Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and central secretory tissues

AIM: To explore the effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and their central secretory tissues and to find out the role leptin and orexin-A play in acute inflammatory responses.METHODS: An intestinal ischemia-reperfusion (I/R)injury model of rats was established and rats were divided randomly into six groups: sham-operation group, 60 min ischemia/30 min reperfusion group (I60'R30'), I60'R90',I60'R150', I60'R240' and I60'R360', 9 rats each group.Two highly-sensitive radioimmunoassays for leptin and orexin-A were established and used to check the change of their concentrations in peripheral blood and central secretory tissues before and after intestinal I/R injury.RESULTS: Compared with the serum leptin level before injury, it decreased significantly in I60'R30' group and increased significantly in I60'R360' group; compared to sham-operation group after injury, serum leptin level increased significantly in I60'R360' group; compared to sham-operation group after injury, adipose leptin levels decreased significantly in I60'R30' and I60'R90' groups,while increased significantly in I60'R360' group. There was no significant difference between the expression levels of orexin-A before and after I/R injury.CONCLUSION: Leptin has a time-dependent response and orexin-A has a delayed response to acute inflammatory stimuli such as intestinal I/R injury and they may participate in metabolic disorders in injury as inflammatory cytokines.

Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Expression of COX-2 in Different Subtypes of Gastric Intestinal Metaplasia and Gastric Carcinoma by Tissue Microarray

Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.

Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion

AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:Male Wistar rats were randomly divided into three groups(36 rats each) :the sham-operation group(group S) ,lower limb ischemia-reperfusion group(group LIR) ,and penehyclidine hydrochloride postconditioning group(group PHC) .Each group was divided into subgroups(n=6 in each group) according to ischemic-reperfusion time,i.e.immediately 0 h(T1) ,1 h(T2) ,3 h(T3) ,6 h(T4) ,12 h(T5) ,and 24 h(T6) .Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h.In group PHC,0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia.The designated rats were sacrificed at different time-points of reperfusion;diamine oxidase(DAO) ,superoxide dismutase(SOD) activity,myeloperoxidase(MPO) of small intestinal tissue,plasma endotoxin,DAO,tumor necrosis factor-α(TNF-α) ,and interleukin(IL) -10 in serum were detected in the rats. RESULTS:The pathological changes in the small intestine were observed under light microscope.The levels of MPO,endotoxin,serum DAO,and IL-10 at T1-T6,and TNF-αlevel at T1-T4 increased in groups LIR and PHC(P<0.05) compared with those in group S,but tissue DAO and SOD activity at T1-T6 decreased(P<0.05) .In group PHC,the tissue DAO and SOD activity at T2-T6,and IL-10 at T2-T5 increased to higher levels than those in group LIR(P<0.05) ;however,the levels of MPO,endotoxin,and DAO in the blood at T2-T6,and TNF-αat T2 and T4 decreased(P<0.05) . CONCLUSION:Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR.Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.

Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion

Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion(IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the(potential) future clinical implications.

Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury

BACKGROUND Intestinal ischemia reperfusion(I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22(USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice.AIM To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury.METHODS An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion.Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo. siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22,Cyclin D1, and proliferating cell nuclear antigen(PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival(viability) and cell cycle were evaluated using the Cell Counting Kit-8and flow cytometry, respectively.RESULTS USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro, which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group(P < 0.05), while opposite results were observed in the USP22 overexpression group(P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration.CONCLUSION USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury.

Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with the preservation of endothelial nitric oxide synthase protein

AIM： To investigate the protective effect of rosuvastatin on ischemia-reperfusion （I-R）-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase （eNOS） protein. METHODS： Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot. RESULTS： The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissueassociated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattracrant-1 （CINC-1） and tumor necrosis factor-α（TNF-α）. These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvo astatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-α was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION： Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.

Engineering biomimetic intestinal topological features in 3D tissue models: retrospects and prospects

Conventional 2D intestinal models cannot precisely recapitulate biomimetic features in vitro and thus are unsuitable for various pharmacokinetic applications,development of disease models,and understanding the host-microbiome interactions.Thus,recently,efforts have been directed toward recreating in vitro models with intestine-associated unique 3D crypt-villus(for small intestine)or crypt-lumen(for large intestine)architectures.This review comprehensively delineates the current advancements in this research area in terms of the different microfabrication technologies(photolithography,laser ablation,and 3D bioprinting)employed and the physiological relevance of the obtained models in mimicking the features of native intestinal tissue.A major thrust of the manuscript is also on highlighting the dynamic interplay between intestinal cells(both the stem cells and differentiated ones)and different biophysical,biochemical,and mechanobiological cues along with interaction with other cell types and intestinal microbiome,providing goals for the future developments in this sphere.The article also manifests an outlook toward the application of induced pluripotent stem cells in the context of intestinal tissue models.On a concluding note,challenges and prospects for clinical translation of 3D patterned intestinal tissue models have been discussed.

THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots. Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54 45±9 80, male/female 1 05,body mass index (BMI)26 48±4 01] and 79 were subjects with non insulin dependent diabetes mellitus (NIDDM)(age 55 86±10 00,male/female 1 08,BMI 26 75±3 30). Design and measurements. An association study of FABP2 Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)]. Results. The geneotype and allele frequencies of FABP2 Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm 2 versus FA<75cm 2 )in NIDDM subjects (X 2 =11 460,P=0 003),with significantly increased in Thr54 carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm 2 (odd ratio for genotype was 4 62,X 2 =10 112,P=0 001;and for allele=2 36,X 2 =5 379,P=0 020).The FA in NIDDM Thr54(+)subgroup was significantly lower than that in subjects with NIDDM Thr54( )sugroup(61 19±21 51cm 2 versus 75 36±31 70cm 2 ,P=0 021). Stepwise regression analysis revealed that FABP2 Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0 003). Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2 Thr54 variant.

EFFECT OF PREOPERATIVE GLUTAMINE ADMINISTRATION ON ICAM-1 EXPRESSION IN RAT LUNG INDUCED BY INTESTINAL ISCHEMIA-REPERFUSION

Objective To evaluate the effect of preoperative glutamine administration on intracellular adhesion molecule-1 （1CAM-l） expression in rat lung induced by intestinal ischemia-reperfusion（ I/R）. Methods Sprague-Dawley rats （n = 25） were randomly divided into 5 groups： sham group （sham surgery）, glutamine groups （three different doses） and control group. All groups except sham were subjected to intestinal 1/R injury, and superior mesenteric artery （SMA） occluded for 60 min followed by 90 min of reperfusion. Lung injury was evaluated with Evans blue dye concentration and histopathologic examination. The immunohistochemical expression and mRNA expression of 1CAM-1 were measured with immunohistochemical staining and RT-PCR method respectively. The level of myeloperoxidase （MPO） was also measured with biochemistry method. Results Intestinal 1/R resulted in lung injury characterized by an increase in Evans blue dye concentration, neutrophil sequestration, and obvious staining for expression of pulmonary 1CAM-l, compared with sham group. The expression of 1CAM-1 and the level of MPO in rat lung were lower in glutamine groups compared with control group. Conclusion 1-R injury increases the expression of 1CAM-1 within the lung. This may contribute to the migration, accumulation and activation of polymorphonuclear neutrophils （PAINs） after such injury. Preoperative glutamine administration attenuates rat lung injury induced by intestinal I-R, and inhibiting 1CAM-1 expression maybe one of the potential mechanisms.

Effect of blood transfusion therapy on oxygen saturation in brain and intestinal tissues of children with premature anaemia

Objective: To study the effect of blood transfusion therapy on oxygen saturation in brain and intestinal tissues of children with premature anaemia. Methods: Ninety-five children with premature anaemia in our hospital from August 2016 to July 2018 were selected and divided into three groups according to the different degrees of anemia, namely, mild group (n=30), moderate group (n=30) and severe group (n=35), meanwhile, another 35 premature without anemia were set as control group. Then the basal vital signs, levels of hemoglobin (Hb) and hematocrit (Hct), as well as the oxygen saturation in brain and intestinal tissue were compared among the four groups. Results: The SBP and DBP between the four groups after treatment had no difference. The HR and RR after treatment in the control group and the mild group were significantly higher than those in the severe group. The RR of the mild group was significantly lower than that of the control group, with statistical difference. The Hb in the control group and the mild group was significantly higher than that in the moderate group and the severe group. The Hb in the moderate group was significantly higher than that in the severe group. Hct in the control group and the mild group was significantly higher than that in the severe group. The Hct in the moderate group had no statistic difference with that of the mild group and severe group. The cerebral oxygen saturation after treatment in the control group and the mild group was significantly higher than that in the severe group, meanwhile the intestinal tissue oxygen saturation after treatment of the control group was significantly higher than that in the severe group. Cerebral oxygen saturation after treatment showed no difference between the severe group and the moderate group, and the intestinal tissue oxygen saturation after treatment either had no difference among the severe group, the moderate group and the mild group. Conclusion: Blood transfusion therapy can significantly improve the oxygen saturation of brain and intestinal tissues in children with premature anaemia without affecting blood pressure, and improve the degree of anemia, which can be used reasonably under the strict control of clinical indications.

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

AIM： To evaluate whether pyrrolidine dithiocarbamate （PDTC）, an enhancer of HO production, attenuates intestinal IR injury. METHODS： Eighteen male rats were randomly allocated into three groups： （a） sham; （b） IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and （c） PDTC treatment before IR. Intestinal microvascular perfusion （IMP） was monitored continuously by laser Doppler flowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase （LDH） levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period. RESULTS： At the end of the reperfusion in the IR group, IMP recovered partially to 42.5% of baseline （P〈0.05 vs sham）, whereas PDTC improved IMP to 67.3% of baseline （P〈0.01 vs IR）. There was a twofold increase in HO activity in PDTC group （2 062.66±106.11） as compared to IR （842.3±85.12） （P〈0.001）. LDH was significantly reduced （P〈0.001） in PDTC group （585.6±102.4） as compared to IR group （1 973.8±306.5）. Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group. CONCLUSION： Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine.

Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn’s disease

In this letter,we commented on the article by Wu et al.We examined the interactions between mesenteric adipose tissue,creeping fat,and gut microbiota in Crohn’s disease(CD),a condition marked by chronic gastrointestinal inflammation with a rising global incidence.The pathogenesis of CD involves complex genetic,environmental,and microbial factors.Dysbiosis,which is an imbalance in gut microbial communities,is frequently observed in CD patients,highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response.Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines.The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation,further complicating disease management.Recent research has suggested that fecal microbiota transplantation could help restore microbial balance,offering a promising therapeutic strategy to improve clinical disease response.

Advances in the research of intestinal fungi in Crohn's disease

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology,delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease(CD).Insights were gained from fecal microbiota transplantation(FMT)in mouse models,revealing the intricate interplay between the gut microbiota,mesenteric adipose tissue(MAT),and creeping fat.The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD;moreover,through the FMT mouse model,it observed the impact of samples from healthy patients and those with CD on symptoms.The pathogenesis of CD is complex,and its etiology remains unclear;however,it is widely believed that gut microbiota dysbiosis plays a significant role.Recently,with the development and application of next-generation sequen-cing technology,research on the role of fungi in the pathogenesis and chronicity of CD has deepened.This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

Zinc pretreatment for protection against intestinal ischemiareperfusion injury

BACKGROUND Intestinal ischemia-reperfusion(I/R)injury(II/RI)is a critical condition that results in oxidative stress,inflammation,and damage to multiple organs.Zinc,an essential trace element,offers protective benefits in several tissues during I/R injury,but its effects on intestinal II/RI remain unclear.METHODS C57BL/6 mice were pretreated with zinc sulfate(ZnSO4,10 mg/kg)daily for three days before I/R injury was induced via superior mesenteric artery occlusion(SMAO)and abdominal aortic occlusion(AAO)models.Tissue and serum samples were collected to evaluate intestinal,liver,and kidney damage using Chiu’s score,Suzuki score,and histopathological analysis.Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species(ROS)and superoxide dismutase(SOD)levels.RESULTS Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models(P<0.001).The serum levels of liver enzymes(alanine aminotransferase,aspartate aminotransferase)and kidney markers(creatinine and urea)were lower in the zinc-treated mice than in the control mice,indicating reduced hepatic and renal injury.In vitro,zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury.Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls.CONCLUSION Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage.These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.

A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine

A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophago gastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano’s classification, its staging was clinically diagnosed as stage Ⅱ. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone) regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow- up EGD and histological examinations detected no recurrence of the disease.

The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

bFGF and TGFβ expression in rat kidneys after ischemic/reperfusional gut injury and its relationship with tissue repair

INTRODUCTION Intestinal isehemia/rePerfusion(I/R)oeeureommonly in eritieally 111 Patients.It 15 wellreeognized that gutl/R may eause tissue damageand dysfunetion of intestine,and induee

L-arginine administration ameliorates serum and pulmonary cytokine response after gut ischemia-reperfusion in immature rats

AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats. METHODS: Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor a (TNFα) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage. RESULTS: When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17±42.93 μmol/L) when compared with IR group (87.57±23.17 μmol/L, t=3.190, P= 0.008 <0.01). Serum MDA reduced significantly in IR+L-arg group (8.93±1.50 nmol/L) when compared with SHAM (23.78±7.81 nmol/L, t= 3.243, P= 0.007<0.01) and IR (25.54±9.32 nmol/L, t= 3.421, P= 0.006<0.01). ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81±7.84 pg/mL) than that in SHAM (35.52±10.82 pg/mL, t= 2,571, P= 0,03<0.05) and IR (50.83±22.05 pg/mL, t= 3.025, P= 0.009<0.01) groups. MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73±1.99 nmol/L) than in SHAM (16.62±2.28 nmol/L, t= 3.280, P = 0.007<0.01) and IR (21.90±4.82 nmol/L, t= 3.322, P= 0.007<0.01) groups. Serum and lung TNFα concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50±8.92, 33.20±16.59, and 22.50±6.09 in SHAM, IR, and IR+L-arg groups, respectively. CONCLUSION: Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group. L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).