Search Results (15,939)

Neospora caninum, as well as Toxoplasma gondii, secrete proteins that facilitate the invasion of host cells and the regulation of host immune response and metabolism. However, the localization of the secretory proteins in infected animal brains has not been studied in detail. Here, we investigate the brain and intracellular distribution of the secretory proteins in experimentally infected mice and naturally infected calves through histopathology and immunohistochemistry (IHC) to detect surface antigen 1 (NcSAG1), cyclophilin (NcCYP), profilin (NcPF), dense granule protein 6 (NcGRA6), and NcGRA7. These methods revealed that numerous tachyzoites positive for NcSAG1, NcCYP, NcPF, NcGRA6, and NcGRA7 were localized in and around the animals’ necrotic lesions, and NcGRA7 was diffusely observed in the necrotic lesions of the infected mice. Moreover, IHC revealed that NcGRA6 and NcGRA7 were distributed in the cytoplasm of infected neurons around the parasites in the infected mice and calves. This suggests that NcGRA6 and NcGRA7 might be directly related to the alteration of neuronal metabolism and activity, and that NcGRA7 might be related to the formation of necrotic lesions. Full article

Background: This study aimed to investigate the impact of the diabetic environment on the development of experimental autoimmune uveoretinitis (EAU) and the activation status of microglia in the eye. Methods: EAU was induced in wild-type (WT) and streptozotocin (STZ)-induced diabetic mice (STZ-EAU mice). Disease severity was assessed using funduscopy, optical coherence tomography (OCT), and histopathological analysis. The proportions of Th1, Th17, and regulatory T cells in the spleen were analyzed by flow cytometry. Retinal microglia were quantified using immunohistochemistry. To further characterize retinal cell populations and gene expression profiles, single-cell RNA sequencing (scRNA-seq) was performed. Results: STZ-EAU mice exhibited significant reductions in both the incidence and severity of EAU compared with WT-EAU mice. These were accompanied by a decreased proportion of Th1 cells, which are crucial for EAU pathogenesis, in the spleens of STZ-EAU mice. Retinal microglial accumulation was markedly reduced in STZ-EAU mice compared with WT-EAU mice. scRNA-seq analysis revealed a significant change in the microglial phenotype in STZ-EAU mice, characterized by decreased expression of MHC class I/II and the suppression of antigen presentation signaling pathways. Activated microglia in STZ-EAU mice showed reduced gene expression of M1 markers (CD68, CD74, and IL1B) and increased gene expression of M2 markers (MSR1, CD163, and MRC1), suggesting a shift toward an anti-inflammatory M2 phenotype. Conclusions: EAU is suppressed in STZ-induced diabetic mice, likely due to alterations in microglial polarization toward an M2 phenotype. These results suggest a decrease in T cell responses to pathogens in a diabetic environment, which could be one of the underlying factors for the increased susceptibility to infection in diabetic patients. Inhibiting the M2 polarization of microglia may reduce the susceptibility to infection in patients with diabetes. Full article

Objectives: The aim of the present study was to better understand the antibody concentrations in healthcare workers (HCWs) from a hospital in Mexico City with a high density of COVID-19 patients. Methods: Up to 243 HCWs were recruited in 2020 and 2022 and were sorted into three groups: hybrid immunity (HI, natural infection plus vaccination), vaccine-induced immunity (VI), and unvaccinated but RT-qPCR negative at the beginning of the pandemic (UV). Peripheral blood and nasopharyngeal swab samples were obtained; additionally, saliva samples were obtained from the UV group. The titers of IgG, IgM, and IgA against the SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid (NCP) proteins were assessed using an in-house ELISA, and positivity to the virus was determined via RT-qPCR. Results: Most HI and VI participants were positive for serum anti-RBD IgG (92.8% and 100%, respectively), while 26.6% (for HI) and 19% (for VI) were positive for anti-NCP IgG. Regarding serum anti-RBD IgA, the VI and HI groups had positive rates of 87.3% and 66%, respectively. In contrast, the UV group showed a rate of 5.7% but the positivity for IgA in saliva was higher (52% for RBD and 35% for NCP). In addition, the highest antibody titers were obtained for anti-RBD IgG and IgA in the HI and VI groups, respectively. In saliva, the IgA antibody titer was higher for the RBD antigen (1:1280). Conclusions: These results strengthen our understanding of antibody concentrations in HCWs during two critical years of the pandemic in a general hospital with many COVID-19 patients. Full article

Multiple studies have assessed the potential for improvement for genetic and antigenic match of influenza vaccines to circulating viruses by altering the timing of vaccine strain decisions. The advent of new technologies for vaccination has generated global discussion around moving the seasonal influenza strain recommendations closer to the start of the vaccination period. The window between influenza vaccine strain recommendations and the availability of vaccine supply for immunization comprises sequential processes required to produce vaccine components, reagents for manufacture and release, and regulatory approvals. This commentary examines one company’s perspective on requirements for enabling manufacture and release of seasonal influenza vaccine in more detail, describes preparations to reduce risk, and highlights the potential impact on vaccine supply for all platforms (egg, cell, mRNA) when strain decisions are issued closer to the desired vaccination timing. Full article

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from ⁶⁸Ge/⁶⁸Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications. Full article

Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview discusses the current situation of influenza vaccination, including the numerous types of vaccines—inactivated, live attenuated, and recombinant vaccines—and their effectiveness, efficacy, and associated challenges. It highlights the effects of the COVID-19 pandemic on the trends of influenza vaccination and the level to which innovation should be practiced. In the future universal influenza vaccines will be developed that target conserved viral antigens to provide long-term protection to people. In the meantime, novel vaccine delivery platforms, such as mRNA technology, virus-like particle (VLP), and nanoparticle-based systems, and less cumbersome and invasive administration routes, as well as immune responses are also under development to increase access and production capacity. Collectively, these innovations have the potential to not only reduce the global influenza epidemic but also to change the way influenza is prevented and prepare the world for a pandemic. Full article

Aim: In sub-Saharan Africa, approximately 40 million pregnant women are exposed to parasitic diseases such as malaria caused by Plasmodium falciparum, Schistosome parasites, and soil-transmitted helminths (STHs). When parasitic diseases share the same habitat and overlap in distribution, then high co-infection rates occur. The co-infection can lead to consequences for the child, such as intrauterine growth retardation, low birth weight, pre-term delivery, and neonatal mortality. Methods: The objective of the study was to determine the nature and extent of coinfection from 100 samples collected from the Battor (50) and Adidome (50) towns of Ghana in collaboration with the Noguchi Memorial Institute for Medical Research, University of Ghana. Results: Out of 50 for the Adidome towns determined for P. falciparum by Rapid Diagnostic Test (RDT), Malaria Pan-specific Antigen (PAN), and Malaria Pf kit, 39 were true positive (TP), 8 were true negative (TN), and 30 were false negative (FN). For Battor, 19 were TP, 12 TN, and 20 FN. For S. mansoni in Adidome via polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), 21 tested positive, and 29 were negative, with 52.5% sensitivity and 100% specificity. For S. haematobium, 28 were positive and 22 negative using PCR with 70% sensitivity and 100% specificity. In LAMP, 28 were positive, and 22 negatives, with 70% sensitivity and 100% specificity. In Battor PCR for S. mansoni, 28 positives and 22 negatives with 68.3% sensitivity and 100% specificity. In LAMP, 32 were positive, and 18 were negative, with 80% sensitivity and 100% specificity. For S. haematobium, PCR showed 30 positive and 20 negative, with 73.2% sensitivity and 100% specificity. With LAMP, 21 were positive, and 29 negatives, with 51% sensitivity and 100% specificity. In both towns, 20–30 years had the highest infection prevalence for P. falciparum, S. mansoni, S. haematobium, and Strongyloides stercoralis. Conclusion: The results will be utilized as a part of the continuous surveillance for future research aiming at gathering nationally representative data in Ghana on the prevalence of coinfection and proposing interventions based on that for the vulnerable pregnant women population. Full article

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD₅₀ RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity. Full article

Fruit bats in the genus Pteropus are the natural reservoirs for zoonotic paramyxoviruses, notably henipaviruses and pararubulaviruses, which are found across Southeast Asia and Oceania. The genetic and antigenic diversity of viruses in both genera, and region specificity, are ill-defined, limiting health security measures aimed at minimizing spillover. For example, Nipah virus has been isolated from bats in the Battambang province of western Cambodia, and surveys suggest bat foraging behaviors occur in close proximity to human settlements. However, there have been no historical cases of Nipah virus in Cambodia. Here, we use a multiplex microsphere immunoassay to identify cryptic human exposure to selected henipaviruses and pararubulaviruses in Cambodia. Convalescent human sera from persons presenting with acute respiratory illness were screened to detect the presence or absence of antibodies reactive with attachment glycoprotein antigens from Nipah virus, Hendra virus, Cedar virus, and Ghana virus, and a hemagglutinin-neuraminidase antigen from Menangle virus. In this sero-survey, we detected antibodies that were specifically reactive with Cedar virus and Menangle virus, including one serum sample that neutralized a recombinant Cedar virus. Additionally, we detected a pattern of cross-reactivity with Hendra virus, Cedar virus, and Ghana virus, suggesting previous infection by an antigenically-related henipavirus. We did not detect high antibody reactivity with the NiV glycoprotein. Future studies should expand serological surveillance for these transboundary pathogens, including genetic surveillance to aid in henipavirus discovery, and focused biosurveillance where interfaces with livestock and humans occur. Full article

Background/Objectives: Human endogenous retroviruses (ERVs) are genomic sequences integrated into the human genome from ancestral exogenous retroviruses and are epigenetically silenced under normal conditions. Growing evidence has shown that they can be reactivated in human diseases such as cancers and autoimmune diseases. However, their clinical implications in colon cancer are yet to be explored. Methods: RNA-seq data were downloaded from RNA Atlas and TCGA for cell lines and tissue samples, respectively. After alignment, ERV expression was quantified against comprehensively compiled ERVs (3220). ERV expression profiles were compared between sequencing protocols, cancer and normal cells, and matched tumor and normal tissue pairs. Unsupervised clustering was used to identify ERV-defined tumor subtypes and their associations with clinical and other molecular features. ERV association with disease-specific survival (DSS) was performed using the Cox regression model. Results: PolyA and total RNA protocols were comparable in ERV expression detection. Cancer cells had significantly increased ERV expression and reactivation. Upregulated ERVs were significantly enriched in viral protein interactions with cytokine and cytokine receptors. ERV expression-defined tumor classes were significantly associated with tumor mutation burden and immuno-phenotypes such as antigen processing and presenting machinery and tumor immune infiltration score. Survival analysis identified 152 ERVs to be independently associated with DSS. Conclusions: ERV abnormal expression is common in colon cancer. The ERV-defined subtypes are associated with tumor immunity, and some ERVs are independently associated with patient outcomes. Full article

This systematic review aimed to evaluate the association between Helicobacter pylori in the oral cavity as an extragastric reservoir and oral diseases in patients with or without gastritis. Following the PRISMA guidelines, a comprehensive search was conducted on the PubMed, Scopus, Cochrane Central, and Embase databases (2010–2025) using MeSH terms and keywords related to H. pylori, the oral cavity, and oral diseases. Inclusion criteria included observational studies, clinical trials, and case–control studies. Data extraction and quality assessment were performed using the Newcastle–Ottawa Scale (NOS). Of the 298 records initially identified, 22 studies met the inclusion criteria. The presence of H. pylori in the oral cavity (plaque, saliva) was variably associated with gastritis, periodontitis, dental caries, and halitosis. Detection rates varied widely (0–100%), influenced by methodological differences (PCR, culture, antigen tests). Some studies reported an improvement in oral health after eradication therapy, while others found no significant association. The oral cavity may serve as a reservoir for H. pylori, with implications for oral and systemic health. Standardized diagnostic methods and integrated treatment approaches (combining gastric eradication and oral hygiene) are needed to clarify their role and optimize clinical outcomes. Further research is warranted to establish causal relationships and therapeutic strategies. Full article

Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. This study aimed to evaluate the effects of dietary MOS supplementation on growth performance, serum biochemical parameters, muscle composition, digestive enzyme activity, antioxidant and immune status, and the mTOR signaling pathway in juvenile GIFT tilapia (Oreochromis niloticus). Juveniles (initial body weight: 16.17 ± 1.32 g) were randomly assigned to six treatment groups (three replicate tanks per group) and fed diets supplemented with MOS at 0, 0.2%, 0.4%, 0.6%, 0.8%, and 1% (equivalent to 0, 2, 4, 6, 8, and 10 g/kg of diet, respectively) for 60 days. Compared with the control group, fish fed MOS-supplemented diets exhibited significantly higher (p < 0.05) weight gain rates, specific growth rates, and protein efficiency ratios, along with a significantly lower (p < 0.05) feed conversion ratio. Serum albumin, high-density lipoprotein, and lysozyme levels were significantly increased (p < 0.05), whereas triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels were significantly decreased (p < 0.05). In the liver, head kidney, and spleen, the expression of pro-inflammatory genes (tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, and interferon γ) was significantly downregulated (p < 0.05), while the expression of antioxidant and protective genes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, lysozyme, alkaline phosphatase, interleukin-10, transforming growth factor β, and heat shock protein 70) as well as mTOR signaling pathway-related genes (mammalian target of rapamycin, akt protein kinase B, phosphatidylinositol 3 kinase, and ribosomal protein S6 kinase polypeptide 1) was significantly upregulated (p < 0.05). Overall, MOS positively affects tilapia’s growth, health, and immunity, with 0.60% identified as the optimal dietary level based on growth performance. Full article

Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such as sialylation, fucosylation, and sulfation underpins their functional specificity and regulatory capacity. This review provides a comprehensive overview of glycan biosynthesis, with a focus on N-glycans, O-glycans, glycosaminoglycans (GAGs), and glycolipids. It explores their essential roles in maintaining cellular homeostasis, development, and immune surveillance. In health, glycans mediate cell–cell communication, protein interactions, and immune responses. In disease, however, aberrant glycosylation is increasingly recognized as a hallmark of numerous pathological conditions, including cancer, neurodegenerative disorders, autoimmune diseases, and a wide range of infectious diseases. Glycomic alterations contribute to tumor progression, immune evasion, therapy resistance, neuroinflammation, and synaptic dysfunction. Tumor-associated carbohydrate antigens (TACAs) and disease-specific glycoforms present novel opportunities for biomarker discovery and therapeutic targeting. Moreover, glycan-mediated host–pathogen interactions are central to microbial adhesion, immune escape, and virulence. This review highlights current advances in glycomics technologies, including mass spectrometry, lectin microarrays, and glycoengineering, which have enabled the high-resolution profiling of the glycome. It also highlights the emerging potential of single-cell glycomics and multi-omics integration in precision medicine. Understanding glycome and its dynamic regulation is essential for uncovering the molecular mechanisms of disease and translating glycomic insights into innovative diagnostic and therapeutic strategies. Full article

Enhancing protein–protein interactions is a key therapeutic strategy to ensure effective protein function in terms of pharmacokinetics and pharmacodynamics and can be accomplished with methods like directed evolution or rationale design. Previously, two papers suggested the possible enhancement of protein–protein binding affinity via destabilizing mutations. This paper reviews the results of the previous literature and adds new data to show the generality of the strategy that destabilizing the unbound protein without significantly changing the free energy of the complex can enhance protein–protein interactions for therapeutic benefit. The first example presented is that of a variant of human growth hormone (hGHv) containing 15 mutations that improve the binding to the hGH binding protein (hGHbp) by 400-fold while retaining full biological activity. The second example is that of the YTE mutations (M252Y/S354T/T256E) in the Fc region of a monoclonal antibody (mAb). The YTE mutations improve the binding of the mAb to FcRn at pH 6.0 10-fold, resulting in elongated serum half-life of the mAb. In both cases, (i) chemical titration or differential scanning calorimetry (DSC) showed the mutations destabilize the unbound mutant proteins, (ii) isothermal titration calorimetry (ITC) showed extremely favorable enthalpy (ΔH) and unfavorable entropy (ΔS) upon binding to their respective target molecule compared with the wildtype, and (iii) hydrogen/deuterium exchange–mass spectrometry (HDX-MS) revealed that these mutations increase the free energy of unbound mutant protein without significantly affecting the free energy of the bound state, resulting in an enhancement to the binding affinities. The third example presented is that of the JAWA mutations (T437R/K248E) also located in the Fc region of a mAb. The JAWA mutations facilitate antibody multimerization upon binding to cell surface antigens, allowing for enhanced agonism and effector functions. Both DSC and HDX-MS showed that the JAWA mutations destabilize the unbound Fc, although the complex was not characterized due to weak binding. Enhancement of protein–protein interactions through incorporation of mutations that increase the free energy of a protein’s unbound state represents an alternative route to decreasing the protein–protein complex free energy through optimization of the binding interface. Full article

A post-COVID surge of Bordetella pertussis was observed globally. China has reported a high level of macrolide-resistant Bordetella pertussis (MRBP) in recent years; however, the epidemiology of MRBP in Hong Kong remains unknown. We retrieved archived B. pertussis isolates from respiratory samples collected at five regional public hospitals in Hong Kong between 2015 and 2024 and tested their minimum inhibitory concentration (MIC) for macrolides and other non-macrolide antibiotics using the Etest method. All isolates were also subjected to whole genome sequencing for genotypic resistance, Multi-locus Antigen Sequence Typing (MLST) and Multi-locus Variable Number of Tandem Repeat Analysis (MLVA) typing. Twenty-nine isolates of B. pertussis were included in the study. All isolates demonstrating phenotypic macrolide resistance harbored the A2047G mutation while showing low MIC to trimethoprim-sulfamethoxazole, doxycycline, levofloxacin, piperacillin-tazobactam and meropenem. In 2023 and 2024, 100% were MRBP and all belonged to the MT28 clone with the ptxP3 antigenic type. The MRBP isolates in Hong Kong were phylogenetically related to those from mainland China during the same period. There was no obvious correlation between macrolide resistance and clinical presentation, laboratory findings, management and outcome. Phylogenetic analysis suggests that MRBP isolates in Hong Kong and mainland China are closely related. Full article