Search Results (5,280)

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility—particularly human leukocyte antigen (HLA) class II alleles—is a major risk factor, accumulating evidence implicates viral infections as potential environmental triggers in disease onset and progression. This narrative review synthesizes current findings on the role of viral pathogens in T1DM pathogenesis. Enteroviruses, especially Coxsackie B strains, are the most extensively studied and show strong epidemiological and mechanistic associations with beta-cell autoimmunity. Large prospective studies—including Diabetes Virus Detection (DiViD), The environmental determinans of diabetes in the young (TEDDY), Miljøfaktorer i utvikling av type 1 diabetes (MIDIA), and Diabetes Autoimmunity Study in the Young (DAISY)—consistently demonstrate correlations between enteroviral presence and the initiation or acceleration of islet autoimmunity. Other viruses—such as mumps, rubella, rotavirus, influenza A (H1N1), and SARS-CoV-2—have been investigated for their potential involvement through direct cytotoxic effects, immune activation, or molecular mimicry. Interestingly, certain viruses like varicella-zoster virus (VZV) and cytomegalovirus (CMV) may exert modulatory or even protective influences on disease progression. Proposed mechanisms include direct beta-cell infection, molecular mimicry, bystander immune activation, and dysregulation of innate and adaptive immunity. Although definitive causality remains unconfirmed, the complex interplay between genetic predisposition, immune responses, and viral exposure underscores the need for further mechanistic research. Elucidating these pathways may inform future strategies for targeted prevention, early detection, and vaccine or antiviral development in at-risk populations. Full article

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I² = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine. Full article

Toxoplasma gondii is an intracellular protozoan found worldwide that is capable of infecting nearly all warm-blooded animals, including humans. Its parasitic success lies in its capacity to create chronic infections while avoiding immune detection, altering host immune responses, and disrupting programmed cell death pathways. This review examines the complex relationship between T. gondii and host immunity, focusing on how the parasite influences innate and adaptive immune responses to survive in immune-privileged tissues. We present recent findings on the immune modulation specific to various parasite strains, the immunopathology caused by imbalanced inflammation, and how the parasite undermines host cell death mechanisms such as apoptosis, necroptosis, and pyroptosis. These immune evasion tactics enable prolonged intracellular survival and pose significant challenges for treatment and vaccine development. We also review advancements in therapeutic strategies, including host-directed approaches, nanoparticle drug delivery, and CRISPR-based technologies, along with progress in vaccine development from subunit and DNA vaccines to live-attenuated candidates. This review emphasizes the importance of T. gondii as a model for chronic infections and points out potential avenues for developing innovative therapies and vaccines aimed at toxoplasmosis and similar intracellular pathogens. Full article

COVID-19 vaccine hesitancy (VH), like attitudes towards other vaccines, is a critical global public health concern. Despite numerous studies covering psychological, sociodemographic, and other determinants of vaccine acceptance, resistance, and hesitance, few studies have reported these factors among students, particularly in politically unstable settings like Ukraine. This cross-sectional, descriptive, and quantitative study assesses hesitancy towards COVID-19 vaccines, utilizing the 5Cs Model. Among 936 respondents surveyed in 2023, 64% received at least one shot of the COVID-19 vaccine (acceptant), 11% were still considering getting vaccinated (hesitant), and 25% refused vaccination (resistant). Vaccination behavior is significantly associated with the 5Cs. Higher collective responsibility significantly increased acceptance and reduced resistance, while higher constraints lowered the chances of being either acceptant or resistant. Confidence protected against resistance. Complacency, counterintuitively, reduced odds of resistance, pointing to differences between passive hesitancy and active refusal. Male gender and sources of information and misinformation influenced confidence. Collective responsibility was positively associated with official sources and negatively with conspiracy beliefs. Complacency increased with official sources, while constraints and calculation were least explained by predictors. Practical barriers should be tackled through improved accessibility and fostering collective responsibility via targeted communication strategies. These findings provide actionable insights for policymakers, healthcare providers, and academic institutions to enhance vaccine uptake among university students, particularly in crisis settings. Full article

African, Caribbean, and Black (ACB) communities face increased COVID-19 morbidity and mortality, coupled with significant barriers to vaccine acceptance and uptake. Addressing these challenges requires innovative, multifaceted strategies. Peer-led interventions, grounded in critical health literacy (CHL) and critical racial literacy (CRL), and integrating collaborative equity learning processes, can enhance community capacity, empowerment, and health outcomes, contributing to long-term health equity. This paper describes and presents the evaluative outcomes of a peer-led intervention aimed at enhancing COVID-19 vaccine confidence and acceptance. The Peer-Equity Navigator (PEN) intervention consisted of a specialized training curriculum grounded in CHL and CRL. Following training, PENs undertook a 5-month practicum in community or health settings, engaging in diverse outreach and educational activities to promote vaccine literacy in ACB communities. The evaluation utilized a modified Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, using quantitative and qualitative methods to collect data. Sources of data included tracking records with community feedback, and a PEN focus group, to assess program feasibility, outreach, and effectiveness. From 16 September 2022, to 28 January 2023, eight trained PENs conducted 56+ community events, reaching over 1500 community members. Both PENs and community members reported high engagement, endorsing peer-led, community-based approaches and increased vaccine literacy. The PEN approach proves feasible, acceptable, and effective in promoting positive health behaviors among ACB communities. This intervention has clear implications for health promotion practice, policy, and research in equity-deserving communities, including immigrants and refugees, who also face multiple and intersecting barriers to health information and care. Full article

Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs. Full article

Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs. Full article

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

Background: Vaccine hesitancy (VH) represents a growing concern among healthcare professionals and students, potentially undermining public health efforts. Nursing, pediatric nursing, and midwifery students are future vaccinators and educators, making it essential to understand their attitudes, knowledge, and confidence toward vaccination. This study aims to assess vaccine-related perceptions and behaviors among these student populations in an Italian university. Methods: A cross-sectional survey was conducted between November 2022 and February 2024 at the University of Rome “Tor Vergata.” A structured, anonymous questionnaire, including the Vaccination Attitudes Examination (VAX) scale, vaccine knowledge items, and sources of information, was administered to students in nursing (n = 205), pediatric nursing (n = 46), and midwifery (n = 21). Statistical analyses included descriptive statistics, ANOVA, post hoc tests, and Mann–Whitney U tests. Results: Among the 272 participants, 20.6% reported refusing at least one recommended vaccine, and 18.4% delayed vaccination for non-medical reasons. Vaccine knowledge and confidence increased significantly with academic progression (p < 0.001). Midwifery students showed both the highest concern for long-term vaccine effects and the greatest confidence in vaccine safety. Institutional and scientific sources were the most trusted, though traditional and non-institutional media also influenced perceptions, particularly among midwifery students. Conclusions: Despite high COVID-19 vaccine uptake, VH persists among health professional students. Discipline-specific patterns highlight the need for early, targeted educational strategies to enhance vaccine literacy and reduce hesitancy. Tailored training may empower future professionals to become informed and credible advocates for vaccination. Full article

Recombinant vesicular stomatitis virus (rVSV) is a promising viral vaccine vector for addressing the COVID-19 pandemic. Inducing mucosal immunity via the intranasal route is an ideal strategy for rVSV-based vaccines, but it requires extremely stringent safety standards. In this study, we constructed two rVSV variants with amino acid mutations in their M protein: rVSV-M2 with M33A/M51R mutations and rVSV-M4 with M33A/M51R/V221F/S226R mutations, and developed COVID-19 vaccines based on these attenuated vectors. By comparing viral replication capacity, intranasal immunization, intracranial injection, and blood cell counts, we demonstrated that the M protein mutation variants exhibit significant attenuation effects both in vitro and in vivo. Moreover, preliminary investigations into the mechanisms of virus attenuation revealed that these attenuated viruses can induce a stronger type I interferon response while reducing inflammation compared to the wild-type rVSV. We developed three candidate vaccines against SARS-CoV-2 using the wildtype VSV backbone with either wild-type M (rVSV-JN.1) and two M mutant variants (rVSV-M2-JN.1 and rVSV-M4-JN.1). Our results confirmed that rVSV-M2-JN.1 and rVSV-M4-JN.1 retain strong immunogenicity while enhancing safety in hamsters. In summary, the rVSV variants with M protein mutations represent promising candidate vectors for mucosal vaccines and warrant further investigation. Full article