Search Results (269)

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

The Inula japonica flower is traditionally used to alleviate lung inflammatory symptoms. While the therapeutic effect of the I. japonica flower on lung diseases has been suggested, the efficacy of the I. japonica flower in treating atopic dermatitis (AD) remains unknown. We investigated the effects of a water extract of the I. japonica flower (WEIF) on Dermatophagoides farinae extract (DfE)-induced AD-like inflammation in NC/Nga mice. Histological analysis of the epidermal structure, mast cell infiltration, and barrier protein expression were examined. Serum inflammatory mediator levels were assessed. To elucidate the regulatory pathway of WEIF, the effects of 1,5-dicaffeoylquinic acid (DCQA) and 1-O-acetylbritannilactone (ABL) in WEIF on the JAK/STAT pathway were evaluated in interferon-γ/tumor necrosis factor (TNF)-α-stimulated human adult epidermal keratinocytes. WEIF ameliorated DfE-induced skin inflammation by reducing dermatitis scores, mast cell infiltration, skin structural damage, and serum inflammatory mediator levels. Additionally, DCQA and ABL significantly inhibited JAK/STAT activation in interferon-γ/TNF-α-treated keratinocytes. Furthermore, ligand-binding analysis revealed high binding affinities of DCQA and ABL for JAK. These results suggest the pharmacological potential of WEIF to alleviate DfE-induced skin inflammation by inhibiting the JAK/STAT signaling pathway. In conclusion, these findings support the development of WEIF as a therapeutic treatment for AD-like skin inflammatory diseases. Full article

Physalis Alkekengi L. var. franchetii (Mast.) Makino (PAF), which is used in both food and medicine, has a long history of about 1800 years of application in China. There are many active constituents in the calyx of PAF. Physalins and physalins with a single oxygen bridge are the unique components of the PAF calyx. Physalins with multiple biological activities, including anticancer activity, antimicrobial activity, anti-inflammatory activity, etc., have been found. As such, physalins deserve to be studied further. In this study, we aimed to extract, separate, and identify the effective components of physalins from the calyx of PAF and investigate ability to inhibit the proliferation of tumor cell lines. Three new physalins, physalin VIII (1), 3α-hydroxy-2,3,25,27-tetrahydro-4,7-didehydro-7-deoxyneophysalin A (2), and physalin IX (3), along with three known compounds, physalin L (4), physalin D (5), and alkekengilin A (6) were isolated from PAF calyxes. Physalin D was superior to the positive control drug cisplatin in inhibiting the proliferation of five tumor cell lines. The physalin compounds exhibited potential antitumor activity, being deemed worthy of further research in the fields of antitumor drug development and the application in health foods. Full article

Studies worldwide report cutaneous neoplasms in dogs; however, data in the arid regions of Mexico remain scarce. Here we report the main malignant cutaneous neoplasms diagnosed by fine needle aspiration cytology (FNAC), and describe the associations with age, sex and breed in Mexicali. Neoplastic lesions accounted for 25.52% (698/2735) of the cases, of which 56.59% (395/698) were malignant. The highest prevalence was observed in dogs aged 9–12 years (n = 193), intact males (n = 162), and mixed-breed dogs (n = 247). Round cell neoplasms (n = 309), including lymphoma, transmissible venereal tumors (TVT), and mast cell tumors (MCT), were the most common cell lineage. Using dogs aged 0–4 years as the reference group, dogs aged 9–12 years had 0.241 times the odds of developing malignant neoplasms (95% CI: 0.141–0.415, p = 0.0025). Using neutered males as the reference group, intact females showed 2.499 times the odds of developing malignant neoplasms (95% CI: 1.462–4.271, p = 0.0042). Compared to mixed-breed dogs, Schnauzers (OR = 0.161) showed significantly lower odds of malignancy (95% CI: 0.082–0.317, p = 0.0004), while Pitbull Terriers had 1.748 times more chance of present malignant neoplasia (95% CI: 1.014–3.013, p < 0.0001). This study provides significant epidemiological evidence on canine cutaneous neoplasms in an arid region of Mexico, identifying key risk factors and distribution patterns that can guide preventive, diagnostic, and therapeutic strategies tailored to regional characteristics. Full article

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets. Full article

Cutaneous neoplasia is among the most common illnesses in dogs and can pose significant risks. Accurate morphological diagnosis of these conditions is vital for effective treatment and management. In this retrospective study, a total of 3746 canine skin biopsies were submitted to a veterinary reference diagnostic laboratory and evaluated using histopathology. The variables assessed included age, sex, breed, lesion, location, and histopathological diagnosis. Non-neoplastic lesions accounted for 61% of all analyzed samples, while neoplastic tumors accounted for 39%. When looking at age, dogs ranging 3–6 years and 7–9 years had at least six times higher risk of developing malignant neoplasia compared to those aged 0–2 years. Among the malignant neoplasms, mast cell tumors, hemangiosarcoma, and squamous cell carcinoma were the most observed, representing 30%, 18%, and 12% of cases, respectively. The breeds most frequently affected by malignant neoplasms included Pit Bull Terriers, Boxers, and mixed breeds, all of which comprised the majority of mast cell tumor cases at 50.54%. These findings are novel in this field and may assist small animal veterinarians in making preliminary diagnoses, while also helping pet owners understand the importance of skin cancer and its early detection. Full article

The tumor microenvironment (TME) is crucial for the onset, development, and resistance to treatment of lung cancer. The tumor microenvironment consisting of a complex array of immune cells, fibroblasts, endothelial cells, extracellular matrix elements, and signaling molecules, facilitates tumor growth and spread while inhibiting the body’s antitumor immune response. In lung cancer, tumor-associated macrophages, cancer-associated fibroblasts, mast cells, and dendritic cells interact through cytokines, chemokines, growth factors, and matrix metalloproteinases to create an immunosuppressive and proangiogenic milieu. Hypoxic conditions within the TME further enhance cancer cell adaptability through hypoxia-inducible factors (HIFs), promoting epithelial–mesenchymal transition, immune evasion, and metastasis. Moreover, miRNAs have emerged as key regulators of gene expression within the TME, offering novel insights into tumor behavior and potential therapeutic targets. Targeting dynamic interactions within the TME, particularly through the modulation of immune responses, angiogenesis, and stromal remodeling, offers promising avenues for precision pharmacological approaches. This review covers the current understanding of the lung TME, highlighting its impact on cancer pathophysiology and treatment strategies. Understanding and therapeutically reprogramming the TME may pave the way for personalized and more effective interventions for lung cancer treatment. Full article

Here, the authors report the first case of a primary mast cell tumor originating from the inguinal lymph node in a nine-year-old intact female Maltese dog that had undergone a left ureteral stent, ureterotomy and splenectomy, and left-side mastectomy, including inguinal lymph node removal and ovariohysterectomy, in South Korea in May 2024. The splenic mass, mammary gland mass, and inguinal lymph node underwent histopathological examination, resulting in the diagnosis of nodular hyperplasia, grade 1 mammary complex carcinoma, and a mast cell tumor (MCT), respectively. To clarify the origin of the MCT from the inguinal lymph node, a computed tomography (CT) scan was performed. In addition, through a blood smear test, mast cell leukemia was ruled out. After CT scanning by veterinary radiologists and a biopsy of all possible masses, it was finally concluded that the MCT primarily originated from lymph nodes, which is extremely rare in dogs. The patient is recovering well as of February 2025, just 7 months after the first diagnosis, following surgery and 16 weeks of chemotherapy with a combination of prednisolone and vinblastine, considering the C-kit PCR results of the left inguinal lymph node after the surgical removal of the MCT. This report is significant for two reasons, firstly because of the rarity of MCTs originating from lymph nodes other than the skin and gastrointestinal organs, and secondly because the authors propose a hypothesis for the rarity of primary lymph node mast cell tumors and the correlation between mammary gland tumors and mast cell tumor growth based on a comparative literature review in humans, focusing on molecular mechanisms. Full article

Background/Objectives: AllergoOncology is a new field of study that investigates the relationship between allergic inflammation and cancer. Mast cells and eosinophils are two critical players in allergy reactions, where they can interact and release bioactive granules. The electron microscope is an indispensable tool for analyzing membrane contacts and degranulation patterns in mast cells and eosinophils. The aim of the present ultrastructural study is to analyze the interactions between tumor-associated eosinophils and mast cells (TATEM) in nine cases of gastric cancer. Methods: Seventy-two gastric cancer samples were analyzed using light microscopy, and nine cases exhibiting TATEM were selected for additional examination by transmission electron microscopy. Results: In seven cases, there was direct interaction between non-activated eosinophils and mast cells demonstrating piecemeal degranulation and/or exocytosis. In cases 8 and 9, both cell types showed more advanced stages of degranulation. Mast cells exhibited either massive degranulation (anaphylactic type) or signs of recovery, while eosinophils displayed cytolysis, with or without extracellular trap formation (ETosis). The concurrent activation of both cell types may indicate a collaborative immune response that could affect tumor behavior. There was a trend toward an association with low-stage (I-II) gastric cancer in patients with TATEM, but this difference was not statistically significant (p = 0.06). Conclusions: This work is the first investigation to present ultrastructural evidence of the intimate relationship between degranulating mast cells and cytolytic eosinophils, with or without ETosis, in gastric cancer. These findings support the emerging field of AllergoOncology, which examines the role of allergy-like immune responses in tumor immunity. Full article

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment. Full article

CD300 family members are immunoglobulin superfamily receptors that regulate immune cell function through either activating or inhibitory signals. Among them, CD300a is a prototypical inhibitory receptor, highly expressed in both myeloid and lymphoid lineages, and plays a pivotal role in the pathogenesis of inflammation and tumor immunity. CD300a transduces inhibitory signals in several immune cells—including mast cells, eosinophils, monocytes, dendritic cells (DCs), neutrophils, and natural killer (NK) cells—by recruiting SHP-1 phosphatase to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and suppressing activation pathways such as Toll-like receptor (TLR)-MyD88 and FcεRI signaling. Recent studies suggest that tumor cells may hijack CD300a-associated pathways to establish an immunosuppressive microenvironment that facilitates immune evasion, tumor survival, and potentially metastatic spread. Proposed mechanisms include reduced DC-mediated type I interferon (IFN) production, diminished NK cell cytotoxicity, and negative regulation of mast cell– and eosinophil-dependent anti-tumor responses. Although some of these findings are derived from in vivo models, the cumulative evidence positions CD300a as a critical immune checkpoint in tumor-associated immune regulation. In addition to its established roles in hematologic malignancies—including chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia—CD300a has also been implicated in modulating tumor-associated immune responses in other pathological contexts. While most studies emphasize its immune cell–mediated effects, emerging evidence suggests that CD300a may directly influence tumor progression by regulating immune homeostasis, intracellular signaling, and tumor microenvironment interactions. Collectively, these findings establish CD300a as a pleiotropic immunoregulatory molecule in both hematologic and non-hematologic malignancies, underscoring the need to further explore its broader relevance and therapeutic potential in cancer immunology. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer, characterized by a highly desmoplastic tumor microenvironment. One main risk factor is chronic pancreatitis (CP). Progression of CP to PDAC is greatly influenced by persistent inflammation promoting genomic instability, acinar–ductal metaplasia, and pancreatic intraepithelial neoplasia (PanIN) formation. Components of the extracellular matrix, including immune cells, can modulate this progression phase. This includes cells of the innate immune system, such as natural killer (NK) cells, macrophages, dendritic cells, mast cells, neutrophils, and myeloid-derived suppressor cells (MDSCs), either promoting or inhibiting tumor growth. On one hand, innate immune cells can trigger inflammatory responses that support tumor progression by releasing cytokines and growth factors, fostering tumor cell proliferation, invasion, and metastasis. On the other hand, they can also activate immune surveillance mechanisms, which can limit tumor development. For example, NK cells are cytotoxic innate lymphoid cells that are able to kill tumor cells, and active dendritic cells are crucial for a functioning anti-tumor immune response. In contrast, mast cells and MDSCs rather support a pro-tumorigenic tumor microenvironment that is additionally sustained by platelets. Once thought to play a role in hemostasis only, platelets are now recognized as key players in inflammation and cancer progression. By releasing cytokines, growth factors, and pro-angiogenic mediators, platelets help shape an immunosuppressive microenvironment that promotes fibrotic remodeling, tumor initiation, progression, metastasis, and immune evasion. Neutrophils and macrophages exist in different functional subtypes that can both act pro- and anti-tumorigenic. Understanding the complex interactions between innate immune cells, platelets, and early precursor lesions, as well as PDAC cells, is crucial for developing new therapeutic approaches that can harness the immune and potentially also the coagulation system to target and eliminate tumors, offering hope for improved patient outcomes. Full article

TGF-β is a pleiotropic cytokine with both stimulatory and inhibitory effects on immune cells, depending on the microenvironmental context. It targets mast cells (MCs) in different physio-pathological conditions, such as inflammation and cancer. Besides acting as a potent chemoattractant for MCs, TGF-β regulates many other aspects of MCs’ physiology, including the secretion of many regulatory molecules. MCs secrete a variety of mediators, either pre-formed or newly synthesized, upon appropriate stimulation. CCL-2 chemokine and TNF cytokine act as potent chemoattractants for several immune cells and participate in the initiation of inflammatory responses by recruiting them to injured tissues. TGF-β regulates CCL-2 and TNF secretion in different cell types and under distinct cellular contexts. Here, we report that the treatment with TGF-β alone induces the secretion of both pre-formed and newly synthesized CCL-2 in the rat RBL-2H3 mast cells but not in mouse bone marrow-derived mast cells (BMMCs). TGF-β-induced CCL-2 secretion depends on rapid rearrangements of the actin cytoskeleton and, remarkably, on the early secretion of soluble TNF that triggers an autocrine TNF signaling. In conclusion, we found cooperation between TGF-β and TNF signaling pathways to promote the secretion of CCL-2 chemokine by MCs in a cell-context specific manner. Full article

The etiopathogenesis and treatment response of sensitive skin remain poorly understood. We used 4-tert-butylcyclohexanol (4-TBLH) and 1% pimecrolimus ointment to treat sensitive skin in mice models constructed using tape stripping, propylene glycol, and capsaicin. This study aimed to further investigate the sensitivity and responsiveness of this sensitive mouse skin model. Sensitivity and responsiveness were assessed by measuring transepidermal water loss (TEWL), skin hydration, skin flakes, vascular dilatation, itching, stinging, and histological changes, including mast cell, lymphocyte, and granulocyte infiltration, tumor necrosis factor-α (TNF-α) expression, and transient receptor potential vanilloid 1 receptor (TRPV1) expression. The application of 4-TBLH and pimecrolimus revealed distinct responses in skin sensitivity indicators, including TEWL, capillary dilation, and mass cell activity, depending on the treatment timing and substance used. The prophylactic and therapeutic applications of 4-TBLH revealed distinct responses in skin sensitivity indicators, including skin flakes, TEWL, itching, stinging, epidermal thickness, mast cell activity, TNF-α, and TRPV1 expression. The prophylactic and therapeutic applications of pimecrolimus ointment revealed distinct responses in skin sensitivity indicators, including skin flakes, skin water content, itching, epidermal thickness, mast cell activity, CD45, CD11b, TNF-α, and TRPV1 expression. The mouse sensitive skin model demonstrates robust sensitivity and responsiveness to different treatment factors, and the model can be applied to the development of prophylactic and therapeutic medications for sensitive skin. Full article