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
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
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are...Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.展开更多
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation ...Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.展开更多
2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-...2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.G...BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).展开更多
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clost...Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.展开更多
BACKGROUND Anal fistula is increasingly prevalent due to modern lifestyle factors,and surgery remains the primary treatment.However,the rising incidence of antibiotic resistance,particularly to cefuroxime,complicates ...BACKGROUND Anal fistula is increasingly prevalent due to modern lifestyle factors,and surgery remains the primary treatment.However,the rising incidence of antibiotic resistance,particularly to cefuroxime,complicates perioperative management.The role of gut microbiota in influencing this resistance is not well understood.AIM To investigate the relationship between gut microbiota composition and cefuroxime resistance in anal fistula patients and to assess probiotic intervention impact.METHODS This study included 30 anal fistula patients categorized into cefuroxime-sensitive(Cefur-S)and cefuroxime-resistant(Cefur-NS)groups.Gut microbiota samples were collected during colonoscopy,and 16S ribosomal DNA sequencing was performed to analyze microbial diversity.Patients in the Cefur-NS group received a 7-day course of Clostridium butyricum tablets.Post-intervention,microbial composition and cefuroxime resistance were reassessed.RESULTS Alpha and beta diversity analyses showed no significant differences in microbial diversity between the Cefur-S and Cefur-NS groups.However,effect size analysis identified Roseburia and Butyricicoccus as dominant genera in the Cefur-S group,with higher butyrate production potentially protecting against cefuroxime resistance.Post-intervention,the Cefur-NS group showed a significant reduction in cefuroxime resistance,improved stool consistency,and reduced bowel movement frequency.CONCLUSION This study suggests that specific gut microbiota,particularly Butyricicoccus and Roseburia,may mitigate cefuroxime resistance in anal fistula patients by increasing butyrate production.Probiotic intervention targeting gut microbiota composition presents a promising strategy for reducing antibiotic resistance and improving clinical outcomes.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.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 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.
基金supported by the National Natural Science Foundation of China,No.82171080Nanjing Medical Science and Technology Development Project,No.YKK23264Postgraduate Research&Practice Innovation Program of Jiangsu Province,Nos.JX10414151,JX10414152(all to KL)。
文摘Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
基金supported by the Chengdu University of Traditional Chinese Medicine"Xinglin Scholars"Program,China(Grant No.:MPRC2023014).
文摘Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.
基金financially supported by the National Key Research and Development Program of China(2022YFF1100402)National Center of Technology Innovation for Dairy(2022-Open subject-11)+1 种基金Young Elite Scientist Sponsorship Program by CAST(YESS20200271)the National Natural Science Foundation of China(32101919)。
文摘2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.
文摘BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
基金supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金supported by China Agriculture Research System Program(Project No.CARS-41-G04)。
文摘Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.
基金Supported by the Jiaxing Science and Technology Project,No.2023AD11016 and No.2023AD31028.
文摘BACKGROUND Anal fistula is increasingly prevalent due to modern lifestyle factors,and surgery remains the primary treatment.However,the rising incidence of antibiotic resistance,particularly to cefuroxime,complicates perioperative management.The role of gut microbiota in influencing this resistance is not well understood.AIM To investigate the relationship between gut microbiota composition and cefuroxime resistance in anal fistula patients and to assess probiotic intervention impact.METHODS This study included 30 anal fistula patients categorized into cefuroxime-sensitive(Cefur-S)and cefuroxime-resistant(Cefur-NS)groups.Gut microbiota samples were collected during colonoscopy,and 16S ribosomal DNA sequencing was performed to analyze microbial diversity.Patients in the Cefur-NS group received a 7-day course of Clostridium butyricum tablets.Post-intervention,microbial composition and cefuroxime resistance were reassessed.RESULTS Alpha and beta diversity analyses showed no significant differences in microbial diversity between the Cefur-S and Cefur-NS groups.However,effect size analysis identified Roseburia and Butyricicoccus as dominant genera in the Cefur-S group,with higher butyrate production potentially protecting against cefuroxime resistance.Post-intervention,the Cefur-NS group showed a significant reduction in cefuroxime resistance,improved stool consistency,and reduced bowel movement frequency.CONCLUSION This study suggests that specific gut microbiota,particularly Butyricicoccus and Roseburia,may mitigate cefuroxime resistance in anal fistula patients by increasing butyrate production.Probiotic intervention targeting gut microbiota composition presents a promising strategy for reducing antibiotic resistance and improving clinical outcomes.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
