Search Results (496)

Oxidative stress is considered one of the cancer hallmarks, influencing tumor initiation, progression, and metastasis. High levels of reactive oxygen species (ROS) impair the effectiveness of the immune response in cancer patients. We examined changes in oxidative stress during immunotherapy, exploring the relationship between the immune system and clinical parameters related to oxidative burden. Several T-cell and myeloid subsets from 79 metastatic non-oncogene-addicted non-small-cell lung cancer (NSCLC) patients were analyzed using flow cytometry. Additionally, 20 cytokines were measured in serum samples, and sNox2-dp levels, an indicator of NOX2 activity, were assessed by ELISA. Seventy-nine healthy donors served as controls. The data showed that cancer patients had higher levels of sNox2-dp compared to healthy donors (p < 0.0001). Elevated sNox2-dp levels were associated with inflammation-related comorbidities (p = 0.008) and platelet counts (p = 0.03) in NSCLC patients. Furthermore, sNox2-dp displayed a negative correlation with immune cells involved in activation, such as proliferating (Ki67⁺) CD8⁺, PD1⁺ and effector lymphocytes, and a positive correlation with immunosuppressive PMN-MDSCs and inflammatory soluble immune factors, including IL1α, IL1β, IL6, IL10, CCL3, and CCL4. Oxidation levels decreased after immunotherapy (p = 0.04) and increased only in non-responder patients (p = 0.02). Oxidative stress may be indirectly affected by immunotherapy and could serve as a novel tool to identify responding patients in the NSCLC setting. Full article

Road target detection is a crucial aspect of current research in automotive advanced driver assistance systems and intelligent transportation systems, where accuracy, speed, and lightweight design are key considerations. Compared to various sensors employed in driving assistance systems, millimeter-wave radar offers advantages such as all-weather operation, low hardware cost, strong penetration capability, and the ability to extract rich spatial information about targets. This paper tackles the challenges posed by the characteristics of Range-Angle map data from 77 GHz Frequency-Modulated Continuous Wave radar—namely, non-visible light imagery, abstract representation, rich fine details, and overlapping features. To this end, this paper proposes MMPFNet, a lightweight model based on the hypergraph mechanism with attention enhancement, as an extension of YOLOv13. First, an M-DSC3k2 module is proposed based on the hypergraph mechanism to enhance attention toward small targets. Second, a detection head with a double-bottleneck inverted MBConv-block structure is designed to improve the model’s accuracy and generalization capability. Third, a lightweight PPLConv module is customized to transform the backbone network, enhancing the model’s lightweight design while slightly reducing its accuracy. Considering the differences from traditional visible light datasets, the Focus Expansion-IoU loss function is introduced into the model to focus attention on different regression samples. The MMPFNet model achieves significant improvements in detecting common road targets such as pedestrians, bicycles, cars, and trucks on the Frequency-Modulated Continuous Wave radar Range-Angle dataset compared to the baseline YOLOv13n model: mAP50-95 increases by 16%, precision improves by 6%, and recall rises by 8.7%. MMPFNet is also evaluated on other non-visible light datasets such as CRUW-ONRD and soundprint datasets. Compared to commonly used detection models like FCOS and RetinaNet, MMPFNet achieves significant performance gains, attaining state-of-the-art results. Full article

Breast cancer (BC) is a prevalent malignancy worldwide among women. HER2 overexpression in a subset of BC (HER2+ BC) serves as a critical oncogenic driver and contributes to immune evasion. The Raf Kinase Inhibitor Protein (RKIP), a metastasis suppressor and an immune enhancer, is underexpressed in HER2+ BC. The treatment of HER2+ BC with anti-HER2 mAbs or chemical inhibitors has resulted in significant clinical responses in a subset of patients; however, unresponsiveness in a larger subset was due to acquired and induced resistance. These findings highlight the need for the development of new effective therapies. By analyzing the signaling pathways mediated by both RKIP and HER2 in HER2+ BC, we have found that RKIP and HER2 downstream signaling and inductions showed an inverse relationship. These suggested the presence of a dysregulated RKIP-HER2 axis in HER2+ BC mediating immune evasion. These findings were corroborated by bioinformatic analyses. The immune evasion induced by the overexpression of HER2 was due, in part, to its regulation of the expression of PD-L1, the polarization of TAMs, the infiltration of suppressor cells (Tregs, MDSCs), and the inhibition of anti-tumor CD8+ T cells, resulting in an overall immunosuppressive TME. In contrast, RKIP expression inhibits critical signaling pathways that regulate HER2 expression, including the Raf-MEK-ERK, NF-kB, and PI3K/Akt pathways, thereby aborting HER2-mediated mechanisms of immune evasion. Overall, we analyzed the cross-talk signaling pathways between RKIP and HER2, established a novel dysregulated axis in HER2+ BC, and delineated the various mechanisms involved in the regulation of immune evasion by RKIP and HER2. Hence, we present various therapeutic strategies aimed at targeting the RKIP-HER2 axis in HER2+ BC to circumvent unresponsiveness to therapeutics and immune evasion. Full article

Prostate cancer remains largely refractory to immunotherapy, implying the existence of context-specific immune landscape programs that diverge between circulation and tumor. Here, we integrate bulk RNA sequencing from three cohorts (patient peripheral mononuclear cells, primary prostate tissue, and biochemical-recurrence tumors) with multiparameter flow cytometry, unsupervised UMAP/T-REX (Tracking Responders Expanding) mapping, and de novo discovery of long non-coding RNAs (lncRNAs) to characterize context-specific immunoregulation. Patient PBMCs revealed a coherent IL-1/TNF/IL-17 inflammatory architecture with strong chemotactic programs and an unexpected neutrophil-like signal despite density-gradient isolation, consistent with low-density PMN-MDSCs. In contrast, tumors broadly repressed chemokines and innate immune mediators, yet upregulated prostate cancer-associated lncRNAs, indicating local immune quiescence coupled with non-coding regulatory programs. Recurrent tumors acquired epithelial–mesenchymal transition and metabolic remodeling, accompanied by relapse-associated lncRNA signatures, whereas long-term nonrecurrent tumors preserved epithelial and stress-response networks. High-dimensional cytometry confirmed discrete, cancer-enriched myeloid clusters expressing CD47, SIRPα, PD-L1, CD73, and Galectin-9. Network analysis highlighted inflammatory hubs (CXCL2, PTGS2) in PBMCs and loss of mechanotransduction modules in tumors. Structural modeling uncovered a three-way junction and 3′ triple helix in lncRNA. Collectively, these data suggest that circulating inflammatory rewiring is associated with checkpoint-rich suppressor expansion and tumor immune quiescence, outlining integrated myeloid- and RNA-directed strategies for cancer research. Full article

To address the problem of insufficient detection accuracy, high false negative rate of small targets, and large positioning errors of ships in complex marine environments and foggy conditions, an improved DBL-YOLO method based on YOLOv11 is proposed. This method customizes and optimizes modules according to the characteristics of foggy scenes—the C3k2-MDSC module is designed to efficiently extract and fuse multi-scale spatial features, and a dynamic weight allocation mechanism is adopted to balance the contributions of features at different scales in the foggy and blurred environment; a lightweight BiFPN structure is introduced to enhance the efficiency of cross-scale feature transmission and solve the problem of feature attenuation in foggy conditions; a novel fusion of the Deformable-LKA attention mechanism is innovated, which combines a large receptive field and spatial adaptive adjustment capabilities to focus on the key contour features of blurred ships in foggy conditions; an Inner-SIoU regression loss function is proposed, which optimizes the positioning accuracy of dense and small targets through an auxiliary bounding box dynamic scaling strategy. Experimental results show that in foggy scenes, the recall rate is increased by 3.4%, the F1 score is increased by 1%, and mAP@0.5 and mAP@0.5:0.95 are increased by 1.4% and 3.1%, respectively. The final average precision reaches 98.6%, demonstrating excellent detection accuracy and robustness. Full article

It is broadly realized that the body’s metabolism has a profound impact on tumor progression. However, pathophysiological mechanisms underlying the metabolic modulation of the tumor immune microenvironment remain incompletely understood. Here, we report that long-chain fatty acids (LCFAs) can directly modulate the function of myeloid-derived suppressor cells (MDSCs), a central component of establishing the tumor immune microenvironment. In vitro or in vivo exposure to LCFAs significantly reduces the expression levels of signature immunosuppressive genes of both monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). As a result, mice fed with a diet of high LCFA content exhibit delayed tumor progression and prolonged survival in different cancer models. Furthermore, this LCFA-mediated inhibition of M-MDSCs and PMN-MDSCs correlates with enhanced CD8⁺ T antitumor immunity, which is abolished in tumor-bearing nude mice. These results have revealed a previously under-recognized role of LCFAs in the tumor immune microenvironment, implicating novel therapeutic strategies for cancer treatment. Full article

Ovarian cancer remains the most lethal gynaecological malignancy primarily due to late-stage diagnosis, high recurrence rate, and limited treatment efficacy. Current diagnostic tools, including imaging and serum markers, lack sufficient sensitivity and specificity for early detection. Increasing evidence highlights the critical role of myeloid-derived immune cells within the tumour microenvironment in shaping ovarian cancer progression and therapy response. Monocytes and their derivatives are central regulators of immune suppression, chemoresistance, and metastatic dissemination in ovarian tumours. Their recruitment and polarisation are governed by several signalling pathways offering promising therapeutic targets. Strategies including monocyte depletion, TAM reprogramming, MDSC maturation, DC vaccines, and their synergistic use with chemotherapy or immune checkpoint inhibitors are being explored to restore anti-tumour immunity in ovarian cancer. Parallel to therapeutic potential, the lymphocyte-to-monocyte ratio and its reciprocal monocyte-to-lymphocyte ratio have also emerged as potential accessible and cost-effective prognostic tools that predict disease aggressiveness and survival in ovarian cancer. This review features the diagnostic, prognostic, and therapeutic significance of monocytes and their derivatives in ovarian cancer management and highlighting new opportunities for next-generation immunomodulatory therapies. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

β-lactose is an anomer of interest for the pharmaceutical and food industries due to its techno-functional properties; however, its production is often costly and complex. In this study, the feasibility of using food-grade lactose (F-αL) to produce β-lactose was evaluated as an accessible and cost-effective alternative. For this purpose, the physicochemical characterization of this lactose was carried out through X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Modulated Differential Scanning Calorimetry (MDSC), Fourier Transform Infrared Spectroscopy (FTIR), and Raman Spectroscopy. The mutarotation process was also performed using alcoholic KOH solutions. Physicochemical characterization confirmed that commercial lactose consists mainly of α-lactose monohydrate, which is an ideal precursor for β-lactose production. Likewise, the conversion process efficiently yielded β-lactose, validating the feasibility of using food-grade lactose in this process, with a residual α-lactose content below 10%, indicating a high conversion efficiency. Thus, food-grade lactose emerges as a viable alternative for producing high-purity β-lactose. This finding represents a 90% reduction in production costs of this anomer, promoting the development of high-quality products in the pharmaceutical and food sectors. Full article

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that strongly suppress immunity and expand during tumor progression. Various antitumor chemotherapy agents can induce MDSC accumulation, reducing treatment effectiveness. We investigated the impact of the CHOP regimen and its components (cyclophosphamide (CTX), doxorubicin, vincristine, and prednisolone) on the dynamics of MDSC accumulation and the associated changes in immune cell profiles in the peripheral blood and spleen of healthy and lymphosarcoma RLS₄₀-bearing CBA mice. CHOP induced significant thymic atrophy and splenomegaly, T-cell depletion, and robust accumulation of MDSCs, primarily polymorphonuclear MDSCs. Kinetic analysis in healthy mice revealed splenic MDSC expansion and T-cell depletion peaked 10-day post-CHOP, driven mainly by CTX; whereas doxorubicin, vincristine, and prednisolone exerted minimal immunological effects. To mitigate CTX-induced MDSCs, glycyrrhizic acid (GLZ), a natural triterpenoid with known immunomodulatory properties, and febroxolone methyl (FM), its novel cyano enone derivative, were administered to CTX-treated mice. GLZ significantly attenuated splenic MDSC accumulation, partially restored T-cell function, and improved immune organ morphology. Conversely, FM exacerbated immunosuppression by expanding MDSCs, enhancing their function by upregulation of Nos1 and Ido1 in vivo, and promoting the generation of highly immunosuppressive bone marrow-derived MDSCs in vitro. Thus, our results highlight CTX’s central role in CHOP-induced MDSC expansion. The structure-dependent duality of triterpenoids, countering (GLZ) or promoting (FM) MDSC expansion, offers therapeutic potential for pathologies ranging from chemotherapy-induced side effects to autoimmunity. Full article

Artifacts remain a major challenge in electroencephalogram (EEG) recordings, often degrading the accuracy of clinical diagnosis, brain computer interface (BCI) systems, and cognitive research. Although recent deep learning approaches have advanced EEG denoising, most still struggle to model long-range dependencies, maintain computational efficiency, and generalize to unseen artifact types. To address these challenges, this study proposes MDSC-VA, an efficient denoising framework that integrates multi-scale (M) depth-wise separable convolution (DSConv), variational autoencoder-based (VAE) latent encoding, and a multi-head self-attention mechanism. This unified architecture effectively balances denoising accuracy and model complexity while enhancing generalization to unseen artifact types. Comprehensive evaluations on three open-source EEG datasets, including EEGdenoiseNet, a Motion Artifact Contaminated Multichannel EEG dataset, and the PhysioNet EEG Motor Movement/Imagery dataset, demonstrate that MDSC-VA consistently outperforms state-of-the-art methods, achieving a higher signal-to-noise ratio (SNR), lower relative root mean square error (RRMSE), and stronger correlation coefficient (CC) values. Moreover, the model preserved over 99% of the dominant neural frequency band power, validating its ability to retain physiologically relevant rhythms. These results highlight the potential of MDSC-VA for reliable clinical EEG interpretation, real-time BCI systems, and advancement towards sustainable healthcare technologies in line with SDG-3 (Good Health and Well-Being). Full article

For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, especially Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, to malignancies across gastrointestinal, respiratory, hepatobiliary, pancreatic, breast, and urogenital systems. We summarize organ-specific associations from saliva, tissue, and stool studies, noting the recurrent enrichment of oral taxa in tumor and peri-tumoral niches of oral, esophageal, gastric, colorectal, lung, pancreatic, liver, bladder, cervical, and breast cancers. Convergent mechanisms include the following: (i) persistent inflammation (lypopolysacharide, gingipains, cytolysins, and collagenases); (ii) direct genotoxicity (acetaldehyde, nitrosation, and CDT); (iii) immune evasion/suppression (TLR/NLR signaling, MDSC recruitment, TAN/TAM polarization, and TIGIT/CEACAM1 checkpoints); and (iv) epigenetic/signaling rewiring (NF-κB, MAPK/ERK, PI3K/AKT, JAK/STAT, WNT/β-catenin, Notch, COX-2, and CpG hypermethylation). Plausible dissemination along an oral–gut–systemic axis, hematogenous, lymphatic, microaspiration, and direct mucosal transfer enables distal effects. While causality is not yet definitive, cumulative data support oral dysbiosis as a clinically relevant cofactor, motivating biomarker-based risk stratification, saliva/stool assays for early detection, and microbiome-targeted interventions (periodontal care, antimicrobials, probiotics, and microbiota modulation) alongside conventional cancer control. Full article

The complement system plays a pivotal role in the body’s immune defense mechanism. Its key effector molecule C5a and its primary receptor C5aR1 exhibit complex “double-edged sword” effects in various disease processes, including infectious diseases, inflammatory conditions, tumors, and metabolic disorders. Under normal physiological conditions, moderate levels of C5a bind to the C5aR1 receptor, recruiting immune cells to the site of infection to participate in immune defense and enhancing the body’s ability to clear pathogens. However, in various disease states, the C5a-C5aR1 pathway primarily shapes the disease microenvironment through regulating cellular pro-inflammatory and immune functions, angiogenesis processes, and tissue repair processes. It also promotes tumor immune escape through a novel mechanism through modulating the polarization of myeloid-derived suppressor cells (MDSCs) and regulating T cell function. The C5a-mediated “inflammation–fibrosis–metabolic reprogramming” vicious cycle has become a key molecular basis driving disease progression, maintaining pathological states, and promoting abnormal tissue damage repair in chronic inflammatory diseases. Through elucidating the structural biology of C5aR1 and designing allosteric modulators, nanobodies, and bifunctional molecules as new targeted intervention strategies, we aim to accelerate research progress in related medical fields. This article reviewed the molecular mechanisms of the complement system in tumor immune escape, chronic inflammation, fibrosis, and cardiovascular diseases, and explored the translational potential of targeted interventions. These discussions provide a solid theoretical foundation and new research perspectives for the medical field, aiding in the advancement of further discoveries. Full article

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

Recently, we observed that pars planitis (PP) patients present alterations in peripheral blood (PB) Th17/Treg associated with dysregulation in the Th1 response. Yet, little is known about the systemic distribution of myeloid cells, which drive the recruitment and differentiation of the adaptive effectors toward pathogenic inflammatory Th1 and Th17 as well as regulatory lymphocytes in PP. Although myeloid populations in patients with uveitis have previously been addressed, the data did not provide an exact description of PP patients. Using flow cytometry, we evaluated monocyte and IDO-expressing monocyte-like myeloid-derived suppressor cell (MDSC) subpopulations in PB samples from 15 patients with different courses of PP (cystoid macular edema and non-macular edema subgroups; CME and nCME, respectively) and 17 healthy controls (HCs) in relation to the Th1, Th17, and immunoregulatory subsets. We observed that only PP patients from the CME subgroup presented a significantly higher fraction of CD16⁺ IDO-expressing MDSCs and intermediate CD14^highCD16⁺ monocytes compared to the HCs; this corresponded with relative up-regulation of Th1 and Th17, and down-regulation of Treg. In addition, alongside the increased percentage of IDO-expressing CD16+ MDSCs, the MDSC compartment displayed an inappropriate level of IDO (more pronounced in the CD16⁻ subset) only in CME patients. At the same time, the fraction of CD16⁻ myeloid cells did not differ significantly among the patient cohorts and healthy participants. Our study is the first to evaluate subpopulations of circulating myeloid cells in PP patients and indicates that an increased fraction of CD16⁺ myeloid cells might reflect the immunological and clinical severity of PP. Full article