Search Results (300)

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

A novel bivalent oral vaccine candidate against H5N1 and H9N2 avian influenza virus (AIV) was developed using Lactobacillus surface display technology without genetic modification. The hemagglutinin subunit 1 (HA1) antigens from both subtypes were fused to the surface layer-binding domain of Lactobacillus crispatus K313, expressed in Escherichia coli, and purified. Wild-type Lactobacillus johnsonii H31, isolated from chicken intestine, served as a delivery vehicle by adsorbing and stably displaying the HA1 proteins on its surface. This approach eliminates the need for bacterial engineering while utilizing lactobacilli’s natural capacity to protect surface-displayed antigens, as evidenced by HA1’s protease resistance. Mouse immunization studies demonstrated induction of strong systemic IgG and mucosal IgA responses against both H5N1 and H9N2 HA1. The system offers several advantages, including safety through non-GMO probiotics, potential for multivalent vaccine expansion, and intrinsic antigen protection by lactobacilli. These findings suggest this platform could enable development of cost-effective, multivalent AIV vaccines. Full article

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

Mucosal immunization represents a promising strategy for preventing enteric infections. Rotavirus (RV), a leading gastrointestinal pathogen distinguished by its remarkable stability and segmented double-stranded RNA genome, has been engineered into a versatile oral vaccine vector through advanced reverse genetics systems. The clinical efficacy of live-attenuated RV vaccines highlights their unique capacity to concurrently induce mucosal IgA responses and systemic neutralizing antibodies, positioning them as a multiple action vector for multiple immune protection. In this review, we summarize the RV colonization of the intestine and stimulation of intestinal immunity, as well as recent advancements in RV reverse genetics, and focus on their application in the rational design of a multivalent mucosal vaccine vector targeting enteric pathogens considering the advantages and challenges of RV as a vector. We further propose molecular strategies to overcome genetic instability in recombinant RV vectors, including the codon optimization of heterologous inserts. These insights provide a theoretical foundation for developing next-generation mucosal immunization platforms with enhanced safety, stability, and cross-protective efficacy. Full article

Background: Secretory immunoglobulin A (sIgA) plays a key role in oral and mucosal immunity, serving as a first-line defense against pathogens. Smoking is known to negatively affect immune function, but data on the impact of heated tobacco products such as IQOS^® on sIgA levels are limited. Objective: To assess and compare the effects of conventional cigarette smoking and IQOS^® use on the concentration of salivary sIgA in healthy individuals. Methods: A total of 200 participants were enrolled and divided into three groups: 60 non-smokers, 70 conventional cigarette smokers, and 70 IQOS^® users. Unstimulated whole saliva samples were collected and analyzed for sIgA concentration using ELISA method. Statistical analysis was performed using IBM SPSS Statistics 25. Results: Mean salivary sIgA levels were significantly lower in both cigarette smokers (246.03 μg/mL) and IQOS^® users (243.54 μg/mL) compared to non-smokers (380.74 μg/mL, p < 0.05). No significant difference was observed between cigarette smokers and IQOS^® users. A pronounced reduction in sIgA was seen in female users of both tobacco products, whereas male users did not show a statistically significant decline. Conclusions: Both cigarette smoking and IQOS^® use are associated with a significant decrease in salivary sIgA levels, particularly in females. The findings suggest that IQOS^® does not offer an immunological advantage over conventional smoking in terms of preserving mucosal immunity. Further studies are needed to confirm these findings and explore underlying mechanisms. Full article

Human cytomegalovirus (CMV) is the leading cause of congenital infections, often leading to mental retardation and neurological disorders. It is a major public health priority to develop a vaccine for preventing and controlling human CMV infection. In this report, we generated an oral Salmonella-based vaccine to express the M33 protein of murine cytomegalovirus (MCMV) and investigated the anti-MCMV immune responses induced in mice immunized with this vaccine. Compared to those administered with phosphate-buffered saline (PBS) or a control vaccine without M33 expression, mice immunized with the vaccine expressing the M33 protein exhibited a remarkable induction of antiviral serum IgG and mucosal IgA humoral responses and a significant elicitation of antiviral T cell responses. Successful inhibition of viral growth in lungs, spleens, livers, and salivary glands was also found in the vaccinated animals compared to the PBS-treated animals or those immunized with the control vaccine without M33 expression. Furthermore, substantial protection against MCMV challenge was observed in mice immunized with the vaccine. Thus, Salmonella-based vaccine expressing MCMV M33 can induce anti-MCMV effective immune responses and protection. Our study implies that attenuated Salmonella expressing human CMV antigens, including its homologue to M33, may represent promising oral anti-CMV vaccine candidates. Full article

Constipation affects around 30% of children and in 95% of cases is functional (FC), a consequence of alterations in digestive tract peristalsis, modulated by the immune and nervous systems, bile acid metabolism, and the gut microbiota. The aim of this review was to assess the role of gut microbiota and the use of probiotics in children with constipation. The current treatment involves education, toilet training, and oral laxatives, effective in only 50% of patients. In chronic FC, the composition of the microbiota is altered, with increased abundance of Bacteroidetes, Enterobacteriaceae, and Firmicutes and decreases in Prevotella, Bifidobacteria, Faecalibacterium prausnitzii, and Clostridium leptum. Probiotics replenish lacking beneficial resident bacteria, downregulate mucosal inflammation, or produce short-chain fatty acids (SCFAs). Probiotics like Bifidobacterium breve and Bifidobacterium longum increase the defecation frequency and decrease the episodes of both fecal incontinence and abdominal pain. Bifidobacterium animalis subsp. lactis XLTG11 improves the gut microbiota by upregulating SCFA genes and downregulating those related to methane metabolism. Lactobacilli produce organic acids that stimulate bowel peristalsis and augment fecal bolus moisture. The heterogeneity of the current studies involving pediatric subjects thus far hinders the use of probiotics as a standard in the management of children with constipation. Full article

Gastric cancer (GC) remains a major global health burden, with high morbidity and mortality rates, particularly in regions with prevalent Helicobacter pylori (H. pylori) infection. While H. pylori has long been recognized as a primary carcinogenic agent, recent research has underscored the broader contribution of the gastric microbiota to gastric carcinogenesis. Alterations in the microbial community, or dysbiosis, contribute to chronic inflammation, immune modulation, and epithelial transformation through a range of mechanisms, including disruption of mucosal integrity, activation of oncogenic signaling pathways (e.g., PI3K/Akt, NF-κB, STAT3), and epigenetic alterations. Furthermore, microbial metabolites, such as short-chain fatty acids, secondary bile acids, and lactate, play dual roles in either promoting or suppressing tumorigenesis. Oral and gut-derived microbes, translocated to the gastric niche, have been implicated in reshaping the gastric microenvironment and exacerbating disease progression. The composition of the microbiota also influences responses to cancer immunotherapy, suggesting that microbial profiles can serve as both prognostic biomarkers and therapeutic targets. Emerging strategies, such as probiotics, dietary interventions, and fecal microbiota transplantation (FMT), offer new avenues for restoring microbial balance and enhancing therapy response. This review synthesizes current knowledge on the complex interplay between microbiota and gastric cancer development and emphasizes the potential of microbiome modulation in both preventive and therapeutic frameworks. Full article

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate. Methods: Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8–12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology. Results: The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage. Conclusions: These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. Full article

Background and Objectives: Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert immunoregulatory effects in various models of inflammation. This study aimed to evaluate the protective effects of Indoximod in an acetic acid-induced colitis model in rats, focusing on histopathological changes and inflammatory mediators. Materials and Methods: Thirty male Wistar albino rats were randomly assigned to three groups (n = 10 per group): Group 1 (Control) received 0.9% saline oral gavage; Group 2 (Colitis) received intrarectal 4% acetic acid to induce colitis and were then treated with saline; Group 3 (Colitis + Indoximod) received 4% acetic acid followed by oral gavage administration of Indoximod (30 mg/kg) for 15 consecutive days. Histopathological evaluation of colonic tissues was performed using hematoxylin and eosin (H&E) staining. Colonic expression of Toll-like receptor 4 (TLR4) and plasma levels of tumor necrosis factor-alpha (TNF-α), pentraxin-3 (PTX-3), and platelet-activating factor (PAF) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Acetic acid-induced colitis significantly increased mucosal damage, TLR4 expression, and circulating levels of TNF-α, PTX-3, and PAF compared with controls (p < 0.001). Indoximod treatment markedly reduced histological injury and significantly suppressed TLR4 and TNF-α levels (p < 0.01), along with partial reductions in PTX-3 (p < 0.05). However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. Conclusions: Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators. Full article

Background: Self-administered orally dissolving films (ODFs) encapsulating inactivated influenza vaccines represent an effective strategy for stimulating mucosal immunity. While this vaccination method offers several advantages over conventional influenza vaccines, a comparative efficacy study remains lacking. Methods: Female BALB/c mice were immunized with inactivated A/PR/8/34 (H1N1) either via orogastric inoculation or through the oral mucosal delivery using pullulan and trehalose-based ODF vaccines. Each group received equivalent antigen doses across three immunizations. Humoral responses and antibody functionality were assessed using sera collected post-immunization. After lethal viral challenge, other immunological and virological parameters were determined in corresponding tissues. Body weight and survival were monitored over a 14-day period after challenge. Results: ODF vaccination elicited significantly higher virus-specific IgA levels, HAI titers, and neutralizing antibody activity than oral gavage. After the viral challenge, ODF-immunized mice exhibited stronger IgG and IgA responses in respiratory tissues, increased antibody-secreting cells in lungs and spleen, and elevated germinal center B cells and CD8⁺ T cell responses. Both vaccination methods reduced lung pro-inflammatory cytokines and provided full protection against lethal challenge; however, the ODF group showed lower cytokine levels, better weight maintenance, and reduced viral loads. Conclusions: ODF vaccination elicits more robust systemic and mucosal immune responses than oral vaccination and may serve as a promising alternative method of influenza vaccine delivery. Full article

The rapid expansion of aquaculture is vital for global food security, yet it faces persistent threats from disease outbreaks, vaccine inefficacy, and antibiotic overuse, all of which undermine sustainability. Conventional vaccines often fail to induce robust mucosal immunity, spurring interest in probiotics as adjuvants to enhance immunogenicity. Probiotics such as Bacillus subtilis and Lactobacillus casei modulate fish microbiomes, fortify mucosal barriers, and activate innate immune responses via mechanisms including Toll-like receptor signaling and cytokine production. These actions prime the host environment for prolonged adaptive immunity, improving antigen uptake and pathogen clearance. Experimental advances—such as Bacillus subtilis-engineered spores increasing survival rates to 86% in Vibrio anguillarum-challenged European seabass—demonstrate the potential of this synergy. Innovations in delivery systems, including chitosan–alginate microcapsules and synbiotic formulations, further address oral vaccine degradation, enhancing practicality. Probiotics also suppress pathogens while enriching beneficial gut taxa, amplifying mucosal IgA and systemic IgM responses. However, challenges such as strain-specific variability, environmental dependencies, and unresolved ecological risks persist. Optimizing host-specific probiotics and advancing multi-omics research is critical to unlocking this synergy fully. Integrating probiotic mechanisms with vaccine design offers a pathway toward antibiotic-free aquaculture, aligning with One Health principles. Realizing this vision demands interdisciplinary collaboration to standardize protocols, validate field efficacy, and align policies with ecological sustainability. Probiotic–vaccine strategies represent not merely a scientific advance but an essential evolution for resilient, ecologically balanced aquaculture systems. Full article

Background: Brucellosis poses a significant public health challenge, necessitating effective vaccine development. Current vaccines have limitations such as safety concerns and inadequate mucosal immunity. This study aims to develop an FcRn-targeted mucosal Brucella vaccine by fusing the human Fc domain with Brucella’s multi-epitope protein (MEV), proposing a novel approach for human brucellosis prevention. Methods: The study developed a recombinant antigen (h-tFc-MEV) through computational analyses to validate antigenicity, structural stability, solubility, and allergenic potential. Molecular simulations confirmed FcRn binding. The vaccine was delivered orally via chitosan nanoparticles in murine models. Immunization was compared to MEV-only immunization. Post-challenge assessments were conducted to evaluate protection against Brucella colonization. Mechanistic studies investigated dendritic cell activation and antigen presentation. Results: Computational analyses showed that the antigen had favorable properties without allergenic potential. Molecular simulations demonstrated robust FcRn binding. In murine models, oral delivery elicited enhanced systemic immunity with elevated serum IgG titers and amplified CD4+/CD8+ T-cell ratios compared to MEV-only immunization. Mucosal immunity was evidenced by significant IgA upregulation across multiple tracts. Long-term immune memory persisted for six months. Post-challenge assessments revealed markedly reduced Brucella colonization in visceral organs. Mechanistic studies identified FcRn-mediated dendritic cell activation through enhanced MHC-II expression and antigen presentation efficiency. Conclusions: The FcRn-targeted strategy establishes concurrent mucosal and systemic protective immunity against Brucella infection. This novel vaccine candidate shows potential for effective human brucellosis prevention, offering a promising approach to address the limitations of current vaccines. Full article

Background: Oral mucositis (OM) remains a significant toxicity of concomitant chemoradiation (CRT) for head and neck cancer (HNC). This trial assessed the safety and efficacy of EC-18, an innate immune response mitigator, in attenuating severe OM (SOM) in HNC patients being treated with CRT. Methods: This was a two-stage, Phase 2, randomized, double-blind, placebo-controlled, multi-institutional trial. Stage 1 consisted of a blinded parallel group dose-finding safety and tolerability study of 24 subjects in four equally sized groups of EC-18 (500 mg, 1000 mg, or 2000 mg or placebo). Stage 2 randomized subjects (1:1) to receive placebo or 2000 mg of EC-18. Twice-daily dosing was carried out from the first to the last day of radiation (LDRT). Patients were assessed twice weekly. OM scores were assigned centrally using WHO criteria. Adverse events were reported using NCI-CTCAE v4.0 criteria. Tumor response was reported up to 12 months following the LDRT. Results: Among patients who received a cumulative radiation dose of at least 55 Gy, at least 80% were compliant with the study’s drug dosing during the first 28 days of treatment and continued to use the study drug for more than 4 weeks. EC-18 effectively reduced the duration, onset, and incidence of SOM compared to placebo. Opioid use was delayed in EC-18-treated patients. Efficacy was associated with weekly cisplatin use and HPV positivity. No significant differences in AEs were observed between study cohorts. Conclusions: EC-18 administered orally may be a safe and effective CRT-associated SOM intervention in patients with HNC. Full article