Intestinal Sites Research Articles

P0099 Histone H4 lysine 12 lactylation in CD4+ T cells promotes the progression of Ulcerative Colitis through PKM2/glycolysis loop and PKM2/STAT3 signaling pathway

Abstract Background Immune dysfunction- the imbalance of Th17/Treg ratio is the main pathogenic factor of ulcerative colitis (UC). Histone lactylation is a new protein modification and could regulate immune function. However, the roles of histone lactylation in the naïve CD4+ T cell differentiation and UC progression remain unclear. Methods We employed a mouse model to elucidate the mechanism by which lactic acid facilitates the progression of ulcerative colitis through the inhibition of PKM2 and targeted knockout of Pkm2 in CD4+ T cells. Results Our study shows a high level of H4K12la in CD4+ T cells at the intestinal inflammatory sites in UC, which is specifically enriched at the promoters of glycolytic genes including pyruvate kinase 2 (PKM2). Then PKM2 can activate the transcriptional activation protein 3 (STAT3) signaling pathway, thereby inducing the differentiation of naïve CD4+ T cells into Th17 cells and inhibiting Treg cell differentiation, and cause sustained release of pro-inflammatory cytokines, which finally exacerbates intestinal inflammation. In addition, as a key glycolysis enzyme, the upregulation of PKM2 expression could accelerate more lactate production in a positive feedback way. Both pharmacologic inhibition of PKM2 and CD4+ T cell-specific ablation of Pkm2 could block lactate production and then downregulate the ratio of Th17/Treg to alleviate colitis. Conclusion The study demonstrate the pro-inflammatory role of H4K12la in CD4+ T cells, and PKM2 may be a potential target for the treatment of UC.

Adhesive polyelectrolyte coating through UV-triggered polymerization on PLGA particles for enhanced drug delivery to inflammatory intestinal mucosa

Administering medication precisely to the inflamed intestinal sites to treat ulcerative colitis (UC), with minimized side effects, is of urgent need. In UC, the inflammation damaged mucosa contains a large number of amino groups which are positively charged, providing new opportunities for drug delivery system design. Here, we report an oral drug delivery system utilizing the tacrolimus-loaded poly (lactic-co-glycolic acid) (TAC/PLGA) particles with an adhesion coating by in situ UV-triggered polymerization of polyacrylic acid and N-hydroxysuccinimide (PAA-NHS). The negatively charged carboxyl groups effectively interact with the positively charged focal mucosa, and the NHS ester groups form the covalent bonds with the amino groups, thereby synergically enhancing the adhesion of the PLGA particles to the focal mucosa. Our findings reveal that, compared to the naked particles, the PAA-NHS coating increases the adhesion of particles to the inflammatory intestine. In a dextran sulfate sodium-induced acute colitis mouse model, the TAC/PLGA particles with PAA-NHS coating exhibits substantial retention of TAC within the inflammatory intestine, enhancing drug delivery efficiency and therapeutic effects. This approach holds promise for UC management, minimizing systemic side effects and optimizing therapeutic outcomes.Graphical abstract

Manipulated Slow Release of Florfenicol Hydrogels for Effective Treatment of Anti-Intestinal Bacterial Infections.

The difficulty of establishing slow release at intestinal infection sites, weak antibacterial effects, as well as the limited broad use of florfenicol oral formulations are the main targets of the current study. Novel hydrogels derived from sodium alginate were developed using a complexation form for florfenicol delivery to achieve slow release at the site of intestinal infection and enhance its antibacterial activity against Escherichia coli. The optimal formulation, physicochemical properties, stability, pH-responsive performance, antibacterial activity, and in vitro biosafety of the florfenicol hydrogels have been studied systematically. The created hydrogels had a consistent spherical morphology, with an average diameter of 531.9±12.6 nm. Energy dispersive spectroscopy and Fourier transform infrared indicated that florfenicol hydrogels have been successfully prepared through complexation force. Furthermore, it is shown that florfenicol hydrogels hold outstanding stability, excellent sustained release, and faster swelling and release at intestinal pH due to pH-responsiveness. The florfenicol hydrogels had no obvious structural destruction in simulated gastric juice (pH=1.2) for 12 hrs and were highly stable. However, the hydrogels began to be destroyed after 5minutes in simulated intestinal fluid (SIF), and this decomposition was continuous. With the decomposition of the structure of florfenicol hydrogels, the encapsulated florfenicol was also slowly released, and thus, it achieves the slow-release effect. Additionally, the florfenicol hydrogels showed a low hemolytic ratio and greater antibacterial activity compared with florfenicol. The blended formulation creates a promising oral matrix intended for the slow-release of florfenicol along the gastrointestinal tract.

Release-modulating mechanism and comparative pharmacokinetics in beagle dogs of bethanechol-loaded oral dosage forms.

Bethanechol chloride (BTC), a quaternary ammonium compound used in bladder dysfunction treatment, requires challenges in developing optimal oral dosage forms due to its high water-solubility, short half-life, rapid elimination and four times a day administration. The aim of this study was to develop optimal BTC-loaded oral dosage forms that could provide both rapid onset and sustained therapeutic effects while reducing the frequency of conventional four-times-daily dosing (Mytonin® tablets). Four different BTC-loaded oral dosage forms were designed including gastro-retentive tablet (GRT), controlled-release tablet (CRT), bilayer tablet (BLT), and tablet-in-tablet (TIT). Then, release-modulating mechanism and in vivo pharmacokinetics in beagle dogs were compared. The release profiles of the four BTC-loaded dosage forms varied according to system design and formulation composition. The optimized GRT F-5 showed rapid buoyancy within 15 s and floated for 12 h, while continuously releasing the drug. CRT showed Fickian diffusion release, whereas BLT and TIT exhibited biphasic immediate and sustained release profiles. Polymer swelling behavior was analyzed using the Vergnaud model, where GRT F-5 and CRT showed n values < 0.5, confirming diffusion-controlled polymer hydration mechanism. In the instrumental analysis, the hydrogen bonding formation of BTC with release-modulating polymers, such as hydroxypropyl methylcellulose and polyethylene oxide and loosening of the polymer structure was crucial as the water influx increased. In pharmacokinetic studies in beagle dogs, the area under the plasma concentration-time curve (AUC) by normalizing dose for 48 h for GRT, CRT, BLT, and TIT were 90.2 %, 108.6 %, 83.8 %, and 76.4 %, respectively, compared with that of the reference drug (Mytonin® tablets, immediate release, four times a day). Interestingly, the plasma maximum concentration (Cmax) and AUC)0-12h of GRT F-5 and and Mytonin® tablets for the first 12-h period were much higher compared with that of other BTC-loaded CRT, BLT, and TIT. BTC was absorbed throughout the gastrointestinal tract, but is preferably absorbed in the stomach and upper intestinal sites. However, the GRT F-5 could provide more therapeutic potential for improving patient compliance in bladder dysfunction treatment by achieving both rapid onset and sustained drug release with reduced dosing frequency.

Population genetics and molecular xenomonitoring of Biomphalaria freshwater snails along the southern shoreline of Lake Malawi, Malawi

BackgroundIntestinal schistosomiasis was confirmed endemic in Mangochi District, Malawi, in May of 2018 following an unexpected encounter with discreet populations of Biomphalaria spp. freshwater snails during routine malacological surveillance activities. Since then, only limited malacological surveillance of Biomphalaria has been carried out, and so the distribution of Biomphalaria populations in this area is currently unclear. Additionally, sites of active Schistosoma mansoni transmission in this area are also unknown. In the present study, through extensive malacological surveillance, we aimed to formally document the distribution of Biomphalaria in Mangochi District. We also aimed to identify active intestinal schistosomiasis transmission sites in this area through subjecting all collected Biomphalaria to a recently developed S. mansoni-specific molecular xenomonitoring PCR.MethodsThree malacological surveys were carried out along the southern shoreline of Lake Malawi, Mangochi District, Malawi, in November 2021, July 2022 and October/November 2022. All collected Biomphalaria were subjected to cercarial shedding analysis to identify active Schistosoma infections. Shed cercariae were then genotyped to species level using a standard multi-locus PCR and Sanger sequencing protocol. Following this, a subset of Biomphalaria from each collection site were also genotyped to species level using a standard PCR and Sanger sequencing protocol. All collected Biomphalaria were then subjected to a recently developed S. mansoni-specific molecular xenomonitoring PCR to identify infected, but non-shedding, Biomphalaria.ResultsA total of 589 Biomphalaria were collected across all three surveys. One single Biomphalaria (0.17%) specimen was found to be actively shedding Schistosoma cercariae, which were molecularly confirmed as S. mansoni. All genotyped Biomphalaria (n = 42) were molecularly identified as B. pfeifferi. A further 19 Biomphalaria specimens, collected from four different surveillance sites, were found to be infected with S. mansoni through molecular xenomonitoring. Intestinal schistosomiasis transmission was therefore identified at four different foci in Mangochi District.ConclusionsOur study highlights the importance of molecular approaches to investigate Biomphalaria populations and monitor Biomphalaria-associated intestinal schistosomiasis transmission in endemic areas. As such, the continued development and use of such approaches, in particular the development and use of molecular xenomonitoring assays that can be carried out in resource-poor schistosomiasis-endemic settings, is encouraged. The revision of ongoing schistosomiasis control programmes in Mangochi District, in line with WHO recommendations, is also encouraged.Graphical abstract

Initial pig developmental stage influences intestinal organoid growth but not cellular composition.

Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig. Organoids were derived from jejunal and colonic ISC obtained from 1-, 7-, 28-, 36- and 180-day-old pigs and passaged three times. We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (p < 0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, p < 0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (p < 0.05), spheroids were larger during the primary culture but smaller after two passages (p < 0.05) and organoids were smaller after one passage (p > 0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) was observed between organoids originating from 7- or 180-day-old pigs, but differences between intestinal site origins were noticed. In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence the phenotype.

Investigation and evaluation of gastrointestinal toxicity biomarkers in rats with different sites of gastrointestinal injury

There are few reliable biomarkers for gastrointestinal toxicity, and the further identification of such markers can improve the accuracy and speed of toxicological evaluations. This study aimed to evaluate the effectiveness of several recently proposed biomarkers—plasma citrulline, fecal calprotectin, fecal bile acid, and plasma miRNAs (miR-194 and -215)—in detecting intestinal toxicity. To this end, cysteamine hydrocholoride (cysteamine, 600 or 900 mg/kg, PO), indomethacin (10 mg/kg, PO), or 2,4-Dinitrobenzenesulfonic acid hydrate (DNBS, 20 mg/kg, IR) were administered to male Wistar rats to establish models of gastric/duodenal, jejunum/ileum, or colonic damage, respectively. Both novel biomarkers and traditional toxicological parameters were evaluated in these rat models. Standard in-life observations, such as fecal properties or body weight, were inadequate for monitoring intestinal toxicity, as there were few observable changes indicative of intestinal injury, especially in the cysteamine and indomethacin models. Plasma citrulline drastically decreased in cysteamine or indomethacin-treated rats, with a milder decrease in DNBS-treated animals. Fecal total bile acids and calprotectin levels increased only in rats treated with indomethacin or DNBS, but not with cysteamine. While plasma miR-194 remained unchanged across all models, miR-215 levels decreased after cysteamine treatment. Together, these results suggest that plasma citrulline and fecal calprotectin may be effective biomarkers for monitoring intestinal injury. Fecal TBA and plasma miR-215 also show potential as useful biomarkers, but further research is needed to confirm their efficacy. Specifically, plasma citrulline is indicative of damage from the stomach to the ileum, fecal total bile acids and calprotectin are indicative of damage from the jejunum to the rectum, and plasma miR-215 is indicative of damage from the stomach and the duodenum. Integrating these novel biomarkers with standard toxicological parameters will help in predicting actual intestinal sites of damage. This integration has the potential to improve the quality of toxicological evaluations. Our findings support the use of these biomarkers in clinical settings.

Aonchotheca annulosa and Aonchotheca murissylvatici, which is which? A reappraisal of the gastrointestinal Aonchotheca (Nematoda: Capillariidae) species common in wood mice and bank voles.

Wood mice (Apodemus sylvaticus) and bank voles (Myodes glareolus) are often employed as natural study models in infectious disease ecology. Yet the identities of some elements of their parasite fauna have been subject to long-standing confusion. One instance of this relates to 2 nominal species of the capillariid nematode genus Aonchotheca: Aonchotheca annulosa (Dujardin, 1845) and A. murissylvatici (Diesing, 1851). Through literature review, analysis of recorded host- and site-specificity and tracing of taxonomic precedence, it is possible to confirm that A. annulosa is a valid species with a spicule c. 1000 microns long, a small intestinal site of infection and a wide host range centred in murine rodents (with A. sylvaticus the most common host). On the other hand, tracing the provenance of A. murissylavtici through to the works of the early naturalists reveals it is best assigned as a nomen nudum (lacking sufficient establishing description) or a junior synonym of A. annulosa and does not have precedence for the other Aonchotheca morphotype commonly found in Eurasian rodents. The first description consonant with this other morphotype, which has a short spicule (200–250 microns in length) and occurs primarily in the stomach of bank voles and other cricetids, was as Capillaria halli by Kalantarian in 1924. We thus recommend the suppression of A. murissyvatici in favour of Aonchotheca halli (Kalantarian, 1924) for this gastric-specialist short-spicule morphotype, particularly as the use of the A. murissylvatici name and its variants has previously been associated with substantial inconsistency and misidentification with A. annulosa.

Intestinal incision site infections: Evaluation of antimicrobial-coated vicryl sutures in preventing postoperative infections

This research focused on the development of an antimicrobial polymeric composite coating of polyethylene glycol (PEG) infused with zinc oxide nanoparticles (ZnO) and herbal extracts from Curcuma longa (turmeric). The synthesized composite is coated on a biodegradable vicryl suture via the dip coating method. Instrumental characterization, including Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), was utilized to confirm the chemical composition and surface of the coated suture. The antimicrobial activity was evaluated against bacterial pathogens, Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). The water contact angle was measured to determine surface wettability. Degradation studies were conducted in simulated intestinal fluid (SIF) to determine the coated suture’s longevity.

Advances in Yeast Probiotic Production and Formulation for Preventative Health.

The use of probiotics has been gaining popularity in terms of inclusion into human diets over recent years. Based on properties exerted by these organisms, several benefits have been elucidated and conferred to the host. Bacteria have been more commonly used in probiotic preparations compared to yeast candidates; however, yeast exhibit several beneficial properties, such as the prevention and treatment of diarrhea, the production of antimicrobial agents, the prevention of pathogen adherence to intestinal sites, the maintenance of microbial balance, the modulation of the immune system, antibiotic resistance, amongst others. Saccharomyces boulardii is by far the most studied strain; however, the potential for the use of other yeast candidates, such as Kluyveromyces lactis and Debaryomyces hansenii, amongst others, have also been evaluated in this review. Furthermore, a special focus has been made regarding the production considerations for yeast-based probiotics and their formulation into different delivery formats. When drafting this review, evidence suggests that the use of yeasts, both wild-type and genetically modified candidates, can extend beyond gut health to support skin, the respiratory system, and overall immune health. Hence, this review explores the potential of yeast probiotics as a safe, effective strategy for preventative health in humans, highlighting their mechanisms of action, clinical applications, and production considerations.

Neutrophil Hitchhiking Enhances Liposomal Dexamethasone Therapy of Sepsis.

Sepsis is characterized by a dysregulated immune response and is very difficult to treat. In the cecal ligation and puncture (CLP) mouse model, we show that nanomedicines can effectively alleviate systemic and local septic events by targeting neutrophils. Specifically, by decorating the surface of clinical-stage dexamethasone liposomes with cyclic arginine-glycine-aspartic acid (cRGD) peptides, we promote their engagement with neutrophils in the systemic circulation, leading to their prominent accumulation at primary and secondary sepsis sites. cRGD-targeted dexamethasone liposomes potently reduce immature circulating neutrophils and neutrophil extracellular traps in intestinal sepsis induction sites and the liver. Additionally, they mitigate inflammatory cytokines systemically and locally while preserving systemic IL-10 levels, contributing to lower IFN-γ/IL-10 ratios as compared to control liposomes and free dexamethasone. Our strategy addresses sepsis at the cellular level, illustrating the use of neutrophils both as a therapeutic target and as a chariot for drug delivery.

In Vivo tissue healing mechanism at the intestinal anastomosis site following high-frequency electric welding.

To investigate the effect of High-Frequency Electric Welding (HFEW) on intestinal tissue healing, we performed end-to-end anastomosis experiments in New Zealand rabbits. Within one week post-surgery, animals exhibited normal vital signs, replaced necrotic tissue with healthy collagen, and showed improved tissue strength while inflammation decreased. By day 60, tissue pathology and function fully recovered, resembling normal tissue. Healing at the anastomotic site occurred in three phases: immediate adhesion, inflammation, and remodeling, with macrophages crucial for phagocytosis and regeneration of necrotic tissue. This study enhances understanding of HFEW's healing mechanisms and supports further preclinical investigations.

The intestinal microbiome, but not clinical aspects of inflammatory bowel disease, is impacted by lactose malabsorption compared to lactose digestion in children

BackgroundDietary exclusion of lactose from patients with inflammatory bowel disease (IBD) persists with speculation that deleterious effects are mediated through intestinal microbes. ObjectivesTo compare IBD characteristics and changes in the intestinal microbiome (IM) at diagnosis in children with and without lactose malabsorption (LM). MethodsA cross-sectional cohort of children (8–17 y of age) diagnosed with Crohn’s disease [n = 149 (63%)] or ulcerative colitis (n = 86) that had undergone lactose breath hydrogen testing was evaluated. The IM of mucosal luminal aspirates was profiled at the time of diagnosis using 16S ribosomal ribonucleic acid gene amplicon sequencing of the V6 hypervariable region. ResultsOf the 235 children, 61 (26%) had LM. Microbial characterization yielded differences in bacterial differential abundance between children who could and could not absorb lactose, which varied by intestinal site and between subtypes of IBD. There were no differences in the ages [13.2 ± 3.0 y (mean ± standard deviation) compared with 12.7 ± 3.4 y; P = 0.25], sex (P = 0.88), extent of disease involvement or severity of disease at presentation (P = 0.74) when comparing those that could or could not absorb lactose nor was there a difference in the need for initiation of biological agents (P = 0.43) during 2 y of follow-up. ConclusionsLM does not affect the clinical presentation or outcomes of children with IBD. However, this study establishes that a single nonabsorbed fermentable food product can alter the IM in both a regional and disease-specific manner. As we continue to learn more about the pathophysiology of IBD and the role of the IM in disease onset and progression, it would be of benefit to examine the impact of other potential fermentable nutrients and their products on IBD outcomes.

Evaluation of early and systematic ultrasound examination to determine postoperative dehiscence after small intestinal surgery (114 cases in dogs and cats).

To evaluate the feasibility and reliability of early ultrasound diagnosis for postsurgical bowel dehiscence and find the most reliable ultrasound criteria for dehiscence identification. Additionally, to determine the impact of early ultrasound detection of leakage in terms of survival and duration of hospitalization. Finally, to assess the need for systematized screening or checkup of the population at risk of dehiscence only. 31 cats and 83 dogs. A retrospective, records-based study was performed on 83 dogs and 31 cats (114 total) undergoing small intestinal surgery. Epidemiologic data, clinical signs, surgical procedures, pre- and postoperative ultrasound findings at 48 to 96 hours, hospitalization duration, complications, and general outcomes were recorded. Univariate and multivariate analyses were used to identify ultrasound findings associated with dehiscence. Dehiscence was suspected by ultrasound for 0 of 31 cats and 7 of 83 dogs (2 of 49 for enterotomy and 5 of 34 for enterectomy). Every suspected dehiscence was confirmed during revision surgery except one enterectomy revision, which was declined by the owner. Neither this case nor those without ultrasound evidence of dehiscence developed clinical signs of intestinal leakage. Direct visibility of wall discontinuity, presence of gas bubbles, and liquid in vicinity of the intestinal surgical site were statistically associated with early dehiscence. Survival rate after the second surgery was 83%. Median hospitalization time after the second surgery for dehiscence was 2 days (minimum, 2 days; maximum, 4 days). Postoperative ultrasound examination between 48 and 96 hours after intestinal surgery allows early and sensitive detection of intestinal dehiscence. Survival rate after revision surgery was significantly higher than that associated with septic peritonitis.

Microbial diversity and biogeography across gastrointestinal tracts of Takifugu pufferfish revealed by full-length 16S amplicon sequencing

Fish, which are vital for both aquatic ecosystem functionality and global food supply, rely heavily on their gastrointestinal tract (GIT) microbiota for the digestion that underpins their growth and health. Takifugu pufferfish, which are an example of species evolved through adaptive radiation, possess a GIT that is specialized for antipredator defense and gluttonous feeding behaviors, offering a unique model to explore the effects of GIT compartmentalization and host genetics on gut microbial communities. Here we compiled 78 full and partial-length 16 ​S rRNA amplicon datasets across three anteroposteriorly distinct intestinal sites in a cohort of cohabitating artificial hybrid and purebred Takifugu pufferfishes. Our findings reveal a compositional and functional biogeography of pufferfish gut microbiota along the GIT and between host genetics. Additionally, the differential abundance of specific amplicon sequence variants and their correlation with host genetic backgrounds and intestinal sections highlight the role of environmental filtering in shaping microbial communities, with certain bacterial taxa exhibiting strong preferences for particular intestinal sites or genetic backgrounds, suggesting potential localized adaptation or functional specialization. This study enhances our understanding of the intricate interplay between host genetics, gut anatomy, and microbiota in fish, underscoring the importance of detailed microbial profiling in conservation efforts and aquaculture practices, and emphasizing the necessity of integrating full-length 16 ​S rRNA sequencing with partial-length datasets to comprehensively understand microbial diversity and function, paving the way for improved fish health management and sustainable aquaculture strategies.

Co-delivery of novel valsartan and hydrochlorothiazide pH-responsive electrospun polymeric nanofibers for improved oral delivery

Valsartan (VAL) and Hydrochlorothiazide (HCTZ) as a fixed-dose combination are widely used for the management of hypertension. To enhance the dissolution and oral delivery of VAL (BCS class II drug) and HCTZ (BCS class IV drug), nanofibers containing both drugs were prepared using an electrospinning technique. VAL/HCTZ-loaded NFs were prepared using Eudragit L100-55 (EUD L100-55) and Poly (ethyne oxide) (PEO) polymer mixture and the formulation process was optimized through three process variables of polymer composition, polymer concentration, and spinning voltage. VAL/HCTZ-loaded NFs were characterized for their size, surface morphology, entrapment efficiency (%EE), drug-polymer interaction, in vitro drug release, ex-vivo permeation, and in vivo studies. Smooth, beadles and uniform drug-loaded NFs were successfully fabricated using optimum polymer composition (EUD L100-55/PEO 3:1), concentration (12 % w/v), and applied voltage (30 KV). The optimum formula (F9) showed a low average nanosize of 300 nm and a high drug loading of > 90 % was achieved. In vitro, release results showed a pH-dependent drug release, with minimum drug released at pH lower than 4.5, but a significant and complete release of both drugs was achieved at pH 6.5. The EUD L100-55/PEO improved the dissolution of VAL and HCTZ compared to free drugs at the intestinal site of absorption. Differential Scanning calorimetry and Fourier Transform Infra-Red studies showed both drugs’ amorphization and compatibility between drugs and polymers. Permeability behavior for the VAL/HCTZ-loaded NFs was found to be significantly higher than free drug suspensions of both drugs which indicated the improvement of VAL and HCTZ permeability through the intestinal membrane. The in vivo study proved the enhanced oral anti-hypertensive action of drugs-loaded NFs compared to free drug suspensions. The superior in vitro release, ex-vivo permeation, and in vivo anti-hypertensive effect indicate that drug-loaded nanofibers have the potential to improve the biological activity and hence oral delivery of the fixed-drug combination.

Technetium-99m radiolabeling of graphene quantum dots (GQDs) as a new probe for glioblastoma tumor imaging

Purpose Cancer diagnosis involves a multi-step process. Accurate identification of the tumor, staging and development of cancer cells is crucial for selecting optimal treatments to minimize disease recurrence. Quantum dots (QDs) represent an exciting class of fluorescent nanoprobes in molecular detection and targeted tumor imaging. Materials and methods In this study, graphene quantum dots (GQDs) were synthesized by pyrolysis of citric acid (CA) as a carbon precursor under high temperatures. The morphology of the obtained GQDs was first characterized using physical (TEM and DLS) and spectroscopic (fluorescence, FTIR and UV–Vis) methods. In the following,99mTc-labeled GQDs were prepared in the presence of SnCl2.2H2O as a reducing agent between 95 and 100 °C. The biodistribution and tumor targeting efficiency of radiolabeled GQDs as a novel agent for C6 glioma tumor scintigraphy in an animal model were evaluated. Furthermore, organ uptake, human serum albumin binding and tumor accumulation were measured. Results The TEM image of the prepared GQDs showed a relatively uniform size distribution in the range of diameter 6-9 nm and spherical shape. Radiolabeled GQDs showed a radiochemical yield of >97% (n = 3). Through incubation in human serum, almost 15% of 99mTc-labeled GQDs degraded after 6 h. The amount of uptake in xenograft models of glioma C6 rats was 1.10 ± 0.36% of injection dose per gram after 1 h. The kidneys, intestinal and glioma tumor sites were observed via scintigraphy imaging. Conclusion Our data suggest that 99mTc-labeled GQDs, as a new radiotracer, efficiently accumulate in the tumor site and could be included as a radiotracer for detecting glioma tumors.

Food antigens suppress small intestinal tumorigenesis.

Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using Apcmin/+ mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer's patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.

Enteric-coated cerium dioxide nanoparticles for effective inflammatory bowel disease treatment by regulating the redox balance and gut microbiome

Reactive oxygen species (ROS) play crucial roles in the pathogenesis of inflammatory bowel disease (IBD) by disrupting the mucosal barrier and subsequently leading to the dysregulation of the gut microbiome. Therefore, ROS scavengers present a promising and comprehensive strategy for the effective IBD treatment. In the current work, we explored the therapeutic potential of cerium dioxide (CeO2) nano-enzyme, which is well-known for their potent antioxidant properties and capability to mimic natural antioxidant enzymes in the regulation of oxidative stress. We developed a novel enteric-coated nanomedicine (CeO2@S100) aiming at improving the oral delivery efficacy of CeO2 in the complex gastrointestinal environment. CeO2@S100 is composed of a CeO2 nanoparticle core and a protective polyacrylic acid resin shell (Eudragit S100), ensuring targeted delivery of the core specifically at inflamed intestinal sites due to the negative surface charge. In vivo experiments revealed CeO2@S100 significantly alleviates the IBD by balancing oxidative stress and regulating gut microbiota in a dextran sulfate sodium-induced mouse colitis model. The uncomplicated synthesis of CeO2@S100 highlights its promise for clinical use, presenting an effective and safe approach to managing IBD.

Pathological Findings in the Carcass of a Dog following Ovariohysterectomy, and Intestinal Resection and Anastomosis

This report presented the gross and histopathological findings in the carcass of a Nigerian Indigenous Dog (NID) following ovariohysterectomy, intestinal resection and anastomosis. The carcass of a 9-month-old NID was presented to the Necropsy Unit of the Veterinary Teaching Hospital, Ahmadu Bello University Zaria, Nigeria. History was obtained, general examination of the carcass and necropsy were conducted. History revealed sudden death 2 days post-abdominal surgical procedures (ovariohysterectomy, and small intestinal resection and anastomosis). The clinical signs observed before death were weakness and dyspnea, while mild tick infestations and bilateral congested ocular mucus membranes were on general examination of the carcass. The gross pathological findings were hemorrhagic trachea, congested and hemorrhagic lungs, enlarged heart with epicardial and endocardial hemorrhages, enlarged and congested liver, enlarged spleen, hemorrhage in the gastric mucosa, intestinal hemorrhages, and an area of hemorrhagic infarct at the intestinal anastomosed site. On histopathological examination, there was slightly thickened interalveolar walls with inflammatory cellular infiltrations, cardiac hemorrhage, and hepatic congestion. These gross and histopathological findings suggest possible systemic complications, thus, emphasizing the importance of comprehensive pre-operative assessment, and post-operative care and monitoring in veterinary surgeries.