Search Results (3,927)

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C₂B₉H₁₁)₂], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of ¹⁰B-enriched trimethylammonium salt of nido-[7,8-C₂¹⁰B₉H₁₂]⁻o-carborane, along with the cesium and sodium salts of [o-¹⁰COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[¹⁰B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-¹⁰COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-¹⁰COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-¹⁰COSAN] would be potentially useful to treat head and neck cancer with BNCT. Full article

Experimental evidence suggests that, in the inflamed gut of inflammatory bowel disease (IBD) patients, interleukin-34 (IL-34) triggers detrimental signaling pathways. Factors/mechanisms regulating IL-34 production in IBD remain poorly characterized. Bromodomain-containing 4 (BRD4), a transcriptional and epigenetic regulator, is over-expressed in IBD, and studies in cancer cells suggest that BRD4 might positively control IL-34 expression. This study aimed to assess whether, in IBD, BRD4 regulates IL-34 expression. In IBD, there was an up-regulation of both IL-34 and BRD4 compared to the controls, and the two proteins co-localized in both lamina propria mononuclear cells (LPMCs) and epithelial cells. Flow cytometry analysis of CD45+ LPMCs confirmed that the percentages of IL-34- and BRD4-co-expressing cells were significantly higher in IBD than in the controls and showed that more than 80% of the IL-34-positive CD45-LPMCs expressed BRD4. IL-34 and BRD4 were mainly expressed by T cells and macrophages. IL-34 expression was reduced in IBD LPMCs transfected with BRD4 antisense oligonucleotide and in the colons of mice with dextran sulfate sodium-induced colitis treated with JQ1, a pharmacological inhibitor of BRD4. These data indicate that BRD4 is a positive regulator of IL-34 in IBD, further supporting the pathogenic role of BRD4 in IBD-associated mucosal inflammation. Full article

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case–control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05–1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications. Full article

Background: Gastrointestinal mucosal damage due to human immunodeficiency virus (HIV) infection leads to microbial translocation and immune activation, contributing to the development of non-infectious comorbidities (NICM) in people living with HIV (PLWH). Additionally, persistent proviral HIV-1 in the gut-associated lymphatic tissue (GALT) can trigger immunological changes in the epithelial environment, impacting the mucosal barrier. However, the role of zonulin, a modulator of epithelial tight junctions in GALT during HIV infection, remains poorly understood. Methods: We measured zonulin in serum and intestinal tissue sections from five treatment-naive (HIV⁺_NAIVE) and 10 cART-treated (HIV⁺_cART) HIV⁺ individuals, along with 11 controls (CTRL). We compared zonulin levels with clinical characteristics, inflammatory markers (IFN-α, CXCR3, and PD-1), and the viral reservoir in peripheral blood (PB) and terminal ileum (TI). Results: Upon HIV infection, TI was found to harbor more HIV DNA than PB. Circulating zonulin levels were highest in HIV⁺_NAIVE compared to HIV⁺_cART or CTRL. Surprisingly, in the gut tissue sections, zonulin levels were higher in CTRL than in HIV⁺ individuals. Elevated circulating zonulin levels were found to be correlated with CD4⁺T-cell depletion in PB and TI, and with intestinal IFN-α. Conclusions: The findings of this study indicate a shift in zonulin levels from the gut to the bloodstream in response to HIV infection. Furthermore, elevated systemic zonulin levels are associated with the depletion of intestinal CD4⁺ T cells and increased gut inflammation, suggesting a potential link between systemic zonulin and intestinal damage. Gaining insight into the regulation of gut tight junctions during HIV infection could offer valuable understanding for preventing NICM in PLWH. Full article

Background/Objectives: The aetiology of inflammatory bowel disease (IBD), particularly if occurring early in childhood, is a diverse and patient-focused treatment that is required when standard therapy is ineffective. Materials and Methods: A clinical case report is presented of a child with very early-onset IBD (VEOIBD) and evidence of high serum IL-18 responding to anti-IL-18 immunotherapy. Detailed cytokine profiling was performed by ELISA and multiplex assay flow cytometry. Results: A four-year-old girl with recalcitrant VEOIBD from six weeks old due to an IL-18opathy, characterised by high blood IL-18 concentration, responded to therapy with a novel neutralising anti-IL-18 antibody (GSK1070806). After two years of hospitalisation, the child’s systemic inflammation and extensive upper and lower gastrointestinal mucosal ulceration remitted with this cytokine inhibitor, allowing the discontinuation of total parenteral nutrition and the resumption of normal oral intake and daily activities. After 18 months on regular GSK1070806, the patient remains in disease remission. Conclusions: VEOIBD can be associated with evidence of an underlying IL18opathy and responds to anti-IL-18 antibody therapy. IL-18 should be measured in patients with IBD unresponsive to conventional treatments, and, if elevated, anti-IL-18 antibody therapy should be considered as a potential therapy. Full article

The purpose of this experiment was to investigate the effects of Hot Water Extract of Juncao-substrate Ganoderma lucidum Residue (HWE-JGLR) on the immune function and intestinal health of yellow-feather broilers. In an animal feeding experiment, 288 male yellow-feather broilers (1 day old) were randomly allocated to four treatment groups with six replicates of 12 birds each. The control (CON) group was fed a basal diet. HJ-1, HJ-2, and HJ-3 were fed a basal diet supplemented with 0.25%, 0.50%, and 1.00% HWE-JGLR, respectively. The feeding trial lasted for 63 d. The results showed increased ADFI (p = 0.033) and ADG (p = 0.045) of broilers in HJ-3, compared with the CON group. Moreover, higher contents of serum IL-4 and IL-10 and gene expression of IL-4 and IL-10 in jejunum mucosa and lower contents of serum IL-1β and gene expression of IL-1β in jejunum mucosa in HJ-3 were observed (p < 0.05). Additionally, the jejunal mucosal gene expression of Claudin-1 and ZO-1 in HJ-2 and HJ-3 was higher than that in the CON group (p < 0.05). As for the microbial community, compared with the CON group, the ACE index, Shannon index, and Shannoneven index of cecal microorganisms in HJ-2 and HJ-3 were elevated (p < 0.05). PCoA analysis showed that the cecal microbial structure of broilers in HJ-2 and HJ-3 was different from the CON group (p < 0.05). In contrast with the CON group, the broilers in HJ-2 and HJ-3 possessed more abundant Desulfobacterota at the phylum level and unclassified Lachnospiraceae, norank Clostridia vadinBB60 group and Blautia spp. at the genus level, while Turicibacter spp. and Romboutsia spp. were less (p < 0.05). In conclusion, dietary supplementation with HWE-JGLR can improve growth performance, enhance body immunity and intestinal development, and maintain the cecum microflora balance of yellow-feather broilers. Full article

Nasal delivery is a non-invasive strategy for effective drug delivery. Nevertheless, in order to promote drug uptake by the nasal mucosa, it is fundamental to increase its residence time in the administration site. To this aim, nano-sized drug delivery systems are widely exploited. Within this context, the commercially available nanoemulsion for parenteral nutrition is a biocompatible, safe and clinically approved vehicle for drug delivery. Furthermore, the nanodroplet surface can be modified via a well-established protocol to graft Concavalin A, a lectin capable of improving the mucosal adhesion, by binding to the α-mannose and α-glucose residues of the mucosal glycocalyx. The obtained targeted formulation is able to induce haemagglutination, as opposite to non-modified nanoemulsion. Furthermore, the ConA grafting maintains the physicochemical properties of the nanodroplets (size~230 nm, Z < −35 mV) and does not interfere with the loading of the Rose Bengal fluorescent probe. Fluorescently labelled ConA grafted nanodroplets showed enhanced permeation and accumulation in ex vivo bovine nasal mucosa. This study is a proof of concept that Concanavalin A can be used to decorate the surface of nanodroplets, acting as a permeation promoter. Full article

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system’s structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota–thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation. Full article

Inflammatory bowel disease is a chronic condition characterized by recurrent intestinal inflammation. Its etiopathogenesis is driven by a series of events that disrupt the mucosal barrier, alter the healthy balance of intestinal microbiota, and abnormally stimulate intestinal immune responses. Therefore, numerous studies suggest the use of short-chain fatty acids and their immunomodulatory effects as a therapeutic approach in this disease. The objective of this systematic review was to synthesize previous evidence on the relevance and therapeutic use of short-chain fatty acids, particularly butyrate, in the immune regulation of inflammatory bowel disease. This systematic review of articles linking inflammatory bowel disease with short-chain fatty acids was conducted according to the PRISMA-2020 guidelines. The Medline and the Web of Science databases were searched in August 2024. The risk of bias was assessed using the Joanna Briggs Institute checklists. A total of 1460 articles were reviewed, of which, 29 met the inclusion criteria. Short-chain fatty acids, particularly butyrate, play a critical role in the regulation of intestinal inflammation and can be used as a strategy to increase the levels of short-chain fatty acid-producing bacteria for use in therapeutic approaches. Full article

Background/Objectives: Cow’s milk allergy is one of the most common food allergies in children, and its pathomechanism is still under investigation. Recently, an increasing number of studies have linked food allergy to intestinal barrier dysfunction. The present study aimed to investigate changes in the intestinal microenvironment during the development of β-lactoglobulin (β-lg) allergy under conditions of early intestinal dysfunction. Methods: BALB/c mice received intraperitoneal β-lg with Freund’s adjuvant, followed by oral β-lg while receiving dextran sulphate sodium salt (DSS) in their drinking water (0.2% w/v). The immunized group without DSS and the groups receiving saline, oral β-lg, or DSS served as controls. Results: The study showed that the immunization effect was greater in mice with mild intestinal barrier dysfunction. Although DSS did not affect the mice’s humoral response to β-lg, in combination with β-lg, it significantly altered their cellular response, affecting the induction and distribution of T cells in the inductive and peripheral tissues and the activation of immune mediators. Administration of β-lg to sensitized mice receiving DSS increased disease activity index (DAI) scores and pro-inflammatory cytokine activity, altered the distribution of claudins and zonulin 1 (ZO-1) in the colonic tissue, and negatively affected the balance and activity of the gut microbiota. Conclusions: The research model used appears attractive for studying food allergen sensitization, particularly in relation to the initial events leading to mucosal inflammation and the development of food hypersensitivity. Full article

Background: Methionine (Met) is a popular nutritional supplement in humans and animals. It is routinely supplemented to pigs as L-Met, DL-Met, or DL-2-hydroxy-4-(methylthio) butanoic acid (DL-HMTBA). Methods: We investigated the effect of these Met supplements on jejunal amino acid (AA) transport in male castrated Piétrain × Danbred pigs, also including a non-supplemented group. The mucosal-to-serosal flux of ten [¹⁴C]-labeled AAs (L-glutamine, glycine, L-leucine, L-lysine, L-Met, L-serine, L-threonine, L-tryptophan, L-tyrosine and L-valine) was investigated at two concentrations (50 µM and 5 mM). Inhibition of apical uptake by mucosal L-Met was also measured for these AAs. The intestinal expression of apical AA transporters, angiotensin-converting enzyme II and inflammation-related genes were compared with those of a previous study. Results: Except for tryptophan and lysine at 5 mM, all AA fluxes were Na⁺-dependent (p ≤ 0.05), and the uptake of most AAs, except glycine and lysine, was inhibited by L-Met (p < 0.001). A correlation network existed between Na⁺-dependent fluxes of most AAs (except tryptophan and partly glycine). We observed the upregulation of B⁰AT1 (SLC6A19) (p < 0.001), the downregulation of ATB^0,+ (SLC6A14) (p < 0.001) and a lower expression of CASP1, IL1β, IL8, TGFβ and TNFα in the present vs. the previous study (p < 0.001). Conclusions: The correlating AAs likely share the same Na⁺-dependent transporter(s). A varying effect of the Met supplement type on AA transport in the two studies might be related to a different level of supplementation or a different inflammatory status of the small intestine. Full article

Introductions: cancer of unknown primary site (CUP) is a heterogeneous group of cancers in which metastases are found, and the primary tumor is not detected with available diagnostic methods. CUP is a disease that has not been fully researched, and its biology is unclear. The clinical characteristics of CUP are variable, but the prognosis of patients is usually unfavorable, and the possibilities of radical treatment are limited. The microbiome is the genes and gene products of microorganisms residing in a human body. In recent years, thanks to the use of next-generation sequencing, it is possible to assess the impact of the microbiome on human body functions. Head and neck cancers, due to the rich microbiome of this area, are influenced by it, and dysbiosis may be a risk factor for the development of cancer. Objective of this work: the aim of this study was to evaluate prognostic factors, clinical features including the microbiome, and treatment outcomes in patients with cancer of unknown primary site. Results: in the study group, increased numbers of bacteria of the phyla Bacteroides, Fusobacteria, Bacillota, Actinomycetota, Actinobacteria, and Candidatus were detected, while Firmicutes and Proteobacteria were detected in smaller numbers. Independent predictors of CUP occurrence were the following: leukocyte count of at most 6.49 × 10³/mm, bacteria from the Proteobacteria phylum in the microbiome below 11.6%, Firmicutes below 22.1%, and Actinobacteria at least 11.0%. Increased numbers of Porphyromonas and Fusobacterium bacteria were associated with the risk of radiotherapy complications and shortened survival rate. Conclusions: clinical diagnosis and treatment of patients with CUP is complicated and difficult due to the lack of consensus on this issue. Treatment and prognosis of patients with CUP is unsatisfactory. The clinical value of the influence of the microbiome on the development, course, and treatment of cancer is becoming increasingly important. The microbiome may become a marker of response to anticancer treatment and the risk of its complications. Immunity modulation with the microbiome provides opportunities for further research on improving the effectiveness of oncological treatment. Fusobacterium and Porphyromonas seem to be the bacteria most important for the development of cancer, also worsening the prognosis of patients by increasing the risk of complications of radiotherapy and shortening the survival rate of patients. Streptococcus and Lactobacillus seem to be bacteria that reduce the risk of cancer, reduce the risk of complications, and improve the prognosis of patients. Total protein deficiency and elevated inflammatory markers are also important predictors of cancer risk. Full article

Background/Objectives: Dysgeusia contributes to the derangement of nutritional status in patients with cancer as well as worsening the quality of life. There has been a lack of effective treatments for taste disorders provided by the pharmaceutical industry. Methods: This was a pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB or placebo tablet before each main meal. Using the nanopore methodology, we analyzed the oral microbiome of patients with cancer using saliva samples. Results: All patients with cancer and dysgeusia had dysbiosis in terms of lower bacterial diversity and richness. DMB consumption was associated with changes in oral microbiome composition. Neither selected bacteria nor taste perception, type of diet, and cytokine levels were associated with mucositis. Likewise, alcohol and tobacco consumption as well as general and digestive toxicity due to systemic therapy were not associated with specific changes of the oral microbiome, according to logistic binary regression. The standard dose of DMB resulted in a lower abundance of Veillonella compared with the high DMB dose and placebo at 3 months after intervention with DMB. In particular, some species such as Streptococcus parasanguinis, Veillonella parvula, and Streptococcus mutans were less abundant in the DMB standard-dose group. Additionally, the consumption of a standard dose of DMB revealed a negative association between the concentrations of TNF-α and the abundance of species such as Streptococcus thermophilus, Streptococcus pneumoniae, Streptococcus dysgalactiae and Streptococcus agalactiae. Conclusions: Accordingly, regular DMB consumption could modify the oral microbiome in patients with cancer and dysgeusia, which may contribute to maintaining an appropriate immune response. However, as the present pilot study involved a small number of participants, further studies are necessary to draw robust conclusions from the data. Full article

Background/Objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access. Methods: This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery. Results: While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa. Conclusions: With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health. Full article

The salmonid industry faces challenges due to the susceptibility of fish to opportunistic pathogens, particularly in early developmental stages. Understanding the immunological capacity during these stages is crucial for developing effective disease control strategies. IL-8R, a member of the G-protein-coupled receptor family, acts as a receptor for Interleukin 8 (IL-8). The binding of IL-8 to IL-8R plays a major role in the pathophysiology of a wide spectrum of inflammatory conditions. This study focused on the immune response capacity of rainbow trout (Oncorhynchus mykiss) larvae by analyzing IL-8/CXCR1 response to lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Previous research demonstrated that LPS from P. aeruginosa acts as a potent immunostimulant in teleost, enhancing pro-inflammatory cytokines. The methodology included in silico analysis and the synthesis and characterization of an omCXCR1-derived epitope peptide, which was used to produce omCXCR1-specific anti98 serum in mice. The research revealed that rainbow trout larvae 19 days post-hatching (dph) exhibited pronounced immune responses post-stimulation with 1 µg/mL of LPS. This was evidenced by the upregulated protein expression of IL-8 and omCXCR1 in trout larvae 2 and 8 h after LPS challenge, as analyzed by ELISA and immunohistochemistry. Furthermore, fluorescence microscopy successfully revealed the colocalization of IL-8 and its receptor in cells from mucosal tissues after LPS challenge in larvae 19 dph. These findings underscore the efficacy of LPS immersion as a method to activate the innate immune system in trout larvae. Furthermore, we propose IL-8 and its receptor as molecular markers for evaluating immunostimulation in the early developmental stages of salmonids. Full article