DRUG DEVELOPMENT RESEARCH
·
2019
·Vol. 80
·期 7
·958-969
·
IF 1.742
Ying Huang,Zhengwei Huang,Mingjun Wu,Yanpeng Liu,Cheng Ma,Xuejuan Zhang,Ziyu Zhao,Xuequn Bai,Hu Liu,Lili Wang,Xin Pan,Chuanbin Wu
To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY-containing modified-release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP-55 (HPMCP HP-55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale-up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40-NF35 standard for DOXY modified-release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long-term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system.
研究领域:
药剂学
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药物释放系统
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生物医学工程
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yihan Hu,Yiming Sun,Haolin Zhang,Linghuan Luo,Haibin Wang,Ruili Zhang,Ming Ge
2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.
研究领域:
毒理学
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家禽健康
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环境科学
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PubMed
高影响因子
Journal of Diabetes
·
2023
·
IF 4.5
Guangwei Yang,Zitian Liu,Shuohui Dong,Xiang Zhao,Zheng Ge,Zhiqiang Cheng,Xiang Zhang,Kexin Wang
Background Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. Methods High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. Results DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. Conclusions DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway—and not solely by improving blood glucose—to improve oxidative stress in the heart of diabetic cardiomyopathy rats.
研究领域:
外科手术
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糖尿病
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心脏病学
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分子生物学
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PubMed
高影响因子
DIABETOLOGIA
·
2025
·
IF 10.2
Yun Yue,Liu Yu-Dan,Yang Ze-Mian,Wang Yi-Qiao,Zhang Nan,Li Wen-Jing,Gao Di,Sha Lei
Aims/hypothesis While Roux-en-Y gastric bypass (RYGB) effectively treats diabetes, its underlying mechanisms remain unclear, highlighting the need to develop less-invasive alternatives. Emerging evidence suggests duodenal involvement in metabolic homeostasis and type 2 diabetes pathophysiology, yet the role of duodenal myoelectrical activity in diabetes and RYGB is poorly understood. This study aims to characterise duodenal myoelectrical changes in diabetes and RYGB, and evaluate their therapeutic potential. Methods Duodenal myoelectrical activity was recorded in male Sprague Dawley rats and high-fat diet/streptozocin (HFD/STZ)-induced diabetic rats, with or without RYGB. An antro-duodenum electrical stimulation (ADES) system was developed to mimic RYGB-associated myoelectrical hyperactivity. Its effects were examined by reducing stimulating power or chemically ablating duodenal myoelectrical activity with benzalkonium chloride, alongside pancreatic morphometric analyses. ADES was further validated in male Zucker diabetic fatty (ZDF) rats. Results RYGB induced duodenal myoelectrical hyperactivity in HFD/STZ rats, characterised by shortened migrating myoelectric complex cycles, a nearly doubled phase III duration, and a 50.9% increase in fed-state spike frequency. By replicating these specific patterns, ADES achieved glucose-lowering effects comparable with those of RYGB, decreasing fasting glucose levels, reducing the OGTT AUC by approximately 40%, and enhancing insulin secretion by 71.7% at the 30 min time point. These glycaemic improvements were attenuated by either reducing the stimulating power or through benzalkonium chloride-mediated ablation of myoelectrical activity. Furthermore, ADES promoted pancreatic beta cell recovery, increasing beta cell mass by 1.5-fold through a 65.3% enhancement in proliferation and a 39.0% reduction in apoptosis. It also preserved beta cell identity, as evidenced by upregulated expression and promoted nuclear localisation of the key transcription factors pancreatic and duodenal homeobox factor-1 (PDX1) and MAF bZIP transcription factor A (MAFA). In ZDF rats, ADES similarly improved glucose homeostasis, significantly lowering 120 min OGTT glucose, and ameliorated hyperinsulinaemia, reducing plasma insulin levels by 35.1%. Conclusions/interpretation ADES mimics RYGB-induced duodenal hyperactivity, offering comparable glucose-lowering effects. Targeting duodenal myoelectrical activity may provide a minimally invasive alternative to RYGB for diabetes treatment. Graphical
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Pharmaceutics
·
2020
·Vol. 12
·期 8
·731
·
IF 4.421
Kaixiang Zhou,Yuanyuan Yan,Dongmei Chen,Lingli Huang,Chao Li,Kuiyu Meng,Shuge Wang,Samah Attia Algharib,Zonghui Yuan,Shuyu Xie
Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmaxwas shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.Keywords:antimicrobial-resistance;tilmicosin enteric granules;P-glycoprotein;duodenum-targeted release;oral absorption;reduce consumption
研究领域:
药剂学
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兽医学
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生物医学工程
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PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
Xiao Guo,Kaikai Li,Ailing Guo,Erhu Li
In this study, an in vivo animal experiment was performed, to investigate the intestinal absorption and distribution of naringin, hesperidin, and their metabolites by using UPLC-ESI-MS/MS and HPLC-PDA analysis. The bioavailability of naringin or hesperidin in duodenum, jejunum, ileum, cecum, and colon was calculated. A total of 7 and 13 metabolites were found and tentatively identified in intestinal tissue after orally administered naringin and hesperidin in mice, respectively. Sulfates of naringin could be absorbed by ileum and cecum, de-glycosylation metabolites could be absorbed by duodenum, and phenolic acids could be absorbed by the cecum and colon. Sulfates of hesperidin could be absorbed by duodenum and ileum, de-glycosylation metabolites could be absorbed by cecum, and phenolic acids could be absorbed by ileum, cecum and colon. Jejunum did not absorb metabolites of naringin or hesperidin. Results could be beneficial for understanding the intestinal bioactivities of naringin and hesperidin.
研究领域:
药理学
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生物化学
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营养学
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高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 2
·607-615
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IF 3.641
Wang Yingkai,Jie Jiepeng,Qian Bo,Qiao Yongping,Yu Pengming,Zhang Jijun
The objective of this work was to investigate the effect of magnetic resonance cholangiopancreatography (MRCP) based on super-paramagnetic iron oxide nanoparticles (SPIONs) on the recurrence diagnosis of periampullary diverticulum (PAD) and bile duct stone (BDS), so as to provide a
scientific research basis for the recidivation factors of bile duct stones in clinic. Patients with PAD diagnosed in hospital from July 2019 to March 2021 (who had undergone endoscopic gallstone surgery) were selected for study in this work. They were rolled into two groups, the parapapillary
group (123 cases) and the cholangiopancreatic duct directly opening in the diverticulum group (97 cases), according to the clinical classification. Then, 100 patients without PAD who had undergone bile duct node therapy were selected as the control group. The recidivation of BDS, serological
index, and biliary pressure index before and after treatment were compared. The relationship between PAD and recidivation of bile duct stones was analyzed. The results showed that the average particle size, hydration kinetic particle size, effective time, and duration of polyethylene glycol
(PEG)/polyethyleneimine (PEI)/poly aspartic acid-super-paramagnetic iron oxide nanoparticles(PASP-SPIONs) were better than PEG/PEI-SPIONs and SPIONs. The recidivation rate of BDS in Groups R and X was remarkably higher than the rate in control group (P < 0.05). Before treatment,
common bile duct pressure in the control group was lower obviously than that in Groups R and X (P < 0.05). After treatment, the indexes including total bilirubin, direct bilirubin, and alkaline phosphatase in control group were lower than those in Groups R and X (P < 0.05).
The incidence of complications in Groups R and X was much higher than in contrast to the control group (P < 0.05). Therefore, PEG/PEI/PASP-SPIONs had good contrast effect and could be used as magnetic resonance imaging contrast agent. Complications such as common bile duct pressure
and infection were increased by PAD, which may be the main factor for the recidivation of BDS.
研究领域:
医学影像
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胃肠病学
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纳米技术
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临床研究
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2020
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IF 3.216
Xuan Zou,Yang Wang,Yuheng Wang,Junting Yang,Huishu Guo,Zhengxu Cai
Introduction Paeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD. Materials and Methods In this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances. Results We found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated. Discussion These results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.
研究领域:
药理学
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胃肠病学
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传统中药
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PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2015
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IF 2.416
Cunshan Zhou,Xiaojie Yu,Xiaopei Qin,Haile Ma,Abu ElGasim A. Yagoub,Jiali Hu
Kinetics modelling, DPPH radical scavenging activity and reducing power of rapeseed meal protein were investigated under simulated duodenum digestion. Kinetics of the reaction was considered in relation to initial substrate concentration, initial enzyme concentration, and hydrolysis time. Optimum hydrolysis conditions were trypsin concentration of 10 g/L, substrate concentration of 4 g/L, time of 40 min and temperature of 37 °C. From the results a general kinetic enzymolysis equation was suggested, providing a rational theoretical basis for determining the parameters of the reaction. The highest antioxidant activity was in accordance with the optimum reaction conditions. Antioxidant free amino acids increased after hydrolysis. Antioxidant oligopeptides of molecular weights of 2608, 1695 and 211 Da were identified. At a concentration of 2 mg/mL, the peptide fraction of CS-F 2 -CC 2 ; with molecular weight of 1000–1500 Da; showed the highest DPPH radical scavenging activity and reducing power, accounting for 70.32% and 0.538, respectively. The trypsin-hydrolysate displayed a potential capacity to scavenge free radicals and binding irons after duodenal digestion, appearing as promising ingredient to formulate functional foods with antioxidant activity.
研究领域:
食品科学
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生物化学
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营养学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Chao-Yue Sun,Wan-Qing Li,Jing-Wen Lu,Ao-Yue Zhang,Qing-Xia Chu,Li Tang,Wei Gao,Jin-Jie Cai,Ying Lu,Dong Liu
Ethnopharmacological relevance Ampelopsis grossedentata (AG) is a popular folk tea that has been used in China for more than 1000 years. It is noteworthy that AG is widely recognized for preventing alcohol hangover in folk, and its protective effects on alcohol-induced hepatic steatosis have been demonstrated. Aim of the study Alcohol overconsumption can induce acute duodenal injury (ADI) that lacks effective therapeutic strategies. This study investigated the gastrointestinal protective effects of AG on alcoholic ADI in mice. Materials and methods AG extract was chemically characterized by HPLC analysis. Institute of Cancer Research (ICR) mice were pre-administered AG extract via gavage, and then subjected to an ethanol-induced ADI. After treatment, duodenal tissues were stained with hematoxylin and eosin (H&E), and cell apoptosis was detected by TUNEL staining and immunofluorescence. Untargeted metabolomics was employed to identify the differentially expressed metabolites, and the gene expressions of duodenal tissues were determined using RNA sequencing, immunofluorescence, immunohistochemistry, and western blotting. Results Acute ethanol administration caused severe duodenal damage, characterized by necrosis and shedding of duodenal villi, hemorrhagic injury, mucosal edema, and disruption of intestinal barrier in mice, which was improved by the pre-treatment with AG extract. Notably, administration of AG aqueous extract suppressed ethanol-induced duodenal villous apoptosis in mice by inhibiting caspase-3/7. In addition, untargeted metabolomics data showed AG extract improved ethanol-induced disruption of amino acid biosynthesis and metabolism, and increased the levels of amino acids, such as L-serine, L-histidine, L-leucine, L-glutamine and L-tryptophan. RNA sequencing analysis revealed that ethanol intake activated TNF, IL-17, MAPK and apoptosis pathways, and these pathways were inhibited by AG extract pre-treatment. Immunofluorescence and immunohistochemistry results showed AG extract reduced the expressions of TNF-a, FADD, TRADD, RIPK1 and caspase-8 activity in duodenal tissue in ethanol-fed mice. In addition, western blotting data showed that pre-treatment with AG extract suppressed ethanol-induced activation of IL-17 and MAPK pathways. Conclusion In conclusion, pre-treatment with AG inhibited ethanol-induced apoptosis of duodenal villi, disruption of intestinal barrier and amino acids metabolic disturbance. AG extract inhibited the TNF-a/FADD/caspase-8 and IL-17/MAPK signaling pathways. These findings highlight the gastrointestinal protective effects of AG extract against alcoholic ADI, and support its application as a duodenal protectant in drug development and dietary supplements.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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代谢组学
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免疫学
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PubMed
高影响因子
Livestock Science
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2024
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IF 1.8
Xue Qin,Menghao Yang,Xiaolin Wang,Haoqi Xiao,Chaoyue Cao,Jiawen Chai,Weijun Pang
Sows commonly suffered ROS due to increased energy demands and metabolic burdens during late gestation (LG) and lactation. Astaxanthin (Asta) is a potent antioxidant, which can enhance livestock health and productivity. Therefore, this study aimed to evaluate the effects of Asta on antioxidant status, reproductive outcomes in sows, and the growth performance of piglets. A total of 80 large white sows were randomly divided equally into dietary treatments supplemented with 0, 4, 8 and 12 mg/kg Asta from 85 days of gestation to 21 days of lactation. The results demonstrated that with increasing levels of dietary Asta, the concentrations of Asta in placenta, colostrum, and piglet liver significantly increased ( P < 0.05), which notably reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while significantly increasing total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity in sow serum, placenta, colostrum, and piglet serum ( P < 0.05). In addition, Asta supplementation significantly increased the number of live births (NLB) in sow and average daily gain (ADG) of piglet with a significant improvement in placental angiogenesis and duodenal development status of piglets ( P < 0.05). Overall, dietary Asta in sows can be transferred to piglets through the placenta or milk, which can improve sow reproductive outcomes and piglet growth by reducing oxidative stress during late gestation (LG) and lactation.
研究领域:
动物科学
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营养学
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生殖生物学
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高影响因子
MICROBIAL PATHOGENESIS
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2023
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IF 3.8
Yuxiao Qian,Yuqian Jiang,Hongrong Hong,Xinxin Gao,Wei Liu,Meiyi Chen,Qinqin Jin,Zha Jin,Xin Li,Xiaocen Wang,Jianhua Li,Quan Liu,Xichen Zhang,Nan Zhang,Zhengkai Wei
Pigeons are natural intermediate host of Neospora caninum ( N. caninum ). In comparison to ruminants, N. caninum causes milder clinical symptoms and less financial loss to pigeons. Natural infectious rates and high prevalence of N. caninum in pigeons, and death cases of N. caninum- infected pigeons under experimental conditions have been reported, but the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum remain not well described. In this study, pigeons were infected intraperitoneally with 10 7 N. caninum tachyzoites . N. caninum in tissues was detected by qPCR. Pathological changes of tissues were examined by hematoxylin-eosin staining. Blood smears were prepared for counting eosinophils changes in blood. Heterophil extracellular traps (HETs) in vivo and in vitro were quantified by Pico Green. N. caninum- induced HETs structures were observed by immunofluorescence staining. The model of pigeons-infected with N. caninum was successfully established. Lung and duodenum were the main target organs of pigeons-infected with N. caninum . N. caninum caused hemorrhage, edema and inflammatory cell infiltration in liver, pulmonary congestion and hemorrhage, organizational destruction in lung, and shorter villi or even disappear in duodenum. N. caninum also increased the number of eosinophils in blood of pigeons. Moreover, N. caninum -induced HETs release in the congenital immunological system of pigeons were first demonstrated, and the HETs structures were consisted of DNA as the skeleton and modified with citH3 and elastase . N. caninum -induced HETs release was related with NADPH oxidase , TLR 2 and 4, ERK 1/2 and p38 MAPK signaling pathways , and glycolysis. In summary, it is the first report on the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum , which may provide theoretical basis for the prevention and control of Neosporosis in pigeons.
研究领域:
兽医学
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免疫学
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病理学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）