, and TSLP expression with no evident systemic toxicity. Our results revealed that long-acting plasma-activated AVC hydrogels could be effective therapeutic agents for local ACD treatment.

Therapeutic potential of plasma-treated solutions in atopic dermatitis

Atopic Dermatitis (AD) is a prevalent inflammatory skin disease that is currently incurable. Plasma-treated solutions (PTS) (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as novel therapy. Recently, PTS is gaining attention due to its advantages over non-thermal plasma (also known as cold atmospheric plasma). Thus, we explore the application of PTS in treating AD. In vivo experiments demonstrated that PTS significantly alleviated AD-like symptoms. It reduced mast cell and macrophage infiltration, decreased scratching times and serum IgE levels. These therapeutic effects of PTS on AD mice were associated with the activation of the antioxidant molecule Nrf2. In vitro experiments revealed that PTS could decrease ROS level and regulate cytokine expression (such as IL-6, IL-10, IL-13 and CCL17) in TNF-α/IFN-γ-stimulated keratinocytes and LPS-stimulated M1 macrophages. Additionally, PTS could upregulate the expression of antioxidant stress molecules such as Nrf2, HO-1, NQO1 and PPAR-γ in both cell types. Overall, PTS demonstrated potent therapeutic potential for AD without notable side effects. Our research provided a promising approach to AD treatment and may serve as a potential therapeutic strategy in other inflammatory skin diseases.

Primary Mast Cell Sarcoma of the Maxillary Sinus and Gingiva Mimicking Malignant Neuroendocrine Tumor: A Case Report

Mast cell sarcoma (MCS) is an extremely rare and aggressive malignancy primarily affecting bones, with limited literature associating it with neuroendocrine marker expression. This report presents a rare case of MCS arising in the maxillary sinus and gingiva. A 74-year-old man presented with a progressively enlarging ulcer on the right-sided upper gingiva. Magnetic resonance imaging revealed a 3.4 cm tumor on the floor of the right maxillary sinus. The patient underwent an inferior maxillectomy and right-sided neck dissection. Microscopically, the tumor consisted of monotonous round cells with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and brisk mitoses. A panel of immunohistochemical stains was initially applied to exclude common sinonasal undifferentiated neoplasms, such as sinonasal undifferentiated carcinoma, melanoma, rhabdomyosarcoma, Ewing sarcoma, and lymphoma. The tumor cells showed patchy staining for INSM1 and synaptophysin, but were negative for AE1/AE3, CAM5.2, p40, chromogranin, S100, HMB45, NKX2.2, desmin, CD45 (LCA), CD3, and CD20, with intact INI1 and BRG1 expression. No specific diagnosis could be rendered based on the staining results, leading to consideration of other rare malignancies. Additional staining revealed positivity for CD117, mast cell tryptase, CD13, CD33, CD43, and CD68, confirming the MCS diagnosis. Molecular testing for KIT mutation was negative. Subsequent bone marrow biopsy demonstrated infiltration of atypical mast cells, which led to a diagnosis of mast cell leukemia. Despite high-dose chemotherapy, the patient died three months after the initial diagnosis. The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.

Enhanced joint pain in diabetic patients with knee osteoarthritis is associated with increased synovitis, synovial immune cell infiltration, and erythrocyte extravasation.

Diabetes mellitus (DM) is an important risk factor for the development of osteoarthritis (OA), increasing OA progression and OA pain. To gain insight into the underlying mechanisms of how DM exacerbates OA processes and OA pain, this study analyzed histological differences of synovial tissues from non-DM and DM patients with OA and correlated these differences with knee pain severity. Synovial tissue was obtained from 12 non-DM and 10 DM patients with advanced knee OA who underwent total knee arthroplasty. Synovial inflammation was assessed using the Synovitis score developed by Krenn. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess knee pain intensity and disability in OA patients. The number of mast cells, macrophages, nerve fibers, capillaries, larger vessels and erythrocyte extravasation were analyzed microscopically in histological and immunostained synovial sections from non-DM and DM patients. Association analyses were performed to determine associations between OA knee pain and synovial changes affected by DM. Synovial tissue from OA patients with DM had a higher synovitis score, more erythrocyte extravasation, and contained higher numbers of mast cells and macrophages compared to non-DM patients. The number of capillaries and vessels in the lining/sublining layer of the synovial tissue was reduced in DM patients. OA patients with DM had more severe knee pain compared to non-DM patients. The KOOS pain score was associated with the synovitis score, the number of tissue macrophages, and the number of mast cells in the synovial tissue (adjusted for age, sex, and BMI). In addition, the erythrocyte extravasation score was associated with the KOOS pain score and with the synovitis score. The study suggests that increased OA progression and pain severity in patients with DM result from more pronounced synovitis and synovial vascular leakage and increased infiltration of macrophages and mast cells.

Preclinical Models of Atopic Dermatitis Suitable for Mechanistic and Therapeutic Investigations.

Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.

TMT-proteomics reveals the therapeutic effects of Lianling decoction against atopic dermatitis through Staphylococcus aureus infection

BackgroundLianling Tang (LLT), a traditional Chinese herbal decoction, is utilized for managing inflammatory skin conditions in China. This study explores the therapeutic effects and molecular mechanisms of LLT on atopic dermatitis (AD) in a mouse model, employing proteomics techniques. MethodsWe evaluated the therapeutic efficacy of LLT on AD in mice by assessing skin inflammation scores, conducting histopathological examinations, and measuring serum levels of IgE, IL-4, and IL-6. Using Tandem Mass Tag (TMT) technology, we performed proteomics analysis of skin samples from Control, Model, LLT-treated, and positive control drug-treated mice, and identified differentially expressed proteins (DEPs). These proteins were then analyzed via GO and KEGG pathways to elucidate LLT's mechanisms in treating AD. ResultsLLT markedly reduced skin inflammation scores, epidermal thickening, and mast cell infiltration, and decreased serum IgE, IL-4, and IL-6 levels in AD model mice, highlighting its therapeutic potential. Proteomics analysis identified Staphylococcus aureus infection as a pivotal AD pathogenesis mechanism and revealed critical proteins such as C1QA, C4B, C5, and FCGR3. LLT's mechanisms, such as modulating the complement activation, and influencing phagocytosis, effectively reduce inflammation and alleviate symptoms caused by Staphylococcus aureus in AD. ConclusionLLT shows potential in AD treatment by modulating pathways associated with Staphylococcus aureus infection, effectively alleviating symptoms.

Anti-inflammatory Capacity of a Medicinal herb extract, Anemarrhena asphodeloides, on In vivo and In vitro models-induced atopic dermatitis

Anemarrhena asphodeloides (AA) Bunge, a rhizomatous plant from the Liliaceae family, is traditionally utilized to manage inflammatory conditions. Nevertheless, its impact on atopic dermatitis (AD) and the associated molecular pathways have not yet been fully explored. This study explored the therapeutic effects of AA on AD both in vivo, using 2,4-dinitrofluorobenzene-induced NC/Nga mice, and in vitro, with tumor necrosis factor-α/interferon-γ-stimulated HaCaT keratinocytes. Topical application of AA ointment on the dorsal skin notably alleviated AD symptoms and skin lesions, enhanced the dermatitis score, and improved parameters such as the rate of trans-epidermal water loss, epidermal thickness, mast cell infiltration, systemic IgE levels, and cytokine expression. Furthermore, AA treatment significantly reduced serum levels of thymic stromal lymphopoietin (TSLP) and locally suppressed mRNA expression of thymus and activation-regulated chemokine (TARC) along with other relevant cytokines in affected skin. Both in vivo and in vitro applications of AA curtailed TSLP levels by inhibiting the expression of signal transducer and activator of transcription 6, a key regulator of pruritus and an initiator of mitogen-activated protein kinase signaling pathways. Additionally, AA affected the expression of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, a pathway of interest in the study of cutaneous inflammatory diseases. Collectively, these findings propose that AA holds potential as an effective therapeutic agent for treating AD-induced skin inflammation.

Enoximone alleviates atopic dermatitis-like skin inflammation via inhibition of type 2 T helper cell development

Atopic dermatitis (AD) is an inflammatory skin disease that affects approximately 15–20 % of the children and 1–3 % of the adults worldwide. Corticosteroids and calcineurin inhibitors are used in AD therapy; however, they cause various side effects. Current studies focus on novel therapeutic targets such as phosphodiesterases (PDEs) to mitigate AD. However, the relationship between PDE3 inhibitors and AD has not yet been reported. This study aimed to investigate the therapeutic effects and pharmaceutical mechanisms of enoximone (Enox), a PDE3 inhibitor. Mice were stimulated with 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin inflammation and were topically treated with Enox for 2 weeks. Treatment with Enox reduced the dermatitis score, skin water loss, IgE production, and expression of cytokines and chemokines that were elevated by DNCB. Histologically, Enox treatment reduced the skin thickness and the infiltration of various inflammatory cells, including macrophages, mast cells, eosinophils, and type 2 T helper (Th2) cells. HuT78, a human T cell line, was used to investigate the differentiation of T cells into Th2 cells. Enox treatment decreased the expression of Th2 cytokines and GATA3, a Th2 cell marker in HuT78, and suppressed signaling pathways that play a crucial role in Th2 cell differentiation. Collectively, the results demonstrate that Enox alleviates AD-like skin inflammation by inhibiting T-cell development. Thus, Enox may be a therapeutic candidate for the treatment of AD.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Paenibacillus exopolysaccharide alleviates Malassezia-induced skin damage: Enhancing skin barrier function, regulating immune responses, and modulating microbiota

Numerous studies have established a strong association between Malassezia and various skin disorders, including atopic dermatitis. Finding appropriate methods or medications to alleviate Malassezia-induced skin damage is of notable public interest. This study aimed to evaluate the therapeutic effect of the exopolysaccharide EPS1, produced by Paenibacillus polymyxa, on Malassezia restricta-induced skin damage. In vitro assays indicated that EPS1 reduced the expression of pro-inflammatory cytokine genes in TNF-α-induced HaCaT cells. In a murine model, EPS1 was found to mitigate clinical symptoms, reduce epidermal thickness and mast cell infiltration, improve skin barrier function, decrease pro-inflammatory cytokine levels associated with type 17 inflammation, enhance Tregs in the spleen, upregulate the transcription of Treg-related genes in skin lesions, and modulate the skin microbiota. This study is the first to report the alleviating effect of Paenibacillus exopolysaccharide on Malassezia-induced skin inflammation and its impact on the skin microbiota. These findings support the potential of Paenibacillus exopolysaccharides as consumer products and therapeutic agents for managing Malassezia-induced skin damage by improving skin barrier function, modulating immune responses, and influencing skin microbiota.

Antibacterial and Antiallergic Effects of Three Tea Extracts on Histamine-Induced Dermatitis.

Atopic dermatitis (AD) is a persistent and recurrent inflammatory skin condition with a genetic basis. However, the fundamental reasons and mechanisms behind this phenomenon remain incompletely understood. While tea extracts are known to reduce histamine-induced skin allergies and inflammation, the specific mechanisms by which various types of Chinese tea provide their protective effects are still not fully elucidated. In this study, a model of skin itching induced by histamine is used to explore the functions and mechanisms of three types of tea extract (Keemun black tea (HC), Hangzhou green tea (LC), and Fujian white tea (BC)) in alleviating histamine-induced dermatitis. The components of three tea extracts are identified by UPLC-Q-TOF-MS, and we found that their main components are alkaloids, fatty acyls, flavonoids, organic acids, and phenols. The inhibitory effects of three types of tea extract on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in skin injury are investigated by MIC and flow cytometry. The three types of tea extract have an inhibitory effect on the growth of bacterial flora, with HC showing the best inhibitory activity. The effect of the three types of tea extract on histamine-induced dermatitis is also evaluated. Furthermore, itchy skin experiments, HE staining, toluidine blue staining, and immunohistochemical staining of mouse skin tissues were performed to determine the variations of scratching, epidermal thickness, mast cell number, IL-1β, and NGF content after the administration of the tea extracts. The three types of tea extracts all alleviate and inhibit skin itching, epidermal hyperplasia, and allergic dermatitis. BC effectively alleviates epidermal hyperplasia caused by skin allergies, and LC significantly downregulates NGF. HC reduces histamine-induced mast cell infiltration and downregulates IL-1β to alleviate skin itching. Consequently, tea emerges a potent natural product that can inhibit the growth of skin wound bacterial flora and exhibit skin repair effects on histamine-induced allergic dermatitis.

Renal Mast Cell-Specific Proteases in the Pathogenesis of Tubulointerstitial Fibrosis.

Chronic kidney disease is detected in 8-15% of the world's population. Along with fibrotic changes, it can lead to a complete loss of organ function. Therefore, a better understanding of the onset of the pathological process is required. To address this issue, we examined the interaction between mast cells (MCs) and cells in fibrous and intact regions, focusing on the role of MC proteases such as tryptase, chymase, and carboxypeptidase A3 (CPA3). MCs appear to be involved in the development of inflammatory and fibrotic changes through the targeted secretion of tryptase, chymase, and CPA3 to the vascular endothelium, nephron epithelium, interstitial cells, and components of intercellular substances. Protease-based phenotyping of renal MCs showed that tryptase-positive MCs were the most common phenotype at all anatomic sites. The infiltration of MC in different anatomic sites of the kidney with an associated release of protease content was accompanied by a loss of contact between the epithelium and the basement membrane, indicating the active participation of MCs in the formation and development of fibrogenic niches in the kidney. These findings may contribute to the development of novel strategies for the treatment of tubulointerstitial fibrosis.

What lies behind melasma: a review of the related skin microenvironment.

Melasma is an acquired chronic pigmentary disorder affecting millions of individuals worldwide. However, the pathogenesis of melasma remains unclear. This article provides a comprehensive review of the pathophysiological changes occurring in the skin microenvironment of melasma lesions, which can be summarized as follows: (1) skin barrier dysfunction and abnormal synthesis, transport, and intracellular distribution of melanin in the epidermis; (2) basement membrane damage; (3) solar elastosis, vascular changes, senescent fibroblasts, mast cell infiltration, and sebocyte participation in the dermis; and (4) systemic factors such as sex hormones and oxidative stress. Furthermore, potential therapeutic strategies are introduced to provide novel perspectives for fundamental and clinical research related to melasma.

Crisaborole combined with vitamin D demonstrates superior therapeutic efficacy over either monotherapy in mice with allergic contact dermatitis

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.