Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.

Experimental study on mechanism and protection of stress ulcer produced by explosive noise

AIM To establish an experimental model of stress ulcer produced by explosive noise, and to probe into its mechanism and protection. METHODS The country standard Wistar white rats were randomly divided into control group ( n =8), which were neither stimulated nor protected, and stimulating group (divided into subgroups A, B and C, including 8 rats each which were decapitated to draw blood for test immediately, 12 hours and 24 hours after stimulation) and prevention group (divided into subgroups A, B and C, having 8 rats each, subgroup A was given cimetidine, B anisodamine and C both drugs). Firing noises of submachine guns were used as inflicting factor. The rats were fasted for 24 hours and stimulated by firing noise for 12 hours. The change of ulcer index, gastric mucosal and related serum hormones were observed. RESULTS Stress ulcer was significant in the stimulating group, and its ulcer index (8 6±0 6) was remarkably higher than that in both the control group and prevention group (0 3±0 1, P <0 01). Its serum gastrin (Gas ng/L , 294±163 vs 63±40, P <0 01) and endothelin (ET ng/L , 181±57 vs 135±42, P <0 01) were apparently higher than those in the control group, and its serum nitric oxide (NO) level was conspicuously lower than that in the control group ( ng/L , 0 2±0 1 vs 0 8±0 5, P <0 05), while the serum gastrin level ( ng/L , 556±225) in prevention group was distinctly higher than that in both the control ( P <0 01) and stimulating group ( P <0 05). There were no significant differences in the changes of ET and NO between the control and the stimulating groups. CONCLUSION Stress ulcer model of rats can be successfully established by the stimulation of explosive noise. Gas, ET and NO are related to the formation of stress ulcer, and play an important role in its mechanism. Hepatic function affected by noise is observed in this experiment.

Effects of acupuncturing Tsusanli (S_T36) on expression of nitric oxide synthase in hypothalamus and adrenal gland in rats with cold stress ulcer

AIM： To study the protective effect of acupuncturing Tsusanli （ST36） on cold stress ulcer, and the expression of nitric oxide synthase （NOS） in hypothalarnus and adrenal gland. METHODS： Ulcer index in rats and RT-PCR were used to study the protective effect of acupuncture on cold stress ulcer, and the expression of NOS in hypothalamus and adrenal gland. Images were analyzed with semi-quantitative method. RESULTS： The ulcer index significantly decreased in rats with stress ulcer. Plasma cortisol concentration was up regulated during cold stress, which could be depressed by pre-acupuncture. The expression of NOS1 in hypothallamus increased after acupuncture. The increased expression of NOS2 was related with stress ulcer, which could be decreased by acupuncture. The expression of NOS3 in hypothalamus was similar to NOS2, but the effect of acupuncture was limited. The expression of NOS2 and NOS3 in adrenal gland increased after cold stress, only the expression of NOS1 could be repressed with acupuncture. There was no NOS2 expression in adrenal gland in rats with stress ulcer. CONCLUSION： The protective effect of acupuncturing Tsusanli （ST36） on the expression of NOS in hypothalamus and adrenal gland can be achieved.

Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis

BACKGROUND Sirtuin 1(SIRT1)is a nicotinamide adenine dinucleotide(NAD+)-dependent protein deacetylase that is involved in various diseases,including cancers,metabolic diseases,and inflammation-associated diseases.However,the role of SIRT1 in ulcerative colitis(UC)is still confusing.AIM To investigate the role of SIRT1 in intestinal epithelial cells(IECs)in UC and further explore the underlying mechanisms.METHODS We developed a coculture model using macrophages and Caco-2 cells.After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide(NAM),the expression of occludin and zona occludens 1(ZO-1)was assessed by Western blot analysis.Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis.Dextran sodium sulfate(DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d.Transferase-mediated dUTP nick-end labeling(TUNEL)assays were conducted to assess apoptosis in colon tissues.The expression levels of glucose-regulated protein 78(GRP78),CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,caspase-9,and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot.RESULTS SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis,whereas NAM administration caused the opposite effects.DSS-induced colitis mice treated with SRT1720 had a lower disease activity index(P<0.01),histological score(P<0.001),inflammatory cytokine levels(P<0.01),and apoptotic cell rate(P<0.01),while exposure to NAM caused the opposite effects.Moreover,SIRT1 activation reduced the expression levels of GRP78,CHOP,cleaved caspase-12,cleaved caspase-9,and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice.CONCLUSION SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12.SIRT1 activation may be a potential therapeutic strategy for UC.

Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statistically significant differences at 3 h(MPO:18.94±1.20 vs 13.51±0.89,P<0.05;MIF:150.67±9.85 vs 122.17±5.67,P<0.05)and 6 h(MPO:13.22±1.54 vs 8.83±0.65,P<0.05;MIF:135.50±9.46 vs 109.83±6.40,P<0.05).With regard to HSP70,HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups.In addition,comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h.The expression of PCNA was higher in the RP and XP groups 3 h after stress induction.Between these two groups,small but statistically significant differences were observed at all of the time points(3 h:69.50±21.52 vs 79.33±15.68,P<0.05;6 h:107.83±4.40 vs 121.33±5.71,P<0.05;24 h:125.33±5.65 vs 128.50±14.49,P<0.05)except 0 h.With regard to apoptosis,the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups.The XP group exhibited a higher inhibition of cell apoptosis than the RP group at3 h(232.58±24.51 vs 174.46±10.35,P<0.05)and6 h(164.74±18.31 vs 117.71±12.08,P<0.05).CONCLUSION:The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers.It exhibited multiple underlying mechanisms and deserves further study.

Proteomics of the mediodorsal thalamic nucleus of rats with stress-induced gastric ulcer

BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.

Effects of endoplasmic reticulum stress on the expressionof inflammatory cytokines in patients with ulcerative colitis

AIM: To explore the changes of X-box binding protein 1splicing(XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis(UC) in response to endoplasmic reticulum stress(ERS).METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1 s and the expression of interleukin(IL)-2, interferon(IFN)-γ, and IL-17α. Differences between patients with UC and normal subjects were then determined.RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs(control), phytohemagglutinin(PHA), thapsigargin(TG), or both PHA and TG. XBP1 s in patients with UC exhibited splicing, which was greater with co-stimulation than single stimulation. Costimulation increased the expression level of IL-2, IFN-γ, and IL-17α.CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s-mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects.

Protective role of metallothionein in stress-induced gastric ulcer in rats

AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.

p53 antibodies,metallothioneins,and oxidative stress markers in chronic ulcerative colitis with dysplasia

AIM:To investigate the role of p53 antibodies (p53Abs),metallothioneins (MTs) and oxidative stress markers in the early detection of dysplasia in chronic ulcerative colitis (UC).METHODS:The study included 30 UC patients,15 without dysplasia (group Ⅱ) and 15 with dysplasia (group Ⅲ),in addition to 15 healthy volunteers (group Ⅰ,control subjects).The enzyme-linked immunosorbent assay technique was used to measure serum p53Abs and MTs,while advanced oxidation protein products (AOPPs),and reduced glutathione (GSH) levels were measured by spectrophotometric method in all subjects.RESULTS:In group Ⅱ and group Ⅲ compared to group Ⅰ,there were significant increases in serum levels of AOPPs (145.94 ± 29.86 μmol/L and 192.21 ± 46.71 μmol/L vs 128.95 ± 3.06 μmol/L,P < 0.002 and P <0.001,respectively),MTs (8.18 ± 0.35 μg/mL and 9.20 ± 0.58 μg/mL vs 6.12 ± 0.25 μg/mL,P < 0.05 and P < 0.05,respectively),and p53Abs (20.19 ± 3.20 U/mL and 34.66 ± 1.34 U/mL vs 9.42 ± 1.64 U/mL,P < 0.001 and P < 0.001,respectively).There were significantly higher levels of AOPPs (P < 0.05) and p53Abs (P < 0.001) in UC patients with dysplasia compared to those without dysplasia,while MTs showed no significant difference between the 2 groups (P > 0.096).In contrast,GSH levels showed a significant decrease in both patients' groups (1.87 ± 0.02 μmol/mL and 1.37 ± 0.09 μmol/mL vs 2.49 ± 0.10 μmol/mL,P < 0.05 and P < 0.05 in groups Ⅱ and Ⅲ,respectively) compared with group Ⅰ,and the levels were significantly lower in group Ⅲ than group Ⅱ (P < 0.05).There was a positive correlation between AOPPs and both MTs (r=0.678,P < 0.001) and p53Abs (r=0.547,P < 0.001),and also between p53Abs and MTs (r=0.739,P < 0.001).There was a negative correlation between AOPPs and GSH (r =-0.385,P < 0.001),and also between GSH and both MTs (r=-0.662,P < 0.001) and p53Abs (r=-0.923,P < 0.001).CONCLUSION:Oxidative stress and oxidative cellular damage play an important role in the pathogenesis of chronic UC and the associated carcinogenetic process.p53Abs levels could help in early detection of dysplasia in these conditions.

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Influence of astragaloside on gastric mucosa of stress ulcer rats

Objective To investigate the effect of astragaloside(AST)on the gastric mucosal injury of water immersion restraint stress ulcer rat.Methods The stress ulcer model was made by water immersion and restraint.The gastric mucosal injury index was observed.The SOD activity,the MDA contents and the gene expression of melatonin receptor 1 and 2 were detected in gastric mucosa.Results Compared with the normal group,the model group showed mucous edema,hyperemia and even ulcer damage.The injury index and the MDA content of gastric mucosa in model group were significantly increased(P<0.05),the SOD activity of gastric obviously depressed(P<0.01),and the melatonin receptor 1 and 2 mRNA expressions of damaged gastric mucosa were also lower.After administration of AST,the gastric mucosal ulcer index and MDA contents relieved obviously(P<0.01,P<0.05),the SOD activity and the expressions of melatonin receptor 1 and 2 mRNA raised up(P<0.01,P<0.05).Conclusions AST could prevent the gastric mucosal damage of rat in stress ulcer.And the mechanism of the gastric mucosal protection should be concerned with regulating the melatonin receptor and lessening the injury of oxygen free radical.

Oral administration of hyperoxygenated solution for the prophylaxis of gastric ulceration induced by stress or Helicobacter pylori

Oxygen was first discovered by Sweden chemist Scheele in 1773 and convinced as an essential factor for living by French scientists in 1777.To tackle with different hypoxic emergencies,corresponding medical approaches,e.g.mask or nasal catheter oxygen inhalation,breathing machine,hyperbaric oxygen therapy etc.,have been contrived in succession.However,one mortal trouble exists in all these conventional ways,i.e.they must rely on the ventilation and gas exchange via lungs,thus not being able to promptly render oxygen to specific hypoxia tissues.Hyperoxygenated solution(HOS),a new kind of medical liquid which can be orally taken or intravenously administrated,has been widely applied as an auxiliary method of offering oxygen in China.A large number of experiments have proved its validity in the treatment of myocardial and cerebral ischemia/reperfusion injury,nerve lesions,shock,respiratory diseases,neonatal hypoxia and so forth.These findings suggest that HOS might not only play a role of increasing oxygen pressure in local region,but also conspicuously contribute to improving the pathologic process of hypoxia,which coincidently is the vital link in stress-induced lesions in the gastrointestinal tract.Additionally,Helicobacter pylori(H.pylori),a kind of microaerophilic(anaerobic)bacterium which can hardly survive in an aerobic atmosphere,has also been identified as an independent risk factor for the occurrence and development of ulceration.Considering the etiology of peptic ulceration and the features of HOS,we hypothesize that drinking HOS might prevent gastric ulceration caused by stress or anaerobic H.pylori.

Gastrointestinal stress ulcer prophylaxis in the intensive care unit,where is the data?

Stress-induced gastrointestinal ulcers are common among patients admitted to the intensive care unit(ICU).These ulcers impose significant morbidity and mortality,therefore,stress ulcer prophylaxis(SUP) is a common clinical practice among healthcare providers dealing with these critically-ill patients.Several strategies for SUP have been suggested over the past four decades,with acid suppressive therapies being the most commonly used in the ICU.Whether SUP is effective and safe,or not,remains a topic of controversy.The data is still conflicting,and provision of a simple answer is not feasible at the present time.Recently,a large phase IV,multicenter,randomized clinical trial(SUP-ICU),negated the benefits(and harms) of proton pump inhibitors as SUP.This article reviews some of these controversies.

Effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis

Objective: To explore the effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis (UC). Method: A total of 90 patients with UC treated in our hospital were selected and randomly divided into the observation group and the control group each with 45 cases. The control group was given Mesalazin Enteric-coated Tablets 1 g/times, 4 times/d, continuous treatment for 1 months:when the clinical symptoms were stable, switched to 500 mg/times, 3 times/d, continuous treatment for 3 months. The observation group on the basis of conventional treatment to give Bifidobacterium triple live bacteria scattered adjuvant therapy (Bifico capsule), 0.84 g/time, 2 times/d, continuous treatment for 3 months. In the two groups, the levels of inflammatory factors (IL-6, IL-10, CRP, TNF-α), oxidative stress markers (MDA, SOD) and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were compared pre and post treatment. Results: The levels of IL-6, CRP, MDA, TNF-α, CD8+ in both two groups were significantly decreased compared with treatment before;the levels of IL-10, SOD, CD3+, CD4+ and CD4+/CD8+were significantly increased compared with treatment before. After treatment, the levels of serum IL-6, CRP, TNF-α, MDA and CD8+ in observation group with the data (72.17±15.18) pg/mL, (21.52±10.21) mg/mL, (15.98±4.12) pg/mL respectively were decreased more significantly than those data in control group which were (86.55±17.26) pg/mL, (43.02±12.27) mg/L, (22.35±3.67) pg/mL, MDA level (5.89±0.56) nmol/mL in observation group was decreased more significantly than the level in the control group (6.75±0.68) nmol/mL;CD8+level (17.24±3.06)% in observation group was decreased more significantly than the level (19.01±2.62)% in the control group. After treatment, IL-10 level (70.21±6.03) pg/mL in observation group was increased more significantly than the level in the control group (56.48+ 8.67) pg/mL;SOD level (1.84±0.06) U/mL in observation group was increased more significantly than the level in the control group (1.32±0.05) U/mL;the levels of CD3+, CD4+, CD4+/CD8+ in the observation group (57.84±6.07)%;(36.78±4.32)%;(1.92±0.29) were increased more significantly than the level in the control group (54.93±6.87)%;(35.42±5.27)%;(1.89±0.12). Conclusion: Bifidobacterium triple live bacteria scattered adjuvant treatment of ulcerative colitis helps regulate oxidative stress and inflammatory cytokines inhibiting inflammatory reaction and improving enhance function, and can effectively improve the clinical symptoms of patients with UC.

Prediction model of stress ulcer after laparoscopic surgery for colorectal cancer established by machine learning algorithm

BACKGROUND Patients with colorectal cancer(CRC)are prone to stress ulcer after laparoscopic surgery.The analysis of risk factors for stress ulcer(SU)in patients with CRC is important to reduce mortality and improve patient prognosis.AIM To identify risk factors for SU after laparoscopic surgery for CRC,and develop a nomogram model to predict the risk of SU in these patients.METHODS The clinical data of 135 patients with CRC who underwent laparoscopic surgery between November 2021 and June 2022 were reviewed retrospectively.They were divided into two categories depending on the presence of SUs:The SU group(n=23)and the non-SU group(n=112).Univariate analysis and multivariate logistic regression analysis were used to screen for factors associated with postoperative SU in patients undergoing laparoscopic surgery,and a risk factor-based nomogram model was built based on these risk factors.By plotting the model's receiver operating characteristic(ROC)curve and calibration curve,a Hosmer-Lemeshow goodness of fit test was performed.RESULTS Among the 135 patients with CRC,23 patients had postoperative SU,with an incidence of 17.04%.The SU group had higher levels of heat shock protein(HSP)70,HSP90,and gastrin(GAS)than the non-SU group.Age,lymph node metastasis,HSP70,HSP90,and GAS levels were statistically different between the two groups,but other indicators were not statistically different.Logistic regression analysis showed that age≥65 years,lymph node metastasis,and increased levels of HSP70,HSP90 and GAS were all risk factors for postoperative SU in patients with CRC(P<0.05).According to these five risk factors,the area under the ROC curve for the nomogram model was 0.988(95%CI:0.971-1.0);the calibration curve demonstrated excellent agreement between predicted and actual probabilities,and the Hosmer-Lemeshow goodness of fit test revealed that the difference was not statistically significant(χ2=0.753,P=0.999),suggesting that the nomogram model had good discrimination,calibration,and stability.CONCLUSION Patients with CRC aged≥65 years,with lymph node metastasis and elevated HSP70,HSP90,GAS levels,are prone to post-laparoscopic surgery SU.Our nomogram model shows good predictive value.

Correlation of cingulin and claudin-2 expression in ulcerative colitis tissues with intestinal flora disturbance, oxidative stress and inflammation

Objective:To investigate the correlation of cingulin and claudin-2 expression in ulcerative colitis (UC) tissues with intestinal flora disturbance, oxidative stress and inflammation. Methods: 70 patients with UC who were diagnosed in our hospitals between July 2013 and February 2018 were selected as the UC group, and 90 patients with colonic polyps who underwent colonoscopy in our hospitals during the same period were selected as the colon polyps group. The differences in cingulin and claudin-2 protein expression in intestinal lesions, intestinal flora distribution in feces specimens as well as indexes related to oxidative stress and inflammation in serum were compared between the two groups.Results: cingulin and claudin-2 protein expression in colon lesions of UC group were higher than those of colon polyps group;Escherichia coli count in intestinal tract was higher than that of colon polyps group whereas bifidobacterium and lactobacillus count were lower than those of colon polyps group;oxidative stress indexes GSH-Px and T-AOC contents in serum were lower than those of colon polyps group whereas ROS and LHP contents were higher than those of colon polyps group;inflammatory factors IL-4, IL-6, IL-17, IL-23 and TGF-β contents in serum were higher than those of colon polyps group. Correlation analysis showed that the cingulin and claudin-2 protein expression in UC lesion tissues were directly correlated with the intestinal flora disturbance, oxidative stress response indexes and inflammatory response indexes. Conclusion: Abnormal high expression of cingulin and claudin-2 in UC lesions can promote the intestinal flora disturbance and systemic inflammatory stress response.

Retrospective Study Efficacy of pantoprazole plus perforation repair for peptic ulcer and its effect on the stress response

BACKGROUND Peptic ulcer(PU)is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract,which not only affects patients'normal life but also causes an economic burden due to its high medical costs.AIM To investigate the efficacy of pantoprazole(PPZ)plus perforation repair in patients with PU and its effect on the stress response.METHODS The study subjects were 108 PU patients admitted between July 2018 and July 2022,including 58 patients receiving PPZ plus perforation repair[research group(RG)]and 50 patients given simple perforation repair[control group(CG)].The efficacy,somatostatin(SS)concentration,stress reaction[malondialdehyde(MDA),lipid peroxide(LPO)],inflammatory indices[tumor necrosis factor(TNF)-α,C-reactive protein(CRP),interleukin(IL)-1β],recurrence,and complications(perforation,hemorrhage,and pyloric obstruction)were compared.RESULTS The overall response rate was higher in the RG than in the CG.Patients in the RG and IL-1β were significantly reduced to lower levels than those in the CG.Lower recurrence and complication rates were identified in the RG group.CONCLUSION Therefore,PPZ plus perforation repair is conducive to enhancing treatment outcomes in PU patients,reducing oxidative stress injury and excessive inflammatory reactions,and contributing to low recurrence and complication rates.

Correlation of substance P expression in diabetic foot ulcer tissue with oxidative stress and apoptosis

Objective: To study the correlation of substance P (SP) expression in diabetic foot ulcer tissue with oxidative stress and apoptosis. Methods: Patients with diabetic foot ulcer who were treated in the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology between January 2016 and March 2017 were selected as the diabetic foot ulcer (DFU) group of the research, the diabetic foot ulcer tissue samples were collected, patients who received debridement surgery due to trauma in the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology during the same period were selected as the control group of the research, and normal wound tissue samples were collected. The contents of SP, oxidative stress molecules and apoptosis molecules in the wound specimens were detected. Results: SP, Prdx6, GSHPX and SOD contents in diabetic foot ulcer wound specimens of DFU group were significantly lower than those in normal wound specimens of control group while MDA, AOPP, Cyto-C, Caspase-9, Fas, FasL, Caspase-8 and Caspase-3 contents were significantly higher than those in normal wound specimens of control group;Prdx6, GSHPX and SOD contents in wound of patients with high SP were significantly higher than those of patients with low SP while MDA, AOPP, Cyto-C, Caspase-9, Fas, FasL, Caspase-8 and Caspase-3 contents were significantly lower than those of patients with low SP. Conclusion: The low expression of SP in diabetic foot ulcer tissue can activate oxidative stress response and apoptosis to participate in the formation of ulcer wound.

Correlation of NOX1 and NOX2 expression in ulcerative colitis tissue with intestinal mucosal oxidative stress response and barrier function injury

Objective: To study the correlation of NOX1 and NOX2 expression in ulcerative colitis tissue with intestinal mucosal oxidative stress response and barrier function injury. Methods: A total of 69 patients who were diagnosed with ulcerative colitis in Yan'an People's Hospital between May 2015 and March 2017 were selected as the UC group of the research, and 78 patients who were diagnosed with colon polyps were selected as the polyps group of the research. The ulcerative colitis lesion and polyp lesion were collected to detect the expression of NOX1 and NOX2, the generation of oxygen free radicals as well as the contents of apoptosis molecules and mucosal barrier molecules. Results: The mRNA expression and protein expression of NOX1 and NOX2 in the intestinal mucosa of UC group were significantly higher than those of polyps group;LPO, MDA, AOPP, NO, PDCD5 and Bax levels in intestinal mucosa of UC group were significantly higher than those of polyps group and positively correlated with the mRNA expression and protein expression of NOX1 and NOX2 while Bcl-2, Cdx1, Cdx2, galectin-1, galectin-3, OCLN, cingulin and ZO-1 levels were significantly lower than those of polyps group and negatively correlated with the mRNA expression and protein expression of NOX1 and NOX2. Conclusion: The high expression of NOX1 and NOX2 in ulcerative colitis tissue can activate the intestinal mucosal oxidative stress response and result in the intestinal mucosal barrier function injury.

Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis

Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.