The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
Humans ; Intestinal Mucosa/cytology* ; Intestine, Small/cytology* ; Animals ; Inflammatory Bowel Diseases/immunology* ; Celiac Disease/immunology* ; Paneth Cells/immunology*

The ideal treatment and recovery of osteoarticular injury remain to be resolved. Small intestinal submucosa (SIS), a naturally-occurring decellularized extracellular matrix, has been recognized as an ideal scaffold for tissue engineering and widely used in repairing various tissues and organs. Nowadays its application has also been gradually increased in the field of orthopedics. We reviewed laboratorial studies and clinical trails about the application of SIS in bone and joint repair, aiming to evaluate its effects on the repair of bone, cartilage, meniscus, ligament and tendon. SIS has showed promising results in repairing bone, meniscus, ligament or tendon. However, additional studies will be required to further evaluate its effects on articular cartilage and tendon-bone healing. How to optimize SIS material,is also a focused problem concerned with making SIS a potential therapeutic option with high value for orthopedic tissue repair.
Animals ; Cell- and Tissue-Based Therapy ; Humans ; Intestinal Mucosa ; cytology ; Intestine, Small ; cytology ; Joint Diseases ; physiopathology ; surgery ; therapy ; Tissue Engineering ; instrumentation ; methods ; Tissue Scaffolds ; chemistry

OBJECTIVETo explore the change in the expression of extracellular heat shock protein 70 (eHSP70) and interleukin 2 (IL-2) and their correlation in intestine of rats with severe scald injury, and to observe the effects of eHSP70 on CD3(+) T lymphocytes in Peyer's patch of intestine in rats with severe scald injury in vitro.

METHODS(1) Sixty male SD rats were divided into normal control group (NC, n=10, only anesthetized) and scald group (S, n=50) according to the random number table. Rats in scald group were inflicted with 30% total body surface area full-thickness scald on the back. Ten rats from group NC immediately after anesthetization and 10 rats from group S at post injury hour (PIH) 3, 6, 12, 24, 48 were sacrificed to harvest their small intestines. The expressions of eHSP70 and IL-2 were determined with enzyme-linked immunosorbent assay (ELISA), and their correlation was analyzed. (2) Another 2 male SD rats were inflicted with the same injury as above. At PIH 12, CD3(+) T lymphocytes in Peyer's patch of small intestine were isolated and cultured with RPMI 1640 nutrient solution containing 10% fetal bovine serum. Cells were divided into blank control group (BC) and 5, 10, 20 μg/mL eHSP70 groups according to the random number table, with 6 wells in each group. Cells in group BC didn't receive any other treatment, while cells in the latter three groups were treated with corresponding mass concentration of recombinant rat eHSP70. After being cultured for 48 hours, the proportions of Th1 and Th2 in CD3(+) T lymphocytes, and the apoptosis rate of CD3(+) T lymphocytes were detected with flow cytometer, while the expressions of IL-2 and IL-10 in culture supernatant of cells were determined with ELISA. The cell experiments were repeated for 10 times. Data were processed with one-way analysis of variance, Kruskal-Wallis rank sum test, SNK-q test, and Pearson correlation analysis.

RESULTS(1) Compared with those in group NC [(1 278±135) and (48.6±4.9) ng/mg], the levels of eHSP70 [(728±93), (412±31), (314±21), (528±40), (1 028±97) ng/mg] and IL-2 [(38.6±2.3), (32.3±1.0), (25.3±3.6), (33.9±4.1), (44.3±2.6) ng/mg] in intestine of rats in group S obviously decreased at PIH 3, 6, 12, 24, 48 (with q values from 3.48 to 5.32, P values below 0.05), reaching the nadir both at PIH 12, with a significantly positive correlation between the level of IL-2 and the level of eHSP70 (r=0.920, P<0.01). (2) Compared with those in group BC [(8.6±1.1)% and (3.75±0.45)%], the proportion of Th1 obviously increased [(11.3±2.1)%, (15.7±1.8)%, (10.8±1.5)%, with q values from 2.97 to 4.57, P values below 0.05], while the proportion of Th2 obviously decreased [(2.39±0.38)%, (1.05±0.23)%, (2.67±0.26)%, with q values from 2.48 to 4.32, P values below 0.05] in CD3(+) T lymphocytes of rats in 5, 10, 20 μg/mL eHSP70 groups. Compared with those in group BC [(34.3±2.2)% and (254±16) pg/mL], the apoptosis rate of CD3(+) T lymphocytes obviously decreased [(26.1±2.6)%, (20.7±1.5)%, (31.5±2.4)%, with q values from 3.47 to 4.95, P values below 0.05], while the level of IL-2 obviously increased [(417±22), (587±19), (307±27) pg/mL, with q values from 3.02 to 4.98, P values below 0.05] in culture supernatant of CD3(+) T lymphocytes of rats in 5, 10, 20 μg/mL eHSP70 groups. There was no significant difference in the level of IL-10 in culture supernatant of CD3(+) T lymphocytes of rats among the four groups (F=2.12, P>0.05).

CONCLUSIONSThe expressions of eHSP70 and IL-2 in intestine of rats are decreased after severe scald, with a obviously positive correlation between them. eHSP70 can promote the differentiation of CD3(+) T lymphocytes in Th1 orientation, decrease the apoptosis rate of the cells, and promote the release of IL-2 of cells in Peyer's patch of intestine in rats with severe scald injury in vitro.

Animals ; Burns ; metabolism ; CD3 Complex ; metabolism ; Enzyme-Linked Immunosorbent Assay ; HSP70 Heat-Shock Proteins ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Intestine, Small ; metabolism ; Male ; Peyer's Patches ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; cytology

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

OBJECTIVETo compare the difference of Euphorbia Pekinensis Radix before and after being processed with vinegar in the toxicity on rat small intestinal crypt epithelial cells IEC-6, and make a preliminary study on the mechanism of detoxication of Euphorbia Pekinensis Radix processed with vinegar.

METHODWith rat small intestinal crypt epithelial cells IEC-6 as the study object, the MTT method was adopted to detect the effect of Euphorbia Pekinensis Radix before and after being processed with vinegar on IEC-6 cell activity. The morphology of cells were observed by the inverted microscope. The down-regulated mitochondrial apoptosis pathway of enterocytes caused by the vinegar processing was analyzed by using the high content screening.

RESULTCompared with the negative control group, the proliferation inhibition experiment showed that Euphorbia Pekinensis Radix showed a relatively high intestinal cell toxicity (P < 0.01). The results of HCS analysis showed that Euphorbia Pekinensis Radix could significantly reduce the cell nucleus Hoechst fluorescence intensity and mitochondria membrane (P < 0.05, P < 0.01), and increase Annexin V-FITC and PI fluorescence intensity and membrane permeability (P < 0.01, P < 0.01, P < 0.01). After being processed with vinegar, compared with Euphorbia Pekinensis Radix groups with different doses, Euphorbia Pekinensis Radix processed with vinegar could significantly decrease the cell proliferation inhibition effect on enterocytes, increase the cell nuclear Hoechst fluorescence intensity and mitochondria membrane (P < 0.05, P < 0.05), and decrease Annexin V-FITC and PI fluorescence intensity and membrane permeability (P < 0.01, P < 0.01, P < 0.05), and showed a certain dose-effect relationship.

CONCLUSIONThe vinegar processing can further reduce the toxicity of Euphorbia Pekinensis Radix on enterocytes. Its possible mechanism can decrease the effect of Euphorbia Pekinensis Radix on the permeability of IEC-6 cell membrane, so as to provide a basis for further explanation of the detoxication mechanism of Euphorbia Pekinensis Radix processed with vinegar.

Acetic Acid ; chemistry ; Animals ; Apoptosis ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Epithelial Cells ; cytology ; drug effects ; Euphorbia ; chemistry ; Intestine, Small ; cytology ; Rats

We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm2 section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals.
Abdominal Wall/*surgery ; Animals ; Biocompatible Materials/*therapeutic use ; Dogs ; Female ; Intestinal Mucosa/cytology/transplantation ; Intestine, Small/cytology/*transplantation ; Polypropylenes/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tensile Strength ; Tissue Adhesions ; *Tissue Scaffolds ; Transplantation, Heterologous/*methods ; *Wound Healing

This paper is aimed to investigate the feasibility of applying the small intestine submucosa (SIS) as the scaffold in constructing tissue engineering cartilage in vitro. We obtained SIS from the small intestine of specific pathogen-free pigs. Then we isolated tunica submucosa layer from the mucosal, muscular, and serosal layers by gentle mechanic abrasion. The SIS was made acellular by combination of detergent and enzyme digestion. The chondrocytes were seeded onto the SIS and were cultured for 3 weeks. The cell growth, attachment and distribution were detected by histochemical stain, immunohistochemical stain and scan electron microscope. The chondrocytes could adhere and grow well on the matrix surface, and synthesize a large of the GAG and type U collagen. However, the chondrocytes grew only on the surface andsuperficial layer of the scaffold, they did not move into the inner part of the scaffold. It could be concluded that SIS has good cellular compatibility without cytotoxicity and provides temporary substrate to which these anchorage-dependent cells can adhere, and stimulate the chondrocytes anchored on the scaffold to proliferate and keep differentiated phenotype. Further study will be needed to promote the ability of chondrocyte chemotaxis in order to distribute the chondrocytes into the whole scaffold uniformly.
Animals ; Cell Adhesion ; Cell Culture Techniques ; Cell Proliferation ; Chondrocytes ; cytology ; Chondrogenesis ; physiology ; Intestinal Mucosa ; cytology ; Intestine, Small ; cytology ; Swine ; Tissue Engineering ; methods ; Tissue Scaffolds

OBJECTIVETo look for the evidences of motilin receptor expression on interstitial cells of Cajal (ICC) of the rabbit.

METHODSmooth muscle segments with ICC were isolated from the small intestine of 10-day old rabbits. The tissue segments equilibrated in Ca(2+)-free Hanks' solution were dispersed with an enzyme solution containing collagenase type II and then Ficoll density centrifugation was used to dissociate ICC. The cells were suspended and cultured in the M199 medium. The c-kit antibody was applied to distinguish the cultured ICC. The motilin receptor was identified by immunocytochemical assay with GPR38 antibody, c-kit antibody and hoechst 33342 combined to label ICC. Cells cultured for a few days were sorted for ICC with c-kit stained green fluorescent through flow cytometry. The total RNA and proteins extracted from the sorted ICC were respectively used to verify motilin receptor on the ICC by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting.

RESULTWe had successfully dissociated and cultured ICC of rabbit small intestine in vitro. Fluorescent staining with c-kit antibody confirmed that the culture ICC was successful. Triple-labeled immunofluorescent staining had detected the motilin receptor on membrane of ICC. Flow cytometry analysis showed that the ratio of c-kit positive cell in the cultured cells was 64.3%. The number of sorted ICC was 6.7 × 10(5) and 5.6 × 10(6). The results of RT-PCR and Western blot confirmed that the ICC had motilin receptor expression.

CONCLUSIONOur study demonstrated presence of motilin receptor on ICC of the rabbit. The present results may suggest that ICC play an important role in gastrointestinal movement induced by motilin.

Animals ; Cells, Cultured ; Interstitial Cells of Cajal ; metabolism ; Intestine, Small ; cytology ; Rabbits ; Receptors, Gastrointestinal Hormone ; metabolism ; Receptors, Neuropeptide ; metabolism

BACKGROUNDThe protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley (SD) rats have been confirmed in our previous research. However, its exact mechanism is unclear. This study was to evaluate the role of PI3K/Akt signal pathway in the protective effect of magnesium sulfate against ischemia-reperfusion injury of the small intestine in SD rats.

METHODSRat model of intestinal ischemia-reperfusion injury was used. The SD rats were divided into four groups randomly: sham operation group, ischemia-reperfusion group, magnesium sulfate group and magnesium sulfate plus LY294002 (an inhibitor of PI3K) group. The pathological changes of intestinal mucosa were examined; the activity of diamine oxidase (DAO) in plasma, the plasma contents of malondialdehyde (MDA), and apoptosis rate of the intestinal mucosal cells were determined and compared. The expression of p-Akt was detected by Western blotting.

RESULTSThere were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), enhanced DAO activity (P < 0.05), elevated contents of MDA (P < 0.05), higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the ischemia-reperfusion group compared with the sham operation group. There were less evident pathological changes of the intestinal mucosa (lower Chiu's score, P < 0.05), lower DAO activity (P < 0.05), lower contents of MDA (P < 0.05), and lower apoptosis rate (P < 0.05), but higher level of p-Akt (P < 0.05) in the magnesium sulfate group compared with the ischemia-reperfusion group. There were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), higher contents of MDA (P < 0.05), higher DAO activity (P < 0.05) and higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the magnesium sulfate plus LY294002 group compared with the magnesium sulfate group.

CONCLUSIONSActivation of PI3K/Akt signal pathway results in the reduction of cell apoptosis, which likely accounts for the protective effect of magnesium sulfate against intestinal ischemia-reperfusion injury.

Amine Oxidase (Copper-Containing) ; metabolism ; Animals ; Apoptosis ; drug effects ; Blotting, Western ; Disease Models, Animal ; Intestinal Mucosa ; cytology ; drug effects ; Intestine, Small ; drug effects ; Magnesium Sulfate ; therapeutic use ; Malondialdehyde ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effect and mechanism of FTY720 on acute graft versus host disease (GVHD) in rat small bowel transplantation (SBTx).

METHODSHeterotopic SBTx was performed using a parent (WF)-into-F1 (WFxACI) rat combination. Recipient rats were divided into experimental group (n=6) and control group (n=6). Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days. Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation. Recipient survival and lymphocyte apoptosis were compared between the two groups.

RESULTSRecipients in the control group died of GVHD after a mean survival time of (16+/-2.1) days. FTY720-treated recipients had a significantly longer survival (>100 days). After administration of FTY720, the percentage of apoptotic lymphocytes was significantly increased in the graft as compared to that in the control group by flow cytometry. The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL.

CONCLUSIONFTY720 effectively induces the lymphocyte apoptosis, inhibits the lesion of target tissues by GVHD, and prolongs the recipient survival.

Animals ; Apoptosis ; drug effects ; Fingolimod Hydrochloride ; Graft vs Host Disease ; immunology ; prevention & control ; Immunosuppressive Agents ; pharmacology ; Intestine, Small ; transplantation ; Lymphocytes ; cytology ; drug effects ; Male ; Propylene Glycols ; pharmacology ; Rats ; Rats, Inbred WF ; Sphingosine ; analogs & derivatives ; pharmacology ; Transplantation, Heterotopic