Search Results (79)

Background: Elite HIV controllers exhibit persistent immune activation despite sustained viral suppression, a phenomenon that challenges the traditional view of immunological equilibrium. In parallel, autoimmune diseases are characterised by chronic inflammation driven by dysregulated immune responses. Objective: This study aimed to analyse the potential pathophysiological convergence between both conditions and to identify a shared inflammatory axis with possible translational implications. Methods: A critical narrative and integrative reflection was conducted using a purposive, concept-driven selection of evidence from PubMed/MEDLINE, Scopus, and Web of Science. A total of 43 sources were included: 28 studies informing mechanistic findings (14 on elite HIV controllers and 14 on autoimmune diseases), 12 addressing modulatory strategies (pharmacological and lifestyle-based), and 3 providing contextual frameworks. Results: Both conditions demonstrate sustained activation of innate immunity, characterised by elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF, type I interferons), increased inflammatory biomarkers (e.g., sCD14, IP-10), and activation of pathways such as NLRP3 inflammasome and NF-κB signalling. Collectively, these findings suggest convergence towards a potential shared inflammatory axis mediated by the inflammasome–interferon pathway, which may contribute to persistent systemic inflammation and tissue damage. Evidence from pharmacological and non-pharmacological interventions suggests that components of this axis may be susceptible to modulation. Conclusions: The observed convergence supports a conceptual model of shared innate inflammatory activation across both conditions. Rather than implying a unified therapeutic approach, the findings suggest a framework of convergent modulation targeting the inflammasome–interferon axis. This hypothesis warrants further investigation to determine its clinical and translational relevance. Full article

Background/Objectives: Batai orthobunyavirus (BATV) is an emerging mosquito-borne zoonotic pathogen for which no licensed vaccine is currently available. The viral envelope glycoprotein plays an important role in viral attachment and host immune recognition, making it a potential target for rational vaccine design. Methods: In this study, an immunoinformatics-based framework was used to design and evaluate a multi-epitope vaccine candidate targeting the BATV envelope glycoprotein. Selected B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were assembled using appropriate linkers and a human β-defensin adjuvant. Population coverage and in silico immune simulations were conducted to evaluate the potential breadth and magnitude of immune response. Results: The final vaccine construct demonstrated favorable physicochemical characteristics, high predicted antigenicity (0.7959), and non-allergenic properties while maintaining favorable predicted structural characteristics and broad predicted population coverage (99.92%). Structural docking revealed a stable interaction between the vaccine construct and human TLR4, with a weighted docking score of −1194.8, suggesting favorable molecular recognition and receptor engagement. Normal Mode Analysis further supported the structural stability and conformational integrity of the vaccine receptor complex. Immune simulation predicted robust primary and secondary immune responses characterized by elevated IgM and IgG antibody production, sustained memory cell formation, and strong IFN-γ and IL-2 responses, indicating the potential to elicit balanced humoral and cellular immunity. Conclusions: This study presents a structurally optimized and validated multiepitope vaccine candidate against the emerging Batai orthobunyavirus. These computational findings identified a promising vaccine candidate for further investigation; however, its immunogenicity, safety, and protective efficacy before further vaccine development can be considered. Full article

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15–30% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders. Full article

HIV-associated neurocognitive disorders (HAND) persist despite effective antiretroviral therapy, indicating that chronic neuroimmune dysfunction extends beyond active viral replication. Among HIV-1-derived factors, the viral proteins Tat and gp120 are contributors to sustained brain inflammation. Nevertheless, their comparative impact in genetically vulnerable neural environments remains unclear. Here, we performed a secondary transcriptomic analysis of publicly available RNA-seq data derived from the striatal tissue of hSNCA^A53T Gba1^+/L444P mice, a model combining α-synuclein overexpression with Gba1-associated lysosomal impairment, following unilateral intrastriatal injection of Tat or gp120. Both proteins induced robust transcriptional remodelling selectively in the injected striatum. Tat primarily elicited a broad inflammatory amplification programme encompassing innate immune sensing, chemokine recruitment, adaptive immune engagement, and loss of homeostatic support. gp120 preferentially activated antigen presentation, complement, oxidative stress, and lysosomal–phagocytic effector pathways consistent with immune-mediated synaptic stress. Despite these distinct profiles, Tat and gp120 converged on a shared microglia-centred effector core. Contralateral striatal tissue was analyzed as distal non-injected tissue to explore the spatial distribution of transcriptional responses and minimal and protein-specific effects were reported. These findings provide a mechanistic framework for HAND heterogeneity and suggest that HIV protein-driven neuroimmune transcriptional programmes may create a molecular environment compatible with increased neurodegenerative vulnerability in lysosome-compromised, α-synuclein-sensitized brains. Full article

The Oropouche virus (OROV), an orthobunyavirus primarily transmitted by the biting midge Culicoides paraensis, is the causative agent of Oropouche fever, a re-emerging arboviral disease associated with significant morbidity in Central and South America. The increasing frequency of outbreaks, including cases of sustained transmission in non-endemic regions and reports of vertical transmission, highlights the growing public health concern posed by OROV. Currently, there are no specific antiviral therapies or licensed vaccines available, underscoring the urgent need for effective therapeutic and preventive strategies. Recent advances in antiviral research have identified promising candidates, including repurposed drugs and bioactive compounds that target key stages of the viral replication cycle. In parallel, vaccine development has progressed through modern platforms, including viral vector-based and nucleic-acid-based technologies, enabling rapid responses to emerging outbreaks. However, major challenges remain, particularly due to the limited understanding of OROV pathogenesis, virus–host interactions, and the correlates of protective immunity. Furthermore, the ongoing evolution of OROV, including the genetic diversity and potential genomic rearrangements observed among circulating strains, represents an additional challenge that may influence viral characteristics and potentially affect the long-term efficacy of antiviral interventions and vaccine-induced protection. This review summarizes recent advances in the discovery of antiviral candidates and the development of vaccine approaches against OROV, both of which are essential for reducing the impact of OROV infections and strengthening preparedness for future outbreaks. Full article

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation. Full article

In Africa, the disease burden of diarrheal and respiratory diseases is amplified by limited surveillance capacity, diagnostic limitations, and socioeconomic inequalities. In rapidly urbanizing settings such as Kigali (Rwanda), integrating wastewater-based epidemiology (WBE) into existing surveillance systems offers a promising strategy for generating real-time epidemiological intelligence, identifying community-level hotspots, and addressing gaps in traditional reporting systems. Gastrointestinal and respiratory infections remain major causes of morbidity and mortality globally, particularly in low- and middle-income countries (LMICs), where traditional clinical surveillance systems frequently underreport the true disease burden. This systematic review synthesizes current evidence on the detection of gastrointestinal and respiratory pathogens in wastewater and evaluates the utility of WBE for early warning and public health action. A narrative review approach was used to identify peer-reviewed literature, global health reports, and surveillance studies focusing on the wastewater detection of gastrointestinal and respiratory pathogens. Databases including PubMed, Scopus, and Google Scholar were searched for studies published between 2000 and 2026. The search yielded 1247 records, of which 312 duplicates were removed. After title/abstract screening, 228 full-text articles were retrieved and assessed for eligibility. After a detailed evaluation, 108 studies were excluded for the following reasons: absence of pathogen-specific wastewater data (n = 46), a focus on environmental monitoring without public health relevance (n = 25), insufficient methodological description (n = 21), or other eligibility limitations such as a lack of primary data (n = 16). WBE provides a non-invasive, cost-effective approach for monitoring symptomatic and asymptomatic infections. Challenges involve variability in sampling, environmental factors affecting viral decay, and differences in laboratory workflows. WBE is a powerful complement to traditional infectious disease surveillance, offering early warning capabilities, population-level coverage, and real-time insights into pathogen circulation. Integrating WBE into surveillance programs, especially in LMICs such as Rwanda, can significantly strengthen epidemic preparedness, guide resource allocation, and improve outbreak response. Sustained investment in laboratory capacity, standardized protocols, and multisector collaboration is essential to fully leverage WBE for public health protection. Full article

Bovine Viral Diarrhoea (BVD) is an infectious disease caused by the Bovine Viral Diarrhoea Virus (BVDV), a member of the genus Orthopestivirus. The disease remains endemic across Australian beef and dairy production systems, imposing a multi-million-dollar annual burden on animal health, welfare, and industry sustainability. BVDV can be transmitted both horizontally and vertically, with persistently infected (PI) animals serving as the primary source of infection. Rapid identification and subsequent culling of PI animals are fundamental requirements for any successful eradication program. Currently, Australia’s decentralised, non-compulsory approach places the responsibility of biosecurity on individual producers, resulting in a fragmented national landscape. This review proposes that the strategic deployment of rapid, field-deployable point-of-care (POC) diagnostics serves as the transformative catalyst needed for a coordinated national eradication pathway. POC approaches utilising technologies such as lateral flow assays, nucleic acid amplification tests, and biosensors enable real-time, crush-side diagnosis and high-throughput surveillance, proving effective for early detection and control of infectious diseases. When integrated with robust biosecurity measures and optimised vaccination strategies, these POC advancements offer a scientifically sound and commercially viable pathway toward the systematic eradication of BVDV in the Australian cattle industry. Full article

Background: This case report presents a 12-year-old male with vertically transmitted chronic hepatitis B virus (HBV) infection, exhibiting a rare pan-reactive serological profile (concurrent HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb positivity) alongside fluctuating low-level viremia (HBV DNA: 1.06 × 10² IU/mL to undetectable). Rigorous exclusion of technical artifacts confirmed the authenticity of this atypical serologic pattern, observed in <0.001% of the general population. Methods: Liver biopsy and immunohistochemical staining were performed to evaluate hepatic inflammation and fibrosis. HBV serological markers and viral load were quantified using commercial diagnostic kits, with longitudinal monitoring for 18 months. Results: Liver biopsy revealed Grade 2 inflammation with focal HBsAg/HBcAg expression, supporting immune-active chronic hepatitis B (CHB) despite partial seroconversion. The patient’s clinical course highlights key challenges in pediatric HBV management: (1) delayed immune reconstitution (18-month longitudinal HBeAg/HBeAb dynamics), (2) non-linear virologic-ALT correlation, and (3) diagnostic ambiguity in pan-positive serology—potentially reflecting S-gene escape mutants or transitional immune responses. Initiation of tenofovir disoproxil fumarate (TDF) achieved sustained virologic suppression, underscoring the importance of early antiviral therapy in pediatric CHB with atypical markers. Conclusions: This case provides preliminary insights into the complex interplay between viral evolution and immature host immunity, advocating for refined monitoring protocols integrating high-sensitivity HBV DNA, quantitative serology, and non-invasive fibrosis assessment in pediatric HBV care. Full article

Crop fungal and viral diseases cause annual economic losses exceeding USD 150 billion globally, demanding rapid, sensitive, and field-deployable diagnostic technologies. This review critically evaluates recent advances in electrochemical biosensing platforms for early crop pathogen detection, focusing on immunosensors, genosensors, aptasensors, and VOC-based systems. Reported analytical performances demonstrate ultralow detection capabilities, including 0.3 fg mL⁻¹ for viral coat proteins, 15 DNA copies for bacterial pathogens, 0.5 fg µL⁻¹ RNA detection for viroids, and nanomolar-level VOC sensing (35–62 nM), with response times ranging from 2 to 60 min. Comparative analysis reveals that genosensors and aptasensors generally achieve the lowest LODs due to nucleic acid amplification or high-affinity recognition, while immunosensors provide robust protein-level specificity validated against ELISA. Volatile organic compound (VOC) sensors enable non-invasive, pre-symptomatic monitoring but face specificity challenges. Despite strong laboratory performance, practical adoption is limited by matrix-derived electrochemical interference, environmental instability of biorecognition elements, workflow complexity, and insufficient standardization across studies. Emerging innovations, including magnetic bead enrichment, nanoporous and graphene-based electrodes, microfluidic integration, AI-assisted impedance interpretation, and biodegradable substrates, are progressively addressing these bottlenecks. This review emphasizes that successful field translation requires holistic workflow engineering, matrix-matched validation, and harmonized performance metrics rather than incremental sensitivity improvements alone. By integrating analytical chemistry, nanomaterials engineering, and agricultural decision-support frameworks, electrochemical biosensing platforms hold significant potential to enable decentralized, rapid, and sustainable crop disease management. Full article

Viral and bacterial pathogen pathogens cause disease outbreaks that challenge the pearl gentian grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) industry’s sustainable development. The lack of monoclonal antibodies (mAbs) targeting serum immunoglobulin M (IgM) in this hybrid grouper impedes the development of non-lethal immunoassays for detecting pathogen infections, as well as research on immune responses following vaccination. We purified serum IgM from hybrid pearl gentian grouper and generated two mAbs—designated 41-H2-E1 and 62-E8-G9—against the purified IgM, finding that mAb 62-E8-G9 specifically recognized the IgM heavy chain, whereas mAb 41-H2-E1 specifically recognized the light chain. In indirect immunofluorescence assays, both mAbs reacted with surface Ig-positive (sIg⁺) lymphocytes. A double-antibody sandwich ELISA was subsequently established using mAb 62-E8-G9 as the capture antibody and HRP-conjugated mAb 41-H2-E1 as the detection antibody, enabling accurate quantification of serum IgM levels. Significant differences in IgM concentrations were observed between larger and smaller individuals (9.11 μg/mL vs. 3.84 μg/mL, p < 0.05). In immunostimulant administration experiments, both low-and high-dose groups exhibited approximately 2.0-fold higher IgM levels than the control group (p < 0.05). In contrast, vaccination with inactivated vaccines did not result in statistically significant differences in total IgM levels. mAb 41-H2-E1 was further applied to detect Vibrio parahaemolyticus- and Vibrio harveyi-specific immunoglobulins in serum under different vaccination regimens. Collectively, these findings demonstrated that the mAbs developed in this study served as reliable immunological tools for investigating immune function in hybrid pearl gentian grouper. Full article

The soil–water interface (SWI) represents a critical biogeochemical hotspot where steep physicochemical gradients across millimetre-to micrometre-scales create diverse ecological niches controlling nutrient cycling, carbon stabilisation, and contaminant transformation. This review synthesises emerging understanding of micro-scale microbial dynamics, biofilm architecture, and functional processes shaping SWI ecosystems. We examine redox stratification driving microbial community assembly, biofilm-mediated nutrient trapping and soil aggregate stabilisation, and dynamic drivers including hydrological fluctuations, viral lysis, and differential transport at gas–water versus solid–water interfaces. Advanced methodologies, microsensor profiling, cryo-sectioning, spatially resolved metatranscriptomics, and non-destructive imaging, now enable unprecedented resolution of SWI microhabitat chemistry and microbial organisation. Horizontal gene transfer within interface biofilms accelerates adaptive responses to environmental stressors. Integration of micro-scale observations into ecosystem-level models remains challenging but essential for predicting soil carbon sequestration, contaminant fate, and microbial resilience under climate change. Strategic SWI management through biofilm engineering and controlled redox manipulation offers novel pathways for sustainable agriculture and bioremediation, though it requires careful balance of multiple ecosystem functions. Full article

Background: Immunomodulatory compounds can modify or regulate the immune responses. Given that vaccine-induced immune responses can vary in magnitude and durability depending on antigen properties and adjuvant selection. Immunomodulators that enhance antigen-specific immune responses with low toxicity may complement existing adjuvant systems. Recent studies indicate that adenosine receptor–mediated signaling can modulate dendritic cell (DC) function through mechanisms distinct from classical pathogen-associated molecular pattern (PAMP)-driven Toll-like receptor pathways. Methods: In this context, the present study comparatively evaluates poly-(lactic-co-glycolic acid) (PLGA) microparticle–encapsulated β-L-adenosine (BLA MPs) alongside established FDA-approved adjuvants to assess their immunomodulatory potential under limited-antigen conditions. FDA-approved PLGA was used to encapsulate BLA in combination with multiple viral antigens, including H1N1 influenza, Zika virus, and canine coronavirus, to enable sustained delivery, antigen protection, and efficient uptake by antigen-presenting cells. Results: Physicochemical characterization demonstrated uniform particle size distribution, a low polydispersity index, and a stable negative surface charge. Release studies showed more than 50% payload release within 12 h, with release kinetics best described by the Korsmeyer–Peppas model. Cytotoxicity evaluation using DC2.4 cells confirmed that BLA MPs were non-cytotoxic at concentrations up to 250 μg/mL. Comparative in vitro immunological assessments revealed that BLA MPs induced dendritic cell activation, including upregulation of antigen-presenting and co-stimulatory molecules, at levels largely comparable to those observed with Alum- and MF59-based formulations across multiple antigen groups. Nitric oxide production remained within comparable ranges, indicating balanced immunostimulatory activity without excessive inflammatory signaling. In select conditions, co-formulation of BLA MPs with MF59 further enhanced DC activation, supporting its role as a complementary immunomodulatory component. Conclusion: These findings align with previously reported adenosine-dependent pathways involved in DC maturation and antigen presentation. Overall, this comparative study demonstrates that PLGA-encapsulated β-L-adenosine functions as an effective immunomodulatory agent, with performance comparable to that of established FDA-approved adjuvants across diverse vaccine antigens. Further in vivo studies are warranted to evaluate dose dependency, cytokine profiles, and antibody responses to define its role within combinatorial vaccine adjuvant strategies. Full article

Background: Sepsis is a life-threatening organ dysfunction that results from an exaggerated host immune response to disseminated infection. The relationship between lymphopenia and sepsis has been extensively studied, and in particular, sepsis-induced lymphopenia is gradually being recognized as an essential factor in the prognosis of sepsis. Notably, sepsis-induced lymphopenia has been associated with worse outcomes, including increased risk of secondary infections, multiple organ failure, and death. Few studies have directly compared the dynamic evolution of lymphocyte counts between different etiologies of sepsis or evaluated their prognostic value using serial measurements. This study aims to explore the temporal dynamics of lymphopenia, but also of neutrophil-to-lymphocyte (NLR) ratio in patients with severe systemic infections and to assess their relationship with in-hospital mortality. Methods: A prospective cohort of 95 adult patients was analyzed. Absolute lymphocyte counts (ALCs) and neutrophil-to-lymphocyte (NLR) ratio values were recorded on Days 1, 3, 5, and 7. Comparisons were made between different infectious etiologies and outcomes, and ROC analysis assessed predictive performance. Results and Conclusions: Patients with viral sepsis (“COVID-19”) showed a significant and sustained decrease in lymphocyte counts (p < 0.001) and a progressive increase in NLR (p < 0.001), unlike patients with bacterial sepsis. In correlation with outcome, regardless of etiology, lymphocyte counts were significantly lower in non-survivors from Day 3 onward, while NLR was significantly higher on Day 7 (p = 0.002). Early NLR and ALC had limited predictive value, but longitudinal trends were associated with poor prognosis. Full article

Background: Direct-acting antiviral (DAA) therapy has transformed chronic hepatitis C virus (HCV) infection into a curable disease. Beyond viral eradication, increasing attention has been directed toward metabolic changes following sustained virological response (SVR), particularly alterations in lipid metabolism. This study aimed to assess the long-term evolution of lipid parameters after HCV cure in a real-world clinical cohort. Methods: We conducted a prospective, single-center observational study including 85 patients with chronic HCV infection who achieved SVR after DAA therapy. Lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, were assessed at baseline and during post-SVR follow-up at 24, 48, and 96 weeks. Body mass index (BMI) and non-invasive fibrosis indices were also evaluated. Longitudinal changes were analyzed using mixed-effects models. Results: Total cholesterol increased from 157.7 ± 35.6 mg/dL at baseline to 179.6 ± 42.9 mg/dL at SVR 24 and further to 189.0 ± 40.3 mg/dL at SVR 48, stabilizing at 177.7 ± 38.3 mg/dL at SVR 96. LDL-C showed a similar trajectory from 94.6 ± 30.8 mg/dL at baseline to 107.5 ± 33.3 mg/dL at SVR 24, further raising to 115.7 ± 36.2 mg/dL at SVR48, and 111.8 ± 39.5 mg/dL at SVR 96. HDL-C showed minimal change, while triglycerides demonstrated greater interindividual variability without a consistent population-level trend. BMI remained stable over follow-up (26.6 ± 4.7 to 27.6 kg/m²). Linear mixed-effects models confirmed a significant effect of time after SVR on total cholesterol and LDL-C (p < 0.05). Conclusions: In this real-world cohort, HCV cure with DAA therapy was associated with sustained long-term changes in lipid metabolism, characterized by increases in total cholesterol and LDL-C independent of major weight changes. These findings support the importance of continued metabolic monitoring after SVR, particularly in patients with additional cardiometabolic risk factors. Full article