Search Results (1,385)

Background/Objectives: Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a naturally occurring flavonol present in strawberries, apples, grapes, onions, cucumbers, and other plant sources. It has attracted considerable interest because of its antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, cardioprotective, and senolytic properties. This review comprehensively evaluated the pharmacological activities, mechanisms of action, translational challenges, and global research trends associated with fisetin. Methods: A comprehensive literature review was conducted to synthesise evidence on the traditional uses, pharmacological properties, molecular mechanisms, and therapeutic applications of fisetin. Bibliometric analysis of publications from 2005 to 2024 was performed using the Web of Science Core Collection. A total of 664 records were retrieved using the keywords “fisetin” and “3,3′,4′,7-tetrahydroxyflavone”. Following refinement using Bibliometrix (version 5.0) and the Biblioshiny interface in RStudio, 658 publications were included in the final analysis. Results: Fisetin exhibited diverse biological activities through modulation of oxidative stress, inflammation, apoptosis, autophagy, mitochondrial function, and cellular senescence. Experimental evidence supports its therapeutic potential against cancer, cardiovascular, neurodegenerative, metabolic, and infectious diseases. However, poor aqueous solubility, low oral bioavailability, rapid metabolism, and limited clinical evidence continue to impede its clinical translation. Nanotechnology-based delivery systems, computational modelling, and multi-omics approaches show promise for improving its pharmacokinetic profile and therapeutic efficacy. Bibliometric findings revealed substantial growth in fisetin research, with China leading scientific output and Africa contributing comparatively few publications. Conclusions: Fisetin is a promising multifunctional phytochemical with broad therapeutic potential. Future research should emphasise advanced formulations, rigorous clinical trials, and international collaboration to accelerate its translation into evidence-based clinical practice. Full article

The COVID-19 pandemic underscored the need to better characterize immune and molecular responses following SARS-CoV-2 infection and vaccination. Beyond antibody and cellular immunity, COVID-19 involves oxidative stress and DNA damage, affecting repair mechanisms and metabolic adaptation linked to immune resilience. Here, we present a multidimensional analysis of 20 individuals who recovered from mild COVID-19, integrating clinical features with humoral and cellular immune responses, T cell and myeloid phenotypes, oxidative stress, DNA damage, and metabolomic and lipidomic profiles. Although most individual parameters fell within physiological ranges, network modeling revealed structured associations spanning multiple biological domains. A central finding was a coherent cluster organized around vaccine dose number, linking anti-Spike antibody titers, oxidative stress, bioenergetic signatures, and granulocyte activation. Higher vaccination was associated with stronger humoral responses, lower oxidative stress, and a more balanced myeloid–metabolic profile, suggesting a potential protective role extending beyond antibody induction. Additional associations linked symptom patterns to T cell differentiation states, anti-nucleocapsid responses to systemic inflammation, and anaerobic signatures to DNA damage markers, revealing interconnections between immunometabolism, clinical expression, and genomic stress. Despite the small sample size, these findings offer a preliminary systems-level perspective on mild COVID-19 recovery and illustrate the value of integrative exploratory frameworks in infectious disease research, laying the groundwork for validation in larger longitudinal cohorts. Full article

Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood donors globally. In addition, sexual contact with individuals chronically infected with hepatitis B virus (HBV) is recognized as one of the primary routes of HBV transmission. Blood donors may acquire HBV infection through sexual contact with chronically infected partners, particularly with occult hepatitis B infections (OBIs), which are characterized by intermittent and extremely low viral loads. Therefore, the prevalence of OBIs among syphilis-positive blood donations and the corresponding risks to blood safety require further investigation. This study aimed to investigate the prevalence of OBIs among syphilis-positive blood donors and assess the surrogate value of TP testing for evaluating OBI-related risks to blood supply. After routine screening using serological assays and nucleic acid testing (NAT), blood donation samples with positive anti-TP enzyme-linked immunosorbent assay (ELISA) results were collected and further confirmed by the Treponema Pallidum Particle Agglutination Assay (TPPA). For blood donations confirmed positive for syphilis, further tests were performed to characterize whether the donations had HBV co-infection, including electrochemiluminescence immunoassay (ECLI) for the detection of hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), anti-hepatitis B e antibody (anti-HBe), and anti-hepatitis B core antibody (anti-HBc). Additionally, quantitative real-time polymerase chain reaction (qPCR) was used for HBV DNA quantification, and nested PCRs for the S and basal core promoter/precore (BCP/PC) region were conducted in combination with high-volume nucleic acid extraction. Subsequently, molecular characterization of HBV DNA in these co-infected samples was carried out by DNA sequencing to analyze the viral genetic features. Of 252 anti-TP ELISA+ donations screened from 64,871 blood samples, 138 (138/250, 55.2%) donations were confirmed syphilis-positive but NAT−, among which 78 (78/138, 56.5%) were anti-HBc-positive, and 88 (88/138, 63.7%) had anti-HBs. Notably, seven donations (7/138, 5.1%) were diagnosed as OBI co-infections, and available sequence analysis revealed that three cases were genotype B and one case was genotype C. In addition, several mutations in the S region of the HBV genome were identified, including Q101R, K122R, Q129H, T131N, M133T, G145R, and Y161F mutations. Furthermore, nucleotide mutations such as T1719G, A1752T, G1896A, and A1762T/G1764A in the BCP/PC regions were also detected in these OBI donations. These mutations may contribute to the extremely low HBV viral loads and/or failure in HBsAg detection, collectively leading to OBIs. These data indicate that syphilis screening of blood donors has potential to serve as an additional safeguard measure for excluding donations co-infected with OBIs. The high prevalence of undetected OBIs in syphilis-positive blood donors further supports that syphilis screening has the potential to serve as a surrogate marker for HBV-related risks in the blood supply. Full article

Background and Clinical Significance: Cryptogenic multifocal ulcerating stenosing enteritis (CMUSE) is a rare idiopathic disorder of the small bowel which remains diagnostically challenging because it can closely mimic Crohn’s disease, celiac disease, and non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy; Case Presentation: We report a 44-year-old man with Down syndrome, Hirschsprung’s disease, celiac disease, and multiple prior abdominal operations who developed recurrent small-bowel strictures of uncertain cause. Initial management involved endoscopic assessment and jejunal dilatation, but this became neither technically feasible nor durable as the disease progressed. He therefore underwent exploratory laparotomy with small-bowel resection to relieve obstruction and to obtain adequate tissue for diagnosis. On balance, the presence of multifocal ulceration, recurrent mucosa-predominant strictures, and non-transmural jejunitis supported a diagnosis of CMUSE; Conclusions: This case highlights the rarity and diagnostic difficulty of CMUSE, which may closely resemble Crohn’s disease in patients with recurrent small-bowel strictures and obstructive symptoms. Early and ongoing MDT coordination (surgery, gastroenterology, radiology, dietetics, and infectious diseases) supports anatomy definition, complication control, and coherent long-term management focused on function and quality of life. Full article

Background/Objectives: Natural products derived from plants, animals, and microorganisms have long been used as nutritional supplements and are increasingly recognized for their potential role in preventing and managing human diseases. This narrative review aims to summarize current evidence on the therapeutic relevance of natural products as dietary supplements across major disease categories and to highlight their mechanisms of action, clinical efficacy, and safety considerations. Methods: A narrative literature review was conducted using peer-reviewed articles, systematic reviews, and clinical studies focusing on natural products used as nutritional supplements in disease management. Relevant data were analyzed thematically, with emphasis on bioactive compounds, mechanisms of action, and evidence from preclinical and clinical research. Results: Natural products, particularly plant-derived polyphenols, flavonoids, terpenoids, omega-3 fatty acids, and probiotic-derived metabolites, exhibit diverse biological activities, including antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial effects. Evidence suggests potential benefits in cardiovascular diseases, metabolic disorders such as diabetes and obesity, neurodegenerative conditions, certain cancers, gastrointestinal disorders, and infectious diseases. However, clinical efficacy varies depending on compound type, dosage, and formulation. Key limitations include low bioavailability, variability in composition, and insufficient large-scale clinical trials. Safety concerns such as herb–drug interactions and lack of standardization remain significant challenges. Conclusions: Natural products as nutritional supplements represent a promising adjunct strategy in the prevention and management of various human diseases. While preclinical and early clinical evidence is encouraging, stronger clinical validation, improved standardization, and clearer regulatory frameworks are required to fully integrate these agents into evidence-based medical practice. Full article

This review examines recent quantum chemical methodologies applied to investigating antibiotic structure and mechanisms of action. The discussion is organised into three sections: (1) enzymatic hydrolysis of the β-lactam ring, (2) interactions of antibiotics with ribosomal subunits and enzyme active sites, and (3) complex formation with metal ions. Each section evaluates how quantum chemical approaches, particularly density functional theory (DFT) and hybrid QM/MM techniques, model molecular processes relevant to antibiotic function, including transition states, electron density analyses, and metal coordination effects on antibacterial activity. Selected studies demonstrate the utility of these methodologies in interpreting experimental data and predicting physicochemical and biological properties of novel compounds. Distinct from previous literature, this review provides a comparative and up-to-date synthesis of quantum chemical methods related to enzymatic mechanisms and metal-based antibiotic systems, emphasising experimental validation strategies and practical guidelines for method selection in antibiotic research. It also identifies areas where quantum chemical modelling can integrate with experimental pharmacology and structural biology to support the rational design of next-generation antimicrobial agents. The review concludes by advocating an interdisciplinary framework combining quantum chemistry, biochemistry, and pharmacology to address antibiotic resistance. The review focuses primarily on antibiotics targeting bacterial cell wall and protein synthesis, particularly β-lactam antibiotics, ribosome-targeting agents, and their interactions with metal ions. Computational methods discussed are mainly limited to DFT, ab initio, and hybrid QM/MM approaches. It does not cover membrane-disrupting antibiotics, antiviral or antifungal agents, machine learning-based prediction methods, or purely molecular dynamics approaches outside a quantum mechanical context. Full article

Messenger RNA (mRNA) vaccines represent a transformative platform in vaccinology, with applications extending beyond SARS-CoV-2 to other infectious diseases and cancer immunotherapy. However, patients with solid tumors receiving active anticancer treatment were largely underrepresented in pivotal vaccination trials, limiting understanding of vaccine-induced immunity in this population. In this prospective exploratory study, we assessed humoral and cellular immune responses after two doses of SARS-CoV-2 mRNA vaccines in 39 patients with solid tumors undergoing active treatment. Blood samples were collected before vaccination and approximately two months after the second vaccine dose, prior to the next treatment cycle. Anti-spike IgG, neutralizing antibodies, receptor-binding domain (RBD) levels, interleukin-6 (IL-6), hematological parameters, immune cell subsets, T-cell differentiation, and early apoptosis in αβ and γδ T-cell subsets were analyzed. Vaccination induced a robust humoral response, with high post-vaccination anti-spike IgG levels (median 988.69 BAU/mL), 97.44% seropositivity, 96.88% true seroconversion among baseline IgG−/NAb− patients, and strong neutralizing antibody activity (median 85.73%). Hematological parameters and IL-6 levels remained broadly stable, suggesting no detectable increase in systemic inflammation during the study period. Cellular analyses identified a reduction in peripheral CD19+ B-cell frequencies and decreased early apoptosis, particularly in CD8+ T cells and CD3+CD56+ NKT-like cells. Although changes in T-cell frequencies and differentiation profiles were also observed, these findings were attenuated after exclusion of participants with possible prior SARS-CoV-2 exposure and should be interpreted as exploratory. Overall, these results show that patients with solid tumors receiving active treatment can mount robust humoral responses to SARS-CoV-2 mRNA vaccination and suggest measurable post-vaccination changes in lymphocyte dynamics, including reduced early T-cell apoptosis. Full article

Infectious wounds are plagued by persistent infection, uncontrolled inflammation, and delayed repair, while traditional therapies suffer from the poor solubility of natural drugs, low bioavailability, and bacterial drug resistance. To address these issues, this study developed a photo-responsive chitosan composite hydrogel (BBR-AS@Ce6@Matrix) cross-linked by chitosan (CS) and oxidized sodium alginate (OSA), co-loaded with Berberine–Asiaticoside cocrystal (BBR-AS) and chlorin e6-loaded chitosan nanoparticles (Ce6@CS NPs). The BBR-AS co-crystal was prepared by solvent method and verified to significantly improve the solubility and dissolution of asiaticoside. The Ce6@CS NPs were fabricated via non-solvent-assisted counterion complexation, showing high encapsulation efficiency, uniform particle size, and efficient singlet oxygen generation under irradiation. The hydrogel exhibited a three-dimensional porous network, favorable rheology, high water content, pH-dependent swelling and erosion behaviors, and significantly promoted BBR/AS release in vitro. In vitro experiments demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus, good cytocompatibility, and enhanced migration of L929 and Hacat cells. In a rat infectious wound model, the hydrogel combined with light irradiation markedly accelerated wound closure, promoted collagen deposition and angiogenesis, upregulated VEGF/CD31, and downregulated TNF-α/IL-6. In conclusion, BBR-AS@Ce6@Matrix integrates co-crystal solubilization, nanoparticle-facilitated release, and photodynamic synergy to achieve antibacterial, anti-inflammatory, pro-angiogenic and tissue remodeling effects, providing a promising multifunctional platform for infectious wound repair. Full article

Background/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive–compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS/PANDAS. Methods: A structured narrative search of PubMed/MEDLINE, Embase, the Cochrane Library, Google Scholar/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein–Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium/calmodulin-dependent protein kinase II signaling, blood–brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia/CSTC circuit dysfunction, and gut–oral–brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials. Full article

Background/Objectives: Vesicular Stomatitis Virus (VSV)-vectored vaccines represent a versatile platform for the development of vaccines against infectious diseases. Replication-competent recombinant VSV vectors in which the native glycoprotein (G) is replaced with a heterologous antigen (rVSVΔG) are widely used and have demonstrated clinical success. In addition to antigen-specific responses, these vaccines induce humoral immunity directed against vector components, which primarily reflects vector exposure and contributes to the overall characterization of vaccine-induced immunity. Standardized assays for quantifying such vector-directed responses are therefore of increasing importance. Methods: We developed and qualified a quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of human IgG antibodies against VSV-Nucleoprotein (N). Assay development included optimization of antigen coating, blocking conditions, and detection reagents. A 10-point standard curve was established using pooled human serum, and assay performance was evaluated by assessing dynamic range, sensitivity, cut point, dilutional linearity, precision, robustness, and sample stability. Results: The optimized assay utilized a coating concentration of 2 μg/mL VSV-N antigen (100 ng/well) and 1% casein as the blocking buffer. The assay demonstrated a dynamic range of 0.33–41.66 arbitrary units per milliliter (AU/mL) with excellent curve fit (R² > 0.996). The cut point was established at an OD₄₅₀ of 0.286. Precision across intra-assay, inter-assay, and inter-operator evaluations met predefined acceptance criteria (≤25% CV). The assay was robust across different plate washers and readers and maintained performance following up to three freeze–thaw cycles. Conclusions: This study describes a robust and reproducible ELISA for quantifying anti-VSV-N IgG responses. The assay provides a fit-for-purpose tool for assessing vector-directed humoral immunity and supports standardized immunogenicity evaluations across VSV-vectored vaccine studies. Full article

The vascular endothelial glycocalyx (EGX) is a gel-like, negatively charged mesh of membrane-bound proteoglycans, glycosaminoglycans, glycoproteins and adsorbed plasma proteins that covers the luminal surface of the endothelium and orchestrates vascular homeostasis through regulation of permeability, leukocyte trafficking, mechanotransduction and anti-thrombotic signalling. Progressive thinning, heterogeneous remodelling and accelerated shedding of the EGX are now recognised as hallmarks of vascular ageing and early drivers of age-related cardiovascular disease. Here, we synthesise current evidence linking EGX integrity to biological ageing, with emphasis on age-dependent remodelling of heparan-sulfate proteoglycans, endothelial progenitor-cell dysfunction, and the heightened susceptibility of the aged EGX to oxidative, inflammatory and infectious insults. We discuss signalling pathways driving EGX shedding—including the IQGAP1/PAR1-2/PI3K/Akt axis—and clinical correlates such as vulnerable coronary plaque in older patients with coronary artery disease and microvascular endotheliopathy in severe COVID-19. Finally, we review emerging anti-ageing strategies targeting the EGX, including direct oral anticoagulants, glycocalyx-mimetic and nitric-oxide-releasing biomaterials, bioinspired antithrombogenic surfaces and microbiome-based modulation, and consider their translational potential for extending cardiovascular healthspan. Full article

Natural products like the isoprenylated flavonoid Kuwanon G (KWG), isolated primarily from Morus alba, offer promising pleiotropic effects against multifactorial diseases, overcoming the limitations of conventional single-target synthetic drugs. This study aims to systematically review the pharmacological activities of KWG and evaluate its underlying molecular mechanisms. A comprehensive literature review was integrated with network pharmacology, protein–protein interaction (PPI) profiling, and KEGG/GO pathway enrichment analyses to identify shared targets across different pathologies. Experimental data demonstrate that KWG exhibits antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, anti-obesity, and anticancer properties. Bioinformatics analyses revealed that KWG exerts these effects by modulating core targets (e.g., TNF, IL-6, SRC, RELA) and key signaling pathways, including NF-κB, PI3K/AKT/mTOR, and Toll-like receptors, which govern inflammation, oxidative stress, and metabolic regulation. In conclusion, KWG is a potent, multi-target compound with significant therapeutic potential for managing chronic and infectious diseases. However, future structure–activity relationship studies and clinical trials are required to address its pharmacokinetic limitations, such as low bioavailability, to facilitate its clinical translation. Full article

Mpox is a zoonotic infectious disease caused by the species Orthopoxvirus monkeypox (MPV), which is becoming an increasing public health concern. While human-to-human transmission of the virus is well established, the role of domestic animals in MPV infection remains poorly understood. Investigating how the virus is transmitted among humans, dogs, and cats can improve our understanding of the disease’s pathogenesis and help develop strategies to limit its dissemination during future outbreaks. In this study samples were collected from four domestic animals (three dogs and one cat) in May 2023. These animals lived in a household where a human mpox case had been confirmed by PCR in March 2023, approximately 2 months before animal sampling. A plaque reduction neutralization test (PRNT) using vaccinia virus was performed to detect anti-orthopoxvirus (OPV) neutralizing antibodies (nAbs). Our data demonstrated that anti-OPV nAbs were present in samples obtained from three dogs and one cat with neutralization titers ranging from 1:5 to 1:20. These results indicate that the domestic animals were exposed to OPVs after contact with an individual with confirmed mpox, suggesting possible human-to-animal transmission within a household. Nevertheless, due to the cross-reactive immune response among OPVs, and the endemic circulation of vaccinia virus in Brazil, it is not possible to determine the specific viral species based solely on PRNT results. Therefore, these serological findings should be interpreted as evidence of OPV’s exposure rather than confirmed MPV infection. Full article

Chronic epididymitis and orchitis represent significant yet frequently under-recognized contributors to male infertility, particularly among men of reproductive age. These conditions arise from persistent inflammatory or immunological processes affecting the epididymis and testis, leading to impaired spermatogenesis, altered sperm maturation and possible obstruction of the male reproductive tract. Infectious aetiologies, especially those linked to sexually transmitted pathogens and uropathogens, remain predominant; however, non-infectious mechanisms, including autoimmune activation, post-vasectomy changes and idiopathic inflammation, also play critical roles. The persistent inflammatory milieu induces cytokine release, oxidative stress and structural tissue remodelling, ultimately compromising the functional and immune-privileged microenvironment necessary for optimal sperm production and transport. Diagnostic evaluation requires a multimodal approach incorporating clinical examination, microbiological testing, semen analysis and scrotal ultrasonography, with advanced imaging and molecular assays reserved for complex or equivocal cases. Management is individualized and may involve antimicrobial therapy, anti-inflammatory treatment, immunomodulation or microsurgical intervention in cases of ductal obstruction. Assisted reproductive technologies provide additional options when natural conception is not feasible. Despite increased recognition of their impact, chronic epididymitis and orchitis remain insufficiently studied, with gaps in standardized definitions, biomarker validation and long-term outcome data. This review provides a focused synthesis and phenotype-driven clinical framework for chronic epididymitis and orchitis through a fertility-preservation lens, bridging urological and andrological perspectives and integrating evidence on subclinical inflammation, contemporary diagnostic biomarkers and a staged therapeutic pathway. Full article

Vaccination is one of the most important measures for infectious disease control. Recently, media-generated concern about vaccine-associated adverse effects has produced a rise in both human and animal “anti-vaccination” movements. This study aimed to understand factors involved in dog owner vaccination decisions and explore whether there has been an increase in titer testing. An online survey targeting dog owners received a total of 2585 responses, which showed 79% of respondents had their dogs vaccinated in the last 12 months. A few owners had never vaccinated their dogs, and 13% of owners used titer testing prior to booster vaccinations. The factors with the strongest positive predictors for vaccination were requirements by third party services (e.g., kennels) and, for a negative response, lack of time. For respondents that had not vaccinated, the factors with the strongest predictive powers to determine if they titer test were education/working in the veterinary industry for a positive response and not having heard of negative side effects after vaccinating for a negative response. Overall, no evidence was found that a rise in anti-vaccination attitudes was pervasive in dog owners; however, the study shows that the veterinary profession has work to do to ensure herd immunity is maintained within dog populations. Full article