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المؤلفون: Wen-Jing Zhao, Yue-Fen Wang, Zhi-Qiang Liu, Xin-Can Jiang, Yanbin Gao, Yuan Meng, Cun Shen, Fang-Qiang Cui, Zhen Cai
المصدر: Journal of Diabetes Research
Journal of Diabetes Research, Vol 2019 (2019)مصطلحات موضوعية: Male, Article Subject, Endocrinology, Diabetes and Metabolism, Apoptosis, medicine.disease_cause, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Antioxidants, Podocyte, Cell Line, Diabetic nephropathy, Rats, Sprague-Dawley, Endocrinology, In vivo, medicine, Animals, Diabetic Nephropathies, Phosphorylation, PI3K/AKT/mTOR pathway, lcsh:RC648-665, Chemistry, Podocytes, Transfection, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, Proteinuria, medicine.anatomical_structure, Glucose, NADPH Oxidase 4, Cancer research, Signal transduction, Phosphatidylinositol 3-Kinase, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Oxidative stress, Drugs, Chinese Herbal, Signal Transduction, Research Article
الوصف: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The ROS-mediated PI3K/AKT pathway plays a key role in podocyte apoptosis and DN progression. Our previous study demonstrated that Baoshenfang (BSF) can decrease proteinuria and attenuate podocyte injury. However, the effects of BSF on podocyte apoptosis induced by the ROS-mediated PI3K/AKT pathway remain unclear. Herein, in vivo and in vitro studies have been performed. In our in vivo study, BSF significantly decreased 24-h urinary protein, serum creatinine, and blood urea nitrogen levels in DN mice. Meanwhile, BSF significantly inhibited oxidative stress and podocyte apoptosis in our in vivo and in vitro studies. Moreover, BSF significantly decreased the inhibition of the PI3K/AKT pathway induced by HG in DN. More importantly, the effects of BSF on podocyte apoptosis were reversed by PI3K siRNA transfection. In conclusion, BSF can decrease proteinuria and podocyte apoptosis in DN, in part through regulating the ROS-mediated PI3K/AKT pathway.
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المؤلفون: Wen‑Jing Zhao, Jin‑Ying Su, Hai‑Fang Zhang
المصدر: Molecular Medicine Reports
مصطلحات موضوعية: 0301 basic medicine, VEGFA, Male, Vascular Endothelial Growth Factor A, Cancer Research, Angiogenesis, Neovascularization, Physiologic, Biology, Biochemistry, cerebral ischemia, Neovascularization, 03 medical and health sciences, angiogenesis, Downregulation and upregulation, miR-195, Cell Movement, microRNA, Genetics, medicine, Human Umbilical Vein Endothelial Cells, Gene silencing, Animals, Cluster Analysis, Humans, Molecular Biology, Tube formation, Gene Expression Profiling, Articles, Cerebral Infarction, Rats, Endothelial stem cell, Vascular endothelial growth factor A, MicroRNAs, 030104 developmental biology, Oncology, Gene Expression Regulation, Cancer research, Molecular Medicine, RNA Interference, medicine.symptom
الوصف: Angiogenesis, the formation of new blood vessels from preexisting endothelium, is a process that involves a series of interassociated and mutually interactive pathophysiological processes. It is accepted that microRNAs (miRNAs) regulate endothelial cell behavior, including their involvement in angiogenesis. However, it remains unclear whether miRNAs are involved in the regulation of angiogenesis following cerebral ischemia. Therefore, the present study aimed to investigate the role of miRNAs in angiogenesis and the underlying mechanism following cerebral ischemia. Expression profiles of miRNAs in rat brain samples following middle cerebral artery occlusion (MCAO) were investigated using a miRNA microarray. The expression of candidate miRNA, miR‑195 was further validated using reverse transcription‑quantitative polymerase chain reaction. Then, the effects of miR‑195 on cell migration and tube formation of human umbilical vein vascular endothelial cells (HUVECs) were investigated following miR‑195 silencing, and overexpression. The specific target genes of miR‑195 were predicted using microRNA prediction bioinformatics software (http://www.microrna.org/microrna/home.do), and then confirmed using a dual‑luciferase reporter assay and rescue experiment. It was demonstrated that miR‑195 was significantly downregulated in the brains of rats following MCAO and in hypoxia‑induced HUVECs. Furthermore, it was revealed that miR‑195 overexpression inhibited the invasion ability and tube formation of HUVECs in vitro, while miR‑195 silencing enhanced these functions. In addition, vascular endothelial growth factor A (VEGFA) was identified as a direct target of miR‑195 and was negatively correlated with miR‑195 expression. In addition, the rescue experiment revealed that overexpression of VEGFA reversed the inhibitory effects of miR‑195 overexpression on the invasion ability and tube formation of HUVECs. The present study has provided a novel insight into the promoting roles of miR‑195 downregulation on angiogenesis following cerebral infarction and suggests that the miR‑195/VEGFA signaling pathway is a putative therapeutic target in cerebral ischemia.
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المؤلفون: Zhi-Qiang Liu, Wen-Jing Zhao, Fang-Qiang Cui, Wei Jing Liu, Yue-Fen Wang, Cun Shen, Yuan Meng, Long Tang, Zi-Long Shen, Yanbin Gao
المصدر: Journal of Diabetes Research, Vol 2019 (2019)
Journal of Diabetes Researchمصطلحات موضوعية: Male, Article Subject, Endocrinology, Diabetes and Metabolism, p38 mitogen-activated protein kinases, Apoptosis, Pharmacology, Kidney, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Antioxidants, Podocyte, Rats, Sprague-Dawley, Diabetic nephropathy, Nephrin, Endocrinology, medicine, Animals, Humans, Diabetic Nephropathies, Single-Blind Method, Aged, chemistry.chemical_classification, Reactive oxygen species, lcsh:RC648-665, biology, Podocytes, Chemistry, Kidney metabolism, Middle Aged, medicine.disease, Rats, Oxidative Stress, Proteinuria, medicine.anatomical_structure, NADPH Oxidase 4, biology.protein, Female, Reactive Oxygen Species, Oxidative stress, Drugs, Chinese Herbal, Research Article
الوصف: Diabetic nephropathy (DN) is a serious kidney-related complication of type 1 and type 2 diabetes. The Chinese herbal formula Baoshenfang (BSF) shows therapeutic potential in attenuating oxidative stress and apoptosis in podocytes in DN. This study evaluated the effects of BSF on podocyte injury in vivo and in vitro and explored the possible involvement of the nicotinamide adenine dinucleotide phosphate-oxidase-4/reactive oxygen species- (NOX-4/ROS-) activated p38 pathway. In the identified compounds by mass spectrometry, some active constituents of BSF were reported to show antioxidative activity. In addition, we found that BSF significantly decreased 24-hour urinary protein, serum creatinine, and blood urea nitrogen in DN patients. BSF treatment increased the nephrin expression, alleviated oxidative cellular damage, and inhibited Bcl-2 family-associated podocyte apoptosis in high-glucose cultured podocytes and/or in diabetic rats. More importantly, BSF also decreased phospho-p38, while high glucose-mediated apoptosis was blocked by p38 mitogen-activated protein kinase inhibitor in cultured podocytes, indicating that the antiapoptotic effect of BSF is p38 pathway-dependent. High glucose-induced upexpression of NOX-4 was normalized by BSF, and NOX-4 siRNAs inhibited the phosphorylation of p38, suggesting that the activated p38 pathway is at least partially mediated by NOX-4. In conclusion, BSF can decrease proteinuria and protect podocytes from injury in DN, in part through inhibiting the NOX-4/ROS/p38 pathway.
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المؤلفون: Peng Wu, Wen‑Jing Zhao, Yan Jin, Jin‑Fei Chen, Wei De, Jun‑Bin Wang, Yang Liu, Fen Yang
المصدر: Oncology reports. 41(2)
مصطلحات موضوعية: 0301 basic medicine, Male, Cancer Research, Epithelial-Mesenchymal Transition, Carcinogenesis, Cell, Down-Regulation, Mice, Nude, Biology, Histones, 03 medical and health sciences, Stomach surgery, Mice, Stomach Neoplasms, Cell Line, Tumor, medicine, Animals, Humans, Promyelocytic Leukemia Zinc Finger Protein, Promoter Regions, Genetic, Cell Proliferation, Regulation of gene expression, Mice, Inbred BALB C, Oncogene, Tumor Suppressor Proteins, Stomach, Polycomb Repressive Complex 2, General Medicine, Methylation, Cell cycle, DNA Methylation, Middle Aged, Molecular medicine, Survival Analysis, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cancer cell, Cancer research, Female, RNA, Long Noncoding
الوصف: Promyelocytic leukemia zinc finger (PLZF) plays important roles in tumorigenic and developmental processes of various types of cancers. However, the expression of PLZF in gastric cancer (GC) has not been reported. The aim of the present study was to investigate the expression level and potential status of PLZF in GC as well as its possible mechanism. In the present study, we found that PLZF was downregulated in the majority of GC cell lines and tumor tissues and that alteration of PLZF expression was closely correlated with a malignant phenotype, epithelial‑mesenchymal transformation and overall survival. Evaluation of in vitro proliferation, colony information, migration and invasion indicated that PLZF gene transduction induced a less malignant phenotype, which was also confirmed through in vivo studies performed in athymic nude mice. Furthermore, we assessed the expression levels of the lncRNA ANRIL in GC and found that it was negatively associated with the level of PLZF and that ANRIL indirectly methylated PLZF to suppress its expression via binding with polycomb repressive complex 2. When GC cells were treated with the methylation inhibitor 5‑Aza‑2'‑deoxycytidine, the expression of PLZF increased, which further confirmed that PLZF was methylated. These results indicated that constitutive ANRIL activation was a possible cause of the lack of PLZF expression in GC cells. Coupled deregulation of PLZF and ANRIL may account for most of the alterations described in GC, and PLZF may become a potential target of GC therapy.
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المؤلفون: Mo-Ran Huang, Zhan-Peng Shang, Jia-Yu Zhang, Wen-Jing Zhao, Zhibin Wang, Qinqing Li, Wenbin He
المصدر: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules, Vol 23, Iss 1, p 151 (2018)
Molecules; Volume 23; Issue 1; Pages: 151مصطلحات موضوعية: 0301 basic medicine, Male, Spectrometry, Mass, Electrospray Ionization, daidzein, metabolic profiling, UHPLC-LTQ-Orbitrap mass spectrometry, data-mining technologies, Glucuronidation, Pharmaceutical Science, Phytoestrogens, Orbitrap, Mass spectrometry, 01 natural sciences, Article, Analytical Chemistry, law.invention, lcsh:QD241-441, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Biotransformation, lcsh:Organic chemistry, law, In vivo, Tandem Mass Spectrometry, Drug Discovery, Animals, Data Mining, Metabolomics, Physical and Theoretical Chemistry, SOY ISOFLAVONES, Chromatography, High Pressure Liquid, Chromatography, Molecular Structure, 010401 analytical chemistry, Organic Chemistry, Daidzein, Metabolism, Isoflavones, 0104 chemical sciences, 030104 developmental biology, chemistry, Chemistry (miscellaneous), Metabolome, Molecular Medicine
الوصف: Daidzein, the main bioactive soy isoflavone in Nature, has been found to possess many biological functions. It has been investigated in particular as a phytoestrogen owing to the similarity of its structure with that of the human hormone estrogen. Due to the lack of comprehensive studies on daidzein metabolism, further research is still required to clarify its in vivo metabolic fate and intermediate processes. In this study, an efficient strategy was established using UHPLC-LTQ-Orbitrap mass spectrometry to profile the metabolism of daidzein in rats. Meanwhile, multiple data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filtering (MMDF), neutral loss fragment (NLF), and diagnostic product ion (DPI) were utilized to investigate daidzein metabolites from the HR-ESI-MS1 to ESI-MSn stage in both positive and negative ion modes. Consequently, 59 metabolites, including prototype compounds, were positively or tentatively elucidated based on reference standards, accurate mass measurements, mass fragmentation behaviors, chromatographic retention times, and corresponding calculated ClogP values. As a result, dehydration, hydrogenation, methylation, dimethylation, glucuronidation, glucosylation, sulfonation, ring-cleavage, and their composite reactions were ascertained to interpret its in vivo biotransformation. Overall, our results not only revealed the potential pharmacodynamics forms of daidzein, but also aid in establishing a practical strategy for rapid screening and identifying metabolites of natural compounds.
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المؤلفون: Wen-Jing Zhao, Qinqing Li, Qiqi Xin, Weihong Cong, Zhan-Peng Shang, Zhibin Wang, Jia-Yu Zhang
المصدر: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
مصطلحات موضوعية: Male, Pueraria, Spectrometry, Mass, Electrospray Ionization, Clinical Biochemistry, Administration, Oral, Orbitrap, Mass spectrometry, 030226 pharmacology & pharmacy, 01 natural sciences, Biochemistry, Analytical Chemistry, law.invention, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Isoflavonoid, Puerarin, law, Genistin, Animals, Data Mining, Daidzin, Chromatography, High Pressure Liquid, Chromatography, biology, 010401 analytical chemistry, Daidzein, Cell Biology, General Medicine, biology.organism_classification, Isoflavones, 0104 chemical sciences, Rats, chemistry
الوصف: Puerarin, a bioactive natural C-glycoside isoflavonoid isolated from Pueraria lobata (Willd.) Ohwi, possesses many potential health benefits. However, the in vivo metabolic fates of puerarin have not been comprehensively clarified yet. In this study, an efficient strategy based on UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes was developed to profile and characterize puerarin metabolites in rat urine and plasma. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filtering (MMDF) were utilized to screen potential puerarin metabolites from HR-ESI-MS1 stage. The mass fragmentation behaviors of five reference standards, including puerarin, daidzin, daidzein, genistin, and genistein, were comprehensively studied for construction of diagnostic product ions (DPIs), which could be employed to implement rapid identification of puerarin metabolites. Finally, a total of 66 metabolites (prototype compound included) were tentatively or positively identified based on standard substances, chromatographic retention times, accurate mass measurement, and corresponding ClogP values. Our results demonstrated that puerarin underwent multiple in vivo metabolic reactions including methylation, hydroxylation, dehydroxylation, hydrogenation, deglycosylation, glycosylation, sulfonation, glucuronidation, and their complicated reactions. In conclusion, the newly discovered puerarin metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies.
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المؤلفون: Zhibin Wang, Lu-Lu Xu, Jiangyu Zhang, Fei Wang, Zhanpeng Shang, Wen-Jing Zhao, Xiaodan Mei, Jian-Qiu Lu
مصطلحات موضوعية: Male, Antioxidant, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Flos, Toxicology, Mass spectrometry, Orbitrap, 01 natural sciences, Biochemistry, Mass Spectrometry, law.invention, Rats, Sprague-Dawley, chemistry.chemical_compound, Chlorogenic acid, law, medicine, Animals, Quadrupole ion trap, Chromatography, High Pressure Liquid, Pharmacology, Chromatography, biology, 010405 organic chemistry, 010401 analytical chemistry, food and beverages, General Medicine, biology.organism_classification, Rats, 0104 chemical sciences, chemistry, Chlorogenic Acid, Ultra high performance
الوصف: 1. Chlorogenic acids (CGAs), one kind of major bioactive constituents isolated from Flos Lonicera Japonica, possess many biological activities, such as antibacterial, antioxidant and antiviral activities. In this study, we established an efficient strategy using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of CGAs in rat urine and plasma. 2. The extract from Flos Lonicera Japonica was orally administrated to Sprague-Dawley (SD) rats at a dose of 1000 mg/kg body weight. Then, a combination of various post-acquisition data mining methods, including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDFs) and diagnostic product ions (DPIs), were adopted to characterize the known and unknown CGA metabolites in SD rats. 3. As a result, a total of 68 CGA metabolites were unambiguously or tentatively screened and characterized. These metabolites, including 18 prototype compounds and 50 metabolites, were deduced to be yielded via methylation, hydrogenation, demethylation, dehydration, sulfate conjugation, glucuronide conjugation, glycosylation conjugation and their composite reactions, which mainly occurred to caffeoylquinic acids, dicaffeoylquinic acids, p-coumaroylquinic acids and feruloylquinic acids. 4. In conclusion, this study profiled CGA metabolites, which are useful in understanding the in vivo metabolic fate, effective forms, and pharmacological and toxic actions of CGAs.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24e5e3d46bf8d1183f730fe14050c9d2
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المؤلفون: Paul M. Pilowsky, Ruichen Guo, Debra Birch, Mandy S. Y. Lung, Wen-Jing Zhao, Qi-Jian Sun
المصدر: Respiratory Physiology & Neurobiology. 178:337-340
مصطلحات موضوعية: Male, Pulmonary and Respiratory Medicine, Serotonin, medicine.medical_specialty, Tyrosine 3-Monooxygenase, Physiology, Presynaptic Terminals, Neuropeptide, Substance P, Biology, law.invention, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Trigeminal Caudal Nucleus, 0302 clinical medicine, Confocal microscopy, law, Internal medicine, medicine, Animals, 030304 developmental biology, Motor Neurons, Nucleus ambiguus, 0303 health sciences, Tyrosine hydroxylase, General Neuroscience, Rats, Endocrinology, chemistry, Synaptophysin, biology.protein, Brainstem, 030217 neurology & neurosurgery
الوصف: Substance P (SP), tyrosine hydroxylase (TH) and serotonin inputs onto laryngeal motoneurons (LMNs) are known to exist, but the distribution of their terminals in the caudal nucleus ambiguus (NA), remains unclear. Using immunofluorescence and confocal microscopy, we assessed simultaneously the distribution of SP, TH, serotonin and synaptophysin immunoreactive (ir) terminals in the caudal NA. SP, TH and serotonin-ir varicosities were considered to represent immunoreactive synapses if, using confocal microscopy, they were co-localized with the presynaptic protein, synaptophysin. Relative to the total number of synapses, we found only a modest number of SP, TH or serotonin-ir synaptic terminals in the caudal NA. The density of SP-ir synaptic terminals was higher than that of TH-ir and serotonin-ir synaptic terminals. Our results suggest that SP, TH, and serotonin-ir inputs may play only a modest role in regulating the activity of LMN. We conclude that SP, TH and serotonin are not always co-localized in terminals forming inputs with LMN and that they arise from separate sub-populations of neurons.
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المصدر: Journal of Clinical Pharmacy and Therapeutics. 33:289-294
مصطلحات موضوعية: Adult, Male, Anti-Inflammatory Agents, Ethyl acetate, Biological Availability, Capsules, High-performance liquid chromatography, Mass Spectrometry, chemistry.chemical_compound, Pharmacokinetics, Liquid chromatography–mass spectrometry, Humans, Pharmacology (medical), Chromatography, High Pressure Liquid, Pharmacology, Detection limit, Chromatography, Half-life, Bioavailability, Therapeutic Equivalency, chemistry, Area Under Curve, Calibration, Glycyrrhetinic Acid, Ammonium acetate, Half-Life
الوصف: OBJECTIVE: To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. METHODS: The GA in plasma was extracted with ethyl acetate, separated on a C(18) column with a mobile phase of methanol (5 mmol/L ammonium acetate)-water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469.5 for GA and m/z 455.6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. RESULTS: The calibration curve was linear over the range of 0.5-200 ng/mL (r = 0.9974). The limit of quantification for GA in plasma was 0.5 ng/mL, the recovery was 76.0-80.0%, and the inter- and intra-day relative standard deviations (RSD) were
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المؤلفون: Ying, Zhang, Shi Gong, Wang, Yu Xia, Ma, Ke Zheng, Shang, Yi Fan, Cheng, Xu, Li, Gui Cai, Ning, Wen Jing, Zhao, Nai Rong, Li
المصدر: Biomedical and environmental sciences : BES. 28(5)
مصطلحات موضوعية: Adult, Male, China, Emergency Medical Services, Adolescent, Respiratory Tract Diseases, Infant, Middle Aged, Young Adult, Cardiovascular Diseases, Air Pollution, Child, Preschool, Humans, Female, Seasons, Cities, Child, Aged
الوصف: To investigate the association between ambient air pollution and hospital emergency admissions in Beijing.In this study, a semi-parametric generalized additive model (GAM) was used to evaluate the specific influences of air pollutants (PM10, SO2, and NO2) on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction.It was found that a 10 μg/m3 increase in concentration of PM10 at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 μg/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 μg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions.This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.
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