Search Results (315)

Leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1) is a functional inhibitor of the epidermal growth factor receptor. Lrig1-positive stem cells are located in the isthmus region of the mouse hair follicle (HF) and are known contributors to sebaceous gland (SG) formation and homeostasis. In this study, we performed a topical tamoxifen inducible diphtheria toxin-mediated ablation of Lrig1-expressing cells in transgenic mice to investigate their function in vivo. Selective depletion of Lrig1-positive cells resulted in a complete but reversible loss of SGs, with atrophy beginning at day 14 and full recovery occurring after six months. In the absence of the Lrig1 niche, junctional-zone keratinocytes adopted an interfollicular epidermis-like phenotype (K1-positive), and repopulating cells from other epidermal compartments failed to differentiate into the sebocyte lineage. These findings demonstrate that Lrig1-positive progenitors are crucial for proper sebaceous gland morphogenesis and maintenance. Our results highlight the importance of Lrig1-positive cells in SG-related skin physiology. Full article

Esophageal squamous cell carcinoma (ESCC) represents a major therapeutic challenge due to the rapid development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Recent evidence highlights that this resistance is driven not only by genetic mutations but also by spatial heterogeneity of tumor microenvironments and compensatory signaling mechanisms. In this review, we propose a “spatial-signaling-intervention” framework with a particular focus on the NTRK2/MAPK signaling axis, which plays dual roles in signaling compensation and immune evasion. By integrating spatial multi-omics, proteomics, and AI-assisted topological modeling, three resistant niches are identified: (1) cancer stemness-enriched zones, (2) MAPK hyperactive islands, and (3) immune-cold regions. Based on this atlas, we design precision nanotherapeutic platforms, including responsive, dual-target, and feedback-loop nanocarriers, to selectively modulate resistant spatial niches. Preclinical validation in patient-derived xenografts and organoid models further demonstrates the translational potential of these strategies. This work provides a conceptual and technological roadmap for overcoming EGFR-TKI resistance in ESCC. Atlas-guided nanocarrier systems offer a promising avenue for spatially targeted and feedback-responsive therapy, highlighting the role of pharmaceutics in advancing precision oncology. Full article

Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that S100a4 promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (Ivl, Cux1, K14, Klk5), as well as pluripotency genes (Itga6, Krt15), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. Full article

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to tissue repair, immunomodulation, and regenerative therapies for cardiac, orthopedic, and hematological disorders. Accurate identification and characterization of these stem cells are essential for both research and clinical applications. MSCs are typically defined by plastic adherence, expression of surface markers CD105, CD73, and CD90, low or absent expression of hematopoietic markers (CD45, CD34), and in vitro differentiation potential. Understanding the expression patterns and functional relevance of these surface markers is critical for improving isolation strategies, enhancing therapeutic efficacy, and minimizing adverse effects. This review provides a comprehensive overview of the principal surface markers of MSCs, highlighting their significance in stem cell biology and clinical translation. Full article

The WUSCHEL-related homeobox (WOX) transcription factors (TF) regulate critical developmental processes in plants, including organ formation and stem cell maintenance. Although characterized in model species, the WOX family remains unexplored in passion fruit (Passiflora edulis). In this study, 10 WOX genes were identified in passion fruit, which are distributed across six chromosomes. We analyzed the phylogenetic relationships, gene structure, conserved motifs, and syntenic relationships of the PeWOX genes. Multiple sequence alignment analysis revealed strong conservation of the homeodomain region among WOX TF family members. Phylogenetic reconstruction further demonstrated that the 10 identified PeWOX genes in passion fruit could be classified into three distinct evolutionary clades: the WUS clade, the Intermediate clade, and the Ancient clade. The conserved motif and gene structure of WOX TF family members in the same evolutionary clade were highly consistent. Expression analysis based on RNA-seq and RT-qPCR showed that most PeWOX genes were expressed during ovule development. The expression level of PeWOX genes varies with different stress conditions. Subcellular localization analysis of tobacco leaf epidermal cells showed that PeWOX3/7/10 proteins were localized in the nucleus and cell membrane. Collectively, this study lays a foundation for future functional studies of passion fruit WOX genes. Full article

Galactic cosmic ray (GCR) radiation is a major barrier to human space exploration beyond Earth’s magnetic field protection. Mesenchymal stem cells (MSCs) are found in all organs and play a critical role in repair and regeneration of tissue. We engineered bone marrow-derived MSCs and evaluated their response to ionizing radiation exposure. Epidermal growth factor receptor (EGFR) expression by certain types of cancers has been shown to induce radioresistance. In this study, we tested the feasibility of transfecting MSCs to overexpress EGFR (eMSC-EGFR) and their capacity to tolerate and recover from X-ray exposure. Quantitative real-time PCR (qRT-PCR) and immunoblotting results confirmed the efficient transfection of EGFR into MSCs and EGFR protein production. eMSC-EGFR maintained characteristics of human MSCs as outlined by the International Society for Cell & Gene Therapy. Then, engineered MSCs were exposed to various dose rates of X-ray (1–20 Gy) to assess the potential radioprotective role of EGFR overexpression in MSCs. Post-irradiation analysis included evaluation of morphology, cell proliferation, viability, tumorigenic potential, and DNA damage. eMSC-EGFR showed signs of radioresistance compared to naïve MSCs when assessing relative proliferation one week following exposure to 1–8 Gy X-rays, and significantly lower DNA damage content 24 h after exposure to 4 Gy. We establish for the first time the efficient generation of EGFR overexpressing MSCs as a model for enhancing the human body to tolerate and recover from moderate dose radiation injury in long-term manned space travel. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article

Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes in most cell types within the tumor to hijack therapeutic responses. Cancer therapies further stimulate TGF-β release to potentiate this problem. Molecular mechanisms of TGF-β action supporting resistance include upregulation of drug efflux pumps, enhanced DNA Damage Repair, elaboration of stiffened extracellular matrix, and decreased neoantigen presentation. TGF-β also activates pro-survival pathways, such as epidermal growth factor receptor, B-cell lymphoma-2 expression, and AKT-mTOR signaling. TGF-β-induced epithelial-to-mesenchymal transformation leads to tumor heterogeneity and acquisition of stem-like states. In the tumor microenvironment, TGF-β induces extracellular matrix production, contractility, and secretion of immunosuppressive cytokines by cancer-associated fibroblasts that contribute to drug resistance. TGF-β also blunts cytotoxic T and NK cell activities and stimulates recruitment and differentiation of immunosuppressive cells, including T-regulatory cells, M2 macrophages, and myeloid-derived suppressor cells. The importance of TGF-β signaling in development of drug resistance cannot be understated and should be further explored mechanistically to identify novel molecular approaches and combinatorial drug dosing strategies to prevent drug-resistance. Full article

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease. Evidence on the efficacy of different mesenchymal stem cell (MSC) exosomes for psoriasis remains limited. This study aimed to evaluate the therapeutic effects of different MSC exosomes in mitigating psoriasis. Methods: The efficacy of human placenta MSC (hPMSC) and human umbilical cord MSC (hUCMSC) exosomes was compared in an imiquimod (IMQ)-induced psoriasis murine model. A meta-analysis was performed to incorporate the results of studies using IMQ-induced psoriasis murine models to compare MSC exosome treatments (exosome group) with vehicle or no-treatment controls (control group). Results: In this murine study, both the hPMSC and hUCMSC exosomes showed better effectiveness in reducing epidermal thickness and skin tissue cytokines than controls, but no significant difference was observed between the two MSC exosomes. Seven studies were included in the meta-analysis. Clinical severity scores were significantly lower in the exosome group than in the controls (standardized mean difference [SMD]: −1.886; 95% confidence interval [CI]: −3.047 to −0.724). Epidermal thickness was significantly reduced (SMD: −3.258; 95% CI: −4.987 to −1.529). No significant differences were found in most skin cytokines between the groups, although tumor necrosis factor-α mRNA (SMD: −0.880; 95% CI: −1.623 to −0.136) and interleukin-17A protein levels (SMD: −2.390; 95% CI: −4.522 to −0.258) were both lower in the exosome group. Meta-regression revealed a greater improvement in clinical scores in studies using hUCMSC exosomes compared to other MSC sources (p = 0.030). Conclusions: hUCMSC exosomes have been studied more extensively than other MSC exosomes. MSC exosomes reduce clinical severity and epidermal hyperplasia. Full article

Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. Full article

Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological mechanisms, causing significant discomfort and reduced quality of life. Prophylactic measures and symptom-based treatment are recommended, emphasizing patient education, topical agents, and systemic therapies for severe cases. A 41-year-old female with advanced colonic mucinous adenocarcinoma developed severe acneiform rash and pruritus during EGFRI therapy with panitumumab. Initial standard treatment with oral doxycycline was discontinued after two days due to severe gastrointestinal intolerance characterized by intense nausea and dyspepsia. With limited access to dermatological consultation, treatment with rose stem cell-derived exosomes (RSCEs) provided rapid symptom relief. Significant improvement was observed within 24 h, with complete resolution of pruritus and substantial reduction in inflammatory lesions within 72 h. RSCEs demonstrate anti-inflammatory effects through the modulation of pro-inflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting fibroblast proliferation and collagen synthesis enhancement. They may represent a possible alternative to corticosteroids, avoiding associated side effects such as skin atrophy, delayed wound healing, and local immunosuppression. This case underscores the potential of innovative treatments like RSCEs in managing EGFRI-induced skin complications when standard therapies are not tolerated, particularly in healthcare systems with limited dermato-oncological resources. Full article

A study was conducted to examine the effects of the spray application of nine antifungal products, including microbial-derived fungicides, plant-derived fungicides, and chemical fungicides, on the grass Achnatherum inebrians that was either host to Epichloë gansuensis (E+) or E. gansuensis-free (E−) and that was exposed to Blumeria graminis, the fungal pathogen causing powdery mildew. The Epichloë endophyte is a seed-borne mutualistic biotrophic fungus whose growth is fully synchronized with the host grass. Bl. graminis is a biotrophic pathogen that continually infects leaves and stems via conidia, the formation of appressoria, leading to the presence of haustoria in epidermal cells. Prior to fungicide application, the presence of endophytes significantly increased the resistance of A. inebrians to powdery mildew and was able to increase the chlorophyll content. However, the positive effects of the Epichloë endophyte on the plant were suppressed with the use of some fungicides and the increase in the number of sprays, but the reciprocal relationship between the Epichloë endophyte and the plant was not significantly disrupted. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease stemming from genetic susceptibility and environmental factors. It is characterized by immune dysregulation, increased mast cell activity, elevated levels of immunoglobulin E (IgE), and excessive proinflammatory mediator expression. These factors contribute to hallmark symptoms such as pruritus, erythema, and skin barrier dysfunction. In this study, we investigated the antioxidant and anti-inflammatory effects of Taraxacum mongolicum (WTM) water extract, as well as its skin barrier regulation and immune functions in AD. In the present study, we explored the therapeutic efficacy and underlying mechanisms of WTM in a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB). Mice were administered WTM orally or topically for 14 consecutive days. The results demonstrated that WTM treatment significantly alleviated clinical severity, showing reductions in skin lesion scores, epidermal thickness, mast cell infiltration, and scratching behavior, compared to the DNCB-treated group. Mechanistically, WTM reduced serum levels of IgE and proinflammatory cytokines (IL-4, IL-6, IL-1β, TNF-α, and IL-31) while suppressing the expression of the JAK/STAT/TSLP signaling pathway in skin tissues. Furthermore, WTM inhibited the TLR4/NF-κB and MAPK pathways and enhanced antioxidant defense by elevating superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. These findings indicate that WTM attenuates DNCB-induced AD progression in mice, likely through the dual modulation of inflammatory signaling and oxidative stress. These findings suggest that WTM may modulate the immune response and alleviate AD symptoms by inhibiting the TLR4/NF-κB, MAPK, and JAK/STAT/TSLP pathways. Full article

AT-hook motif nuclear-localized (AHL) genes play critical roles in chromatin remodeling and gene transcription regulation, profoundly influencing plant growth, development, and stress responses. While AHL genes have been extensively characterized in multiple plant species, their biological functions in pepper (Capsicum annuum L.) remain largely uncharacterized. In this study, we identified 45 CaAHL genes in the pepper genome through bioinformatics approaches. Comprehensive analyses were conducted to examine their chromosomal distribution, phylogenetic relationships, and the structural and functional features of their encoded proteins. Phylogenetic clustering classified the CaAHL proteins into six distinct subgroups. Transcriptome profiling revealed widespread expression of CaAHL genes across diverse tissues—including roots, stems, leaves, flowers, seeds, pericarp, placenta, and fruits—at various developmental stages. Quantitative real-time PCR further demonstrated that CaAHL1, CaAHL33, and CaAHL23 exhibited consistently high expression throughout flower bud development, whereas CaAHL36 showed preferential upregulation at early bud development stages. Expression profiling under hormone treatments and abiotic stresses indicated that CaAHL36 and CaAHL23 are auxin-inducible but are repressed by ABA, cold, heat, salt, and drought stress. Subcellular localization assays in Nicotiana benthamiana leaf epidermal cells showed that both CaAHL36 and CaAHL23 were predominantly localized in the nucleus, with faint expression also detected in the cytoplasm. Collectively, this study provides foundational insights into the CaAHL gene family, laying the groundwork for future functional investigations of these genes in pepper. Full article