Search Results (23,660)

Chinese rice-field eel rhabdovirus (CrERV) is a serious epidemic pathogen of Chinese rice-field eel and causes severe economic losses to aquaculture. However, there are no commercial drugs presently available to control CrERV infection. Eugenol is a bioactive compound extracted from clove plants and exhibits potential antiviral activity. In the study, the antiviral activity of eugenol against CrERV was investigated in Chinese rice-field eel (Monopterus albus). Eugenol reached the highest inhibition rate of 96.6% at 40 mg/L in Chinese rice-field eel kidney cells (CrEK). Notably, eugenol exhibits antiviral activity by directly targeting CrERV and additionally confers prophylactic effects against infection via its action on CrEK cells. The results of exploring the viral invasion cycle demonstrated that eugenol primarily exerted its antiviral effect during the middle stage and late stage (12 h and 24 h) of viral infection. In addition, eugenol inhibited CrERV-induced apoptosis of CrEK cells, maintained mitochondrial membrane potential levels, maintained physiological cellular morphology and structure, and protected cells from loss of cellular morphology, formation of apoptotic vesicles, and cell fragmentation. For the in vivo study, eugenol increased the survival rate of CrERV-infected rice-field eel by 56% and 48%, in prevention experiments and treatment experiments, respectively. Concurrently, eugenol significantly reduced viral loads and induced the upregulation of anti-inflammatory and antioxidant genes, indicating its potential for immunoregulation. In summary, eugenol holds potential for both preventing and treating CrERV infections in the aquaculture context. Full article

Background: Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health concern, and there is a continued need for new antitrypanosomal agents. Thiosemicarbazone (TSC) derivatives have emerged as a promising class of compounds with potential antiparasitic activity. Objectives: This study aimed to report the synthesis, characterization, and biological profiling of a novel series of thiosemicarbazone derivatives as antitrypanosomal agents against Trypanosoma cruzi. Methods: Fourteen new compounds and six previously described analogues were prepared and characterized by ¹H/¹³C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). As a preliminary in vitro screen, activity was assessed by direct parasite counting in epimastigote and bloodstream trypomastigote forms, as tractable models of replicative and infective stages sharing core metabolic targets with intracellular amastigotes. Epimastigote potency was quantified as half-maximal effective concentrations (EC₅₀) derived from dose–response curves, whereas trypomastigote response was evaluated as percent viability after treatment at a fixed concentration of 20 µM. Mechanistic profiling included inhibition assays against the cysteine protease cruzipain (CZP) and selected redox defense enzymes, complemented by in silico similarity clustering and binding-pose affinity scoring. Results: A nitro-methoxy-substituted TSC showed potent CZP inhibition but limited trypomastigote efficacy, whereas brominated analogues displayed dual-stage activity independent of CZP inhibition. Tanimoto similarity analysis identified distinct structure–activity clusters, linking nitro-methoxy substitution to epimastigote selectivity and brominated scaffolds to broader antiparasitic profiles, with hydrophobicity and steric complementarity as key determinants. Enzymatic assays revealed no significant inhibition of cytosolic tryparedoxin peroxidase (cTXNPx) or glutathione peroxidase type I (TcGPx-I), suggesting redox disruption is not a primary mode of action. In vitro and in silico analyses showed low or no non-specific cytotoxicity under the tested conditions, supporting further optimization of these derivatives as antitrypanosomal preliminary hits. Key hits included derivative 3e (epimastigote EC₅₀ = 0.36 ± 0.02 µM) and brominated analogues 2c and 2e (epimastigote EC₅₀ = 3.92 ± 0.13 and 4.36 ± 0.10 µM, respectively), while docking supported favorable binding-pose affinity (e.g., ΔG_S-pose = −20.78 ± 2.47 kcal/mol for 3e). Conclusions: These results support further optimization of the identified thiosemicarbazone derivatives as preliminary antitrypanosomal hits and provide insight into structure–activity relationships and potential mechanisms of action. Full article

Background/Objectives: The study aimed to characterize perioperative complications and their relationship with nutritional risk in gastrointestinal cancer patients undergoing surgical treatment. Methods: An observational, prospective, and multicenter study was carried out in 469 patients with gastrointestinal malignancies undergoing elective major abdominal surgical procedures in public hospitals throughout Spain. Complications developed during hospitalization and at 30 days after surgery were recorded, and the patients’ nutritional status was evaluated using the MUST screening tool. Results: Colorectal and gastric cancer were the most common tumors. Complications during hospitalization occurred in 146 patients (rate 31.1%). Infections accounted for 68.5% of complications, in particular surgical site infections (SSIs), followed by paralytic ileus (40.4%). At 30 days, the complication rate was 9%, with infections as the most common events. In patients with severe nutritional risk at discharge (MUST score ≥ 2), the percentage of patients with complications was 24.7% as compared to 9.2% in patients without complications (p < 0.0001). Conclusions: Clinicians should be aware of the high frequency of SSIs and that complications are higher among patients with severe nutritional risk. These findings emphasize the need for routine nutritional screening and targeted perioperative support in cancer patients undergoing gastrointestinal cancer surgery. Full article

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the “prehabilitation” concept. We aimed to investigate the prognostic value of cachexia in the “Western” patient population with resectable GC and to evaluate its utility as an indicator for a home-based prehabilitation program. Methods: This cohort study included 147 patients who underwent surgical treatment for GC from 2019 to 2023. A multivariable analysis was conducted to study the impact of cachexia on postoperative outcomes in 122 patients with resectable GC. The prehabilitation group included 25 patients with cachexia who underwent a 2-week-long multimodal prehabilitation program prior to surgery. The functional results, as well as the 30-day incidence of postoperative complications and 90-day mortality, were evaluated. Results: There were 76 (51.7%) patients with cachexia. Multivariate analysis revealed that cachexia was a significant predictor of all postoperative complications (OR = 5.48, 95% CI 1.85–18.39, p = 0.001), severe postoperative complications (OR = 15.87, 95% CI 3.05–131.81, p < 0.001) and surgical site infection (SSI) (OR = 8.03, 95% CI 1.89–49.09, p = 0.038). Patients in the prehabilitation group had a lower incidence of SSI than in the control group (8.3% vs. 23.5%, p = 0.049). Conclusions: Preoperative cachexia is a potentially modifiable predictor of complications after gastric cancer surgery, and its identification may help define high-risk patients for proactive multimodal prehabilitation. Full article

Background and Clinical Significance: Malaria remains a significant public health issue in Latin America, where Plasmodium vivax predominates but P. falciparum continues to circulate. Mixed-species infections are uncommon and can pose diagnostic challenges, particularly when parasite densities differ markedly, increasing the risk of underdetecting P. falciparum with conventional methods. Case report: We report a 9-year-old boy from an endemic area with a six-day febrile syndrome. Thick smear and peripheral blood film microscopy, complemented by rapid diagnostic tests for pan-Plasmodium and HRP2 antigens, confirmed a mixed infection with P. vivax (5500 parasites/µL) and P. falciparum (562 parasites/µL). The patient was hemodynamically stable, without severe malaria criteria, and laboratory values were within normal limits. Following confirmation of normal glucose-6-phosphate dehydrogenase activity, treatment with artemether–lumefantrine was initiated, followed by primaquine for hypnozoite eradication. Clinical evolution was favorable, with progressive defervescence, treatment tolerance, and documented parasite clearance. Conclusions: This case illustrates the risk of underestimating P. falciparum in mixed infections with disparate parasitemias and highlights the value of integrated diagnostic approaches in resource-limited endemic settings. It also underscores surveillance limitations that can misclassify mixed infections, potentially affecting epidemiological estimates and treatment strategies. Timely recognition and comprehensive diagnostic evaluation are essential to ensure appropriate antimalarial therapy, prevent complications, and inform public health interventions in regions where both species coexist. Full article

Grapevine downy mildew is a major disease in vineyards all around the world, caused by the oomycete Plasmopara viticola (Berk. & M. A. Curtis) Berl. & De Toni. Normally, its control depends almost exclusively on chemical and copper-based fungicides, especially in high-incidence areas with high relative humidity and mild temperatures. However, the European Union is determined to reduce the application of these phytochemicals by at least 50% by 2030, forcing winegrowers to seek alternative low-input strategies for proper sanitary maintenance. Basic substances (BSs), described in European Regulation (EC) 1107/2009, stand out as promising alternatives, but their molecular mechanism of action remains mostly unknown. In this context, this study analyzed the genetic effect in grapevine plants of several commercial products composed of BSs (chitosan, soy lecithin, Equisetum arvense and Salix cortex). All products exhibited promising results, triggering the induction of similar defence mechanisms, which included pathogenesis-related proteins (PRs), involved in direct pathogen repression; stilbenes, capable of producing antimicrobial compounds such as resveratrol and pterostilbene; several hormones, including oxylipins, ethylene, salicylic acid and terpenes, mediating immune signalling; and genes related to structural features of the plant, such as lignin, callose, cellulose and cuticular wax, constituting a first physiological barrier against P. viticola. Disease severity reduction differed among treatments, with Salix cortex showing the highest efficacy (58%), followed by BABA (38%) and LESOY (35%), while LECI and CHIT had minor effects (<9%). Gene expression analyses revealed that Salix cortex modulated the highest percentage of genes (41%), followed by natural infection without treatment (32%), LESOY (27%), BABA (26%), LECI (23%) and CHIT (23%). In terms of defence mechanisms, Salix cortex promoted the most pathways, LESOY induced eight, BABA and LECI seven and CHIT five. Overall, these results indicate that BSs can modulate several defence pathways in grapevine, supporting their potential use as sustainable alternatives for controlling downy mildew. Full article

As an important zoonotic parasite, Capillaria hepatica poses a threat to human health that cannot be ignored due to its association with high mortality and serious damage to the liver, although there are relatively few human infections. The infection rate of Capillaria hepatica in rodents is very high, which poses a great threat to the health of rodents, and Rattus norvegicus has been found to be the main group carrying Capillaria hepatica. Capillaria hepatica’s unique biological characteristics, including its morphological features and complex life history, determine the specificity of its infection and pathogenicity. In terms of epidemiology, Capillaria hepatica has a worldwide distribution, a wide variety of hosts (mainly rodents), and various transmission routes, all of which increase the difficulty of its prevention and control. Children are more likely to be infected by it, and there is little gender difference among the infected population. Although there are a variety of diagnostic methods for hepatic capillariasis, all of them have certain limitations. In addition, due to its non-specific clinical manifestations, early accurate diagnosis of hepatic capillariasis is still a challenge. This article reviews the biological characteristics and pathogenic mechanism of Capillaria hepatica, the epidemiology of human infection, the epidemiology of animal infection, and the diagnosis and treatment of hepatic capillariasis, so as to provide a useful reference for related research and clinical practice. Full article

Background: Kaposi sarcoma (KS) is a multifocal, angioproliferative neoplasm strongly associated with human herpesvirus-8 infection. Radiotherapy(RT) is a well established treatment due to the intrinsic radiosensitivity of KS lesions. High-dose-rate contact brachytherapy allows precise dose delivery with optimal sparing of surrounding tissues; however, its application in KS remains poorly documented. Methods: We conducted a retrospective analysis of 10 patients with histologically confirmed KS treated with c-HDR-BRT between June 2010 and June 2023. A total of 40 cutaneous lesions were treated using Leipzig applicators with hypofractionated regimens: 10 Gy in 1 fraction, 20 Gy in 2 fractions, or 30 Gy in 3 fractions. Treatment parameters were individualized based on lesion size and location. Local control (LC), overall survival (OS), disease-specific survival (DSS), and toxicity (graded by the RTOG criteria) were evaluated. Follow-up assessments were performed every four months during the first year and annually thereafter. Results: At a median follow-up of 10.3 years, the 2-year LC, OS, and DSS rates were 100%. Complete response was achieved in 62.5% of lesions, with a partial response observed in 37.5%. Grade 1–2 acute skin toxicities were recorded in 55% of treated lesions, while grade 3 toxicity occurred in a single case (2.5%) and was managed conservatively. The hypofractionated schedule significantly improved patient compliance, particularly in those with multiple lesions requiring sequential irradiation. Conclusions: Our long-term institutional experience supports c-HDR-BRT as a feasible and well tolerated local treatment option for the management of KS, providing favorable long-term local outcomes. These results support the inclusion of c-HDR-BRT in the multidisciplinary treatment of KS, warranting further prospective evaluation. Full article

Despite a thorough understanding of the structure of human papillomavirus (HPV) and its genotypic variations (high-risk and low-risk variants), the mechanisms underlying HPV-induced cervical cancer (CC) pathogenesis and the molecular signatures of drug resistance remain to be fully understood. Accumulating evidence has shown the involvement of kinase targets in the induction of drug resistance in high-risk (HR) HPV-CC. Molecularly, the genome of high-risk HPV is reported to control the expression of host kinases. In particular, Aurora kinases A, B, and C (ARKA, ARKB, and ARKC), phosphotidylinositol–trisphosphate kinase (PI3K)-Akt, and Glycogen synthase kinase3-α/β (GSK3 α/β) promote the transformation of infected cells, and also enhance the resistance of cells to various chemotherapeutic agents such as nelfinavir and cisplatin. However, the precise mechanisms through which HPV activates these kinases are yet to be fully elucidated. Furthermore, there is still ambiguity surrounding whether targeting HPV-induced kinases along with HPV-targeted therapies (such as phytopharmaceuticals and PROTAC/CRISPR-CAS-based systems) synergistically inhibit cervical tumor growth. Given the critical role of kinases in the pathogenesis and treatment of CC, a comprehensive review of current evidence is warranted. This review aims to provide key insights into the mechanisms of HPV-induced CC development, the involvement of kinases in drug resistance induction, and the rationale for combination therapies to improve clinical outcomes. Full article

Introduction: The health care burden of chronic hepatis B virus (CHB) infection can be reduced by appropriate workup, treatment, and monitoring. Methods: As a primary objective, we determined whether adequate initial hepatitis B virus (HBV) laboratory workup in CHB patients is associated with improved CHB complications risk. Secondary outcomes assessed included: mortality, hospitalization, emergency department, and liver specialist visits. We conducted a retrospective cohort study from 1 January 2012 to 31 December 2018. Participants were followed from 12 months post index event until outcome occurrence, death, loss of eligibility, or 31 March 2023. Health administrative data from Ontario, Canada was utilized. The study cohort included individuals with at least one positive result of either hepatitis B surface antigen, hepatitis B e antigen, or HBV DNA viral load documented during the study window. The exposure of interest was defined as adequate laboratory workup, defined as having subsequent quantitative HBV DNA, and alanine aminotransferase testing completed within 12 months of the index event. CHB-related complications were assessed using previously validated diagnostic codes. Modified Poisson regression modelling was used to estimate relative risks. Results: The study cohort consisted of 30,794 CHB patients, with a mean age 45.7 years. The majority were male (53.5%) and within the lowest two income quintiles (50.2%). In total, 68.0% underwent adequate workup. Individuals with adequate workup were more likely to be older, male, urban based, and of the highest racialized and newcomer populations quintile. The risk for CHB complications was 1.50 (95% CI 1.36–1.65) times greater among those with adequate workup. By multivariable analysis, adequate workup was associated with a lower risk of mortality (RR 0.78; 95% CI 0.69–0.87), all-cause hospitalizations (RR 0.77; 95% CI 0.74–0.80), all-cause (RR 0.77; 95% CI 0.75–0.78), and liver-related (RR 0.67; 95% CI 0.60–0.75) ED visits. Conclusions: Adequate CHB clinical workup is associated with improved patient outcomes. Our findings advocate for the comprehensive evaluation of CHB patients using key laboratory tests to optimize clinical management and improve long-term health outcomes. We identified gaps in the workup of young adults, females, and those residing in rural settings, which should be addressed to ensure equity of HBV care. Full article

Leaves of Cucumis callosus, traditionally employed in Ayurvedic medicine for the treatment of urinary disorders, were investigated in depth for their therapeutic potential against bacterially induced urinary tract infection (UTI) for the first time. The present work is the first to explore the antibacterial activity of C. callosus leaf fractions with an integrative in silico, in vitro, and in vivo approach. Through bioassay-guided fractionation, the chloroform fraction (F1) was identified as the most active, exhibiting potent activity against Uropathogenic Escherichia spp. species. Liquid chromatography–mass spectrometry (LC-MS) analysis of F1 revealed the presence of bioactive compounds, including stigmasterol, 1,2,3,4-tetrahydroisoquinoline, lactose, hydroxy(mesityl)acetic acid, and 2,4-di-tert-butylphenol. Molecular docking studies validated the strong binding affinities of these compounds for bacterial resistance enzymes, including AmpC β-lactamase and carbapenemases, thereby providing plausible mechanisms of antimicrobial action. In vivo studies carried out on female rats infected with Escherichia spp. species revealed a dose-dependent reduction in bacterial load, with a significant decrease in urinary tract inflammation upon F1 administration. Histopathological evaluation confirmed the protective effect, with reduced epithelial damage and inflammation in bladder tissues. These findings indicate significant antibacterial and tissue-protective effects of the C. callosus leaf fraction F1, supporting its ethnomedicinal use and establishing it as a promising phytotherapeutic agent for the treatment of urinary tract infections. Full article

Monogenean parasite infestation in fish leads to economic losses in aquaculture, representing a veterinary challenge and an environmental concern. The common administration procedures of anthelmintics to treat monogeneans in fish have low efficiency and diverse drawbacks. In this study, we produced a nanoparticle using chitosan and alginate, biodegradable and biocompatible polysaccharides, as an oral drug delivery material of albendazole anthelmintic for parasite-infected fingerlings of Nile tilapia. The molecular interaction between the biopolymers was optimized and characterized by titration calorimetry. Freeze-drying of nanoparticles resulted in a fine powder with a particle size in the order of 400 nm. The nanoparticles provided 98% encapsulation of albendazole and sustained delivery with predominantly Fickian diffusion. The palatability of the nanoparticle formulation facilitated the oral administration of albendazole. The treatment of 100% prevalence of monogeneans was effective with a six-day dosage providing a total of 915 mg/kg b.w. of drug, resulting in total parasite clearance after 10 days from the treatment beginning, evidenced by microscopy analysis, and no mortality occurred. Therefore, molecular interactions between biofriendly polyelectrolytes yielded albendazole-carrying nanoparticles for high-efficiency parasite treatment in fish farming. Full article

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

Anti-GQ1b antibody syndrome (AGABS) unifies triad-defined Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE), and the ophthalmoplegic variant of Guillain–Barré syndrome (GBS-O) under a post-infectious immune mechanism centered on IgG to disialosyl gangliosides. The spectrum also encompasses triad-minus phenotypes—acute ophthalmoparesis without ataxia, acute vestibular syndrome, optic involvement, and acute sensory-ataxic neuropathy. A molecular-mimicry model with complement-mediated nodal/paranodal dysfunction explains severe early deficits despite bland limb nerve conduction studies (NCSs), the cranial/proprioceptive predilection, and generally favorable treatment responsiveness to immunotherapy. In practice, a serology-first strategy, complemented by targeted electrophysiology—blink and H-reflex testing, and, where feasible, paired SEP–ABR showing a literature-supported dissociation (normal ABR with impaired median-nerve cortical SEPs), which, in our series, was documented in one illustrative BBE case—and by structured neuro-otologic examination, mitigates the “normal-NCS trap” and enables timely treatment. Intravenous immunoglobulin (IVIg) is first-line; plasma exchange (PLEX) is an alternative in severe or IVIg-ineligible cases; and intravenous methylprednisolone (IVMP) may be added selectively for central/optic-weighted phenotypes without routine oral taper. We consolidate actionable diagnostic and therapeutic steps and examine them in an institutional series of 16 consecutive seropositive patients (2015–2025): all were anti-GQ1b-positive with frequent GT1a co-reactivity; most reported an antecedent infection—typically upper respiratory, less often gastrointestinal—within the two weeks before onset; limb NCSs were often nondiagnostic whereas reflex/evoked-potential studies were informative; two required intubation in addition to IVIg; outcomes were generally favorable with early immunotherapy. The practical message: order anti-GQ1b at first contact, pair targeted electrophysiology with neuro-otology, and treat early to exploit reversible nodal/paranodal dysfunction. Full article

Gastrointestinal nematode (GIN) infections are the most prevalent parasitic diseases in grazing sheep worldwide, causing significant productivity losses, high mortality and, as a result, economic losses and emerging animal welfare concerns. Conventional control strategies, primarily relying on anthelmintic treatments, face limitations due to rising drug resistance and environmental concerns, underscoring the need for sustainable alternatives. Selective breeding for host genetic resistance has emerged as a promising strategy, while recent advances in transcriptomics and integrative omics research are providing deeper insights into the immune pathways and molecular and genetic mechanisms that underpin host–parasite interactions. This review summarizes current evidence on transcriptomic signatures associated with resistance and susceptibility to H. contortus and T. circumcincta GIN infections, highlighting candidate genes, functional genetic markers, key immune pathways, and regulatory networks. Furthermore, we discuss how other omics approaches, including genomics, proteomics, metabolomics, microbiome, and multi-omics integrations, provide perspectives that enhance the understanding of the complexity of the GIN resistance trait. Transcriptomic studies, particularly using RNA-Sequencing technology, have revealed differential gene expression, functional genetic variants, such as SNPs and INDELs, in expressed regions and splice junctions, and regulatory long non-coding RNAs that distinguish resistance from susceptible sheep, highlighting pathways related to Th2 immunity, antigen presentation, tissue repair, and stress signaling. Genomic analyses have identified SNPs, QTL, and candidate genes linked to immune regulation and parasite resistance. Proteomic and metabolomic profiling further elucidates breed- and tissue-specific alterations in protein abundance and metabolic pathways, while microbiome studies demonstrate distinct microbial signatures in resistant sheep, suggesting a role in modulating host immunity. In conclusion, emerging multi-omics approaches and their integration strategies provide a comprehensive framework for understanding the complex host–parasite interactions that govern GIN resistance, offering potential candidate biomarkers for genomic selection and breeding programs aimed at developing sustainable, parasite-resistant sheep populations. Full article