Intestine Organs Research Articles

Acquisition of innate B cell properties and generation of autoreactive IgA antibodies by follicular B cells during homeostatic proliferation

The physiologic process of homeostatic proliferation serves to restore the pool of peripheral lymphocytes in response to lymphopenia. However, functional changes in B cell responses during homeostatic proliferation are still only insufficiently characterized. Mature peripheral B cells consist of functionally distinct B cell subsets, such as adaptive follicular B cells (FoBs) and the innate B cell subsets, marginal zone B cells (MZBs) and B1a B cells. During homeostatic proliferation, B cells undergo antigen-independent clonal expansion and differentiation into antibody-producing plasma cells (PCs). However, it is still largely unknown which B cell lineages are involved in the formation of antibodies in response to lymphopenia and what functional properties these antibodies have. Employing adoptive transfer of different mature B cell subsets into lymphopenic Rag2-/- hosts, we here show that not only innate B cells – MZBs and B1a cells – but also adaptive FoBs were capable to differentiate into PCs and to produce IgM and class-switched IgA serum antibodies in a T cell-independent fashion during homeostatic proliferation. In light of the poor reactivity of FoBs to innate stimulation in vitro, the observed high expansion capacity of FoBs, their sustained repopulation of lymphoid and intestinal organs and their particularly prominent ability to induce class-switched auto-/polyreactive IgA antibodies in this antigen- and T cell-independent system was rather unexpected. These properties, which are more typical for innate B cells, were associated with a striking plasticity of FoBs that transdifferentiate into MZB-like cells under lymphopenic conditions. Together, our study indicates that the reconstitution of antibodies in response to lymphopenia-induced homeostatic B cell proliferation is mainly elicited by innate MZB-like B cell responses via antigen- and T cell-independent pathways resulting in the selection of autoreactive IgA antibodies. In addition, our data point to the pathogenic potential of the conversion of conventional adaptive B cells, which are the most common population of mature B cells, into innate-like B cells and the production of autoreactive IgA antibodies during homeostatic proliferation. This process could also manifest as clinical complication of therapy-induced lymphopenia in the context of transplantation and cancer in human patients.

Potential Impact of Probiotics on Human Health and Prospects in Clinical Application

This article discusses the detailed effects of probiotics and the potential uses in curing diseases. Research shows that certain living organisms can bring about the following benefits for man; they help maintain the ratio of the good bacteria in the intestines, improve the immune system, reduce allergic reactions, aid intestinal movement and digestion. On the other hand, probiotics may also help to modulate emotions, cognition, and stress by influencing the communication between the gut-brain axis and neurotransmitter. Furthermore, the identified probiotic metabolites, the short-chain fatty acids, are involved in metabolic processes within the intestine and other organs. Probiotics also have some anti-cancer, anti-disease and anti-inflammatory effects, and can suppress pathogens and inflammation by affecting immune cells. This article also discusses the link between probiotics in the intestinal and nervous system diseases and chronic diseases and their roles in future medical science and clinical practice. Most of the current research work is done on probiotics is done in vitro and animal studies and future clinical study has to be undertaken to ascertain their mechanisms and effectiveness in human beings.

IDENTIFICATION OF Anisakis simplex IN PURPLE SPOTTED BIG EYE FISH (Priacanthus sp.) FROM SOUTH BALI WATER AREA

Anisakis simplex infection in fishery products can be dangerous because it has zoonotic can transmitted infection from fish to humans. Purple spotted big eye fish (Priacanthus sp.) is one of the reef fish species produced in the waters of South Bali and is not immune to the zoonotic threat Anisakis simplex poses. This study was conducted to identify Anisakis simplex which is known to infect Purple Spotted Big Eye Fish (Priacanthus sp.) in the South Bali Water Area. The parameters observed in this study were related to the prevalence and intensity of Anisakis simplex in Purple Spotted Big Eye Fish (Priacanthus sp.). The research method used was descriptive quantitative with purposive sampling of fish samples. The samples used were 30 fish obtained from 15-20% of the catch of purple spotted big eye fish in the South Bali Water Area. The results of the study showed that the morphological identification that had been carried out showed that Anisakis simplex found to infect Purple Spotted Big Eye Fish (Priacanthus sp.) was an Anisakis simplex type III larva with a prevalence rate of 26.3% classified as a frequent infection. The intensity value of Anisakis simplex in this study was 4.92 ind/fish and was classified as a low category. The predilection from this study showed that the most infections were in the intestinal organs.

Quantification of Salmonella enterica serovar Typhimurium Population Dynamics in Murine Infection Using a Highly Diverse Barcoded Library.

Salmonella is a prevalent food-borne pathogen that infects hundreds of millions of people worldwide. Here, we created a highly complex barcoded Salmonella enterica serovar Typhimurium library containing ∼55,000 barcodes to further understand and quantify Salmonella population dynamics in experimental murine infection. Through comparisons of barcode abundance and frequency in different samples and following different routes of inoculation, we quantify key facets of Salmonella infection, including bottleneck sizes and dissemination patterns, and uncover hidden routes of spread that drive heterogeneity in infection outcome. These observations provide a detailed map of Salmonella infection and demonstrate the power of high-diversity barcoded libraries in deciphering microbial population dynamics.

Gut microbiota profiles of patients with idiopathic pulmonary fibrosis.

Purpose/Aim: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia. Multiple genetic factors, environmental exposures, micro-aspirations secondary to gastroesophageal reflux, age, sex, smoking habit, and infections contribute to its etiology; consequently, its pathogenesis remains unclear. The homeostasis of gut microbiota, including bacteria, archaea, and fungi, can influence the functions of both the intestine and remote organs. There are still many unknowns regarding the effects and mechanisms of gut microbiota dysbiosis on the development of IPF. In this study, we aimed to characterize the gut microbiota of patients with IPF compared with that of healthy controls. Furthermore, we assessed the effects of antifibrotic drugs on gut dysbiosis. Materials and Methods: This study involved 12 patients with IPF receiving antifibrotic drug therapy, 12 patients with IPF not receiving antifibrotic drug therapy, and 8 healthy controls. The clinical parameters of the patients were recorded, and DNA extracted from stool samples was subjected to 16S ribosomal RNA gene sequencing of the V1-V9 hypervariable regions. Results: Campylobacterota species were detected in the patient groups but not in the control group. Staphylococcales and Gemellaceae species were not detected in the IPF groups; however, a significant relationship was observed in the control group. In the IPF groups, Actinobacteria, Bifidobacteriales, Burkholderiales, Bacteroidaceae, Dorea, Fusicatenibacter, and Ruminococcus -gauvreauii abundance was low and Enterobacterales, Erysipelotrichaceae, Holdemanella, and Alloprevotella abundance was high compared with those in the control group. When the IPF group using antifibrotic drugs and that not using antifibrotic drugs were compared, only Lachnospiraceae UCG 004 abundance was found to be lower in the patient group receiving antifibrotic drugs. Conclusions: Patients with IPF exhibit higher or lower abundance of certain taxa compared to healthy controls, providing novel perspectives on the pathogenesis and treatment of various illnesses. Examining changes in intestinal microbiota during treatment may guide the clinical strategy for managing adverse effects.

Molecular Dynamics and Spatial Response of Proliferation and Apoptosis in Wound Healing and Early Intestinal Regeneration of sea cucumber Apostichopus japonicus

The sea cucumber, Apostichopus japonicus, exhibits significant regenerative capabilities. To ensure survival and reduce metabolic costs under adverse conditions, A. japonicus can expel intestine, respiratory trees and other internal organs. It takes only 14 days to regenerate a fully connected, lumen-containing intestine. Despite numerous reports characterizing the cellular events in intestinal regeneration, limited investigation has been conducted on the molecular events that occur during wound healing and the initial stages of regeneration after evisceration. Here, we identified differentially expressed genes (DEGs) during wound healing (6 hours post-evisceration, Aj6hpe) and early intestinal regeneration (Aj1dpe, Aj3dpe, Aj7dpe). Cell proliferation and apoptosis were detected by EdU and TUNEL assays, respectively. Results demonstrated that calcium ion and neuroactive ligand-receptor interaction were involved in the transmission of injury signals from evisceration to Aj1dpe. The main events occurring in the wound healing and early regeneration process were autophagy, apoptosis, dedifferentiation, migration and shutdown of feeding. Cell proliferation was primarily observed during the lumen formation stage. Maximal number of apoptotic cells were found during wound healing stage (6 hpe - 1 dpe). Consequently, the immune response is mainly mobilized by neural regulation after evisceration. Our findings bridge the gap between evisceration and regeneration, illuminating the molecular events that mediate damage response and initiate regeneration. This study significantly advances our understanding of the mechanisms underlying intestinal regeneration.

Анализ заболеваемости солидными злокачественными новообразованиями в Уральской когорте потомков облученного населения

Purpose: The study of regularities in the incidence of solid cancer in the Urals Cohort of the Exposed Population Offspring over a 65-year follow-up period. Material and methods: The study was conducted by cohort method. The cohort under study is the Urals Cohort of the Exposed Population Offspring. It includes offspring of the population exposed in the period from 1950 to 1960 in the Southern Urals (on the Techa River and at the East Urals radioactive trace). The catchment area includes 5 districts of the Chelyabinsk region, as well as the city of Chelyabinsk and the city of Ozyorsk. The follow-up period was 65 years, from 01.01.1956 to 31.12.2020, the number of the analytical cohort for 2024 is 24952 people, the number of person-years under follow-up is 850698. Calculation of cases, incidence rates, person-years and statistical processing of data were performed by standard methods using the DATAB program module of the Epicure statistical package. Results: During the 65-year period, 569 cases of solid cancers were registered in the catchment area. In women the most frequent cases were neoplasms of female reproductive organs, breast, thyroid gland, whole intestine and upper digestive tract organs; in men - respiratory organs, upper digestive tract and whole intestine. A significant increase in the incidence rates was found in women in age groups older than 20 years and in men in groups older than 30 years. Statistically significant sex-depended differences were observed only in the age groups between 30 and 50 years. No significant differences in the incidence rates among offspring of different ethnic groups were found. An assessment of incidence rates by calendar periods was carried out: in women, a significant increase in incidence rates began in 1990, in men in 2005 and significant differences by sex were observed only in the period from 2005 to 2020. Conclusion: The study revealed patterns in the incidence of solid malignant neoplasms within the offspring cohort by sex, age and depending on the calendar period. These patterns will be taken into account in future studies when assessing the dependence of the incidence of solid malignant neoplasms in offspring on parental gonadal dose.

Endothelial RIPK3 minimizes organotypic inflammation and vascular permeability in ischemia-reperfusion injury.

Recent studies have revealed a link between endothelial receptor-interacting protein kinase 3 (RIPK3) and vascular integrity. During mouse embryonic development, hypoxia can trigger elevated endothelial RIPK3 that contributes to lethal vascular rupture. However, it is unknown whether RIPK3 regulate endothelial barrier function in adult vasculature under hypoxic injury conditions such as ischemia-reperfusion (I/R) injury. Here we performed inducible genetic deletion of endothelial Ripk3 (RipkiECKO) in mice, which led to elevated vascular permeability in the small intestine and multiple distal organs after intestinal I/R injury. Mechanistically, this vascular permeability correlated with increased endothelial secretion of IL-6 and organ-specific expression of VCAM-1 and ICAM-1 adhesion molecules. Circulating monocyte depletion with clodronate liposomes reduced permeability in organs with elevated adhesion molecules, highlighting the contribution of monocyte adhesion and extravasation to RipkiECKO barrier dysfunction. These results elucidate mechanisms by which RIPK3 regulates endothelial inflammation to minimize vascular permeability in I/R injury.

The structure of parastomal complications, predictors of their development: regional experience of the Center of Coloproctology of the Surgut District Clinical Hospital

Objective: to study the structure of parastomal complications and predictors of their development in patients with intestinal stoma.Materials and methods: a single-center retrospective analysis of the treatment results of 770 (100.0%) patients with colostomy and ileostomy observed in 2019–2023 in the District Center of Coloproctology of the Surgut District Clinical Hospital was carried out. There were 353 (45.8%) women and 417 (54.2%) men in the study group. The average age was 62 (55–68) years. The causes of the stoma were: malignant tumors of the intestine and pelvic organs in 617 (80.1%) patients, benign diseases of the abdominal cavity and pelvis in 153 (19.9%) patients.Results: parastomal complications were detected in 457 (59.4%) people. The most common skin complication is maceration – it was noted in 111 (24.3%) people. The most common complication in the postoperative period was the formation of a parastomal hernia in 142 (31.1%) patients. The average age of people with stoma complications was 63 [56; 69] years (p = 0.003). In addition, it was found that a statistically significant risk factor for complications in the analyzed group was the presence of a loop stoma (p = 0.018). The chances of complications in the group of patients with a loop stoma were 1.511 times higher, the odds differences were statistically significant (95% CI: 1,071–2,131).Conclusions: parastomal complications develop in 59.4% of patients. The most common complications associated with the presence of a stoma develop in persons of both sexes over the age of 63, more oſten in patients with a loop stoma.

EFFECT OF ADDING BIOACTIVE COMPOUNDS FROM BROWN ALGAE (Sargassum sp.) IN FEED ON INTESTINE AND LIVER HISTOLOGY OF SIAM PATIN FISH (Pangasius hypopthalmus) SEEDS

Addition of Sargassum sp. into feed as a feed supplement is one effort that can be done to increase fish growth and immunity. This research aims to determine the effect of adding bioactive compounds from Sargassum sp. extract in feed on the health picture of Siamese catfish through structural changes that occur in the intestines and liver. Fish observations were carried out for 40 days. The results obtained regarding the survival rate (SR) value of Siamese catfish seeds show that there is no difference or has the same percentage, namely 100%. The results of observations on the histopathology of intestinal organs analyzed in a comparative descriptive manner showed that Siamese catfish fry were fed with Sargassum sp. extract experienced damage than fish seeds fed without the addition of Sargassum sp. extract (control). The damage that occurs includes leukocyte infiltration (IfL), necrosis (Ne), goblet cell proliferation (Psg), hyperplasia (Hpl), and hemorrhage, with a damage score analyzed using the semiquantitative scoring method, namely 1. Damage to the liver, namely experiencing congestion in the blood vessels.

Performance, egg quality and organ traits of laying hens fed black soldier fly larvae products

Due to consumer demands and institutional pressure, the egg production sector, is looking for alternative protein sources for laying hen feed to support more sustainable, circular production. black soldier fly (BSF) larvae could be used as a protein source. In addition to protein the larvae contain large quantities of fat and can either be fed to laying hens unprocessed (alive) or processed (meal and oil). The current study was performed with 560 Brown Nick laying hens from 20 to 27 wk of age. The laying hens were divided over 5 treatments, each replicated 8 times. Treatments consisted of standard laying hen feed (control) and standard feed in which soybean meal was partly exchanged with live BSF larvae or BSF larvae meal and oil combined, at 2 inclusion levels. During the experiment production parameters, egg-quality, and length and weight of various organs were measured. Laying hens fed BSF larvae products consumed less feed compared to those of the control group. Most egg production parameters were similar, however laying hens fed diets with BSF larvae meal plus oil produced eggs with lower egg weight during the last 2 wk of the experiment, compared to the control group. All egg-quality characteristics remained the same across treatments, except for darker yolk colors when feeding BSF meal and oil and high inclusion of live BSF larvae. This is a favorable characteristic for European consumers. The weight of intestinal organs was largely unaffected by the treatments. The jejunum and ileum weight of laying hens fed live larvae was lower compared to the control group. As FCRs were similar or improved compared to the control group, we assume that nutrient utilization was not impaired. For most detected differences the type of BSF larvae product (live larvae or meal plus oil) rather than inclusion level was of significance.

WTAP promotes the progression of ulcerative colitis by silencing the expression of CES2 through m6A modification

ObjectiveThis study will explore the function of WTAP, the critical segment of m6A methyltransferase complex, in UC and its regulation on immune response. MethodsThe expression levels of key proteins were detected in colon tissues which were derived from UC patients and mice. Macrophage polarization and CD4+ T cell infiltration were detected by flow cytometry and IF staining. ELISA assay was utilized to analyze the level of the inflammatory cytokines. m6A-RIP-PCR, actinomycin D test, and RIP assays were utilized to detect the m6A level, stability, and bound proteins of CES2 mRNA. A dual luciferase reporter assay was conducted to confirm the transcriptional interactions between genes. A co-culture system of intestinal epithelium-like organs was constructed to detect the primary mouse intestinal epithelial cells (PMIEC) differentiation. The interaction between proteins was detected via Co-IP assay. ResultsThe expression of WTAP and CES2 in UC tissues was increased and decreased, respectively. Knockdown of WTAP inhibited the progression of UC in mice by inhibiting M1 macrophage polarization and CD4+ T cell infiltration. WTAP combined YTHDF2 to promote the m6A modification of CES2 mRNA and inhibited its expression. CES2 co-expressed with EPHX2 and overexpression of CES2 promoted the differentiation of PMIEC. The inhibitory effect of WTAP knockdown on the progress of UC was partially abrogated by CES2 knockdown. ConclusionWTAP/YTHDF2 silences CES2 by promoting its m6A modification and then promotes the progression of UC. WTAP could be a promoting therapy target of UC.

Characteristics and radiological hazard assessment of 210Po in tilapia (Oreochromis niloticus) in Vietnam.

210Po is one of the most toxic natural radionuclides. This isotope's characteristics and radiological hazard assessment have been concerned in different objects. In this study, the 210Po activities were determined in different tilapia organs/parts of 20 sample groups by alpha spectrometry. The 210Po activities in muscle, bone, intestine organs, and stomach contents unevenly distributed with a wide range from 0.5 ± 0.2 to 2.8 ± 0.4 and 1.4 ± 0.2Bq·kg-1 wet.wt on average, from 0.6 ± 0.3 to 6.3 ± 0.7 and 3.5 ± 0.4Bq·kg-1 wet.wt on average, from 46.3 ± 2.9 to 263 ± 9.7 and 115 ± 6Bq·kg-1 wet.wt on average, and 20.9 ± 1.2 to 800 ± 29 and 197 ± 9Bq·kg-1 wet.wt on average, respectively. The average 210Po activities in different parts of tilapia trend in order of CMuscle < CBone < CIntestine < CStomach contents. Insignificant correlations were observed between 210Po activities in tilapia organs with their total fish mass. The result could depend on feeding types, diet, different nutrient levels, metabolism, and excretion of 210Po in different ages. The concentration ratios (CRs) of tilapia muscle and bone organs were recorded with low values, while it was far greater than the CRs for the intestine organ. Annual committed effective doses contributing from 210Po concentration due to tilapia fish consumption were within the allowable limits for muscle and bone organs, while those values for intestine organs were far higher than the allowable limit value (assuming similar amount consumption of 30kg·year-1 for each organ). The Erica tool was used to estimate the dose and risk to tilapia from 210Po exposure. Based on the calculated results, it can be seen that there was insignificant concern for tilapia due to ionizing radiation in the study area.

Microbiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions.

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.

Clinicopathology and Ultrastructural Alterations of Experimentally Induced Necrotic Enteritis in Chickens

Background: This study was designed to elucidate the clinicopathological and ultrastructural alterations in experimentally induced necrotic enteritis (NE) in chickens and the present study acknowledged pronounced clinical signs, gross, histopathological and ultrastructural lesions in the chickens infected by both Clostridium perfringens type A, type C and coccidia infection. Methods: The day-old chickens were divided in to five groups including control. NE was induced by Clostridium perfringens, type-A and C with and without coccidia infection to the designated experimental groups in this study. Result: The clinical signs, hematology and biochemical parameters were evaluated in this study. Clinical indicators included diarrhea, ruffled feathers, dehydration, depression and a drop in TEC, Hb% and PCV% were noticeable. There was also a large increase in TLC and DC, a significant increase in ALT, AST and a decrease in total protein. In the intestine and other organs, there were noticeable inflammatory gross lesions and histological lesions. Transmission electron microscopic (TEC) observation of intestine revealed disruption of intercellular junction complexes, delimitation of enterocytes, disintegration of nucleus, dilatation of endoplasmic reticulum and cristeolysis of mitochondria. The present work will be an admiring contribution to inclusive study of the NE in chicken in terms of clinicopathology and ultrastructural lesions.

A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut.

Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays of molecularly defined neuron subsets and of immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, and immunocyte transcriptomics in intestinal organs. Distinct immune perturbations followed neuronal activation: Nitrergic neurons regulated T helper 17 (TH17)-like cells, and cholinergic neurons regulated neutrophils. Nociceptor neurons, expressing Trpv1, elicited the broadest immunomodulation, inducing changes in innate lymphocytes, macrophages, and RORγ+ regulatory T (Treg) cells. Neuroanatomical, genetic, and pharmacological follow-up showed that Trpv1+ neurons in dorsal root ganglia decreased Treg cell numbers via the neuropeptide calcitonin gene-related peptide (CGRP). Given the role of these neurons in nociception, these data potentially link pain signaling with gut Treg cell function.

Association between Autoimmune Hepatitis and Celiac Disease among Egyptian Children and Adolescents

Abstract Background Celiac disease (CD) is an immune-mediated intolerance to gluten .CD has been recognized as a multisystem disorder which may affect other extra intestinal organs, such as the skin, thyroid, heart, nervous system, pancreas and liver. Individuals with CD are at increased risk of liver disease namely cryptogenic liver disorder and autoimmune liver disorder. However, until now, it remains unknown whether these two forms of liver disease are really different entities or only different severities of the same disorder. Objective To evaluate the association of CD with autoimmune hepatitis in pediatrics. Subjects and Methods This was a cross-sectional study that was conducted at the Pediatric Hepatology Clinic and Pediatric Gastroenterology Clinic, Children’s Hospital, Ain Shams University. The study included 2 groups of patients each comprised 20 children and adolescents as follow: Group I: Patients with established diagnosis of autoimmune hepatitis (AIH). All patients were receiving corticosteroids and azathioprine Group II: Patients with established diagnosis of CD. In group I patients with AIH, CD was screened for using anti-tissue transglutaminase (tTG) IgA in addition to measuring serum IgA to determine the need to measure anti-tTG IgG. Immunological markers (ANA, anti-smooth muscle antibody (ASMA) and liver and kidney microsomal (LKM) antibodies in addition to protein electrophoresis were done for group II patients with CD to screen for AIH. Results All patients in group I with AIH had normal serum IgA levels and were found negative for anti-tTG IgA. Also, group II patients with CD were negative for ANA, ASMA and LKM antibodies with normal protein electrophoresis. Conclusion The current study showed that CD does not seem to have significant association with AIH, however, the small sample size is a study limitation. Further wider scale studies are needed to evaluate the risk of AIH in CD.

Study of Microplastic Contamination in the Digestive Organs of Parrotfish (Scarus rivulatus) Caught in Ekas Bay

Microplastics have become a major concern in global environmental research due to their significant impact on marine ecosystems. Microplastic pollution has been detected in almost all aquatic environments, including oceans, rivers and lakes. This study aims to evaluate the level of microplastic contamination in the digestive organs of old parrot fish caught in Ekas Bay. Focusing on the digestive organs is important because ingested microplastics can have detrimental effects on fish health, including digestive disorders and bioaccumulation of harmful chemicals. The research method used was descriptive with a sample size of six parrot fish. Based on research conducted on the digestive organs of parrot fish, it was found that the types of microplastics found were in the form of fragments, films, pellets and fibers. The total abundance of microplastics in the intestinal organs ranges from 290 par/gr to 410 par/gr, while in the stomach organs it is 272 par/gr to 310 par/gr. The highest percentage of microplastics in the intestinal organs was pellets at 47% and in the stomach organs it was fragments at 54%.

Application and challenge of pancreatic organoids in therapeutic research

The in-vivo non-human primate animal and in-vitro cell disease models play a crucial part in the study of the mechanisms underlying the occurrence and development of pancreatic diseases, but with increasingly prominent limitations with in-depth research. Organoids derived from human pluripotent and adult stem cells resemble human in-vivo organs in their cellular composition, spatial tissue structure and physiological function, making them as an advantageous research tool. Up until now, numerous human organoids, including pancreas, have been effectively developed, demonstrating significant potential for research in organ development, disease modeling, drug screening, and regenerative medicine. However, different from intestine, liver and other organs, the pancreas is the only special organ in the human body, consisting of an exocrine gland and an endocrine gland. Thus, the development of pancreatic organoid technology faces greater challenges, and how to construct a composite pancreatic organoid with exocrine and endocrine gland is still difficult in current research. By reviewing the fundamental architecture and physiological role of the human pancreas, along with the swiftly developing domain of pancreatic organoids, we summarize the method and characteristics of human pancreatic organoids, and its application in modeling pancreatic diseases, as a platform for individualized drug screening and in regenerative medicine study. As the first comprehensive review that focus on the pharmacological study of human pancreatic organoid, the review hopes to help scholars to have a deeper understanding in the study of pancreatic organoid.

#753 Targeted anti-IL-1β bacteroides fragilis outer membrane vesicles alleviate inflammatory injury in diabetic nephropathy

Abstract Background and Aims It is accepted that diabetic nephropathy (DN) is not only a disease caused by impaired glucose metabolism, but also a chronic inflammatory disease. The interleukin-1β (IL-1β) plays an important role in inflammation-mediated renal injury in DN. IL-1β blocking therapy can prevent inflammatory cytokine-mediated kidney injury. However, the high cost and systemic side effects of IL-1β antibodies limit its application. Therefore, firstly this study aimed to construct kidney-targeting outer membrane vesicles (OMVs) of Bacteroides fragilis loaded with IL-1β single-chain variable fragment (scFv). These OMVs derived from human commensal non-toxigenic Bacteroides fragilis have been proven to play an immunosuppressive role in the intestine and distant organs. This targeted drug delivery platform built with this as a carrier is expected to relieve kidney inflammation in the development of DN. Methods We recombinantly expressed the scFv based on the Gevokizumab sequence in Escherichia coli, and loaded it into the OMVs derived from Bacteroides fragilis by multiple ultrasounds. The targeting peptide with the sequence (KKEEE)3{Lys(N3)} was connected to the membrane surface through a copper-free catalyzed click chemistry reaction. The package, which consisted of OMVs and the scFv targeting IL-1β in the kidney (OMV-KTP-scFv) was obtained. OMV-KTP-scFv treated in HK-2 cells and healthy mice respectively, and evaluated its in vitro and in vivo drug safety. The concentration of IL-1β scFv in blood and kidney tissues at different time points were measured using streptozotocin (STZ)-induced diabetic mice. DID-labeled OMVs was used for ex vivo infrared imaging of various organs to evaluate the delivery efficiency of the targeted carrier. In vitro, OMV-KTP-scFv was used to prevent inflammation in mouse primary renal tubular epithelial cells induced by high glucose, and in vivo to alleviate kidney injury in STZ-induced diabetic mice. Results We successfully prepared OMV-KTP-scFv and confirmed the co-localization of OMVs, KTP, and scFv using super-resolution microscopy. The prepared OMV-KTP-scFv had high stability, effectively extended the plasma half-life of scFv, and could deliver scFv accurately to the proximal renal tubules. Furthermore, OMV-KTP-scFv also had good safety in vitro and in vivo, and no obvious biotoxicity was found during long-term in vivo administration. In addition, our results show that OMV-KTP-scFv significantly inhibited the expression of inflammatory factors in renal tubular cells of DN, reduced the infiltration of renal interstitial inflammatory cells, and alleviated renal tubular injury. Conclusion Our findings demonstrated that OMVs of Bacteroides fragilis targeting the kidney can deliver the IL-1β scFv to the renal tubulointerstitium and reduce the renal interstitial injury in DN by antagonizing local inflammation.