Search Results (3,555)

Background: Current treatments for inflammatory bowel disease (IBD) are relatively futile and the extended use of drugs may reduce effectiveness. Several probiotic strains have shown promise in relieving/treating IBD symptoms. Objectives: The current study investigated the impact of fermented soymilk with a mixture of probiotic starter cultures containing Lactobacillus rhamnosus, L. casei, L. plantarum, L. acidophilus, Bifidobacterium longum, and B. animalis subsp. lactis in rats with dextran sulfate sodium (DSS)-induced colitis compared to control. Methods: Rats were randomly assigned to five groups (5 rats/group; n = 25): G1: negative normal control; G2: positive control (DSS); G3: DSS with sulfasalazine (DSS-Z); G4: DSS with soymilk (DSS-SM), and G5: DSS with fermented soymilk (DSS-FSM). Parameters monitored included the following: the disease activity index (DAI), macroscopic and histological assessments of colitis, and a fecal microbial analysis performed to assess the severity of inflammation and ulceration. Results: The DSS-FSM rats group exhibited lower DAI scores (p < 0.05) than other treated groups during the induction period. A macroscopical examination revealed no ulceration or swelling in the intestinal mucosa of rats in the DSS-FSM-treated group, resembling the findings in the negative control group. In the positive control (DSS group), the colon tissue showed increased inflammation (p < 0.05), whereas those in the DSS-SM- and DSS-FSM-treated rats groups did not show significant macroscopic scores of colitis. The positive DSS control and DSS-Z groups had crypt erosion and ulceration areas, severe crypt damage, and epithelial surface erosion, which were absent in the negative control and DSS-FSM groups. The counts of Lactobacillus spp. and Bifidobacterium spp. remained stable in both G1 and G5 over 4 weeks. The consumption of fermented soymilk with a mixture of probiotics could minimize the severity of DSS-induced colitis in rats. Conclusion, it was found that fermented soymilk containing Lactobacilli and Bifidobacterium might be an effective vehicle for reducing the severity of DSS-induced colitis in rats. Full article

Helicobacter pylori (H. pylori) has been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology. Immunoglobulin (Ig) A and G antibody responses to thirteen proteins of H. pylori were measured by a Luminex-based multiplex assay in plasma from patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85) and controls (n = 100). Multivariable logistic regression was used to assess the association of bacterial seropositivity with colorectal neoplasia. The threshold for overall seropositivity required subjects to be positive for at least 4 out of the 13 tested antigens. In a cohort subset with matched data (n = 34), H. pylori seropositivity was correlated with bacterial abundance in both neoplastic and matched normal tissue. While no association was found between H. pylori seropositivity and the presence of CRC, IgA seropositivity to CagA was associated with a decreased risk of advanced adenoma (odds ratio, OR = 0.48, 95% confidence intervals, CIs: 0.24–0.96). Regarding IgG, higher antibody responses to HpaA was associated with advanced adenoma occurrence (OR = 2.46, 95% CI: 1.00–6.01), while responses to HP0395, CagA and Catalase were associated with polyp development (OR = 2.65, 95%, CI: 1.31–5.36, OR = 1.83, 95% CI: 1.01–3.32, and OR = 2.16, CI: 1.09–4.29, respectively). Positive correlations were found between H. pylori abundance in the normal mucosa and levels of both the IgA and IgG antibody response to Catalase and VacA antigens (r = 0.48, p < 0.01; r = 0.37, p = 0.04; r = 0.51, p < 0.01; and r = 0.71, p = 0.04, respectively). Conversely, H. pylori abundance was negatively correlated with levels of IgA antibody response to HpaA and with IgG antibody response to HP0231 in the diseased tissue (r = −0.34, p = 0.04 and r = −0.41, p = 0.01, respectively). The association between levels of H. pylori antigens and colorectal neoplasia risk gradually decreased with the adenoma progression, implicating the early activation of the immune response at the polyp stage. Thus, the evaluation of antibody response to certain bacterial antigens may indicate the presence of early-stage colorectal neoplasia. Further studies are needed to clarify the role H. pylori or the immune response to its antigens may have in colorectal carcinogenesis stages. Full article

Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot’s fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot. Full article

(Background) Cancer-associated fibroblasts (CAFs) are major cancer stromal components. CAFs have diverse functions and cell origins. Podoplanin (PDPN), a lymphatic vessel marker, is also a CAF marker in certain cancers. On daily diagnosis of early colorectal carcinoma (CRC), PDPN upregulation in the stroma is often encountered, suggesting PDPN-positive CAFs have emerged. However, PDPN-positive CAFs in early CRC have not been studied well. (Methods) On immunohistochemistry, PDPN expression in the lamina propria or stroma of adenomas, early CRCs, and neuroendocrine tumors, their normal neighbors, and non-neoplastic colorectal lesions were compared. Single-cell RNA sequencing (scRNA-seq) of CRC was used to explore PDPN^high CAFs’ cell origins. (Results) Reticular cells or pericryptal fibroblasts in the lamina propria of adenomas and early CRCs showed higher PDPN expression than did normal mucosae and non-neoplastic lesions (p < 0.01). Pericryptal PDPN expression was a diagnostic feature of adenomas and early CRCs. scRNA-seq of CRCs highlighted that PDPN^high CAFs had distinctly higher COL4A1, COL4A2, and WNT5A expression, unlike well-known CAFs characterized by high FAP, POSTN, or ACTA2 expression. (Conclusions) We demonstrated that pericryptal fibroblasts and reticular cells in the lamina propria are origins of early-stage CRC CAFs and thus have potential as a diagnostic marker for distinguishing colorectal non-neoplastic from neoplastic lesions. 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

Background: Oral lichen planus (OLP) is a mucocutaneous disease associated with the formation of symptomatic lesions in the mouth that are often refractory to treatment. An as-yet-unknown antigen triggers an inflammatory reaction in which various immune and non-immune cells release multiple cytokines that contribute to disease progression. The ability of photobiomodulation (PBM) to reduce the symptoms and signs of the disease has been shown, but little is known about its molecular and cellular effects. The aim of this study was to evaluate changes in pro-inflammatory cytokine levels and in histological findings in OLP patients treated with photobiomodulation therapy. Methods: Twenty OLP patients underwent PBM with diode laser (810 nm), (0.50 W, 30 s, 1.2 J/cm²), 3 times weekly for a month. Pain level and clinical scores of lesions were recorded before and after therapy. Salivary levels of IL-1β, IL-6, and TNF-α in OLP patients were measured before and after PBM and compared with those of 10 healthy controls. Biopsies were taken at the beginning and end of treatment to assess pathomorphological changes. Results: PBM significantly reduced the level of pain and clinical scores of the lesions. Salivary levels of IL-1β, IL-6, and TNF-α in OLP patients were significantly higher compared to those in healthy controls and decreased after therapy. 60% of the post-treatment OLP biopsies demonstrated histological improvement, characterized by inflammatory infiltrate reduction (50%), epithelial hyperplasia reduction (30%), epithelial thickening (15%), or epidermal-dermal attachment repair (5%). Conclusion: The effectiveness of PBM therapy in OLP patients was confirmed at the clinical, molecular, and histomorphological levels. Full article

The immune system is inexperienced before birth and tends to be tolerogenic, rather than immunogenic. After birth, the adaptive immune system develops while facing microbial challenges, but it can become impaired as old age progresses and persistent inflammation can lead to chronic morbidity, disability and frailty. To investigate the potential contributions of lymphocyte subsets to immunity from birth until old age, we enumerated circulating innate and conventional lymphocytes and measured serum cytokine levels in 10 cord blood samples and in peripheral blood from 10 healthy term neonates, 23 healthy school-age children, 25 young adults and 11 older subjects. Flow cytometric analysis revealed that B cell frequencies increase during childhood and gradually decrease into adulthood, whereas natural killer cell frequencies increase throughout life. T cell frequencies remained relatively constant throughout life, as did their expression of CD4 and CD8. However, all four innate T cell populations studied—invariant natural killer T cells, mucosa-associated invariant T cells and the Vδ1 and the Vδ2 subsets of γδ T cells—were extremely rare in cord blood and in peripheral blood of neonates, but they expanded after birth reaching highest levels in adulthood. Analysis of serum cytokine levels revealed that proinflammatory and T helper type 1 (Th1) cytokine levels increase in adulthood, whereas Th2 and Th17 cytokine levels remain relatively constant. These changes in lymphocyte numbers and cytokine levels across the lifetime are likely to affect immunocompetence, leaving newborn and elderly people susceptible to infection, cancer and immune-mediated disease. Full article

Aberrant signaling through damage-associated molecular patterns (DAMPs) has been linked to several health disorders, attracting considerable research interest over the last decade. Adenosine triphosphate (ATP), a key extracellular DAMP, activates the purinergic receptor P2X7, which acts as a danger sensor in immune cells and is implicated in distinct biological functions, including cell death, production of pro-inflammatory cytokines, and defense against microorganisms. In addition to driving inflammation mediated by immune and non-immune cells, the persistent release of endogenous DAMPs, including ATP, has been shown to result in epigenetic modifications. In intestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), consequent amplification of the inflammatory response and the resulting epigenetic reprogramming may impact the development of pathological changes associated with specific disease phenotypes. P2X7 is overexpressed in the gut mucosa of patients with IBD, whereas the P2X7 blockade prevents the development of chemically induced experimental colitis. Recent data suggest a role for P2X7 in determining gut microbiota composition. Regulatory mechanisms downstream of the P2X7 receptor, combined with signals from dysbiotic microbiota, trigger intracellular signaling pathways and inflammasomes, intensify inflammation, and foster colitis-associated CRC development. Preliminary studies targeting the ATP−P2X7 pathway have shown favorable therapeutic effects in human IBD and experimental colitis. Full article

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we present a literature review of gallbladder Burkitt’s lymphoma (BL) cases that includes also an unpublished case in an HIV-infected child, observed by our center. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy, and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. The patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. A biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH), especially in children. Full article

Background/Objectives: The diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) represent a significant challenge in oral medicine. Optical coherence tomography (OCT) shows promise for evaluating oral tissue microstructure but lacks standardized diagnostic protocols tailored to the structural variability and lesions of oral mucosa. Methods: This cross-sectional observational study aims to evaluate the diagnostic accuracy of targeted biopsy-based and site-coded OCT protocols for common OPMDs and OSCC. Adult patients clinically diagnosed with OPMDs, including oral leukoplakia (OL), oral lichen planus (OLP), and OSCC were enrolled. Clinical and OCT evaluation before and after punch scalpel-site registration preceding diagnostic biopsy on the target site was performed. Blinded observers analyzed the OCT scans for OCT-based diagnoses. Sensitivity, specificity, and diagnostic accuracy for OCT evaluations before and after punch scalpel-site registration were statistically compared with histological findings. Results: A dataset of 2520 OCT scans and 210 selected images from 21 patients was obtained. Sensitivity and specificity post-target site registration were high for OSCC (98.57%, 100.00%), OL (98.57%, 98.57%), and OLP (97.14%, 98.57%). The positive predictive values ranged from 97.14% to 100.00%, while negative predictive values ranged from 98.57% to 99.29%. Inter-observer agreements were strong for OSCC (0.84) and moderate for OL (0.54) and OLP (0.47–0.49). Targeted OCT scans significantly improved diagnostic accuracy for all conditions (p < 0.001). Conclusions: This preliminary study supports using site-targeted OCT scans followed by a site-targeted punch biopsy, enhancing precision in oral diagnostics. This approach is foundational for developing pioneering automated algorithms guiding oral cancer and pre-cancer diagnosis via OCT imaging. 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

Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut–brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut–brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels. Full article

Amaranthus hypochondriacus is rich in nutrients and represents a feed resource with significant potential. This experiment aimed to study the effects of different proportions of Amaranthus hypochondriacus stem and leaf powder (AHSL) on intestinal digestive enzyme activities, cecal volatile fatty acids, and the microbiota of broilers. A total of 288 one-day-old male broilers (Ross 308) were randomly assigned to the control diet group and the 3%, 6%, and 9% AHSL diet group for days 0–21. Subsequently, the 3%, 6%, and 9% AHSL diets were switched to 5%, 10%, and 15% AHSL diets for days 22–42. The results demonstrated that the dietary inclusion of AHSL significantly affected sucrase activity in the jejunal mucosa (p < 0.05). The 5% AHSL group exhibited the highest sucrase activity, followed by the control group, both of which showed significantly higher activity compared to the 10% and 15% AHSL groups (p < 0.05). The cecal pH in the 5%, 10%, and 15% AHSL groups was significantly lower than that in the control group (p < 0.05). The contents of acetate, propionate, butyrate, and valerate in the cecum of the 10% and 15% AHSL groups were significantly higher than those of the control group (p < 0.05). The addition of AHSL had no significant effect on the alpha diversity of cecum microorganisms. The relative abundance of Ruminococcaceae_UCG_005 and Lactonifactor was significantly higher in the 10% AHSL group compared to the control group, whereas the 15% AHSL group had a significantly higher relative abundance of Clostridium_sensus_tricto12, Peptoclostridium, Anaerofilum, and Peptococcaceae. In summary, the inclusion of 5% AHSL in the diet enhances sucrase activity in the jejunum of broilers, while 10% or 15% AHSL increases the volatile fatty acid content and reduces the pH value in the cecum, without adverse effects on the cecal microbiota. Full article

Crohn’s disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diagnosing CD is challenging and requires close collaboration between clinicians and pathologists due to the lack of specific diagnostic criteria. Histologically, CD is characterized by transmural inflammation, crypt distortion, metaplasia, and granulomas, although granulomas are not always present. Schaumann bodies (SB), initially described in sarcoidosis, are rare in CD but have been reported in about 10% of cases. This case report presents a 4-year-old female with chronic hemorrhagic diarrhea, severe anemia, and elevated inflammatory markers. Endoscopic and histological evaluations suggested CD, with the presence of SB in the gastric mucosa. Further investigations ruled out sarcoidosis, confirming a diagnosis of multi-segmental, very early onset CD with atypical histological features. SB are inclusions composed of calcium carbonate crystals and conchoid bodies, typically found within giant cells. The presence of SB in the mucosa is rare, limiting their diagnostic significance in endoscopic biopsies. Differential diagnosis should exclude other granulomatous diseases such as intestinal tuberculosis and sarcoidosis. This case highlights the importance of considering SB in the diagnosis of CD, particularly in pediatric patients. Full article