Search Results (4,400)

 Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, continues to be a significant global health issue, especially in Latin America, with increasing international prevalence due to migration. Despite advancements in diagnosis and treatment, it remains a neglected tropical disease characterized by significant morbidity and mortality, mainly influenced by the complex interaction between parasite diversity and host immune responses. Importantly, the remarkable genetic diversity of T. cruzi lineages also contributes to clinical heterogeneity, influencing immune evasion, therapeutic responses, and vaccine feasibility. This review analyzes the impact of immunogenetics on host–parasite interactions in Chagas disease and explores its implications for personalized therapy approaches. Recent research, particularly over the last decade, has indicated that processes including antigenic variation, extracellular vesicle-mediated regulation, and disruption of host signaling pathways facilitate parasite persistence. Host genetic variables significantly influence susceptibility, disease development, and treatment outcomes, including changes in Human Leukocyte Antigen (HLA) genes, cytokine gene polymorphisms, and immunogenetic determinants of cardiac pathology. These findings underscore the potential of immunogenetic markers as tools for prognosis and as targets for personalized therapies. However, there are still considerable research deficiencies. Inadequate comprehension of gene–environment interactions, lack of representation of varied populations, and inconsistencies in study design limit the use of immunogenetic findings in therapeutic settings. At present, the concept of personalized medicine in Chagas disease remains largely aspirational, better understood as a framework for precision public health or stratified interventions guided by host immunogenetic and parasite lineage data. Addressing these issues necessitates comprehensive genomic research, mechanistic investigations of host–parasite interactions, and clinical validation of genetic markers. This study emphasizes the necessity of incorporating immunogenetics into personalized patient management strategies based on existing evidence. This integration has the potential to improve diagnosis, enhance treatment efficacy, and inform preventive interventions, thereby advancing personalized therapy for Chagas disease.  Full article

The respiratory mucosal system plays a critical role in the pathogenesis of allergic asthma (AA). Currently, therapeutic Fc fusion proteins are as a promising strategy for mucosal vaccine delivery systems. In this work, a plasmid encoding the Mycobacterium tuberculosis ESAT6-Fc fusion protein was successfully constructed, and high-purity ESAT6-Fc fusion protein was subsequently obtained. Administered via intranasal immunization in OVA-induced allergic asthma model mice, ESAT6-Fc fusion protein significantly alleviated airway inflammation and mucus production, and reduced the proportions of Th2 cells, Th17 cells, and eosinophils, while increasing the proportions of Th1 cells with no histopathological changes to major organs. To elucidate the underlying immune regulatory mechanisms of ESAT6, integrated transcriptomic and proteomic analyses were performed, revealing Th1/Th2 cell differentiation and Th17 cell differentiation as the two most significantly enriched pathways at both the gene and protein levels. CD3e (CD3E) and CD3g (CD3G), two essential subunits of the TCR–CD3 complex, were identified as core target factors. The validations from the ESAT6-Fc-treated AA lung tissues, as well as co-cultured TH0 cells from C57BL/6J mice and CD2.4 dendritic cells exposed to the ESAT6-Fc protein, were consistent with the aforementioned findings. ESAT6-Fc exhibits a safe profile with favorable efficacy against OVA-induced AA via intranasal immunization, and ESAT6 ameliorates AA by regulating the differentiation of Th0 cells into Th1 cells, which were closely associated with the down-regulation of CD3e and CD3g expression, presumably leading to the impairment of TCR–CD3 complex assembly. ESAT6-Fc fusion protein demonstrates promise as a potential safe intranasal immunotherapy agent for the treatment of AA. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

Dendritic cell (DC) immunotherapy is a promising approach for treating cancers such as melanoma and prostate cancer. Although DC-based vaccines can elicit potent anti-tumor immune responses, dosing schedules in both preclinical and clinical settings are often chosen empirically rather than through quantitative optimization. In this work, we develop an enhanced mathematical model of tumor-immune dynamics that incorporates a more realistic tumor growth law and an estimated immune-response delay, enabling the systematic design of DC vaccination protocols. Tumor-growth and immunotherapy parameters were calibrated using experimental melanoma data and two metaheuristic optimization methods: Genetic Algorithm and Particle Swarm Optimization. Using the calibrated model, we derived vaccination schedules consisting of three injections totaling $2.4 \times {10}^6$ DCs. Despite using the same total dose as the baseline four-injection protocol, the optimized schedules reduced tumor burden by approximately $52\%$ over a 5000-h window, as measured by the area under the tumor-time curve, while also lowering the number of administrations. These results demonstrate that effective tumor control can be achieved without increasing treatment intensity and with substantially fewer vaccinations than previously assumed. Prior optimization studies often required cumulative doses exceeding $1 \times {10}^7$ cells to obtain comparable therapeutic effects. In contrast, our findings show that metaheuristic algorithms can produce dose-efficient and biologically grounded schedules that significantly enhance treatment performance. This work highlights the value of computational optimization as a decision-support tool for designing efficient and clinically meaningful DC immunotherapy protocols. Full article

Background: Cervical cancer remains a major global health challenge, ranking fourth among malignancies in women, with an estimated 660,000 new cases and 350,000 deaths in 2022. Despite advances in vaccination and screening, incidence and mortality remain disproportionately high in low- and middle-income countries. The disease is strongly linked to persistent infection with high-risk human papillomavirus (HPV) types, predominantly HPV 16 and 18, whose E6 and E7 oncoproteins drive cervical intraepithelial neoplasia (CIN) and invasive cancer. This review summarizes current evidence on clinically relevant biomarkers in HPV-associated CIN and cervical cancer, emphasizing their role in screening, risk stratification, and disease management. Methods: We analyzed the recent literature focusing on validated and emerging biomarkers with potential clinical applications in HPV-related cervical disease. Results: Biomarkers are essential tools for improving early detection, assessment of progression risk, and personalized management. Established markers such as p16 immunostaining, p16/Ki-67 dual staining, and HPV E6/E7 mRNA assays increase diagnostic accuracy and reduce overtreatment. Prognostic indicators, including squamous cell carcinoma antigen (SCC-Ag) and telomerase activity, provide information on tumor burden and recurrence risk. Novel approaches—such as DNA methylation panels, HPV viral load quantification, ncRNAs, and cervico-vaginal microbiota profiling—show promise in refining risk assessment and supporting non-invasive follow-up strategies. Conclusions: The integration of validated biomarkers into clinical practice facilitates more effective triage, individualized treatment decisions, and optimal use of healthcare resources. Emerging biomarkers, once validated, could further improve precision in predicting lesion outcomes, ultimately reducing the global burden of cervical cancer and improving survival. Full article

Diffuse pleural mesothelioma (PM) is a rare thoracic malignancy with historically limited treatment options and poor outcomes. Despite the recent breakthrough of dual immune checkpoint blockade (ICB)—notably the combination of anti-PD-1 and anti-CTLA-4 therapies—clinical responses remain variable and overall survival gains modest. Consequently, there is an urgent need for multidimensional biomarkers and adaptive trial designs to unravel the complexity of PM immune biology. This review provides a comprehensive overview of current evidence on how histological subtypes (epithelioid vs. non-epithelioid) influence ICB efficacy, highlighting distinct genetic landscapes (e.g., BAP1, CDKN2A, NF2 mutations) and tumor microenvironment (TME) features, including immune infiltration patterns and PD-L1 or VISTA expression, that underlie differential responses. We further examine intrinsic tumor factors—such as mutational burden and checkpoint ligand expression—and extrinsic determinants, including immune cell composition, stromal architecture, patient immune status, and microbiota, as modulators of immunotherapy outcomes. We also discuss the rationale behind emerging strategies designed to enhance ICB efficacy, currently under clinical evaluation. These include combination regimens with chemotherapy, radiotherapy, surgery, epigenetic modulators, anti-angiogenic agents, and novel immunotherapies such as next-generation checkpoint inhibitors (LAG-3, VISTA), immune-suppressive cell–targeting agents, vaccines, cell-based therapies, and oncolytic viruses. Collectively, these advancements underscore the importance of integrating histological classification with molecular and microenvironmental profiling to refine patient selection and guide the development of combination strategies aimed at transforming “cold” mesotheliomas into “hot,” immune-responsive tumors, thereby enhancing the efficacy of ICB. Full article

Conventional cancer treatments often fail due to the immunosuppressive tumor microenvironment, immune tolerance, and chronic inflammation. Therefore, new therapeutic approaches are urgently needed. Cancer vaccines can stimulate natural killer cells and cytotoxic T-lymphocytes, and induce long-lasting memory responses that help overcome the immunosuppressive tumor microenvironment. Recent advances in nucleic acid, peptide, and dendritic cell-based vaccines have improved antigen delivery and immune activation, while combinations with immune checkpoint inhibitors and ablative therapies enhance therapeutic efficacy and durability. Preclinical and clinical studies targeting tumor-associated antigens have shown promising outcomes. With poor survival rates and limited treatment options, hepatocellular carcinoma (HCC) appears to be the most prevalent cause of cancer-related deaths worldwide. Advances in antigen discovery, vaccine delivery systems, and synergistic combination strategies are paving the way for more effective and durable immune responses. By integrating molecular insights with clinical innovation, cancer vaccines hold the potential not only to improve treatment outcomes but also to redefine long-term disease management and survival in HCC. Full article

Tuberculosis remains one of the most prevalent infectious diseases, and the only currently available vaccine is the Mycobacterium bovis bacillus Calmette–Guèrin (BCG) vaccine. The uncontrolled passaging of the BCG strain led to genetically diverse BCG strains. Seven samples from clinical BCG-associated disease were obtained from the National Tuberculosis Reference Laboratory. Whole-genome sequencing and bioinformatics analysis were performed using tools such as fastqc, Trimmomatic, and CLC Genomics Workbench 24.0.3 to obtain consensus sequences and analyse deletions between M. bovis AF2122/97, BCG Danish, and clinical samples. Snippy was used to generate the phylogenomic tree, Prokka for annotation, and an in-house script to detect potential drug resistance. Four deletions were identified between M. bovis wildtype and M. bovis BCG. The phylogenomic tree showed that of the seven strains analysed, one was phylogenetically close to M. tuberculosis H37Rv, and another to the Danish BCG vaccine. Other samples were distantly related to each other and to reference strains. Two of the samples showed possible resistance to ethambutol. This would imply original misdiagnosis of the disease and subsequent ineffective treatment. This study emphasises the importance of genomic testing for accurate diagnosis of BCG disease and underscores the need for phylogenomic surveillance of M. bovis BCG strains circulating in South Africa. Full article

High-risk human papillomavirus (HPV), including types 16–18, is the established cause of cervical intraepithelial neoplasia (CIN) and invasive carcinoma of the cervix. While preventive vaccination is highly effective in preventing infection from becoming reconstituted following treatment of existing disease, its use among cervical intraepithelial neoplasia (CIN)-positive females has remained sporadic. The following review provides an update on the current state of evidence about the acceptance, awareness, or perception of HPV vaccination by women following a diagnosis or treatment of CIN. Methods: A narrative synthesis of literature from the publication period of 2010 to 2025 was performed on PubMed, Scopus, and Google Scholar. Surveys that quantified literature on post-CIN vaccination attitudes, risk perceptions, or behavioral factors were considered. Results: Acceptance levels varied from 20–95% across all continents. The highest acceptance levels (≥80%) among the populations belong to the European and Oceanian groups, followed by moderate acceptance among the North Americans (60–80%), which was influenced by financial costs, misconceptions, and sociocultural stigmas. Several systemic-level features in Europe and Oceania have been shown to be consistently associated across these regions with high acceptance rates. These features include public funding of HPV vaccine delivery universally in these regions and reminder and recall systems established in their electronic health records. In these two regions, provider recommendation demonstrates particular significance because there is follow-up care after treatment of CIN. In these regions, mass awareness about HPV conducted in conjunction with their cervical screening programs increases baseline knowledge and favorability towards HPV vaccination. The lowest levels (20–70%) of awareness of HPV diseases and vaccination programs among Asians and Africans can be attributed to obstacles that include misconceptions about fertility concerns. In the case of Asia, there are various socially ingrained stigma factors that contribute to the poor awareness and acceptance levels. These factors include the possibility of being perceived as promiscuous, embarrassment linked to STI conditions, as well as the possibility of rejection from partners and in-laws. In particular regions, there might be stigmas attached to HPV vaccination that cause tension within married women who perceive the vaccine as an indicator of being unfaithful. Also, distrust from the general community has been driven by past incidents, including the halting of proactive HPV vaccine recommendations in Japan in 2013. Moreover, there are numerous myths concerning infertility and menstruation linked to poor vaccine acceptance. The key determinant of acceptance levels was physician endorsement, lack of knowledge of the association of HPV-CIN, or the belief that there is no need for vaccination after treatment. Conclusion: The acceptance of HPV vaccination among women following CIN is influenced by educational level, the structure of the healthcare system, and sociocultural factors. Incorporating evidence-based cervical vaccination counseling into follow-up care after biopsy could help increase its acceptance and prevent recurrent high-grade lesions. Full article

Cancer immunotherapy has transformed oncology, but lasting responses are still limited due to resistance mechanisms within the tumor microenvironment. MicroRNAs (miRNAs) have emerged as critical regulators of immune checkpoint pathways, antigen presentation, T-cell activity, and macrophage polarization. By modulating both tumor-intrinsic and immune cell–intrinsic processes, miRNAs influence the efficacy of immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapies. Additionally, circulating and exosomal miRNAs are being investigated as minimally invasive biomarkers to predict patient response and resistance to immunotherapy. Clinical trials of miRNA-based treatments, including mimics and inhibitors, have highlighted both the promise and challenges of translating these molecules into clinical use. Advances in delivery systems, RNA chemistry, and combinatorial strategies are paving the way for their integration into precision immuno-oncology. This review offers a comprehensive overview of the mechanistic, biomarker, and therapeutic roles of miRNAs in cancer immunotherapy, highlighting ongoing clinical progress and prospects. Full article

Shellfish allergy is among the most common food allergies (FAs) worldwide and represents a severe immunoglobulin E (IgE)-mediated FA with tropomyosin functioning as the predominant pan-allergen. Current management of shellfish allergies is strictly palliative with allergen avoidance, underscoring the critical need for disease-modifying therapies. While conventional allergen-specific immunotherapy (AIT) approaches, namely oral and sublingual immunotherapies, demonstrate capacity for desensitization, more clinical applications are needed in the potential safety concerns and prolonged treatment durations. Innovative treatments, such as the design of modified shellfish allergens, DNA vaccine technologies, and nanoparticle-based delivery platforms such as virus-like particles (VLP), show efficacy and potential in inducing protective antibodies while promoting antigen-specific immune tolerance with reduced allergenic risks. These innovative approaches hint at a promising pathway in achieving safe, effective, and long-lasting clinical tolerance for shellfish allergy. This review describes the current perspectives on allergen immunotherapy regarding shellfish allergy and analyzes emerging therapeutic strategies poised to overcome these limitations. Full article

The specific objective of the current paper was the description of some health-related outcomes in sheep and goat farms in Greece with common grazing with wildlife ruminants. Faecal samples were collected and information regarding health management applied on farms was obtained from sheep and goat farms located throughout Greece (325 and 119 farms, respectively). Common grazing of livestock (sheep, goats) with wildlife ruminants (roe deer, red deer) was reported in 9.2% of farms. Faecal epg counts in farms with common grazing with wildlife ruminants were higher than in farms with no common grazing: respective median values were 270 epg versus 150 epg; also, there was a tendency for faecal counts >300 epg to be recorded more frequently among the former farms (36.1% versus 23.1% of farms). Median annual incidence of cases of abortion and of cases of diarrhoea in lambs/kids was significantly higher in farms with common grazing with wildlife ruminants: 1.7% and 9.0%, respectively, versus 0.0% and 1.7%, respectively, in farms with no common grazing. The findings have revealed associations of common grazing with wildlife ruminants with the health of sheep and goats. These can have implications in the health management of farms, for example, in the administration of anthelmintic treatments and in the development of vaccination programmes in livestock farms. Full article

The West Nile Virus (WNV), transmitted by Culex mosquitoes as a major vector, has been reported worldwide. Also, West Nile neuroinvasive disease (WNND) caused by WNV lineage 1a and 2 neuroinvasive infections has been constantly reported with high fatality rates. Nevertheless, there are no treatments and vaccinations, so diagnosis in the early stages is important. Recently, a molecular diagnostic technique using DNA endonuclease-targeted CRISPR trans reporter (DETECTR) with the CRISPR-Cas12a system integrated with isothermal nucleic acid amplification has newly emerged. In this study, we designed a 2-Step WNV DETECTR with reverse transcription–recombinase polymerase amplification (RT-RPA) for rapid and sensitive WNV diagnosis. It successfully detected down to 1.0 × 10² RNA copies for both WNV lineage 1a and 2 with demonstrating similar sensitivity to qRT-PCR without cross-reactivity to other viruses. Additionally, we designed a 1-Step WNV DETECTR, incorporating all processing steps into a single tube, capable of detecting down to 1.0 × 10³ RNA copies for both lineages. Furthermore, we developed a more streamlined method, the 1-Step with Filter WNV DETECTR, which achieved detection limits comparable to the 2-Step method, while reducing the processing time by 5 min. This study also explored the potential of the Punch-it™ NA-Sample Kit as an efficient alternative lysis method by comparing the detection differences across various lysis methods. Through this method, we achieved rapid and simple amplification and detection processes suitable for field diagnostics with high specificity and sufficient sensitivity. Therefore, DETECTR methods presented themselves as promising alternatives to conventional diagnostic tools, potentially overcoming financial and technical constraints in diverse medical settings. Full article

Background/Objectives: Cervical cancer is one of the most common cancers among women of reproductive age, with 80% of the cases occurring in developing countries. Cervical cancer is largely preventable by effective screening programs. This study assessed the knowledge, attitudes, cultural beliefs, and screening practices related to cervical cancer among women in the rural community of Lutubeni, Eastern Cape Province. Methods: A descriptive cross-sectional study was conducted among 95 women aged 25 years or older attending Lutubeni Clinic. Data was collected using a structured, validated questionnaire covering demographics, reproductive health, knowledge of cervical cancer, attitudes, cultural perceptions, and screening practices. Statistical analysis involved descriptive summaries, chi-square tests, and binary logistic regression. Results: Most participants exhibited poor knowledge of cervical cancer symptoms (47.4%) and risk factors (61.1%), with only 3.2% demonstrating good overall knowledge. Vaginal bleeding (60.0%) and foul-smelling discharge (50.5%) were the most recognized symptoms. Only 40.0% were aware of human papillomavirus (HPV) vaccination. While 87.4% knew about cervical cancer screening, only 55.8% had ever been screened. Of these, 43.2% had screened only once, primarily at the clinic (33.7%), mostly initiated by health professionals (41.1%). Positive attitudes toward screening were observed in 52.6%, while 88.4% held cultural beliefs that hindered open discussion about sexual health. Statistically significant factors associated with screening uptake included educational level (p = 0.047), knowledge of symptoms (p = 0.04), risk factors (p < 0.0001), prevention (p < 0.0001), treatment (p = 0.001), and attitudes (p < 0.0001). Independent predictors of poor screening practice were holding an associate degree (OR = 0.04, p = 0.042), having good preventive knowledge (OR = 0.02, p = 0.012), and having negative attitudes (OR = 36.22, p = 0.005). Conclusions: High awareness alone does not guarantee participation in cervical cancer screening in rural South Africa. Interventions must address cultural barriers, stigma, and negative perceptions while strengthening health education that links HPV vaccination with screening awareness. The unexpected association between associate degree attainment and poor screening underscores the complexity of behavioral determinants and warrants further investigation in larger cohorts. Full article

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail. Full article