Search Results (13,450)

Tumor-associated glycosylation is a defining hallmark of cancer, exerting profound effects on multiple aspects of tumor biology. This phenomenon arises from the central role of glycosylation in a wide range of cellular processes and its inherently diverse structural complexity. In cancer cells, aberrant glycosylation often results in the modification of glycoconjugate structures, leading to alterations in cell surface architecture that disrupt cellular homeostasis and signaling pathways. These changes can enhance tumor cell proliferation, invasion, and metastasis by modulating cell adhesion, receptor activation, and intracellular communication. Beyond its direct impact on cancer cells, tumor-associated glycosylation plays a pivotal role in shaping the tumor microenvironment. Aberrant glycan structures influence immune cell infiltration by altering antigen presentation and immune checkpoint interactions, contributing to immune evasion. Additionally, these modifications regulate angiogenesis by affecting endothelial cell function and promoting the formation of aberrant vasculature, which supports tumor growth and metastasis. Glycosylation also mediates tumor–stroma interactions, influencing extracellular matrix remodeling and fibroblast activation, further enhancing cancer progression. This interplay between cancer-associated glycan modifications and their functional roles in tumorigenesis presents a promising therapeutic approach. Unlike conventional treatments, glycan-targeting therapies confer high tumor specificity, operate independently of canonical immune checkpoint targets, and help mitigate immune cell exhaustion. This review explores commonly dysregulated glycan motifs implicated in tumorigenesis and delves into their mechanistic contributions to cancer pathogenesis. We then highlight emerging opportunities for therapeutic intervention, including the development of glycan-targeted therapies and biomarker-driven strategies for cancer diagnosis and treatment. We also outline where glycan-targeted agents (e.g., desialylating biologics, glycomimetics, and anti-glycan mAbs) can complement checkpoint blockade and potentially overcome immune escape. Full article

In vitro fertilisation via oocyte donation is a unique reproductive technique in which the embryo is fully separate from the receiver. This compels the immune system to exert more effort at the interface between the uterus and the remainder of the body. This setting has maintained interest in peri-transfer glucocorticoid treatment as a possible approach to modify endometrial immunity and enhance implantation. Nevertheless, the data for this procedure are disjointed and mostly derive from investigations on autologous in vitro fertilisation. This narrative review consolidates contemporary evidence on endometrial immunology in oocyte donation cycles, analysing the mechanistic basis, clinical results, and constraints related to peri-implantation glucocorticoid therapy. Outcomes from randomised studies in autologous cycles consistently demonstrate that there is no advantage in live birth rates, but the claimed improvements in clinical pregnancy rates are from heterogeneous and low-quality data. Limited research exists on people who have received oocyte donations. The majority are diminutive and non-random, often integrating glucocorticoids with other therapies such as antibiotics, granulocyte colony-stimulating factor, or endometrial damage. These designs inhibit the dissociation of the independent impact of glucocorticoids. Recent comprehensive randomised studies on recurrent implantation failure further demonstrate the lack of advantages in live births and highlight possible safety issues. The current data do not support the usual use of peri-transfer glucocorticoids in oocyte donation for in vitro fertilisation; nevertheless, short-term, low-dose treatment may be justified in meticulously chosen immunological profiles. There is an urgent need for rigorously designed randomised studies focused only on oocyte-donation recipients to elucidate the therapeutic effectiveness, safety, and suitable clinical context for glucocorticoid treatment in this expanding patient demographic. Full article

Background/Objectives: Despite the clinical success of immune checkpoint blockade (ICB), its efficacy remains limited in immunologically “cold” tumors, primarily due to poor immunogenicity and an immunosuppressive tumor microenvironment (TME). Chemo-immunotherapy offers a potential strategy to enhance ICB response, yet its application is often hindered by inadequate tumor-targeted delivery and systemic immunosuppressive side effects. Biomimetic nanotechnology represents a promising approach to overcoming these limitations by improving drug delivery and facilitating effective combination regimens. Methods: We developed a biomimetic nanosystem (NVs@DOX) through genetic engineering of cellular membranes and optimized nanoformulation techniques, enabling co-delivery of doxorubicin (DOX) and ICB agents. This design aims to maximize synergistic antitumor effects while minimizing adverse impacts. Results: In vitro studies demonstrated the potent cytotoxicity of NVs@DOX, including significant inhibition of cancer cell proliferation and complete suppression of colony formation. In a 4T1 murine breast cancer model, NVs@DOX treatment led to substantial tumor growth inhibition (approximately 72%) without notable body weight loss, underscoring a favorable safety profile alongside enhanced therapeutic efficacy. Conclusions: The NVs@DOX platform effectively integrates doxorubicin with ICB within a biomimetic nanocarrier, significantly improving chemo-immunotherapy outcomes. This strategy highlights the potential of genetically engineered cellular nanoparticles as a promising combinatorial approach for the treatment of breast cancer. Full article

Current research on glial cells has primarily focused on central nervous system glial cells (CNS glia), with relatively fewer studies on EGCs. Given the critical role of EGCs in maintaining intestinal homeostasis and neural function, this study aimed to investigate their immunomodulatory effects under inflammatory conditions. Primary EGCs were isolated and an inflammatory model was established by treatment with lipopolysaccharide (LPS). Following LPS induction, cellular samples were collected for transcriptomic analysis to identify differentially expressed genes. The analysis revealed that 88 genes were significantly altered, with 60 upregulated and 28 downregulated. Through Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping, and protein–protein interaction (PPI) network analysis, several key regulatory genes were identified: chemokine-related genes (IL8L2, IL8L1, CCL4, CCL5, and CX3CL1); negative feedback regulation-related genes (TNFAIP3 and ZC3H12A); homeostasis-maintaining genes (C1QB and LY86); and arachidonic acid metabolism-related genes (PTGS2 and GGT2). Under LPS stimulation without impairing EGC viability, EGCs may recruit immune cells by regulating the aforementioned genes. Additionally, arachidonic acid and its metabolites likely play important regulatory roles in EGC-mediated immunomodulation. These findings provide new theoretical insights and potential targets for further elucidating the pathogenesis of intestinal inflammation and developing targeted therapies. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Objective: Glaucoma is a complex optic neuropathy characterized by the progressive loss of retinal ganglion cells (RGCs). Animal models are crucial tools for deciphering its multidimensional pathogenesis and evaluating novel therapeutic strategies. This review aims to systematically summarize the establishment methods, application advances, and future development trends of various glanimal models. Methods: The literature for this review was identified through systematic searches of electronic databases, including PubMed, Web of Science Core Collection, and Google Scholar. The search strategy utilized a combination of keywords and their variants: “glaucoma”, “animal models”, “retinal ganglion cells”, “intraocular pressure”, “neuroprotection”, “immune inflammation”, “fibrosis”, and “filtration surgery”. The search focused on articles published between 2015 and 2025 to cover the major advances of the last decade. The scope encompassed original research articles, reviews, and meta-analyses. Results: Diverse glanimal models successfully replicate different facets of glaucoma, elucidating multidimensional pathogenesis involving mechanical stress, immune inflammation, excitotoxicity, oxidative stress, and fibrosis. These models have played an indispensable role in screening neuroprotective agents, evaluating anti-fibrotic strategies, and validating the application of advanced imaging and functional assessment technologies. Current research is evolving towards model standardization, multi-factor simulation, and the integration of novel drug delivery systems and immunomodulatory strategies. Conclusions: The diversification of glanimal models provides a powerful platform for in-depth investigation of disease mechanisms and the development of innovative therapies. Future research should focus on establishing standardized models that better mimic the clinical pathological state and deeply integrating multimodal assessment technologies with targeted therapies. This will facilitate the translation of basic research into clinical applications, ultimately achieving personalized precision medicine for glaucoma. Full article

With the global increase in population aging, allergic diseases in older adults are becoming an increasingly relevant clinical and public health challenge. Age-related molecular and cellular alterations significantly affect the pathophysiology, clinical manifestations, diagnosis, and management of major allergic diseases in the elderly. This review focuses on immunosenescence in major allergic conditions, including asthma, chronic urticaria and angioedema, dermatitis, food and drug allergies, and hymenoptera venom hypersensitivity. Particular emphasis is placed on molecular mechanisms underlying immune aging, such as inflammaging, dysregulation of innate and adaptive immune responses, epithelial barrier dysfunction, microbiota alterations, neuro-immune interactions, and age-related comorbidities. Sex-related differences in immune responses are also addressed, together with current diagnostic and therapeutic strategies, including the opportunities and limitations of biologic therapies in aging populations. Despite growing interest in this field, a major limitation remains the paucity of studies specifically targeting geriatric populations, underscoring the need for age- and sex-specific research and dedicated clinical trials. A personalized approach integrating frailty assessment and immune profiling is essential to optimize the management of allergic diseases in older adults. Full article

Background/Objectives: Sulfated polysaccharides from Spirulina platensis have shown various promising biological activities, but their anticancer effects in lung cancer models remain poorly characterized. In this study, sulfated polysaccharide-rich fractions (SPPs) were tested on A549 non-small cell lung cancer (NSCLC) cells to evaluate their cytotoxic, oxidative, and immunomodulatory activity. Methods: The potential of SPPs to interfere with A549 cell viability, to modulate intracellular reactive oxygen species (ROS) levels, to produce pro-inflammatory effects, and to induce apoptosis was evaluated. Co-administration experiments were also performed using Gefitinib, a drug commonly used in NSCLC therapy. Non-cancerous human bronchial epithelial cells (16HBE) were included to assess the ability of SPPs to selectively target tumoral cells. Results: Our findings show that SPPs significantly reduced A549 cell viability in a concentration-dependent manner and increased ROS levels. This effect was associated with apoptotic DNA fragmentation and modulation of apoptosis-related genes, including upregulation of BAX and CASP-9, and downregulation of BCL-2, MTOR, and BIRC5. SPPs also induced a controlled pro-inflammatory response by increasing ACE2, NF-κB1, and CCL2 expression while reducing COX-2 levels. In co-administration experiments with Gefitinib, a cancer drug used to treat NSCLC, enhanced cytotoxic and pro-apoptotic effects were observed. Importantly, at active concentrations (150–250 µg/mL) SPPs were not found to produce cytotoxicity or apoptosis in 16HBE cells. Conclusions: Overall, these findings suggest that SPPs may selectively target NSCLC cells by promoting redox imbalance, apoptosis, and immune response, without affecting healthy cells, supporting their potential as natural adjuvants in lung cancer treatment. Full article

Peripheral inflammation is increasingly recognized as a critical driver of sustained neuroinflammation and cognitive dysfunction in neurodegenerative and inflammation-associated disorders. Systemic inflammatory mediators can compromise blood–brain barrier integrity, activate glial cells, and initiate maladaptive neuroimmune cascades that disrupt hippocampal–prefrontal circuits underlying learning and memory. Here, we investigated whether early systemic administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) mitigates inflammation-driven cognitive deficits in a chronic lipopolysaccharide (LPS) mouse model. Adult mice received daily LPS injections for seven days to induce persistent systemic and central inflammation, which was confirmed by serum and hippocampal cytokine analyses in a separate cohort at the time of MSC administration, followed by intravenous MSC treatment immediately after cessation of the inflammatory insult. Behavioral testing revealed significant impairments in spatial working memory, recognition memory, and associative learning. These deficits were accompanied by pronounced microglial activation, immune cell accumulation, astrocytosis, and a shift toward a pro-inflammatory cytokine milieu with suppression of IL-10 in the hippocampal CA1 region and medial prefrontal cortex. Early MSC treatment attenuated glial reactivity, reduced pro-inflammatory cytokines, restored IL-10 expression, and partially rescued cognitive performance. Collectively, these findings identify a post-inflammatory therapeutic window in which early MSC-based immunomodulation can rebalance neuroimmune signaling and limit inflammation-induced hippocampal–prefrontal circuit dysfunction, highlighting a clinically relevant strategy for targeting cognitive impairment associated with chronic systemic inflammation. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder with limited effective therapies. NRICM102, a traditional multi-herbal formulation originally developed for COVID-19, exhibits anti-inflammatory and immunomodulatory potential. Objectives: The aim of this study was to investigate the therapeutic efficacy of NRICM102 in a COPD-relevant inflammatory lung injury mice model. Methods: Mice were exposed to lipopolysaccharide (LPS) and benzo[a]pyrene (B[a]P) to induce chronic airway inflammation and structural lung damage and treated with NRICM102 (1.5–3.0 g/kg) or dexamethasone. Lung function, histopathology, transcriptomic profiling, and protein expression of key inflammatory markers were assessed. Results: NRICM102 significantly restored LPS+B[a]P-induced enhanced pause (Penh) and arterial oxygen saturation (aO₂%), similar to the effect of dexamethasone. Histological analysis revealed marked alveolar damage, inflammatory cell infiltration, and fibrosis in the model group, all of which were significantly attenuated by NRICM102 in a dose-dependent manner, with high-dose (3.0 g/kg) treatment showing pronounced structural preservation. Transcriptomic profiling revealed that NRICM102, particularly at 3.0 g/kg, partially reversed COPD-associated gene expression patterns, characterized by reduced activation of cytokine signaling, chemokine activity, and antigen presentation pathways. GO, DO, and KEGG enrichment analyses indicated selective modulation of immune-related pathways, with high-dose NRICM102 affecting genes involved in adaptive immunity and cytokine receptor interactions, including a subset of 150 reverted genes. Immunofluorescence analysis confirmed dose-dependent reductions in key inflammatory, immune, and mucus-related markers, including IL-1β, NLRP3, Muc5ac, and MMP12 expression. Conclusions: NRICM102 confers significant protective effects against COPD-relevant inflammatory lung injury by improving pulmonary function, preserving lung architecture, and selectively modulating immune and inflammatory pathways. These results provide preclinical evidence supporting the potential of NRICM102 to modulate inflammation and immune responses associated with COPD-related pathology, although further studies are needed to establish its therapeutic relevance. Full article

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

Epstein–Barr virus (EBV) is a key oncogenic pathogen implicated in the development of lymphomas, particularly among HIV-positive and immunocompromised individuals. While the association between EBV and lymphoma is well established, the mechanisms underlying progression from infection to malignancy—especially in the head and neck region—remain incompletely understood. This review offers a comprehensive analysis of the pathophysiological pathways by which EBV and HIV contribute to lymphomagenesis, with an emphasis on latency patterns, immune evasion, and epigenetic “hit and run” oncogenesis. Notably, it integrates novel findings on the diagnostic implications of EBV latency proteins, explores HIV-mediated B-cell dysregulation, and evaluates the emerging landscape of targeted therapies, including monoclonal antibodies and lytic cycle inducers. By focusing specifically on head and neck lymphomas, this review underscores a clinically underrepresented domain and offers insights that may guide future diagnostics, surveillance, and treatment strategies in vulnerable patient populations. This review also highlights the pressing need for improved animal models and continued research into EBV-specific therapeutic targets. Full article

The tumor microenvironment (TME), composed of various immune and non-immune cells, as well as cancer stem cells, plays a critical role not only in promoting cancer cell proliferation and metastasis but also in modulating therapeutic response. A wide range of therapeutic strategies targeting the TME are currently employed in cancer treatment, including standard chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapies, agents targeting cancer-associated fibroblasts (CAFs), oncolytic viruses (OVs), cold atmospheric plasma therapy, and nanovaccines. This review provides a comprehensive overview of the influence of the TME on cancer sensitivity to these therapies across all types of solid tumors. Full article

Objective: The aim of this study was to develop and evaluate non-antibiotic strategies against Helicobacter pylori by establishing a bovine immune milk platform and designing a synergistic multi-antigen immunogen to enhance humoral immune responses. Methods: Inactivated Helicobacter pylori (H. pylori) was used to immunize dairy cows, and the resulting immune milk was characterized for antibody specificity, acid stability, and target antigens via ELISA, Western blot, agglutination assays, and mass spectrometry. Key identified antigens (UreA, UreB, UreE, UreG, HypA, FlaA, and FlaB) were produced as recombinant proteins. Their immunogenicity was evaluated in a murine model, comparing single antigens with various protein combinations. Immune responses were assessed by antigen-specific IgG ELISA, bacterial agglutination titers, flow cytometry for T-cell activation, and histopathology for safety. Results: Immune milk contained high-titer, acid-stable IgG antibodies targeting multiple H. pylori virulence factors. In mice, while single proteins induced specific IgG, a multi-antigen cocktail (FlaA + FlaB + HypA + UreA + UreB + UreE + UreG) elicited significantly higher serum agglutination titers (~7 × 10³) than single antigens or inactivated whole-cell vaccine, alongside robust CD4⁺ T-cell activation. No formulations showed any hepatorenal or splenic toxicity. Conclusion: Bovine immune milk is a viable platform for acid-stable antibody delivery. A rationally designed multi-antigen cocktail synergistically enhances functional humoral immunity in vivo, providing a promising foundation for developing antibody-based or subunit vaccine strategies against H. pylori. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article