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-“aging gastropathy”-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-α-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.

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.

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.

Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

Gastric mucosal injury due to hemorrhagic reperfusion and efficacy of Salvia miltiorrhizae extract F and cimetidine

AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it. METHODS: A model of hemorrhage/reperfusion injury was produced by Itoh method. Wistar rats were randomly divided into three groups: 0.9% sodium chloride treatment group (NS group), SEF treatment group (SEF group), and CI treatment group (CI group). Saline, SEF and CI were injected respectively. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesion area in the gastric mucosa. The degree of gastric mucosal lesions was categorized into grades 0, 1, 2, 3. Atom absorption method was used to measure the intracellular calcium content. Radioimmunoassay was used to measure the concentrations of prostaglandins. RESULTS: IGML (%) and grade 3 (%) were 23.18±6.82, 58.44±9.07 in NS group, 4.42±1.39, 20.32±6.95 in SEF group and 3.74±1.56, 23.12±5.09 in CI group, and the above parameters in SEF group and CI group decreased significantly (IGML: SEF vs NS, t=6.712, P=0.000<0.01; CI vs NS, t=6.943, P=0.000<0.01; grade 3: SEF vs HS, t=8.386, P=0.000; CI vs HS, t=8.411, P= 0.000), but the grade 0 and grade 1 damage in SEF group (22.05±5.96, 34.12±8.12) and CI group (18.54±4.82, 30.15±7.12) were markedly higher than those in NS group (3.01±1.01, 8.35±1.95; grade 0: SEF vs HS, t=8.434, P=0.000<0.01; CI vs NS, t=7.950, P=0.000<0.01; grade 1: SEF vs NS, t =8.422, P=0.000<0.01; CI vs NS, t=8.448, P=0.000<0.01). The intracellular calcium content (μg/mg) in SEF group (0.104±0.015) and CI group (0.102±0.010) was markedly lower than that in NS group (0.131±0.019, SEF vs NS, t=2.463, P=0.038<0.05; CI vs HS, t=3.056, P=0.017<0.05). The levels (pg/mg) of PGE_2, 6-keto-PGF_(1α) and 6-keto-PGF_(1α)/TXB_2 were 540±183, 714±124,17.38±5.93 in NS group and 581±168, 737±102, 19.04±8.03 in CI group, 760±192,1 248±158, 33.42±9.24 in SEF group, and the above parameters in SEF group markedly raised (PGE_2: SEF vs NS, t=2.282, P=0.046<0.05; SEF vs CI, t=2.265, P=0.047<0.05; 6-keto-PGF_(1α): SEF vs NS, t=6.583, P=0.000<0.000; SEF vs CI, t=6.708, P=0.000<0.01; 6-keto-PGF_(1α)/TXB_2: SEF vs NS, t=3.963, P=0.003<0.001; SEF vs Cl, t=3.243, P=0.009<0.01), whereas TXB_2 level in SEF group (45.37±7.54) was obviously lower than that in NS group (58.28±6.74, t=3.086, P=0.014<0.05) and CI group (54.32±6.89, t=2.265, P=0.047<0.05). No significant difference was shown between NS group and CI group (PGE_2: t=0.414, P=0.688>0.05; 6-keto-PGF_(1α): t=0.310, P=0.763>0.05; TXB_2: t=1.099, P=0.298>0.05; 6-keto-PGF_(1α)/TXB_2: t=0.372, P=0.718>0.05). CONCLUSION: Both SEF and CI could inhibit reperfusioninduced injury in gastric mucosa, but with different mechanisms. SEF could not only enhance the protective effect of gastric mucosa, but also abate the injury factors, while CI can only abate the injury factors.

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.

Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT- PCR). RESULTS:The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and theexposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.

Role of Injury of Gastric Parietal Vessels by Immunocomplexes in the Mechanism of Gastric Mucosal Lesion in Portal Hypertension with Cirrhosis

The present experiment employed the immunohistochemical technique and morphological observation to investigate the expression and distribution of C3, C4, IgG, IgE and 5-HT in portal hypertensive pigs with pathological change of gastric mucosa and gastric parietal vessels. The wall of gastric mucosal microvessels in portal hypertensive pigs had a positive or strong positive reaction of C3,C4, IgG, IgE and 5-HT with obvious injury of gastric mucosa normal pigs imparted negative or feeble positive reaction, suggesting that during portal hypertension, the gastric mucosal micr0-vessels has deposit of immunocomplexes resulting in the injury of the micro-vessels. It might be a factor inv01ved in the pathogenesis of the gastric mucosal lesion during portal hypertension with cirrhosis.

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

AIM:This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 μmol/kg), diclofenac (60 μmol/kg), piroxicam (150 μmol/kg) or ketoprofen (150 μmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 umol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 μmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 μmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 μmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 μmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which is also responsible for an increment of sulfhydryl radical bioavailability. It is also suggested that lansoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

Relationship between trefoil factor 1 expression and gastric mucosa injuries and gastric cancer

AIM:To determine whether trefoil factor 1 (TFF1) is associated with mucosa healing and carcinoma suppression, we assess the expression of trefoil factor 1 in normal and pathologic gastric mucosa. METHODS: TFF1 in normal and pathologic gastric mucosa was assessed by immunohistochemical method, and the average positive A was estimated by Motic Images Advanced 3.0 software. RESULTS: Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer compared with normal mucosa. The same result could be seen in multiple and compound ulcer compared with simple ulcer. There was no significant difference between gastric ulcer and duodenal ulcer, gastritis and simple ulcer respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric adenocarcinoma compared with normal mucosa. The expression of TFF1 in gastric adenocarcinoma was related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma, the weaker the expression of TFF1. There was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of TFF1 in middle and highly differentiated adenocarcinoma was a little lower than that in normal mucosa. But there was no significant difference. No TFF1 was assessed in esophageal squamous carcinoma and peripheral tissue. There was no significant difference between male and female. CONCLUSION: The expression of TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was also higher in multiple and compound ulcer than in simple ulcer. It seems that TFF1 plays a role in gastric mucosa protection and epithelial restitution. Increased expression of TFF1 in peripheral tissue suggests that TFF1 is associated with mechanism of carcinoma suppression and differentiation. Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma.

Effect of acupuncture at different meridian acupoints on changes of related factors for rabbit gastric mucosal injury

AIM： To explore the regularity of multi-meridians controlling a same viscus （MMCSV）. METHODS： The rabbit gastric ulcer model was established by ethanol intragastric instillation. Fifty-six rabbits were randomly divided into normal group, model group （MG）, model plus acupuncture at Foot Yangming Meridian group （YMG）, model plus acupuncture at Foot Taiyin Meridian group （TYG）, model plus acupuncture at Foot Shaoyang Meridian group （SYG）, model plus acupuncture at Foot Jueyin Meridian group （JYG）, model plus acupuncture at Foot Taiyang Meridian group （TYMG）, with eight rabbits in each group. Gastric mucosal nitric oxide （NO） and nitric oxide synthase （NOS） were assayed by the nitric acid reductase method, and prostaglandin E2 （PGE2） and epidermal growth factor （EGF） were measured by radioimmunoassay. The comprehensive effects were analyzed by weighing method. RESULTS： Compared to MG, SYG, JYG and TYMG, the rabbits gastric mucosal injury index （GMII） reduced very significantly in YMG （P〈0.01）. Compared to MG, the GMII also reduced significantly in TYG （P〈0.05）. NO, NOS, PGE2 and EGF increased very significantly in YMG （P〈0.01）. The EGF in YMG also increased significantly than that in TYG compared to those in MG, SYG, JYG and TYMG （P〈0.05）. The PGE2 and EGF also increased very significantly in TYG than those in MG, JYG and TYMG （P〈0.01）. While compared to SYG, the NOS increased significantly in TYG （P〈0.05）. NOS was the highest in YMG （P〈0.01）, and was higher in TYG than in MG （P〈0.01）. CONCLUSION： MMCSV is common. The Foot Yangming Meridian is most closely related to the stomach, followed by Foot Taiyin Meridian, Foot Shaoyang Meridian and Foot Jueyin Meridian. Foot Taiyang Meridian has no correlation with the stomach.

Hydrogen sulfide attenuates gastric mucosal injury induced by restraint water-immersion stress via activation of KATPchannel and NF-κB dependent pathway

AIMTo explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect.METHODSMale Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group. Gastric mucosal injury was induced by RWIS for 3 h in rats, and gastric mucosal damage was analyzed after that. The PS, NaHS (100 μmol/kg body weight), Gl (100 μmol/kg body weight), Gl (100 μmol/kg or 150 μmol/kg body weight) plus NaHS (100 μmol/kg body weight), PDTC (100 μmol/kg body weight), and PDTC (100 μmol/kg body weight) plus NaHS (100 μmol/kg body weight) were respectively injected intravenously before RWIS.RESULTSRWIS induced serious gastric lesions in the rats in the PS pretreatment group. The pretreatment of NaHS (a H2S donor) significantly reduced the damage induced by RWIS. The gastric protective effect of the NaHS during RWIS was attenuated by PDTC, an NF-κB inhibitor, and also by glibenclamide, an ATP-sensitive potassium channel blocker, in a dose-dependent manner.CONCLUSIONThese results suggest that exogenous H2S plays a protective role against RWIS injury in rats, possibly through modulation of KATP channel opening and the NF-κB dependent pathway.

Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries

The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.

Camellia oil (Camellia oleifera Abel.) alleviates gastric injury induced by ethanol associated with modulation of gut microbiota in mice

Oil from Camellia oleifera Abel. seed is a popular edible oil in Asia, which has gained much attention for itsmedicinal applications on relieving various inflammation, however, the mechanism is still unknown. The presentstudy was to investigate the gastroprotective effect of camellia oil against ethanol-induced gastric mucosal injuryin mice. The results showed that camellia oil pretreatment significantly reduced gastric ulcer injury. A remarkableinhibited oxidative stress by reducing the concentration of malondialdehyde and a significant decrease of thelevels of pro-inflammatory factors in gastric tissue were observed in camellia oil pretreated group. In addition,camellia oil improved the diversity of gut microbiota and changed the community structure and composition byincreasing Bacteriodes and Dorea. And the feces metabolomics found that metabolism of cofactors and vitamins,and lipid, carbohydrate and amino acid metabolism were modulated by admiration of camellia oil. Takentogether, the findings of this study suggested that camellia oil could ease the ethanol-induced gastric mucosalinjury via the improvement of anti-oxidant and anti-inflammatory status, as well as the regulation of gutmicrobiota and its metabolites.

Dendrobium offi cinale flowers flavonoids enriched extract protects against acute ethanol-induced gastric ulcers via AMPK/PI3K signaling pathways

Gastric ulcer is a widespread disease caused by various etiologies.Dendrobium offi cinale flowers exert several health benefits owing to their rich flavonoid content.In this study,protective effects and possible action mechanisms of D.offi cinale flowers’flavonoid enriched extract(DOFF)were assessed against gastric ulcer.The result of sodium nitrite-aluminum nitrate colorimetry showed that 52.34%of the total extractive was flavonoid,and ultra-high performance liquid chromatography time of flight mass spectrometer(UPLC-QTOF/MS)revealed the presence of 28 components in DOFF of which 14 belonged to flavonoids.In addition,in vivo assay revealed DOFF potential in reducing the formation of ethanol-induced gastric mucosal lesions,with drop-in ulcer index from 64.33±8.76 to 32.00±4.47.Similar results were revealed in human gastric mucosal epithelia cells,with cells viability to increase from 27.2%to 61.6%post DOFF administration.To analyzed the protect effect of DOFF,we used Western blotting and immunofluorometric assay to revealed the expression levels of key proteins in cell pathways.The results showed that DOFF(320μg/mL)could increase the level of oxidation marker protein(HO-1),apoptosis regulatory protein(Bcl-2)and autophagy marker(LC3β)by 50.84%,43.85%,and 59.21%compared with ethanol-treated group respectively.Further analyzed of the mitochondrial activity and apoptosis pathway,we found that DOFF appeared to mitigate against ethanolinduced gastric mucosal injury via AMPK/mTOR/ULK1 and PI3K/AKT autophagy signaling pathways.

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.

Total triterpenes from fruits of Chaenomeles speciosa(Sweet) Nakai protect against indomethacin-induced gastric mucosal injury: involvement of TFF1-mediated EGF/EGFR and apoptotic pathways

OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the first guard to protect the stomach from ulcer injury,while the aetiology of gastric ulcer is relative to imbalances between gastric mucosal protective and aggressive factors.Therefore,reducing or eliminating the aggressive factors,returning to the balance of between mucosal protective and aggressive factors,and then restoring the normal functional of gastric mucosal barrier could be crucial for treating the gastric ulcer.The fruits of Chaenomeles speciosa(TCS),also known as"mugua",might be processed into edible and health care derived products,and used as a commonly used traditional medicine in China for thousands of years.In China folk,there is a saying that"apricot one benefit,pear two benefits,mgua hundred benefits",so it has a"hundred-benefit"fruit reputation.Tujia nationality inhabitants in Southwestern China should have rheumatic diseases and peptic ulcers for living in the damp environments and bingeing on spicy and pungent foods.For the exis⁃tence of the fruit derived products of Chaenomeles speciosa as their complementary foods or snacks,the habit makes them rarely suffer from the two kinds of diseases.Enlightened by these,we had investigated the structure-activity rela⁃tionships,screened out CSTT with gastroprotective activity.Our previous studies demonstrated that TCS owned effec⁃tively therapeutic effects on gastric ulcer patients and animals,and further confirmed that TFF1 and apoptotic pathway were closely interrelated with its exerting gastroprotection.However,its underlying molecular mechanisms involved have not been fully elucidated.The current study was to further investigate its protective effect on indomethacin(IND)-damaged RGM-1 cells and rats and its underlying mechanisms through modulating TFF1-mediated EGF/EGFR and apoptotic pathways.METHODS The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats.In vitro,the proliferation,migration,mitochondrial viability and apoptosis were assessed,In vivo,ulcer index,ulcer inhibition rate,gastric juice acidity,gastric wall mucus(GWM),histopathology of gastric mucosa were detected.The gastroprotective effects of TCS through the TFF1-mediated EGFR/EGFR and apoptotic pathways were presented and measured by qRT-PCR and Western blotting assays.RESULTS TCS had gastroprotective function,which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration,hoisting gastric juice acidity and GWM,improving ulcer index and ulcer inhibition rate,attenuating the hemorrhage,edema,epithelial cell loss and inflammatory cell infiltration of gastric mucosa,upregulating proliferation cell nuclear antigen,Bcl-2,Bcl-xl mRNA and TFF1,EGF,p-EGFR,p-Src,pro-caspase-3,pro-caspase-9 protein expressions,mitochondrial viability,mitochondrial cytochrome C concentration and p-EGFR/EGFR,p-Src/Src,Bcl-2/Bax,Bcl-xl/Bad ratioes,downregulating Bax,Bad,Apaf-1 mRNA and cleaved-caspase-3,cleaved-caspase-9,cleaved-PARP-1 protein expressions,cytosol cytochrome C concentration.CONCLUSION TCS′s gastroprotective effect was closely connected with boosting TFF1 expression,acti⁃vating TFF1-mediated EGF/EGFR pathway,thus restraining mitochondrial-dependent apoptosis,which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.

EFFECT OF ELECTROACUPUNCTURE OF "ZUSANLI" ON VIP CONTENTS OF THE PERIPHERAL BLOOD, GASTRIC MUCOSAL AND BRAIN TISSUES IN GASTRIC MUCOSAL INJURY RATS

Objective: To observe the therapeutic effect of electroacupuncture (EA) of "Zusanli"(ST 36) on vasoactive intestinal peptide (VIP) levels in the peripheral blood, gastric mucosal and brain tissues in experimental gastric injury rats. Methods: Gastric mucosal injury model was established by using cold restraining stress method. 40 Wistar rats were randomly and evenly divided into normal control group, model group, EA group and non acupoint group. VIP contents of plasma and gastric mucosal and medulla oblongata tissues were assayed using radioimmunoassay and gastric mucosal blood flow (GMBF) was measured by employing hydrogen clearing method. Results: In cold restraining stress rats, spot and strip like bleeding necrosis foci in the gastric mucous primarily in the gastric antrum could be seen clearly, GMBF and VIP contents in plasma, gastric mucous and brain tissues declined significantly (P<0.05, 0.01), while the gastric mucosal lesion index (LI) raised significantly (P<0.05) in comparison with those of normal control group. Following EA of "Zusanli" (ST 36), GMBF decreased pronouncedly, VIP contents of the plasma, bulba and gastric mucosal tissues increased strikingly in comparison with model group (P<0.01). Conclusion: EA of "Zusanli" (ST 36) possesses a protection effect on gastric mucous under stress condition and VIP is involved in the effect of EA.

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.