• angiogenesis
• organogenesis
• disease model
• respiratory distress syndrome
• intrauterine growth
• neonatology
• paediatric research
• preterm birth

• Animals
• Animals, Newborn
• Heparin/administration & dosage
• Heparin/adverse effects
• Lung/drug effects
• Lung/growth & development
• Lung/pathology
• Mice
• Mice, Inbred C57BL
• Bronchopulmonary Dysplasia
• Heparin, Low-Molecular-Weight/administration & dosage
• Heparin, Low-Molecular-Weight/adverse effects
• Female
• Disease Models, Animal
• Male

• T32 HL007734 NHLBI NIH HHS
• 5T32HL007734 NIH HHS
• T35 HL110843 NHLBI NIH HHS
• 5T35HL110843 NIH HHS
• 2T32DK007754-22 NIH HHS
• T32 DK007754 NIDDK NIH HHS
• NIH
• the Richard and Sandra Cummings Research Fellowship of the Beth Israel Deaconess Medical Center Department of Surgery
• The Boston Children’s Hospital Vascular Biology Program
• The Boston Children’s Hospital Surgical Foundation
• The Hannah Lillie Fund
• The Maisie Ellis & Friends Fund
• The Luke Raymond Celaya Research Fund

• Bone cement
• Enoxaparin sodium
• Inflammation
• Macrophage

• Heparin
• Pharmacological activity
• Sustained-release strategies

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent relapsing inflammation in the colon. Whole grains have been promoted as healthy and sustainable foods; however, the use of whole gains in UC is inconclusive. The aim of this study was to investigate the effects of ethanol extracts of rice bran (RBE) and whole-grain adlay seeds (ADE) on inflammation, oxidative stress, and colonic damage in UC. Male C57BL/6JNarl mice were intra-rectal injected twice with 2,4-dinitrobenzene sulfonic acid to induce (day 0) and reactivate (day 21) UC. Control mice were fed AIN-93M diet (R group) and injected with a vehicle. UC mice were fed AIN-93M diet (UC group) supplemented with RBE (RBE group) or ADE (ADE group) for 21 days. The results showed that the UC group had an increased disease activity index, plasma interleukin (IL)-6 and glutathione levels, microscopic injury scores, and inflammatory cytokine and chemokine levels in the colon and decreased colonic claudin-4 compared to the R group. RBE and ADE supplementation significantly reduced UC-elevated plasma IL-6 and colonic glutathione and pro-inflammatory cytokines and a chemokine. In addition, RBE and ADE supplementation significantly decreased T-helper-cell-associated cytokines in the plasma and colon. Moreover, RBE supplementation increased colonic IL-10 and tight junction protein claudin-4 levels, and ADE supplementation alleviated diarrhea in UC mice. In conclusion, these results suggest that RBE and ADE may mitigate colonic inflammation, oxidative stress, and damage in UC relapse.

• cytokines
• oxidative stress
• rice bran
• tight junction
• ulcerative colitis
• whole-grain adlay seeds

• Dextran sulfate sodium induced colitis
• L-citrulline
• L. helveticus
• fermented milk with La. helveticus
• inflammation
• tight junction proteins

• Amelioration
• Colitis
• Cytokine
• Diacylglycerol
• Intestinal microflora
• Vitamin D

Oxidative stress is a key player of the inflammatory cascade responsible for the initiation of ulcerative colitis (UC). Although the short chain quinone idebenone is considered a potent antioxidant and a mitochondrial electron donor, emerging evidence suggests that idebenone also displays anti-inflammatory activity. This study evaluated the impact of idebenone in the widely used dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was induced in C57BL/6J mice via continuous exposure to 2.5% DSS over 7 days. Idebenone was co-administered orally at a dose of 200 mg/kg body weight. Idebenone significantly prevented body weight loss and improved the disease activity index (DAI), colon length, and histopathological score. Consistent with its reported antioxidant function, idebenone significantly reduced the colonic levels of malondialdehyde (MDA) and nitric oxide (NO), and increased the expression of the redox factor NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase quinone-1 (NQO-1) in DSS-exposed mice. Immunohistochemistry revealed a significantly increased expression of tight junction proteins, which protect and maintain paracellular intestinal permeability. In support of an anti-inflammatory activity, idebenone significantly attenuated the elevated levels of pro-inflammatory cytokines in colon tissue. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by simultaneously inducing antioxidative and anti-inflammatory pathways.

• cytokines
• idebenone
• inflammatory bowel disease
• lipid peroxidation
• superoxide dismutase
• tight junction proteins and ulcerative colitis

• Bacillus spores
• IBD
• dietary fibre
• prebiotic
• probiotic
• sugar cane fibre
• synbiotic
• ulcerative colitis

• Animals
• Bacillus coagulans
• C-Reactive Protein/analysis
• Colon/ultrastructure
• Diet
• Dietary Fiber/administration & dosage
• Dietary Supplements
• Disease Models, Animal
• Female
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/pathology
• Inflammatory Bowel Diseases/therapy
• Interleukin-1beta/blood
• Male
• Mice
• Mice, Inbred C57BL
• Probiotics/administration & dosage
• Saccharum
• Spores, Bacterial
• Synbiotics/administration & dosage
• Tight Junctions/pathology

• RT111031 KFSU Ltd.

MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1β, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1β release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.

Mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), a paracaspase and essential regulator for nuclear factor kB (NF-κB) activation, plays an important role in innate and adaptive immunity. Suppression of MALT1 protease activity with small molecule inhibitors showed promising efficacies in subtypes of B cell lymphoma and improvement in experimental autoimmune encephalomyelitis model. However, whether MALT1 inhibitors could ameliorate colitis remains unclear. In the present study, we examined the pharmacological effect of two specific MALT1 inhibitors MI-2 and mepazine on the dextran sulfate sodium (DSS)-induced experimental colitis in mice, followed by mechanistic analysis on NF-κB and NLRP3 inflammasome activation. Treatment with MI-2 and mepazine dose-dependently attenuated symptoms of colitis in mice, evidenced by reduction in the elevated disease activity index, the shortening of colon length as well as the histopathologic improvement. Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF, IL-1β, IL-6, IL-18, IL-17A and IFN-γ, were markedly suppressed by MALT1 inhibitors. The underlying mechanisms for the protective effect of MALT1 inhibitors in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in macrophages. The in vitro study showed that MALT1 inhibitors decreased production of IL-1β/IL-18 in phorbol myristate acetate-differentiated THP-1 cells and bone marrow derived macrophage via suppressing the activation of NF-κB and NLRP3 inflammasome. Taken together, our results demonstrated that inhibition of the protease activity of MALT1 might be a viable strategy to treat inflammatory bowel disease and the NLRP3 inflammasome and NF-κB activation are critical components in MALT1 signaling cascades in this disease model.

• IL-1β
• MALT1
• NF-κB
• NLRP3 inflammasome
• colitis

• LMWH
• Ulcerative colitis
• macrophages
• nanoparticles
• polymethacrylate

• Animals
• Colitis
• Colitis, Ulcerative
• Drug Delivery Systems
• Heparin, Low-Molecular-Weight
• Mice
• Nanoparticles

Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH) remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed cerebral ischemia that accompany the disease. This narrative review examines how heparin may mitigate the non-vasospastic pathological aspects of aSAH, particularly those related to neuroinflammation. Following a brief review of early brain injury in aSAH and heparin’s general pharmacology, we discuss potential mechanistic roles of heparin therapy in treating post-aSAH inflammatory injury. These roles include reducing ischemia-reperfusion injury, preventing leukocyte extravasation, modulating phagocyte activation, countering oxidative stress, and correcting blood-brain barrier dysfunction. Following a discussion of evidence to support these mechanistic roles, we provide a brief discussion of potential complications of heparin usage in aSAH. Our review suggests that heparin’s use in aSAH is not only safe, but effectively addresses a number of pathologies initiated by aSAH.

• brain injury
• edema
• enoxaparin
• heparin
• inflammation
• subarachnoid hemorrhage

• Acidosis
• Endothelial cell
• GPR4
• Inflammation
• Inflammatory bowel disease (IBD)

• heparin
• inflammatory bowel disease
• low molecular weight heparin
• mechanism
• ulcerative colitis