Search Results (14,818)

The risk of developing some types of head and neck squamous cell carcinoma (HNSCC) is seven times higher in males, and such disparities may not be associated only with tobacco and alcohol consumption or HPV infection. Therefore, the endocrine microenvironment is considered another risk factor, as epidemiologic studies have unequivocally shown the protective effect of estrogen in women. This research was focused on progesterone receptors (PRs), the least-studied sex hormone receptors in HNSCC. Our study included fresh tissue samples from 95 primary tumors, 25 metastatic lymph nodes and 40 healthy oral mucosa. Gene expression of nuclear (PGR) and seven membrane PRs (PAQR5, PAQR6, PAQR7, PAQR8, PAQR9, PGRMC1 and PGRMC2) was analyzed by qRT-PCR and associated with clinicopathological characteristics. The results showed that, compared to control tissue, PGR was increased in metastatic lymph nodes, while PAQR5, PAQR7, PAQR8 and PAQR9 were decreased in primary tumors (all p < 0.05). The expression of almost all PRs was greater in older patients and showed moderate to strong positive mutual correlations in both tumors and controls. PARQ8 and PAQR9 were increased in females and pT4 tumors (all p < 0.05). Survival analysis showed that higher PAQR5 (hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.19–6.57, p = 0.019) and PAQR7 (HR 2.0, 95% CI 1.01–3.81, p = 0.048) were associated with worse overall survival, but their independence was not proven in multivariate analysis. Although most PRs were reduced in primary tumors, an increased PAQR5 expression, also associated with tumor invasion markers, could likely mark a specific aggressive, advanced stage of primary tumors and potentially serve as a negative prognostic biomarker for HNSCC. Full article

Infected wound repair remains a global healthcare challenge, primarily due to bacterial infection and a pathological microenvironment characterized by elevated glucose levels and oxidative stress. In this work, a quaternized carboxymethyl chitosan (QCMCS)/oxidized sodium alginate (OSA)/tannic acid (TA)/sodium tetraborate (STB) hydrogel was developed for controlled TA release and diabetic wound repair. The QCMCS/OSA/TA/STB hydrogel exhibited potent antibacterial activity, with inhibition rates exceeding 99% against S. aureus and MRSA and 86% against E. coli, arising from the synergistic action of QCMCS and TA. Meanwhile, the introduction of TA enhanced antioxidant performance (radical scavenging rates of 66.72% and 93.16% against DPPH and ABTS, respectively), and STB reinforced mechanical strength with a compressive resistance of 140.78 kPa through a dual cross-linking network. In vitro biocompatibility evaluations demonstrated that the hemolysis ratios of all hydrogels were below 5%, and the survival rate of Human umbilical vein endothelial cells (HUVECs) was over 93%. Reversible borate ester linkages between STB and the catechol groups of TA protect TA from oxidative degradation and allow stimulus-responsive release under elevated glucose and oxidative conditions. This responsive hydrogel represents a promising multifunctional platform for diabetic wound management. Full article

Natural antibacterial food packaging materials endowed with environmental responsiveness are garnering substantial research interest in sustainable food preservation. This study reports the development of a pH-responsive antimicrobial composite film through encapsulation of eugenol—a natural phenolic compound—within zeolitic imidazolate framework-8 (ZIF-8). The engineered eugenol@ZIF-8 system demonstrated pH-dependent release characteristics, with cumulative release reaching 32.2% at pH 6 versus merely 0.61% at pH 7 over 4 h. Subsequent integration of this nanocarrier into a polyvinyl alcohol (PVA)/hydroxypropyltrimethyl ammonium chloride chitosan (HACC) matrix yielded a multifunctional composite film for active food packaging applications. The characterization of film revealed that while eugenol@ZIF-8 incorporation slightly compromised mechanical strength (tensile resistance decreased by 18.7%) and flexibility (elongation at break reduced to 54.3% of control), it significantly enhanced hydrophobicity (water contact angle increased to 92.5°) and thermal stability (decomposition temperature elevated by 34 °C). The composite film demonstrated synergistic antibacterial efficacy through the combined action of Zn²⁺ ions, ZIF-8 nanostructures, and eugenol, achieving 88% inhibition against E. coli. Practical validation through fresh noodle preservation trials confirmed the material’s effectiveness, with the optimized formulation (PVA-HACC-2% eugenol@ZIF-8, PHEZ2) extending shelf life by >5 days compared to conventional packaging. This work establishes a novel strategy for engineering intelligent ZIF-based packaging systems that respond to food spoilage microenvironments, offering significant potential for reducing food loss. Full article

Saline–alkali soil salinization is a global ecological crisis affecting 932 million hectares of land worldwide, posing a severe threat to food security and ecological sustainability. Traditional improvement methods, such as chemical amendments and hydraulic engineering, are limited by high costs and environmental risks, whereas microbial amendments have emerged as eco-friendly and sustainable alternatives due to their ability to regulate soil microenvironments and enhance plant stress resistance. However, a comprehensive synthesis of their core mechanisms, global application progress, and regional adaptation characteristics is still lacking, hindering the standardization and promotion of related technologies. This review, conducted in accordance with PRISMA guidelines, systematically synthesizes 112 core studies (1990–2025) retrieved from Web of Science, Scopus, and CNKI databases, focusing on three core research objects: salt-tolerant microbial communities in saline–alkali soils (dominant taxa, functional genes, metabolic characteristics), development and optimization of microbial amendments (strain screening, composite formulation, carrier selection), and mechanisms and application effects of microbial remediation (soil–plant–microbe interactions, physicochemical improvement, crop growth promotion). Key findings include the following. (1) Dominant microbial taxa (e.g., Proteobacteria, Actinobacteria) exhibit region-specific adaptation strategies, with salt tolerance thresholds and functional characteristics varying by soil type (coastal vs. inland saline–alkali soils). (2) Composite microbial amendments, especially those combined with biochar or organic fertilizers, achieve synergistic effects in desalination, alkali reduction, and fertility improvement. (3) Core mechanisms involve organic acid-mediated pH regulation, EPS-driven ion adsorption, and plant hormone-induced stress tolerance. (4) Microbial remediation technologies have been successfully applied globally (e.g., China, Africa, Americas), resulting in average crop yield increases of 15–42% and soil salinity reductions of 30–50%. This review provides a standardized technical framework for the development and application of microbial amendments, offers theoretical support for region-specific remediation strategies, identifies key challenges (e.g., strain stability, cost control) and future research directions (e.g., gene-edited strains, smart monitoring integration), and thus facilitates the industrialization and large-scale promotion of microbial remediation technologies to address global saline–alkali soil issues. Full article

Environmental hazard-induced male infertility has become a major public health issue. The concealment and accumulation of environmental hazards, and their interactions with the endogenous immune network, have long been underappreciated. As the central organ for sperm maturation and motility acquisition, the epididymis plays a vital role in male fertility, and the homeostasis of the epididymal immune microenvironment (EIM) is essential. Nevertheless, a systematic synthesis of common environmental hazards and their impact on EIM, which can lead to male infertility, remains lacking. This review comprehensively summarizes the composition, functionality, and key characteristics of the EIM and underscores its critical role in preserving male reproductive health. We further evaluate and delineate the disruption of EIM homeostasis resulting from major categories of environmental exposures—including chemical, physical, biological, and behavioral hazards—and discuss their shared pathophysiological mechanisms. By integrating evidence linking environmental insults, EIM dysregulation, and male infertility, this work aims to identify pivotal molecular mechanisms from an immunological perspective. The findings provide a mechanistic foundation for the development of targeted interventions and preventive strategies against environmental hazard-induced male infertility. Full article

Photodynamic therapy (PDT) is a technique based on the use of photosensitizers activated by light to destroy cancer cells in the presence of oxygen. This enables localized cancer treatment and, in some settings, fluorescence-guided visualization. However, the efficacy and clinical translation of PDT have been limited by the low specificity of traditional photosensitizers. The aim of the study is to create a ligand-guided PDT approach for pancreatic ductal adenocarcinoma (PDAC) using a peptide-conjugated photosensitizer binding to integrin αvβ6, which is a receptor linked to tumor growth and prevalent in PDAC cells. Current treatment options for this tumor are limited, with surgical resection and chemotherapy only effective when the tumor is detected early. Given the limited treatment options for PDAC, PDT via αvβ6 offers a new pathway for precision treatment. The cyclic peptide cyclo[FRGDLAFp(NMe)K], recognized for its high affinity to αvβ6, was chosen to guide a phthalocyanine-class photosensitizer toward αvβ6-expressing PDAC models. The PDT approach was further refined by developing 3D spheroid models and in vivo BxPc3 xenograft models in NOD/SCID mice, where its therapeutic efficacy was assessed. In the absence of a non-targeted control photosensitizer, a contribution from non-specific accumulation and EPR effects in the in vivo setting cannot be fully ruled out. This study highlights the potential of a peptide-guided photosensitizer, demonstrating uptake and photodynamic activity in spheroids, with moderate in vivo results addressing tumor microenvironment challenges. Optimization of PDT dosing, laser precision, and preclinical models, such as patient-derived xenografts, are crucial to enhance clinical translation. Full article

Background/Objectives. Globally, hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and represents the third leading cause of cancer-related mortality. Despite advances in diagnosis and treatment, the overall prognosis of HCC remains poor, largely due to late-stage presentation and high rates of vascular invasion. Portal vein thrombosis constitutes a significant complication of HCC, with an occurrence rate of 35–50%. Portal vein tumour thrombosis (PVTT) represents an aggressive form that is closely linked to decreased patient survival. The incidence of PVTT increases over time, from approximately 21% in the first year after diagnosis to nearly 46% by the third year, highlighting its high prevalence and progressive nature. The introduction of immunotherapy has marked a paradigm shift in the management of HCC. Immune checkpoint inhibitors, particularly those targeting the PD-1/PD-L1 and CTLA-4 pathways, have demonstrated durable responses and significant survival benefits in certain patients with advanced HCC. Furthermore, emerging evidence suggests that combining immunotherapy with local or systemic therapies, such as trans arterial chemoembolization, hepatic arterial infusion chemotherapy, radiotherapy or tyrosine kinase inhibitors, may further enhance antitumor efficacy by modulating the tumour microenvironment and promoting synergistic immune activation. Method: This narrative review provides a comprehensive evaluation of immunotherapy in patients with HCC and PVTT, with a focus on its efficacy as both monotherapy and in combination with other treatment modalities in terms of tumour response, progression-free survival, and overall survival. It also addresses safety, patient selection, and emerging strategies to optimize outcomes in this high-risk population. Conclusions: The combination of multiple therapies could improve the patient’s prognosis by achieving objective response rate of almost 82%, disease control rate of 97% and progression free survival of 12.9 months with quadruple therapy (HAIC-TACE combined with targeted and immunotherapy). Full article

Large bone defects remain a major clinical challenge, as current treatments primarily provide mechanical stability while often insufficiently addressing the biological microenvironment. The cell-deposited extracellular matrix (CD-ECM) represents a promising strategy to improve implant bioactivity by mimicking key features of the native tissue. In this study, we compared CD-ECMs from adipose tissue-derived mesenchymal stromal cells (ASCs), ASC-derived osteoprogenitor cells, and dermal fibroblasts. ECM composition was analyzed, and its ability to support the osteogenesis of reseeded skeletal stem cells (SSCs) was assessed. Subsequently, the best performing cells were used to produce CD-ECM on a 3D scaffold. Furthermore, we improved the ECM by treating the ECM-producing cells with dextran sulfate (Dx-S). Fibroblast-derived ECM showed higher collagen and glycosaminoglycan contents compared to ASC-ECM or osteoprogenitor-ECM. Furthermore, only the fibroblast-derived ECM (Fibro-ECM) exerted a supportive effect on the osteogenesis of SSCs. SSCs seeded on ECM showed a higher proliferation rate and enhanced osteogenesis. Supplementation with dextran sulfate further increased ECM deposition and osteogenic potential. We showed that fibroblasts produced substantially more ECM with a stronger pro-osteogenic effect than ASCs or osteoprogenitor cells. The ECM and its pro-osteogenic effect could further be increased when fibroblasts were treated with Dx-S. Together, these results highlight Fibro-ECM as a promising and easily accessible cell-derived ECM deposition strategy to improve the biological performance of implants in bone regeneration. Full article

Osteoarthritis (OA) is a prevalent degenerative disease of the musculoskeletal system worldwide. Self-assembled hydrogels, as a novel drug delivery system, have demonstrated significant advantages in the treatment of OA. Through non-covalent interactions such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and π-π stacking, these hydrogels spontaneously form a three-dimensional network structure under physiological conditions without the need for chemical crosslinking agents, offering excellent biocompatibility, injectability, and controllable degradation properties. This system enables in -situ gelation within the joint, minimally invasive injection, sustained and controlled drug release, and intelligent responsive release. It is suitable for various delivery forms, including single-drug targeted delivery, exosome-based composite synergistic delivery, and microenvironment-responsive precise delivery, effectively inhibiting inflammation and promoting cartilage repair. Despite facing challenges in clinical translation, such as consistency in large-scale production, long-term safety evaluation, and regulatory standards, continued optimization in material design and preparation processes holds promise for self-assembled hydrogels to become a key platform for precise and minimally invasive OA treatment, offering new solutions for joint disease therapy. Full article

Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may require multiple surgical interventions with associated morbidity. Increasing evidence has highlighted that nonunion is a multifaceted problem, not only a result of mechanical failure, but also a product of persistent dysregulation of the osteoimmune microenvironment manifested as impaired osteogenesis and bone healing. While current approaches focus on enhanced fixation and various bone grafting strategies, these treatments often fail to coordinate healing with osteoimmune regulation. This review summarizes the emerging biologic and bioengineering approaches that target osteoimmunology to enhance fracture repair. Scaffold systems, including metals, bioceramics, hydrogels, and micro/nanoparticle formulations, are being increasingly engineered to provide structural support while directing macrophage polarization and stimulating osteogenic signaling. We also review cell-based therapies and gene-modified constructs that are being developed to introduce osteoimmunology cues that halt chronic inflammation and promote an osteogenic microenvironment. Full article

Gastric cancer (GC), one of the most common malignancies worldwide, is strongly linked to metastasis, significantly worsening prognosis and survival rates. Metastasis initiation relies on epithelial cells undergoing an epithelial–mesenchymal transition and on an abnormal, leaky vasculature. Although the tumor cells involved in the metastatic process have a progression-associated gene signature associated with extracellular matrix organization and the epithelial-to-mesenchymal transition, they must originate from an immune-evasive ecosystem that allows tumors to hinder or evade immune surveillance, either by secreting immunosuppressive chemicals, recruiting regulatory immune cells, or expressing negative stimulatory immune checkpoint molecules such as PD-L1. Although the mechanism underlying the so-called “metastatic cascade” is beginning to emerge, the tumor microenvironment, or niche, in which metastatic cells arise, remains unknown. In this review, we speculate that the epithelial–mesenchymal transition generates PD-L1-expressing cancer stem cells within the primary tumor, which can form tumor niches that serve as sources of metastatic cells within the gastric adenocarcinoma microenvironment. Understanding the regulatory pathways governing metastasis may offer new avenues for developing more effective therapeutic approaches. Full article

Culturing cells and micro-tissue samples in 3D bio-scaffolding structures is gaining popularity; however, precise control of tissue micro-environment in such systems remains challenging. We describe a family of new hybrid bio-scaffolds with 3D O₂-sensing ability, produced by simple means from readily available bio-scaffolding and O₂-sensing materials. Three different types of phosphorescent O₂-sensing materials—polymeric microparticles (MPs), supramolecular probe MitoXpress and nanoparticulate probes NanO2 and Nano-IR (NPs)—were integrated in Matrigel and agarose scaffolding materials and evaluated. Key working characteristics of such hybrid scaffolds, including heterogeneity, stability, cytotoxicity, optical signals and O₂-sensing properties, ease of fabrication and use, were compared. The results show superiority of the Matrigel hybrids with NanO2 and Nano-IR probes. Demonstration experiments were conducted with HCT116 cells and individual spheroids derived from these cells, culturing them in the Matrigel–NP hybrid scaffolds and monitoring oxygenation and local O₂ gradients on a time-resolved fluorescence plate reader and by phosphorescence lifetime imaging microscopy (PLIM). Full article

Epstein–Barr virus (EBV) is an oncogenic virus implicated in several epithelial malignancies; however, its role in the tumor microenvironment of oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the association between EBV infection and clinicopathological and microenvironmental features of OSCC. A cross-sectional analysis was conducted on 62 archived OSCC biopsy specimens. EBV was detected using polymerase chain reaction (PCR), and clinical data were obtained from medical records. Tumor–stroma ratio (TSR), perineural invasion (PNI), lymphovascular invasion (LVI), and histological differentiation were assessed microscopically, while tumor-infiltrating lymphocytes (TILs) were quantified using ImageJ software version 1.54j (National Institutes of Health, Bethesda, MD, USA). EBV DNA was identified in 43.5% of cases. EBV positivity was significantly associated with older age (p = 0.046), especially among patients aged 60 years or older. All EBV-positive tumors exhibited a high tumor–stroma ratio, which was significantly associated with EBV status (p = 0.031). No significant associations were observed between EBV status and sex, tumor site, clinical stage, TILs, PNI, LVI, or histological differentiation. These findings indicate that EBV-positive OSCC is characterized by distinct microenvironmental features, particularly an elevated tumor–stroma ratio, and suggest a potential role for EBV status in microenvironmental profiling and prognostic stratification. Full article

Background/Objectives: Physical exercise reduces breast cancer (BC) risk and improves survival, yet the biological mechanisms remain incompletely understood. Exercise may modulate systemic immunity and local immune cell infiltration in the tumor microenvironment. In this systematic review and meta-analysis, we examined the effects of exercise on immune cells and immune-related markers in patients with BC. Methods: This study followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251082444). Four databases (PubMed, Web of Science, Scopus, and Cochrane Library) were searched from inception through December 2025. Randomized controlled trials evaluating exercise interventions in patients with BC or BC survivors and reporting immune cell outcomes were included. Meta-analyses were performed on studies reporting natural killer cells, natural killer cell activity, T-cell subpopulations, and B cells. Results: A total of 18 studies involving 911 participants (539 in exercise intervention groups) were included in the systematic review, with eight studies included in meta-analyses. Exercise interventions did not show significant effects on circulating natural killer cell counts, natural killer cell activity, T-cell subpopulations (CD3⁺, CD4⁺, and CD8⁺), or B-cell levels when compared to control groups. Conclusions: Exercise does not appear to induce consistent changes in resting circulating immune cell populations in patients with BC or BC survivors, indicating that exercise is immunologically safe while potentially exerting effects beyond circulating cell counts. Further large-scale research is required. Full article

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes, lacking expression of estrogen receptor, progesterone receptor, and HER2. Conventional chemotherapy and immune checkpoint inhibitors provide some benefit, but resistance and relapse are frequent. The search for novel targets has therefore become central to developing more effective and durable therapies. Recent advances in proteomics, structural biology, and targeted protein degradation are rapidly expanding the repertoire of actionable molecules in TNBC. This review summarizes current and emerging therapeutic strategies for TNBC, with a focus on targeted approaches designed to address tumor heterogeneity and resistance mechanisms. To this end, recent advances in targeted therapies are examined, including immune checkpoint inhibitors, PARP inhibitors, Trop-2–directed antibody–drug conjugates, anti-angiogenic agents, PI3K/Akt/mTOR pathway inhibitors, androgen receptor antagonists, and CDK4/6 inhibitors, highlighting results from completed and ongoing clinical trials. In addition, we explore novel targets identified through integrative omics approaches, as well as the role of the tumor metabolism and microenvironment in modulating therapeutic efficacy. Finally, we outline innovative radiotherapy strategies based on targeted radiation delivery and biological integration with systemic therapies. Collectively, this review provides an updated and novel overview of the evolving TNBC therapeutic landscape and highlights promising directions for the development of next-generation, biomarker-driven treatment strategies aimed at improving patient outcomes, maintaining a broad perspective on a very large class of targets. Full article