A ROLE OF EGF IN GASTRIC MUCOSAL CYTOPROTECTION OF MOXIBUSTION

Moxibustion at Shenque (RN 8) for three weeks had no effect on the content of EGF (epidermic growth factor) in plasma, but significantly incresased the totoal amount of EGF in 2h’s gastric juice (P<0. 01 ); After salivoectomy, the concentration of EGF ingastric juice decreased significantly and moxibustion could not recover it. Moxibustion for three weeks in advance could accelerate the healing process of the acetic acid-produced gastric ulcer (P< 0. 05). Salivoectomy obviously weakened the gastric cytoprotective effect of moxibustion. The results suggest that the gastric cytoprotective effect of moxibustion may relate to its stimulation of secretion of EGF by salivary gland.

Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances,ischemia-reperfusion injury following Pringle maneuver,and Budd-Chiari syndrome

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.

Cytoprotection behind heme oxygenase-1 in renal diseases

Renal insults are considered a public health problem and are linked to increased rates of morbidity and mortality worldwide. The heme oxygenase(HO) system consists of evolutionary specialized machinery that degrades free heme and produces carbon monoxide, biliverdin and free iron. In this sense, the inducible isoform HO-1 seems to develop an important role and is widely studied. The reaction involved with the HO-1 molecule provides protection to injured tissue, directly by reducing the toxic heme molecule and indirectly by the release of its byproducts. The up regulation of HO-1 enzyme has largely been described as providing antioxidant, antiapoptotic, anti-inflammatory and immunomodulatory properties. Several works have explored the importance of HO-1 in renal diseases and they have provided consistent evidence that its overexpression has beneficial effects in such injuries. So, in this review we will focus on the role of HO-1 in kidney insults, exploring the protective effects of its up regulation and the enhanced deleterious effects of its inhibition or gene deletion.

ACUPUNCTURE-MOXIBUSTION, HEAT SHOCK PROTEIN 70 AND CYTOPROTECTION

Pleat shock protein 70 （HSP70） is a kind of non-specific cytoprotective protein, and its generation can be induced by acupuncture and moxibustion. In the present paper, the authors review the protective actions of HSP70 on the heart, gastric mucosa, liver, brain tissues, kidney, etc., and the relationship among acupuncture/moxibustion, heat shock protein and the cytoprotective actions. It is worth studying the cytoprotective effect of acupuncture and moxibustion by way of the resultant generation of HSP70 in the organism.

Effects of sulfhydryl compounds on pancreatic cytoprotection in acute necrotic pancreatitis

Objective To observe sulfhydryl compound variation in the injury of pancreatic cells and the effects of external sulfhydryl compounds on cytoprotection.Methods Male Wistar mice were divided randomly into three groups: groups A and B served as animal models (retrograde duct infusion with 5% sodium taurocholate), in group A, 45 animals were treated with normal saline therapy, in group B, 45 aminals were treated with Tiopronin therapy; and group C, 15 animals, were designated as normal control. Animals were killed at 2, 4, 6, 12 and 24 h, and pancreatic tissue was analyzed for total sulfhydryl (TSH), nonprotein sulfhydryl (NPSH) and malondialdehyde (MDA). Histopathology, serum amylase (Sam) and C reactive protein (CRP) were assessed as well.Results Levels of Sam and CRP increased in both group A and group B, with corresponding pathological changes of acute nerotic pancreatitis (ANP). Levels of TSH, NPSH and protein sulfhydryl (PSH) in group A decreased markedly during pancreatitis (P<0.01), but MDA increased significantly (P<0.01). The depletion of NPSH in group B was markedly ameliorated at 4 h or 6 h, when Tiopronin was prophylactically administered (P<0.05), after which the level of MDA showed very little increase when compared to group A (P<0.01). Histopathological damage was attenuated to a certain extent, in regards to serum amylase and CRP.Conclusions All sulfhydryl compounds decreased significantly during ANP; external sulfhydryl compound could protect the pancreatic cells most likely as a type of scavengers of oxygen free radicals, which are critically involved in the pathophysiology of ANP. Sulfhydryl plays an important role in the action of pancreatic cytoprotection.

αB-crystallin mini-peptides support corneal healing in vitro and in vivo in rabbit model

AIM:To evaluate if topical use of αB-crystallin minipeptides supports corneal healing following flap surgery.METHODS:Cultured corneal cells were treated with fluorescent taggedαB-crystallin mini-peptides to assess its internalization.Cultured corneal cells pre-treated with or without the mini-peptides were exposed to H_(2)O_(2) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Elongation of neurites of cultured trigeminal neurones was examined following treatment either withαB-crystallin mini-peptides or protein.Cultured trigeminal neurones were pre-treated either with αB-crystallin mini-peptides or crystallin protein and exposed to H_(2)O_(2) and presence of beading in the dendrites and axons was assessed.Corneal flap surgery was conducted on rabbit cornea and treated topically either withαB-crystallin peptide(0.5 mg/mL thrice daily for 14d)or phosphate-buffered saline(PBS).Corneal healing was evaluated under slit-lamp biomicroscope,mRNA expression of inflammatory cytokines were assessed and the corneas were evaluated by histopathology.RESULTS:Internalization ofαB-crystallin mini-peptides was ascertained by the detection of fluorescence within the corneal cells.The MTT assay revealed that treatment withαB-crystallin mini-peptide reduced cell death induced by H_(2)O_(2) treatment.The mini-peptides did not influence the elongation of trigeminal neurites,but significantly(P<0.05)reduced beading in the neurites.In rabbit eye,the treated corneas showed reduced hyper-reflective zones(P<0.05)and suppression in the expression of inflammatory cytokines.Histopathological examination also revealed reduction of inflammatory response in treated corneas.CONCLUSION:TheαB-crystallin mini-peptides restrict the damage to corneal cells and neurons and aids in corneal healing.

The cytoprotection of milk-derived MFG-E8 on mitochondria-injured L6 cell via mediation of Akt/bcl-2/bax-caspase-3 signaling pathway

Mitochondria-dependent myoblast apoptosis induced by oxidative stress and decrease in successful protein synthesis play a crucial role in loss of muscle mass and functionality further to result in sarcopenia.Here,we investigated the relationship between milk fat globule-EGF factor VIII(MFG-E8)and mitochondrial-dependent apoptosis pathway.MFG-E8 exert cytoprotection through increasing L6 cells survival/apoptotic ratio,increasing mitochondrial membrane potential and regulating S and G2/M phases.By observing cell ultrastructure,MFG-E8 improved mitochondrial homeostasis mainly through decreasing cytochrome-c release,expression of caspase-9 and caspase-3,mitochondrial vacuolation and mitophagy thereby inhibiting cell apoptosis.From molecular perspective,MFG-E8 repaired mitochondria fragmentation by increasing mitochondrial DNA replication and regulated expression of key mitochondrial-apoptotic factors(upregulation:B-cell lymphoma-2 like 1(bcl2l1),bcl2l2,cyclooxygenase-1 and mitochondrial uncoupling protein-2;Downregulation:p21 and p53)further to improve mitochondrial function and inhibit apoptosis.Moreover,MFG-E8 inhibited mitochondrialdependent apoptosis via Akt/bcl-2/bax/caspase-3 signaling cascades.Taken together,our research provided a promising approach for deep exploration of MFG-E8 on cytoprotection against mitochondrial injury and mitochondrial-mediated apoptosis and application of anti-apoptosis in alleviating sarcopenia.

Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division, differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase （HO）. Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte. This review describes the recent literature on the diverse properties of heme/HO in the intestine tract. The roles of heme/HO in the regulation of the cell cycle/ apoptosis, detoxification of xenobiotics, oxidative stress, inflammation, development of colon cancer, hemeiron absorption and intestinal motility are specifically examined.

Heme oxygenase-1 and gut ischemia/reperfusion injury: A short review

Ischemia/reperfusion (I/R) injury of the gut is a significant problem in a variety of clinical settings and is associated with a high morbidity and mortality. Although the mechanisms involved in the pathogenesis of gut I/R injury have not been fully elucidated, it is generally believed that oxidative stress with subsequent inflammatory injury plays an important role. Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of CO, biliverdin, and free iron. The HO system is believed to confer cytoprotection by inhibiting inflammation, oxidation, and apoptosis, and maintaining microcirculation. HO-1, an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of intestinal I/R injury. HO-1 system is an important player in intestinal I/R injury condition, and may offer new targets for the management of this condition.

A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers

AIM:To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection(ESD) gastric ulcers.METHODS:Patients with gastric tumors indicated for ESD were prospectively studied.After ESD,all patients were treated with intravenous omeprazole for the first 3 d.Patients were then randomly assigned to oral lafutidine or rabeprazole.Ulcer size,ulcer size reduction rate,and ulcer stage were evaluated 4 wk later.Occurrence of complication was monitored throughout the 4-wk period.RESULTS:Sixty five patients were enrolled in the study,and 60 patients were subjected to the final analysis.In the lafutidine group(30 lesions in 29 patients),initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm,respectively.In the rabeprazole group(34 lesions in 31 patients),the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm,respectively.Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%,respectively(P=0.974).Ulcer stage 4 wk post-ESD did not differ significantly between the two groups(P=0.868).Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period,although the difference of bleeding rate between the two groups was not statistically significant(P=0.157).CONCLUSION:Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.

Autophagy in fate determination of mesenchymal stem cells and bone remodeling

Mesenchymal stem cells(MSCs)have been widely exploited as promising candidates in clinical settings for bone repair and regeneration in view of their self-renewal capacity and multipotentiality.However,little is known about the mechanisms underlying their fate determination,which would illustrate their effectiveness in regenerative medicine.Recent evidence has shed light on a fundamental biological role of autophagy in the maintenance of the regenerative capability of MSCs and bone homeostasis.Autophagy has been implicated in provoking an immediately available cytoprotective mechanism in MSCs against stress,while dysfunction of autophagy impairs the function of MSCs,leading to imbalances of bone remodeling and a wide range of aging and degenerative bone diseases.This review aims to summarize the up-to-date knowledge about the effects of autophagy on MSC fate determination and its role as a stress adaptation response.Meanwhile,we highlight autophagy as a dynamic process and a double-edged sword to account for some discrepancies in the current research.We also discuss the contribution of autophagy to the regulation of bone cells and bone remodeling and emphasize its potential involvement in bone disease.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers

AIM: To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.

Rocket “Eruca sativa”:A salad herb with potential gastric anti-ulcer activity

AIM： To validate gastric anti-ulcer properties of Rocket ＂Eruca sativa＂ on experimentally-induced gastric secretion and ulceration in albino rats. METHODS： Gastric acid secretion studies were undertaken using pylorus-ligated rats. Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong alkalis, indomethacin and hypothermic restraint stress. The levels of gastric wall mucus （GWM）, nonprotein sulfhydryls （NP-SH） and malondialdehyde （MDA） were also measured in the glandular stomach of rats following ethanol administration. The gastric tissue was also examined histologically. The extract was used in two doses （250 and 500 mg/kg body weight） in all experiments. RESULTS： In pylorus-ligated Shay rats, the ethanolic extract of Rocket ＂Eruca sativa L.＂ （EER） significantly and dose-dependently reduced the basal gastric acid secretion, titratable acidity and ruminal ulceration. Rocket extract significantly attenuated gastric ulceration induced by necrotizing agents （80% ethanol, 0.2 mol/L NaOH, 25% NaCl）, indomethacin and hypothermic restraint stress. The anti-ulcer effect was further confirmed histologically. On the other hand, the extract significantly replenished GWM and NP-SH levels, as well as the MDA level significantly reduced by extract pretreatment. CONCLUSION： Rocket extract possesses antisecretory, cytoprotective, and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect is possibly through prostaglandinmediated activity and/or through its anti-secretory and antioxidant properties.

Hydrogen sulfide inhibits beta-amyloid peptide-induced apoptosis in PC12 cells and the underlying mechanisms

BACKGROUND：Studies have demonstrated that hydrogen sulfide（H2S） levels are 55% lower in brains of Alzheimer＇s disease（AD） patients than in age-matched normal individuals,which suggests that H2S might be involved in some aspects of AD pathogenesis.OBJECTIVE：To observe the protective mechanisms of varied concentrations of H2S against β-amyloid-peptide（Aβ） induced apoptosis in pheochromoytoma（PC12） cells,and to analyze the pathway of action.DESIGN,TIME AND SETTING：A controlled,observational,in vitro experiment was performed at Neurophysiology Laboratory in Zhongshan Medical School,Sun Yat-sen University between July 2006 and May 2007.MATERIALS：PC12 cells were provided by the Animal Experimental Center of Medical School of Sun Yat-sen University.Glybenclamide,rhodamine123,and dihydrorhodamine123 were purchased from Sigma（USA）.METHODS：PC12 cells were incubated at 37 ℃ in a 5% CO2-enriched incubator with RPMI-1640 medium,supplemented with 5% horse-serum and 10% fetal bovine serum.Cells in logarithmic growth curves received different treatment：The PC12 cells were maintains at 37 ℃ with the original medium,then incubated in Aβ25-35,sodium hydrosulfide（NaHS）,glybenclamide,NaHS＋ Aβ25-35,or pretreated with glybenclamide 30 minutes prior to administration of and Aβ25-35,respectively.MAIN OUTCOME MEASURES：（1） The survival rate of PC12 cells was detected by MTT assay and Hoechst staining.（2） The apoptosis rate of PC12 cells was detected utilizing flow cytometry with propidium iodide staining,and morphological changes of apoptotic cells were observed.（3） The mitochondrial membrane potential was detected by Rhodamine123-combined flow cytometry.（4） The intracellular reactive oxygen species content was detected by dihydrorhodamine123-combined flow cytometry.RESULTS：Aβ25-35 induced significantly decreased viability and increased percentage of apoptosis in PC12 cells,as well as dissipated mitochondrial membrane potential expression and an overproduction of reactive oxygen species.When PC12 cells were co-treated with NaHS and Aβ25-35,the decreased cell viability induced by 20 μmol/L Aβ25-35 was concentration-dependently blocked by NaHS（50,100,and 200 μmol/L）.NaHS（100 μmol/L） obviously reduced the percentage of apoptotic PC12 cells induced by 20 μmol/L Aβ25-35.In addition,100 μmol/L NaHS inhibited mitochondrial membrane potential dissipation and reactive oxygen species overproduction.When the ATP-sensitive K channel（KATP） inhibitor,glybenclamide,was administered 30 minutes prior to NaHS and Aβ25-35 treatment,the NaHS-dependent cellular protection was partly blocked.This resulted in reduced PC12 cell viability and increased the percentage of apoptosis,as well as significantly blocked mitochondrial membrane potential preservation and inhibited reactive oxygen species overproduction due to NaHS treatment.CONCLUSION：NaHS protected PC12 cells against Aβ25-35-induced damage.NaHS-dependent cellular protection was associated with mitochondrial membrane potential preservation and inhibition of reactive oxygen species overproduction.The KATP channel inhibitor,glybenclamide,significantly blocked the cellular protective effects of NaHS,indicating that KATP channel activation plays an important role in NaHS-induced protection of PC12 cells to Aβ25-35-induced damage.

Neuroprotective effects of salvianolic acid B on secondary spinal cord damage

Salvianolic acid B （Sal B）, an effective ingredient of Danshen （salvia miltiorrhiza root）, has been shown to exhibit anti-oxidative and anti-inflammatory effects. The present study investigated whether Sal B has a neuroprotective effect on secondary spinal cord injury when administrated alone. In addition, the effects of Sal B on attenuating expression of tumor necrosis factor-α （TNF-α） following acute spinal cord injury were analyzed, as well as the effects of combined treatment of Sal B and etanercept. Immunohistochemical staining demonstrated that Sal B significantly reduced matrix metalloproteinase-1 and c-Fos expression at 24 hours after spinal cord injury, and decreased tissue edema was detected using the dry-wet weight method at 3 days after injury. In addition, Sal B significantly promoted recovery of motor function in rats. These effects were most significant at a dose of 20 mg/kg Sal B. At 24 hours after spinal cord injury, reverse transcription-polymerase chain reaction and western blot assay results showed that Sal B, etanercept, or the combination significantly suppressed increased TNF-α mRNA and protein expression, although the combination resulted in more significant outcomes. These results suggested that Sal B exerted neuroprotective effects against secondary spinal cord injury by reducing expression of matrix metalloproteinase-1, c-Fos, and TNF-α. Moreover, Sal B combined with etanercept resulted in more significant anti-inflammatory effects.

Pentadecapeptide BPC 157 and the central nervous system

We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157,three very recent demonstrations that may be essential in the gut-brain and braingut axis operation,and therapy application in the central nervous system disorders,in particular.Firstly,given in the reperfusion,BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke,sustained brain neuronal damages were resolved in rats as well as disturbed memory,locomotion,and coordination.This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats.Secondly,there are L-NG-nitro arginine methyl ester(L-NAME)-and haloperidol-induced catalepsy as well as the rat acute and chronic models of 'positivelike' schizophrenia symptoms,that BPC 157 counteracted,and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine(dopamine agents application),MK-801(non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration(to induce sensitivity).Thirdly,after rat spinal cord compression,there were advanced healing and functional recovery(counteracted tail paralysis).Likewise,in BPC 157 therapy,there is specific support for each of these topics:counteracted encephalopathies;alleviated vascular occlusion disturbances(stroke);counteracted dopamine disturbances(dopamine receptors blockade,receptors super sensitivity development,or receptor activation,over-release,nigrostriatal damage,vesicles depletion),and nitric oxide-system disturbances("L-NAME non-responsive,L-arginine responsive," and "L-NAME responsive,L-arginine responsive")(schizophrenia therapy);inflammation reduction,nerve recovery in addition to alleviated hemostasis and vessels function after compression(spinal cord injury therapy).Thus,these disturbances may be all resolved within the same agent's beneficial activity,i.e.,the stable gastric pentadecapeptide BPC 157.

Cytoprotective effects of quercetin and its sugar-containing natural congeners in cultured HEK293 cells injured by anoxia/hypoglycemia and the structure-effect relationship thereto

Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium;Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined;The effect intensity of the 3 flavonoids were compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD,and reduced LDH level;the all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I>R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.

Anti-free radical and cytoprotective effects of quercetin and its sugar-containing natural congeners in cultured HEK293 cells injured by anoxia/hypoglycemia and the structure-effect relationship thereto

Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium.Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined.The effect intensity of the 3 flavonoids was compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD and reduced LDH level.The all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I >R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.

Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect

BACKGROUND Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research,we focused on the first demonstration of the severe occlusion/occlusion-like syndrome induced by stomach perforation.The revealed stomachinduced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure.This general point was particularly reviewed.As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels,peripheral and central,and other similar noxious procedures that severely affect endothelium function,the stable gastric pentadecapeptide BPC 157 was resolving therapy.AIM To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect.METHODS The procedure included deeply anesthetized rats,complete calvariectomy,laparotomy at 15 min thereafter,and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome.At 5 min post-perforation time,rats received therapy[BPC 157(10μg or 10 ng/kg)or saline(5 mL/kg,1 mL/rat)(controls)]into the perforated defect in the stomach).Sacrifice was at 15 min or 60 min post-perforation time.Assessment(gross and microscopy;volume)included:Brain swelling,peripheral vessels(azygos vein,superior mesenteric vein,portal vein,inferior caval vein)and heart,other organs lesions(i.e.,stomach,defect closing or widening);superior sagittal sinus,and peripherally the portal vein,inferior caval vein,and abdominal aorta blood pressures and clots;electrocardiograms;and bleeding time from the perforation(s).RESULTS BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect(raised vessel presentation;less bleeding,defect contraction)and occlusion/occlusion-like syndromes counteraction.BPC 157 therapy(into the perforated defect),induced immediate shrinking and contraction of the whole stomach(unlike considerable enlargement by saline application).Accordingly,BPC 157 therapy induced direct blood delivery via the azygos vein,and attenuated/eliminated the intracranial(superior sagittal sinus),portal and caval hypertension,and aortal hypotension.Thrombosis,peripherally(inferior caval vein,portal vein,abdominal aorta)and centrally(superior sagittal sinus)BPC 157 therapy markedly reduced/annihilated.Severe lesions in the brain(swelling,hemorrhage),heart(congestion and arrhythmias),lung(hemorrhage and congestion),and marked congestion in the liver,kidney,and gastrointestinal tract were markedly reduced.CONCLUSION We revealed stomach perforation as a severe occlusion/occlusion-like syndrome,peripherally and centrally,and rapid counteraction by BPC 157 therapy.Thereby,further BPC 157 therapy may be warranted.

Potato protease inhibitors,a functional food material with antioxidant and anticancer potential

Potato protease inhibitors(PPIs),as the main component of potato protein isolate,have good safety,nutrition and great market potential.The antioxidant and anticancer properties of PPIs were evaluated with cellbased biological assays.The results showed that when the concentration of PPIs was 5 mg/mL,the peroxyl radical scavenging value was(2119±204)mg VCE/100 g,and the cellular antioxidant activity values were(45.83±3.5)(no PBS wash)and(33.25±4.4)μmol QE/100 g(PBS wash).Cells pretreated with PPIs could significantly prevent the oxidative damage induced by H_(2)O_(2),inhibit the morphological changes of cells and maintain the integrity.Furthermore,PPIs had selective anti-proliferative effects on GIST882 cells(IC50=(10.53±3.87)mg/mL)and demonstrated potent inhibition of the growth,migration and invasion of cancer cells.These findings provide a scientific basis for PPIs as promising candidates for functional foods to aid in the prevention of oxidative damage and cancer.