BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on ...BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.展开更多
The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α...The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α and the incremental duodenum of the elastic modulus are both larger than those of the jejunum. It means that the duodenum is more deformable than the jejunum. The experimental results of this work provide basal data for kinematics study of a robotic endoscope.展开更多
In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical techniq...In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical technique.The results showed that the NOS-pos展开更多
Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea,...Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea, vomiting, abdominal pain. The present study demonstrated that red beetroot juice (RBRJ) contains a compound or compound complex with the ability to specifically stimulate duodenal iron absorption, shown in experiments in vitro, in situ and in vivo. The effect does not depend on juice sugar and ascorbic acid concentration. Fractionated RBRJ impact on iron absorption is dose dependent. This phenomenon is described for the first time.展开更多
480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with...480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with wheat-based diet supplemented with xylanase(1.2×l0~4 U/kg diet).On day 16,two birds per replication with average live weight were selected and sacrificed.Tissue samples of jejunum and ileum were collected to detect mRNA expression of cationic amino acid transporters using RT-PCR.The results showed that xylanase significantly increased the abundance of mRNA for rBAT and CAT4 in the intestines of broilers fed with wheat-based diets(P<0.05)and had a tendency to increase the mRNA expression of y^+LAT2 and CAT1 in jejunum(P>0.05),y^+LAT2,CAT1 and CAT4 in ileum(P>0.05).The treatment had no effect on the expression of rBAT mRNA in ileum(P>0.05).展开更多
The aim of this study was to investigate the effects of rare earth elements (REEs) in preventing Hg^2+ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2+ , La^3...The aim of this study was to investigate the effects of rare earth elements (REEs) in preventing Hg^2+ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2+ , La^3+ , the mixture of La^3+ and Hg^2+ and DNA by spectroscopy. The interactions between Hg^2+ , La^3+ , the mixture of La^3+ and Hg^2+ and DNA from fish intestine in vitro was investigate by using absorption spectrum and fluorescence emission spectrum. Ultraviolet absorption spectra indicated that the addition of Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ to DNA generated obvious hypochromic effect. Meanwhile, the 205.2 nm peak of DNA blue and the 258.2 nm peak of DNA red shifted. The hypochromic effect and peak shift was caused by these ions in an order of Hg^2+ 〉 Hg^2+ + La^3+ 〉 La^3+ . The fluorescence emission spectra showed that as the addition of Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ , the emission peak at about 416.2 nm of DNA did not obviously change, but the fluorescence intensity reduced gradually with the order in treatment was Hg^2+ 〉 Hg^2+ 〉 La^3+ 〉 La^3+ . Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ had 1.12, 0.58, and 0.81 binding sites to DNA, the fluorescence quenching of DNA caused by them all attributed to static quenching. The binding constants KA of binding sites were 3.82×10^4 and 4.22×10^2 L·mol^-1 ; 2.50×10^4 and 2.95×10^3 L·mol^-1 ; 3.05×10^4 and 1.00×10^3 L·mol^-1. The results showed that La^3+ could relieve destruction caused by Hg^2+ on the DNA structure.展开更多
Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim o...Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim of this study was to investigate the expression of surfactant proteins in the intes-tines and pancreas of murine fetuses. Methods: Immunostaining for SP-A and SP-D was assessed in the small intestine and pancreas of ICR murine fetuses on days 15, 16, 17 and 18 of gestation (normal duration of pregnancy: 19 - 21 days). RT-PCR was performed to detect the expression of spa and spd mRNA in the small intestine and pancreas on day 16, 17 and 18 of gestation. Results: Immunoreactivity for SP-A and SP-D in the acinar cells of pancreas and intestinal mucosal surface were positive on day 16 of gestation onward. RT-PCR revealed that the expression of spa and spd mRNA was significant in the pancreas but weak in the small intestine. Conclusions: Our data revealed that surfactant proteins are present in the fetal intestines and pancreas and that a significant expression of spa and spd mRNA is detected in the fetal pancreas. Pancreas may be a possible organ involved in the synthesis and secretion of surfactant proteins into the intestinal lumen.展开更多
In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and his...In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5<sup>th</sup>. The fetuses were removed on the 20.5<sup>th</sup> (G-1) and 21.5<sup>th</sup> days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were...Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were transplanted heterotopically in two pigs. And after 28 days of heterotopic transplantation, the transplanted intestine was interposed into continuity of host intestine as orthotopic transplant. During the experiment, tests were made on 6th day after the first operation (period 1), the 14th (II), 28th (III) day after heterotopic transplantation, and 3 weeks after interposition (IV) respectively for the levels of glucose, palmitate and leucine. Additionally, at period I, III, and IV, a 3 cm length of intestinal mucosa was excised for morphologic observation and determination of DNA, RNA and protein contents. After heterotopic transplantation, the absorptive function of transplanted intestine was severely impaired for two weeks. The absorption of glucose! and palmitate was partially recovered by period III, at which time leucine level had return to normal. At period IV, the absorptive function of glucose and leucine had surpassed normal levels, while palmitate had risen to the level of pretransplantation. After transplantation, at period III, DNA, RNA and protein contents were well below normal. Three weeks after orthotopic transplantation, RNA and protein had risen to normal level, while DNA content remained below normal, The morphologic changes during the experiment were correlated with the changes of contents in RNA, protein and DNA. The area, height, width of villi and the area, depth, width:of crypt were below normal at III and recovered by 3 weeks after orthotopic transplantation (period IV), but were still lower than the levels at pretransplantation. Crypt depths were deeper than those of pretransplantation.展开更多
Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in dis...Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.展开更多
A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-caten...A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
这是来自里斯本(葡萄牙首都)的一则消息。还没有读完本文的主题句。读者就会大吃一惊:A man carrying no fewer than 1,304 uncut diamonds in his intestines(肠子)has been arrested…。本句有圆周句(periodic sentence)的色彩。所谓p...这是来自里斯本(葡萄牙首都)的一则消息。还没有读完本文的主题句。读者就会大吃一惊:A man carrying no fewer than 1,304 uncut diamonds in his intestines(肠子)has been arrested…。本句有圆周句(periodic sentence)的色彩。所谓periodic sentence,即指主要意义至句尾始明白的句子。A man carrying no fewer than 1,304 uncut diamonds是正常的,让人惊骇并觉得恶心的,是后面的介词短语:in his intestines(肠子)!】展开更多
Shear deformation induced by shear stress is one of the major forms of interaction between the locomotion mechanism and the intestines. Relatively few experimental studies using locomotion mechanisms have been perform...Shear deformation induced by shear stress is one of the major forms of interaction between the locomotion mechanism and the intestines. Relatively few experimental studies using locomotion mechanisms have been performed to investigate the viscoelastic property of intestines. There is a lack of reliable data regarding the relative movement between various locomotion mechanisms and the small intestine, and how that movement affects the measurement of shear displacement. In this work, a novel platform was constructed with two elaborately designed clamps that could securely fix both sides of an intestine sample using negative gas adsorption. The platform was also integrated with noncontact measuring equipment to record the thickness of the intestine sample. Subsequently, preservation measure was applied to porcine intestine, and multiple intestine samples were prepared and tested under strains of 20%, 50%, 80% and 100%. A five-element viscoelastic model that was fitted to multiple sets of data could accurately predict the biomechanical property of the intestines. Finally, a new criterion, the loss factor, was calculated with the parameters of the five-element model to represent the dynamic behavior of soft tissue, and it was used to verify the reliability and effectiveness of the experimental setup and results.展开更多
Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1...Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.展开更多
Transport stress is commonly suffered by animals with gastrointestinal dysfunction a common symptom.Currently,the mechanisms of transport stress-induced intestine impairment are largely unknown.The aim of this study w...Transport stress is commonly suffered by animals with gastrointestinal dysfunction a common symptom.Currently,the mechanisms of transport stress-induced intestine impairment are largely unknown.The aim of this study was to investigate the effects of transport stress on the expression of neuronal nitric oxide synthase(nNOS)and the distribution of nNOS-positive neurons of the intestines in rats and to explore the neuroendocrine mechanism of transport stress.In this study,Sprague Dawley rats(n=6)were subjected on a constant temperature shaker for 1(S1d)or 3 d(S3d).Rats exhibited increased serum glucose and diminished total number of leukocytes,in which lymphocytes level was also decreased in the S1d group(P<0.05).Also,normal intestinal morphology was disrupted in the S1d rats,and the thickness of muscle layers was decreased in duodenum,jejunum and colon of S3d rats.In addition,it was found that nNOS expression,as well as the number of nNOSpositive neurons in the myenteric plexus were downregulated in duodenum,jejunum and colon of S3d rats compared with that of unstressed rats(P<0.05).These data reveals that transport stress induced intestinal damage and uncovers potential action mechanisms that nNOS-positive neurons and nNOS expression might be involved in modulating this process.展开更多
There are major gaps in illustrating the risk to freshwater fish that are exposed to environmental microplastics(MPs),even though MPs in freshwater environments has drawn much concern.To explore the potentially negati...There are major gaps in illustrating the risk to freshwater fish that are exposed to environmental microplastics(MPs),even though MPs in freshwater environments has drawn much concern.To explore the potentially negative effects of microplastics on freshwater fish,grass carp(averaging 9.215±0.035g)were exposed to microplastics(32-40μm in diameter)at two environmental concentrations(100 and 1000μg/L)for 21 days,and evaluated for physio-biochemical performance,gut microbiome,and metabolome responses.After exposure,microplastics were detected in the intestine and within basal nuclei and goblet cells hyperplasia.Antioxidant enzyme activities(superoxide dismutase and catalase)also significantly decreased within the intestines(P<0.05).Through 16S rRNA gene sequencing analysis,a decrease in diversity and richness was observed in the MPs-H and MPs-L groups.The abundance of opportunistic pathogens increased and beneficial bacteria decreased in both MP treatments.For example,Acinetobacter and Bosea proportions were higher in the MPs-L group,while Bacteroides and Shewanella increased in the MPs-H group.Furthermore,abundance of Lactobacillus decreased both in the MPs-H and MPs-L groups.Metabolomics analysis revealed primary bile acid biosynthesis metabolism upregulated in the MPs-L and purine metabolism downregulated in the MPs-H group.Additionally,an integration analysis of the gut microbiome and metabolomics identified significant associations between several bacteria taxa and metabolites related to intestinal repair.Taken together,these results highlighted the negative effects on intestinal morphology,oxidative stress,and microbiome and emphasized the relationship between microbiota and metabolites in response to microplastics,which could provide comprehensive insights into the potential risks of MPs on freshwater fish intestines.展开更多
The purpose of this study was to gain insight into the mechanism of iron dextran(DexFe)absorption in the intestines.A total of 72 piglets(average BW=7.12±0.75 kg,male to female ratio=1:1)weaned at 28 d of age wer...The purpose of this study was to gain insight into the mechanism of iron dextran(DexFe)absorption in the intestines.A total of 72 piglets(average BW=7.12±0.75 kg,male to female ratio=1:1)weaned at 28 d of age were randomly divided into two treatment groups with six replicates for each group.The experimental diets included the basal diet supplemented with 100 mg/kg iron dextran(DexFe group)and the basal diet supplemented with 100 mg/kg FeSO_(4)$H_(2)O(CON group).The experiment lasted for 28 d.The piglets'intestinal iron transport was measured in vitro using an Ussing chamber.Porcine intestinal epithelial cell line(IPEC-J2)cells were used to develop a monolayer cell model that explored the molecular mechanism of DexFe absorption.Results showed that compared to the CON group,the ADG of pigs in the DexFe group was improved(P=0.022),while the F/G was decreased(P=0.015).The serum iron concentration,apparent iron digestibility,and iron deposition in the duodenum,jejunum,and ileum were increased(P<0.05)by dietary DexFe supplementation.Piglets in the DexFe group had higher serum red blood count,hemoglobin,serum iron content,serum ferritin and transferrin levels and lower total iron binding capacity(P<0.05).In the Ussing chamber test,the iron absorption rate of the DexFe group was greater(P<0.001)than the CON group,and there was no significant difference between the DexFe group and the glucose group(P>0.05).Furthermore,when compared to the CON group,DexFe administration improved(P<0.05)SLC2A5 gene and glucose transporter 5(GLUT5)protein expression but had no effect(P>0.05)on SLC11A2 gene or divalent metal transporter 1(DMT1)protein expression.Once the GLUT5 protein was suppressed,the iron transport rate and apparent permeability coefficient were decreased(P<0.05)in IPEC-J2 monolayer cell models.The findings suggest the effectiveness of DexFe application in weaned piglets and revealed for the first time that DexFe absorption in the intestine is closely related to the glucose transporter GLUT5 protein channel.展开更多
基金Supported by the National Natural Science Foundation of China,No.82174461Capacity Enhancement Program of Xiyuan Hospital,China Academy of Traditional Chinese Medicine,No.XYZX0201-22Science and Technology Innovation Project of China Academy of Traditional Chinese Medicine,No.CI2021A01811.
文摘BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.
文摘The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α and the incremental duodenum of the elastic modulus are both larger than those of the jejunum. It means that the duodenum is more deformable than the jejunum. The experimental results of this work provide basal data for kinematics study of a robotic endoscope.
文摘In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical technique.The results showed that the NOS-pos
文摘Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea, vomiting, abdominal pain. The present study demonstrated that red beetroot juice (RBRJ) contains a compound or compound complex with the ability to specifically stimulate duodenal iron absorption, shown in experiments in vitro, in situ and in vivo. The effect does not depend on juice sugar and ascorbic acid concentration. Fractionated RBRJ impact on iron absorption is dose dependent. This phenomenon is described for the first time.
基金supported by National Key Basic Research Development Program 973 of China(No.2004CB117501)National Natural Science Foundation of China(No.30671519)Guangdong Province Scientific Technology Research Project(No.2005B20201016)
文摘480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with wheat-based diet supplemented with xylanase(1.2×l0~4 U/kg diet).On day 16,two birds per replication with average live weight were selected and sacrificed.Tissue samples of jejunum and ileum were collected to detect mRNA expression of cationic amino acid transporters using RT-PCR.The results showed that xylanase significantly increased the abundance of mRNA for rBAT and CAT4 in the intestines of broilers fed with wheat-based diets(P<0.05)and had a tendency to increase the mRNA expression of y^+LAT2 and CAT1 in jejunum(P>0.05),y^+LAT2,CAT1 and CAT4 in ileum(P>0.05).The treatment had no effect on the expression of rBAT mRNA in ileum(P>0.05).
基金Project supported by the National Natural Science Foundation of China (20671067)
文摘The aim of this study was to investigate the effects of rare earth elements (REEs) in preventing Hg^2+ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2+ , La^3+ , the mixture of La^3+ and Hg^2+ and DNA by spectroscopy. The interactions between Hg^2+ , La^3+ , the mixture of La^3+ and Hg^2+ and DNA from fish intestine in vitro was investigate by using absorption spectrum and fluorescence emission spectrum. Ultraviolet absorption spectra indicated that the addition of Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ to DNA generated obvious hypochromic effect. Meanwhile, the 205.2 nm peak of DNA blue and the 258.2 nm peak of DNA red shifted. The hypochromic effect and peak shift was caused by these ions in an order of Hg^2+ 〉 Hg^2+ + La^3+ 〉 La^3+ . The fluorescence emission spectra showed that as the addition of Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ , the emission peak at about 416.2 nm of DNA did not obviously change, but the fluorescence intensity reduced gradually with the order in treatment was Hg^2+ 〉 Hg^2+ 〉 La^3+ 〉 La^3+ . Hg^2+ , La^3+ , and the mixture of La^3+ and Hg^2+ had 1.12, 0.58, and 0.81 binding sites to DNA, the fluorescence quenching of DNA caused by them all attributed to static quenching. The binding constants KA of binding sites were 3.82×10^4 and 4.22×10^2 L·mol^-1 ; 2.50×10^4 and 2.95×10^3 L·mol^-1 ; 3.05×10^4 and 1.00×10^3 L·mol^-1. The results showed that La^3+ could relieve destruction caused by Hg^2+ on the DNA structure.
文摘Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim of this study was to investigate the expression of surfactant proteins in the intes-tines and pancreas of murine fetuses. Methods: Immunostaining for SP-A and SP-D was assessed in the small intestine and pancreas of ICR murine fetuses on days 15, 16, 17 and 18 of gestation (normal duration of pregnancy: 19 - 21 days). RT-PCR was performed to detect the expression of spa and spd mRNA in the small intestine and pancreas on day 16, 17 and 18 of gestation. Results: Immunoreactivity for SP-A and SP-D in the acinar cells of pancreas and intestinal mucosal surface were positive on day 16 of gestation onward. RT-PCR revealed that the expression of spa and spd mRNA was significant in the pancreas but weak in the small intestine. Conclusions: Our data revealed that surfactant proteins are present in the fetal intestines and pancreas and that a significant expression of spa and spd mRNA is detected in the fetal pancreas. Pancreas may be a possible organ involved in the synthesis and secretion of surfactant proteins into the intestinal lumen.
文摘In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5<sup>th</sup>. The fetuses were removed on the 20.5<sup>th</sup> (G-1) and 21.5<sup>th</sup> days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
文摘Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were transplanted heterotopically in two pigs. And after 28 days of heterotopic transplantation, the transplanted intestine was interposed into continuity of host intestine as orthotopic transplant. During the experiment, tests were made on 6th day after the first operation (period 1), the 14th (II), 28th (III) day after heterotopic transplantation, and 3 weeks after interposition (IV) respectively for the levels of glucose, palmitate and leucine. Additionally, at period I, III, and IV, a 3 cm length of intestinal mucosa was excised for morphologic observation and determination of DNA, RNA and protein contents. After heterotopic transplantation, the absorptive function of transplanted intestine was severely impaired for two weeks. The absorption of glucose! and palmitate was partially recovered by period III, at which time leucine level had return to normal. At period IV, the absorptive function of glucose and leucine had surpassed normal levels, while palmitate had risen to the level of pretransplantation. After transplantation, at period III, DNA, RNA and protein contents were well below normal. Three weeks after orthotopic transplantation, RNA and protein had risen to normal level, while DNA content remained below normal, The morphologic changes during the experiment were correlated with the changes of contents in RNA, protein and DNA. The area, height, width of villi and the area, depth, width:of crypt were below normal at III and recovered by 3 weeks after orthotopic transplantation (period IV), but were still lower than the levels at pretransplantation. Crypt depths were deeper than those of pretransplantation.
基金funding by National Natural Science Foundation of China(No.82174492)National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Project(N o.ZJJBGS2024002-1).
文摘Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.
文摘A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
文摘这是来自里斯本(葡萄牙首都)的一则消息。还没有读完本文的主题句。读者就会大吃一惊:A man carrying no fewer than 1,304 uncut diamonds in his intestines(肠子)has been arrested…。本句有圆周句(periodic sentence)的色彩。所谓periodic sentence,即指主要意义至句尾始明白的句子。A man carrying no fewer than 1,304 uncut diamonds是正常的,让人惊骇并觉得恶心的,是后面的介词短语:in his intestines(肠子)!】
基金supported by the National Key R&D Program of China(Grant No.2018YFC0115101)the National Natural Science Foundation of China(Grant No.61503370)Open Fund of State Key Laboratory of Robotics of China(Grant No.2017-O10)
文摘Shear deformation induced by shear stress is one of the major forms of interaction between the locomotion mechanism and the intestines. Relatively few experimental studies using locomotion mechanisms have been performed to investigate the viscoelastic property of intestines. There is a lack of reliable data regarding the relative movement between various locomotion mechanisms and the small intestine, and how that movement affects the measurement of shear displacement. In this work, a novel platform was constructed with two elaborately designed clamps that could securely fix both sides of an intestine sample using negative gas adsorption. The platform was also integrated with noncontact measuring equipment to record the thickness of the intestine sample. Subsequently, preservation measure was applied to porcine intestine, and multiple intestine samples were prepared and tested under strains of 20%, 50%, 80% and 100%. A five-element viscoelastic model that was fitted to multiple sets of data could accurately predict the biomechanical property of the intestines. Finally, a new criterion, the loss factor, was calculated with the parameters of the five-element model to represent the dynamic behavior of soft tissue, and it was used to verify the reliability and effectiveness of the experimental setup and results.
基金supported by the Innovative Antiviral Therapy Program,Leibniz Institute of Virology(LIV),the German Center for Infection Research(DZIF),EFRE 2014-2020 REACT-EU,Dutch Digestive Fund(MLDS CDG 15-02)Deutsche Forschungsgemeinschaft(BU 3630/2-1)+1 种基金Hüet Roëll Foundation.MK is supported by a Walter Benjamin Fellowship of the Deutsche Forschungsgemeinschaft(KA5554/1-1,KA5554/1-2)The Leibniz Institute of Virology is supported by the Free and Hanseatic City of Hamburg and the Federal Ministry of Health.
文摘Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.
基金supported by the National Natural Science Foundation of China(31772686 and 31502025)the National TwelveFive Technological Supported Plan of China(2011BAD34B01)。
文摘Transport stress is commonly suffered by animals with gastrointestinal dysfunction a common symptom.Currently,the mechanisms of transport stress-induced intestine impairment are largely unknown.The aim of this study was to investigate the effects of transport stress on the expression of neuronal nitric oxide synthase(nNOS)and the distribution of nNOS-positive neurons of the intestines in rats and to explore the neuroendocrine mechanism of transport stress.In this study,Sprague Dawley rats(n=6)were subjected on a constant temperature shaker for 1(S1d)or 3 d(S3d).Rats exhibited increased serum glucose and diminished total number of leukocytes,in which lymphocytes level was also decreased in the S1d group(P<0.05).Also,normal intestinal morphology was disrupted in the S1d rats,and the thickness of muscle layers was decreased in duodenum,jejunum and colon of S3d rats.In addition,it was found that nNOS expression,as well as the number of nNOSpositive neurons in the myenteric plexus were downregulated in duodenum,jejunum and colon of S3d rats compared with that of unstressed rats(P<0.05).These data reveals that transport stress induced intestinal damage and uncovers potential action mechanisms that nNOS-positive neurons and nNOS expression might be involved in modulating this process.
基金supported by National Natural Science Foundation of China Youth Project (31802285)the China’s Agricultural Research System (CARS-45-03)Special Fund for Science and Technology Development of Shanghai Ocean University.
文摘There are major gaps in illustrating the risk to freshwater fish that are exposed to environmental microplastics(MPs),even though MPs in freshwater environments has drawn much concern.To explore the potentially negative effects of microplastics on freshwater fish,grass carp(averaging 9.215±0.035g)were exposed to microplastics(32-40μm in diameter)at two environmental concentrations(100 and 1000μg/L)for 21 days,and evaluated for physio-biochemical performance,gut microbiome,and metabolome responses.After exposure,microplastics were detected in the intestine and within basal nuclei and goblet cells hyperplasia.Antioxidant enzyme activities(superoxide dismutase and catalase)also significantly decreased within the intestines(P<0.05).Through 16S rRNA gene sequencing analysis,a decrease in diversity and richness was observed in the MPs-H and MPs-L groups.The abundance of opportunistic pathogens increased and beneficial bacteria decreased in both MP treatments.For example,Acinetobacter and Bosea proportions were higher in the MPs-L group,while Bacteroides and Shewanella increased in the MPs-H group.Furthermore,abundance of Lactobacillus decreased both in the MPs-H and MPs-L groups.Metabolomics analysis revealed primary bile acid biosynthesis metabolism upregulated in the MPs-L and purine metabolism downregulated in the MPs-H group.Additionally,an integration analysis of the gut microbiome and metabolomics identified significant associations between several bacteria taxa and metabolites related to intestinal repair.Taken together,these results highlighted the negative effects on intestinal morphology,oxidative stress,and microbiome and emphasized the relationship between microbiota and metabolites in response to microplastics,which could provide comprehensive insights into the potential risks of MPs on freshwater fish intestines.
基金financially supported by the Hunan Engineering Research Center of Intelligent Animal Husbandry(grant number:20211231GCZX)of ChinaEvaluation of the Effectiveness of Iron Dextran Supplementation in Pig Diets(grant number,2022xczx-214)of Hunan Agricultural University.
文摘The purpose of this study was to gain insight into the mechanism of iron dextran(DexFe)absorption in the intestines.A total of 72 piglets(average BW=7.12±0.75 kg,male to female ratio=1:1)weaned at 28 d of age were randomly divided into two treatment groups with six replicates for each group.The experimental diets included the basal diet supplemented with 100 mg/kg iron dextran(DexFe group)and the basal diet supplemented with 100 mg/kg FeSO_(4)$H_(2)O(CON group).The experiment lasted for 28 d.The piglets'intestinal iron transport was measured in vitro using an Ussing chamber.Porcine intestinal epithelial cell line(IPEC-J2)cells were used to develop a monolayer cell model that explored the molecular mechanism of DexFe absorption.Results showed that compared to the CON group,the ADG of pigs in the DexFe group was improved(P=0.022),while the F/G was decreased(P=0.015).The serum iron concentration,apparent iron digestibility,and iron deposition in the duodenum,jejunum,and ileum were increased(P<0.05)by dietary DexFe supplementation.Piglets in the DexFe group had higher serum red blood count,hemoglobin,serum iron content,serum ferritin and transferrin levels and lower total iron binding capacity(P<0.05).In the Ussing chamber test,the iron absorption rate of the DexFe group was greater(P<0.001)than the CON group,and there was no significant difference between the DexFe group and the glucose group(P>0.05).Furthermore,when compared to the CON group,DexFe administration improved(P<0.05)SLC2A5 gene and glucose transporter 5(GLUT5)protein expression but had no effect(P>0.05)on SLC11A2 gene or divalent metal transporter 1(DMT1)protein expression.Once the GLUT5 protein was suppressed,the iron transport rate and apparent permeability coefficient were decreased(P<0.05)in IPEC-J2 monolayer cell models.The findings suggest the effectiveness of DexFe application in weaned piglets and revealed for the first time that DexFe absorption in the intestine is closely related to the glucose transporter GLUT5 protein channel.