INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Cheng-Suo Huang,Qing-Sheng Hou,Xiao-wen Wen,Ben-Shi Wang,Zhen-Yu Zhu,Lei Zou
Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10 -/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.
研究领域:
胃肠病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Liming Liu,Ning Ma,Lu Wang,Yu Zhang,Yi-Zhen Wan,Tianze Wang,Weiping Qian
Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12–6000 and 10–2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.
研究领域:
生物医学工程
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心血管疾病
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药物开发
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干涉测量
·
纤溶
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianwei Wang,Xiaojia Lv,Ying Li,Haiqiang Wu,Meiwan Chen,Hua Yu,Jianwei Wu,Chenyang Li,Wei Xiong
Intestinal mucosal barrier loss is responsible for the chronic and recurrent ulcerative colitis. Myosin light chain kinase (MLCK) is a potential therapeutic target of the intestinal mucosal barrier dysfunction. Here, we developed a reactive oxygen species (ROS)-sensitive hydrogel (ATG-CS-Gel) derived from a diselenide-bridged arctigenin (ATG) and chitosan (CS) conjugate, with the aims of targeting to inflamed mucosa and modulating MLCK. Our results demonstrated that ATG-CS-Gel achieved ROS-responsive release and significantly inhibited ROS production and mitochondrial depolarization in the Caco-2 and HT-29/MTX-E12 cells under H 2 O 2 -induced stress conditions. Compared with normal tissues, orally-administrated ATG-CS-Gel preferentially adhered to the inflamed mucosa for 24 h, which was attributed to the adhesion between CS and mucin. Therapeutically, ATG-CS-Gel reduced inflammatory symptoms, accelerated intestinal mucosal healing, scavenged excessive ROS, reshaped intestinal flora, and eventually achieved much better therapeutic efficacy in DSS-induced colitis mice when compared to 5-aminosalicylic acid. Moreover, ATG-CS-Gel was demonstrated to reverse intestinal mucosal barrier loss by blocking MLCK activation and maintaining tight junction expression. In summary, this study highlights the potential of MLCK modulation in the restoration of intestinal mucosal barrier using ATG-CS-Gel. The development of ATG-CS-Gel represents a novel and promising strategy for the treatment of ulcerative colitis.
研究领域:
药理学
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胃肠病学
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生物材料科学
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炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Food Engineering
·
2023
·
IF 1.6
Zhonghua An,Yitong Wang,Mengran Wu,Haotian Zheng,Xuelin Feng,Yiming Jiang,Yanling Gong
Atractylodes chinensis volatile oil (ACVO) microcapsules were prepared with chitosan as parietal material. The optimal conditions for encapsulation were investigated by the Response Surface Method (RSM). ACVO microcapsules were characterized by scanning electron microscopy (SEM), particle size analyzer and Fourier Transform infrared spectroscopy (FTIR), respectively. In vitro release properties of ACVO microcapsules were investigated at pH 1.5 and 7.4, respectively. The effects of ACVO microcapsules on the length of rat gastric smooth muscle cells (GSMC), mRNA and protein expression of calmodulin (CaM) and myosin light chain kinase (MLCK) were investigated. Results showed that under optimal conditions, encapsulation efficiency (EE) was 82.19 %. ACVO microcapsules were spherical with a particle size of 1100 nm. ACVO microcapsules had a good release profile at pH 1.5, and the cumulative release within 72 h reached 85.32 %. Cell experiments showed that ACVO microcapsules (0.02, 0.04 μg/mL) had no effect on cell activity, while induced GSMC to contract, and improved the mRNA, protein expressions of CaM and MLCK in GSMC.
研究领域:
药学
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生物技术
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药理学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Minxuan Xu,Fang Shi,Yongshen Gao,Shumei Han,Chensuo Huang,Qinsheng Hou,Xiaoweng Wen,Bengshi Wang,Zhenyu Zhu,Lei Zou,Mingxin Xiong,Wei Dong,Jun Tan
There is a growing amount of research that highlights the significant involvement of metabolic imbalance and the inflammatory response in the advancement of colitis. Arabinose is a naturally occurring bioactive monosaccharide that plays a crucial role in the metabolic processes and synthesis of many compounds in living organisms. However, the more detailed molecular mechanism by which the administration of arabinose alleviates the progression of colitis and its associated carcinogenesis is still not fully understood. In the present study, arabinose is recognized as a significant and inherent protector of the intestinal mucosal barrier through its role in preserving the integrity of tight junctions within the intestines. Also, it is important to note that there is a positive correlation between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), as well as chemically-induced colitis in mice, and lower levels of arabinose in the bloodstream. In two mouse models of colitis, caused by dextran sodium sulfate (DSS) or by spontaneous colitis in IL-10 -/- mice, damage to the intestinal mucosa was reduced by giving the mice arabinose. When arabinose is administrated to model with colitis, it sets off a chain of events that help keep the lysosomes together and stop cathepsin B from being released. During the progression of intestinal epithelial injury, this process blocks myosin light chain kinase (MLCK) from damaging tight junctions and causing mitochondrial dysfunction. In summary, the results of the study have provided evidence supporting the beneficial effects of arabinose in mitigating the progression of colitis. This is achieved through its ability to avoid dysregulation of the intestinal barrier. Consequently, arabinose may hold promise as a therapeutic supplementation for the management of colitis.
研究领域:
胃肠病学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2014
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IF 2.216
Yong-Jian Xiong,Da-Peng Chen,Bo-Chao Lv,Fang-Fei Liu,Li Wang,Yuan Lin
Nobiletin , a citrus polymethoxylated flavone , exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segments in all 6 different low contractile states, and meanwhile significant inhibitory effects in all 6 different high contractile states, showing characteristics of bidirectional regulation (BR). Nobiletin-exerted BR on jejunal contractility was abolished in the presence of c-kit receptor tyrosine kinase inhibitor imatinib or Ca 2 + channel blocker verapamil . In the presence of neuroxin tetrodotoxin , nobiletin only exerted stimulatory effects on jejunal contractility in both low and high contractile states. Hemicholinium-3 and atropine partially blocked nobiletin-exerted stimulatory effects on jejunal contractility in low-Ca 2 + -induced low contractile state. Phentolamine or propranolol or l -NG-nitro-arginine significantly blocked nobiletin-exerted inhibitory effects on jejunal contractility in high-Ca 2 + -induced high contractile state respectively. The effects of nobiletin on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin light chain phosphorylation extent were also bidirectional. In summary, nobiletin-exerted BR depends on the contractile states of rat jejunal segments. Nobiletin-exerted BR requires the enteric nervous system, interstitial cell of Cajal, Ca 2 + , and myosin phosphorylation-related mechanisms.
研究领域:
药理学
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胃肠病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 23
·11956-11965
·
IF 5.396
Fangfang Yan,Wanbing Chen,Li Zhao,Qun Lu,Chengming Wang,Rui Liu
Procyanidins can alleviate small-intestine damage induced by acrylamide (ACR). However, little is known about whether procyanidins, after gastrointestinal digestion, can prevent ACR-induced intestinal barrier damage and the possible mechanism. Here, Caco-2 cells were differentiated into an intestinal epithelial cell monolayer membrane, which was stimulated with or without ACR in the presence or absence of procyanidin A1 (A1) and its digestive products (D–A1). Our findings show that both A1 and D–A1 significantly increased the transepithelial electrical resistance (TEER) value; decreased FITC-dextran 4 kDa (FITC-4 kDa) permeability, apoptosis and lactic dehydrogenase (LDH) release; and enhanced the expression of claudin-1, occludin and zonula occludens-1 (ZO-1) in ACR-induced Caco-2 cell monolayer membrane. In addition, A1 and D–A1 suppressed ACR-induced phosphorylation of mitogen-activated protein kinase (MAPK). Finally, A1 and D–A1 inhibited the myosin light chain kinase (MLCK) signaling pathway, thereby maintaining normal intestinal barrier functions, similar to the MLCK inhibitor in ACR-induced Caco-2 cell monolayer membrane. These findings indicate that A1 can alleviate ACR-induced intestinal barrier dysfunction via inhibiting the MAPK/MLCK signaling pathway, and it still has excellent inhibitory effects after digestion.
研究领域:
营养学
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毒理学
·
细胞生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2013
·Vol. 65
·期 5
·734-744
·
IF 2.033
Chen Da-Peng,Xiong Yong-Jian,Lv Bo-Chao,Liu Fang-Fei,Wang Li,Tang Ze-Yao,Lin Yuan
ObjectivesThe aim of the study was to evaluate berberine-induced bidirectional regulation on the contractility of jejunum.MethodsDifferent low and high contractile states of isolated jejunal segment from rat were established to investigate the effects of berberine.Key findingsStimulatory effects on jejunal segment were exerted by berberine in six low contractile states and inhibitory effects were produced on jejunal segment in six high contractile states. The effects of berberine on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin phosphorylation in jejunum were also bidirectional. Bidirectional regulation was not observed in the presence of tetrodotoxin. No regulatory effects of berberine on jejunal contractility were observed in the presence of verapamil. The stimulatory effects of berberine on jejunal contractility were blocked by atropine. The inhibitory effects of berberine on jejunal contractility were abolished by phentolamine, propranolol and L-NG-nitro-arginine, respectively.ConclusionsBerberine-induced bidirectional regulation needed the presence of the enteric nervous system, and depended on the influx of extracellular Ca2+, related to the cholinergic system while jejunum was in low contractile states, and related to the adrenergic system and nitric oxide relaxing mechanism while jejunum was in high contractile states. The results suggested the potential clinical implication of berberine for alternating-type irritable bowel syndrome.
研究领域:
药理学
·
胃肠病学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
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