Dapsone Ameliorates Colitis through TLR4/NF-kB Pathway in TNBS Induced Colitis Model in Rat.


  • 影响因子:2.10
  • DOI:10.1016/j.arcmed.2021.03.005
  • 作者列表:"Mohammad Jafari R","Shayesteh S","Ala M","Yousefi-Manesh H","Rashidian A","Hashemian SM","Sorouri M","Dehpour AR
  • 发表时间:2021-04-01

BACKGROUND:Crohn's disease (CD), a type of inflammatory bowel disease (IBD), emerges with severe gastrointestinal (GI) tract inflammation, sometimes known as hostile abdomen. Conventional treatment of CD has several limitations such as insufficient response to treatment, and intolerable side effects of drugs. In addition, the high cost of biologic drugs prevents patients from continuing their treatment. Dapsone showed vigorous anti-inflammatory effects on the skin diseases, lung diseases and inflammatory diseases of the nervous system. Hence, we decided to investigate the effect of dapsone on animal model of CD. METHODS:In this study, colitis was induced by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) 100 mg/kg. Rats were treated with daily gavage of dapsone (10, 12.5 and 20 mg/kg). Seven days after induction of colitis, specimens were collected for pathological and molecular assessments. RESULTS:Dapsone (12.5 and 20 mg/kg) preserved the histologic architecture of the colon and prevented crypts irregularity. Additionally, it decreased tissue edema and hindered inflammatory cells infiltration. Besides, all doses of dapsone decreased tissue concentration of tumor necrosis factor α (TNF-α) and interferon γ (INFγ). Western blot revealed that dapsone could attenuate inflammation via downregulation of toll-like receptor 4 (TLR4) and dephosphorylation of nuclear factor kB (NF-kB). CONCLUSION:Based on these findings, dapsone attenuates inflammation and decreases TNF-α and INF-γ in animal model of CD. It acts through TLR4/NF-kB pathway to exert these effects.


背景: 克罗恩病 (CD) 是一种炎症性肠病 (IBD),伴有严重的胃肠道炎症,有时称为腹部不适。CD的常规治疗具有若干限制,例如对治疗的反应不足,以及药物的不可耐受的副作用。此外,生物药物的高成本使患者无法继续治疗。氨苯砜对皮肤疾病、肺部疾病和神经系统炎症性疾病具有强烈的抗炎作用。因此,我们决定研究氨苯砜对CD动物模型的影响。 方法: 在本研究中,通过滴注2,4,6-三硝基苯磺酸 (TNBS) 100 mg/kg诱导结肠炎。每天用氨苯砜 (10、12.5和20 mg/kg) 管饲处理大鼠。结肠炎诱导后7天,收集样本用于病理学和分子评估。 结果: 氨苯砜 (12.5和20 mg/kg) 保留了结肠的组织学结构,并防止了隐窝不规则。此外,它减少组织水肿和阻碍炎性细胞浸润。此外,所有剂量的氨苯砜降低肿瘤坏死因子 α (TNF-α) 和干扰素 γ (ifn γ) 的组织浓度。Western blot显示氨苯砜可通过下调toll样受体4 (TLR4) 和去磷酸化核因子kB (NF-kB) 减轻炎症反应。 结论: 氨苯砜能减轻CD动物模型的炎症反应,降低TNF-α 和INF-γ 水平。它通过TLR4/NF-kB途径发挥这些作用。



作者列表:["Juan-Carlos PM","Perla-Lidia PP","Stephanie-Talia MM","Mónica-Griselda AM","Luz-María TE"]

METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.

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作者列表:["Sawada H","Oeda T","Kohsaka M","Tomita S","Umemura A","Park K","Yamamoto K","Kiyohara K"]

METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

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作者列表:["Louvrier A","Terranova L","Meyer C","Meyer F","Euvrard E","Kroemer M","Rolin G"]

METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

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