Search Results (2,891)

Hantaviruses are emerging rodent-borne pathogens that pose increasing global public health concerns due to their association with hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), both of which can result in substantial morbidity and mortality. Environmental change, climate variability, urbanization, and land-use transformation are increasingly recognized as critical drivers of hantavirus emergence and transmission. This review summarizes current evidence regarding hantavirus virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, surveillance systems, prevention strategies, and One Health preparedness approaches. Emphasis is placed on the influence of climate change and ecological disruption on rodent reservoir dynamics and spillover risk, as well as major surveillance and diagnostic gaps in tropical and Caribbean regions where hantavirus circulation may be underrecognized. Advances in molecular diagnostics, genomic surveillance, vaccine development, monoclonal antibody therapies, and climate-based early warning systems are also discussed. Existing evidence highlights the importance of integrated One Health surveillance systems that combine human, animal, and environmental monitoring to improve early detection and outbreak preparedness. Strengthening laboratory capacity, ecological surveillance, regional collaboration, and public health infrastructure will be essential for reducing the global burden of hantavirus infections and improving preparedness for future zoonotic disease threats. Full article

Triple-negative breast cancer (TNBC), characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is a highly aggressive molecular subtype with high recurrence and metastasis rates. Due to the absence of reliable molecular targets, surgery combined with chemotherapy remains the mainstay of clinical treatment. In recent years, immunotherapy has provided new strategies for TNBC management. Immune checkpoints are key regulatory molecules that maintain immune homeostasis, and blocking these checkpoints can restore T cell activity and enhance tumor cell killing. Immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit, particularly in combination with chemotherapy for patients with locally advanced or metastatic TNBC. This review focuses on immune checkpoint–based immunotherapy in TNBC, providing an overview from mechanistic insights to clinical applications and emerging therapeutic strategies. In addition to ICIs, we discuss alternative approaches, such as bispecific antibodies, antibody–drug conjugates (ADCs), chimeric antigen receptor T cell (CAR-T) therapy, tumor vaccines, and oncolytic viruses (OVs), highlighting their current research progress and clinical applications in TNBC treatment. Full article

Macrophages are highly plastic innate immune cells that adopt context-dependent phenotypes along a continuum, integrating developmental origin with local microenvironmental cues rather than conforming to discrete M1/M2 states. This review delineates the molecular circuits shaping macrophage identity—TLR/cytokine signaling, microRNA networks, metabolic rewiring, and epigenetic mechanisms including histone lactylation—and traces how circulating monocyte subsets contribute to tissue macrophage diversity. We examine macrophage plasticity across a broad disease spectrum—oncology, autoimmune and rheumatic diseases, inflammatory bowel disease, infectious diseases, metabolic disorders, and neurological conditions—showing that the pathogenic phenotype is strikingly context-dependent: for instance, M2-like tumor-associated macrophages promote immune evasion in solid tumors, whereas M1-skewed programs drive tissue damage in autoimmunity. Soluble markers (sCD163, sCD14, soluble mannose receptor) are emerging biomarkers of disease activity and prognosis. High-dimensional flow cytometry and mass cytometry (CyTOF) bridge molecular biology and clinical phenotyping, enabling integrated readouts of surface phenotype, intracellular signaling, and metabolic state. Therapeutic strategies discussed include selective tumor-associated macrophage (TAM) reprogramming, chimeric antigen receptor (CAR)-M cell therapies, and biomaterial-based platforms. Future priorities encompass spatially resolved multi-omics, epigenetic and metabolic targeting, and macrophage-centered vaccine approaches. Standardized cytometry panels will be essential for biomarker-guided stratification and context-specific interventions. Full article

Human papillomavirus (HPV) infection remains a major global health challenge, particularly when persistent high-risk genotypes lead to oncogenic progression. While prophylactic vaccines are effective, their role in accelerating the clearance of existing infections is still being explored. This study aimed to investigate the potential efficacy of adjunctive Pidotimod therapy combined with the nonavalent HPV vaccine in reducing persistent genotypes and promoting clearance in men. This retrospective pilot study included 23 HIV-negative men with anal and/or genital HPV infections. Participants were divided into two groups: 7 received the standard nonavalent HPV vaccine alone (control), and 16 received oral Pidotimod (800 mg twice daily for 10 days surrounding each vaccine dose) in addition to the vaccine (treatment). HPV genotyping (28 types) was performed at baseline and 12 months using real-time PCR. At 12 months, the HPV-negative conversion rate was 62.5% in the Pidotimod + vaccine group compared to 28.6% in the control group (p = 0.19). While this primary difference in total clearance was not statistically significant due to the limited sample size, the treatment group showed a substantial per-patient reduction in the number of persistent genotypes, decreasing from a mean of 2.75 ± 2.05 to 0.50 ± 0.82, compared to a decrease from 3.43 ± 2.37 to 1.86 ± 1.07 in the control group. The Pidotimod group achieved a significantly lower number of persistent genotypes at 12 months compared to the control group (p = 0.008, Mann–Whitney U test). Additionally, the use of pre-exposure prophylaxis (PrEP) was significantly associated with a lower rate of HPV clearance (12.5% vs. 73.3%, p < 0.01). Adjunctive therapy with Pidotimod suggests a promising trend in facilitating the reduction in HPV strain burden when combined with the HPV vaccine in men. While larger prospective studies are needed to confirm these effects, this exploratory approach could represent a promising immunomodulatory strategy for managing multiple and persistent HPV infections, even in high-risk groups such as PrEP users. Full article

Mayaro virus (MAYV) is an emerging arbovirus from the Togaviridae family where inflammation plays a central role in disease development. As the cause of Mayaro fever, MAYV triggers strong production of pro-inflammatory cytokines, which can result in long-lasting arthralgia in affected individuals. Macrophages are both targets for viral infection and key regulators of inflammatory responses. Human monocyte-derived macrophages (MDMs) are susceptible to MAYV infection in vitro and support productive viral replication. With no approved antivirals or vaccines, finding host-directed therapies is an urgent priority. Cannabinoids are compounds with antiviral and immunomodulatory properties, suggesting potential against MAYV infection. Here, we examined the effects of cannabidiol (CBD) and the synthetic cannabinoid WIN 55,212-2 on MAYV-infected MDMs in pre- and post-treatment conditions. Cells and supernatants were collected at 6 and 24 h post-infection (h.p.i). To understand the mechanisms involved, transcriptomic and functional analyses were performed at 24 h.p.i in the post-treatment setting, focusing on inflammatory, antiviral, and endoplasmic reticulum (ER) stress pathways. WIN 55,212-2 post-treatment significantly decreased viral replication at 24 h.p.i without any direct virucidal activity and was independent of type I interferon activation or interferon-stimulated gene induction, instead being linked to the modulation of ER stress signaling. Specifically, WIN 55,212-2 increased IRE-1α RNase activity, promoting the alternative splicing of sXBP1, while the integrated stress response appeared central to its antiviral effect. Additionally, WIN 55,212-2 downregulated inflammation-related genes and altered cytokine and chemokine production, counteracting the strong inflammatory response caused by MAYV. Remarkably, it also exerted broader immunomodulatory effects independent of infection. Full article

Background: Conventional drug delivery systems often lead to fluctuating plasma concentrations (“Peak and Trough” phenomenon), causing toxicity or inefficacy. Microfluidics has emerged as a revolutionary tool to overcome, among other applications, the limitations of conventional bulk encapsulation methods, such as polydispersity and poor reproducibility. Methods: A systematic review of the literature published between 2020 and 2025 was conducted to evaluate the application of microfluidics in the synthesis of advanced nanomedicines. The review focused on Lipid Nanoparticles (LNPs), Polymeric Nanoparticles (PNPs), and Hydrogel Microspheres. Results: Microfluidics enables the production of monodisperse particles with precise control over geometry and drug loading stoichiometry. Key therapeutic applications include oncology (passive and active targeting), gene therapy (mRNA vaccines), and regenerative medicine (diabetic wound healing). Conclusions: While microfluidics offers superior quality control compared to bulk methods, industrial scalability remains the primary challenge, currently addressed through parallelization and continuous flow strategies. Full article

Background: Toxoplasma gondii (T. gondii) is one of the most prevalent parasitic zoonoses worldwide, and the host’s immunological state significantly influences its clinical manifestations, which can be potentially fatal in immunocompromised hosts. The unavailability of a vaccine, combined with the considerable toxicity of existing medications, necessitates the urgent search for new therapies or adjunctive techniques, including regenerative and immunomodulatory approaches. Hence, the present study investigated, for the first time, the therapeutic potential of syngeneic platelet rich plasma (PRP) against T. gondii ME49 strain-induced chronic toxoplasmosis in both immunocompetent and immunosuppressed mouse models. Methods: 72 albino mice were divided into two sections, immunocompetent and immunosuppressed. Each section contained six groups: healthy, model, cotrimoxazole (CTZ)-treated, PRP-treated, half-dose of both CTZ and PRP-treated, and full-dose of both CTZ and PRP-treated. Treatment efficacy was assessed via parasitological, histological, immunohistochemical, and immunological analyses. Results: PRP, especially when coadministered with the CTZ, mitigated the consequences of toxoplasmosis by significantly reducing brain cyst counts (p < 0.0001), restoring brain tissue architecture, modulating apoptotic pathways by restoring caspase-3 expression in the brain, and normalizing systemic IFN-γ, TNF-α, and IL-10 cytokine profiles. Conclusions: The findings highlight PRP as an adjunct to the reference treatment, CTZ, for controlling toxoplasmosis in both immunocompetent and immunosuppressed conditions via anti-infective, neuroprotective, and immunomodulatory activities. Full article

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1), driven by high mutation and recombination rates, poses significant challenges for diagnostics, therapy, and vaccine development. While variable regions enable immune escape, hyperconserved regions are critical for viral function and represent promising targets for novel therapeutic interventions. This study aimed to develop and validate a bioinformatic algorithm for quantitative assessment of sequence conservation and automated identification of functionally significant conserved regions across all major HIV-1 proteins. A total of 1119 full-length HIV-1 genome sequences representing major subtypes (A1, A2, A6, B, C, D, F1, F2, G, H, J, K) were analyzed. Normalized Shannon entropy (S-index) was calculated for each alignment column. Statistical thresholds for conserved regions were established using 95% confidence intervals derived from bootstrap resampling. Two complementary algorithms, clustering and local maxima detection, were applied to identify conserved regions, which were subsequently mapped to known functional domains based on literature data. Protein conservation varied markedly, with S_m values ranging from 0.784 (Vpu) to 0.920 (Pol). Gag, Pol, and Vpr demonstrated the highest overall conservation, while Env, Rev, Tat, and Vpu exhibited pronounced variability interspersed with conserved domains. In total, 25 conserved regions in Gag, 49 in Pol, 28 in Env, and 6–4 regions in accessory proteins (Vif, Vpr, Rev, Tat, Nef, Vpu) were identified. These regions corresponded to critical functional elements including enzyme catalytic centers, zinc fingers, receptor-binding sites, protein interaction interfaces, and membrane-anchoring domains. The developed computational framework enables statistically grounded identification of evolutionarily constrained regions across analyzed HIV-1 subtypes. The identified conserved regions represent candidate sites for further investigation and may inform downstream studies focused on antiviral target prioritization, immunogen design, and diagnostic assay development. However, their translational applicability requires additional analytical, structural, and experimental validation. Full article

The aim of this study was to identify the main causes of neonatal mortality in dairy calves (0–30 days of age) in Poland and to assess how infectious factors and management practices influenced the pattern of mortality. A retrospective analysis was performed on 498 calves from 312 herds between 2018 and 2024. The protocol included necropsy, enteropathogen diagnostics (PCR and ELISA), and analysis of herd management questionnaires. The leading causes of death were chronic diarrhea (42.4%), acute diarrhea (25.3%), and septicemia (10.8%). Calves that died from septicemia were the youngest (mean age 7.7 days), whereas those that died from chronic diarrhea were the oldest (20.3 days; p < 0.001). Lack of dam vaccination was associated with a higher occurrence of acute diarrhea (RR = 2.04) and septicemia (RR = 2.01) within the necropsied calf population. Inappropriate colostrum management was also associated with a higher occurrence of septicemia (RR = 1.99). Despite widespread antimicrobial use (>80%), intensive fluid therapy was used rarely (<7% in diarrheal cases). ETEC, rotavirus, and coronavirus were detected significantly more frequently in acute diarrhea, whereas Cryptosporidium parvum (C. parvum) was significantly more frequent in chronic diarrhea. Antimicrobials were used extensively, while intensive fluid therapy for diarrhea was implemented infrequently and inadequately relative to disease severity. This study makes an important contribution to the understanding of calf mortality in dairy herds by combining comprehensive postmortem diagnostics with pathogen detection (PCR and ELISA) and the assessment of management practices, thereby providing a holistic perspective on the problem. The analysis of 498 calves from 312 farms over a 7-year period offers an unprecedented and representative picture of the situation in Poland, one of Europe’s major milk producers. These results emphasize the crucial importance of proper colostrum management and vaccination, while also indicating a clear and urgent need to expand the use of fluid therapy in calves requiring treatment. The results identify not only the dominant pathogens and differences in disease course, but also management factors with direct implications for animal welfare and preventive strategies in dairy production. Full article

Therapeutic vaccines are a key strategy to achieve the goal of “functional cure” of chronic viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human papillomavirus (HPV), and Epstein–Barr virus (EBV). Various platforms (such as viral vectors, nucleic acid vaccines, recombinant proteins, etc.) have successfully induced strong virus-specific T-cell responses in early trials, but their clinical efficacy is still limited by the immunosuppressive environment formed by the host. The core bottlenecks are severe T-cell exhaustion, viral immune escape, and various forms of local immune tolerance. Therefore, the field is moving toward combination therapies, including reduction of viral load, targeting of immune activation, and inhibition of inhibitory signaling pathways. This article summarizes the preclinical and clinical progress of therapeutic vaccines in the past decade, analyzes the major challenges in vaccine development, and discusses the future development directions in this field. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Fungal β-1,3-glucans are structurally conserved polysaccharide components of the fungal cell wall that exhibit potent immunomodulatory activity. These molecules are recognized by pattern recognition receptors, Toll-like receptors, complement receptor 3, lactosylceramide, scavenger receptors, and EphA2. Binding of β-1,3-glucans through these receptors triggers coordinated innate and adaptive immune responses such as cytokine production, phagocytosis, and trained immunity. In addition to receptor-mediated immune activation, dietary β-1,3-glucans function as fermentable prebiotic fibers that modulate gut microbiota composition, increase short-chain fatty acid production, and strengthen epithelial barrier integrity. These combined immunological and microbiome-mediated effects position β-1,3-glucans as key regulators of gut homeostasis. Preclinical and emerging clinical evidence supports broad therapeutic potential across multiple disease domains, including inflammatory bowel disease, metabolic disorders, respiratory infections, and cancer. In oncology, β-1,3-glucans enhance anti-tumor immunity, improve responses to monoclonal antibodies and chemotherapy, and serve as promising adjuvants in vaccine-based strategies. Additionally, β-1,3-glucan is widely used as a biomarker for invasive fungal infections and represents a validated target of antifungal therapies such as echinocandins. Despite these advances, clinical translation remains limited by heterogeneity in glucan source, structure, and formulation, as well as a lack of appropriately powered, standardized human clinical trials. Future efforts should focus on clarifying mechanisms of action, as well as rigorous clinical evaluation, to fully define the therapeutic utility of fungal β-1,3-glucans. Full article

Biologic and targeted synthetic therapies have substantially improved the management of autoimmune diseases (ADs), achieving unprecedented disease control. However, by modulating key immune pathways, these agents increase susceptibility to a wide spectrum of infections. This narrative review synthesizes current evidence on infectious risks associated with biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in AD, characterizing infection profiles across different drug classes, identifying patient- and treatment-related risk factors, and providing evidence-based recommendations for screening, prevention, and management. A comprehensive literature search was conducted through March 2026, across PubMed, Embase, and the Cochrane Library, using predefined search terms combining biologic and targeted synthetic drug classes with infection-related outcomes. Evidence from major international registries (BSRBR-RA, DANBIO, RABBIT) and society guidelines (ACR, EULAR, IDSA) was prioritized. Among bDMARDs, TNF-α inhibitors (TNF-α i) and rituximab were associated with the highest rates of serious infections, whereas IL-17 and IL-23 inhibitors demonstrated comparatively lower infectious risk profiles. Steroids, older age, and prior serious infections emerged as the most consistent patient-related risk modifiers. Unlike prior reviews focused on single diseases or drug classes, this work provides an integrated, cross-disciplinary risk stratification framework. bDMARDs and tsDMARDs remain among the most innovative treatments available for effective management of ADs, with favorable benefit–risk profiles when accompanied by systematic prevention strategies. Universal pre-treatment screening for tuberculosis and viral hepatitis, risk-stratified parasitic screening, evidence-based vaccination, and selective antimicrobial prophylaxis can mitigate infectious complications. Full article

Therapeutic cancer vaccines are a promising immunotherapy approach in genitourinary (GU) cancers, designed to stimulate antitumor immune responses through antigen-specific T-cell activation. Although agents such as bacillus Calmette–Guérin in bladder cancer and sipuleucel-T in prostate cancer have shown success, vaccine monotherapy has generally produced limited clinical benefit due to tumor heterogeneity, poor immune infiltration, and immunosuppressive tumor microenvironments. Multiple vaccine platforms have demonstrated safety and immunogenicity in prostate, renal cell, and urothelial cancers, but efficacy remains modest. Current strategies focus on multi-antigen targeting, improved antigen presentation, and combination therapies with immune checkpoint inhibitors, radiotherapy, and targeted agents to enhance antitumor activity. Advances in personalized vaccine design and delivery systems are driving progress, though challenges such as manufacturing complexity, cost, and biomarker development remain. Ongoing translational and clinical research will be critical to improving the effectiveness of vaccine-based immunotherapy in GU malignancies. Full article

The role of adjuvant therapy in stage III melanoma is well established in clinical practice. Because stage IIB–IIC melanoma carries a risk of recurrence and melanoma-specific mortality comparable to that of stage III disease, adjuvant approaches have also been developed for patients with thick stage II tumors. Both pembrolizumab and nivolumab have demonstrated efficacy in reducing the risk of local and distant recurrence in patients with high-risk stage II melanoma, whereas evidence supporting the use of BRAF-MEK inhibitors in this setting remains inconclusive. Combinations of immune checkpoint inhibitors, as well as immunotherapy combined with mRNA-based vaccines, are currently under investigation in clinical trials. However, given the non-trivial risk of immune-related adverse events, careful selection of patients with stage II disease who are most likely to derive meaningful benefit from adjuvant therapy is essential. In this context, several clinicopathologic variables and gene expression profiling-based prognostic tools have been proposed to refine risk stratification. To date, however, none of these instruments have been incorporated into routine clinical practice, and no validated predictive biomarkers are available. Accordingly, optimal patient selection for adjuvant therapy remains an important unmet clinical need in early-stage melanoma. Full article