Gastrointestinal Injury Research Articles

Acute Gastrointestinal Injury and Feeding Intolerance as Prognostic Factors in Critically Ill COVID-19 Patients

BackgroundAlthough acute gastrointestinal injury (AGI) and feeding intolerance (FI) are known independent determinants of worse outcomes and high mortality in intensive care unit (ICU) patients, the incidence of AGI and FI in critically ill COVID-19 patients and their prognostic importance have not been thoroughly studied. MethodsWe reviewed 218 intubated patients at Stony Brook University Hospital and stratified them into three groups based on AGI severity, according to data collected in the first 10 days of ICU course. We used chi-square test to compare categorical variables such as age and sex and two-sample t-test or Mann-Whitney U-tests for continuous variables, including important laboratory values. Cox proportional hazards regression models were utilized to determine whether AGI score was an independent predictor of survival, and multivariable analysis was performed to compare risk factors that were deemed significant in the univariable analysis. We performed Kaplan-Meier survival analysis based on the AGI score and the presence of FI. ResultsThe overall incidence of AGI was 95% (45% AGI I/II, 50% AGI III/IV), and FI incidence was 63%. Patients with AGI III/IV were more likely to have prolonged mechanical ventilation (22 days vs 16 days, P-value <0.002) and higher mortality rate (58% vs 28%, P-value <0.001) compared to patients with AGI 0/I/II. This was confirmed with multivariable analysis which showed that AGI score III/IV was an independent predictor of higher mortality (AGI III/IV vs AGI 0/I/II hazard ratio (HR), 2.68; 95% confidence interval (CI), 1.69–4.25; P-value <0.0001). Kaplan-Meier survival analysis showed that both AGI III/IV and FI (P-value <0.001) were associated with worse outcomes. Patients with AGI III/IV had higher daily and mean D-dimer and CRP levels compared to AGI 0/I/II (P-value <0.0001). ConclusionsThe prevalence of AGI and FI among critically ill COVID-19 patients was high. AGI grades III/IV were associated with higher risk for prolonged mechanical ventilation and mortality compared to AGI 0/I/II, while it also correlated with higher D-dimer and C-reactive protein (CRP) levels. FI was independently associated with higher mortality. The development of high-grade AGI and FI during the first days of ICU stay can serve as prognostic tools to predict outcomes in critically ill COVID-19 patients.

Effects of Non-directional Mechanical Trauma on Gastrointestinal Tract Injury in Rats.

Mechanical trauma can (MT) cause secondary injury, such as cardiomyocyte apoptosis and cardiac dysfunction has been reported. However, the effects of mechanical trauma on gastrointestinal tract is unclear. This study aims to observe the main location and time of gastrointestinal tract injury caused by non-directional trauma and explain the reason of the increase of LPS in blood caused by mechanical injury. Morphological changes in the stomach, ileum and cecum at different time points after MT were observed in this experiment. The results reveal that the injury to the cecal mucosa in the rats was more obvious than that in the ileum and the stomach. The cecal epithelial cell junction was significantly widened at 20 min after MT, and the plasma LPS and D-lactic acid concentrations increased significantly at the same time point. In addition, some bacterial structures in the widened intercellular space and near the capillary wall of the cecal mucosa were detected at 12 h after MT. This finding suggests that the main reason for the increase in LPS in plasma after MT is cecal mucosal injury. This study is important for the early intervention of the gastrointestinal tract to prevent secondary injury after MT.

Antioxidant and hepatoprotective property of squalene for counteracting the oxidative damage induced by methotrex- ate in experimental rats

Methotrexate (MTX), an antifolate drug, is extensively prescribed for patients suffering from diseases like cancer, psoriasis, neoplasms, and rheumatoid arthritis. Despite its effectiveness, MTX sometimes finds limited application because its undesirable side effects, including hepatic or renal impairment, bone marrow toxicity and gastrointestinal mucosal injury. Squalene, a highly unsaturated isoprenoid compound, isolated from shark liver oil has great potential in neutralizing the damaging effects triggered by free radicals. Therefore, in this study, the protective role of dietary squalene supplementation on oxidative stress induced by methotrexate in experimental rats was evaluated. A significant reduction was displayed in the activities of catalase (CAT) and superoxide dismutase (SOD) in MTX-intoxicated groups compared to other groups. Similarly, the activities of glutathione dependant enzymes (GPx and GST) and reduced glutathione (GSH) in MTX-induced groups were shown to be lower compared to the untreated control. Increased LPO (lipid peroxide) level was found in MTX-intoxicated groups compared to other groups. In addition, alterations in the levels of liver marker enzymes like AST, ALP, ALT, and LDH were noticed in MTX intoxicated groups compared to other groups. Biochemical results were confirmed by the histopathological examination of liver sections. In conclusion, the result obtained in the present study proposes that squalene exerts antioxidant activity and is capable of ameliorating oxidative stress and liver injury induced by MTX.

The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-O-desmethyldonepezil, and Gastric Myoelectric Activity in Experimental Pigs.

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20–30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.

Radiation-induced acute injury of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a prospective cohort study

To address whether the addition of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT) aggravate radiation-induced acute injury of locoregionally advanced nasopharyngeal carcinoma (LANPC) patients with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). We conducted a prospective study of 182 patients in the stage III to IVb with biopsy-proven nonmetastatic LANPC who newly underwent radiotherapy and sequentially received IC, followed by CCRT at our institution. Occurring time of radiation-induced toxicities were estimated and compared using the Kaplan–Meier method and Log-rank test. The most severe acute toxicities included oral mucositis in 97.25% and dermatitis in 90.11%. Subset analysis revealed that Grade 3–4 acute dermatitis were significantly higher in the IMRT than 3D-CRT. Oral mucositis and dermatitis were the earliest occurrence of acute injuries (2 years: 60.44% and 17.58%). Patients in IMRT group achieved significantly lower risk of bone marrow toxicity, but higher risk of leukopenia and gastrointestinal injury. Multivariate analyses also demonstrated that IMRT, female gender and hepatitis were the independent prognostic factors for bone marrow toxicity. In a combined regimen of IC followed by CCRT for the treatment of LANPC, IMRT seems to be an aggressive technique with a trend towards increased gastrointestinal and hematological toxicities, but decreased bone marrow toxicity than those treated with 3D-CRT. This study provides a comprehensive summary of prospective evidence reporting the side effects in the management of LANPC patients. We quantify the occurrence risks of chemoradiotherapy-induced acute injuries through analysis of time-to-event.

Significance of changes of serum heat shock protein 70 levels in patients with traumatic brain injury and acute gastrointestinal injury

Significance of changes of serum heat shock protein 70 levels in patients with traumatic brain injury and acute gastrointestinal injury

Valproic acid protects intestinal organoids against radiation via NOTCH signaling.

Radiotherapy is a leading treatment for various types of cancer. However, exposure to high-dose ionizing radiation causes acute gastrointestinal injury and gastrointestinal syndrome. This has significant implications for human health, and therefore, radioprotection is a major area of research. Radiation induces the loss of intestinal stem cells; hence, the protection of stem cells expressing LGR5 (a marker of intestinal epithelial stem cells) is a key strategy for the prevention of radiation-induced injury. In this study, we identified valproic acid (VPA) as a potent radioprotector using an intestinal organoid culture system. VPA treatment increased the number of LGR5+ stem cells and organoid regeneration after irradiation. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, an inhibitor of NOTCH signaling) blocked the radioprotective effects of VPA, indicating that NOTCH signaling is a likely mechanism underlying the observed effects of VPA. In addition, VPA acted as a radiosensitizer via the inhibition of histone deacetylase (HDAC) in a colorectal cancer organoid. These results demonstrate that VPA exerts strong protective effects on LGR5+ stem cells via NOTCH signaling and that the inhibition of NOTCH signaling reduces these protective effects, providing a basis for the improved management of radiation injury.

Intestinal microbiota and antibiotic-associated acute gastrointestinal injury in sepsis mice.

Background: To investigate the changes of intestinal microbiota and metabolites in sepsis mice with acute gastrointestinal injury before and after the use of antibiotics, and to explore the possible effects of these changes on the body.Methods: Twenty-four 6-8-w-old SPF-grade C57BL/6J male mice were selected, and the mice were randomly divided into three groups. The mice were treated by tail vein injection for 3 days. The intestinal motility of mice after administration was detected. The mice feces were collected for 16S rRNA and Untargeted metabonomics detection.Results: The use of antibiotics in sepsis mice can change the composition of intestinal microbiota and metabolites. LD3, AD3 and LAD3 samples had significant differences in bacterial species. Desulfovibrio was the species with a significant difference in LAD3. In addition, we found that the composition of those intestinal microbiota were correlated with changes in intestinal motility. The untargeted metabolomics analysis showed that the fecal metabolites of LD3 and LAD3 samples were significantly different. In addition to the basic metabolites, Benzoic acid and 4-Hydroxybenzoic acid were also found, and Desulfovibrio was associated with them.Conclusions: The use of antibiotics in sepsis mice can lead to changes in the intestinal microbiota and metabolite levels, which may be related to the severity of acute gastrointestinal injury in sepsis mice. Inhibiting Desulfovibrio in the intestine and using Benzoic acid and 4-Hydroxybenzoic acid as a marker for the production of Desulfovibrio may reduce the inflammatory degree of acute gastrointestinal injury in sepsis.

Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BackgroundThere is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine.MethodsSegments of small intestine, 1.5–3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer’s solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5–3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury.ResultsAfter a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP.ConclusionsThis novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

Gastrointestinal Manifestations and Liver Injury: Correlation with Mortality and Clinical Outcomes in Patients with COVID-19

Background and aims: Reports indicate that patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection present with gastrointestinal (GI) manifestations and abnormal liver function; however, the impact on clinical findings is unclear. The aim of this study is to report the impact of gastrointestinal and liver injury (LI) associated with coronavirus disease (COVID-19). Material and methods: The authors retrospectively evaluated patients who presented to the emergency department and were diagnosed with COVID-19 by PCR nasopharyngeal swab. Primary outcomes were the impact of GI findings and LI on in-hospital mortality. Secondary outcomes were length of stay in hospital and need for intensive care unit (ICU) level care. Results: Of the entire cohort, 64.0% had LI during hospitalisation. LI was present in 88.7% of those who died. In multivariate analysis, GI manifestations were associated with decreased risk of mortality (odds ratio [OR]: 0.46; 95% confidence interval [CI]: 0.24–0.90; p=0.002). GI symptoms did not impact length of stay, 5.06 days for patients with GI symptoms versus 4.74 in patients without (OR: 1.01; 95% CI: 0.96–1.07; p=0.43), or need for ICU (OR: 0.97; 95% CI: 0.60–1.58; p=0.9076) (Table 1). In multivariate analysis, LI was associated with increased mortality (OR: 8.60; 95% CI: 3.49–21.15; p&lt;0.0001), need for ICU (OR: 10.94; 95% CI: 4.07–29.45; p&lt;0.0001), and length of stay 5.87 days versus 3.01 days (OR: 1.23; 95% CI: 1.14–1.32; p&lt;0.0001). Conclusion: The results of the data analysis show that GI symptoms may inversely correlate with mortality, while LI is associated with increased mortality, length of stay, and ICU admission.

Antenatal Dietary Butyrate Supplementation Reduces Postnatal Gastrointestinal Injury in a Murine Model of Colitis

Antenatal Dietary Butyrate Supplementation Reduces Postnatal Gastrointestinal Injury in a Murine Model of Colitis

A Molecular Dynamics of Radiation-Induced DNA Damage Response: Exploring the Pathways of Signaling, Repair, and Cell Death

Purpose: In this review, we summarized the latest information related to accidentally and/or un-accidental exposure of ionizing radiation triggered by oxidative stress and/or cytotoxicity and adverse effects on human health such as hematopoietic, gastrointestinal and cerebrovascular injury collectively referred to as acute radiation syndromes. Directly or indirectly IR induced oxidation of biomolecules, especially DNA, resulting in altered genomic stability and DNA strand breaks. DNA strand breaks are recognized by DNA damage sensory protein that activates downstream checkpoint kinases as well as initiate compensatory multiple intracellular and intranuclear signaling pathways, resulting in cell cycle arrest and DNA repair. Simultaneously activates tumor suppressor genes leading to death signaling pathway or triggering of numerous autocrine/paracrine loops leading to structural dis-organization and programmed cell death. These signaling pathways work together to decrease the magnitude of radiotherapy and promote the development of radiation resistance in cancer cells. The fate of the cells and DNA damage repair depending on the severity of radiation exposure and types of DNA damage. Conclusions: Based on the recent invested reports related to IR and DNA damage signaling, this review would be helpful for researchers and healthcare providers to develop a new research concept and translate this information into a cancer therapeutic approach. Moreover, target specific screening and development of radiation countermeasures agent for radiological emergencies.

Intestinal fatty acid‐binding protein and acute gastrointestinal injury grade in postoperative cardiac surgery patients

Gastrointestinal complications post cardiac surgery are infrequent but difficult to diagnose and carry a high mortality. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations and the relationship between I-FABP, gastrointestinal dysfunction, and postoperative outcomes were investigated in patients who developed gastrointestinal dysfunction (acute gastrointestinal injury [AGI] grade ≥2) and those with normal gastrointestinal function. Patients with (AGI 2 group, n = 11) and without (matched controls, AGI 0 group, n = 22) early postoperative gastrointestinal dysfunction were extracted from a larger single-center prospective observational study, including adults undergoing elective cardiac surgery with extracorporeal circulation, and investigated in this nested case-control analysis. Both groups displayed variations in I-FABP concentrations with higher I-FABP on postoperative Day 1 compared to baseline and postoperative Days 2 and 3 (p < .001 and p = .005, respectively). The AGI 2 group had higher I-FABP concentrations on Day 2 compared to the AGI 0 group (p = .024). I-FABP on Day 2 correlated positively with AGI grade over the first 3 days (p = .036, p = .021 and p = .018, respectively). High I-FABP (defined as fourth quartile concentrations) on Day 1 was associated with more prolonged surgical procedures (p < .05). Furthermore, fourth quartile I-FABP on Day 1 and early gastrointestinal dysfunction were associated with higher frequencies of postoperative organ dysfunction (p < .05) and gastrointestinal complications (p < .05), and higher 365-day mortality. The present study indicates an association between intraoperative gastrointestinal injury, postoperative gastrointestinal dysfunction and gastrointestinal complications. A high-powered study is needed to further explore this relationship and the interpretation of I-FABP concentrations in individual cardiac surgery patients.

Novel Multiparametric Nomogram for Overall Survival Prediction in Complicated Intra-Abdominal Infection: A Multicenter Study in China.

Background: Complicated intra-abdominal infections (cIAIs) in the abdominal cavity or within an abdominal organ are numerous and frequent dangerous entities in the treatment of critically ill patients. Early clinical evaluation is necessary.Methods: This retrospective multicenter study included patients from 10 intensive care units (ICUs). Risk factors for the overall survival (OS) of patients with cIAI were selected using least absolute shrinkage and selection operator regression, and a nomogram was constructed subsequently. Calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discriminative ability.Results: In total, 544 patients diagnosed with cIAI were enrolled and divided into the study (n = 276) and validation (n = 268) sets. Sex, acute gastrointestinal injury, acute kidney injury, rare bacterium infection, Charlson score, and APACHE II score were identified as independent risk factors and were constructed for the nomogram. The nomogram showed marked calibration capability with a concordance index (C-index) of 0.909 and 0.831 in the study and validation set, respectively. Compared with the common clinical prognostic scoring system, the nomogram achieved the highest discrimination ability with an area under the curve (AUC) value of 0.91 and 0.83 in the study set and validation set, respectively.Conclusions: Our newly constructed nomogram provides a useful tool for risk stratification and prognosis evaluation of cIAI.

The role of inflammatory cytokines in anemia and gastrointestinal mucosal injury induced by foot electric stimulation

Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.

Prevalence of gastrointestinal lesions in dogs chronically treated with nonsteroidal anti‐inflammatory drugs

BackgroundNonsteroidal anti‐inflammatory drugs (NSAIDs) are the most common pharmaceutical associated with gastroduodenal ulceration and perforation. The prevalence of gastrointestinal (GI) injury associated with chronic use of NSAIDs in dogs is unknown.Objective/HypothesisTo determine the prevalence of GI mucosal erosions in dogs receiving chronic treatment with NSAIDs. We hypothesized that dogs receiving NSAIDs would have more GI mucosal erosions and longer GI transit time than a control population.AnimalsFourteen client‐owned medium‐ and large‐breed dogs receiving an NSAID for at least 30 days and 11 client‐owned control dogs undergoing video capsule endoscopy (VCE) for evaluation of chronic GI disease.MethodsDogs were prospectively recruited after determining no clinically relevant comorbidities were present and VCE was performed. The GI transit time and the presence of mucosal lesions were recorded.ResultsTwelve dogs receiving NSAIDs and 11 retrospectively evaluated control dogs were included. The NSAIDs administered included carprofen (9 dogs), meloxicam (2 dogs), and firocoxib (1 dog) for a median of 6 months. Ten (83.3%; 95% confidence interval; 51.6%‐97.9%) NSAID‐treated dogs had GI erosions. Erosions were seen with all 3 NSAIDs in at least 1 dog. Three of 11 control dogs had gastric erosions. Dogs receiving NSAIDs had more erosions detected (P = .004).Conclusions and Clinical RelevanceSubclinical GI erosions are more common in dogs receiving chronic treatment with NSAIDs than in control dogs with chronic GI disease, suggesting that NSAIDs be used with caution, particularly in dogs with comorbidities predisposing them to GI ulceration.

Research progress and analysis on mechanism of polysaccharides against type 2 diabetes mellitus

Polysaccharides are macromolecular compounds formed by more than 10 monosaccharide molecules linked by glycosidic bonds. Polysaccharides have a wide range of sources, high safety and low toxicity, with a variety of biological activities, such as anti-tumor, anti-virus, immune regulation, lowering blood glucose, and lowering blood lipids. Type 2 diabetes mellitus(T2 DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance and low inflammation. In recent years, the treatment of T2 DM with polysaccharide has become a research hotspot. Polysaccharides can not only make up for the side effects such as hypoglycemia, weight gain, gastrointestinal injury caused by long-term treatment of acarbose, biguanidine and sulfonylurea, but also play an effective role in reducing glucose by regulating glucose metabolism, oxidative stress, inflammatory response, intestinal flora, etc. In this paper, the research progress of polysaccharides in the treatment of T2 DM was reviewed. In addition, the hot spots such as the hypoglycemic activity of polysaccharides with structural modifications were summarized, providing theoretical guidance for the development of active polysaccharide hypoglycemic medicines and the further study of action mechanism.

Association of Changes in Acute Gastrointestinal Injury Grade with Prognosis in Critically Ill Patients: A Prospective, Single-Center, Observational Study.

PurposeTo investigate the association between the change of acute gastrointestinal injury (AGI) grade and the outcome in critically ill patients.MethodsThis was a prospectively observational study. All patients admitted in the ICU from October 2013 to June 2015, with the duration of ICU > 72 h and age >18 years, were enrolled in this study. The AGI grade and gastrointestinal symptoms were evaluated during ICU stay following the 2012 ESICM recommendation. The ICU mortality, duration of ICU stay, mechanical ventilation (MV) use, vasoactive drug use, and continuous renal replacement therapy of patients were recorded accordingly.ResultsA total of 320 patients were included, and 265 of them were diagnosed with AGI. The overall ICU mortality was 11.88%, while it was 13.58% in patients with AGI. In logistic regression analyses, the decreasing trend of AGI grade was identified as a protective factor for ICU death (odds ratio (OR), 0.484; 95% confidence interval (CI), 0.26–0.90), while the max AGI grade was a risk factor (OR, 3.464; 95% CI, 2.71–8.47) for ICU death.ConclusionThe changes of AGI grades in critically ill patients were associated with their clinical outcomes. The ICU-acquired AGI patients associated with longer ICU stay days.

Qingke β-glucan synergizes with a β-glucan-utilizing Lactobacillus strain to relieve capsaicin-induced gastrointestinal injury in mice

Capsaicin (CAP) is the main pungent component in capsicum fruits. Eating too much CAP leads to gastrointestinal injury. Previously, Qingke β-glucan combined with β-glucan-utilizing Lactobacillus plantarum S58 (LP.S58) ameliorated high fat-diet-induced obesity, but their effects on CAP-induced gastrointestinal injury have not been investigated. Our results showed that Qingke β-glucan reduced the CAP-induced gastrointestinal injury in Kunming mice. The serum levels of inflammatory cytokines and gastrointestinal hormones, and the localized inflammation and the expression of EGF, EGFR, VEGF, and ZO-1 in the gastrointestinal tissues in CAP-treated mice were partly restored by Qingke β-glucan. The CAP-induced increase in the abundances of proinflammatory intestinal bacteria was also reduced by Qingke β-glucan. More importantly, we found that these beneficial effects of Qingke β-glucan were markedly enhanced by β-glucan-utilizing LP.S58 supplementation. Our study indicated that Qingke β-glucan coupled with β-glucan-utilizing LP.S58 relieved CAP-induced gastrointestinal injury.

Coenzyme Q10 attenuates inflammation and fibrosis implicated in radiation enteropathy through suppression of NF-kB/TGF-β/MMP-9 pathways

Radiation enteropathy is one the most common clinical issue for patients receiving radiotherapy for abdominal/pelvic tumors which severely affect the quality of life of cancer patients due to dysplastic lesions (ischemia, ulcer, or fibrosis) that aggravate the radiation damage. Herein, this study demonstrated the prophylactic role of coenzyme Q10 (CoQ10), a powerful antioxidant, against radiotherapy-induced gastrointestinal injury. Male Sprague Dawley rats were divided into four groups: group 1 was defined as control, and group 2 was the irradiated group. Group 3 and 4 were CoQ10 control and radiation plus CoQ10 groups, respectively. CoQ10 (10 mg/kg) was orally administered for 10 days before 10 Gy whole-body radiation and was continued for 4 days post-irradiation. CoQ10 administration protected rats delivered a lethal dose of ϒ-radiation from changes in crypt-villus structures and promoted regeneration of the intestinal epithelium. CoQ10 attenuated radiation-induced oxidative stress by decreasing lipid peroxidation and increasing the antioxidant enzyme catalase activity and reduced glutathione level. CoQ10 also counteracts inflammatory response mediated after radiation exposure through downregulating intestinal NF-ĸB expression which subsequently decreased the level of inflammatory cytokine IL-6 and the expression of COX-2. Radiation-induced intestinal fibrosis confirmed via Masson's trichrome staining occurred through upregulating transforming growth factor (TGF)-β1 and matrix metalloproteinase (MMP)-9 expression, while CoQ10 administration significantly diminishes these effects which further confirmed the anti-fibrotic property of CoQ10. Therefore, CoQ10 is a promising radioprotector that could prevent intestinal complications and enhance the therapeutic ratio of radiotherapy in patients with pelvic tumors through suppressing the NF-kB/TGF-β1/MMP-9 signaling pathway.