Search Results (4,200)

Adipose tissue has emerged as a pivotal endocrine organ, secreting bioactive proteins termed adipokines that regulate metabolic and immune processes across multiple organ systems. In the context of sepsis and critical illness, conditions defined by a dysregulated host response to infection with life-threatening organ dysfunction, the role of novel adipokines has attracted considerable research interest. This review focuses on three novel adipokines: chemerin, vaspin (SERPINA12), and omentin-1 (intelectin-1). We will discuss current in vitro, in vivo experimental animal models, and clinical evidence, emphasizing their biology, mechanisms of action, and potential as diagnostic and prognostic biomarkers in critically ill patients. All three adipokines are elevated in sepsis compared with healthy controls and correlate with established severity scores, including APACHE II and SOFA. Chemerin and omentin-1 have both been independently associated with 28-day mortality in prospective cohort studies. Vaspin exhibits robust cardioprotective effects in murine sepsis models via inhibition of kallikrein 7 (KLK7) and attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) both in vitro and in vivo. Omentin-1 suppresses LPS-induced macrophage activation through TLR4/MyD88/NF-κB inhibition in vitro and protects against LPS-induced ALI in murine models. Despite these promising findings, substantial methodological heterogeneity and limited large-scale clinical data currently preclude clinical implementation. Future research that standardizes assays, expands to multicenter cohorts, and investigates therapeutic modulation of these pathways is urgently needed. Full article

Background/Objective: African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious viral disease affecting domestic pigs and wild boars, causing severe economic losses. Although commercial ASF vaccines have recently been approved in Vietnam, controlling ASF transmission remains challenging. Since injection-based vaccination is impractical for wild boars, oral vaccination is considered essential. This study aimed to evaluate the safety, immunogenicity, protective efficacy, and dose-related outcomes of ASFV-G-ΔI177L/ΔLVR, a live attenuated ASFV vaccine candidate with deletion in the I177L gene and left variable region (LVR), administered orally to convention pigs. Methods: The ASFV-G-ΔI177L/ΔLVR vaccine candidate was orally administered to conventional pigs at three dose levels (10^2.25, 10^5.0, and 10^6.0 TCID₅₀/dose). At 28 days post-vaccination, pigs were challenged intramuscularly with a virulent ASFV field strain at 10^2.0 HAD₅₀/mL and monitored clinically. Protection was assessed by ASFV-specific antibody responses (p32) and survival following challenge. Results: Oral immunization was well tolerated, with no vaccine-associated clinical signs observed before challenge. Following challenge, vaccinated pigs showed different protective outcomes among the tested dose groups, with survival rates of 1/4 (10^2.25 TCID₅₀/dose), 4/4 (10^5.0 TCID₅₀/dose), and 3/4 (10^6.0 TCID₅₀/dose), respectively. Pigs that succumbed to infection showed neither detectable viremia nor ASFV-specific antibodies before challenge, suggesting incomplete vaccine uptake may have resulted in insufficient immune induction rather than an adverse effect associated with vaccination. In contrast, pigs that seroconverted prior to challenge were fully protected and exhibited lower viral loads than the control animals. Conclusions: ASFV-G-ΔI177L/ΔLVR was well tolerated as an oral live attenuated vaccine candidate and induced protective immunity against virulent ASFV challenge under the present experimental conditions. Notably, complete protection was observed in the 10^5.0 TCID₅₀/dose group, supporting the potential of this vaccine candidate for oral immunization strategies against ASF. However, the present data do not allow a definitive conclusion regarding the dose–response relationship, and further studies with larger group sizes and field-relevant models are needed to refine dose selection and practical applicability, particularly for wild boar vaccination. Full article

The consequences of foot and mouth disease (FMD) outbreaks in non-endemic countries are devastating. Early detection and confirmation of foot and mouth disease virus (FMDV) are critical for controlling outbreaks. Diagnostic sampling currently uses direct sampling of suspected animals, including swabs and/or vesicular fluid. In the event of an FMD outbreak, there is limited veterinary capacity to sample all animals in the control zones. Thus, environmental sampling methods (shoe booties, ropes, and environmental swabs) were assessed and compared to direct animal sampling for experimentally infected cattle and swine. Environmental sampling methods such as shoe booties were sufficient to identify FMDV by reverse transcription quantitative PCR (RT-qPCR) and nanopore sequencing, similarly to oral swabs collected from animals. Furthermore, a loop-mediated isothermal amplification (LAMP)-based point-of-care test produced by ZiP Diagnostics was able to rapidly detect FMDV from clinical and environmental samples with Cq values of 30 or less. This study demonstrates a proof of concept that shoe booties can be used to detect FMDV in animal pens prior to the onset of clinical signs in animals. The use of shoe booties for surveillance sampling of non-clinical animals on multiple premises in a given zone would increase operational capacity and enable earlier detection for a faster response to FMD outbreaks. Full article

Human T-Lymphotropic virus type 1 (HTLV-1) lifelong infects at least 5–10 million people worldwide, a minority of whom develop severe lethal diseases including adult T-cell Leukemia/lymphoma and HTLV-1-associated myelopathy or tropical spastic paraparesis. Currently, no vaccines or curative therapies to fight HTLV-1 infection or diseases are available. Recently we found that a tributyltin molecule, Bu₃SnOCOCF₃ (TBT), which is more potent than cisplatin in inducing cytotoxic effects towards a panel of cell lines including high-tumorigenic cells, also exerted potent cytotoxic effects even towards HTLV-1-infected cell lines, mimicking different states of virus-driven transformation. The type of cell death involved was elusive. In the present study, the effects of TBT on virological and cell death parameters were investigated in HTLV-1-infected immortalized lymphocytes generated by in vitro infection and rendered with or without progressive independence from interleukin-2 as a growth factor. Molecular studies demonstrated that TBT affected HTLV-1 viral gene expression, especially HBZ. TBT confirmed its high cytotoxic potential on the HTLV-1-infected cell lines assayed, especially towards the IL-2-independent HTLV-1-infected cells. Investigation of mechanisms involved in cell death induced by TBT in HTLV-1-infected cells confirmed that caspase 3 and 8 activation, as well as apoptotic response, were relevant. In addition, pyroptosis as well as other unspecifed forms of lytic death presumably contribute to cell death induced by TBT in HTLV-1-infected cells, while a concomitant activation of an autophagic response by this compound seems to mitigate it. Overall, these experimental results outline a particular profile of TBT-induced cell death in HTLV-1-infected cells that is useful for future studies aimed at verifying the real potential of tin-based compounds to contrast diseases caused by HTLV-1. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global public health threat, compromising prevention and treatment of infectious diseases. This narrative review examines AMR as a multifactorial and transnational crisis through epidemiological, One Health, social and bioethical perspectives, and discusses emerging non-antibiotic preventive and therapeutic strategies. Methods: PubMed and Scopus were searched using terms related to AMR, epidemiology, public health, surveillance, One Health, bioethics, equity and alternative therapies. Peer-reviewed medical and public health articles were considered, together with selected reports from international organizations and public health agencies. Results: AMR is driven by inappropriate antibiotic use in human medicine, livestock, aquaculture and agriculture, combined with weaknesses in infection prevention, stewardship, environmental control and surveillance. Epidemiological evidence shows a substantial global burden, marked regional inequalities in resistance patterns, surveillance capacity and policy response, and major consequences, including increased mortality, prolonged hospitalization, rising healthcare costs and disproportionate effects on vulnerable populations. Key bioethical concerns include collective responsibility, equitable access to effective treatment, stewardship, global justice and intergenerational accountability. Emerging non-antibiotic strategies vary in translational maturity: vaccines and selected microbiome-based interventions have preventive or supportive roles in defined settings, bacteriophage therapy is used mainly in compassionate or specialized contexts, and many antimicrobial peptides and nanotechnology-based platforms remain experimental or early translational. Conclusions: AMR requires coordinated global action grounded in One Health, strong public health systems, integrated surveillance, responsible antimicrobial use and sustained innovation. Effective containment must also address social inequalities, ethical stewardship, equitable access to diagnostics and treatment, and responsibility toward future generations. Full article

Heparin-binding protein (HBP) is an activation-dependent neutrophil granule protein involved in innate immune activation, endothelial barrier disruption, and inflammatory tissue injury. Although HBP has been extensively investigated in infectious diseases, particularly sepsis, its potential relevance to transplantation has only recently attracted attention. Several post-transplant complications, including infection, ischemia–reperfusion injury (IRI), microvascular dysfunction, and allograft rejection, share common pathological features such as neutrophil activation, endothelial injury, and excessive inflammatory amplification, suggesting a possible mechanistic role for HBP. This review summarizes the current understanding of HBP biology and evaluates its potential contribution to transplant-associated complications. We also discuss the feasibility of using HBP as an early biomarker for infection surveillance, inflammatory risk stratification, and graft injury monitoring. Furthermore, emerging therapeutic approaches targeting HBP or HBP-mediated vascular inflammation, including neutralizing antibodies, heparin derivatives, and albumin, are critically assessed. While experimental studies have provided preliminary evidence supporting HBP-targeted intervention, clinical validation in transplant populations remains insufficient. Future studies should define the temporal dynamics, cellular sources, and context-specific effects of HBP after transplantation. Collectively, available evidence indicates that HBP may serve as a potential biomarker and therapeutic target, but its clinical application requires further validation through mechanistic and prospective studies. Full article

Apple (Malus domestica Borkh.) production is increasingly threatened by fungal diseases under conditions of intensive horticulture and ongoing climate change. In southeastern Kazakhstan, symptoms associated with Alternaria spp. have become more frequent in commercial orchards; however, molecularly confirmed data on the pathogen associated with these symptoms remain limited. This study aimed to identify, using multigene molecular phylogenetic analysis, an Alternaria isolate obtained from infected apple leaves and fruits, to confirm its pathogenicity experimentally, and to compare the susceptibility of apple cultivars to this pathogen. For molecular identification, nucleotide sequences of four genetic markers—the ITS region of rDNA, SSU, tef1-α, and RPB2—were obtained by PCR and sequencing. The sequences were compared with reference data from the GenBank database using BLASTn, and phylogenetic relationships were inferred using the maximum likelihood method based on a concatenated dataset of the four loci. The isolate KZ17 clustered within the A. alternata clade, with the broader node uniting this group with A. gossypina and A. longipes receiving a bootstrap value of 78%. A total of 20 fungal isolates were obtained from 112 symptomatic apple leaf and fruit samples. Among them, one representative isolate, KZ17, was selected for multilocus molecular identification and pathogenicity testing. The pathogenicity of isolate KZ17 was confirmed in inoculation experiments on apple microshoots under controlled conditions. Artificial inoculation of detached leaves and ripe fruits of 14 apple cultivars revealed significant cultivar-dependent differences in susceptibility. Lesion diameters ranged from 12.3 ± 0.20 to 19.2 ± 0.35 mm on detached leaves and from 15.0 ± 1.2 to 30.0 ± 2.4 mm on ripe fruits. The least susceptible cultivars were ‘Granny Smith’, ‘Zaman’, and ‘Maksat’, whereas ‘Voskhod’, ‘Saltanat’, and ‘Kamila’ showed the greatest susceptibility. These differences were statistically significant (p < 0.001). This study provides the first multigene-based confirmation of the association of A. alternata with apple leaf and fruit lesions in southeastern Kazakhstan and demonstrates cultivar-dependent differences in susceptibility to this pathogen. These findings contribute to improved pathogen diagnostics, germplasm screening for resistance, and the development of plant protection strategies for commercial apple orchards. Full article

Chronic obstructive pulmonary disease (COPD) represents a major global health issue, characterized by persistent airflow limitation, chronic inflammation, and progressive tissue remodeling. Its clinical and molecular heterogeneity, combined with the lack of resolutive therapies, underscores the urgent need for advanced experimental tools to improve understanding and therapeutic development. Traditional 2D cell culture systems, though historically useful, fail to replicate the complexity of the human lung. In this review, we analyze the remarkable relevance of advanced 3D models for studying COPD pathophysiology, including epithelial injury and regeneration, extracellular matrix remodeling, and interactions with environmental triggers such as cigarette smoke and airborne pollutants. Three-dimensional in vitro models, such as ALI cultures, lung organoids, and lung-on-a-chip platforms, PCLS, and lung ECM-derived hydrogels offer more physiologically relevant environments to investigate epithelial dysfunction, immune responses, and host-pathogen interactions. We discuss the contribution of viral and bacterial infections to COPD exacerbations, and explore how 3D models have become essential tools for modeling these events. We also highlight recent advances in personalized medicine that use patient-derived organoids and ALI cultures for drug screening and biomarker discovery. Furthermore, we examine the therapeutic potential of probiotics and extracellular vesicle-associated microRNAs to modulate inflammation and epithelial repair. Collectively, these innovative systems represent powerful platforms to promote precision medicine in COPD. Full article

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, remains a major neglected tropical disease, with millions of people living with the infection worldwide. Current treatments are effective in the acute stage of the disease, but are poorly tolerated and show reduced efficacy in chronic infections, highlighting an urgent need for novel therapeutic strategies. A key bottleneck in early-stage drug discovery is target identification, which is traditionally dependent on costly and low-throughput experimental methods. Computational approaches offer a cost-effective and fast alternative to traditional methods. Methods: In this study, we present an integrated in silico pipeline that combines ligand-based and structure-based computational approaches to prioritize potential molecular targets for bioactive compounds against T. cruzi. The ligand-based component performed similarity searches across curated bioactivity databases containing known ligand–protein associations, and the most similar candidates were then further evaluated using a structure-based approach through pairwise structural alignment against the T. cruzi proteome from AlphaFold. Results: The pipeline was validated using eight compounds with known targets, successfully recovering the correct target in six cases. Additionally, two compounds with anti-T. cruzi activity but unknown mechanisms of action were analyzed to hypothesize their potential targets. Conclusions: Overall, the pipeline demonstrated moderate success, with limitations arising from challenges in handling novel chemotypes and poorly annotated targets. Nevertheless, its modular nature allows for an easy adaptation to other neglected tropical diseases, providing a flexible and cost-effective framework for early-stage target prioritization. Full article

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways were analyzed using miRWalk, Cytoscape/ClueGO, and cytoHubba. Pregnancy was associated with DE miRNAs (29 upregulated and 131 downregulated) targeting 2733 validated genes. Enriched pathways (FDR < 0.05) included adaptive immune response, Hippo Signaling, Cellular Senescence, HSV-1 infection, and two cancer-related pathways. Pregnancy-enriched targets within each pathway overlapped with the HIV–host interactome by 37–88%. Network analysis identified 47 hub genes interacting with 18 HIV-1 proteins, with Tat and gp120 being most connected viral and HLA-A being the most connected host protein. These findings indicate that pregnancy-driven systemic miRNAs target the HIV–host interactome and specifically identify pregnancy-enriched central hub genes involved in cell cycle control, viral immune evasion and replication to be further investigated for their predictive value in HIV acquisition and pathogenesis in longitudinal cohorts and experimental settings. Full article

Bovine Mycoplasma bovis pneumonia (MBP) is an important component of bovine respiratory disease, and its management is complicated by persistent infection and antimicrobial stewardship concerns. Houttuynia cordata Thunb. has reported anti-inflammatory and immunomodulatory activities, but its potential host-directed mechanisms in MBP remain unclear. This in silico study used network pharmacology and molecular docking to identify candidate compounds, common drug–disease targets, enriched biological functions, and predicted ligand–target interactions. A total of 145 putative targets of H. cordata and 474 MBP-associated disease targets were obtained from TCMSP, GeneCards, OMIM, and CTD, yielding 43 common drug–disease targets. Dual-confidence STRING analysis, cytoHubba ranking, and MCODE module analysis prioritized TNF, IL6, IL1B, PTGS2, PPARG, IFNG, CASP3, and MMP9 as candidate core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated convergence on cytokine-mediated signaling, inflammatory response, immune regulation, oxidative stress, IL-17 signaling, and TNF signaling. Molecular docking suggested favorable predicted interactions for quercitrin–PTGS2, quercetin–TNF, quercetin–IL6, and quercitrin–CASP3. These computational findings suggest that H. cordata may be associated with host inflammatory and immune-response modulation in MBP, mainly through flavonoid-related interactions with inflammation- and apoptosis-related targets. Further bovine-specific experimental validation is required before biological activity or practical application can be inferred. Full article

Cowpea mild mottle virus (CPMMV) is a carlavirus that is transmitted by whiteflies and can also be spread through seeds in cowpea, soybean, and common bean. Seed transmission of CPMMV has been described in various countries; however, it was only recently reported in Brazil as a seed-transmitted virus in soybean. CPMMV has spread widely in bean-growing areas in recent years. Most Brazilian farmers use harvested grains as seed for reseeding, increasing the risk of seedborne infection. In this study, we examine seed transmission of CPMMV in two bean cultivars using RT-PCR in combination with nucleic acid hybridization. The plants evaluated were obtained from seeds harvested in commercial and experimental fields and from seeds collected in transmission experiments using either mechanical or whitefly inoculation. The observed seed transmission was estimated between 10 to 45% for ‘BRS FC 401 RMD’ and 13 to 22% for ‘Pérola’. In addition, evidence of secondary transmission (23.3%) by Bemisia tabaci MEAM1 was observed. These results suggest that CPMMV could be spread in bean fields by sowing infected seeds and that germinated plants could serve as an inoculum for whitefly transmission. This is the first report of seed transmission of CPMMV in common bean in Brazil. Full article

Gammaherpesviruses (GHVs) represent a global clinical burden as the causative agents of Kaposi’s sarcoma and mononucleosis, among other diseases. Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are the most studied human GHVs, and murine gammaherpesvirus 68 (MHV-68) is a recognized experimental model. GHVs are defined by their modulation of the host cell to establish lifelong latent infections and increase host dysregulation during periodic reactivation. Due to their ubiquitous changes in host cells, systems-level techniques are well-suited to study GHV infections at all stages of the central dogma: genomics, transcriptomics, and proteomics. Furthermore, metabolomics can reveal the final metabolic changes across numerous host cellular pathways. This review assesses the current knowledge on GHV infections gained through omics techniques. We also identify gaps and propose future directions, including the development of new therapeutic strategies. Early omics techniques have characterized large swaths of infection for EBV, KSHV, and MHV-68, revealing conserved genes, homologous transcripts, and proteins. Modern omics techniques have enabled higher-resolution studies, yielding insights into heterogeneity in viral-host gene, transcript, and protein modulation strategies across geographical populations, viral subtypes, inter- and intra-patient infections, and latent and lytic states. The metabolome during GHV infections remains the least understood, but current studies have identified essential modulations of nucleotide, amino acid, and lipid synthesis by EBV, KSHV, and MHV-68. Importantly, the application of integrative omics methods to GHV infections remains a promising direction of study as the increased resolution of modern techniques meets the need for greater understanding of differences in each GHV infection. Full article

The protective effect of Compound terminalia chebula extract (HL) against colonic injury induced by Porcine epidemic diarrhea virus (PEDV) infection in neonatal piglets remains unclear. This study aimed to evaluate the mitigating effects of HL on PEDV-induced colonic injury and elucidate the underlying mechanisms. Eighteen 7-day-old Duroc × Landrace × Large White piglets (2.58 ± 0.05 kg) were randomly assigned to three groups (n = 6/group): CON (blank control), PEDV (infected), and HL + PEDV (HL-supplemented + infected). The 11-day trial included 3 days of acclimatization (days 0–3) and an 8-day experimental period (days 4–11). HL (10 mg/kg BW) was orally administered daily to the HL + PEDV group. On day 8, PEDV and HL + PEDV groups were challenged with 3 mL PEDV (3 × 10⁶ TCID₅₀/mL), while CON received Dulbecco’s Modified Eagle Medium (DMEM). All piglets were euthanized on day 11 for colonic tissue collection. Results indicated that PEDV infection induced colonic injury, manifested by a significant increase in crypt depth and disruption of intestinal homeostasis. This was evidenced by impaired barrier integrity (upregulation of matrix metalloproteinase-7 gene [MMP7] and matrix metalloproteinase 13 gene [MMP13], mucus disorganization (elevation of mucin 5AC gene [MUC5AC]), oxidative stress (reduced catalase [CAT] activity and increased malondialdehyde [MDA] levels in serum and colon), and inflammation (upregulation of regenerative islet-derived protein 3γ gene [REG3G], S100 calcium-binding protein A8/A9 gene [S100A8/A9], and interleukin-1β gene [IL-1β]). Additionally, PEDV impaired colonic ion transport by downregulating calcium channel genes (Transient Receptor Potential Cation Channel Subfamily V Member 6 gene [TRPV6], Transient Receptor Potential Cation Channel Subfamily M Member 6 gene [TRPM6]). Notably, HL supplementation effectively reversed these adverse effects. HL restored colonic morphology, increased CAT activity, reduced MDA accumulation, and suppressed inflammatory gene expression. Furthermore, HL modulated the expression of genes involved in water and ion transport upregulating Aquaporin 7 gene (AQP7), Chloride Channel Accessory 4 gene (CLCA4), Sodium-Hydrogen Exchanger 3 gene (NHE3), Transient Receptor Potential Vanilloid 6 (TRPV6), and Transient Receptor Potential Melastatin 6 gene (TRPM6) and significantly inhibited PEDV replication, as indicated by the downregulation of the transcription levels of PEDV membranegene (M), nucleocapsid gene (N), and spike gene (S). Taken together, HL alleviates PEDV-triggered colonic tissue damage in suckling piglets via improving colonic antioxidant capacity, mitigating inflammatory response, partially regulating intestinal barrier and ion/water transport-related genes, and downregulating the transcription of PEDV structural genes at molecular and histological levels. Full article

Haemonchus contortus is one of the most prevalent gastrointestinal nematodes in all ecosystems in Mexico, where sheep are raised on pasture, and it poses a significant threat. This study aimed to examine the surgical isolation of a Mexican H. contortus strain, its morphological and molecular characterization, and the maintenance of this strain for future research. Biological behavior and some phenotypic aspects of the adults were considered. Fecal samples were obtained from naturally infected sheep, larval cultures were performed, and a nematode-free lamb was infected. Once the infection was established, the donor sheep were euthanized, the adults recovered, and H. contortus females and males were selected. A surgical transfer from H. contortus adult to the abomasum of a receptor lamb was performed, and the beginning of the egg excretion was confirmed three days post-transfer; fecal cultures from the receptor lamb were conducted to verify the purity of the strain. After three lambs were infected with 3000, 5000, and 10,000 L3, the pre-patent period, prolificacy, and measurements of the adult stages of the strain were studied. The molecular characteristics were evaluated by qPCR; primers were designed based on NCBI genomic DNA sequences of H. contortus to amplify a 176 bp fragment, and the amplicon was sequenced for taxonomic identification. The results of this study describe biological characteristics and some phenotypic aspects of the adults, as well as eggs and infective larvae, and molecular characteristics of the isolated strain, and establish a successful methodology for isolating and maintaining a pure strain of H. contortus (FESC-strain); it can be used as a reference in experimental infections or anthelmintic resistance studies. Full article