Protective Action of Acupuncture and Moxibustion on Gastric Mucosa in Model Rats with Chronic Atrophic Gastritis

Objective: To probe the mechanism of acupuncture and moxibustion in atrophic gastritis so as to provide a basis for clinical treatment. Method: Observe the effects of acupuncture and moxibustion at the points of Zusanli, Zhongwan and Tianshu on gastric mucosa in model rats with chronic atrophic gastritis. Results:Acupuncture and moxibustion can increase the contents of PGE2α, PGF2α and cAMP, and decrease the content of cGMP in the tissue of gastric mucosa. Conclusion: Acupuncture and moxibustion shows cytoprotection on gastric mucosa, so it is an effective method for treating chronic atrophic gastritis.

Role of constitutive nitric oxide synthase in regulation of <i>Helicobacter pylori</i>-induced gastric mucosal cyclooxygenase-2 ac-tivation through S-nitrosylation: mechanism of ghrelin action

Gastric mucosal inflammatory responses to H. pylori lipopolysaccharide (LPS), are characterized by the excessive NO and prostaglandin (PGE2) generation due to the disturbances in nitric oxide synthase (NOS) and cyclooxygenase (COX) systems. Here, we report that the LPS-induced enhancement in gastric mucosal inducible (i) iNOS) activity and up-regulation in PGE2 production was associated with the suppression in Akt kinase activity and the impairment in constitutive (c) cNOS activation. The stimulatory effect of the LPS on PGE2 production, furthermore, was susceptible to suppression by COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400 W. Further, we show that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in up-regu- lation in Akt activity and the increase in cNOS activation through phosphorylation, and accompanied by the suppression in iNOS expression and the reduction in COX-2 activity associated with the loss in COX-2 protein S-nitrosylation. Moreover, the effect of ghre-lin on the LPS-induced COX-2 S-nitrosylation was subject to repression by Akt inhibition. Our findings demonstrate that induction in iNOS with H. pylori in- fection leads to COX-2 activation through S-nitro- sylation and up-regulation in PGE2 generation, and that ghrelin counters these untoward consequences of the LPS through Akt-mediated up-regulation in cNO- S activation required for the iNOS gene repression.

Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.

Could near focus endoscopy,narrow-band imaging,and acetic acid improve the visualization of microscopic features of stomach mucosa?

BACKGROUND Conventional magnifying endoscopy with narrow-band imaging(NBI)observation of the gastric body mucosa shows dominant patterns in relation to the regular arrangement of collecting venules,subepithelial capillary network,and gastric pits.AIM To evaluate the effectiveness of a new one-dual(near)focus,NBI mode in the assessment of the microscopic features of gastric body mucosa compared to conventional magnification.METHODS During 2021 and 2022,68 patients underwent proximal gastrointestinal endoscopy using magnification endoscopic modalities subsequently applying acetic acid(AA).The GIF-190HQ series NBI system with dual focus capability was used for the investigation of gastric mucosa.At the time of the endoscopy,the gastric body mucosa of all enrolled patients was photographed using the white light endoscopy(WLE),near focus(NF),NF-NBI,AA-NF,and AA-NF-NBI modes.RESULTS The WLE,NF and NF-NBI endoscopic modes for all patients(204 images)were classified in the same order into three groups.Two images from each patient for the AA-NF and AA-NF-NBI endoscopic modes were classified in the same order.According to all three observers who completed the work independently,NF magnification was significantly superior to WLE(P<0.01),and the NF-NBI mode was significantly superior to NF magnification(P<0.01).After applying AA,the three observers confirmed that AA-NF-NBI was significantly superior to AA-NF(P<0.01).Interobserver kappa values for WLE were 0.609,0.704,and 0.598,respectively and were 0.600,0.721,and 0.637,respectively,for NF magnification.For the NF-NBI mode,the values were 0.378,0.471,and 0.553,respectively.For AA-NF,they were 0.453,0.603,and 0.480,respectively,and for AA-NF-NBI,they were 0.643,0.506,and 0.354,respectively.CONCLUSION When investigating gastric mucosa in microscopic detail,NF-NBI was the most powerful endoscopic mode for assessing regular arrangement of collecting venules,subepithelial capillary network,and gastric pits among the five endoscopic modalities investigated in this study.AA-NF-NBI was the most powerful endoscopic mode for analyzing crypt opening and intervening part.

Quantitative ultrastucture analysis of neuroendocrine cells of gastric mucosa on normal and pathological conditions

AIMS To study the quantitative ultrastucture of neu- roendocrine cells of gastric mucosa on normal anc pathological conditions including the duodenal ulcer (DU) and Zollinger-Ellison syndrome (ZES). METHODS The neuroendocrine cells of the gastric mucosa of eight normal subjects,six patients with DU and five patients with ZES were quantitatively investi- gated with electro microscope and ultrastructure image analyzer. RESULTS The volume density of neuroendocrine cells in DU was 1.3% and 0.8% (vs 1.6% and 0.9%,P>0.05) in gastric antrum and corpus respectively. In antrum,G cells was of 65% (P< 0.05),D cells decreased in cell density (3% vs 9.5%) and in number of cell per unit area (P<0.01). In corpus,the cell density of ECL cells increased (49% vs 30%,P<0.05);D cells and EC cells decreasec (2% P<0.01 and 4% P<0.05,respectively),and the number of D cell per unit area markedly decreased. In ZES,D cells in corpus decreased in cell density (4% vs 22%,P<0.01) and P cells also decreased (11% vs 24%,P<0.05). The density of ECL cells increased (65% vs 30%,P<0.01). CONCLUSIONS In DU and ZES,both the number and type of NE cells present some changes. Incresed gastrin in DU and ZES patients may be caused by the decrease of D cells and somatostatin secretion.

Effect of Helicobacter pylori infection on gastric epithelial proliferation in progression from normal mucosa to gastric carcinoma

AIM To study the effect of Helicobacter pylori ( H. pylori ) infection on gastric epithelial proliferation in the progression from normal mucosa to gastric carcinoma. METHODS Gastric biopsy specimens from normal controls ( n =11), superficial gastritis ( n =32), atrophic gastritis with intestinal metaplasia ( n =83), dysplasia ( n =25) and gastric carcinoma ( n =10) were studied by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). RESULTS The gastric epithelial proliferation, expressed as PCNA labeling index (LI)%, was progressively increased in successive stages from normal mucosa to gastric carcinoma regardless of H. pylori status. There was significant difference in PCNA LI% among all groups ( P <0 01). The analysis pursuing the effect of H. pylori infection on gastric epithelial proliferation in the progression from normal mucosa to gastric carcinoma showed that in superficial gastritis and mild atrophic gastritis groups, PCNA LI% in H. pylori positive patients were 13 14±1 6 and 19 68±2 22 respectively, significantly higher than 6 95±0 78 and 11 34±1 89 in H. pylori negative patients ( P <0 01); but there was no such difference in other groups ( P >0 05). CONCLUSION H. pylori infection causes increased gastric epithelial proliferation in the stages of superficial and mild atrophic gastritis and may play a part in triggering gastric carcinogenesis.

Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection,histological types and staging

AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer（GC）and other gastric mucosallesions and their relations to Helicobacter pylori（H.pylori）infection,tumor staging andhistological subtypes.METHODS Three hundred and twenty-sevenspecimens of gastric mucosa obtained viaendoscopy or surgical resection,and ABCimmunohistochemical staining were used todetect the expression of p53,p16,Bcl-2 andCOX-2 proteins.H.pylori was determined byrapid urea test combined with pathologicalstaining or14C urea breath test.Cellular image analysis was performed in 66 patients withintestinal metaplasia（IM）and/or dysplasia（Dys）.In 30 of them,both cancer and theparacancerous tissues were obtained at the timeof surgery.Histological pattern,tumor staging,lymph node metastasis,grading ofdifferentiation and other clinical data werestudied in the medical records.RESULTS p16 expression of IM or Dys wassignificantly lower in positive H.pylori chronicatrophic gastritis（CAG）than those withnegative H.pylori（CAG:54.8% vs 88.0%,IM:34.4% vs 69.6%,Dys:23.8% vs 53.6%,allP【0.05）,Bcl-2 or COX-2 expression of IM orDys in positive H.pylori cases was significantlyhigher than that without H.pylori（Bcl-2:68.8%vs23.9%,90.5% vs 60.7%;COX-2:50.0% vs10.8%,61.8% vs 17.8%;all P【0.05）.Themean number of most parameters of cellularimage analysis in positive H.pylori group wassignificantly higher than that in negative H.pylori group（Ellipser:53±14,40±12μm,Area1:748±572,302±202 μm2,Area2:3050±1661,1681±1990 μm2,all P【0.05;Ellipseb:79±23,58±15 μm,Ratio1:22%±5%,13%±4%,Ratio2:79%±17%,53%±20%,all P【0.01）.There was significant correlation between Bcl-2and histologic pattern of gastric carcinoma,andbetween COX-2 and tumor staging or lymph nodemetastasis（Bcl-2:75.0% vs 16.7%;COX-2:76.0% vs 20.0%,79.2% vs 16.7%;allP【0.05）.CONCLUSION p1l6, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/ progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.

Increased susceptibility of aging gastric mucosa to injury:The mechanisms and clinical implications

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-&#x0201c;aging gastropathy&#x0201d;-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-&#x003b1;-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.

Endoscopic diagnosis of cervical esophageal heterotopic gastric mucosa with conventional and narrow-band images

AIM: To compare the diagnostic yield of heterotopic gastric mucosa (HGM) in the cervical esophagus with conventional imaging (CI) and narrow-band imaging (NBI).

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa

AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Histological changes of gastric mucosa after Helicobacter pylori eradication:a systematic review and meta-analysis

AIM: To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication.

Sleep deprivation increase the expression of inducible heat shock protein 70 in rat gastric mucosa

AIM: To investigate if sleep deprivation is able to increase the expression of inducible heat shock protein 70 in gastric mucosa and its possible role in mucosal defense. METHODS: Rats for sleep disruption were placed inside a computerized rotating drum, gastric mucosa was taken from rats with 1, 3 and 7d sleep deprivation. RT-PCR, immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70. Ethanol (500mL.L(-1), i.g.) was used to induce gastric mucosa damage. RESULTS: RT-PCR, Western blotting and immunostaining confirmed that the sleep deprivation as a stress resulted in significantly greater expression of inducible heat shock protein 70 in gastric mucosa of rats. After the 500mL.L(-1) ethanol challenge, the ulcer area found in the rats with 7d sleep deprivation (19.15 +/- 4.2)mm(2) was significantly lower (P【0.01) than the corresponding control (53.7 +/- 8.1) mm(2). CONCLUSION: Sleep deprivation as a stress, in addition to lowering the gastric mucosal barrier, is able to stimulate the expression of inducible heat shock protein 70 in gastric mucosa of rats, the heat shock protein 70 may play an important role in gastric mucosal protection.

Protection of gastric mucosa from ethanol induced injury by recombinant epidermal growth factor in rats

AIM To determine whether recombinant human epidermal growth factor (rhEGF) can protect gastric mucosa against ethanol induced injury in rats. METHOD Fifty four SD rats weighing 200g - 500g each were divided into six groups after fasting for 24 hours. Three groups received different doses of oral rhEGF (30, 60 and 120μg·kg -1 ·d -1 ), one group was given cimetidine, one subcutaneous rhEGF (rhEGFⅣ) and one received saline as control. RESULTS Acute gastric dilatation developed in the control and cimetidine groups and bloody gastric juice was found in the control group. The ulcer index was 58 in control group, 53 in rhEGFⅠ, 46 in rhEGFⅡ ( P <0 01) , 11 in rhEGFⅢ ( P <0 01) , 19 in rhEGFⅣ ( P <0 01) , and 39 in cimetidine group ( P <0 05) . CONCLUSION rhEGF protected gastric mucosa against ethanol induced damage. The effect was dose dependent with blood levels of epidermal growth factor (EGF) at a dosage range of 60μg·kg -1 ·d -1 -120μg·kg -1 ·d -1 . It was more effective by injection than via oral route at the same dosage.

Increased susceptibility of aging gastric mucosa to injury and delayed healing:Clinical implications

In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury. Aspirin is widely used not only for the management of acute and chronic pain and arthritis, but also importantly for the primary and secondary prevention of cardiovascular events such as myocardial infarcts and strokes. Clinical trials have consistently shown that antiplatelet therapy with long term, low dose aspirin(LDA)-75 to 325 mg daily, dramatically reduces the risk of non-fatal myocardial infarcts, stroke and mortality in patients with established arterial diseases. However, such treatment considerably increases the risk of gastrointestinal(GI) ulcerations and serious bleeding by > 2-4 fold, especially in aging individuals. This risk is further increased in patients using LDA together with other antiplatelet agents, other nonsteroidal anti-inflammatory agents(NSAIDs) and/or alcohol, or in patients with Helicobacter pylori(H. pylori) infection. Previous studies by our group and others have demonstrated prominent structural and functional abnormalities in gastric mucosa of aging individuals(which we refer to as aging gastric mucosa or "aging gastropathy") compared to the gastric mucosa of younger individuals. Aging gastric mucosa has impaired mucosal defense, increased susceptibility to injury by a variety of noxious agents such as aspirin, other NSAIDs and ethanol, and delayed and impaired healing of injury. The mechanism underlying these abnormalities of aging gastric mucosa include reduced mucosal blood flowcausing hypoxia, upregulation of PTEN, activation of proapoptotic caspase-3 and caspase-9, and reduced survivin(anti-apoptosis protein), importin-α(nuclear transport protein), vascular endothelial growth factor, and nerve growth factor. The decision regarding initiation of a long-term LDA therapy should be made after a careful consideration of both cardiovascular and GI risk factors. The latter include a previous history of GI bleeding and/or ulcers, age ≥ 70, male gender, concurrent use of other NSAIDs, alcohol consumption and H. pylori infection. Furthermore, the incidence of GI ulcers and bleeding can be reduced in patients on long term LDA treatment by several measures. Clinicians treating such patients should test for and eradicate H. pylori, instruct patients to avoid alcohol and non-aspirin NSAIDs, including cyclooxygenase-2-selective NSAIDs, and prescribe proton pump inhibitors in patients on LDA therapy. In the future, clinicians may be able to prescribe one of several potential new drugs, which include aspirin associated with phosphatidylcholine(PL2200), which retains all property of aspirin but reduces by approximately 50% LDA-induced GI ulcerations.

Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis

AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis.METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory andsimultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile refluxpositive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including activeinflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance ＞0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH ＞4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance ＞0.14) and 11 patients (7 men and 4 women, mean age 46.2 years,range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH ＞4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region, and has no influence on acid-exposing status of gastric mucosa in patients with dyspepsia or chronic gastritis.

Effects of infusion of different fluids during controlled hypotension on gastric intramucosal pH and postoperative gastroenterological function

The present study was aimed to investigate the effects of infusion of different fluids combined with control-led hypotension on gastric intramucosal pH （pHi） and postoperative gastrointestinal function in patients undergo-ing hepatocarcinoma surgery. Forty-five patients （ASAⅡ） scheduled for surgical resection of hepatocarcinoma undergoing controlled hypotension were randomly assigned to three groups and received infusion of 20 mL/kg Ringer’s solution （R group）, 6% HAES（H group） or 6% Voluven group （W group）. Intragastric PgCO2, pHi, he-matocrit and hemoglobin were measured. The significant decrease of pHi and increase of PgCO2 were produced at 1 and 2 h after controlled hypotension in the R group （P 0.05 or P 0.01）. The time of bowel movement af-ter operation was shorter in the W group than the R group. Meanwhile, we also did not find obvious difference in blood gas indexes among the three groups. The infusion of HAES and Voluven during controlled hypotension could improve gastrointestinal perfusion and accelerate the recovery of postoperative gastrointestinal function.

NKX6.3 protects against gastric mucosal atrophy by downregulatingβ-amyloid production

BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2.CONCLUSION NKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells.

Association of high expression in rat gastric mucosal heat shock protein 70 induced by moxibustion pretreatment with protection against stress injury

AIM:To study the effect of moxibustion on Zusanli or Liangmeng point on gastric mucosa injury in stress-induced ulcer rats and its correlation with the expression of heat shock protein 70 (HSP70). METHODS:Sixty healthy SD rats (30 males,30 females) were divided into control group,injury model group,Zushanli point group,Liangmeng point group. Stress gastric ulcer model was induced by binding cold stress method. Gastric mucosa ulcer injury (UI) index was calculated by Guth method. Gastric mucosa blood flow (GMBF) was recorded with a biological signal analyzer. Protein content and gene expression in gastric mucosal HSP70 were detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). Thiobarbital method was used to determine malondialdehyde (MDA) content. Gastric mucosal endothelin (ET) and prostaglandin E2 (PGE2) were analyzed by radioimmunoassay. RESULTS:High gastric mucosal UI index,high HSP70 expression,low GMBF and PGF2,elevated MDA and ET were observed in gastric mucosa of rats subjected to cold stress. Moxibustion on Zusanli or Liangmeng point decreased rat gastric mucosal UI index,MDA and ET. Conversely,the expression of HSP70,GMBF,and PGE2 was elevated in gastric mucosa after pretreatment with moxibustion on Zusanli or Liangmeng point. The observed parameters were significantly different between Zusanli and Liangmeng points. CONCLUSION:Pretreatment with moxibustion on Zusanli or Liangmeng point protects gastric mucosa against stress injury. This protection is associated with the higher expression of HSP70 mRNA and protein,leading to release of PGE2 and inhibition of MDA and ET,impairment of gastric mucosal index.

Molecular cross-talk between Helicobacter pylori and human gastric mucosa

Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.

Gene expression profiles in gastric mucosa of sleep deprivation rats

INTRODUCTIONStress has been shown to induce gastric mucosallesions and lower the effectiveness of the mucosa asa barrier.In rats,gastric ulcers can beproduced by cold-restraint stress and it isfrequently employed as a model for the study of themechanisms of stress on ulcer formation.Cold-restraint stress however is not normally