Search Results (2,793)

T cells play a pivotal role in cancer research, particularly in immunotherapy, which harnesses the immune system to target malignancies. However, conventional expansion methods face limitations such as high reagent consumption, contamination risks, and difficulties in maintaining suspension cells in dynamic culture environments. This study presents a microfluidic system for long-term culture of non-adherent cells, featuring automated perfusion and image acquisition. The system integrates deep learning-based image analysis, which quantifies cell coverage and estimates cell numbers, and efficiently processes large volumes of data. The performance of this deep learning approach was benchmarked against the widely used Trainable Weka Segmentation (TWS) plugin for Fiji. Additionally, two distinct lab-on-a-chip (LOC) devices were evaluated independently: the commercial ibidi^® LOC and a custom-made PDMS LOC. The setup supported the proliferation of Jurkat cells and primary human T cells without significant loss during medium exchange. Each platform proved suitable for long-term expansion while offering distinct advantages in terms of design, cell seeding and recovery, and reusability. This integrated approach enables extended experiments with minimal manual intervention, stable perfusion, and supports multi-reagent administration, offering a powerful platform for advancing suspension cell research in immunotherapy. Full article

Background/Objectives: The long-term impact of the COVID-19 pandemic is not just limited to socioeconomic aspects; there are also important health issues to consider. Among these, one of the most important and obvious is long COVID. Despite a significant amount of scientific work having been published, this condition is still semi-unknown. The objective of this study was to collect useful information for the clarification of some epidemiological, clinical, and laboratory characteristics of this disease. Methods: This was a single-center study carried out at the Infectious Diseases Clinic of the hospital “AUO delle Marche” on all patients hospitalized for COVID-19 between November 2021 and March 2022. Results: From the data, it emerged that, following the resolution of the acute phase of SARS-CoV-2 infection, the majority of people experienced health problems that persisted for at least 6 months. The manifestations and outcomes affect different systems; therefore, long COVID, like COVID-19, has systemic involvement and the clinical manifestations may be residues of the damage caused by the disease during the acute phase, or new manifestations whose pathogenesis is still a matter of discussion. Conclusions: The persistence of inflammation and the dysregulation of the immune system represent some of the pathogenetic hypotheses. Inflammation could therefore represent one of the physiopathogenetic mechanisms of long COVID, and it is possible that it is responsible for the clinical symptoms that appear in the months following the resolution of the acute phase of the disease. Full article

Environmental stressors during the crucial period of fetal development can have a substantial impact on long-term health outcomes. A major concern is dietary exposure to endocrine-disrupting chemicals (EDCs), which can readily cross the placenta and disrupt fetal hormonal signaling and developmental programming. Examples of these chemicals include bisphenols, phthalates, pesticides, and persistent organic pollutants (POPs). Prenatal exposure to EDC has been associated with long-term effects in children, including immune disruption, metabolic dysregulation, impaired neurodevelopment, and reproductive alterations, as evidenced by human cohort studies and experimental models. Epigenetic reprogramming, direct interference with endocrine signaling, and oxidative stress (OS) are hypothesized pathways for these adverse consequences, which often combine to produce long-lasting physiological changes. This narrative review summarizes current research on maternal dietary exposure to EDCs during pregnancy, highlighting associations with adverse child health outcomes. It also discusses the growing evidence of transgenerational effects, the potential mechanisms linking prenatal exposure to long-term outcomes, and the importance of understanding the roles of timing, dosage, and chemical type. By highlighting the necessity of focused interventions to lower maternal EDC exposure and lessen threats to the health of offspring, the review concludes by discussing implications for future research, preventive measures, and public health policy. Full article

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which environmental factors modulate genetically determined immune dysregulation. Vitamin D has emerged as a plausible modifier of disease expression because its active metabolite signals through the vitamin D receptor on innate and adaptive immune cells and influences antigen presentation, cytokine balance, and lymphocyte differentiation. This narrative review synthesizes current evidence on vitamin D status and supplementation in SLE with attention to organ-specific domains. Observational studies consistently report high rates of hypovitaminosis D in SLE and associations with less favorable clinical profiles, including higher global and renal disease activity, adverse cardiometabolic features, greater infection vulnerability, and neuropsychiatric manifestations. Preclinical models demonstrate neuroprotective and barrier-stabilizing actions of vitamin D analogs, supporting biological plausibility. Interventional trials indicate that supplementation safely corrects deficiency and shows signals of benefit for selected outcomes (e.g., modest activity reductions or fatigue in specific contexts), although effects on interferon signatures, complement, and autoantibodies are heterogeneous and often limited. Overall, current evidence supports optimization of vitamin D status as a low-risk adjunct in comprehensive SLE care while highlighting the need for adequately powered, organ-focused randomized trials using standardized measurements and prespecified endpoints to define causality, therapeutic targets, and long-term safety. Full article

Following restrictions on antibiotic growth promoters in poultry production, there is growing interest in natural feed additives that support health and productivity. Among these, black cumin (Nigella sativa) has emerged as a promising candidate due to its antioxidant, antimicrobial, and immunomodulatory properties. Most studies report that black cumin, in the form of whole seeds, seed meal, or seed oil, improves body weight gain and feed conversion ratio, enhances antioxidant and immune status, and provides additional benefits on lipid profiles, liver enzymes, and cecal microbial balance. This review provides a focused synthesis of recent studies (2014–2025) on black cumin supplementation in broiler chickens, considering its various forms (whole seeds, seed meal, seed oil, and nano-formulations) and production contexts (healthy, heat-stressed, and disease-challenged birds). Specifically, this review compares responses across different forms and doses, evaluates effects on growth performance, immune function, gut health, antioxidant status, liver metabolism, and meat and carcass quality, and highlights inconsistencies among studies. Additionally, it identifies key research gaps to guide future investigations, including optimal dosing, long-term safety, and practical applications in commercial production. Overall, black cumin shows potential as a natural alternative to antibiotics, but further standardized, large-scale studies are needed to confirm its efficacy and feasibility in sustainable poultry farming. Full article

Background: Seborrheic dermatitis (SD) is a chronic, recurrent inflammatory dermatosis that primarily affects seborrheic areas such as the scalp, face, and upper trunk. Its etiology is multifactorial, involving sebaceous gland activity, immune dysregulation, skin barrier dysfunction, and alterations in the microbiome, particularly an overgrowth of Malassezia spp. Objective: This review provides an updated overview of the pathophysiological mechanisms of seborrheic dermatitis and critically examines current therapies and emerging treatments. Methods: A narrative review of the recent literature was conducted, including preclinical studies, clinical trials, and real-world evidence regarding SD pathogenesis and therapy. Special attention was paid to molecular pathways, microbiome-modulating strategies, and novel therapeutic agents. Results: Advances in transcriptomic and microbiome profiling have revealed a complex immunoinflammatory environment in SD, involving predominantly Th1, Th17, and Th22 axes. Conventional therapies are mainly based on antifungals, topical corticosteroids, and calcineurin inhibitors. However, new therapeutic approaches are under investigation, including PDE4 inhibitors (roflumilast, crisaborole, and apremilast), topical and oral JAK inhibitors, probiotics, and microbiome-targeted therapies. These agents offer promising results in selected patients, particularly those with refractory disease or facial involvement. Conclusions: SD remains a challenging condition due to its relapsing course and limited long-term therapeutic options. Emerging therapies represent a valuable opportunity to address unmet clinical needs, particularly in patients with severe, recurrent, or treatment-resistant forms. Full article

Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 antibodies—such as nivolumab, pembrolizumab, and cemiplimab—and examines pharmacokinetic–pharmacodynamic (PK-PD) relationships, highlighting the impact of clearance variability on drug exposure, efficacy, and safety. Baseline clearance and its reduction during therapy, together with interindividual variability, emerge as important dynamic biomarkers with potential applicability across different cancer types for guiding individualized dosing strategies. The review also discusses established biomarkers for anti-PD-1 therapies, including tumor PD-L1 expression and immune cell signatures, and their relevance for patient stratification. The evidence supports a shift from traditional weight-based dosing toward adaptive dosing and therapeutic drug monitoring (TDM), especially in long-term responders and cost-containment contexts. Notably, the inclusion of clearance-based biomarkers—such as baseline clearance and its reduction—into therapeutic models represents a key step toward individualized, dynamic immunotherapy. In conclusion, optimizing anti-PD-1 therapy through PK-PD insights and biomarker integration holds promise for improving outcomes and reducing toxicity. Future research should focus on validating PK-based approaches and developing robust algorithms (machine learning models incorporating clearance, tumor burden, and other validated biomarkers) for tailored cancer treatment. Full article

Visible Light Positioning (VLP) has emerged as a pivotal technology for industrial Internet of Things (IoT) and smart logistics, offering high accuracy, immunity to electromagnetic interference, and cost-effectiveness. However, fluctuations in signal gain caused by target motion significantly degrade the positioning accuracy of current VLP systems. Conventional approaches face intrinsic limitations: propagation-model-based techniques rely on static assumptions, fingerprint-based approaches are highly sensitive to dynamic parameter variations, and although CNN/LSTM-based models achieve high accuracy under static conditions, their inability to capture long-term temporal dependencies leads to unstable performance in dynamic scenarios. To overcome these challenges, we propose a novel dynamic VLP algorithm that incorporates a Spatio-Temporal Feature Information Network (STFI-Net) for joint localization and orientation estimation of moving targets. The proposed method integrates a two-layer convolutional block for spatial feature extraction and employs modern Temporal Convolutional Networks (TCNs) with dilated convolutions to capture multi-scale temporal dependencies in dynamic environments. Experimental results demonstrate that the STFI-Net-based system enhances positioning accuracy by over 26% compared to state-of-the-art methods while maintaining robustness in the face of complex motion patterns and environmental variations. This work introduces a novel framework for deep learning-enabled dynamic VLP systems, providing more efficient, accurate, and scalable solutions for indoor positioning. Full article

Background: Immune checkpoint inhibitors (ICIs) are effective against various advanced and metastatic cancers, but patient responses vary and can change over time, complicating treatment prediction. Therefore, better tools for patient stratification, response prediction, and response assessment are needed. This study presents the development and clinical translation of a fluorescently labelled ICI tracer pair used to perform multispectral fluorescent molecular imaging and simultaneously gain spatial and temporal insight in both programmed death ligand 1 (PD-L1) and programmed death receptor 1 (PD-1) expression. Methods: We conjugated the anti-PD-L1 antibody durvalumab to IRDye 680LT and the anti-PD-1 antibody nivolumab to IRDye 800CW. Tracers were developed and optimized for conjugation efficiency and purity to allow use in clinical trials. Stability was tested up to 12 months. An extended single-dose toxicity study in mice was performed for durvalumab-680LT and the unconjugated IRDye 680LT to demonstrate safety for first-in-human administration. Results: Durvalumab-680LT and nivolumab-800CW were successfully conjugated and purified. Conjugation optimization resulted in a robust production with labelling efficiencies of ≥88%. Long-term stability study of both tracers showed all parameters within end of shelf-life specifications for at least 12 months at 2–8 °C. No toxic effects were observed in doses up to 1000x the intended human dose for both IRDye 680LT and durvalumab-680LT, which are therefore considered safe for first-in-human use. Conclusions: We succeeded in the development and clinical translation of two novel fluorescent ICI tracers, durvalumab-680LT and nivolumab-800CW. Moreover, we demonstrated for the first time the safety of IRDye 680LT and durvalumab-680LT, enabling first-in-human use. Together, this makes durvalumab-680LT and nivolumab-800CW suitable for phase I/II clinical trials. Full article

Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mureș County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-γ, IL-4, IL-10, IL-13, IL-17, and TNF-α, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-γ, IL-17, and TNF-α at admission (p < 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg/mL), IFN-γ, and TNF-α, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-γ remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy. Full article

Background/Clinical Significance: Development of acute antibody-mediated rejection (AMR) of allograft is one of the leading causes of mortality in heart-transplant recipients; however, the standard therapy does not always resolve severe forms of rejection. Extracorporeal photopheresis (ECP) is a method of immunomodulatory therapy that involves separating a patient’s white blood cells and treating them with a photosensitizer and ultraviolet A irradiation. Case Presentation: An 18-year-old female patient was urgently hospitalized with complaints of shortness of breath. She had undergone heart-transplant surgery 9 months before due to congenital heart disease restrictive cardiomyopathy, complicated with end-stage chronic heart failure. During the admission she admitted that for 3 weeks she discontinued tacrolimus and mycophenolate mofetil. AMR3 and CAV were verified. Conclusions: The use of standard approaches in the treatment of acute AMR is not always able to suppress an expressed immune reaction against the cardiac allograft, which leads to disruption of its function and rejection in the early or long-term follow-up. The inclusion of ECP in the treatment regimen allowed us to stabilize the patient’s condition and achieve regression in the severity of the AMR. It is believed that an important role in this was played by the activity of the immune system, which we assessed by changing the profile of cytokines, chemokines, and other growth factors. Thus, ECP demonstrated its effectiveness in the treatment of AMR of the cardiac allograft, with a change in the severity of the cytokine storm, as well as with an increase in the contribution of cytokines associated with the Th17 response. Full article

In this research, precision temperature sensing for electromagnetically harsh environments was achieved utilizing a low-threshold frequency-stable optoelectronic oscillator (OEO) leveraging stimulated Brillouin scattering (SBS). The sensing mechanism relied on the temperature-dependent frequency shift in the SBS-induced notch filter. By embedding this filter in the OEO feedback loop, the oscillator’s output frequency was locked to the difference between the optical carrier frequency and the SBS notch center frequency. The temperature variations were translated into microwave frequency shifts through OEO oscillation, which was quantified with heterodyne detection. To suppress environmental perturbations, a Faraday rotation mirror (FRM) was integrated at the fiber end, creating a dual-pass SBS interaction that simultaneously enhanced the vibration immunity and reduced the SBS power threshold by 2.7 dB. The experimental results demonstrated a sensitivity of 1.0609 MHz/°C (R² = 0.999) and a long-term stability of ±0.004 °C. This innovative scheme demonstrated significant advantages over conventional SBS-OEO temperature sensing approaches, particularly in terms of threshold reduction and environmental stability enhancement. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Cancer-induced cardiac dysfunction has become a major clinical challenge as advances in cancer therapies continue to extend patient survival. Once regarded as a secondary concern, cardiotoxicity is now recognized as a leading contributor to morbidity and mortality among cancer patients and survivors. Its pathophysiology is multifactorial, involving systemic inflammation (e.g., TNF-α, IL-6), oxidative stress driven by reactive oxygen species (ROS), neurohormonal imbalances (e.g., angiotensin II, endothelin-1), and metabolic disturbances. These mechanisms collectively promote cardiomyocyte apoptosis, atrophy, mitochondrial dysfunction, and impaired cardiac output. Cardiac complications may arise directly from cancer itself or as adverse effects of oncologic therapies such as anthracyclines, trastuzumab, and immune checkpoint inhibitors. These agents have been linked to heart failure (HF), systolic dysfunction, and cardiac atrophy, often progressing insidiously and underscoring the importance of early detection and careful monitoring. Current preventive and therapeutic strategies include pharmacological interventions such as ACE inhibitors, beta-blockers, statins, dexrazoxane, and endothelin receptor antagonists like atrasentan. Emerging compounds, particularly Withaferin A (WFA), have shown potential through their anti-inflammatory and cardiac protective properties. In addition, antioxidants and lifestyle modifications may provide supplementary cardioprotective benefits, while interventional cardiology procedures are increasingly considered in selected patients. Despite encouraging progress, standardized treatment protocols and robust long-term outcome data remain limited. Given the heterogeneity of cancer types and cardiovascular responses, a personalized and multidisciplinary approach is essential. Continued research and close collaboration between oncologists, cardiologists, and basic scientists will be the key to advancing care, reducing treatment-related morbidity, and ensuring that improvements in cancer survival are matched by preservation of cardiovascular health. Full article

Background/Objectives: Understanding the durability of immunity induced by mRNA COVID-19 vaccines, especially in individuals with chronic health conditions, remains essential for guiding booster strategies. We conducted a longitudinal study to evaluate humoral and cellular immune responses up to 21 months after a primary two-dose BNT162b2 vaccination followed by a booster, either homologous (BNT162b2) or heterologous (mRNA-1273). Methods: Twenty-eight adults, mostly with chronic conditions, were assessed at approximately 9, 12 and 21 months post-primary vaccination. Serum anti-trimeric Spike IgG levels were quantified, and peripheral blood mononuclear cells were analyzed at 21 months for Spike-specific memory B-cell and T-cell responses by flow cytometry. Results: Participants were stratified by booster type, prior SARS-CoV-2 infection and health status. Anti-Spike IgG persisted in all participants but declined over time. The heterologous mRNA-1273 booster induced higher antibody titers at 9 months, while the homologous BNT162b2 booster led to more sustained antibody levels and higher frequencies of Spike-specific memory B cells at 21 months. Prior infection significantly enhanced antibody titers, particularly in homologous booster recipients. Surprisingly, individuals with chronic health conditions exhibited equal or higher antibody levels compared to healthy participants at all time points. At 21 months, robust Spike-specific class-switched memory B cells and polyfunctional CD4⁺ and CD8⁺ T-cell responses were detected. Conclusions: These findings demonstrate that BNT162b2 vaccination elicits durable, multi-layered immunity lasting nearly two years, even in individuals with chronic conditions, and support the use of both homologous and heterologous mRNA boosters to sustain protection in diverse populations. Full article