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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

Chitosan-gentamicin conjugate attenuates heat stress-induced intestinal barrier injury via the TLR4/STAT6/MYLK signaling pathway: In vitro and in vivo studies

Xueting Niu,Canying Hu,Shengwei Chen,Jiaying Wen,Xiaoxi Liu,Yanhong Yong,Zhichao Yu,Xingbin Ma,Chengpeng Li,Mohamad Warda,A.M. Abd El-Aty,Ravi Gooneratne,Xianghong Ju

Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly ( P  < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin , claudin1, and claudin2. However, pretreatment with CS-GT significantly increased ( P  < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4 . In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo . This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury.

研究领域: 药理学 · 分子生物学 · 细胞生物学 · 动物科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer

Dong-mei Li,Fu-cui Zhu,Jie Wei,Jia-xiu Xie,Jun-hui He,Dong-mei Wei,Yi Li,Ke-dao Lai,Li-min Liu,Qi-biao Su,Gui-ning Wei,Bin Wang,Yan-cheng Liu

Ethnopharmacological relevance Polyrhachis vicina Roger ( P. vicina ), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis , hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia . Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. Aim of the study The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. Methods To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology , molecular docking, qRT-PCR, western blotting , CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. Results Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. Conclusion According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

CAS / MDL: 51-21-8
研究领域: 药理学 · 肿瘤学 · 传统中药 · 分子生物学 · 细胞生物学
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Food & Function · 2021 ·Vol. 12 ·期 23 ·11956-11965 · IF 5.396

Procyanidin A1 and its digestive products prevent acrylamide-induced intestinal barrier dysfunction via the MAPK-mediated MLCK pathway

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.

CAS / MDL: 79-06-1
研究领域: 营养学 · 毒理学 · 细胞生物学 · 胃肠病学
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Human Cell · 2024 · IF 3.4

Inhibition of the AP-1/TFPI2 axis contributes to alleviating cerebral ischemia/reperfusion injury by improving blood–brain barrier integrity

Cao Yue,Xing Ruixian,Li Qiushi,Bai Yang,Liu Xuewen,Tian Buxian,Li Xin

Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood–brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p  < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90 min and reperfusion (R) for 48 h. Then AAV2-shTFPI2 particles (5 × 10 10 vg) were injected into the right lateral ventricle of rats 3 weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6 h and reoxygenation (R) for 18 h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.

CAS / MDL: 47165-04-8
研究领域: 神经科学 · 分子生物学 · 细胞生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY · 2017 · IF 3.505

Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans

Jun Tian,Zhaoqun Lu,Yanzhen Wang,Man Zhang,Xueyan Wang,Xudong Tang,Xue Peng,Hong Zeng

The antifungal activity of Nerol (NEL) against Candida albicans , a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4   mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca 2+ ) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot . The results showed that an increase in intracellular Ca 2+ and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay , and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis of C. albicans cells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca 2+ and ROS leading to apoptosis in C. albicans . This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.

研究领域: 微生物学 · 药理学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Poly(sebacoyl diglyceride) Cross-Linked by Dynamic Hydrogen Bonds: A Self-Healing and Functionalizable Thermoplastic Bioelastomer

Shuo Chen,Xiaoping Bi,Lijie Sun,Jin Gao,Peng Huang,Xianqun Fan,Zhengwei You,Yadong Wang

Biodegradable and biocompatible elastomers (bioelastomers) could resemble the mechanical properties of extracellular matrix and soft tissues and, thus, are very useful for many biomedical applications. Despite significant advances, tunable bioelastomers with easy processing, facile biofunctionalization, and the ability to withstand a mechanically dynamic environment have remained elusive. Here, we reported new dynamic hydrogen-bond cross-linked PSeD-U bioelastomers possessing the aforementioned features by grafting 2-ureido-4[1H]-pyrimidinones (UPy) units with strong self-complementary quadruple hydrogen bonds to poly(sebacoyl diglyceride) (PSeD), a refined version of a widely used bioelastomer poly(glycerol sebacate) (PGS). PSeD-U polymers exhibited stronger mechanical strength than their counterparts of chemically cross-linked PSeD and tunable elasticity by simply varying the content of UPy units. In addition to the good biocompatibility and biodegradability as seen in PSeD, PSeD-U showed fast self-healing (within 30 min) at mild conditions (60 °C) and could be readily processed at moderate temperature (90–100 °C) or with use of solvent casting at room temperature. Furthermore, the free hydroxyl groups of PSeD-U enabled facile functionalization, which was demonstrated by the modification of PSeD-U film with FITC as a model functional molecule.

研究领域: 材料科学 · 生物材料 · 生物医学工程 · 聚合物化学
✓ 已验证 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2023 · IF 8.8

Microfluidic synthesis of pH-responsive molecularly imprinted silica nanospheres for fluorescence sensing target glycoprotein

Qianjin Li,Meng Wang,Yu Jin,Yongling Lu,Shuqing Xiong,Mengdi Wang,Jianhong Xu,Chenhong Wei,Jianlin Li

Here, fluorescent artificial antibodies for sensing ovalbumin in food were synthesized by molecular imprinting technique in a microfluidic reactor. A phenylboronic acid-functionalized silane was employed as the functional monomer to enable the polymer has pH-responsive property. Fluorescent molecularly imprinted polymers (FMIPs) could be produced continuously in a short time. Both fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RB)-based FMIPs can specifically recognize the target ovalbumin, particularly FITC-based FMIP, giving an imprinting factor of 2.5 and cross-reactivity factors of 2.7 (ovotransferrin), 2.8 (β-lactoglobulin) and 3.4 (bovine serum albumin), and was applied for the detection of ovalbumin in milk powder with recovery rates of 93–110%; moreover, the FMIP can be reused at least four times. Such FMIPs have promising future in replacing the fluorophore-labelled antibodies to fabricate fluorescent sensing devices or establish immunoassay methods, which have extra merits of low-cost, high stability and recyclability, easy to carry and store at ambient environments.

CAS / MDL: 9048-46-8 9003-99-0
研究领域: 分析化学 · 纳米技术 · 材料科学 · 食品科学 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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