280 results on '"Ying Ji"'
Search Results
2. Improving Effects of Laccase-Mediated Pectin–Ferulic Acid Conjugate and Transglutaminase on Active Peptide Production in Bovine Lactoferrin Digests
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Mingxia Xing, Ying Ji, Lianzhong Ai, Fan Xie, Yan Wu, and Phoency F. H. Lai
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lactoferrin ,pectin–ferulic acid conjugate ,laccase ,transglutaminase ,active peptide ,UPLC-MS-MS ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
Bovine lactoferrin (bLf) is a multifunctional glycoprotein and a good candidate for producing diverse bioactive peptides, which are easily lost during over-digestion. Accordingly, the effects of laccase-mediated pectin–ferulic acid conjugate (PF) and transglutaminase (TG) on improving the production of bLf active peptides by in vitro gastrointestinal digestion were investigated. Using ultra-high-performance liquid chromatography tandem mass spectroscopy (UPLC-MS-MS), the digests of bLf alone, PF-encapsulated bLf complex (LfPF), and TG-treated LfPF complex (LfPFTG) produced by conditioned in vitro gastric digestion (2000 U/mL pepsin, pH 3.0, 37 °C, 2 h) were identified with seven groups of active peptide-related fragments, including three common peptides (VFEAGRDPYKLRPVAAE, FENLPEKADRDQYEL, and VLRPTEGYL) and four differential peptides (GILRPYLSWTE, ARSVDGKEDLIWKL, YLGSRYLT, and FKSETKNLL). The gastric digest of LfPF contained more diverse and abundant detectable peptides of longer lengths than those of bLf and LfPFTG. After further in vitro intestinal digestion, two active peptide-related fragments (FEAGRDPYK and FENLPEKADRDQYE) remained in the final digest of LfPFTG; one (EAGRDPYKLRPVA) remained in that of bLf alone, but none remained in that of LfPF. Conclusively, PF encapsulation enhanced the production of bLf active peptide fragments under the in vitro gastric digestion applied. TG treatment facilitated active peptide FENLPEKADRDQYE being kept in the final gastrointestinal digest.
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- 2023
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3. The Influence of a Novel Chitosan-Based Coating with Natural Antimicrobial Agents on the Storage Properties and Reactive Oxygen Species Metabolism of Harvested Tangelo Fruit
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Ying Ji, Jieqiong Wang, Ye Liu, Shaoyan Liu, Xuanjing Jiang, Huaming Huang, and Ling Li
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Chemistry ,QD1-999 - Abstract
This study investigated the effects of a novel antibacterial film based on chitosan, carboxymethyl cellulose, sodium alginate, tea polyphenols, ascorbic acid, and tangelo peel extract on the postharvest quality and reactive oxygen species metabolism of tangelo fruit during storage. The composite film significantly reduced the fruit decay rate and weight loss, delayed the reduction in total soluble solids and titratable acidity, and retained fruit firmness and the appearance of tangelo fruit during storage. Furthermore, the composite film effectively reduced the fruit respiration rate, inhibited the increase in cell-membrane permeability, markedly reduced the generation of superoxide anion, hydrogen peroxide, and malondialdehyde, and enhanced the activity of the antioxidant enzymes superoxide dismutase, catalase, and ascorbate peroxidase. The composite film also reduced losses of the nonenzymatic antioxidants ascorbic acid and glutathione. Overall, the chitosan-based composite antibacterial film effectively maintained the quality of tangelo fruit during storage, enhanced ROS scavenging capacity and antioxidant properties, and then reduced the rot rate of postharvest tangelo.
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- 2022
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4. Oral Administration of Omega-3 Fatty Acids Attenuates Lung Injury Caused by PM2.5 Respiratory Inhalation Simply and Feasibly In Vivo
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Juan Li, Meiru Mao, Jiacheng Li, Ziteng Chen, Ying Ji, Jianglong Kong, Zhijie Wang, Jiaxin Zhang, Yujiao Wang, Wei Liang, Haojun Liang, Linwen Lv, Qiuyang Liu, Ruyu Yan, Hui Yuan, Kui Chen, Yanan Chang, Guogang Chen, and Gengmei Xing
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PM2.5 ,lung injury ,omega-3 fatty acids ,docosahexaenoic acid ,eicosapentaenoic acid ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.
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- 2022
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5. Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis
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Fengjin Wu, Leifeng Wang, Ying Ji, Ge Zou, Hong Shen, David A. Nicewicz, Jiean Chen, and Yong Huang
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Chemistry ,Catalysis ,Organic Synthesis ,Science - Abstract
Summary: Polysubstituted bicyclic acetals are a class of privileged pharmacophores with a unique 3D structure and an adjacent pair of hydrogen bond acceptors. The key, fused acetal functionality is often assembled, via intramolecular cyclization, from linear substrates that are not readily available. Herein, we report a formal cycloaddition between cinnamyl alcohols and cyclic enol ethers under ambient photoredox catalysis conditions. Polysubstituted bicyclic acetals can be prepared in one step from readily available building blocks. Employment of sugar-derived enol ethers allows easy access to a library of scaffolds with intriguing conformation and medicinal chemistry potential.
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- 2020
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6. Cathepsin B Nuclear Flux in a DNA-Guided 'Antinuclear Missile' Cancer Therapy
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Fei Cao, Caroline Tang, Xiaoyong Chen, Zewei Tu, Ying Jin, Olivia M. Turk, Robert N. Nishimura, Allen Ebens, Valentina Dubljevic, James A. Campbell, Jiangbing Zhou, and James E. Hansen
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Chemistry ,QD1-999 - Published
- 2024
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7. Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner
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Dong-Xiao Duan, Fang-Xiao Shi, Xiang-Shu Cheng, Jun Zhang, Kun-Peng Zhao, Rui Zhu, Xin-Ying Ji, Xin-Wen Zhou, Jin Du, Jian-She Wei, Wang Lin, Yao-Yao Bu, Xiao-Ying Li, Xiao-Hong Li, and Jian-Zhi Wang
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AMPK ,Agonist ,Amyloid ,Aging ,medicine.drug_class ,ADAM10 ,AMP-Activated Protein Kinases ,amyloid-β ,Cofactor ,Cell Line ,ADAM10 Protein ,Mice ,medicine ,Animals ,Humans ,Nicotinamide-Nucleotide Adenylyltransferase ,Senile plaques ,biology ,Chemistry ,nicotinamide mononucleotide adenylyltransferase 2 ,Antagonist ,Membrane Proteins ,Cell Biology ,medicine.disease ,Up-Regulation ,Cell biology ,biology.protein ,NAD+ kinase ,Amyloid Precursor Protein Secretases ,Alzheimer disease ,Alzheimer's disease ,Research Paper - Abstract
Amyloid-β (Aβ) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer’s disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aβ productions in AD patient’s brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aβ in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aβ production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aβ production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD+/NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aβ1-40/1-42. Taken together, Nmnat2 suppresses Aβ production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.
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- 2021
8. B-Ring-extended flavonol-based photoCORM: activated by cysteine-ratiometric fluorescence sensing and accurate control of linear CO release
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Ying-Ji Sun and Chao Yu
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Fluorophore ,Flavonols ,Light ,Membrane permeability ,Biomedical Engineering ,Sensitivity and Specificity ,Fluorescence ,HeLa ,symbols.namesake ,chemistry.chemical_compound ,In vivo ,Stokes shift ,Animals ,Humans ,General Materials Science ,Cysteine ,Zebrafish ,Carbon Monoxide ,Molecular Structure ,biology ,General Chemistry ,General Medicine ,Glutathione ,Hydrogen-Ion Concentration ,Photochemical Processes ,biology.organism_classification ,chemistry ,Drug Design ,Larva ,symbols ,Biophysics ,HeLa Cells - Abstract
The first B-ring-extended (to biphenyl) flavonol-based Cys-ratiometric fluorescent probe B-bph-fla-acr (2-([1,1'-biphenyl]-4-yl)-4-oxo-4H-chromen-3-yl acrylate) is developed. B-bph-fla-acr can ratiometrically sense and non-ratiometrically image endogenous and exogenous cysteine (Cys) in living HeLa cells and zebrafish rapidly (45 s), selectively (vs. homocysteine and glutathione), sensitively (detection limit: 18.5 nM), and with a large Stokes shift (186 nm). Quantitatively released (from the reaction of B-bph-fla-acr with Cys) fluorophore B-bph-fla-OH (2-([1,1'-biphenyl]-4-yl)-3-hydroxy-4H-chromen-4-one) is designed as a photoCORM (photo-triggered CO releasing molecule). Under O2 and visible light irradiation, the amount of CO released by B-bph-fla-OH can be accurately controlled linearly by adjusting the light irradiation intensity, irradiation time, or photoCORM dose. This process is accompanied by fluorescence quenching; therefore, the location of the photoCORM and the CO release process can be monitored in real time. B-bph-fla-acr and all reaction products exhibit good membrane permeability and low toxicity for living HeLa cells. In living HeLa cells and zebrafish, B-bph-fla-acr can image endogenous and exogenous Cys, and the released B-bph-fla-OH can photo-release CO under O2 at room temperature. This study is the first to combine a B-ring-extended flavonol-based fluorescent probe (for the effective ratiometric sensing and non-ratiometric imaging of endogenous and exogenous Cys in vitro and in vivo) with a photoCORM (Cys-activated, visible light-triggered linear CO release under O2). Our study provides important insights into the biological roles of Cys and CO, as well as a reliable method for safely supplying accurately controlled amounts of CO to living systems, thereby facilitating the development of convenient clinical diagnostic molecular tools and therapeutic prodrugs.
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- 2021
9. Programmed cell death ligand 1 expression in esophageal squamous cell carcinoma: a comparative analysis of three different assays
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Lei Guo, Ying Ji, Wei Guo, Peng Song, Xue-Min Xue, Guang-Yu Bai, Bin Qiu, Jian-Ming Ying, Shu-Geng Gao, and Pei-Fang Wei
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Esophageal Neoplasms ,Chemistry ,Apoptosis ,General Medicine ,Ligands ,Prognosis ,Esophageal squamous cell carcinoma ,B7-H1 Antigen ,Programmed cell death ligand 1 ,Cancer research ,Carcinoma, Squamous Cell ,Medicine ,Humans ,Clinical Observation ,Esophageal Squamous Cell Carcinoma - Published
- 2021
10. miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces the release of CGRP via inhibition of SIRT1 in rat trigeminal ganglion neurons
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Sheng-Dong He, Hui Zhang, Dan-Dan Zong, Xue-Mei Zhang, Feng-Zheng Zhang, Hua Jiang, and Xiao-Ying Ji
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0301 basic medicine ,Interleukin-1beta ,Apoptosis ,Pathogenesis ,Trigeminal ganglion ,0302 clinical medicine ,Sirtuin 1 ,migraine ,CGRP ,Prostaglandin E2 ,Research Articles ,Cells, Cultured ,Neurons ,Chemistry ,Up-Regulation ,Trigeminal Ganglion ,030220 oncology & carcinogenesis ,PGE2 ,medicine.symptom ,COX2 ,Research Article ,Signal Transduction ,medicine.drug ,medicine.medical_specialty ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Primary Cell Culture ,Down-Regulation ,Neuropeptide ,Inflammation ,Calcitonin gene-related peptide ,Dinoprostone ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,SIRT1 ,Internal medicine ,medicine ,Animals ,Humans ,Gene silencing ,Trigeminal nerve ,miR‐34a‐5p ,Rats ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Animals, Newborn ,Cyclooxygenase 2 - Abstract
miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces apoptosis and the release of calcitonin gene‐related peptide via inhibition of SIRT1 expression in trigeminal ganglion neurons. This suggests that miR‐34a‐5p may have potential for development into a therapeutic target for the treatment of migraine., Migraine is a debilitating neurological condition, with a global prevalence rate of 10.68% in men and 18.79% in women. Elucidation of the molecular mechanisms underlying migraines is of great importance for improving the quality of life of patients. The release of the neuropeptide calcitonin gene‐related peptide (CGRP) from trigeminal nerve terminals is involved in the pathogenesis of migraine. Recent studies have shown that up‐regulation of miR‐34a‐5p expression is associated with acute migraine attacks. Here, we investigated whether alteration of the expression of miR‐34a‐5p induces the release of the vasoactive peptide CGRP. We isolated primary rat trigeminal ganglion neurons and performed gain‐ and loss‐of‐function assays to alter the expression level of miR‐34a‐5p. Down‐regulation of miR‐34a‐5p inhibited the expression of interleukin‐1β (IL‐1β)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), decreased IL‐1β, PGE2 and CGRP release, and up‐regulated the expression of silencing information regulator 1 (SIRT1) in trigeminal ganglion, whereas overexpression of miR‐34a‐5p enhanced the expression of IL‐1β/COX2/PGE2, increased the release of IL‐1β, PGE2 and CGRP, and decreased the expression of SIRT1 in trigeminal ganglion. In addition, overexpression of miR‐34a‐5p induced apoptosis in primary rat trigeminal neurons. In summary, these findings suggest that miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway, induces apoptosis and enhances release of CGRP via inhibition of SIRT1 expression in trigeminal ganglion neurons; thus, miR‐34a‐5p may have potential as a therapeutic target for the treatment of migraine.
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- 2020
11. LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy
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Ping Jiang, Jing-Sen Dong, Ying-Ji Fang, and Hui Zhai
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0301 basic medicine ,Chemistry ,Autophagy ,medicine.disease ,medicine.disease_cause ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,In vivo ,Cell culture ,Tumor progression ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Gene silencing ,Pharmacology (medical) ,Ovarian cancer ,Carcinogenesis - Abstract
Background Early detection and diagnosis of ovarian cancer (OC) is complicated due to the concealment of the ovarian anatomical position and the lack of clinical manifestations and specific indicators of early OC. Therefore, it is urgent to study the pathogenesis of OC, especially the molecular mechanism. Results LncRNA GAS8-AS1 was decreased in OC tissues and cell lines, and high expression of GAS8-AS1 indicated a higher 5-year survival rate of OC patients. Overexpression of GAS8-AS1 suppressed growth of OC cells, while deletion of GAS8-AS1 promoted the progression of OC cells. Further data indicated GAS8-AS1 activated autophagy in OC cells. Functional experiments showed that 3-MA removed the inhibitory effect of GAS8-AS1 in OC cells. On the contrary, Rapamycin reversed the promoting effect of GAS8-AS1 in OC cells. Furthermore, GAS8-AS1 bound with Beclin1 and promoted its expression, and silencing of Beclin1 reversed the inhibitory role of GAS8-AS1 in OC progression. In vivo tumorigenesis assay showed GAS8-AS1 suppressed OC progression and activated Beclin1 mediated autophagy. Conclusion Our study suggested GAS8-AS1 inhibited OC progression by activating autophagy via binding with Beclin1, and GAS8-AS1 might be a potential therapeutic target for OC clinical treatment.
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- 2020
12. Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals
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Yuelan Liang, Jenny Cheng, Juan Li, Wei Liang, Guogang Chen, Ying Ji, Kui Chen, Kai Wu, Yanan Chang, Gengmei Xing, Junmao Tong, Jianglong Kong, Hui Sun, and Jiaxin Zhang
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biology ,Chemistry ,Endoplasmic reticulum ,Biochemistry (medical) ,Biomedical Engineering ,General Chemistry ,Pharmacology ,Endocytosis ,behavioral disciplines and activities ,Bioavailability ,Biomaterials ,Ovalbumin ,Transcytosis ,In vivo ,Oral administration ,Sirolimus ,mental disorders ,biology.protein ,medicine ,medicine.drug - Abstract
Nanocrystallization can improve the dissolvability of insoluble medicines in water, making them easier to administer. In the present study, sirolimus (SRL) was nanocrystallized, and the transport mechanism and efficacy of both formulations were compared in vitro and in vivo. The results showed that the 120 nm sirolimus nanocrystals (SRL NCs) had better ability to pass through the Caco-2 cell monolayer. SRL NCs were uptaken by Caco-2 cells via multiple endocytosis pathways, and the endoplasmic reticulum (ER), Golgi apparatus, and microtubules were identified as vital organelles for expelling SRL NCs out of the cells. SRL NCs decreased CD4+/CD8+ in normal mice after 14 days of daily gavage administration. Furthermore, SRL NCs enhanced the immune tolerance in an ovalbumin (OVA)-sensitized mouse model. SRL NCs significantly increased the percentage of Tregs (CD25+Foxp3+) among CD4+T cells. Collectively, these findings demonstrate that nanocrystallization of SRL enhances oral bioavailability, transcytosis, and...
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- 2022
13. The optimal strategies in the supply chain with stochastic demand sensitivity to carbon emission
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Mohamed Nabe, Ying Ji, Guoqing Jiang, and Zhong Wu
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0209 industrial biotechnology ,Control and Optimization ,Computer Networks and Communications ,Supply chain ,chemistry.chemical_element ,02 engineering and technology ,Environmental economics ,Human-Computer Interaction ,020901 industrial engineering & automation ,chemistry ,Artificial Intelligence ,Control and Systems Engineering ,Signal Processing ,0202 electrical engineering, electronic engineering, information engineering ,Environmental science ,020201 artificial intelligence & image processing ,Sensitivity (control systems) ,Game theory ,Carbon ,Information Systems - Abstract
With the increasing awareness of low-carbon environmental protection, consumers prefer to purchase low-carbon products. In this paper, a two-echelon low-carbon supply chain consisting of one manufa...
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- 2020
14. A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo
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Shen-Gen Wu, Tong-Ying Ji, Xiaoyong Lei, Xuan Cao, Chang-Feng Qin, Zhizhong Xie, Jin-Mei Qiu, and Guotao Tang
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Male ,Antioxidant ,DPPH ,medicine.medical_treatment ,Pharmacology ,behavioral disciplines and activities ,Antioxidants ,Superoxide dismutase ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Rutin ,Caffeic Acids ,0302 clinical medicine ,Picrates ,Superoxides ,Malondialdehyde ,mental disorders ,Drug Discovery ,medicine ,Animals ,Carbon Tetrachloride ,biology ,Superoxide Dismutase ,Superoxide ,Biphenyl Compounds ,Glutathione ,Catalase ,Ascorbic acid ,eye diseases ,stomatognathic diseases ,Liver ,chemistry ,Resveratrol ,030220 oncology & carcinogenesis ,Lactates ,biology.protein ,Chemical and Drug Induced Liver Injury ,030217 neurology & neurosurgery - Abstract
E-DRS is a novel salvianolic acid A (SAA) analog, which was synthesized from resveratrol (RES) and methyldopate. Its structure is similar to that of SAA, but the 3',4'-dihydroxy-trans-stilbene group and the ester structure in SAA were replaced by the RES structure and an amine group, respectively. E-DRS scavenged free oxygen radicals effectively, including superoxide anion (ascorbic acid > E-DRS > SAA ≥ rutin > RES) and DPPH radical (rutin > E-DRS ≥ ascorbic acid > SAA > RES), and exhibited powerful total antioxidant capacity (ascorbic acid > E-DRS > SAA ≥ rutin > RES) in vitro. Furthermore, oral administration of E-DRS dose-dependently and significantly decreased CCl4 -induced oxidative stress in mice as indicated by the decreased content of hepatic malondialdehyde (MDA). In addition, oral administration of E-DRS also increased the content of nonenzymatic antioxidant glutathione (GSH) and the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in the liver of mice. All these results demonstrated that E-DRS had good antioxidant activities both in vitro and in vivo, and could be a potential antioxidant agent after further optimization and evaluation.
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- 2020
15. Discovery of Pyrido[2,3-b]indole Derivatives with Gram-Negative Activity Targeting Both DNA Gyrase and Topoisomerase IV
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Maarten Vercruysse, Yimin Hu, Yunhua Xu, Hua Lv, Waikwong Wu, Fabian Dey, Tianyi Jiang, Xuefei Tan, Wen Wang, Ying Ji, Zhiheng Xu, Zhang Zhiwei, Yi Mao, Kenneth Bradley, Guanglei Zhai, Liu Yongqiang, Xiangyu Yao, Qingcheng Ren, Hong C. Shen, S. Frank Yan, Xiao Ding, Weixing Zhang, Xiaomin Yu, Shi Houguang, Zhu Wei, Chengang Zhou, Mingwei Zhou, and Zheng Zhou
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0303 health sciences ,Modern medicine ,biology ,Topoisomerase IV ,medicine.drug_class ,Chemistry ,Topoisomerase ,Antibiotics ,Drug resistance ,01 natural sciences ,DNA gyrase ,0104 chemical sciences ,Microbiology ,Multiple drug resistance ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,Drug Discovery ,biology.protein ,medicine ,Molecular Medicine ,Efflux ,030304 developmental biology - Abstract
The rise of multidrug resistant (MDR) Gram-negative (GN) pathogens and the decline of available antibiotics that can effectively treat these severe infections are a major threat to modern medicine. Developing novel antibiotics against MDR GN pathogens is particularly difficult as compounds have to permeate the GN double membrane, which has very different physicochemical properties, and have to circumvent a plethora of resistance mechanisms such as multiple efflux pumps and target modifications. The bacterial type II topoisomerases DNA gyrase (GyrA2B2) and Topoisomerase IV (ParC2E2) are highly conserved targets across all bacterial species and validated in the clinic by the fluoroquinolones. Dual inhibitors targeting the ATPase domains (GyrB/ParE) of type II topoisomerases can overcome target-based fluoroquinolone resistance. However, few ATPase inhibitors are active against GN pathogens. In this study, we demonstrated a successful strategy to convert a 2-carboxamide substituted azaindole chemical scaffold with only Gram-positive (GP) activity into a novel series with also potent activity against a range of MDR GN pathogens. By systematically fine-tuning the many physicochemical properties, we identified lead compounds such as 17r with a balanced profile showing potent GN activity, high aqueous solubility, and desirable PK features. Moreover, we showed the bactericidal efficacy of 17r using a neutropenic mouse thigh infection model.
- Published
- 2020
16. Detrimental role of sphingosine kinase 1 in kidney damage in DOCA-salt hypertensive model: evidence from knockout mice
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Joseph K. Ritter, Bingqing Lyu, Xin-Ying Ji, Weili Wang, and Ningjun Li
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0301 basic medicine ,Nephrology ,Male ,T-Lymphocytes ,030204 cardiovascular system & hematology ,Kidney ,urologic and male genital diseases ,lcsh:RC870-923 ,Nephrectomy ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Sphingosine ,Mice, Knockout ,Leukosialin ,biology ,α-Smooth muscle actin ,Collagen, hypertension ,Immunohistochemistry ,female genital diseases and pregnancy complications ,SPHK2 ,Phosphotransferases (Alcohol Group Acceptor) ,medicine.anatomical_structure ,Sphingosine kinase 1 ,Hypertension ,Collagen ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Signal Transduction ,medicine.medical_specialty ,Sphingosine-1-phosphate ,Blotting, Western ,Antigens, Differentiation, Myelomonocytic ,03 medical and health sciences ,Desoxycorticosterone Acetate ,Antigens, CD ,Internal medicine ,Mineralocorticoids ,medicine ,Albuminuria ,Animals ,RNA, Messenger ,cardiovascular diseases ,Renal Insufficiency, Chronic ,Sodium Chloride, Dietary ,business.industry ,urogenital system ,Macrophages ,Glomerulosclerosis ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Fibrosis ,Actins ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,biology.protein ,Lysophospholipids ,business ,Kidney disease - Abstract
Background Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice. Methods Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA. Results The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice. Conclusions SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.
- Published
- 2020
17. Orange-red and white-emitting nonconventional luminescent polymers containing cyclic acid anhydride and lactam groups
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Yaxin Zhao, Cong Shang, Jiayu Long, Ying Ji, and Huiliang Wang
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chemistry.chemical_classification ,Photoluminescence ,Materials science ,Cyclic acid ,Caprolactam ,General Chemistry ,Polymer ,Chromophore ,Photochemistry ,Fluorescence ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,Copolymer ,Luminescence - Abstract
Polymeric luminescent materials containing nonconventional chromophores are of great fundamental and practical importance. However, most nonconventional polymeric luminogens (NPLs) normally emit in the blue region. In this work, we synthesized poly(itaconic anhydride-co-vinyl caprolactam) (PIVC) and poly(itaconic anhydride-co-vinyl pyrrolidone) (PIVP) copolymers through a conventional free radical precipitation copolymerization method. The photoluminescence of the copolymers in solutions and in the solid state is studied. PIVC and PIVP exhibit obvious aggregation enhanced emission (AEE) and aggregation induced emission (AIE) characteristics, showing maximum emission wavelengths in the orange-red region (627 nm and 611 nm), and, very impressively, emit orange-red and bright white emissions under 365 nm UV irradiation, respectively. The copolymers show concentration-dependent luminescence, as their emissions change from blue to orange with the increase of polymer concentration. In addition, they also exhibit significant excitation-dependent fluorescence (EDF) characteristics and emit dark red light when excited with red light. The fluorescence mechanism of the copolymers has been discussed by comparing the PL behaviors of the homopolymers and the structures of the polymers, focusing on possible interactions between cyclic acid anhydride and lactam groups. This study provides a strategy for preparing nonconventional luminescent polymers with strong and red-shifted fluorescence emissions.
- Published
- 2020
18. An aromatic selenite bridged Mn(<scp>iii</scp>) chain compound showing the coexistence of single chain magnet and metamagnet behaviour
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Xin-Chao Li, Lei Chen, Xian-Hui Hou, Shan-Shan Li, Shao-Liang Zhang, Xiao-Ying Ji, and Zhi-Cheng Wang
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Crystallography ,Chain (algebraic topology) ,chemistry ,Magnet ,Materials Chemistry ,Antiferromagnetism ,chemistry.chemical_element ,General Chemistry ,Single chain ,Catalysis ,Selenium - Abstract
A new chain compound consisting of Mn2(salen)2 building blocks bridged by aromatic selenite was synthesized and characterized. The compound displays antiferromagnetic interactions through the O–Se–O bridges. The coexistence of single chain magnet and metamagnet behaviour was observed in the compound. The compound is one of the rare examples of Mn-salen coordinated aromatic selenite-based magnetic materials.
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- 2020
19. Structure‐Reactivity Relationship in ES Models of Co(II)‐Containing Quercetin 2,4‐Dioxygenase
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Jian-Jun Zhang, Yanqin Li, Ying-Ji Sun, and Yan‐Fang Liu
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chemistry.chemical_compound ,chemistry ,Dioxygenase ,Stereochemistry ,General Chemistry ,Structure reactivity ,Quercetinase ,Quercetin - Published
- 2019
20. Deletion of bem46 retards spore germination and may be related to the polar growth of Aspergillus fumigatus
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Jing Yang, Yan Ma, Wen Cen, Jiajuan Li, Yan Wang, Wenli Feng, Wen Li, and Ying Ji
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Hypha ,Hydrolases ,Recombinant Fusion Proteins ,Mutant ,Hyphae ,Aspergillus fumigatus ,Microbiology ,Conidium ,Neurospora crassa ,Fungal Proteins ,03 medical and health sciences ,Spore germination ,Amino Acid Sequence ,skin and connective tissue diseases ,030304 developmental biology ,0303 health sciences ,biology ,Strain (chemistry) ,030306 microbiology ,Chemistry ,Genetic Complementation Test ,General Medicine ,Spores, Fungal ,biology.organism_classification ,Infectious Diseases ,Germination ,Sequence Alignment ,Gene Deletion - Abstract
Bud emergence 46 (BEM46), a member of the α/β hydrolase superfamily, has been reported to be essential for polarized growth in Neurospora crassa. However, the role of BEM46 in aspergillus fumigatus (A. fumigatus) remains unclear. In this study, we constructed an A. fumigatus strain expressing BEM46 fused with enhanced green fluorescent protein, and a Δbem46 mutant, to explore the localization and the role of growth of BEM46 in A. fumigatus, respectively. Confocal laser scanning microscopy revealed that BEM46 was dominantly expressed in the sites where hyphae germinated from conidia in A. fumigatus. When compared with the control strain, the Δbem46 mutant exhibited insignificant morphological changes but delayed germination. No significant changes were found regarding the radial growth of both strains in response to various antifungal agents. These results suggest that BEM46 plays an essential role in timely germination in A. fumigatus. From the observation of fluorescence localization, we infer that that BEM46 might be involved in polarized growth in A. fumigatus.
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- 2019
21. Recent advances of lignin valorization techniques toward sustainable aromatics and potential benchmarks to fossil refinery products
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Shao Yuan Leu, Chun Yin Lau, Jianyu Guan, Ying Ji, Duu-Jong Lee, Jun Zhao, Huaimin Wang, Jingliang Xu, Chun Ho Lam, and Rabia Jalil Khan
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Environmental Engineering ,Renewable Energy, Sustainability and the Environment ,Fossils ,Oil refinery ,Bioengineering ,General Medicine ,Biorefinery ,Lignin ,Refinery ,Carbon ,Catalysis ,chemistry.chemical_compound ,Benchmarking ,Carbon neutrality ,chemistry ,Greenhouse gas ,High value products ,Environmental science ,Biochemical engineering ,Waste Management and Disposal - Abstract
Aromatic compounds are important fuels and key chemical precursors for organic synthesis, however the current aromatics market are mainly relying on fossil resources which will eventually contribute to carbon emissions. Lignin has been recognized as a drop-in substitution to conventional aromatics, with its values gradually realized after tremendous research efforts in the recent five years. To facilitate the development of a possible lignin economics, this study overviewed the recent advances of various biorefinery techniques and the remaining challenging for lignin valorization. Starting with recent discovery of unexplored lignin structures, the potential functions of lignin related chemical structures were emphasized. The important breakthrough of lignin-first pretreatment, catalytic lignin depolymerization, and the high value products with possible benchmark with modern aromatics were reviewed with possible future targets. Possible retrofit of conventional petroleum refinery for lignin products were also introduced and hopefully paving a way to progressively migrate the industry towards carbon neutrality.
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- 2021
22. Dramatically Enhanced and Red-shifted Photoluminescence Achieved by Introducing an Electron-withdrawing Group into a Non-traditional Luminescent Small Organic Compound
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Huiliang Wang, Jiayu Long, Yaxin Zhao, Hongwei Tan, Jiankai Shan, and Ying Ji
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chemistry.chemical_classification ,Photoluminescence ,Cyan ,Organic Chemistry ,General Chemistry ,TFAM ,Chromophore ,Photochemistry ,Biochemistry ,Fluorescence ,Organic compound ,chemistry ,Molecule ,Luminescence - Abstract
Small organic compounds without any traditional fluorescent chromophores are generally non-emissive, and only very few are reported to emit weak blue fluorescence. Here we synthesized a non-traditional luminescent small organic compound N-(2,2,2-trifluoroethyl)acrylamide (TFAM) with dramatically enhanced and red-shifted photoluminescence by introducing a strong electron-withdrawing group into acrylamide (AM). Very impressively, TFAM emits cyan (472 nm) and yellow-green (560 nm) fluorescence in solutions and solid state, respectively. TFAM also shows aggregation-induced emission enhancement (AIEE) and excitation-dependent fluorescence (EDF) characteristics, as well as temperature and metal cations-responsive fluorescence. Theoretical calculations show that the introduction of electron-withdrawing group leads to a lower energy gap between the HOMO-LUMO energy levels in TFAM than in AM. And strong cooperative hydrogen bonds are formed in TFAM molecules, resulting in rigidification of molecular conformations. The study provides a strategy for preparing non-traditional luminescent compounds with enhanced and red-shifted photoluminescence.
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- 2021
23. Role of Hydrogen Sulfide in the Endocrine System
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Hao-Jie Chen, Ebenezeri Erasto Ngowi, Lei Qian, Tao Li, Yang-Zhe Qin, Jing-Jing Zhou, Ke Li, Xin-Ying Ji, and Dong-Dong Wu
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0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,hormone ,hydrogen sulfide ,Review ,medicine.disease_cause ,Endocrine System Diseases ,Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Endocrine system ,Animals ,Humans ,pancreas ,hypothalamus ,Chemistry ,Metabolism ,medicine.disease ,equipment and supplies ,RC648-665 ,030104 developmental biology ,medicine.anatomical_structure ,endocrine system ,Hypothalamus ,030220 oncology & carcinogenesis ,Signal transduction ,Carcinogenesis ,Pancreas ,Hormone - Abstract
Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.
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- 2021
24. Investigating the Mechanism of Chufan Yishen Formula in Treating Depression through Network Pharmacology and Experimental Verification
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Haohao Zhu, Zhiqiang Du, Rongrong Lu, Qin Zhou, Yuan Shen, and Ying Jiang
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Chemistry ,QD1-999 - Published
- 2024
- Full Text
- View/download PDF
25. Prevalence and distribution of domoic acid and cyclic imines in bivalve mollusks from Beibu Gulf, China
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Lei Zhang, Guowang Yan, Wenlu Lan, Guixiang Wang, Ying Ji, Zhaohui Wang, Jianwei Liu, Yeju Yan, Yilei Fu, Weiguo Li, Xin Luo, Aifeng Li, Zhixuan Tang, Tianshen Li, Wanyu Pan, and Jiangbing Qiu
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China ,Environmental Engineering ,South china ,Kainic Acid ,business.industry ,Health, Toxicology and Mutagenesis ,Zoology ,Domoic acid ,Biology ,Alexandrium ostenfeldii ,Pollution ,Bivalvia ,chemistry.chemical_compound ,Aquaculture ,chemistry ,Prevalence ,Environmental Chemistry ,Animals ,Marine Toxins ,Imines ,business ,Waste Management and Disposal ,Shellfish ,Karenia selliformis - Abstract
Beibu Gulf is an important shellfish aquaculture area in the northwest of the South China Sea, China. In this study, the toxin profile and spatial-temporal distribution of domoic acid (DA) and 10 lipophilic phycotoxins were systematically analyzed in the bivalve mollusks collected in Beibu Gulf from October 2018 to October 2020. Neurotoxin DA was first detected in the mollusks from the investigative regions with a prevalence of 17.7%, peaking at 401 µg kg−1. Cyclic imines (CIs) including gymnodimine-A (GYM-A, 46.6%) and 13-desmethyl-spirolide-C (SPX1, 15.8%) predominated the lipophilic phycotoxins in shellfish, peaking at 10.1 µg kg−1 and 19.6 µg kg−1, respectively. Gymnodimine-A partially accompanied by SPX1 was detected in all batches of shellfish samples, suggesting that Alexandrium ostenfeldii and Karenia selliformis were possible sources of CIs-group toxins in Beibu Gulf. During the investigative period, relatively higher levels of DA occurred in shellfishes from March to August, while slightly higher contents of CIs in mollusks appeared in October and December. Spatial distribution of the targeted phycotoxins demonstrated that shellfishes tended to accumulate relatively higher contents of toxins in Lianzhou, Qinzhou and Tieshan bays.
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- 2021
26. Cotreatment with Aspirin and Azole Drugs Increases Sensitivity of
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Ying Ji, Shaoyan Wang, Yan Ma, Jing Yang, Wenli Feng, Zhiqin Xi, Qiao Ren, and Huan Ning
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0301 basic medicine ,Itraconazole ,030106 microbiology ,Pharmacology ,invasive fungus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Candida albicans ,Original Research ,chemistry.chemical_classification ,biology ,Broth microdilution ,Biofilm ,acetylsalicylic acid ,biology.organism_classification ,Corpus albicans ,virulence ,Infectious Diseases ,chemistry ,Infection and Drug Resistance ,Azole ,synergistic effects ,Fluconazole ,Salicylic acid ,medicine.drug - Abstract
Wenli Feng, Jing Yang, Yan Ma, Zhiqin Xi, Ying Ji, Qiao Ren, Huan Ning, Shaoyan Wang The Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Wenli Feng; Jing YangThe Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi, 030001, People’s Republic of ChinaTel +86-0351-3365410Email wenlifeng2010@163.com; yangjing7962@126.comPurpose: This study aimed to investigate the effects of aspirin (acetyl salicylic acid [ASA]) combined with fluconazole (FCA), itraconazole (ITR), or voriconazole (VRC) on Candida albicans under planktonic and biofilm conditions.Methods: A total of 39 clinical C. albicans strains were used to perform the in vitro drug sensitivity assay under different conditions using the M27-A4 broth microdilution method. The minimal inhibitory concentrations (MICs) and fractional inhibitory concentration index (FICI) values were calculated. C. albicans ZY23 was chosen for the further analyses.Results: Under planktonic conditions, the half maximal MIC (MIC50) values of FCA, ITR, and VRC were 64– 0.5 μg/mL, 32– 0.0625 μg/mL, and 16– 0.125 μg/mL, respectively, when applied, whereas in combination with ASA, the values decreased to 32– 0.25 μg/mL, 8– 0.0313 μg/mL, and 8– 0.0313 μg/mL, respectively. Under biofilm conditions, FCA, ITR, or VRC alone showed MIC50 values of 128– 8 μg/mL, 32– 4 μg/mL, and 32– 0.5 μg/mL, whereas in combination with ASA the values were decreased to 32– 0.5 μg/mL, 16– 0.5 μg/mL, and 8– 0.0625 μg/mL, respectively. Analysis of the FICI showed that the sensitization rate of ASA to FCA, ITR, and FCA under planktonic conditions was 43.59%, whereas the sensitization rates of ASP to FCA, ITR, and FCA under biofilm conditions were 46.15%, 46.15%, and 48.72%, respectively. Additionally, the time-growth and time-kill curves of C. albicans ZY23 further verified the synergistic effects of ASA on azole drugs.Conclusion: ASA may act as an enhancer of the inhibitory effects of azole drugs on the growth of clinical C. albicans under planktonic and biofilm conditions.Keywords: acetylsalicylic acid, synergistic effects, invasive fungus, virulence
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- 2021
27. Spatial distribution and source of biotoxins in phytoplankton from the South China Sea, China
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Tianying Chen, Lei Liu, Yang Li, Zhaohui Wang, Aifeng Li, Yunyun Zhuang, Chao Liu, Ying Ji, Jiangbing Qiu, Biaobiao Niu, and Lei Zhang
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China ,Environmental Engineering ,South china ,Health, Toxicology and Mutagenesis ,0211 other engineering and technologies ,02 engineering and technology ,010501 environmental sciences ,Biology ,Spatial distribution ,01 natural sciences ,chemistry.chemical_compound ,Phytoplankton ,Okadaic Acid ,Environmental Chemistry ,Mariculture ,Waste Management and Disposal ,Ecosystem ,0105 earth and related environmental sciences ,Saxitoxin ,Diatoms ,021110 strategic, defence & security studies ,Phycotoxin ,geography ,geography.geographical_feature_category ,Domoic acid ,Estuary ,Pollution ,Oceanography ,chemistry ,Dinoflagellida - Abstract
Marine phycotoxins severely threaten ecosystem health and mariculture. This study investigates the spatial distribution and source of diverse phycotoxins in the South China Sea (SCS), during four 2019/2020 cruises. Saxitoxin (STX) and okadaic acid (OA) -groups, azaspiracids, cyclic imines, pectenotoxins (PTX), yessotoxins, and domoic acid (DA) toxins were analyzed in microalgal samples. PTX2 occurred with the highest (93.5%) detection rate (DR) during all cruises, especially in the Pearl River Estuary (PRE) in June 2019. Homo-yessotoxin (hYTX) and DA were found during three cruises in August 2020, and high DR of hYTX (67.7%, 29.3%) and DA (29.0%, 29.3%) in the PRE and Guangdong coast, respectively, in June 2019 and 2020, peaking at concentrations of 777 pg hYTX L-1 and 38514 pg DA L-1. The phycotoxin distribution demonstrated that DA-producing microalgae gathered close to the PRE and Guangdong coast, while hYTX-producing microalgae distributed relatively far offshore. Microalgae producing PTX2- and STX-group toxins were more widely living in the SCS. High-throughput sequencing results suggested that Alexandrium pacificum and Gonyaulax spinifera were responsible for STX-group toxins and hYTX, respectively, while Pseudo-nitzschia cuspidata was the main source of DA. Widely distributed PTX2, hYTX, and DA were reported for the first time in the SCS.
- Published
- 2021
28. Noradrenaline depresses spontaneous complex spikes activity of cerebellar Purkinje cells via α2-adrenergic receptor in vivo in mice
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De-Lai Qiu, Chun-Ping Chu, Ying-Ji Hong, Bing-Xue Li, Na Sun, and Yan-Hua Bing
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Male ,0301 basic medicine ,Agonist ,Adrenergic receptor ,medicine.drug_class ,Adrenergic beta-Antagonists ,Action Potentials ,Cerebellar Purkinje cell ,Pharmacology ,Norepinephrine ,Purkinje Cells ,03 medical and health sciences ,0302 clinical medicine ,Phentolamine ,Receptors, Adrenergic, beta ,otorhinolaryngologic diseases ,Prazosin ,medicine ,Animals ,Adrenergic alpha-Antagonists ,Mice, Inbred ICR ,Chemistry ,General Neuroscience ,Antagonist ,Receptors, Adrenergic, alpha ,030104 developmental biology ,nervous system ,Cerebellar cortex ,Locus coeruleus ,Female ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Locus coeruleus (LC) noradrenergic neurons afferents release noradrenaline (NA) in the cerebellar cortex for modulating cerebellar neuronal circuitry function. Our previous study found that NA inhibited the spontaneous simple spikes activity of cerebellar Purkinje cells (PC) through activation of molecular layer interneurons (MLIs) in vivo in mice. We here examined the effects of NA on spontaneous complex spikes (CSs) activity of cerebellar PC in urethane-anesthetized mice by electrophysiology recording technique and pharmacological methods. Our results showed that cerebellar surface perfusion of NA significantly reduced the number of spikelets and the area under curve (AUC) of the spontaneous CSs. Application of nonselective adrenergic receptor (AR) antagonist, phentolamine, abolished the NA-induced inhibition of CSs. However applying a nonselective β-AR blocker, propranolol, failed to prevent the NA-induced inhibition of CSs activity. The NA-induced inhibition of CSs activity was not blocked by α1-AR antagonist, prazosin, but it was abolished by α2-AR antagonist, yohimibine. Moreover, application of α2-AR agonist, UK14304 induced a depression of CSs activity and mimicked the NA-induced inhibition of CS activity. These results indicate that NA regulates spontaneous CSs activity of cerebellar PCs via activation of α2-AR in vivo in mice. Our present results suggest that noradrenergic neurons of LC may modulate the outputs of cerebellar PCs via inhibition of CSs activity.
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- 2019
29. Electronic and Functional Structure of Copper in Plant Cu/Zn Superoxide Dismutase with Combined Site-directed Mutagenesis and Electron Paramagnetic Resonance
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Zuo-Jun Liu, Ming-Hao Li, Chen Ming, Ji-Hu Su, Ying-Ji Mao, Wei Tong, Jinyan Hou, Shengwei Huang, and Li-Fang Wu
- Subjects
chemistry.chemical_classification ,Reactive oxygen species ,biology ,Active site ,chemistry.chemical_element ,Copper ,Redox ,Analytical Chemistry ,law.invention ,Superoxide dismutase ,Directed mutagenesis ,chemistry ,law ,Biophysics ,biology.protein ,Electron paramagnetic resonance ,Histidine - Abstract
Arabidopsis thaliana copper-zinc superoxide dismutase 1 (AtSOD1) is a typical metalloenzyme conferring cellular protection against the excessive accumulation of toxic reactive oxygen species, and is therefore considered as a critical protein. However, the structure and function of the vital amino acids around the active site of AtSOD1 remain poorly understood. Herein, the coordinated geometry of the catalytic center in AtSOD1 was reconstructed by electron paramagnetic resonance (EPR) technique, and it was found to be composed of copper and four histidine (H) residues using site-directed mutagenesis. Analysis of the mutants showed that H45 and H62 play essential roles in the catalytic reaction, and H119 plays an accessary role in facilitating substrate or proton transfer. The results indicated that the redox change of the Cu ion and the overall enzymatic activity of the protein were sustained by the H45-Cu-H62 core structure. In contrast, the residue H47 showed nearly no effect on the SOD catalytic activity. These data should contribute to a deeper understanding of the catalytic mechanism of the enzyme, and provide a new approach for the effective molecular modification of copper/zinc SODs to facilitate further research in this field.
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- 2019
30. Knockout of Sphingosine Kinase 1 Attenuates Renal Fibrosis in Unilateral Ureteral Obstruction Model
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Xiwen Zhang, Joseph K. Ritter, Xin-Ying Ji, Ningjun Li, and Weili Wang
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Male ,medicine.medical_specialty ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Kidney ,urologic and male genital diseases ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Renal fibrosis ,Animals ,Sphingosine-1-phosphate ,Phosphorylation ,Renal Insufficiency, Chronic ,Receptor ,Inflammation ,Mice, Knockout ,biology ,Sphingosine ,urogenital system ,business.industry ,Fibroblasts ,Fibrosis ,female genital diseases and pregnancy complications ,Mice, Inbred C57BL ,Disease Models, Animal ,Phosphotransferases (Alcohol Group Acceptor) ,SPHK2 ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Sphingosine kinase 1 ,Nephrology ,Immune System ,biology.protein ,Tubulointerstitial fibrosis ,business ,Gene Deletion ,Ureteral Obstruction - Abstract
Background: Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in various diseases. S1P also plays significant roles in the differentiation of fibroblasts into myofibroblasts, being implicated in fibrotic diseases. S1P is produced by the phosphorylation of sphingosine catalyzed by sphingosine kinases (SphK1 and SphK2). It remains unclear if the activation of endogenous SphK1 contributes to fibrogenesis in kidneys. The present study determined the effect of SphK1 gene knockout (KO) on fibrotic markers in kidneys. Methods: The renal fibrosis was produced using the unilateral ureteral obstruction (UUO) model in wild-type (WT) and SphK1 gene KO mice. Renal mRNA levels of SphK1 and S1P receptors (S1PR) were measured by real-time RT-PCR. Fibrotic and immune cell markers in kidneys were measured by Western blot analysis and immunostaining, respectively. Renal morphological damage was examined by Periodic-Acid Schiff staining. Results: The mRNA levels of SphK1 and S1PRs were dramatically increased in renal tissues of WT-UUO mice, whereas the increase in renal SphK1 mRNA was blocked in KO-UUO mice. Interestingly, the increased levels of fibrotic markers, collagen and α-smooth muscle actin, in kidneys were significantly attenuated in KO-UUO versus WT-UUO mice. Meanwhile, kidney damage indices were remarkably attenuated in KO-UUO mice compared with WT-UUO mice. However, increased numbers of CD43+ and CD48+ cells, markers for T cell and macrophage, respectively, showed no significant difference between WT-UUO and KO-UUO kidneys. Conclusion: The activation of the SphK1-S1P pathway may contribute to tubulointerstitial fibrosis in UUO kidneys by affecting fibrotic signaling within renal cells independent of immune modulation.
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- 2019
31. A light-facilitated drug delivery system from a pseudo-protein/hyaluronic acid nanocomplex with improved anti-tumor effects
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Juan Li, Ying Ji, Shuo Shan, Chih-Chang Chu, and Jihui Zhao
- Subjects
Biodistribution ,Light ,Cell Survival ,Endosome ,Mice, Nude ,Antineoplastic Agents ,02 engineering and technology ,Arginine ,010402 general chemistry ,01 natural sciences ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Neoplasms ,Hyaluronic acid ,medicine ,Animals ,Humans ,Tissue Distribution ,General Materials Science ,Doxorubicin ,Hyaluronic Acid ,Drug Carriers ,Chemistry ,021001 nanoscience & nanotechnology ,Controlled release ,Endocytosis ,Nanostructures ,0104 chemical sciences ,Drug delivery ,Biophysics ,Nanomedicine ,Female ,Peptides ,0210 nano-technology ,medicine.drug - Abstract
Reduction-sensitive nanomedicine is a promising strategy to achieve controlled release of payloads in response to intracellular reductive milieu. However, endolysosomal sequestration of internalized carriers and insufficient redox potential in endolysosomes may delay the release of payloads and impact their therapeutic efficacy. Photochemical internalization (PCI), which takes advantage of light-induced endolysosomal rupture, is an effective technique for endosomal escape and cytosolic release of cargos. In this study, a biodegradable and reduction-sensitive nanocomplex was developed from arginine based poly(ester amide)s and hyaluronic acid (HA), and the PCI-photosensitizer AlPcS2a was conjugated to the surface of the nanocomplex (ArgPEA-ss-HA(AP)). This nanocomplex was used for the co-delivery of both PCI-photosensitizers and therapeutic agents to eliminate the biodistribution discrepancy resulting from the separated administration of free therapeutics. The PCI effect of the ArgPEA-ss-HA(AP) nanocomplex was validated in both monolayers and 3D spheroid models of MDA-MB-231 breast cancer cells. Synergism was detected between the PCI effect and doxorubicin-loaded nanocomplex in the inhibition of MDA-MB-231 cells. In addition, the ArgPEA-ss-HA(AP) nanocomplex also provided enhanced intratumoral penetration in 3D spheroids compared to free AlPcS2a. The in vivo results suggested that the conjugation of AlPCs2a in the nanocomplex enabled the consistent and preferential accumulation of both doxorubicin and AlPcS2a in tumor sites. A light-enhanced anti-tumor effect was observed for the doxorubicin-loaded nanocomplex at well-tolerable dosage. The ArgPEA-ss-HA(AP) nanocomplex, as a reduction-responsive delivery vehicle, can hold great potential to achieve spatio-temporally controllable anti-tumor effects.
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- 2019
32. The protective role of lutein on isoproterenol-induced cardiac failure rat model through improving cardiac morphology, antioxidant status via positively regulating Nrf2/HO-1 signalling pathway
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Zi-Li Li, Heng-Sheng Zhang, Xiong-Ying Ji, Bo Ouyang, Jiang-Wei Huang, and Chang-Rong Jiang
- Subjects
Male ,Lutein ,Antioxidant ,medicine.medical_treatment ,cardioprotective ,Pharmaceutical Science ,Pharmacology ,030226 pharmacology & pharmacy ,01 natural sciences ,Antioxidants ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Myocardial infarction ,Carotenoid ,chemistry.chemical_classification ,food and beverages ,General Medicine ,Hedgehog signaling pathway ,myocardial infarction ,Nrf2 ho 1 ,Molecular Medicine ,Research Article ,Signal Transduction ,cardiac markers ,Cardiotonic Agents ,NF-E2-Related Factor 2 ,Rat model ,Context (language use) ,RM1-950 ,03 medical and health sciences ,medicine ,Animals ,infarct size ,Myocardium ,Isoproterenol ,medicine.disease ,eye diseases ,Rats ,0104 chemical sciences ,Disease Models, Animal ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Heme Oxygenase (Decyclizing) ,Therapeutics. Pharmacology ,Biomarkers - Abstract
Context: Lutein (LU) is a major carotenoid with various pharmacological activities including anti-inflammatory, antioxidant and anti-apoptosis. Objective: The cardioprotective efficacy of LU was determined by evaluating the biochemical and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) rat model. Materials and methods: Healthy male albino rats (n = 40) were segregated into 4 equal groups. Group I (control) rats were administered with olive oil, Group II (LU) rats were orally pre-treated with only 40 mg of LU for 28 days, Group III (MI induced) rats were injected (subcutaneously; s.c) with 85 mg/kg of ISO for 2 consecutive days, whereas Group IV (LU + ISO) rats were pre-treated with 40 mg of LU for 28 days before ISO induction. Results: ISO-induced group showed increased infarct size and cardiac/inflammatory/apoptotic markers. However, pre-treatment with LU (28 days) considerably reduced (p
- Published
- 2019
33. Peptide V3 Inhibits the Growth of Human Hepatocellular Carcinoma by Inhibiting the Ras/Raf/MEK/ERK Signaling Pathway
- Author
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Xin-Ying Ji, Yanzhang Li, Qianqian Zhang, Jun Wang, Tieshan Teng, Hongju Wang, Ailing Ji, Zhengguo Liu, Jianmei Li, Lei Zhang, Zhongwen Xie, Wenke Tian, Ying-Ran Gao, Mengli Zheng, Mengling Li, and Dongdong Wu
- Subjects
signaling pathway ,0301 basic medicine ,MAPK/ERK pathway ,Angiogenesis ,Peptide ,angiogenesis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,peptide V3 ,HCC ,Protein kinase A ,chemistry.chemical_classification ,Chemistry ,apoptosis ,Cancer ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Oncology ,Mechanism of action ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,medicine.symptom ,Signal transduction ,Research Paper - Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. Peptide V3 has shown anti-angiogenic and anti-tumor effects on S180 and H22 xenografts in nude mice. However, the detailed mechanism of action of peptide V3 has not yet been fully elucidated. In the present study, the effects of peptide V3 on the growth of human HCC cells were examined both in vitro and in vivo. Our results showed that peptide V3 inhibited the proliferation, viability, migration, and invasion of human HCC cells. However, no obvious effect was observed in HL-7702 cells. Peptide V3 increased the apoptosis and decreased the protein levels of H-RAS, phospho (p)-RAF, p-MEK, and p-extracellular signal-regulated protein kinase (ERK) in human HCC cells. Peptide V3 suppressed the growth of human HCC xenografts by down-regulating angiogenesis and up-regulating apoptosis. In conclusion, peptide V3 could inhibit the growth of human HCC by inhibiting the Ras/Raf/MEK/ERK signaling pathway. Novel peptides and modification strategies could be designed and applied for the treatment of different types of cancer.
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- 2019
34. Carboxyl-functionalized mesoporous molecular sieve/colloidal gold modified nano-carbon ionic liquid paste electrode for electrochemical determination of serotonin
- Author
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Ying Ji, Yonghong Li, Xinsheng Liu, Guodong Ma, Leina Jia, and Binbin Ren
- Subjects
Detection limit ,Materials science ,Mechanical Engineering ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Molecular sieve ,Electrochemistry ,01 natural sciences ,0104 chemical sciences ,Carbon paste electrode ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Mechanics of Materials ,Colloidal gold ,Ionic liquid ,Electrode ,General Materials Science ,0210 nano-technology ,Mesoporous material - Abstract
A new sensor based on carboxyl-functionalized mesoporous molecular sieve/colloidal gold modified nano-carbon ionic liquid paste electrode (MCM-41-COOH/Au@nano-CILPE) was developed for electrochemical determination of serotonin (5-HT). The carboxyl-functionalized mesoporous molecular sieve was characterized by FTIR spectroscopy. The electrochemical behavior of 5-HT was studied using square pulse voltammetry (SWV). Compared with the traditional carbon paste electrode, the current response of 5-HT was significantly increased on the modified electrode. Under the optimal experimental conditions, the developed sensor showed a linear response in the concentration range of 0.2–20 μM with a detection limit of 0.1 μM for 5-HT. The method was successfully applied for the determination of 5-HT in human blood serum samples.
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- 2019
35. Development of a novel rat model of heterogeneous hepatic injury by injection with colchicine via the splenic vein
- Author
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Wan-Ying Ji, Xuan Jiang, Chao-Xu Zhang, Yi Liu, Yong-Fang Wang, Yan-Yan Zhang, Yang Sun, Jun Wang, and Yu Li
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Rat model ,Lymphatic System ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Humans ,Colchicine ,T2-weighted images ,business.industry ,Gastroenterology ,Diffusion weighted imaging ,General Medicine ,Basic Study ,Heterogeneous hepatic injury ,Rats ,Disease Models, Animal ,Diffusion Magnetic Resonance Imaging ,Liver ,chemistry ,Splenic Vein ,Splenic vein ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Chemical and Drug Induced Liver Injury ,business - Abstract
AIM To develop a novel rat model of heterogeneous hepatic injury. METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group (n = 10) and a colchicine group (n = 60). A 0.25% colchicine solution (0.4 mL/kg) was injected via the splenic vein in the colchicine group to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. At days 3, 7, and 14 and weeks 4, 8, and 12 after the operation, at least seven rats of the colchicine group were selected randomly for magnetic resonance imaging (MRI) examinations, and then they were euthanized. Ten rats of the control group underwent MRI examinations at the same time points, and then were euthanized at week 12. T2-weighted images (T2WI) and diffusion weighted imaging (DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, and correlated with the results of MRI study. RESULTS Obvious pathological changes occurred in the hepatic parenchyma in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point (P < 0.05). There was a significant difference in apparent diffusion coefficient (ADC) of DWI and liver-to-muscle ratio (LMR) of T2WI between the left and right lobes of rats in the colchicine group (P < 0.05) at each time point, and similar results were observed between the colchicine and control groups. Besides, there was a significant correlation between hepatic injury scores and ADC values or LMR (r = -0.682, P = 0.000; r = -0.245, P = 0.018). CONCLUSION Injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. DWI and T2WI may help evaluate the heterogeneous injury among liver lobes.
- Published
- 2018
36. Heterometallic Hexanuclear [Ln4Cr2] Cluster-Based Three-Dimensional Sulfate Frameworks as a Magnetic Refrigerant and Single Molecular Magnet
- Author
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Ying-Ji Sun, Shu-Qin Liu, Xiao-Yu Liu, Hui Zhang, Bin Zhai, Jianjun Zhang, and Zhong-Yi Li
- Subjects
Materials science ,Molecular magnets ,Spintronics ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Refrigerant ,chemistry.chemical_compound ,Crystallography ,chemistry ,Magnet ,Magnetic refrigeration ,Cluster (physics) ,General Materials Science ,Sulfate ,0210 nano-technology ,Cluster based - Abstract
Three heterometallic 3d-4f cluster-based, three-dimensional sulfate frameworks, [Ln4Cr2(μ4-O)2(μ3-OH)4(H2O)9(SO4)5]·3H2O (Ln = Gd/Tb/Dy), were obtained. They are built from the hexanuclear [Ln4Cr2] cluster and sulfate bridge, showing a 6-connected pcu topology network. The [Gd4Cr2]-based compound displays a large magnetocaloric effect of −ΔSm = 38.33 J kg–1 K–1, making it a hopeful magnetic cooler at low temperature, while the Tb- and Dy-containing compounds display interesting single-molecule magnet behavior, indicating that they are potential materials to make spintronic devices.
- Published
- 2018
37. The triptolide-induced apoptosis of osteoclast precursor by degradation of cIAP2 and treatment of rheumatoid arthritis of TNF-transgenic mice
- Author
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Shengli Wang, Yifei Wang, Xin-Ying Ji, Jianhua Liu, Jingchun Wang, Xinchun Wang, and Zhigang Liu
- Subjects
Pharmacology ,Genetically modified mouse ,0303 health sciences ,Chemistry ,030302 biochemistry & molecular biology ,Triptolide ,medicine.disease ,In vitro ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.anatomical_structure ,Apoptosis ,Osteoclast ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,medicine ,Splenocyte ,Tumor necrosis factor alpha - Abstract
This study aims to discuss the effect of triptolide (TPL) on rheumatoid arthritis (RA) and the mechanism related to osteoclast precursor (OCP) and osteoclast (OC). TNF-transgenic RA mice were treated with different doses of TPL by gavage. After the administration was finished, the curative effects were evaluated and compared, and the OCP apoptosis rates, the OC number, and the OC differentiation ability in vitro were detected. Finally, splenocytes of wild-type mice were cultured in vitro and induced to differentiate into OCP, and the cell apoptosis rate, cIAP2, and apoptotic effectors expression level were detected after cIAP2 overexpression and TPL administration. After TPL administration, the RA symptoms in the TPL groups were all better, the apoptosis rate of OCP was higher, and the amount of OC in vitro were lower than that in the control group (all P < 0.05), and all of the changes in the high-dose group were more obvious than the low-dose group. In splenocytes cells cultured in vitro, cIAP2 overexpression could decrease the apoptosis rate of OCPs and increase the OC number, and TPL treatment could down-regulate the cIAP2 and promote OCP apoptosis and OC reduction. In conclusion, TPL could induce OCP apoptosis and inhibit OC formation to effectively treat RA by mediating cIAP2 degradation.
- Published
- 2018
38. Combination Chemo‐Immunotherapy for Pancreatic Cancer Using the Immunogenic Effects of an Irinotecan Silicasome Nanocarrier Plus Anti‐PD‐1
- Author
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Waveley Qiu, Xiang Wang, Zev A. Wainberg, Chong Hyun Chang, Huan Meng, Kuo-Ching Mei, Jinhong Jiang, Ying Ji, Ivanna Tang, Qi Liu, Emily Zheng, Xiangsheng Liu, Andre E. Nel, Matthew Lin, and Yu-Pei Liao
- Subjects
autophagy ,chemo‐immunotherapy ,General Chemical Engineering ,pancreatic cancer ,General Physics and Astronomy ,Medicine (miscellaneous) ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,PD‐1/PD‐L1 axis ,Immunophenotyping ,Pancreatic cancer ,medicine ,General Materials Science ,lcsh:Science ,biology ,Full Paper ,Chemistry ,Autophagy ,General Engineering ,Full Papers ,021001 nanoscience & nanotechnology ,medicine.disease ,digestive system diseases ,0104 chemical sciences ,Granzyme B ,Irinotecan ,Perforin ,biology.protein ,Cancer research ,Immunogenic cell death ,lcsh:Q ,irinotecan silicasome ,0210 nano-technology ,Calreticulin ,medicine.drug - Abstract
There is an urgent need to develop new life‐prolonging therapy for pancreatic ductal adenocarcinoma (PDAC). It is demonstrated that improved irinotecan delivery by a lipid bilayer coated mesoporous silica nanoparticle, also known as a silicasome, can improve PDAC survival through a chemo‐immunotherapy response in an orthotopic Kras‐dependent pancreatic cancer model. This discovery is premised on the weak‐basic properties of irinotecan, which neutralizes the acidic lysosomal pH in PDAC cells. This effect triggers a linked downstream cascade of events that include autophagy inhibition, endoplasmic reticulum stress, immunogenic cell death (ICD), and programmed death‐ligand 1 (PD‐L1) expression. ICD is characterized by calreticulin expression and high‐mobility group box 1 (HMGB1) release in dying Kras‐induced pancreatic cancer (KPC) cells, which is demonstrated in a vaccination experiment to prevent KPC tumor growth on the contralateral site. The improved delivery of irinotecan by the silicasome is accompanied by robust antitumor immunity, which can be synergistically enhanced by anti‐PD‐1 in the orthotopic model. Immunophenotyping confirms the expression of calreticulin, HMGB1, PD‐L1, and an autophagy marker, in addition to perforin and granzyme B deposition. The chemo‐immunotherapy response elicited by the silicasome is more robust than free or a liposomal drug, Onivyde. The silicasome plus anti‐PD‐1 leads to significantly enhanced survival improvement, and is far superior to anti‐PD‐1 plus either free irinotecan or Onivyde., Improved irinotecan delivery by silicasome can improve pancreatic ductal adenocarcinoma (PDAC) survival through a chemo‐immunotherapy response when combined with anti‐PD‐1 in an orthotopic Kras‐dependent PDAC model. This discovery is premised on the weak‐basic properties of irinotecan, which neutralizes the acidic lysosomal pH and triggers a linked downstream cascade of events that include autophagy inhibition, endoplasmic reticulum stress, immunogenic cell death, and PD‐L1 expression.
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- 2021
39. The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases
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Qi-Ying Jiang, Yi-Zhen Wang, Chun-Bo Cai, Hui-Wen Qi, Mi-Rong Jing, Ebenezeri Erasto Ngowi, Dongdong Wu, Xin-Ying Ji, Qing-Lin He, Nazeer Hussain Khan, Saadullah Khattak, Yan-Xia Zhang, and Di Wang
- Subjects
0301 basic medicine ,Cell type ,cardiac protection ,Hydrogen sulfide ,hydrogen sulfide ,Cardiovascular homeostasis ,Neovascularization, Physiologic ,Endogeny ,Review ,030204 cardiovascular system & hematology ,Bioinformatics ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,gas signaling molecule ,heart function ,Cell Movement ,Administration, Inhalation ,Medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,business.industry ,Organic Chemistry ,cardiovascular homeostasis ,Cardiovascular Agents ,General Medicine ,Toxic gas ,medicine.disease ,equipment and supplies ,Computer Science Applications ,Oxidative Stress ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cardiovascular Diseases ,Heart failure ,business - Abstract
Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.
- Published
- 2021
40. Transfunctionalization of graphite fluoride engineered polyaniline grafting to graphene for High-Performance flexible supercapacitors
- Author
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Ying-Ji Sang, Xinping Wang, Lei Dong, Biao Zuo, Wei-Shi Li, Fu-Gang Zhao, and Li Bai
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Supercapacitor ,Materials science ,Nanocomposite ,Graphene ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Capacitance ,Pseudocapacitance ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,Biomaterials ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Chemical engineering ,law ,Polyaniline ,Surface modification ,Graphite ,0210 nano-technology - Abstract
Low energy density is the major obstacle for the practical all-solid-state supercapacitors, which may be raised by the combination of the pseudocapacitance with the electrochemical double-layer capacitance. Although graphene and polyaniline have been demonstrated two effective materials, the synthetic route of graphene and their hybrid mode largely dictated the capacitive performances and cyclability of graphene/polyaniline nanocomposites. Herein, we employed commercial graphite fluoride as the precursor to obtain graphene with a well-preserved carbon lattice. After graphite fluoride functionalization by p-phenylenediamine (pPDA) and in situ oxidative polymerization of anilines, polyaniline (PANI) chains were covalently attached to graphene framework through pPDA bridges. Multiple characterizations were performed to confirm the covalent binding mode between graphene scaffolds and PANI partners, and electrochemical tests unraveled the as-prepared G–pPDA–PANI triads delivered a gravimetric capacitance as high as 638F g−1 and a further amplified volumetric capacitance (up to 759F cm−3). The bendable all-solid-state supercapacitors yielded an encouraging energy density of over 18 W h L−1 at a power density high to 5,950 W L−1, while exhibiting an exceptional rate capability, cycling stability and mechanical flexibility.
- Published
- 2021
41. Bacterial Nanocellulose-Enhanced Alginate Double-Network Hydrogels Cross-Linked with Six Metal Cations for Antibacterial Wound Dressing
- Author
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Gaoquan Hu, Feng Hong, Siyi Hong, Mina Shahriari-Khalaji, and Ying Ji
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Materials science ,Polymers and Plastics ,Composite number ,chemistry.chemical_element ,bacterial nano-cellulose ,Zinc ,engineering.material ,wound dressing ,Article ,Nanocellulose ,Metal ,lcsh:QD241-441 ,lcsh:Organic chemistry ,antibacterial activity ,alginate ,pH-responsive ,General Chemistry ,Chemical engineering ,chemistry ,Wound dressing ,visual_art ,Self-healing hydrogels ,visual_art.visual_art_medium ,engineering ,Biopolymer ,Antibacterial activity ,cationic cross-linking - Abstract
Alginate (Alg) and bacterial nanocellulose (BNC) have exhibited great potential in biomedical applications, especially wound dressing. Non-toxicity and a moisture-maintaining nature are common features making them favorable for functional dressing fabrication. BNC is a natural biopolymer that promotes major advances to the current and future biomedical materials, especially in a flat or tubular membrane form with excellent mechanical strength at hydrated state. The main drawback limiting wide applications of both BNC and Alg is the lack of antibacterial activity, furthermore, the inherent poor mechanical property of Alg leads to the requirement of a secondary dressing in clinical treatment. To fabricate composite dressings with antibacterial activity and better mechanical properties, sodium alginate was efficiently incorporated into the BNC matrix using a time-saving vacuum suction method followed by cross-linking through immersion in separate solutions of six cations (manganese, cobalt, copper, zinc, silver, and cerium). The results showed the fabricated composites had not only pH-responsive antibacterial activities but also improved mechanical properties, which are capable of acting as smart dressings. All composites showed non-toxicity toward fibroblast cells. Rat model evaluation showed the skin wounds covered by the dressings healed faster than by BNC.
- Published
- 2020
42. Gastrodin Alleviates Cerebral Ischaemia/Reperfusion Injury by Inhibiting Pyroptosis by Regulating the lncRNA NEAT1/miR-22-3p Axis
- Author
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Xiong-Ying Ji, Mei-Fang Liu, Heng-Sheng Zhang, and Bo Ouyang
- Subjects
0301 basic medicine ,Male ,Inflammation ,Pharmacology ,Biochemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,In vivo ,Lactate dehydrogenase ,medicine ,Pyroptosis ,Animals ,Viability assay ,Gastrodin ,Benzyl Alcohols ,Neurons ,Cerebral infarction ,Chemistry ,Brain ,Infarction, Middle Cerebral Artery ,General Medicine ,medicine.disease ,Cell Hypoxia ,Oxygen ,MicroRNAs ,030104 developmental biology ,Glucose ,Neuroprotective Agents ,Reperfusion Injury ,RNA, Long Noncoding ,medicine.symptom ,Reperfusion injury ,030217 neurology & neurosurgery - Abstract
Cerebral ischaemia/reperfusion (I/R) injury-induced irreversible brain injury is a major cause of mortality and functional impairment in ageing people. Gastrodin (GAS), derived from the traditional Chinese herbal medicine Tianma, has been reported to inhibit the progression of stroke, but the mechanism whereby GAS modulates the progression of cerebral I/R remains unclear. The middle cerebral artery occlusion method was used as a model of I/R in vivo. Rats were pretreated with GAS by intraperitoneal injection 7 days before I/R surgery and were then treated with GAS for 7 days after I/R surgery. Additionally, an oxygen–glucose deprivation/reoxygenation model using neuronal cells was established in vitro to simulate I/R injury. 2,3,5-Triphenyltetrazolium chloride and Nissl staining were used to evaluate infarct size and neuronal damage, respectively. Lactate dehydrogenase release and cell counting kit-8 assays were used to assess neuronal cell viability. Enzyme-linked immunosorbent assay, qPCR, flow cytometry and western blotting were performed to analyse the expression levels of inflammatory factors (IL-1β, IL-18), lncRNA NEAT1, miR-22-3p, NLRP3 and cleaved caspase-1. Luciferase reporter experiments were performed to verify the association between lncRNA NEAT1 and miR-22-3p. The results indicated that GAS could significantly improve the neurological scores of rats and reduce the area of cerebral infarction. Meanwhile, GAS inhibited pyroptosis by downregulating NLRP3, inflammatory factors (IL-1β, IL-18) and cleaved caspase-1. In addition, GAS attenuated I/R-induced inflammation in neuronal cells through the modulation of the lncRNA NEAT1/miR-22-3p axis. GAS significantly attenuated cerebral I/R injury via modulation of the lncRNA NEAT1/miR-22-3p axis. Thus, GAS might serve as a new agent for the treatment of cerebral I/R injury.
- Published
- 2020
43. Evaluation of different strategies to minimize the matrix effects on LC-MS/MS analysis of multiple lipophilic shellfish toxins in both acidic and alkaline chromatographic conditions
- Author
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Huidan Chen, Jiangbing Qiu, Tianshen Li, Aifeng Li, and Ying Ji
- Subjects
China ,Toxicology ,Tandem mass spectrometry ,Mass spectrometry ,Matrix (chemical analysis) ,Limit of Detection ,Tandem Mass Spectrometry ,Okadaic Acid ,medicine ,Animals ,Spiro Compounds ,Solid phase extraction ,Shellfish ,Pyrans ,Detection limit ,Chromatography ,Chemistry ,Solid Phase Extraction ,Mussel ,medicine.disease ,Ostreidae ,Shellfish poisoning ,Bivalvia ,Pectinidae ,Seafood ,Marine Toxins ,Chromatography, Liquid - Abstract
Lipophilic shellfish toxins (LSTs) accumulated by shellfish pose a potential threat to consumer health. A mandatory routine monitoring of LSTs has been adopted for seafood products by liquid chromatography-mass spectrometry (LC-MS) in many countries. In this study, two methods developed on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) under acidic and alkaline chromatographic conditions were assessed for the determination of multiple LSTs. Different strategies including matrix solid-phase dispersion (MSPD), solid phase extraction (SPE) and sample dilution were applied and evaluated the matrix effects of mussel, scallop, clam, and oyster samples on the signal response of mass spectrometry. Results showed that the alkaline method achieved a lower limit of detection (LOD) and more robust compared to the acidic method. The obvious signal suppression of OA and DTX1 (55%-76%) and signal enhancement of PTX2 (27%-34%) occurred in the crude extracts of shellfish under acidic chromatography. In the alkaline method, no remarkable matrix effects of crude extracts were found except for the scallop matrix on the signal intensity of DTX1, AZA3 and GYM-A (121%-130%). Clean-up methods MSPD, SPE and sample dilution obviously reduced the inhibition of shellfish matrices on the signal response of OA and DTX1, however, which were still subject to signal inhibition under acidic condition. Sample dilution was more effective than SPE and MSPD in minimizing the matrix interference in both acidic and alkaline methods. Furthermore, sample dilution in combination with the alkaline chromatography was the most effective method. Bivalve mollusks harvested from Beibu Bay, South China Sea, were generally contaminated by GYM-A and SPX1 at low concentrations.
- Published
- 2020
44. Enhanced MHC-I antigen presentation from the delivery of ovalbumin by light-facilitated biodegradable poly(ester amide)s nanoparticles
- Author
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Chih-Chang Chu, Ying Ji, and Jihui Zhao
- Subjects
0301 basic medicine ,biology ,Chemistry ,Endosome ,media_common.quotation_subject ,Antigen presentation ,Biomedical Engineering ,02 engineering and technology ,General Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,Ovalbumin ,030104 developmental biology ,Antigen ,MHC class I ,biology.protein ,Biophysics ,Cytotoxic T cell ,General Materials Science ,Photosensitizer ,0210 nano-technology ,Internalization ,media_common - Abstract
The generation of CD8 T cells is crucial in adaptive immunity against cancer and many infectious diseases. Vaccines aimed to stimulate CD8 T cell response typically become ineffective because the antigens are subject to sequestration in endocytic compartments, instead of being delivered cytosolically for MHC-I processing and presentation. In this study, a nano-carrier (Arg-Phe-PEA(AP) nanoparticles) for ovalbumin (OVA) was developed from arginine- and phenylalanine-based poly(ester amide)s, which further formed an electrostatic complex with AlPcS2a, a typical photosensitizer for photochemical internalization (PCI) strategies. The nanocarrier significantly enhanced the internalization efficiency by dendritic cells of both OVA and AlPcS2a. The photochemical interruption of endocytic compartments by the AlPcS2a photosensitizer complexed in the nanocarrier enabled the light-facilitated endosomal escape of OVA. MHC-I presentation and CD8 T cell response were elicited by OVA-loaded Arg-Phe-PEA(AP) nanoparticles when light irradiation was applied at 660 nm. The light-facilitated delivery of OVA was dependent on the light dose and the concentration of the photosensitizer, both in vitro and in vivo. The optimized stimulation of MHC-I response demonstrated the potency of this light-facilitated nano-platform for CD8 T cell-inducing vaccination.
- Published
- 2020
45. Response of fatty acids and lipid metabolism enzymes during accumulation, depuration and esterification of diarrhetic shellfish toxins in mussels (Mytilus galloprovincialis)
- Author
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Mingyue Zhao, Yuan Fang, Qinghui Ai, Jiangbing Qiu, Ying Ji, Aifeng Li, and Shuqin Wang
- Subjects
Food Chain ,Health, Toxicology and Mutagenesis ,chemistry.chemical_compound ,Okadaic Acid ,Microalgae ,Animals ,Shellfish Poisoning ,Shellfish ,chemistry.chemical_classification ,Mytilus ,Fatty acid metabolism ,biology ,Esterification ,Fatty Acids ,Public Health, Environmental and Occupational Health ,Fatty acid ,Esters ,General Medicine ,Metabolism ,Okadaic acid ,Lipid Metabolism ,Pollution ,Eicosapentaenoic acid ,Fatty acid synthase ,chemistry ,Biochemistry ,Seafood ,Docosahexaenoic acid ,biology.protein ,Dinoflagellida ,lipids (amino acids, peptides, and proteins) ,Marine Toxins ,Polyunsaturated fatty acid - Abstract
Bivalve mollusks accumulate diarrhetic shellfish toxins (DSTs) from toxigenic microalgae, thus posing a threat to human health by acting as a vector of toxins to consumers. In bivalves, free forms of DSTs can be esterified with fatty acids at the C-7 site to form acyl esters (DTX3), presumably a detoxification mechanism for bivalves. However, the effects of esterification of DSTs on fatty acid metabolism in mollusks remain poorly understood. In this study, mussels (Mytilus galloprovincialis) were fed the DST-producing dinoflagellate Prorocentrum lima for 10 days followed by an additional 10-days depuration in filtered seawater to track the variation in quantity and composition of DST acyl esters and fatty acids. A variety of esters of okadaic acid (OA) and dinophysistoxin-1 (DTX1) were mainly formed in the digestive gland (DG), although trace amounts of esters also appeared in muscle tissue. A large relative amount of OA (60%-84%) and DTX1 (80%-92%) was esterified to DTX3 in the visceral mass (referred to as digestive gland, DG), and the major ester acyl chains were C16:0, C16:1, C18:0, C18:1, C20:1 and C20:2. The DG and muscle tissues showed pronounced differences in fatty acid content and composition during both feeding and depuration periods. In the DG, fatty acid content gradually decreased in parallel with increasing accumulation and esterification of DSTs. The decline in fatty acids was accelerated during depuration without food. This reduction in the content of important polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), would lead to a reduction in the nutritional value of mussels. Enzymes involved in lipid metabolism, including acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), lipoprotein lipase (LPL) and hepatic lipase (HL), were actively involved in the metabolism of fatty acids in the DG, whereas their activities were weak in muscle tissue during the feeding period. This study helps to improve the understanding of interactions between the esterification of DSTs and fatty acid dynamics in bivalve mollusks.
- Published
- 2020
46. Silencing EPB41 Gene Expression Leads to Cell Cycle Arrest, Migration Inhibition, and Upregulation of Cell Surface Antigen in DC2.4 Cells
- Author
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Wenqiang Wei, Qing Zhao, Wang Xinchun, Yanhong Li, Dongdong Wu, Yongqiang Li, Xin-Ying Ji, and Huimin Li
- Subjects
Small interfering RNA ,Cell cycle checkpoint ,Cell ,Thymus Gland ,Mice ,Cell Movement ,Lab/In Vitro Research ,Cell Line, Tumor ,Myasthenia Gravis ,medicine ,Animals ,Humans ,RNA, Small Interfering ,CD86 ,Chemistry ,Microfilament Proteins ,Cell Cycle ,Cell migration ,General Medicine ,Transfection ,Cell Cycle Checkpoints ,Dendritic Cells ,Cell cycle ,Cell biology ,Up-Regulation ,medicine.anatomical_structure ,Antigens, Surface ,RNA Interference ,CD80 - Abstract
BACKGROUND Protein 4.1R (EPB41) is the main cytoskeleton component of the erythrocyte membrane and may be involved in cell migration and adhesion. Previous research discovered overexpression of 4.1R in the thymus of patients with myasthenia gravis (MG). The protein 4.1R on dendritic cells may play a pivotal role in MG pathogenesis. This research investigated the effects of small interfering RNA 4.1R-siRNA on cell migration, cell cycle, and surface antigen expression of DC2.4 mouse dendritic cells, thus providing a new direction for the study of MG pathogenesis. MATERIAL AND METHODS Three 4.1R-specific siRNAs were designed, and the expression of 4.1R was detected by real-time PCR at the mRNA level and Western blot analysis at the protein level to select out the most efficient siRNAs. Changes in cell morphology were observed and cell migration ability was analyzed by Transwell assay. Cell cycle and surface antigen were both analyzed by flow cytometry. RESULTS The cell bodies of DC2.4 diminished, the synapses were increased, and protuberance became more obvious after being transfected with 4.1R-siRNA. After knockdown of 4.1R, cell migration ability decreased and the proportion of cells in S phase significantly increased (both P
- Published
- 2020
47. Fatty acid ester metabolites of gymnodimine in shellfish collected from China and in mussels (Mytilus galloprovincialis) exposed to Karenia selliformis
- Author
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Elliott J. Wright, Aifeng Li, Ying Ji, Philipp Hess, Pearse McCarron, and Yijia Che
- Subjects
0106 biological sciences ,Oyster ,China ,toxin profiles ,animal structures ,Fatty acid ester ,Karenia selliformis ,Hydrocarbons, Cyclic ,Plant Science ,010501 environmental sciences ,Aquatic Science ,01 natural sciences ,Isochrysis galbana ,Gymnodimines (GYM) ,chemistry.chemical_compound ,antioxidant enzymes ,biology.animal ,Animals ,Humans ,14. Life underwater ,Food science ,Shellfish ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,Mytilus ,fatty acid ester ,biology ,010604 marine biology & hydrobiology ,fungi ,Fatty acid ,Toxin profiles ,biology.organism_classification ,chemistry ,gymnodimines (GYM) ,Crassostrea ,Marine Toxins ,Antioxidant enzymes ,Imines ,Heterocyclic Compounds, 3-Ring ,human activities - Abstract
Marine shellfish exposed to the microalgae Karenia selliformis can accumulate gymnodimines (GYM). Shellfish samples collected from Beihai City in Guangxi Autonomous Region, and Ningde City in Fujian Province, in the South China Sea, as well as mussels Mytilus galloprovincialis fed on K. selliformis under laboratory conditions were analyzed. Gymnodimines and various fatty acid ester metabolites were detected in the clam Antigona lamellaris and pen shell Atrina pectinata, while no esters were found in the oyster Crassostrea sp. and the gastropod Batillaria zonalis despite positive detection of free GYM in both species. When present, the predominant acyl esters observed were 18:0-GYM-A and 20:1-GYM-A. Under laboratory conditions GYM-A was accumulated and metabolized to fatty acid esters in mussels exposed to K. selliformis, with 16:0-GYM-A and 20:1-GYM-A as the major variants. A novel compound with the same accurate mass as GYM-A and its 16:0 fatty acid ester were observed in the experimental mussels but was not present in the microalgal strain to which mussels were exposed. No significant differences of reactive oxygen species (ROS) levels and antioxidant enzymes were found between mussels fed on K. selliformis or GYM-free microalgae Isochrysis galbana. This suggests the accumulation of GYM and its metabolites does not significantly impact the physiological status of mussels. While it is currently not proven that GYM affects human health, risk assessments should consider the presence of GYM esters in naturally contaminated shellfish as part of exposure analysis.
- Published
- 2020
48. Conversion and Stability of New Metabolites of Paralytic Shellfish Toxins under Different Temperature and pH Conditions
- Author
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Yijia Che, Aifeng Li, Ling Ding, Jiangbing Qiu, and Ying Ji
- Subjects
0106 biological sciences ,animal structures ,Trace Amounts ,Food Contamination ,01 natural sciences ,Tandem Mass Spectrometry ,Chemical conversion ,medicine ,Animals ,Shellfish ,Chromatography, High Pressure Liquid ,Molecular Structure ,Chemistry ,010401 analytical chemistry ,technology, industry, and agriculture ,Temperature ,food and beverages ,General Chemistry ,Contamination ,Hydrogen-Ion Concentration ,medicine.disease ,0104 chemical sciences ,Shellfish poisoning ,Bivalvia ,Environmental chemistry ,Marine Toxins ,General Agricultural and Biological Sciences ,010606 plant biology & botany - Abstract
A number of new C-11 hydroxyl metabolites (so-called M-toxins) of paralytic shellfish toxins (PSTs) have been discovered in contaminated shellfish, and trace amounts have also been detected in some...
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- 2020
49. De novo pattern discovery enables robust assessment of functional consequences of non-coding variants
- Author
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Ying Ji, Nancy J. Cox, Hai Yang, Guangze Zheng, Quan Wang, Rui Chen, Qiang Wei, Bingshan Li, and Xue Zhong
- Subjects
Statistics and Probability ,Computer science ,Genome-wide association study ,Computational biology ,Biochemistry ,Genome ,03 medical and health sciences ,chemistry.chemical_compound ,Genome editing ,Genetic variation ,Leverage (statistics) ,Molecular Biology ,Gene ,030304 developmental biology ,Gene Editing ,0303 health sciences ,030302 biochemistry & molecular biology ,Genetic Variation ,DNA ,Biological Evolution ,Original Papers ,Biobank ,Computer Science Applications ,Computational Mathematics ,Phenotype ,Computational Theory and Mathematics ,chemistry ,Software ,Coding (social sciences) - Abstract
Motivation Given the complexity of genome regions, prioritize the functional effects of non-coding variants remains a challenge. Although several frameworks have been proposed for the evaluation of the functionality of non-coding variants, most of them used ‘black boxes’ methods that simplify the task as the pathogenicity/benign classification problem, which ignores the distinct regulatory mechanisms of variants and leads to less desirable performance. In this study, we developed DVAR, an unsupervised framework that leverage various biochemical and evolutionary evidence to distinguish the gene regulatory categories of variants and assess their comprehensive functional impact simultaneously. Results DVAR performed de novo pattern discovery in high-dimensional data and identified five regulatory clusters of non-coding variants. Leveraging the new insights into the multiple functional patterns, it measures both the between-class and the within-class functional implication of the variants to achieve accurate prioritization. Compared to other two-class learning methods, it showed improved performance in identification of clinically significant variants, fine-mapped GWAS variants, eQTLs and expression-modulating variants. Moreover, it has superior performance on disease causal variants verified by genome-editing (like CRISPR-Cas9), which could provide a pre-selection strategy for genome-editing technologies across the whole genome. Finally, evaluated in BioVU and UK Biobank, two large-scale DNA biobanks linked to complete electronic health records, DVAR demonstrated its effectiveness in prioritizing non-coding variants associated with medical phenotypes. Availability and implementation The C++ and Python source codes, the pre-computed DVAR-cluster labels and DVAR-scores across the whole genome are available at https://www.vumc.org/cgg/dvar. Supplementary information Supplementary data are available at Bioinformatics online.
- Published
- 2018
50. Krüppel-like factor 4 promotesc-Metamplification-mediated gefitinib resistance in non-small-cell lung cancer
- Author
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Qianyi Xie, Wei Feng, Chunle Wang, Chunyun Li, Suo Liu, Longyu Jin, and Ying Ji
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Apoptosis ,chemistry.chemical_compound ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,heterocyclic compounds ,skin and connective tissue diseases ,Gene knockdown ,medicine.diagnostic_test ,Gefitinib ,General Medicine ,Proto-Oncogene Proteins c-met ,Tumor Burden ,Oncology ,KLF4 ,030220 oncology & carcinogenesis ,RNA Interference ,medicine.drug ,C-Met ,Kruppel-Like Transcription Factors ,Mice, Nude ,Antineoplastic Agents ,Cell Line ,Kruppel-Like Factor 4 ,03 medical and health sciences ,Western blot ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Lung cancer ,neoplasms ,Protein kinase B ,Cell Proliferation ,business.industry ,Akt/PKB signaling pathway ,Gene Amplification ,medicine.disease ,Xenograft Model Antitumor Assays ,respiratory tract diseases ,030104 developmental biology ,chemistry ,A549 Cells ,Drug Resistance, Neoplasm ,Quinazolines ,Cancer research ,business - Abstract
Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression.
- Published
- 2018
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