Infections caused by multidrug-resistant (MDR) pathogens, both gram-negative and gram-positive organisms, have transformed into a silent global pandemic. These pathogens, especially ESKAPE pathogens, exhibit wide resistance patterns to several clinically significant antibiotics. This has decreased the effectiveness of already available antibiotics, increasing mortality, morbidity, economic burden and prolonged hospital stay. As the discovery of new antibiotics is an extensive and time-consuming process, an urgent need for innovative and practical preventive strategies arises. This review emphasizes the need, advancement and practicality of immunoinformatic tools and in silico vaccine designing and development against MDR pathogens. Research shows that MDR pathogens demonstrate a variety of resistance pathways, including target alteration, enzymatic degradation and efflux pumps, to tolerate therapeutically available antibiotics. The notable benefits of in silico vaccine designing include rapid identification of conserved antigens, even in variable pathogens, epitope prediction with antigenic potential, population coverage across various populations, less time, cost and improved precision in creating a multi-epitope vaccine against these MDR pathogens. Moreover, molecular docking, molecular dynamic simulations, immune simulations and expression analysis assist in predicting the molecular behavior of the designed vaccine. The increasing prevalence of MDR infections emphasizes the critical need for prevention measures rather than conventional therapy options. Use of immunoinformatics and in silico approaches presents a potent, efficient and cost-effective method to design and create multi-epitope vaccines against MDR pathogens. However, limitations such as false positives, reproducibility concerns with varying software and potential bias due to the use of curated databases in reverse vaccinology may pose a challenge. Incorporation of in silico vaccine development in future research can play a pivotal role in combating antimicrobial resistance and improving health outcomes globally.
Autoimmune blistering diseases (AIBDs) are characterized by autoantibody-mediated epithelial damage affecting the skin and mucous membranes. Among them, pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) frequently involve the gingiva, most commonly presenting as desquamative gingivitis (DG). This chronic and painful gingival involvement may compromise oral hygiene and favor secondary inflammatory changes. Consequently, growing interest has focused on the periodontal status of patients with AIBDs and on associated oral microbiological findings. A narrative review was conducted using PubMed and Scopus to identify primary studies evaluating periodontal status in patients with AIBDs. Periodontal conditions were mainly assessed using conventional clinical parameters, including probing depth and clinical attachment loss, along with additional periodontal and oral hygiene indices. Ten studies met the inclusion criteria. Most of them reported significantly worse periodontal status in AIBD compared to controls or DG-unaffected sites. In MMP, disease activity, duration, and DG involvement were associated with poorer periodontal parameters. Notably, adjusting for oral hygiene, as performed in only one study, rendered differences in PD and CAL non-significant, suggesting a potential confounding effect. However, the available evidence remains insufficient to support an independent link with clinically defined periodontitis. Only one study applied the 2017 World Workshop periodontitis classification, with similar conclusions. Microbiological data, limited to three MMP studies with heterogeneous methodologies, frequently detect periodontal pathogens associated with inflammatory tissue damage. Patients with AIBD tend to present worse periodontal status, likely due to pain limited oral hygiene and dysbiotic biofilms. These pathogens may amplify inflammation and perpetuate tissue destruction. Nevertheless, microbial profiles appear dynamic and influenced by disease activity and treatment. Recognizing this association is essential for early diagnosis and interdisciplinary management.
Anthropogenic changes associated with urbanization can bring wildlife species into closer contact with livestock and humans, thereby increasing the risk of pathogen spillover. Recently, urban-adapted (synanthropic) hedgehog species, including Hemiechinus auritus (long-eared) and Paraechinus hypomelas (Brandt's), have been suggested as potential sources of zoonotic pathogens. The increasing number of tick-infested hedgehogs in urban areas and confirmed cases of human rickettsial infections in south-eastern Iran motivated this investigation to identify rickettsial species in ticks collected from hedgehogs to help assess their potential role in spreading tick-borne diseases. So, this study aimed to screen tick pools collected from synanthropic hedgehogs in southeastern Iran for Rickettsia spp. DNA and to perform presumptive species identification using partial gltA sequencing. Among 60 hedgehogs live-trapped and sampled in two cities (Zabol, Kerman), forty of the long-eared and five of Brandt's were tick-infested. We collected 68 ticks from 18 hedgehogs trapped in Zabol and 70 ticks from 27 hedgehogs trapped in Kerman. All collected ticks were adults and were morphologically identified as Rhipicephalus sanguineus s.l. or Rhipicephalus turanicus. Ticks collected from each individual hedgehog were pooled together and each pool consisted of ticks belonging to a single species collected from one individual hedgehog. Tick-pool DNA extracts were screened for Rickettsia spp. using a genus-level SYBR Green real-time PCR targeting the gltA gene. Screening-positive pools were confirmed by a TaqMan real-time PCR targeting the 16 S rRNA gene, and samples with Ct values < 31 were subjected to conventional PCR for amplification of an 834-bp gltA fragment. Species-level identification was performed based on partial gltA sequencing, BLAST analysis, and phylogenetic comparison. A total of 5 of 45 tick pools (11.1%) were positive for Rickettsia spp. DNA, including four Rhipicephalus sanguineus s.l. pools and one Rhipicephalus turanicus pool. Based on partial gltA sequencing, two positive pools were assigned as presumptive Rickettsia sibirica, two as presumptive Rickettsia rhipicephali, and one Rh. turanicus pool showed mixed detection of both species.The presence of Rickettsia spp. DNA in ticks collected from hedgehogs underscores the need for understanding of the potential involvement of synanthropic animals as reservoirs for tick-borne and other pathogens in different parts of Iran and surrounding areas.
Bangladesh's fisheries sector, central to national nutrition, food security, and rural livelihoods, is increasingly threatened by the convergence of zoonotic pathogens, antimicrobial resistance (AMR), and environmental degradation. Using a One Health framework, this review synthesizes evidence from 87 peer-reviewed articles, institutional reports, and regional studies to demonstrate how interactions among aquatic ecosystems, farmed and wild fish populations, and human communities drive the emergence and transmission of disease. Zoonotic parasites including trematodes, cestodes, nematodes, and protozoa persist through contaminated water, inadequate market hygiene, and exposure to domestic and wild animals. Aquaculture systems are further burdened by zoonotic bacteria (e.g., Vibrio spp., Aeromonas spp., and Mycobacterium spp.) and microsporidian parasites (e.g., Enterocytozoon spp.), together posing significant occupational and foodborne risks. Emerging fungal pathogens, notably Saprolegnia spp. and Aphanomyces invadans, intensify disease burdens under poor farm management and environmentally stressed conditions. Critical contamination pathways, industrial and agricultural runoff, cross-contamination in fish markets, unregulated chemical use, and weak biosecurity link aquatic pollution with human and animal health outcomes. The introduction of non-native fish species (e.g., tilapia, pangas, carp) and the expanding ornamental fish trade further amplify pathogen risks, facilitating the silent spread of bacterial, parasitic, and fungal agents with zoonotic potential. Climate change, biodiversity loss, and socioeconomic vulnerabilities exacerbate these pressures by destabilizing aquatic ecosystems, reducing resilience, and accelerating AMR dissemination across aquatic, human, and livestock interfaces. By integrating insights from parasitology, microbiology, epidemiology, and environmental science, this review underscores the urgent need for coordinated surveillance, diagnostic capacity, regulatory enforcement, and risk communication strategies. Embedding One Health and climate-smart approaches into fisheries governance is essential to mitigate zoonotic hazards, safeguard food safety, and ensure the long-term sustainability of Bangladesh's aquaculture sector under accelerating environmental change.
Immunization with antigens presented multivalently on virus-like particles elicits potent immune responses. The SpyTag/SpyCatcher system, which allows spontaneous covalent bond formation between two proteins, provides a simple route to functionalize virus-like particles for multivalent presentation. Termed SpyVLPs, these reactive nanoparticles allow modular plug-and-display of different antigens. SpyCatcher003-mi3 is a resilient SpyVLP that can be produced at high yield, allows efficient coupling, and can be applied to vaccines against a diverse range of pathogens, as well as against cancer and allergy. Here, we describe the procedure for the expression and purification of SpyCatcher003-mi3. We outline considerations related to antigen design, multivalent display, nanoparticle validation, and immunogen preparation that are critical for effective implementation of SpyCatcher003-mi3 and other SpyVLPs. The methods discussed are applicable beyond vaccines, extending to therapeutic targeting, diagnostics, and catalysis.
Invasive fungal infections are life-threatening complications in immunocompromised and critically ill patients. Invasive candidiasis may arise from endogenous fungal reservoirs, particularly under conditions of intestinal barrier disruption. Although conventional antifungal agents remain the therapeutic foundation, their clinical use is increasingly challenged by the emergence of resistant fungal pathogens, such as Candida auris. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microorganisms. Beyond their well-established applications in the food industry, bacteriocins have attracted increasing attention in recent years for their antifungal properties. In this review, we provide an overview of bacteriocins with reported antifungal activity and summarize their underlying mechanisms. In addition, we discuss the potential protective effects of bacteriocins on the microbial, mechanical, chemical, and immune barriers of the intestine. Finally, we evaluate the potential clinical applications of these bacteriocins, along with future challenges and research directions related to invasive fungal infections.
To develop and evaluate a standardized emergency department (ED) adapted framework based on Centers for Disease Control (CDC) surveillance definitions and modified SOFA assessment for reproducible infection and sepsis classification in patients with suspected infection on the ED. As part of the prospective cohort study BIOSEP, adults presenting to the ED with suspected infection and a Modified Early Warning Score ≥2 were consecutively enrolled between 2022 and 2026 at 4 Dutch hospitals. All enrolled patients in this study were retrospectively adjudicated through post hoc review of their electronic health records. Each case was independently assessed by 2 blinded physicians for plausibility of infection, infection diagnosis, causative pathogen, and sepsis occurrence. Disagreements were resolved by a third blinded reviewer. Interobserver agreement was quantified using Cohen's kappa and Gwet's agreement coefficients (gAC). In total, 1062 ED patients were included with 1145 infection episodes. Interobserver agreement for infection diagnosis was 88.9%, and agreement statistics were classified as very good with Cohen's κ of 0.87 (95% CI 0.85-0.89) and a gAC1 of 0.89 (0.87-0.91). Agreement for causative pathogens was 90.1% (κ 0.89 [0.87-0.92]; gAC1 0.97 [0.95-0.98]), and for sepsis occurrence 93.4% (κ 0.80 [0.76-0.85]; gAC1 0.92 [0.90-0.94]). Agreement for plausibility of infection was also high (87.9%; weighted κ 0.87 [0.85-0.89]; gAC2 0.92 [0.90-0.93]). Our ED-adapted adjudication framework based on CDC surveillance definitions yields high interobserver agreement for infection and sepsis classification across a heterogeneous ED population, supporting its use in large-scale observational research.
Genomic research on high-consequence Risk Group 4 (RG4) viruses is significantly hindered by the stringent biosafety level 4 (BSL-4) containment requirements, because virus inactivation prior to removal from containment often compromises nucleic acid integrity. As a focused solution to retain nucleic acid integrity as well as safety compliance, we developed and validated a comprehensive suite of optimized workflows compatible with BSL-4 containment and next-generation sequencing applications. We systematically assessed inactivation, homogenization, and RNA extraction methods to establish robust bulk RNA sequencing workflows for diverse sample types. We also adapted state-of-the-art single-cell RNA sequencing (scRNA-seq) by integrating inactivation steps without compromising data quality. To demonstrate feasibility, we conducted scRNA-seq analysis on cells exposed to Lassa virus. Additionally, we optimized viral genome enrichment strategies for high-depth sequencing of multiple RG4 viruses. These validated workflows enable safe, reproducible, and high-resolution genomic analyses of RG4 pathogens, significantly expanding the experimental toolkit for BSL-4 research.
This study presents a preliminary investigation into the antimicrobial, antibiofilm, and antiproliferative potential of Eremothecium coryli, an endophytic fungus isolated from the seeds of Basella alba L. The biological activities were evaluated using a crude extract-based screening study, employing the lyophilized cell-free supernatant (LCFS) of the fungal culture. Antibacterial and antibiofilm activities were assessed against selected multidrug-resistant bacterial pathogens, while antiproliferative activity was evaluated against breast cancer cell lines and a normal breast epithelial cell line. The LCFS demonstrated measurable antibacterial activity and significant biofilm-inhibition in a concentration-dependent manner. In cytotoxicity assays, selective growth inhibition of breast cancer cell lines was observed when compared with normal cells. Chemical profiling using Liquid Chromatography-Mass Spectrometry and Gas Chromatography-Mass Spectrometry enabled putative metabolite identification, revealing the presence of compounds previously reported to exhibit antimicrobial and anticancer activities. However, these identifications are tentative and based on spectral library matching. Overall, this preliminary investigation highlights the biological potential of E. coryli-derived metabolites. Further purification and validation are necessary to confirm compound identities, elucidate mechanisms of action, and assess in vivo relevance.
Dermacentor andersoni, the Rocky Mountain wood tick, is an important vector for pathogens impacting human and animal health, including bovine anaplasmosis, Colorado tick fever, and Rocky Mountain spotted fever. A better understanding of the biology of this tick is needed for developing disease prevention and vector control strategies. A reference genome was assembled for D. andersoni using high-fidelity (HiFi) long-read PacBio sequences and Hi-C contact mapping, yielding a contiguous assembly in which most contigs matched one of 11 chromosomes. Genome annotation by the NCBI eukaryotic genome annotation pipeline revealed high gene content completeness, yielding a genome completeness score of 94.0% using the Arachnida ortholog dataset. Following genome sequencing, we identified specific genes involved in blood feeding across a range of tissue types and life stages for D. andersoni. To accomplish this, RNA-seq analysis was used to investigate differential gene expression across most organs in adult, nymphal, and larval D. andersoni before and after feeding. Based on this analysis, we identified several gene groups that are involved in blood feeding. Furthermore, we establish sex- and developmental-stage-specific transcriptional profiles. Collectively, this study advances knowledge of D. andersoni biology and enables the development of strategies to limit the spread of diseases transmitted by this tick.
Personalized vaccines provide the advantage of patient-specific antigen selection to optimize immune responses, a strategy extensively explored in oncology through neoantigen-targeted peptide, mRNA, and dendritic cell platforms. Peptide vaccines provide simplicity and stability though often elicit limited cytotoxic T-cell responses. What is more, mRNA vaccines lead to rapid, multiplexed neoantigen delivery, endogenous antigen processing and eventually improved immunogenic coverage. Dendritic cell-based vaccines have the potency to prime potent T-cells although this technology requires labor-intensive manufacturing and extensive production timelines. Integration with immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses further enhances efficacy, suggesting that rational combinations may be more effective than single modalities. Recent advances in sequencing, computational epitope prediction, and bioinformatics pipelines have facilitated neoantigen prioritization and DC vaccine design, enabling more rapid and precise personalization. Hybrid vaccination strategies, such as ex-vivo mRNA-electroporated dendritic cells and in-vivo DC-targeted platforms, bridge the gap between manufacturing feasibility and potent immune activation. Emerging technologies, including AI-driven neoepitope prediction, receptor-targeted antigen delivery, biomaterial-based modulation, and distributed mRNA manufacturing, seem to be promising approaches to accelerate personalized vaccine development in future. From another point of view, lessons learned from the COVID-19 pandemic accelerated the development, large-scale deployment, and validation of mRNA vaccine platforms for infectious diseases. Host HLA diversity, prior immune history, and viral evolution create heterogeneity in immune responses, highlighting opportunities for semi-personalized or adaptive strategies. In this review, we provide a landscape of personalized vaccines, with a focus on DC-based platforms, and explore translational lessons for viral pathogens. A conceptual framework linking cancer immunotherapy and infectious disease preparedness is proposed, emphasizing hybrid personalization approaches, rapid manufacturing, and AI-enabled epitope selection. This perspective highlights how convergence of immunology, computational biology, and advanced vaccine technologies could expand the scope of personalized vaccination, from oncology to future epidemic and pandemic scenarios as well as the current challenges.
Antimicrobial resistance is an important clinical challenge in patients with hematologic malignancies, who are highly susceptible to severe infections due to prolonged neutropenia, disrupted mucosal barriers, intensive chemotherapy, and hematopoietic stem-cell transplantation. This systematic review synthesizes available international evidence on pathogen distribution, antimicrobial resistance patterns, and clinical outcomes in hemato-oncology settings. This systematic review searched PubMed, Scopus, and Google Scholar for English-language studies published from January 2014 to 15 November 2025. Studies reporting microbiologically confirmed infections in patients with hematologic malignancies, with extractable antimicrobial susceptibility or resistance data, were included. Due to substantial clinical, microbiological, methodological, and epidemiological heterogeneity, findings were synthesized qualitatively. Seventeen studies met the inclusion criteria. Gram-negative bacteria predominated across most settings, although pathogen distribution varied by region, age group, infection type, and denominator unit. Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant Gram-negative bacteria, multidrug-resistant Gram-negative organisms, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus were reported across included studies. Where extractable study-level data were available, ESBL-related estimates ranged from 40% to 78%, while carbapenem-resistance estimates varied widely by organism group and study setting, from low carbapenem resistance among Enterobacteriaceae in one pediatric oncology cohort to 38.2% carbapenem-resistant Gram-negative bacteria in an Indian adult febrile neutropenia cohort. Mortality outcomes were heterogeneously reported and were not pooled. In comparative studies, resistant or multidrug-resistant bloodstream infections were associated with worse outcomes, including increased mortality and ICU admission, although causality cannot be inferred from the predominantly observational evidence. Antimicrobial resistance is a clinically important problem in patients with hematologic malignancies, particularly due to resistant Gram-negative pathogens. The findings support strengthened hemato-oncology-specific surveillance, local antibiogram-guided empirical therapy, antimicrobial stewardship, and standardized reporting of resistance phenotypes and clinical outcomes.
The major histocompatibility complex (MHC) is an essential part of the adaptive immune systems that present antigenic peptides at the cell surface for recognition and activation of circulating T lymphocytes, which is vital for our body to recognize and respond to foreign pathogens, including viruses, bacteria, and cancerous cells. Human leukocyte antigen (HLA) genes encode proteins located on the surface of most cells in the body, and studies have shown that protein glycosylation plays a significant role in the folding of human leukocyte antigen (HLA) proteins, loading of peptides, and forming of HLA-peptide complex. In the meantime, some of those peptides presented by the MHC system are also glycosylated. Thus, glycosylation has a huge impact on cellular uptake, proteolytic processing, presentation by MHC, and subsequent T-cell priming. However, glycosylation characterization of the whole MHC system has often been neglected during conventional immunopeptidomics analysis due to the lower abundance of glycosylated peptides and increased complexity of the mass spectrum. To tackle this problem, we utilized hydrophilic interaction chromatography to enrich glycopeptides from both peptides bound to HLA and digest of HLA proteins that obtained from immunoprecipitation of MHC complex from cell lysate. Enriched glycopeptides are analyzed by mass spectrometry that enables the characterization of glycosylation of MHC by database search.
Toilet flushing is a daily activity that can generate bioaerosols in indoor spaces. This exposure pathway is increasingly important in the context of emerging pathogens, changing water systems, and high indoor occupancy. Stronger empirical evidence is needed to support risk-based decision-making to protect human health. This systematic literature review examined factors influencing aerosol and bioaerosol concentrations generated through toilet flushing, with a focus on toilet design, target microorganisms, and air sampling methods relevant to exposure and risk assessment. Twenty-two studies met the inclusion criteria. Across studies, higher seeding concentrations and larger flush volumes were generally associated with higher aerosol and bioaerosol concentrations, indicating that source loading and flushing energy are the primary drivers of exposure-relevant aerosol generation. In contrast, evidence for independent effects of flushing pressure, lid position, and ventilation was limited and inconsistent. Probability density functions of log₁₀-transformed aerosol and bioaerosol concentrations were developed for seeded and unseeded conditions to strengthen quantitative microbial risk assessment (QMRA) inputs where direct air sampling is not feasible. Overall, the findings highlight the central role of toilet design and source microbial loading in shaping bioaerosol exposure, with important implications for risk assessment, building design, and infection control in an era of water security pressures and emerging infectious diseases.
Cyberlindnera fabianii is a rare opportunistic yeast increasingly recognized as a cause of invasive infections. We report two fatal cases of C. fabianii fungemia in elderly patients with multiple comorbidities. Microbiological analysis revealed low minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins, but variable susceptibility to fluconazole. One patient received antifungal therapy with limited response; in the second case, the pathogen was identified postmortem.
Gancao Qinlian Granules (GQG) are a granulated formulation of the classical prescription Gancao Xiexin Tang, originally documented by Zhang Zhongjing in the Treatise on Febrile and Miscellaneous Diseases (Shang Han Za Bing Lun, c. 220 CE). This formula comprises six medicinal components: Glycyrrhiza glabra L. (Gancao), the radix of Scutellaria baicalensis Georgi (Huangqin), Ziziphus jujuba Mill. (Dazao), the rhizomes of Zingiber officinale Roscoe (Ganjiang), the dried tuber of Pinellia ternata (Thunb.) Breit (Banxia) , and the rhizoma of Coptis chinensis Franch (Huanglian). GQG has been extensively employed in traditional and contemporary clinical practice for the treatment of ulcerative colitis (UC). Nevertheless, its candidate bioactive constituents and underlying mechanisms of action remain incompletely elucidated. To comprehensively characterize the chemical composition of GQG and elucidate its therapeutic mechanisms against UC through an integrated strategy combining network pharmacology prediction, serum/colon/fecal multi-omics profiling (metabolomics and microbiome), and experimental validation. Initially, GQG was analyzed by UHPLC-Q-Exactive Orbitrap MS under negative/positive ion modes, with compound identification via mzCloud, HMDB, and literature matching. C57BL/6 mice (n=8/group) were induced with UC using 3% dextran sulfate sodium (DSS) for 15 days. UC-related targets from GeneCard, PharmGkb, TTD, and OMIM were integrated to construct compound-target-pathway networks (Cytoscape 3.10.1). Secondly, GQG (9g/kg/d, 12g/kg/d, 15g/kg/d) or mesalazine (300 mg/kg) was administered orally for 10 days. Disease severity was assessed daily via Disease Activity Index (DAI: weight loss, stool consistency, bleeding). Post-euthanasia, colon length was measured, and histopathology (H&E, Alcian Blue-Periodic Acid Schiff staining) analyzed mucosal damage and goblet cell depletion. Colon IL-1β levels were quantified by immunohistochemistry (IHC). Then, serum, fecal, and colonic tissue samples underwent UHPLC-Q-Exactive Orbitrap MS-based untargeted metabolomics. Differentially expressed metabolites (DEMs) were identified (VIP >1, p<0.05) and pathways enriched via KEGG. Fecal 16S rDNA sequencing (Illumina NovaSeq) analyzed microbial α/β-diversity and differential taxa (LEfSe, LDA score >3). Subsequently, Integrated component analysis, network pharmacology, and metabolomics data to obtain the mechanism by which GQG improves UC, and verify the related target proteins through IHC and Western blot. Finally, obtain the candidate bioactive constituents in GQG through molecular docking, and verify the efficacy of these bioactive constituents with their targets on a cellular model. Chemical profiling revealed 121 constituents in GQG, with 53 flavonoids (43.8%) including core bioactive markers (e.g., licoflavone B, licuroside). In DSS-induced ulcerative colitis mice, GQG (12g/kg/d) exerted potent therapeutic effects: reducing disease activity index, attenuating colon shortening, restoring goblet cells, and suppressing colon IL-1β. Mechanistically, GQG remodeled gut microbiota composition and function, increasing beneficial taxa (Muribaculaceae, Lactobacillus). This microbiota restructuring directly drove metabolic reprogramming. Suppression of pro-inflammatory metabolism: purine degradation (hypoxanthine), tryptophan-derived uremic toxins (kynurenine), pathogenic bile acids (deoxycholic acid). Integrative analysis of the microbiota-metabolite axis reveals that GQG extract can regulate the NF-κB/NLRP3 inflammasome cascade through p-NF-κB p65 expression, NLRP3 assembly (NLRP3, Caspase-1), and ASC speck formation. Combined with molecular docking, six key components in GQG exhibit high affinity for critical targets. In vitro cellular experiments demonstrate that these core candidate bioactive components effectively inhibit key targets within the target pathway. GQG ameliorates UC by modulating gut microbiota structure and function, restoring microbial co-metabolism (e.g., SCFA synthesis, bile acid homeostasis), and subsequently inhibiting the NF-κB/NLRP3 inflammasome axis. This integrated approach substantiates the ethnopharmacological application of GQG for UC.
Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently defined malformation of cortical development that is an important cause of childhood-onset drug-resistant epilepsy. Clinically, the epilepsies associated with MOGHE are heterogeneous, with infantile epileptic spasms syndrome (IESS) being the most common manifestation. Histopathologically, MOGHE demonstrates subtle cortical dyslamination, heterotopic neurons in the white matter, hypomyelination, and a distinctive increase in the density and clustering of oligodendroglial cells, features that distinguish it from other malformations of cortical development such as focal cortical dysplasia (FCD). Recent genetic analyses of epileptogenic tissue resected from individuals with MOGHE have identified somatic mosaic loss-of-function variants in SLC35A2. This gene encodes the Golgi transmembrane UDP-galactose transporter, suggesting disrupted N-glycosylation as a distinct pathogenic mechanism underlying epilepsy in this disorder. In this review, we present the current clinical, histopathological, and molecular understanding of MOGHE, with a particular focus on recent insights gained from experimental rodent and human cellular models of SLC35A2 deficiency. We contextualise these findings against established models of mTORopathies including FCD type 2, placing MOGHE within the broader malformation of cortical development spectrum. Synthesising this evidence, we observe that neuronal activity in models of both MOGHE and mTORopathies such as FCD type 2 converge on reduced action potential firing, despite their distinct genetic aetiologies. Finally, we discuss how these findings inform our understanding of epileptogenesis, especially the emergence of infantile epileptic spasms, and the development of future precision therapeutic strategies across malformations of cortical development.
For decades, infections with the parasite Schistosoma mansoni have been treated with praziquantel, the only available drug, which highlights the urgent need of treatment alternatives. Natural compounds including rocaglates from plants of the genus Aglaia and pateamines isolated from the marine sponge Mycale hentscheli have exhibited promising anti-viral, anti-cancer, and anti-pathogenic properties. These compounds target the eukaryotic translation initiation factor 4A (eIF4A), which is a crucial factor for unwinding RNA structures in the 5'-UTR of selected mRNAs, and prevent the unwinding activity of eIF4A, which interferes with protein synthesis. Preliminary data indicated anthelminthic activity of the rocaglate silvestrol against S. mansoni in vitro. In this study, we confirmed the interaction of rocaglates and pateamines with recombinant S. mansoni eIF4A and analyzed the activity of these compounds against adult S. mansoni in vitro. Our findings showed reduced parasite vitality and stem-cell proliferation as well as impaired embryogenesis after rocaglate or pateamine treatment in the nanomolar range. Furthermore, we observed that rocaglate-treated S. mansoni recovered during washout experiments, while pateamine treatment displayed irreversible effects finally killing most of the worms. Although some properties of the used compounds impede their suitability as anti-schistosomal candidates, eIF4A remains a promising drug target in this parasite.
The immune system plays a crucial role in defending the body against harmful invaders, with immunoglobulins being key players in pathogen recognition and neutralization. Immunoglobulin dysregulation is linked to various diseases, including autoimmune disorders, immunodeficiencies, and allergies. Previous studies suggest that depression can alter immune function by modifying immunoglobulin production, which may contribute to increased vulnerability to infections and autoimmune diseases. In this study, we examined the association between the immunoglobulin (Ig) subclasses IgA, IgG, IgM, and IgE and different types of depression, alongside epidemiological and environmental factors, using two independent samples from the population-based SHIP (Study of Health in Pomerania) project (TREND-0 N = 3750, START-2 N = 1958). Multiple linear regression analyses revealed that the environmental factors showed distinct associations with immunoglobulin levels. In TREND-0, lifetime depressive disorder was associated with decreased total IgA (p = 0.019) and increased total IgM (p = 0.026), indicating a shift toward impaired local immunity and heightened global immunity. Current depressive symptoms correlated with reduced IgG (p = 0.039) levels, reflecting impaired long-term immunity and immunological memory. These associations were specifically observed in depression, with no significant effects from broader psychiatric conditions. Results on current depression were replicated in START-2, a measurement of lifetime depression was not available here. Additionally, a history of childhood trauma was linked to elevated total IgE (p = 0.028), suggesting an increased susceptibility to allergic responses. These findings highlight the complex relationship between depression and immune function, emphasizing the need for further exploration of these associations in immune-related pathologies.