JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Chenjiao Miao,Zijia Wang,Xin Wang,Wanyue Huang,Xiang Gao,Zheng Cao
Deoxynivalenol (DON) is widely present in cereals and processed grains. It can disrupt the blood-testicular barrier (BTB), leading to sterility in males; however, the mechanism is unknown. In this study, 30 Kunming mice and TM4 cells were exposed to 0 or 4.8 mg/kg (28 d) and 0–2.4 μM (24 h) of DON, respectively. Histopathological findings showed that DON increased BTB permeability in mice, leading to tight junction (TJ) structural damage. Immunofluorescence results indicated that DON disrupted the localization of zonula occludens (ZO)-1. The results of protein and mRNA expression showed that the expression of ZO-1, occludin, and claudin-11 was reduced, and that the p38/GSK-3β/snail and p38/ATF-2/MLCK signaling pathways were activated in mouse testes and TM4 cells. Pretreatment with the p38 inhibitor SB203580 maintained TJ integrity in TM4 cells after exposure to DON. Thus, DON induced BTB dysfunction in mice by disrupting p38 pathway-mediated TJ expression and distribution.
研究领域:
毒理学
·
生殖生物学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Jiaxue Liang,Hang Qi,Feng Zhu,Shuqi Chen,Bohua Liu,Chongling Sun,Yanyan Wang
Real-time monitoring the drugs penetration into brain is crucial for clinical therapy of neurodegenerative diseases. In this study, a Blood-Brain Barrier-electrochemical sensing (BBB-ES) platform combining BBB on chip model and electrochemical sensing system was proposed, which facilitated stable BBB growth under fluidic conditions and realized real-time detection of L-Dopa across the BBB. Based on this system, the effects of fluid force on the cell morphology, skeleton arrangement and tight junction protein ZO-1 of BBB growth were evaluated, it was verified that the fluid force promote cell rearrangement. Additionally, L-Dopa detecting performance was optimized by modifying SWNTs-AuNPs-PPy/Tyr(Single-Walled Carbon Nanotubes-Au Nanoparticles-Polypyrrole/Tyrosinase) on electrochemical electrode, which showed a wide linear response range of 10–500 μM and excellent selectivity toward L-Dopa. The integrated BBB-ES system was finally applied to real-time monitor the penetration process of L-Dopa through the BBB, it was proved that the penetration of L-Dopa increased with the increase of flow rate and time, and finding that L-Dopa was delivered by passive diffusion without disrupting the integrity of BBB. Based on these findings, the system can be used to monitor the real-time process of different drugs penetrating BBB and even different organ barriers, which also provide the possibility to solve the clinical demand for drugs screen.
研究领域:
神经科学
·
生物医学工程
·
药学
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
AQUATIC TOXICOLOGY
·
2022
·
IF 5.202
Long Zhu,Yongjing Guan,Xuening Li,Xiaofan Xiong,Jialin Liu,Zaizhao Wang
Bisphenol-A (BPA) has been reported to disrupt blood-testis barrier (BTB) integrity in mammals. However, its effects on fish testis sertoli cell (SC) barrier and the underlying mechanisms have been largely unknown to date. To study the SC barrier toxicity induced by BPA, male rare minnows ( Gobiocypris rarus ) were exposed to 15 μg L − 1 BPA for 7, 14 and 21 d. Meanwhile, a 25 ng L −1 17α-ethynyl estradiol (EE2) group was set up as the positive control. Results showed that BPA induced immune response in the testes and decreased offspring hatching rate. The biotin tracer assay showed that BPA exposure destroyed the integrity of the testis SC barrier. In addition, BPA exposure decreased the expressions of occludin, ZO-1, CX43 and N-cadherin proteins. The transcripts of CX43 and occludin were significantly decreased and SP1 recruitment in each gene promoter was repressed after BPA exposure. Moreover, the cytokines (TNFα and IL-1β) were significantly increased while the JNK signal pathway was activated after BPA exposure. BPA also increased the matrix metalloproteinases 1 (MMP1) and MMP2 levels in the testes. In addition, estrogenic effect did not entirely explain the mechanism by which BPA disrupted the SC barrier in G. rarus testes. These results suggested that BPA disrupted the SC barrier integrity by inhibiting SP1 enrichments within CX43 and occludin 5′ flanking regions through activated cytokines/JNK signaling pathway. MMPs were also involved in the disruption of SC barrier caused by BPA exposure.
研究领域:
环境毒理学
·
生殖生物学
·
水生毒理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Yu Jingao,Zhang Dongbo,Liang Yanni,Zhang Zhen,Guo Jianming,Chen Yanyan,Yan Yafeng,Liu Hongbo,Lei Liyan,Wang Zheng,Tang Zhishu,Tang Yuping,Duan Jin-ao
In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair.
研究领域:
中医
·
药理学
·
胃肠研究
·
蛋白质组学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Yajuan Bai,Xuchao Jia,Fei Huang,Ruifen Zhang,Lihong Dong,Lei Liu,Mingwei Zhang
In this study, LPIIa, a purified polysaccharide from longan pulp, was isolated. Its anti-inflammatory activity and intestinal barrier protection were investigated with LPS-treated co-culture model of Caco-2 cells and RAW 264.7 macrophages. The average molecular weight LPIIa was 159.3 kDa. Its detailed structure was shown below. The backbone of LPIIa was composed of (1→3,4)-linked-α-Rha p , (1→4)-linked-β-Gal p , (1→6)-linked-β-Gal p , and (1→3,6)-linked-β-Gal p , with branches at the O-4 of Rha and O-3 of Gal, consisting of side chains of α-Ara f , β-Gal p , and α-Glc p . In LPS-induced RAW 264.7 macrophages, LPIIa suppressed the production of inflammatory mediators, including TNF-α, IL-6, NO, and PGE2, and inhibited iNOS and COX-2 gene expression. In addition, LPIIa attenuated intestinal tight-junctional channel protein Claudin-2 expression and increased tight-junctional barrier protein ZO-1 expression in Caco-2 cells. Knowing the structural features and activities of longan polysaccharide gives insights into longan polysaccharide application as an anti-inflammatory agent or adjuvant in curing the intestinal inflammation.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2022
·
IF 3.848
Bei-Bei Dou,Xia Yang,Feng-Ming Yang,Kang Yan,Wei Peng,Jia Tang,Ming-Zheng Peng,Qi-Yun He,Huan-Chun Chen,Fang-Yan Yuan,Wei-Cheng Bei
Streptococcus suis ( S. suis ) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important syndrome of S. suis infection. The vancomycin resistance associated sensor/regulator (VraSR) is a critical two-component signal transduction system that affects the ability of S. suis to resist the host innate immune system and promotes its ability to adhere to brain microvascular endothelial cells (BMECs). Prior work also found mice infected with Δ vraSR had no obvious neurological symptoms , unlike mice infected with wild-type SC19. Whether and how VraSR participates in the development of S. suis meningitis remains unknown. Here, we found Δ vraSR -infected mice did not show obvious meningitis, compared with wild-type SC19-infected mice. Moreover, the proinflammatory cytokines and chemokines in serum and brains of Δ vraSR- infected mice, including IL-6, TNF-α, MCP-1 and IFN-γ, were significantly lower than wild-type infected group. Besides, blood-brain barrier (BBB) permeability also confirmed that the mutant had lower ability to disrupt BBB. Furthermore, in vivo and in vitro experiments showed that SC19 could increase BBB permeability by downregulating tight junction (TJ) proteins such as ZO-1, β-Catenin, Occludin , and Clauidn-5, compared with mutant Δ vraSR . These findings provide new insight into the influence of S. suis VraSR on BBB disruption during the pathogenic process of streptococcal meningitis, thereby offering potential targets for future preventative and therapeutic strategies against this disease.
研究领域:
微生物学
·
传染病学
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神经科学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2021
·Vol. 30
·期 5
·631-642
·
IF 2.391
Wu Lu,Tan Li Xia,Gong Fen Fang,Xia Yu,Chu Rui Ge,Yang Hua Sheng
This study was designed to evaluate the absorption promoting capacity of Maillard Reaction Products (MRPs) produced during the stir-frying process of Hordei Fructus Germinatus on catechin, ferulic acid, quercetin and kaempferol by the ex vivo rat everted gut sac model, in situ single-pass intestinal perfusion model and the whole animal model. Moreover, verapamil, EDTA and mannitol were used for determining the transport mechanism of catechin, ferulic acid, quercetin and kaempferol. The tight junction (TJ) proteins including zonula occudens-1(ZO-1) and claudin-1 were chosen to investigate the promoting mechanism of MRPs by quantitative real-time PCR (qRT-PCR) and western blot analyses. The results showed that the MRPs produced during the stir-frying process of Hordei Fructus Germinatus could improve the intestinal absorption of catechin, ferulic acid, quercetin and kaempferol. And the absorption-promoting effect of MRPs was related to chelating effect and the reduced expression of claudin-1 and ZO-1. Our results suggested that MRPs could be promising oral absorption promoters, which might be another processing mechanism of Hordei Fructus Germinatus .
研究领域:
药理学
·
食品科学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Shuangqing Wang,Zhonggao Gao,Lei Liu,Mingxin Li,Along Zuo,Jianpeng Guo
This paper describes the development of a film comprising chitosan (CS), sodium alginate (SA), and ethyl cellulose (EC) for buccal mucosal administration. A film of CS-SA unidirectional release drug-containing water-repellent layer EC was produced by interfacial reaction solvent-drying technique using self-made equipment. The CS-SA-EC film had superior mechanical properties compared to CS-EC and SA-EC films. The existence of the amide bond was confirmed by FT-IR. DSC confirmed that the drug was dispersed in the carrier material in an amorphous form. The drug release studies emerged that the model drugs from CS-SA-EC films presented better release properties. The Ritger-Peppas model best describes all ratios of drugs release mechanisms. The permeability characteristics of the films were evaluated in the TR146 cells model and the rabbit buccal mucosae. The cumulative penetration amounts of the model drugs were significantly increased. The permeability mechanism of the film was studied preliminarily using immunofluorescence and Western Blot. The results showed that the film inhibited the expression of ZO-1 protein, and the expressive trend of ZO-1 protein was consistent with the results of in vitro permeation experiments. The pharmacokinetics of the drugs loaded films were evaluated and compared with oral administration in rats. The relative bioavailability of the model drugs was 246.00% (Zolmitriptan) and 142.12% (Etodolac) relative to oral administration. The results of this study demonstrate the potential of CS-SA-EC vehicle in buccal mucosa drug delivery.
研究领域:
药学
·
生物药剂学
·
药物递送系统
·
药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
·
IF 5.168
Zhen-Huan Lv,Trinh Anh Phuong,Shi-Jie Jin,Xiao-Xue Li,Ming Xu
Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication. Our results found that high glucose significantly induced the formation and activation of NLRP3 inflammasome through NADPH oxidase-dependent reactive oxygen species (ROS) formation, associated with vascular endothelial hyperpermeability causing by ZO-1 and VE-Cadherin disruption in the rat aortic endothelial cells (RAECs). Simvastatin treatment remarkably abolished vascular endothelial hyperpermeability and enhanced the protein expression of ZO-1 and VE-Cadherin through NLRP3 inflammasome. Mechanistically, the inhibitory role of simvastatin endothelial hyperpermeability is attributed to the decreased release of cytoplasmic high mobility group box protein-1 (HMGB1) derived from endothelial NLRP3 inflammasome activation. We further confirm the protective role of simvastatin on vascular leakage in the heart of diabetic rats injected with Evans blue dye, which was associated with HMGB1 release in the serum. Collectively, the mechanism of simvastatin treatment alleviating vascular endothelial permeability dysfunction may be through inhibiting the NLRP3 inflammasome-dependent HMGB1 release in RAECs.
研究领域:
心血管疾病
·
药理学
·
分子生物学
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Xinwen Dong,Yaguang Su,Zheng Luo,Cuiying Li,Jie Gao,Xiaofeng Han,Sanqiao Yao,Weidong Wu,Linqiang Tian,Yichun Bai,Guizhi Wang,Wenjie Ren
Background: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).Methods: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.Results: Hematoxylin–eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.Conclusion: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.
研究领域:
神经科学
·
微生物学
·
药理学
·
代谢组学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Min Zheng,Chen Xie,Dan Ye,Yong Chen,Ziyao Wang,Le Wang,Fang Xiong,Sheng Zhang,Qiang He,Hui Wu,Zhinong Wu,Hongfu Zhou,Ling Li,Jun Xing,Xiaolei Miao
BACKGROUND Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg −1 day −1 ). RESULTS QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6β levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.
研究领域:
药理学
·
胃肠病学
·
营养学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2021
·
IF 4.407
Yu-bo Sun,Mo Liu,Xin-sheng Fan,Li-ping Zhou,Meng-wen Li,Fang-yuan Hu,Qin-fei Yue,Yi-ming Zhang
The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1 −/− ) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1 −/− -OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1 −/− -OVA group and TRPA1 −/− -OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.
研究领域:
免疫学
·
呼吸病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）