Oxidative stress,characterized by the excessive accumulation of reactive oxygen species(ROS),is linked to various pathological conditions,including myocardial infarction,cancer,and neurodegenerative diseases.Addressin...Oxidative stress,characterized by the excessive accumulation of reactive oxygen species(ROS),is linked to various pathological conditions,including myocardial infarction,cancer,and neurodegenerative diseases.Addressing ROS-induced cell damage has become a critical focus of biomedical research.In this study,a thermo-sensitive poly(amino acid)hydrogel,composed of poly(ethylene glycol)-block-poly(l-methionine),was prepared for cytoprotection through ROS scavenging.The sol-to-gel transition mechanism of the hydrogel was elucidated,and its potent antioxidant properties and cell protective effects were validated using hydrogen peroxide(H_(2)O_(2))-induced oxidative stress and oxygen-glucose deprivation(OGD)models.The hydrogel significantly mitigated H_(2)O_(2)-induced damage in L929 cells,doubling their survival rate.Additionally,it scavenged approximately 35.8%of the ROS during OGD,reducing mitochondrial oxidative damage and resulting in a 29.4%decrease in apoptotic cell number.These findings underscore the potential biomedical applications of thermo-sensitive poly(amino acid)hydrogels,particularly in treating oxidative stress-related cell damage.展开更多
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 ...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.展开更多
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 dif...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.展开更多
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 f...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.展开更多
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 H...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.展开更多
For full use of Skipjack tuna(Katsuwonus pelamis)canning by-products,gelatins(STG)were extracted from tuna skins using acid(STG-A),enzyme(STG-E)and hot water(STG-H)methods with yields of 65.30±1.56%,39.83±1....For full use of Skipjack tuna(Katsuwonus pelamis)canning by-products,gelatins(STG)were extracted from tuna skins using acid(STG-A),enzyme(STG-E)and hot water(STG-H)methods with yields of 65.30±1.56%,39.83±1.61%,and 50.97±1.44%,respectively.Due to the high imino acid contents(228,216,and 213 residues/1000 residues for STG-A,STG-E,and STG-H,respectively),STG-A showed the highest transparency and gel strength properties.Amino acid analysis,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE),ultraviolet(UV)and Fourier transform infrared spectroscopy(FTIR)analysis confirmed that STG-A,STG-E,and STG-H kept the main structure of type I collagen,but enzyme and hot water extraction methods showed much stronger hydrolysis ability onαandβchains.Moreover,neutrase hydrolysate(STG-AH)of STG-A showed the highest 1,1-diphenyl-2-picrylhydrazyl radical(DPPH•)scavenging activity and the fraction STG-AH-І(<3.5 kDa)from STG-AH prepared by ultrafiltration could significantly protect human skin fibroblasts(HSFBs)against ultraviolet-A(UVA)injury.Furthermore,nineteen peptides with high antioxidant activity were purified from STG-AH-Іand identified.These results suggested that STG-AH and its derived antioxidant peptides could serve as potential ingredients applied in health benefiting products for preventing UVA injury.展开更多
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 group...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.展开更多
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 i...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.展开更多
Objective:The present study investigated the cytoprotective effects of a Pogonatherum paniceum extract prepared with 80%ethanol(PPE)using synchrotron radiation-based Fourier transform infrared(SR-FTIR)microspectroscop...Objective:The present study investigated the cytoprotective effects of a Pogonatherum paniceum extract prepared with 80%ethanol(PPE)using synchrotron radiation-based Fourier transform infrared(SR-FTIR)microspectroscopy and determined its phytochemical profile.Methods:The volatile and polyphenolic compounds in PPE were characterized using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry,respectively.The antioxidant capacity of PPE was evaluated using chemical and cell-based assays.The SR-FTIR microspectroscopy was performed to evaluate the cytoprotective effect of PPE by identifying changes in macromolecule composition in tert-butyl hydroperoxide(t BuOOH)-induced oxidative damage in RAW264.7 cells.Results:A total of 48 volatile compounds and 28 polyphenol components were found in PPE.PPE exhibited a high potential for antioxidant activity by scavenging the intracellular reactive oxygen species in t Bu OOH-induced oxidative damage in RAW264.7 cells.PPE treatment also significantly protected RAW264.7 cells against t BuOOH-induced toxicity and restored cell viability.The SR-FTIR analysis revealed that t BuOOH increased the lipid and ester lipid content in RAW264.7 cells.The PPE exerted a cytoprotective effect by decreasing the levels of lipid and ester lipid compounds that had been elevated by t BuOOH in RAW264.7 cells.These findings indicate that PPE has cytoprotective potential due to its ability to inhibit endogenous reactive oxygen species.Conclusion:This study extends the current knowledge on the phytochemistry of PPE and its antioxidant and cytoprotective effects.These findings support the use of SR-FTIR microspectroscopy to determine the cytoprotective effects of natural products.PPE extract may be a candidate compound for new therapeutics and nutraceuticals that target the prevention of oxidative stress-associated diseases.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
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 i...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.展开更多
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...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.展开更多
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 gu...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.展开更多
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 pat...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.展开更多
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...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.展开更多
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 ulc...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.展开更多
Alzheimer＇s disease （AD） remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta （Aβ） p...Alzheimer＇s disease （AD） remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta （Aβ） peptides in the brain. The chaperone protein clusterin has, since its first discovery at the end of the 20^th century, been labeled as a cytoprotector. However, epigenetic studies showing that clusterin is associated with the severity and risk of AD, especially in the hippocampus, triggered studies to clarify its role in the pathogenesis of AD. It is true that clusterin can inhibit the aggregation of Aβ and therefore prevent further formation of senile plaques in the AD brain, yet it induces the formation of soluble forms of Aβ which are toxic to neurons. Another problematic finding is that clusterin is involved in a pathway through which Aβ has neurodegenerative effects intracellularly. Although the role of clusterin in the pathogenesis of AD is still not clear, this review specifically discusses the interactions between clusterin and Aβ, to open up the possibility of a potential therapeutic approach for treating AD.展开更多
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 pylo...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.展开更多
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...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.展开更多
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...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.展开更多
基金financially supported by the National Key R&D Program of China(No.2022YFB3808000)the National Natural Science Foundation of China(No.U21A2099)+2 种基金the Science and Technology Development Program of Jilin Province(No.20240101002JJ)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.Y2023066)the Plan for Enhancing Health Science and Technology Capacity in Jilin Province(No.2020J041).
文摘Oxidative stress,characterized by the excessive accumulation of reactive oxygen species(ROS),is linked to various pathological conditions,including myocardial infarction,cancer,and neurodegenerative diseases.Addressing ROS-induced cell damage has become a critical focus of biomedical research.In this study,a thermo-sensitive poly(amino acid)hydrogel,composed of poly(ethylene glycol)-block-poly(l-methionine),was prepared for cytoprotection through ROS scavenging.The sol-to-gel transition mechanism of the hydrogel was elucidated,and its potent antioxidant properties and cell protective effects were validated using hydrogen peroxide(H_(2)O_(2))-induced oxidative stress and oxygen-glucose deprivation(OGD)models.The hydrogel significantly mitigated H_(2)O_(2)-induced damage in L929 cells,doubling their survival rate.Additionally,it scavenged approximately 35.8%of the ROS during OGD,reducing mitochondrial oxidative damage and resulting in a 29.4%decrease in apoptotic cell number.These findings underscore the potential biomedical applications of thermo-sensitive poly(amino acid)hydrogels,particularly in treating oxidative stress-related cell damage.
文摘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.
文摘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.
基金Supported by FAPESP(07/07139-3 and 09/54474-8)CAPES/PNPD,INCT Complex Fluids and CNPq
文摘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.
基金This study is financially supported by Chinese National Foundation of Natural Sciences (NO. 30572310)Hunan Provincial Foundation of Natural Sciences (No. 05JJ4008)
文摘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.
基金funded by the National Natural Science Foundation of China(No.82073764)the Ten-thousand Talents Plan of Zhejiang Province(No.2019R52026).
文摘For full use of Skipjack tuna(Katsuwonus pelamis)canning by-products,gelatins(STG)were extracted from tuna skins using acid(STG-A),enzyme(STG-E)and hot water(STG-H)methods with yields of 65.30±1.56%,39.83±1.61%,and 50.97±1.44%,respectively.Due to the high imino acid contents(228,216,and 213 residues/1000 residues for STG-A,STG-E,and STG-H,respectively),STG-A showed the highest transparency and gel strength properties.Amino acid analysis,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE),ultraviolet(UV)and Fourier transform infrared spectroscopy(FTIR)analysis confirmed that STG-A,STG-E,and STG-H kept the main structure of type I collagen,but enzyme and hot water extraction methods showed much stronger hydrolysis ability onαandβchains.Moreover,neutrase hydrolysate(STG-AH)of STG-A showed the highest 1,1-diphenyl-2-picrylhydrazyl radical(DPPH•)scavenging activity and the fraction STG-AH-І(<3.5 kDa)from STG-AH prepared by ultrafiltration could significantly protect human skin fibroblasts(HSFBs)against ultraviolet-A(UVA)injury.Furthermore,nineteen peptides with high antioxidant activity were purified from STG-AH-Іand identified.These results suggested that STG-AH and its derived antioxidant peptides could serve as potential ingredients applied in health benefiting products for preventing UVA injury.
文摘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.
文摘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.
基金supported by the Basic Research Fund from Thailand Science Research and Innovation through Sisaket Rajabhat University(grant number:FF.13/2564)。
文摘Objective:The present study investigated the cytoprotective effects of a Pogonatherum paniceum extract prepared with 80%ethanol(PPE)using synchrotron radiation-based Fourier transform infrared(SR-FTIR)microspectroscopy and determined its phytochemical profile.Methods:The volatile and polyphenolic compounds in PPE were characterized using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry,respectively.The antioxidant capacity of PPE was evaluated using chemical and cell-based assays.The SR-FTIR microspectroscopy was performed to evaluate the cytoprotective effect of PPE by identifying changes in macromolecule composition in tert-butyl hydroperoxide(t BuOOH)-induced oxidative damage in RAW264.7 cells.Results:A total of 48 volatile compounds and 28 polyphenol components were found in PPE.PPE exhibited a high potential for antioxidant activity by scavenging the intracellular reactive oxygen species in t Bu OOH-induced oxidative damage in RAW264.7 cells.PPE treatment also significantly protected RAW264.7 cells against t BuOOH-induced toxicity and restored cell viability.The SR-FTIR analysis revealed that t BuOOH increased the lipid and ester lipid content in RAW264.7 cells.The PPE exerted a cytoprotective effect by decreasing the levels of lipid and ester lipid compounds that had been elevated by t BuOOH in RAW264.7 cells.These findings indicate that PPE has cytoprotective potential due to its ability to inhibit endogenous reactive oxygen species.Conclusion:This study extends the current knowledge on the phytochemistry of PPE and its antioxidant and cytoprotective effects.These findings support the use of SR-FTIR microspectroscopy to determine the cytoprotective effects of natural products.PPE extract may be a candidate compound for new therapeutics and nutraceuticals that target the prevention of oxidative stress-associated diseases.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
基金Supported by the DST Nano-mission,Govt of India,Grant No DST No.SR/NM/NS-1067/2016Facilities were provided by the West Bengal University of Animal&Fishery Sciences and CSIR-IICB for conducting this research。
文摘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.
文摘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.
基金Supported by Natural Science Foundation of Ningbo City, No.2012A610194National Natural Science Foundation of China,No. 81071697Natural Science Foundation of Guangdong Province, No. S2011040003694
文摘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.
文摘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.
文摘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.
基金Supported by National Institute of Neurological Disorders and Stroke No.P30 NS047101Neurosciences Microscopy Shared Facility,UCSD from the G Harold and Leila Y Mathers Charitable Foundation No.CSD018NIH center grant No.DK080506
文摘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.
基金supported by the National Natural Science Foundation of China(8107007081171252+4 种基金and 81100990)the Major Special Science Project of Ministry of Science and TechnologyChina(2011ZXJ09202-015)the Science and Technology Project of Shanghai MunicipalityChina(11411950203)
文摘Alzheimer＇s disease （AD） remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta （Aβ） peptides in the brain. The chaperone protein clusterin has, since its first discovery at the end of the 20^th century, been labeled as a cytoprotector. However, epigenetic studies showing that clusterin is associated with the severity and risk of AD, especially in the hippocampus, triggered studies to clarify its role in the pathogenesis of AD. It is true that clusterin can inhibit the aggregation of Aβ and therefore prevent further formation of senile plaques in the AD brain, yet it induces the formation of soluble forms of Aβ which are toxic to neurons. Another problematic finding is that clusterin is involved in a pathway through which Aβ has neurodegenerative effects intracellularly. Although the role of clusterin in the pathogenesis of AD is still not clear, this review specifically discusses the interactions between clusterin and Aβ, to open up the possibility of a potential therapeutic approach for treating AD.
文摘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.
基金Medical Research Foundation of Shaoguan, Guangdong Province, No.Y08042
文摘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.
基金the National Natural Science Foundation of China,No. 30901547a Grant from Guangdong Province Technological Plan,No. 2009B050200010+1 种基金a Grant from Chinese Medicine Bureau of Guangdong Province,No. 2008078Grants from Science and Technology Plan Project of Dongguan City of Guangdong Province,No. 200910815255,2007108101007
文摘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.
