50 results on '"Zhilin Wang"'
Search Results
2. Constitutive expression of an A-5 subgroup member in the DREB transcription factor subfamily from Ammopiptanthus mongolicus enhanced abiotic stress tolerance and anthocyanin accumulation in transgenic Arabidopsis.
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Meiyan Ren, Zhilin Wang, Min Xue, Xuefeng Wang, Feng Zhang, Yu Zhang, Wenjun Zhang, and Maoyan Wang
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Medicine ,Science - Abstract
Dehydration-responsive element-binding (DREB) transcription factors (TFs) are key regulators of stress-inducible gene expression in plants. Anthocyanins, an important class of flavonoids, protect plants from reactive oxygen species produced under abiotic stresses. However, regulation of DREBs on anthocyanin accumulation is largely unknown. Here, an A-5 subgroup DREB gene (AmDREB3) isolated from Ammopiptanthus mongolicus, a desert broadleaf shrub with very high tolerance to harsh environments, was characterized in terms of both abiotic stress tolerance and anthocyanin accumulation. AmDREB3 does not contain the transcriptional repression motif EAR, and the protein was located in the nucleus and has transcriptional activation capacity. The transcription of AmDREB3 was differentially induced in the shoots and roots of A. mongolicus seedlings under drought, salt, heat, cold, ultraviolet B, and abscisic acid treatments. Moreover, the transcript levels in twigs, young leaves, and roots were higher than in other organs of A. mongolicus shrubs. Constitutively expressing AmDREB3 improved the tolerance of transgenic Arabidopsis to drought, high salinity and heat, likely by inducing the expression of certain stress-inducible genes. The transgenic Arabidopsis seedlings also exhibited an obvious purple coloration and significant increases in anthocyanin accumulation and/or oxidative stress tolerance under drought, salt, and heat stresses. These results suggest that the AmDREB3 TF may be an important positive regulator of both stress tolerance and anthocyanin accumulation.
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- 2019
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3. Changes in rhizosphere microbial communities in potted cucumber seedlings treated with syringic acid.
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Zhilin Wang, Jianhui Zhang, Fengzhi Wu, and Xingang Zhou
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Medicine ,Science - Abstract
Phytotoxic effects of phenolic compounds have been extensively studied, but less attention has been given to the effects of these compounds on soil microbial communities, which are crucial to the productivity of agricultural systems. Responses of cucumber rhizosphere bacterial and fungal communities to syringic acid (SA), a phenolic compound with autotoxicity to cucumber, were analyzed by high-throughput sequencing of 16S rRNA gene and internal transcribed spacer amplicons. SA at the concentration of 0.1 μmol g-1 soil changed rhizosphere bacterial and fungal community compositions, decreased bacterial community diversity but increased fungal community richness and diversity (P
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- 2018
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4. Non-Heme Iron Absorption and Utilization from Typical Whole Chinese Diets in Young Chinese Urban Men Measured by a Double-Labeled Stable Isotope Technique.
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Lichen Yang, Yuhui Zhang, Jun Wang, Zhengwu Huang, Lingyan Gou, Zhilin Wang, Tongxiang Ren, Jianhua Piao, and Xiaoguang Yang
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Medicine ,Science - Abstract
BACKGROUND:This study was to observe the non-heme iron absorption and biological utilization from typical whole Chinese diets in young Chinese healthy urban men, and to observe if the iron absorption and utilization could be affected by the staple food patterns of Southern and Northern China. MATERIALS AND METHODS:Twenty-two young urban men aged 18-24 years were recruited and randomly assigned to two groups in which the staple food was rice and steamed buns, respectively. Each subject received 3 meals containing approximately 3.25 mg stable 57FeSO4 (the ratio of 57Fe content in breakfast, lunch and dinner was 1:2:2) daily for 2 consecutive days. In addition, approximately 2.4 mg 58FeSO4 was administered intravenously to each subject at 30-60 min after dinner each day. Blood samples were collected from each subject to measure the enrichment of the 57Fe and 58Fe. Fourteen days after the experimental diet, non-heme iron absorption was assessed by measuring 57Fe incorporation into red blood cells, and absorbed iron utilization was determined according to the red blood cell incorporation of intravenously infused 58Fe SO4. RESULTS:Non-heme iron intake values overall, and in the rice and steamed buns groups were 12.8 ±2.1, 11.3±1.3 and 14.3±1.5 mg, respectively; the mean 57Fe absorption rates were 11±7%, 13±7%, and 8±4%, respectively; and the mean infused 58Fe utilization rates were 85±8%, 84±6%, and 85±10%, respectively. There was no significantly difference in the iron intakes, and 57Fe absorption and infused 58Fe utilization rates between rice and steamed buns groups (all P>0.05). CONCLUSION:We present the non-heme iron absorption and utilization rates from typical whole Chinese diets among young Chinese healthy urban men, which was not affected by the representative staple food patterns of Southern and Northern China. This study will provide a basis for the setting of Chinese iron DRIs.
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- 2016
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5. Tetraarsenictetrasulfide and Arsenic Trioxide Exert Synergistic Effects on Induction of Apoptosis and Differentiation in Acute Promyelocytic Leukemia Cells.
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Shuping Wang, Min Zhou, Jian Ouyang, Zhirong Geng, and Zhilin Wang
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Medicine ,Science - Abstract
Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and differentiation of NB4 and primary APL cells. As4S4, acting similarly to As3+, arrested the G1/S transition, induced the accumulation of cellular reactive oxygen species, and promoted apoptosis. Additionally, low concentrations of As4S4 (0.1-0.4 μM) induced differentiation of NB4 and primary APL cells. Compared with the As4S4- or As3+-treated groups, the combination of As4S4 and As3+ obviously promoted apoptosis and differentiation of NB4 and primary APL cells. Mechanistic studies suggested that As4S4 acted synergistically with As3+ to down-regulate Bcl-2 and nuclear factor-κB expression, up-regulate Bax and p53 expression, and induce activation of caspase-12 and caspase-3. Moreover, the combination of low concentrations of As4S4 and As3+ enhanced degradation of the promyelocytic leukemia-retinoic acid receptor α oncoprotein. In summary, As4S4 and As3+ synergistically induce the apoptosis and differentiation of NB4 and primary APL cells.
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- 2015
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6. Effect of proline analogues on activity of human prolyl hydroxylase and the regulation of HIF signal transduction pathway.
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Xiaoyan Ma, Xiaoxin Wang, Jing Cao, Zhirong Geng, and Zhilin Wang
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Medicine ,Science - Abstract
Hypoxia inducible factor 1 (HIF-1) plays a pivotal role in cellular responses to hypoxia. Prolyl hydroxylase 3 (PHD3) degrades HIF-1α under normoxic conditions through the hydroxylation of HIF-1α for proteolysis. Inhibiting PHD3 activity is crucial for up-regulating HIF-1α, thereby acting as a potential target for treating hypoxia-related diseases. In this study, two proline analogues (PA1 and PA2) were screened as PHD3 inhibitors with apparent EC50 values of 1.53 and 3.17 µM respectively, indicating good inhibition potency. Nine proteins, significantly regulated by PA1, were identified using 2-DE coupled with MALDI-TOF/TOF MS. Pyruvate kinase isozymes M1/M2 (PKM) and alpha-enolase 1 (ENO1), which are key modulators of glycolysis, are directly regulated by HIF-1α. Moreover, VEGF, a signal protein stimulating angiogenesis, was strongly promoted by PA1. Our findings suggest that PA1 stabilized HIF-1α as well as up-regulated glycolysis and angiogenesis proteins. Herein, for the first time, we systematically studied proline analogue PA1 as a PHD3 inhibitor, which provides innovative evidence for the treatment of HIF-related diseases.
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- 2014
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7. The functions of crucial cysteine residues in the arsenite methylation catalyzed by recombinant human arsenic (III) methyltransferase.
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Shuping Wang, Zhirong Geng, Nan Shi, Xiangli Li, and Zhilin Wang
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Medicine ,Science - Abstract
Arsenic (III) methyltransferase (AS3MT) is a cysteine (Cys)-rich enzyme that catalyzes the biomethylation of arsenic. To investigate how these crucial Cys residues promote catalysis, we used matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) to analyze Cys residues in recombinant human arsenic (III) methyltransferase (hAS3MT). We detected two disulfide bonds, Cys250-Cys32 and Cys368-Cys369, in hAS3MT. The Cys250-Cys32 disulfide bond was reduced by glutathione (GSH) or other disulfide bond reductants before the enzymatic methylation of arsenite (iAs3+). In addition to exposing residues around the active sites, cleavage of the Cys250-Cys32 pair modulated the conformation of hAS3MT. This adjustment may stabilize the binding of S-Adenosyl-L-methionine (AdoMet) and favor iAs3+ binding to hAS3MT. Additionally, we observed the intermediate of Cys250-S-adenosylhomocysteine (AdoHcy), suggesting that Cys250 is involved in the transmethylation. In recovery experiments, we confirmed that trivalent arsenicals were substrates for hAS3MT, methylation of arsenic occurred on the enzyme, and an intramolecular disulfide bond might be formed after iAs3+ was methylated to dimethylarsinous acid (DMA3+). In this work, we clarified both the functional roles of GSH and the crucial Cys residues in iAs3+ methylation catalyzed by hAS3MT.
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- 2014
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8. Residues in human arsenic (+3 oxidation state) methyltransferase forming potential hydrogen bond network around S-adenosylmethionine.
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Xiangli Li, Jing Cao, Shuping Wang, Zhirong Geng, Xiaoli Song, Xin Hu, and Zhilin Wang
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Medicine ,Science - Abstract
Residues Tyr59, Gly78, Ser79, Met103, Gln107, Ile136 and Glu137 in human arsenic (+3 oxidation state) methyltransferase (hAS3MT) were deduced to form a potential hydrogen bond network around S-adenosylmethionine (SAM) from the sequence alignment between Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase (CmArsM) and hAS3MT. Herein, seven mutants Y59A, G78A, S79A, M103A, Q107A, I136A and E137A were obtained. Their catalytic activities and conformations were characterized and models were built. Y59A and G78A were completely inactive. Only 7.0%, 10.6% and 13.8% inorganic arsenic (iAs) was transformed to monomethylated arsenicals (MMA) when M103A, Q107A and I136A were used as the enzyme. The Vmax (the maximal velocity of the reaction) values of M103A, Q107A, I136A and E137A were decreased to 8%, 22%, 15% and 50% of that of WT-hAS3MT, respectively. The KM(SAM) (the Michaelis constant for SAM) values of mutants M103A, I136A and E137A were 15.7, 8.9 and 5.1 fold higher than that of WT-hAS3MT, respectively, indicating that their affinities for SAM were weakened. The altered microenvironment of SAM and the reduced capacity of binding arsenic deduced from KM(As) (the Michaelis constant for iAs) value probably synergetically reduced the catalytic activity of Q107A. The catalytic activity of S79A was higher than that of WT despite of the higher KM(SAM) , suggesting that Ser79 did not impact the catalytic activity of hAS3MT. In short, residues Tyr59 and Gly78 significantly influenced the catalytic activity of hAS3MT as well as Met103, Ile136 and Glu137 because they were closely associated with SAM-binding, while residue Gln107 did not affect SAM-binding regardless of affecting the catalytic activity of hAS3MT. Modeling and our experimental results suggest that the adenine ring of SAM is sandwiched between Ile136 and Met103, the amide group of SAM is hydrogen bonded to Gly78 in hAS3MT and SAM is bonded to Tyr59 with van der Waals, cation-π and hydrogen bonding contacts.
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- 2013
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9. Identification of the third binding site of arsenic in human arsenic (III) methyltransferase.
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Xiangli Li, Zhirong Geng, Jiayin Chang, Shuping Wang, Xiaoli Song, Xin Hu, and Zhilin Wang
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Medicine ,Science - Abstract
Arsenic (III) methyltransferase (AS3MT) catalyzes the process of arsenic methylation. Each arsenite (iAs(3+)) binds to three cysteine residues, methylarsenite (MMA(3+)) binds to two, and dimethylarsenite (DMA(3+)) binds to one. However, only two As-binding sites (Cys156 and Cys206) have been confirmed on human AS3MT (hAS3MT). The third As-binding site is still undefined. Residue Cys72 in Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase (CmArsM) may be the third As-binding site. The corresponding residue in hAS3MT is Cys61. Functions of Cys32, Cys61, and Cys85 in hAS3MT are unclear though Cys32, Cys61, and Cys85 in rat AS3MT have no effect on the enzyme activity. This is why the functions of Cys32, Cys61, and Cys85 in hAS3MT merit investigation. Here, three mutants were designed, C32S, C61S, and C85S. Their catalytic activities and conformations were determined, and the catalytic capacities of C156S and C206S were studied. Unlike C85S, mutants C32S and C61S were completely inactive in the methylation of iAs(3+) and active in the methylation of MMA(3+). The catalytic activity of C85S was also less pronounced than that of WT-hAS3MT. All these findings suggest that Cys32 and Cys61 markedly influence the catalytic activity of hAS3MT. Cys32 and Cys61 are necessary to the first step of methylation but not to the second. Cys156 and Cys206 are required for both the first and second steps of methylation. The S(C32) is located far from arsenic in the WT-hAS3MT-SAM-As model. The distances between S(C61) and arsenic in WT-hAS3MT-As and WT-hAS3MT-SAM-As models are 7.5 Å and 4.1 Å, respectively. This indicates that SAM-binding to hAS3MT shortens the distance between S(C61) and arsenic and promotes As-binding to hAS3MT. This is consistent with the fact that SAM is the first substrate to bind to hAS3MT and iAs is the second. Model of WT-hAS3MT-SAM-As and the experimental results indicate that Cys61 is the third As-binding site.
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- 2013
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10. CRHCeA→VTA inputs inhibit the positive ensembles to induce negative effect of opiate withdrawal
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Zhilin Wang, Ying Mao, Lan Ma, Changyou Jiang, Guanhong He, Fan Wang, Feifei Wang, Wen-Dong Xu, and Xiao Yang
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business.industry ,Inhibitory postsynaptic potential ,Amygdala ,Ventral tegmental area ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Electrophysiology ,medicine.anatomical_structure ,nervous system ,Opioid ,mental disorders ,Morphine ,medicine ,business ,Molecular Biology ,Psychological repression ,Neuroscience ,psychological phenomena and processes ,Hormone ,medicine.drug - Abstract
Plasticity of neurons in the ventral tegmental area (VTA) is critical for establishment of drug dependence. However, the remodeling of the circuits mediating the transition between positive and negative effect remains unclear. Here, we used neuronal activity-dependent labeling technique to characterize and temporarily control the VTA neuronal ensembles recruited by the initial morphine exposure (morphine-positive ensembles, Mor-Ens). Mor-Ens preferentially projected to NAc, and induced dopamine-dependent positive reinforcement. Electrophysiology and rabies viral tracing revealed the preferential connections between the VTA-projective corticotrophin-releasing hormone (CRH) neurons of central amygdala (CRHCeA→VTA) and Mor-Ens, which was enhanced after escalating morphine exposure and mediated the negative effect during opiate withdrawal. Pharmacologic intervention or CRISPR-mediated repression of CRHR1 in Mor-Ens weakened the inhibitory CRHCeA→VTA inputs, and alleviated the negative effect during opiate withdrawal. These data suggest that neurons encoding opioid reward experience are inhibited by enhanced CRHCeA→VTA inputs induced by chronic morphine exposure, leading to negative effect during opiate withdrawal, and provide new insight into the pathological changes in VTA plasticity after drug abuse and mechanism of opiate dependence.
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- 2021
11. Psychological Resilience of Second-Pregnancy Women in China: A Cross-sectional Study of Influencing Factors
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Junyan Qiu, Xiaohuan Jin, Xinyuan Xu, Lixue Sun, Zexun Xu, Zhilin Wang, and Ling Shan
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China ,Cross-sectional study ,Population ,RT1-120 ,Gravidity ,Nursing ,psychology ,Occupational safety and health ,03 medical and health sciences ,Social support ,resilience, psychological ,0302 clinical medicine ,Rating scale ,Intervention (counseling) ,medicine ,Humans ,030212 general & internal medicine ,Child ,education ,General Nursing ,Pregnancy ,education.field_of_study ,030504 nursing ,General Medicine ,medicine.disease ,Cross-Sectional Studies ,Scale (social sciences) ,factor analysis, statistical ,Female ,Pregnant Women ,pregnancy ,0305 other medical science ,Psychology ,Clinical psychology - Abstract
Purpose The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.
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- 2021
12. The interactions of dopamine D4 receptor and family cohesion or conflict on university students’ prosocial tendency
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Qinyu Ge, Benyu Guo, Yilu Qiu, Weiwei Gu, Zhilin Wang, and Yunqiang Wang
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Multidisciplinary ,Prosocial behavior ,Dopamine ,medicine ,Receptor ,Psychology ,Family cohesion ,Developmental psychology ,medicine.drug - Published
- 2020
13. Targeted copper supplementation oriented theranostic for fluorescence and 19F NMR detection of tumors
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Miaomiao Zhang, Zhilin Wang, Zhirong Geng, Jiao Lu, Zan Li, Zhen Yang, and Taiyu Guo
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chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,Metals and Alloys ,Cancer ,General Chemistry ,Fluorine-19 NMR ,medicine.disease ,Fluorescence ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Apoptosis ,Cancer cell ,Materials Chemistry ,Ceramics and Composites ,Cancer research ,medicine ,Liberation ,Cytotoxicity - Abstract
Alteration of the levels of copper is a promising approach for cancer therapy. Herein, we develop a dual-mode copper vehicle, M985. The biotin-tailed M985 can exert tumor-directed copper supplementation and undergo self-immolative cleavage in living cancerous cells, resulting in the liberation of F542 along with the generation of excess reactive oxygen species. Thus, fluorescence and 19F NMR detection is realized to specifically discriminate cancer cells. F542 acts as a fluorescence reporter and a potent cytotoxic agent, facilitating the visualization of molecular release and distribution, as well as confirming the ER autophagy-induced apoptosis. Therefore, we present a promising dual-mode theranostic M985 for the efficient detection and therapy of cancer.
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- 2020
14. Autophagy in DG engrams mediates Rac1-dependent forgetting via TLR2/4 signals in microglia
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Zhilin Wang, Ruyan Chen, Qing Lin, Yan Jiang, Qiumin Le, Xing Liu, Lan Ma, and Feifei Wang
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Synapse ,medicine.anatomical_structure ,Forgetting ,Microglia ,Dentate gyrus ,Autophagy ,medicine ,RAC1 ,Engram ,Biology ,Optogenetics ,Neuroscience - Abstract
BACKGROUNDEngrams are considered to be substrates for memory storage, and the adaptive plasticity remolding that switch engrams to an inaccessible state cause forgetting. The normal function of engrams is ensured by the crosstalk between neurons and microglia, the major immune cells in the brain implicated in synapse remodeling and memory processing. However, the cellular processes and molecular mediators between engrams and microglia underlying forgetting are poorly understood.METHODSWe utilized doxycycline (Dox)-dependent robust activity marking (RAM) system to label and manipulate DG engrams encoding contexture fear memory in mice. Combining optogenetics, microglia-specific transcriptomics, fluorescence in situ hybridization and spine morphology analysis, we investigated the potential mechanisms of information exchange between engrams and microglia mediating memory forgetting.RESULTSThe expression of Rac1 in dentate gyrus (DG) engrams upregulated memory encoding. Increased Rac1 activity in DG engrams accelerated forgetting, upregulated autophagy influx and the expression of autophagy protein 7 (Atg7). The elevated ATG7 expression in the engrams activated of DG microglia and promoted forgetting. In addition, the Toll-like receptor (TLR) signal in DG microglia was upregulated when overexpressing ATG7 or activating Rac1 in DG engrams, and mediated the ATG7-dependent synapse remodeling and Rac1-dependent forgetting.CONCLUSIONSIn this study, we found that Rac1 increases ATG7-dependent autophagy in DG engrams, which activated microglia via TLR2/4, to promote spine remodeling and forgetting. These results unravel a novel pathway mediating memory forgetting, and provide a potential therapeutic strategy in the treatment of cognitive disorders such as Alzheimer’s disease.
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- 2021
15. Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward
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Cao Liu, Peipei Liu, Changyou Jiang, Guanhong He, Ping Zheng, Feifei Wang, Xueying Wang, Zhilin Wang, Lan Ma, and Qiumin Le
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0301 basic medicine ,endocrine system ,Infralimbic cortex ,Addiction ,Optogenetics ,Neurotransmission ,Inhibitory postsynaptic potential ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Reward ,Interneurons ,medicine ,Molecular Biology ,biology ,Morphine ,Chemistry ,Pyramidal Cells ,Conditioned place preference ,Psychiatry and Mental health ,Electrophysiology ,030104 developmental biology ,medicine.anatomical_structure ,Parvalbumins ,Opioid ,nervous system ,biology.protein ,Neuroscience ,030217 neurology & neurosurgery ,Parvalbumin ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Opioids, such as morphine, are clinic analgesics which induce euphoria. Morphine exposure modifies the excitability and functional interactions between neurons, while the underlying cellular and molecular mechanisms, especially how morphine assembles heterogeneous interneurons (INs) in prelimbic cortex (PrL) to mediate disinhibition and reward, are not clear. Using approaches of optogenetics, electrophysiology, and cell type-specific RNA-seq, we show that morphine attenuates the inhibitory synaptic transmission from parvalbumin+ (PV)-INs onto pyramidal neurons in PrL via μ-opioid receptor (MOR) in PV-INs. Meanwhile, morphine enhances the inhibitory inputs from somatostatin+ (SST)-INs onto PV-INs, and thus disinhibits pyramidal neurons via δ-opioid receptor (DOR)-dependent Rac1 upregulation in SST-INs. We show that MOR in PV-INs is required for morphine-induced behavioral sensitization, while DOR as well as Rac1 activity in SST-INs is required for morphine-induced conditioned place preference and hyper-locomotion. These results reveal that SST- and PV-INs, functioning in PrL as a disinhibitory architecture, are coordinated by morphine via different opioid receptors to disinhibit pyramidal neurons and enhance reward.
- Published
- 2019
16. Sevoflurane pretreatment regulates abnormal expression of MicroRNAs associated with spinal cord ischemia/reperfusion injury in rats
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Fengshou Chen, Xiao-Qian Li, Bo Fang, Zhilin Wang, and Dan Wang
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MAPK/ERK pathway ,medicine.diagnostic_test ,Chemistry ,Kinase ,General Medicine ,Pharmacology ,medicine.disease ,Sevoflurane ,Western blot ,ErbB ,medicine ,Original Article ,Signal transduction ,Protein kinase A ,Reperfusion injury ,medicine.drug - Abstract
Background Spinal cord ischemia/reperfusion injury (SCII) is one of the most serious spinal cord complications that stem from varied spine injuries or thoracoabdominal aortic surgery. Nevertheless, the molecular mechanisms underlying the SCII remain unclear. Methods Male Sprague-Dawley (SD) rats were randomly divided into 5 groups of sham, SCII 24 h, SCII 72 h, sevoflurane preconditioning SCII 24 h (SCII 24 h+sevo), and sevoflurane preconditioning SCII 72 h (SCII 72 h+sevo) group. We then analyzed the expression of differentially expressed micro RNAs (DEmiRNAs) in these groups and their target genes. Functional enrichment analysis of their target genes was further performed using Metascape software. The microRNA-messenger RNA-pathway (miRNA-mRNA-pathway) network and the sevoflurane-miRNA-mRNA-pathway integrative network were further constructed to explore the molecular mechanisms underlying SCII and neuroprotective effects of sevoflurane against SCII. Molecular docking was also performed to evaluate the interactions between hub targets and sevoflurane. Finally, the expression levels of miR-21-5p and its target genes [mitogen-activated protein kinase kinase 3 and protein phosphatase 1 regulatory subunit 3B (MAP2K3 and PPP1R3B)] were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses. Results We found that sevoflurane alters several miRNA expression following SCII at 24 and 72 h after reperfusion. It was shown that miR-221-3p, miR-181a-1-3p, and miR-21-5p were upregulated both at 24 and 72 h in the sevoflurane pre-treatment reperfusion groups. Functional enrichment analysis revealed that target genes for the above co-DEmiRNAs at 24 and 72 h in the SCII group with sevoflurane pretreatment participated in the mitogen-activated protein kinase (MAPK), ErbB, apoptosis, and transforming growth factor-beta (TGF-beta) signaling pathways. Both MAP2K3 and PPP1R3B were found to be common targets for sevoflurane and miRNA-mRNA-pathway (rno-miR-21-5p). It was shown that MAP2K3 regulates the MAPK signaling and the T cell receptor signaling pathways, whereas PPP1R3B regulates the ErbB signaling pathway. Molecular docking further revealed that sevoflurane strongly binds the MAP2K3 and PPP1R3B proteins. Compared to the sham group, SCII induced significant under-expression of miR-21-5p but upregulated PPP1R3B and MAP2K3 proteins; sevoflurane pretreatment increased the expression of miR-21-5p but decreased those of PPP1R3B and MAP2K3 proteins. Conclusions In general, sevoflurane regulates the expression of several miRNAs following SCII. In particular, sevoflurane might protect against SCII via regulating the expression of miR-21-5p, its target genes (MAP2K3 and PPP1R3B), and related signaling pathways.
- Published
- 2020
17. A phenotypic characterization of two isolates of a multidrug - resistant outbreak strain of Mycobacterium tuberculosis with opposite epidemiological fitness
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Zhangyan Dai, Marcelo Abel Soria, Qi Zhang, Angel Cataldi, María Mercedes Bigi, María del Carmen Sasiain, Rosario Durán, Ting Yu, Zhilin Wang, Federico Carlos Blanco, Beatriz López, Viviana Ritacco, Jinlong Bei, Analía Lima, Fabiana Bigi, Silvia de la Barrera, and Zhuang Chen
- Subjects
Proteomics ,0301 basic medicine ,Drug Resistance ,Drug resistance ,Genetic Isolation ,Disease Outbreaks ,stress ,Cell Wall ,Tandem Mass Spectrometry ,Drug Resistance, Multiple, Bacterial ,Tuberculosis, Multidrug-Resistant ,mycolic acids ,Molecular Properties ,biology ,General Medicine ,Hydrogen-Ion Concentration ,Phenotype ,EPIDEMIOLOGICAL ,Mycolic Acids ,Medicine ,purl.org/becyt/ford/3 [https] ,Propiedades Moleculares ,Research Article ,Biological Properties ,Tuberculosis ,Article Subject ,030106 microbiology ,Argentina ,MDR-TB ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,Cell wall ,Mycobacterium tuberculosis ,03 medical and health sciences ,purl.org/becyt/ford/3.3 [https] ,Immune system ,proteomics ,Bacterial Proteins ,medicine ,Resistencia a Medicamentos ,General Immunology and Microbiology ,Aislamiento Genético ,Outbreak ,medicine.disease ,biology.organism_classification ,Multiple drug resistance ,030104 developmental biology ,DevR ,Propiedades Biológicas ,PHENOTYPIC CHARACTERIZATION - Abstract
Tuberculosis (TB) is an infectious disease, caused by Mycobacterium tuberculosis, primarily affecting the lungs. The M. tuberculosis strain of the Haarlem family named M was responsible for a large multidrug-resistant TB (MDR-TB) outbreak in Buenos Aires. This outbreak started in the early 1990s and in the mid 2000s still accounted for 29% of all MDR-TB cases in Argentina. By contrast, a clonal variant of strain M, named 410, has caused a single tuberculosis case since the onset of the outbreak. The molecular bases of the high epidemiological fitness of the M strain remain unclear. To assess its unique molecular properties, herein, we performed a comparative protein and lipid analysis of a representative clone of the M strain (Mp) and the nonprosperous M variant 410. We also evaluated their growth in low pH. The variant 410 had higher levels of latency proteins under standard conditions and delayed growth at low pH, suggesting that it is more sensitive to stress stimuli than Mp. Moreover, Mp showed higher levels of mycolic acids covalently attached to the cell wall and lower accumulation of free mycolic acids in the outer layer than the 410 strain. The low expression of latency proteins together with the reduced content of surface mycolic acids may facilitate Mp to evade the host immune responses. Instituto de Biotecnología Fil: Bei, Jinlong. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Microbiología Agrícola; Argentina Fil: Lima, Analía. Institut Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biológicas Clemente Estable; Uruguay Fil: Zhang, Qi. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina Fil: Yu, Ting. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Wang, Zhilin. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Dai, Zhangyan. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Chen, Zhuang. Guangdong Academy of Agricultural Sciences (GDAAS). AGRO-Biological Gene Research Center; China Fil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Ritacco, Viviana. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina Fil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos; Argentina Fil: Durán, Rosario. Institut Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biológicas Clemente Estable; Uruguay Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
- Published
- 2020
18. Mesorhizobium alexandrii sp. nov., isolated from phycosphere microbiota of PSTs-producing marine dinoflagellate Alexandrium minutum amtk4
- Author
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Xin Zhou, Zhangyan Dai, Zhiwei Jiang, Xi Yang, Zhilin Wang, Zhuang Chen, Bo Dong, Jing Zhang, Jinlong Bei, Zhang Xiaoling, Qiao Yang, Ting Yu, and Lei Wang
- Subjects
0106 biological sciences ,0301 basic medicine ,DNA, Bacterial ,010603 evolutionary biology ,01 natural sciences ,Microbiology ,03 medical and health sciences ,RNA, Ribosomal, 16S ,medicine ,Seawater ,Paralytic shellfish poisoning ,Mesorhizobium amorphae ,Molecular Biology ,Gene ,Phylogeny ,Genetics ,Base Composition ,Phylogenetic tree ,biology ,Strain (chemistry) ,Microbiota ,Fatty Acids ,Dinoflagellate ,Mesorhizobium ,Quinones ,Nucleic Acid Hybridization ,General Medicine ,biology.organism_classification ,medicine.disease ,16S ribosomal RNA ,Bacterial Typing Techniques ,030104 developmental biology ,Genes, Bacterial ,Dinoflagellida - Abstract
An aerobic, Gram-stain-negative, motile and rod-shaped bacterial strain, designated as Z1-4T, was isolated from the phycosphere microbiota of marine dinoflagellate Alexandrium minutum that produces paralytic shellfish poisoning toxins. Phylogenetic analysis based on 16S rRNA gene sequences showed that the new isolate belongs to the genus Mesorhizobium, and it was closely related to Mesorhizobium waimense LMG 28228T and Mesorhizobium amorphae LMG 18977T with both 16S rRNA gene sequence similarities of 97.3%. The values of average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) relatedness between strain Z1-4T and its relatives are both well below the thresholds used for the delineation of a new species. A genome-based phylogenetic tree constructed by up-to-date bacterial core gene set (UBCG) indicates that strain Z1-4T forms an independent branch within the genus Mesorhizobium. The respiratory quinone of strain Z1-4T was Q-10. The major fatty acids were similar to other members of the genus Mesorhizobium containing the summed feature 8, C16:0, C19:0cycloω8c, C17:0 and summed feature 3. The polar lipids are phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminophospholipid, five glycolipids and seven unknown polar lipids. The DNA G + C content was determined to be 62.1 mol % based on its genomic sequence. Combined evidences based on the genotypic, chemotaxonomic and phenotypic characteristics clearly indicates that strain Z1-4T represents a novel species of the genus Mesorhizobium, for which the name Mesorhizobium alexandrii sp. nov. is proposed. The type strain is Z1-4T (= KCTC 72512T = CCTCC AB 2019101T).
- Published
- 2019
19. Iron physiological requirements in Chinese adults assessed by the stable isotope labeling technique
- Author
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Jie Cai, Xiaoguang Yang, Tongxiang Ren, Jun Wang, Zhengwu Huang, Lingyan Gou, Lichen Yang, Yuhui Zhang, Zhilin Wang, and Jianhua Piao
- Subjects
0301 basic medicine ,Trace mineral ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,lcsh:TX341-641 ,Clinical nutrition ,Blood iron ,03 medical and health sciences ,Animal science ,Medicine ,lcsh:RC620-627 ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Isotope ,business.industry ,Research ,Venous blood sample ,Chinese adults ,Iron physiological requirements ,Venous blood ,lcsh:Nutritional diseases. Deficiency diseases ,030104 developmental biology ,Stable Isotope Labeling ,Stable isotope labeling technique ,business ,lcsh:Nutrition. Foods and food supply - Abstract
Background Iron is a kind of essential trace mineral in the human body, while the studies on its physiological requirement are very limited recently, especially in China. And most studies were performed with the radioisotope tracer technique, which was harmful to health. This study aimed to first get the value of iron physiological requirements in Chinese adults assessed by the stable isotope labeling technique. Methods Forty-four eligible young Chinese healthy adults were randomly recruited from the Bethune Military Medical College (Shijiazhuang, Hebei, China) between January 2010 and March 2011, and 19 subjects were included in the final data analysis. After adaptive diets and observation, subjects received 58Fe intravenously. The baseline venous blood sample and general information were collected on day 0. Venous blood samples were also collected on day 14, 30, 60, 100, 120, 150, 240, 330, 425, 515, 605, 767, 1155, respectively. The blood samples were acid digested by a Microwave Digestion System and then analyzed by the MC-ICP-MS and Atomic Absorption Spectroscopy to get the abundance of Fe isotopes and the total iron concentration respectively. The circulation rate (the proportion of blood iron to whole body iron) could be calculated by the intake amount, background content and the peak isotope content. When the abundance changed stably, the iron physiological requirement could be calculated by the iron loss in a period of time. Results The abundance of 58Fe reached its peak on day 14, and changed stably from day 425. The average circulation rate was 84%, with no significance difference between the 2 genders. The mean iron requirement in females was 1101.68 μg/d, and the mean requirement adjusted by body weight was 20.69 μg/kg.d. For males, the mean iron requirement was 959.9 μg/d, and the requirement adjusted by body weight was 14.04 μg/kg.d. Conclusion Our study has obtained the data about the iron physiological requirements of Chinese adults using stable isotope labeling technique, which could provide the basis for adjusting iron DRIs of Chinese people in the future. Trial registration The trial was registered at the Chinese Clinical Trial Registry (No: ChiCTR-TRC-09000581).
- Published
- 2018
20. Dual-modal imaging and excellent anticancer efficiency of cisplatin and doxorubicin loaded NaGdF4:Yb3+/Er3+ nanoparticles
- Author
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Xiaoyan Ma, Zhirong Geng, Zhiyang Zhang, Jiayi Sheng, Zhilin Wang, and Miaomiao Zhang
- Subjects
Cisplatin ,Sodium polyacrylate ,Hydrogen bond ,General Chemical Engineering ,Nanoparticle ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Transmission electron microscopy ,In vivo ,Drug delivery ,medicine ,Doxorubicin ,0210 nano-technology ,Nuclear chemistry ,medicine.drug - Abstract
NaGdF4:Yb3+/Er3+ nanoparticles were synthesized via a modified hydrothermal route. The dependence of structure and morphology on the dosage of sodium polyacrylate was studied by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The as-prepared nanoparticles could be used for T2 weighted magnetic resonance imaging due to the paramagnetism of Gd3+. cis-dichlorodiamineplatinum (CDDP) could be loaded onto NaGdF4:Yb3+/Er3+ nanoparticles through binding carboxyl in the form of Pt–O bonds, and doxorubicin (DOX) could be loaded via hydrogen bonding. DOX could also be loaded onto the NaGdF4–CDDP composite in the same manner, and the loading efficiency of both drugs remained unchanged. Three as-prepared drug delivery systems were used for tumor inhibition both in vitro and in vivo, and the results indicated that NaGdF4–CDDP–DOX displayed the greatest inhibitory capacity.
- Published
- 2018
21. Molecular visualizing and quantifying immune-associated peroxynitrite fluxes in phagocytes and mouse inflammation model
- Author
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Chunxia Chen, Zhilin Wang, Bing-Huan Huang, Zan Li, Jiayin Chang, Shihai Yan, Zhirong Geng, and Chen Chen
- Subjects
inorganic chemicals ,Phagocyte ,Biomedical Engineering ,Biophysics ,Inflammation ,Biosensing Techniques ,Biology ,010402 general chemistry ,01 natural sciences ,Flow cytometry ,Mice ,chemistry.chemical_compound ,Immune system ,In vivo ,Peroxynitrous Acid ,Electrochemistry ,medicine ,Animals ,Phagosome ,Phagocytes ,medicine.diagnostic_test ,010405 organic chemistry ,General Medicine ,In vitro ,0104 chemical sciences ,Disease Models, Animal ,medicine.anatomical_structure ,Biochemistry ,chemistry ,cardiovascular system ,medicine.symptom ,Peroxynitrite ,Biotechnology - Abstract
Reactions of peroxynitrite (ONOO − ) with biomolecules can lead to cytotoxic and cytoprotective events. Due to the difficulty of directly and unambiguously measuring its levels, most of the beneficial effects associated with ONOO − in vivo remain controversial or poorly characterized. Recently, optical imaging has served as a powerful noninvasive approach to studying ONOO − in living systems. However, ratiometric probes for ONOO − are currently lacking. Herein, we report the design, synthesis, and biological evaluation of F 482 , a novel fluorescence indicator that relies on ONOO − -induced diene oxidation. The remarkable sensitivity, selectivity, and photostability of F 482 enabled us to visualize basal ONOO − in immune-stimulated phagocyte cells and quantify its generation in phagosomes by high-throughput flow cytometry analysis. With the aid of in vivo ONOO − imaging in a mouse inflammation model assisted by F 482 , we envision that F 482 will find widespread applications in the study of the ONOO − biology associated with physiological and pathological processes in vitro and in vivo.
- Published
- 2017
22. Changes in the first postoperative night bispectral index of patients after thyroidectomy with different types of primary anesthetic management: a randomized controlled trial
- Author
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Feng Jin, Huang-wei Lu, Wen-Fei Tan, Zhilin Wang, and Hong Ma
- Subjects
Adult ,Male ,Methyl Ethers ,China ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Health Informatics ,Critical Care and Intensive Care Medicine ,Sevoflurane ,law.invention ,Young Adult ,03 medical and health sciences ,Consciousness Monitors ,0302 clinical medicine ,Randomized controlled trial ,030202 anesthesiology ,law ,Anesthesiology ,medicine ,Humans ,Single-Blind Method ,Postoperative Period ,Young adult ,Propofol ,Aged ,business.industry ,Thyroidectomy ,Electroencephalography ,030208 emergency & critical care medicine ,Middle Aged ,Surgery ,Anesthesiology and Pain Medicine ,Anesthesia ,Bispectral index ,Anesthetics, Inhalation ,Anesthetic ,Female ,Sleep ,business ,Anesthetics, Intravenous ,medicine.drug - Abstract
Despite major advances in anesthesia management and developments in anesthetic agents, postoperative sleep disturbances remain dissatisfactory for many patients. We hypothesized that propofol might have a subtle influence on sleep after thyroidectomy compared to sevoflurane. A randomized, single-blinded, controlled trial was conducted at the First Hospital of China Medical University from October 2014 to October 2015. One hundred and twenty-four patients undergoing thyroidectomy were enrolled and received sevoflurane (sevoflurane group) or propofol (propofol group) as anesthesia maintenance. Major assessments were made during the operation (different types of anesthetic management) and on the first postoperative night (sleep status). The primary outcome was postoperative sleep status, measured by the BIS-Vista monitor on the first night after surgery between propofol and sevoflurane groups. A total of 105 patients (79 women, 26 men; mean age 49 years; range 18-65 years) were included in the final study sample. All patients in both groups showed one of the five sleep patterns classified by this trial. The BIS-area under the curve was decreased, the sleep efficiency index was significantly increased, and the durations of postoperative sleep and sleep stage N3 were increased by 110.5 and 36.5 min per patient, respectively, in the propofol compared to the sevoflurane group. Propofol might preserve sleep time immediately after thyroidectomy. Clinical Trials.gov identifier: NCT 02146976.
- Published
- 2017
23. Retrieval-Driven Hippocampal NPTX2 Plasticity Facilitates the Extinction of Cocaine-Associated Context Memory
- Author
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Xueying Wang, Zhilin Wang, Tao Jin, Feifei Wang, Cao Liu, Qiumin Le, and Lan Ma
- Subjects
0301 basic medicine ,Context-dependent memory ,Biology ,Hippocampal formation ,medicine.disease ,Hippocampus ,Conditioned place preference ,Extinction, Psychological ,03 medical and health sciences ,Electrophysiology ,Cocaine-Related Disorders ,030104 developmental biology ,0302 clinical medicine ,Downregulation and upregulation ,Cocaine ,Memory ,Extinction (neurology) ,Translational regulation ,medicine ,Humans ,Receptors, AMPA ,Signal transduction ,Neuroscience ,030217 neurology & neurosurgery ,Biological Psychiatry - Abstract
Background Postretrieval extinction attenuates the pathological memory associated with psychiatric states such as drug addiction in both humans and rodents. The extinction of a learned response requires gene transcription and protein synthesis after memory retrieval in a time-dependent manner, yet the precise physiological basis after retrieval to allow extinction to neutralize a learned behavior is not fully understood. Methods In a cocaine conditioned place preference paradigm, we used a ribosomal tagging strategy to measure the translational state of hippocampal pyramidal neurons after the retrieval of cocaine-associated context memory. Using approaches of electrophysiology, neuronal tracing, and a doxycycline-dependent robust activity marking system, we investigated the cellular and molecular basis of retrieval-induced plasticity that facilitated the extinction. Results Bioinformatics analysis discovered the specific translational regulation of signaling pathways by retrieval and revealed Nptx2 as the hub gene. Manipulating Nptx2 in dorsal hippocampus bidirectionally regulated the extinction of cocaine-associated context memory as well as the retrieval-driven synaptic remodeling. The pentraxin (PTX) domain of NPTX2 recruited GluA1-AMPA receptors and enhanced the extinction and excitatory synaptic transmission that was prevented by overexpressing carboxyl cytoplasmic tail of GluA1. Furthermore, Nptx2 in retrieval-activated neurons was required for the extinction. Conclusions The retrieval-driven upregulation of Nptx2 contributes to the synaptic remodeling in dorsal hippocampus and facilitates the extinction of cocaine-associated context memory, indicating a potential target for the treatment of cue-induced cocaine seeking.
- Published
- 2019
24. Constitutive expression of an A-5 subgroup member in the DREB transcription factor subfamily from Ammopiptanthus mongolicus enhancedabiotic stress tolerance and anthocyanin accumulation in transgenic Arabidopsis
- Author
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Maoyan Wang, Feng Zhang, Wenjun Zhang, Xue-Feng Wang, Zhilin Wang, Meiyan Ren, Min Xue, and Yu Zhang
- Subjects
Leaves ,Arabidopsis ,Intracellular Space ,Gene Expression ,Artificial Gene Amplification and Extension ,Plant Science ,Genetically modified crops ,Genetically Modified Plants ,Polymerase Chain Reaction ,Anthocyanins ,chemistry.chemical_compound ,Plant Resistance to Abiotic Stress ,Gene expression ,Promoter Regions, Genetic ,Abscisic acid ,Plant Proteins ,Abiotic component ,Multidisciplinary ,Ecology ,biology ,Genetically Modified Organisms ,Physics ,Plant Anatomy ,Eukaryota ,Classical Mechanics ,food and beverages ,Fabaceae ,Plants ,Plants, Genetically Modified ,Protein Transport ,Experimental Organism Systems ,Plant Physiology ,Physical Sciences ,Engineering and Technology ,Mechanical Stress ,Medicine ,Genetic Engineering ,Research Article ,Biotechnology ,Transcriptional Activation ,Drought Adaptation ,Arabidopsis Thaliana ,Science ,Bioengineering ,Brassica ,Research and Analysis Methods ,Model Organisms ,Plant and Algal Models ,Stress, Physiological ,Plant-Environment Interactions ,Botany ,Plant Defenses ,Amino Acid Sequence ,Molecular Biology Techniques ,Molecular Biology ,Transcription factor ,Abiotic stress ,Plant Ecology ,Ecology and Environmental Sciences ,fungi ,Organisms ,Biology and Life Sciences ,Correction ,Plant Pathology ,biology.organism_classification ,Thermal Stresses ,chemistry ,Seedlings ,Anthocyanin ,Animal Studies ,Plant Biotechnology ,Transcription Factors - Abstract
Dehydration-responsive element-binding (DREB) transcription factors (TFs) are key regulators of stress-inducible gene expression in plants. Anthocyanins, an important class of flavonoids, protect plants from reactive oxygen species produced under abiotic stresses. However, regulation of DREBs on anthocyanin accumulation is largely unknown. Here, an A-5 subgroup DREB gene (AmDREB3) isolated from Ammopiptanthus mongolicus, a desert broadleaf shrub with very high tolerance to harsh environments, was characterized in terms of both abiotic stress tolerance and anthocyanin accumulation. AmDREB3 does not contain the transcriptional repression motif EAR, and the protein was located in the nucleus and has transcriptional activation capacity. The transcription of AmDREB3 was differentially induced in the shoots and roots of A. mongolicus seedlings under drought, salt, heat, cold, ultraviolet B, and abscisic acid treatments. Moreover, the transcript levels in twigs, young leaves, and roots were higher than in other organs of A. mongolicus shrubs. Constitutively expressing AmDREB3 improved the tolerance of transgenic Arabidopsis to drought, high salinity and heat, likely by inducing the expression of certain stress-inducible genes. The transgenic Arabidopsis seedlings also exhibited an obvious purple coloration and significant increases in anthocyanin accumulation and/or oxidative stress tolerance under drought, salt, and heat stresses. These results suggest that the AmDREB3 TF may be an important positive regulator of both stress tolerance and anthocyanin accumulation.
- Published
- 2019
25. HIF/Ca2+/NO/ROS is critical in roxadustat treating bone fracture by stimulating the proliferation and migration of BMSCs
- Author
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Shuang Qiu, Zhirong Geng, Chunxia Chen, Zhilin Wang, and Shihai Yan
- Subjects
0301 basic medicine ,Femur fracture ,Chemistry ,General Medicine ,Bone healing ,Bone fracture ,Femoral fracture ,medicine.disease ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,stomatognathic system ,Downregulation and upregulation ,In vivo ,medicine ,Cancer research ,CD90 ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Aims Fracture site is regionally hypoxic resulting from vasculature disruption. HIF-1αplays an essential role in fracture repair. This study aims to investigate the influence of FG4592 on the femur fracture of SD rats and the proliferation, migration of BMSCs. Materials and methods After the femoral fracture model was established, computed tomography imaging and histological analyses were used to quantify bone healing and the expression of CD90, HIF-1α, VEGF were observed by means of immunohistochemistry method on Day 10 and Day 20. In addition, CCK-8 assay, transwell, flow cytometric analysis, laser confocal microscopy assay, western blot and rT-PCR were performed to text the proliferation and migration of BMSCs using FG4592. Key findings In vivo, FG4592 facilitated the repair of bone fracture by increasing the number of BMSCs and cartilage formation. In vitro, FG4592 markedly improved the proliferation, migration of BMSCs via upregulation of intracellular Ca2+, NO and concomitant decrease of ROS. Gene silencing of HIF-1α resulted in the opposite phenomenon in BMSCs with the treatment of FG4592. Significance The transplantation of BMSCs is the most promising candidate for the treatment of fracture non-union. We illustrated that FG4592 promoted the proliferation, migration of BMSCs via the HIF/Ca2+/NO/ROS pathway and further accelerated fracture healing. These results provide a deeper understanding for the mechanism of HIF in promoting fracture healing.
- Published
- 2021
26. Hypoxic preconditioning increases the protective effect of bone marrow mesenchymal stem cells on spinal cord ischemia/reperfusion injury
- Author
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Zhilin Wang, Dong Zhang, Bo Fang, Hong Ma, and Zhibin Tan
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Pathology ,Apoptosis ,Cell Separation ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Hypoxia ,Ischemic Preconditioning ,Cells, Cultured ,Evans Blue ,hemic and immune systems ,Articles ,Flow Cytometry ,Neuroprotective Agents ,medicine.anatomical_structure ,Spinal Cord ,Oncology ,spinal cord ischemia/reperfusion injury ,Reperfusion Injury ,Molecular Medicine ,medicine.symptom ,medicine.medical_specialty ,Mesenchymal Stem Cell Transplantation ,03 medical and health sciences ,stomatognathic system ,Genetics ,medicine ,Animals ,Molecular Biology ,hypoxia-inducible factor 1α ,Spinal Cord Ischemia ,business.industry ,bone marrow mesenchymal stem cells ,Mesenchymal Stem Cells ,Hypoxia (medical) ,Hypoxia-Inducible Factor 1, alpha Subunit ,Spinal cord ,medicine.disease ,Transplantation ,030104 developmental biology ,chemistry ,Terminal deoxynucleotidyl transferase ,Ischemic preconditioning ,business ,Reperfusion injury ,hypoxic preconditioning ,030217 neurology & neurosurgery - Abstract
Transplantation of bone marrow mesenchymal stem cells (BMSCs) protect against spinal cord ischemia/reperfusion injury (SCIRI). However, a large number of transplanted BMSCs often undergo apoptosis, which severely affects the treatment outcome. Previous studies have demonstrated that hypoxic preconditioning effectively increases the survival rate of BMSCs following transplantation, and increases their protective effect on injured tissues. However, there have been few reports regarding roles of hypoxic preconditioning in SCIRI. The present study isolated rat BMSCs and separately transplanted hypoxia‑ and non‑hypoxia‑preconditioned BMSCs into the spinal cord tissues of rats with SCIRI. The role of hypoxic preconditioning in the promotion of the protective effect of BMSCs on SCIRI was investigated using neurological function scores, Evans blue staining, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. In addition, reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the expression levels of hypoxia‑inducible factor 1α (HIF‑1α), and to investigate its possible underlying mechanism of action. The results indicated that hypoxic preconditioning effectively increased the protective effects of BMSCs on neurological function, blood spinal cord barrier and tissue damage following SCIRI, and inhibited apoptosis. Furthermore, hypoxic preconditioned BMSCs upregulated the expression of HIF‑1α in spinal cord tissues. Therefore, hypoxic preconditioning effectively increased the protective effect of BMSCs on SCIRI and may be associated with upregulation of the expression of HIF‑1α. Hypoxic preconditioning may serve as an effective means of increasing the protective effect of BMSCs on SCIRI.
- Published
- 2016
27. Analgesic effect of perioperative ketamine for total hip arthroplasties and total knee arthroplasties
- Author
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Zhong Yang, Peng Wang, Zhipeng Cao, Zhilin Wang, and Shimin Shan
- Subjects
Visual Analog Scale ,ketamine ,Visual analogue scale ,Arthroplasty, Replacement, Hip ,Sedation ,Analgesic ,Cochrane Library ,Perioperative Care ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,total knee arthroplasties ,medicine ,Humans ,Ketamine ,030212 general & internal medicine ,Arthroplasty, Replacement, Knee ,Analgesics ,Pain, Postoperative ,total hip arthroplasties ,Morphine ,business.industry ,analgesia ,General Medicine ,Perioperative ,Analgesics, Opioid ,meta-analysis ,030220 oncology & carcinogenesis ,Anesthesia ,medicine.symptom ,business ,Systematic Review and Meta-Analysis ,Postoperative nausea and vomiting ,Research Article ,medicine.drug - Abstract
Background: Total hip arthroplasties (THA) and total knee arthroplasties (TKA) are always associated with a frequent incidence of postoperative pain. Effective pain management after surgery is quite essential for surgeons and patients. The purpose of the present meta-analysis is to evaluate the analgesic effect of perioperative ketamine after THA and TKA. Methods: Seven online databases, Embase, Cochrane Library, Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and Wanfang Data were searched for the related randomized controlled trials (RCT) by August 15, 2019. The qualities of the included studies were assessed based on the Cochrane Handbook for Systematic Reviews of Interventions 5.0. The visual analog scale (VAS), morphine equivalent consumption, and the side effects were used to evaluate the postoperative analgesic effect of ketamine by meta-analysis, which was performed by Review Manager version 5.3 software. Results: The VAS scores at 6 hours, 12 hours, 24 hours, and 48 hours after surgery were statistically lower in the ketamine group. The morphine equivalent consumptions in 24 hours and 48 hours after surgery were also significantly lower in the ketamine group. For the side effects, no statistical differences in odds ratio (OR) of sedation, dizziness, hallucination, sweating, pruritus, urinary retention, constipation, version trouble, nightmares, and delirium were observed between the ketamine group and the control group. But postoperative nausea and vomiting (PONV) showed lower OR in the ketamine group. Conclusion: The present meta-analysis demonstrated perioperative ketamine could be used as a safe and effective analgesic agent for THA and TKA.
- Published
- 2020
28. Mn-TAT PTD-Ngb ameliorates inflammation through the elimination of damaged mitochondria and the activation of Nrf2-antioxidant signaling pathway
- Author
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Zhirong Geng, Xuehui Hao, Ruirui Yang, Zhilin Wang, and Cui Zhang
- Subjects
0301 basic medicine ,NF-E2-Related Factor 2 ,Inflammation ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Cell Line ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Protein kinase A ,Pharmacology ,Manganese ,Chemistry ,Pyroptosis ,Inflammasome ,Recombinant Proteins ,Mitochondria ,Cell biology ,Oxidative Stress ,030104 developmental biology ,030220 oncology & carcinogenesis ,Gene Products, tat ,Inflammation Mediators ,Signal transduction ,medicine.symptom ,Oxidative stress ,Signal Transduction ,medicine.drug - Abstract
Inflammation, mitochondrial dysfunction and oxidative stress are closely associated with neurological diseases. In this study, Mn-TAT PTD-Ngb, a novel artificial recombinant protein, exerted inhibitory effects on the inflammatory response and inflammasome activation. During the lipopolysaccharide (LPS)-induced inflammatory response, Mn-TAT PTD-Ngb suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and the release of proinflammatory cytokines and attenuated the phosphorylation of mitogen-activated protein kinase (MAPK). Furthermore, the recombinant protein blocked reactive oxygen species (ROS) production, abated mitochondrial dysfunction and significantly suppressed the assembly of the inflammasome, which led to the overproduction of proinflammatory cytokines IL-1β and IL-18. Mn-TAT PTD-Ngb increased the level of nuclear factor-erythroid 2 -related factor 2 (Nrf2), which protected against oxidative stress and improved pyroptosis. Mn-TAT PTD-Ngb might be a promising drug for curing neurological diseases.
- Published
- 2020
29. Proteomic alteration of porcine intestinal epithelial cells after pretreatment with Lactobacillus plantarum followed by infection with enterotoxigenic Escherichia coli F4
- Author
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Jinling Ye, Bai Yinshan, Yantao Lv, Zhuang Chen, Cui Zhu, Jun Yang, Zongyong Jiang, and Zhilin Wang
- Subjects
Proteomics ,MAPK/ERK pathway ,Proteome ,Cell division ,Swine ,040301 veterinary sciences ,Immunology ,Biology ,medicine.disease_cause ,Bacterial Adhesion ,Cell Line ,Microbiology ,0403 veterinary science ,03 medical and health sciences ,fluids and secretions ,Enterotoxigenic Escherichia coli ,medicine ,Animals ,Intestinal Mucosa ,KEGG ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Swine Diseases ,0303 health sciences ,General Veterinary ,Proteins ,Epithelial Cells ,04 agricultural and veterinary sciences ,Metabolism ,bacterial infections and mycoses ,biology.organism_classification ,Blot ,Lactobacillus plantarum - Abstract
Enterotoxigenic Escherichia coli (ETEC) F4 causes diarrhea in infants and weaned piglets. The technique of isobaric tags for relative and absolute quantitation (iTRAQ) was used in this study to determine the differentially expressed proteins in porcine intestinal epithelial cells (IPEC-J2) after pretreatment with Lactobacillus plantarum (LP) followed by challenge with ETEC F4. A total of 4771 proteins were identified in IPEC-J2 cells, with 90, 105, and 134 differentially expressed proteins in cells exposed to ETEC, LP, and LP + ETEC, respectively. The COG analysis divided the identified proteins into 20 categories. The GO and KEGG annotation indicated that most of the differentially expressed proteins were enriched in various biological metabolism including cell cycle control, cell division and differentiation. Additionally, western blotting analyses confirmed the reduced abundance of selected proteins of the mTOR and MAPK signal pathways affected by ETEC F4. Moreover, LP pretreatment increased JNK activation in IPEC-J2 cells infected with ETEC F4. These results may provide further insights into the mechanisms involved in the interaction between ETEC F4 and intestinal epithelial cells, and broaden the understanding of the protective effects of LP in alleviating ETEC-provoked diarrhea of piglets.
- Published
- 2020
30. ITRAQ-based quantitative proteomic analysis of MG63 in response to HIF-1α inducers
- Author
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Zhirong Geng, Chunxia Chen, Zhilin Wang, and Xuehui Hao
- Subjects
Proteomics ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,Biophysics ,Regulator ,Biochemistry ,03 medical and health sciences ,Downregulation and upregulation ,Western blot ,Ca2+/calmodulin-dependent protein kinase ,Gene expression ,medicine ,Humans ,Hypoxia ,Bone growth ,030102 biochemistry & molecular biology ,medicine.diagnostic_test ,Chemistry ,NF-kappa B ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Cell biology ,030104 developmental biology ,Apoptosis ,Intracellular ,Signal Transduction - Abstract
Non-healing fractures constitute a serious clinical problem. HIF-1α is a crucial regulator in response to hypoxia and is proven to be pivotal in bone growth; however, the mechanism still needs further research. In this study, iTRAQ was used to study the effects of two HIF-1α inducers on the expression of proteins in MG63 cells. A total of 841 proteins were significantly changed after treatment with HIF-1α inducers. Among these, 12 proteins were functionally involved in the HIF-1 and VEGF signaling pathways. We then studied the protein and gene expression of the twelve proteins by western blot and RT-PCR, respectively. The results confirmed that VEGF, TFRC, ERK1/2, iNOS, GLUT1, ALDOA, ENO1 and IP3R1 were markedly upregulated, while NF-κB, RCN1, PLCγ1 and CaMKII were significantly downregulated upon treatment with HIF-1α inducers. Meanwhile, the intracellular levels of Ca2+, NO and ROS were closely related and significantly changed. Up-regulation of HIF can maintain high levels of Ca2+ and NO while reducing ROS and protect cells from apoptosis induced by low serum. This study presents a new way to study the regulation of HIF on bone growth by investigating the Ca2+, NO and ROS levels. SIGNIFCANCE: We found that the regulation of Ca2+ and NO proteins are tightly associated with HIF pathway using iTRAQ method. Furthermore, the concentration of Ca2+, NO and ROS are closely related in low serum cultured cells. Up-regulation of HIF pathway can maintain high levels of Ca2+ and NO while reducing ROS damage.
- Published
- 2020
31. Upregulation of miR-199a-5p Protects Spinal Cord Against Ischemia/Reperfusion-Induced Injury via Downregulation of ECE1 in Rat
- Author
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Fengshou Chen, Bo Fang, Huang-Wei Lv, Yanhua Jiang, Ning Bao, Hong Ma, and Zhilin Wang
- Subjects
0301 basic medicine ,Transcriptional Activation ,Pathology ,medicine.medical_specialty ,Cord ,Down-Regulation ,Apoptosis ,Endothelin-Converting Enzymes ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Gene silencing ,Animals ,Spinal cord injury ,Spinal Cord Injuries ,Evans Blue ,Neurons ,TUNEL assay ,business.industry ,Cell Biology ,General Medicine ,medicine.disease ,Spinal cord ,Up-Regulation ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Spinal Cord ,Reperfusion Injury ,Neuron ,business ,030217 neurology & neurosurgery ,Immunostaining - Abstract
Ischemia-reperfusion (I/R)-induced spinal cord injury can cause apoptotic damage and subsequently act as a blood-spinal cord barrier damage. MicroRNAs (miRNAs) contributed to the process of I/R injury by regulating their target mRNAs. miR-199a-5p is involved in brain and heart I/R injury; however, its function in the spinal cord is not yet completely clarified. In this study, we investigated the role of miR-199a-5p on spinal cord I/R via the endothelin-converting enzyme 1, especially the apoptosis pathway. In the current study, the rat spinal cord I/R injury model was established, and the Basso Beattie Bresnahan scoring, Evans blue staining, HE staining, and TUNEL assay were used to assess the I/R-induced spinal cord injury. The differentially expressed miRNAs were screened using microarray. miR-199a-5p was selected by unsupervised hierarchical clustering analysis. The dual-luciferase reporter assay was used for detecting the regulatory effects of miR-199a-5p on ECE1. In addition, neuron expression was detected by immunostaining assay, while the expressions of p-ERK, ERK, p-JNK, JNK, caspase-9, Bcl-2, and ECE1 were evaluated by Western blot. The results indicated the successful establishment of the I/R-induced spinal cord injury model; the I/R induced the damage to the lower limb motor. Furthermore, 18 differentially expressed miRNAs were detected in the I/R group compared to the sham group, and miR-199a-5p protected the rat spinal cord injury after I/R. Moreover, miR-199a-5p negatively regulated ECE1, and silencing the ECE1 gene also protected the rat spinal cord injury after I/R. miR-199a-5p or silencing of ECE1 also regulated the expressions of caspase-9, Bcl-2, p-JNK, p-ERK, and ECE1 in rat spinal cord injury after I/R. Therefore, we demonstrated that miR-199a-5p might protect the spinal cord against I/R-induced injury by negatively regulating the ECE1, which could aid in developing new therapeutic strategies for I/R-induced spinal cord injury.
- Published
- 2017
32. Dual-target cancer theranostic for glutathione S-transferase and hypoxia-inducible factor-1α inhibition
- Author
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Zan Li, Zhilin Wang, Bing-Huan Huang, Chunxia Chen, Zhirong Geng, Jie Ding, and Jiayin Chang
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,Theranostic Nanomedicine ,Antineoplastic Agents ,Apoptosis ,Catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Materials Chemistry ,medicine ,Autophagy ,Animals ,Humans ,Prodrugs ,Mice, Inbred BALB C ,Oxadiazoles ,biology ,Chemistry ,Liver Neoplasms ,Metals and Alloys ,Cancer ,General Chemistry ,Glutathione ,Intracellular Membranes ,medicine.disease ,Hypoxia-Inducible Factor 1, alpha Subunit ,Molecular biology ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,030104 developmental biology ,Glutathione S-transferase ,Hypoxia-inducible factors ,Glutathione S-Transferase pi ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Ceramics and Composites ,Cancer research ,biology.protein ,Female ,Lysosomes ,Neoplasm Transplantation - Abstract
We developed a dual-target theranostic F671, which could exhibit synergetic anticancer effects for inhibiting the activities of glutathione S-transferase and the accumulation of hypoxia inducible factor-1α. F671 undergoes self-immolative cleavage when exposed to GSTP1-1 in live cancer cells, facilitating the visualization of molecule release and distribution, as well as confirming the autophagy-induced apoptosis.
- Published
- 2017
33. Inhibitory mechanism of dimercaptopropanesulfonic acid (DMPS) in the cellular biomethylation of arsenic
- Author
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Zhilin Wang, Zhirong Geng, Xiangli Li, Nan Shi, Xin Hu, and Shuping Wang
- Subjects
inorganic chemicals ,Methyltransferase ,Cell Survival ,Stereochemistry ,Antidotes ,Blotting, Western ,Arsenic biochemistry ,Gene Expression ,chemistry.chemical_element ,Arsenic poisoning ,Apoptosis ,Methylation ,Biochemistry ,Arsenic ,chemistry.chemical_compound ,Arsenic Poisoning ,Organometallic Compounds ,medicine ,Humans ,Arsenite ,chemistry.chemical_classification ,Reactive oxygen species ,Dose-Response Relationship, Drug ,integumentary system ,Reverse Transcriptase Polymerase Chain Reaction ,Unithiol ,Hep G2 Cells ,Methyltransferases ,General Medicine ,Metabolism ,medicine.disease ,chemistry ,Reactive Oxygen Species - Abstract
Dimercaptopropanesulfonic acid (DMPS) has been approved for the treatment of arsenic poisoning through promoting arsenic excretion and modulating arsenic species. To clarify how DMPS regulates the excretion of arsenic species, we investigated the effects of DMPS on the biomethylation of arsenite (As(3+)) in HepG2 cells. In the experiments, we found that DMPS at low concentrations dramatically decreased the content of arsenic in HepG2 cells and inhibited the cellular methylation of As(3+). Three aspects, the expression of human arsenic (III) methyltransferase (hAS3MT), the accumulation of cellular reactive oxygen species (ROS) and the in vitro enzymatic methylation of arsenic, were considered to explain the reasons for the inhibition of DMPS in arsenic metabolism. The results suggested that DMPS competitively coordinated with As(3+) and monomethylarsonous acid (MMA(3+)) to inhibit the up-regulation of arsenic on the expression of hAS3MT and block arsenic involving in the enzymatic methylation. Moreover, DMPS eliminated arsenic-induced accumulation of ROS, which might contribute to the antidotal effects of DMPS on arsenic posing.
- Published
- 2014
34. Numerical simulation study on the influence of incident position on erosion characteristics of gas-particle two-phase flow in 90° elbow
- Author
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Luo Peng, Zhilin Wang, Luo Songyang, Huang Shiwei, and Song Xiaoqin
- Subjects
musculoskeletal diseases ,lcsh:Mechanical engineering and machinery ,Elbow ,02 engineering and technology ,Computational fluid dynamics ,01 natural sciences ,010305 fluids & plasmas ,0203 mechanical engineering ,Natural gas ,0103 physical sciences ,medicine ,lcsh:TJ1-1570 ,Simulation ,Computer simulation ,business.industry ,Mechanical Engineering ,Mechanics ,musculoskeletal system ,Collision ,body regions ,020303 mechanical engineering & transports ,medicine.anatomical_structure ,Erosion ,Particle ,Two-phase flow ,business ,Geology - Abstract
In gas gathering pipeline system, 90° elbow suffers constant and severe collision of gas-carrying particles, which causes serious erosion on the inner wall. In this study, models of standard elbows (carbon steel with 210 GPa in elasticity modulus and 8300 kg/m 3 in density) whose diameter varies from 65 to 200 mm with curvature ratio 1.5 are established to predict erosion rate causes by silica sand (100 μm in diameter, 1550 kg/m 3 in bulk density) under gas gathering operating conditions (5.0 MPa, 10 m/s). Unlike most of the previous studies which only focus on erosion result on the wall, in this article, author extracts sample particles as research objects and studies the motion of every single particle. It has been found that there are three typical types of particle motion patterns in the elbow, and a part of sand particles released from lower area of incident plane will not even cause erosion.
- Published
- 2017
35. Water-Soluble Conjugated Polymer as a Fluorescent Probe for Monitoring Adenosine Triphosphate Level Fluctuation in Cell Membranes during Cell Apoptosis and in Vivo
- Author
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Zhirong Geng, Shihai Yan, Zan Li, Zhilin Wang, Jun Cai, and Bing-Huan Huang
- Subjects
Male ,Polymers ,Transplantation, Heterologous ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Analytical Chemistry ,Cell membrane ,chemistry.chemical_compound ,Mice ,Adenosine Triphosphate ,Limit of Detection ,Cell Line, Tumor ,Neoplasms ,medicine ,Fluorescence microscope ,Animals ,Humans ,Fluorescent Dyes ,Cell Membrane ,Optical Imaging ,Water ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Transplantation ,medicine.anatomical_structure ,Membrane ,Biochemistry ,chemistry ,Microscopy, Fluorescence ,Solubility ,Cell culture ,Cytoplasm ,Biophysics ,Cisplatin ,0210 nano-technology ,Energy source ,Adenosine triphosphate - Abstract
Adenosine triphosphate (ATP) is used as the energy source in cells and plays crucial roles in various cellular events. The cellular membrane is the protective barrier for the cytoplasm of living cells and involved in many essential biological processes. Many fluorescent probes for ATP have been successfully developed, but few of these probes were appropriate for visualizing ATP level fluctuation in cell membranes during the apoptotic cell death process. Herein, we report the synthesis of a new water-soluble cationic polythiophene derivative that can be utilized as a fluorescent sensor for detecting ATP in cell membranes. Poly((3-((4-methylthiophen-3-yl)oxy)propyl)triphenylphosphonium chloride) (PMTPP) exhibits high sensitivity and good selectivity to ATP, and the detection limit is 27 nM. The polymer shows low toxicity to live cells and excellent photostability in cell membranes. PMTPP was practically utilized for real-time monitoring of ATP levels in the cell membrane through fluorescence microscopy. We have demonstrated that the ATP levels in cell membranes increased during the apoptotic cell death process. The probe was also capable of imaging ATP levels in living mice.
- Published
- 2017
36. Lysosomal ATP imaging in living cells by a water-soluble cationic polythiophene derivative
- Author
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Zhirong Geng, Zhilin Wang, Cui Zhang, Bing-Huan Huang, Xiaoyan Ma, and Zhiyang Zhang
- Subjects
Fluorescence-lifetime imaging microscopy ,Cell Survival ,Polymers ,Biomedical Engineering ,Biophysics ,02 engineering and technology ,Biosensing Techniques ,Thiophenes ,010402 general chemistry ,01 natural sciences ,Exocytosis ,chemistry.chemical_compound ,Adenosine Triphosphate ,Lysosome ,Electrochemistry ,Fluorescence microscope ,medicine ,V-ATPase ,Humans ,Cytotoxicity ,Fluorescent Dyes ,Chemistry ,fungi ,Optical Imaging ,food and beverages ,Water ,General Medicine ,021001 nanoscience & nanotechnology ,Fluorescence ,0104 chemical sciences ,medicine.anatomical_structure ,Biochemistry ,Solubility ,0210 nano-technology ,Lysosomes ,Adenosine triphosphate ,Biotechnology ,HeLa Cells - Abstract
Lysosomes in astrocytes and microglia can release ATP as the signaling molecule for the cells through ca(2+)-dependent exocytosis in response to various stimuli. At present, fluorescent probes that can detect ATP in lysosomes have not been reported. In this work, we have developed a new water-soluble cationic polythiophene derivative that can be specifically localized in lysosomes and can be utilized as a fluorescent probe to sense ATP in cells. PEMTEI exhibits high selectivity and sensitivity to ATP at physiological pH values and the detection limit of ATP is as low as 10(-11)M. The probe has low cytotoxicity, good permeability and high photostability in living cells and has been applied successfully to real-time monitoring of the change in concentrations of ATP in lysosomes though fluorescence microscopy. We also demonstrated that lysosomes in Hela cells can release ATP through Ca(2+)-dependent exocytosis in response to drug stimuli.
- Published
- 2016
37. Effects of selenium on the structure and function of recombinant human S-adenosyl-l-methionine dependent arsenic (+3 oxidation state) methyltransferase in E. coli
- Author
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Zhirong Geng, Sichun Zhang, Jinlong Geng, Xinrong Zhang, Xiaoli Song, Zhilin Wang, and Zhi Xing
- Subjects
S-Adenosylmethionine ,Circular dichroism ,Methyltransferase ,Stereochemistry ,Molecular Sequence Data ,medicine.disease_cause ,Biochemistry ,Protein Structure, Secondary ,Arsenic ,law.invention ,Inorganic Chemistry ,Selenium ,Structure-Activity Relationship ,law ,Escherichia coli ,medicine ,Humans ,Amino Acid Sequence ,Enzyme Inhibitors ,chemistry.chemical_classification ,Base Sequence ,biology ,Active site ,Methyltransferases ,Methylation ,Molecular biology ,Recombinant Proteins ,Enzyme ,chemistry ,Mutagenesis, Site-Directed ,biology.protein ,Recombinant DNA ,Nucleic Acid Conformation ,Oxidation-Reduction ,Cysteine - Abstract
The effects of Se(IV) on the structure and function of recombinant human arsenic (+3 oxidation state) methyltransferase (AS3MT) purified from the cytoplasm of Escherichia coli were studied. The coding region of human AS3MT complementary DNA was amplified from total RNA extracted from HepG2 cell by reverse transcription PCR. Soluble and active human AS3MT was expressed in the E. coli with a Trx fusion tag under a lower induction temperature of 25 degrees C. Spectra (UV-vis, circular dichroism, and fluorescence) were first used to probe the interaction of Se(IV) and recombinant human AS3MT and the structure-function relationship of the enzyme. The recombinant human AS3MT had a secondary structure of 29.0% alpha-helix, 23.9% beta-pleated sheet, 17.9% beta-turn, and 29.2% random coil. When Se(IV) was added, the content of the alpha-helix did not change, but that of the beta-pleated sheet increased remarkably in the conformation of recombinant human AS3MT. Se(IV) inhibited the enzymatic methylation of inorganic As(III) in a concentration-dependent manner. The IC(50) value for Se(IV) was 2.38 muM. Double-reciprocal (1/V vs. 1/[inorganic As(III)]) plots showed Se(IV) to be a noncompetitive inhibitor of the methylation of inorganic As(III) by recombinant human AS3MT with a K (i) value of 2.61 muM. We hypothesized that Se(IV) interacts with the sulfhydryl group of cysteine(s) in the structural residues rather than the cysteines of the active site (Cys156 and Cys206). When Se(IV) was combined with cysteine(s) in the structural residues, the conformation of recombinant human AS3MT changed and the enzymatic activity decreased. Considering the quenching of tryptophan fluorescence, Cys72 and/or Cys226 are deduced to be primary targets for Se(IV).
- Published
- 2009
38. Tetraarsenictetrasulfide and Arsenic Trioxide Exert Synergistic Effects on Induction of Apoptosis and Differentiation in Acute Promyelocytic Leukemia Cells
- Author
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Zhirong Geng, Min Zhou, Zhilin Wang, Jian Ouyang, and Shuping Wang
- Subjects
Acute promyelocytic leukemia ,Cellular differentiation ,lcsh:Medicine ,Apoptosis ,Biology ,Sulfides ,Arsenicals ,Flow cytometry ,chemistry.chemical_compound ,Arsenic Trioxide ,Leukemia, Promyelocytic, Acute ,medicine ,Humans ,Arsenic trioxide ,lcsh:Science ,Receptor ,chemistry.chemical_classification ,Reactive oxygen species ,Multidisciplinary ,medicine.diagnostic_test ,lcsh:R ,Cell Differentiation ,Drug Synergism ,Oxides ,medicine.disease ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Leukemia ,chemistry ,Drug Resistance, Neoplasm ,Immunology ,Cancer research ,lcsh:Q ,Reactive Oxygen Species ,Research Article - Abstract
Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and differentiation of NB4 and primary APL cells. As4S4, acting similarly to As3+, arrested the G1/S transition, induced the accumulation of cellular reactive oxygen species, and promoted apoptosis. Additionally, low concentrations of As4S4 (0.1-0.4 μM) induced differentiation of NB4 and primary APL cells. Compared with the As4S4- or As3+-treated groups, the combination of As4S4 and As3+ obviously promoted apoptosis and differentiation of NB4 and primary APL cells. Mechanistic studies suggested that As4S4 acted synergistically with As3+ to down-regulate Bcl-2 and nuclear factor-κB expression, up-regulate Bax and p53 expression, and induce activation of caspase-12 and caspase-3. Moreover, the combination of low concentrations of As4S4 and As3+ enhanced degradation of the promyelocytic leukemia-retinoic acid receptor α oncoprotein. In summary, As4S4 and As3+ synergistically induce the apoptosis and differentiation of NB4 and primary APL cells.
- Published
- 2015
39. Effect of proline analogues on activity of human prolyl hydroxylase and the regulation of HIF signal transduction pathway
- Author
-
Xiaoxin Wang, Xiaoyan Ma, Jing Cao, Zhirong Geng, and Zhilin Wang
- Subjects
Proteomics ,Vascular Endothelial Growth Factor A ,Glycobiology ,Biochemistry ,Hydroxylation ,chemistry.chemical_compound ,Cell Signaling ,Molecular Cell Biology ,Cellular Stress Responses ,Multidisciplinary ,Spectrometric Identification of Proteins ,medicine.diagnostic_test ,Recombinant Proteins ,Enzymes ,Chemistry ,Cell Processes ,Physical Sciences ,Medicine ,Signal transduction ,Signal Transduction ,Research Article ,Proline ,Cell Survival ,Proteolysis ,Science ,Biology ,Hypoxia-Inducible Factor-Proline Dioxygenases ,Enzyme activator ,Cell Line, Tumor ,Chemical Biology ,medicine ,Humans ,Protein Interactions ,Enzyme Kinetics ,Biology and Life Sciences ,Proteins ,Cell Biology ,Hypoxia-Inducible Factor 1, alpha Subunit ,Enzyme Activation ,Metabolic pathway ,Kinetics ,chemistry ,Gene Expression Regulation ,Enzymology ,Pyruvate kinase - Abstract
Hypoxia inducible factor 1 (HIF-1) plays a pivotal role in cellular responses to hypoxia. Prolyl hydroxylase 3 (PHD3) degrades HIF-1α under normoxic conditions through the hydroxylation of HIF-1α for proteolysis. Inhibiting PHD3 activity is crucial for up-regulating HIF-1α, thereby acting as a potential target for treating hypoxia-related diseases. In this study, two proline analogues (PA1 and PA2) were screened as PHD3 inhibitors with apparent EC50 values of 1.53 and 3.17 µM respectively, indicating good inhibition potency. Nine proteins, significantly regulated by PA1, were identified using 2-DE coupled with MALDI-TOF/TOF MS. Pyruvate kinase isozymes M1/M2 (PKM) and alpha-enolase 1 (ENO1), which are key modulators of glycolysis, are directly regulated by HIF-1α. Moreover, VEGF, a signal protein stimulating angiogenesis, was strongly promoted by PA1. Our findings suggest that PA1 stabilized HIF-1α as well as up-regulated glycolysis and angiogenesis proteins. Herein, for the first time, we systematically studied proline analogue PA1 as a PHD3 inhibitor, which provides innovative evidence for the treatment of HIF-related diseases.
- Published
- 2014
40. Coordinate chloride and water-assisted assembly of novel 3D-cageworks of cadmium(II) complex with 4-[N,N-bis(2-cyanoethyl)]aminopyridine
- Author
-
Zhong Zhang, Zhilin Wang, Yi-Zhi Li, and Jun Ni
- Subjects
Cadmium ,Hydrogen bond ,Inorganic chemistry ,chemistry.chemical_element ,Chloride ,Ion ,Inorganic Chemistry ,Water assisted ,chemistry ,Polymer chemistry ,Materials Chemistry ,medicine ,Molecule ,Self-assembly ,Physical and Theoretical Chemistry ,medicine.drug - Abstract
Synthesis and structure of the cadmium(II) complex of [CdII(CEAP)2(H2O)(CH3COO)Cl] {CEAP = 4-[N,N-bis(2-cyanoethyl)]aminopyridine} has been reported. The structure exhibits a novel 3D-cagework assembly with the assistance of the coordinated chloride anion and water molecule via forming multiple hydrogen bonds with the cyanoethyl arms of CEAP.
- Published
- 2005
41. Residues in human arsenic (+3 oxidation state) methyltransferase forming potential hydrogen bond network around S-adenosylmethionine
- Author
-
Zhilin Wang, Xiangli Li, Jing Cao, Zhirong Geng, Xiaoli Song, Shuping Wang, and Xin Hu
- Subjects
Models, Molecular ,S-Adenosylmethionine ,Stereochemistry ,Protein Conformation ,Science ,chemistry.chemical_element ,Gene Expression ,Michaelis–Menten kinetics ,Methylation ,Catalysis ,Arsenic ,Substrate Specificity ,chemistry.chemical_compound ,Protein structure ,Oxidation state ,Amide ,Humans ,Amino Acids ,Arsenite ,Multidisciplinary ,Binding Sites ,Hydrogen bond ,Chemistry ,Hydrogen Bonding ,Methyltransferases ,Recombinant Proteins ,Kinetics ,Biochemistry ,Mutation ,Medicine ,Protein Binding ,Research Article - Abstract
Residues Tyr59, Gly78, Ser79, Met103, Gln107, Ile136 and Glu137 in human arsenic (+3 oxidation state) methyltransferase (hAS3MT) were deduced to form a potential hydrogen bond network around S-adenosylmethionine (SAM) from the sequence alignment between Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase (CmArsM) and hAS3MT. Herein, seven mutants Y59A, G78A, S79A, M103A, Q107A, I136A and E137A were obtained. Their catalytic activities and conformations were characterized and models were built. Y59A and G78A were completely inactive. Only 7.0%, 10.6% and 13.8% inorganic arsenic (iAs) was transformed to monomethylated arsenicals (MMA) when M103A, Q107A and I136A were used as the enzyme. The Vmax (the maximal velocity of the reaction) values of M103A, Q107A, I136A and E137A were decreased to 8%, 22%, 15% and 50% of that of WT-hAS3MT, respectively. The KM(SAM) (the Michaelis constant for SAM) values of mutants M103A, I136A and E137A were 15.7, 8.9 and 5.1 fold higher than that of WT-hAS3MT, respectively, indicating that their affinities for SAM were weakened. The altered microenvironment of SAM and the reduced capacity of binding arsenic deduced from KM(As) (the Michaelis constant for iAs) value probably synergetically reduced the catalytic activity of Q107A. The catalytic activity of S79A was higher than that of WT despite of the higher KM(SAM) , suggesting that Ser79 did not impact the catalytic activity of hAS3MT. In short, residues Tyr59 and Gly78 significantly influenced the catalytic activity of hAS3MT as well as Met103, Ile136 and Glu137 because they were closely associated with SAM-binding, while residue Gln107 did not affect SAM-binding regardless of affecting the catalytic activity of hAS3MT. Modeling and our experimental results suggest that the adenine ring of SAM is sandwiched between Ile136 and Met103, the amide group of SAM is hydrogen bonded to Gly78 in hAS3MT and SAM is bonded to Tyr59 with van der Waals, cation-π and hydrogen bonding contacts.
- Published
- 2013
42. Non-Heme Iron Absorption and Utilization from Typical Whole Chinese Diets in Young Chinese Urban Men Measured by a Double-Labeled Stable Isotope Technique
- Author
-
Lingyan Gou, Yuhui Zhang, Jun Wang, Zhengwu Huang, Zhilin Wang, Xiaoguang Yang, Tongxiang Ren, Lichen Yang, and Jianhua Piao
- Subjects
Male ,0301 basic medicine ,Composite Particles ,Iron intake ,Erythrocytes ,Iron absorption ,lcsh:Medicine ,Intestinal absorption ,Geographical Locations ,Isotopes ,Heme metabolism ,Medicine and Health Sciences ,Ethnicities ,Medicine ,Food science ,lcsh:Science ,Multidisciplinary ,Stable isotope ratio ,Physics ,Stable Isotopes ,Agriculture ,Plants ,Chinese diets ,Isotope Labeling ,Physical Sciences ,Research Article ,Adult ,Absorption (pharmacology) ,China ,Atoms ,Asia ,Iron ,Crops ,Heme ,Research and Analysis Methods ,Drug Absorption ,Young Adult ,03 medical and health sciences ,Model Organisms ,Asian People ,Plant and Algal Models ,Humans ,Pharmacokinetics ,Grasses ,Non heme iron ,Particle Physics ,Nutrition ,Pharmacology ,030109 nutrition & dietetics ,business.industry ,lcsh:R ,Organisms ,Biology and Life Sciences ,Diet ,Intestinal Absorption ,Food ,People and Places ,Population Groupings ,lcsh:Q ,Rice ,business ,Chinese People ,Crop Science ,Cereal Crops - Abstract
Background This study was to observe the non-heme iron absorption and biological utilization from typical whole Chinese diets in young Chinese healthy urban men, and to observe if the iron absorption and utilization could be affected by the staple food patterns of Southern and Northern China. Materials and Methods Twenty-two young urban men aged 18–24 years were recruited and randomly assigned to two groups in which the staple food was rice and steamed buns, respectively. Each subject received 3 meals containing approximately 3.25 mg stable 57FeSO4 (the ratio of 57Fe content in breakfast, lunch and dinner was 1:2:2) daily for 2 consecutive days. In addition, approximately 2.4 mg 58FeSO4 was administered intravenously to each subject at 30–60 min after dinner each day. Blood samples were collected from each subject to measure the enrichment of the 57Fe and 58Fe. Fourteen days after the experimental diet, non-heme iron absorption was assessed by measuring 57Fe incorporation into red blood cells, and absorbed iron utilization was determined according to the red blood cell incorporation of intravenously infused 58Fe SO4. Results Non-heme iron intake values overall, and in the rice and steamed buns groups were 12.8 ±2.1, 11.3±1.3 and 14.3±1.5 mg, respectively; the mean 57Fe absorption rates were 11±7%, 13±7%, and 8±4%, respectively; and the mean infused 58Fe utilization rates were 85±8%, 84±6%, and 85±10%, respectively. There was no significantly difference in the iron intakes, and 57Fe absorption and infused 58Fe utilization rates between rice and steamed buns groups (all P>0.05). Conclusion We present the non-heme iron absorption and utilization rates from typical whole Chinese diets among young Chinese healthy urban men, which was not affected by the representative staple food patterns of Southern and Northern China. This study will provide a basis for the setting of Chinese iron DRIs.
- Published
- 2016
43. Effects of polynitrogen compounds on the activity of recombinant human HIF-1α prolyl hydroxylase 3 in E. coli
- Author
-
Zhilin Wang, Zhirong Geng, Jing Cao, Xiaoli Song, Jinlong Geng, Jingshu Zhu, Zhong Zhang, and Ningsheng Bian
- Subjects
Transcriptional Activation ,Proline ,Stereochemistry ,Nitrogen ,Iron ,Procollagen-Proline Dioxygenase ,Peptide ,medicine.disease_cause ,Hydroxylation ,Biochemistry ,Mass Spectrometry ,law.invention ,Inorganic Chemistry ,chemistry.chemical_compound ,Non-competitive inhibition ,law ,Heterocyclic Compounds ,medicine ,Escherichia coli ,Humans ,Enzyme Inhibitors ,chemistry.chemical_classification ,Binding Sites ,Dose-Response Relationship, Drug ,Temperature ,Hypoxia-Inducible Factor 1, alpha Subunit ,Recombinant Proteins ,Kinetics ,Enzyme ,chemistry ,Recombinant DNA ,Peptides ,DNA - Abstract
Hypoxia inducible factor 1α (HIF-1α) becomes an important regulation factor within the histiocyte when it is under the hypoxia condition. Recently, prolyl hydroxylases (PHDs) have been identified to inactivation HIF-lα by hydroxylation. In this study, polynitrogen compounds were screened as HIF-1α PHD3 inhibitors. The coding region of human PHD3 DNA was optimized by using synonymous codons according to the code bias of Escherichia coli . Soluble and active human PHD3 was expressed in the E. coli with a Trx fusion tag under a lower induction temperature of 25 °C. Mass spectrometry analysis of the resultant peptide product indicated a mass increase of 16 daltons, consistent with hydroxylation of the proline residue in the HIF-1α (556–574) peptide substrate. Polynitrogen compounds (1–4) inhibited the enzymatic hydroxylation of HIF-1α peptide in a concentration-dependent manner, and the apparent IC 50 values were 29.5, 16.0, 12.8 and 60.4 μM respectively. Double reciprocal (1/V versus 1/[HIF-1α peptide]) plots showed that these compounds are noncompetitive inhibitors of the hydroxylation by recombinant human PHD3 with K i values of 67.0, 25.3, 67.3, and 82.1 μM respectively. On the other hand, the metal complexes of these polynitrogen compounds (1–4) cannot inhibit the catalytical activity of PHD3. We hypothesized that the inhibitory mechanism of PHD3 activity by polynitrogen compounds is due to their binding to iron to form stable coordination complexes. Our results in this study indicated that polynitrogen compounds (1–4) could be potential inhibitors of PHD3 to regulate the transcriptional activity of HIF-1α.
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- 2010
44. Abstract 3814: Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer
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Yuqi Guo, Yushi Wu, Zhilin Wang, Juncheng Wei, Jian Yang, and Xin Li
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Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Cancer ,medicine.disease ,medicine.disease_cause ,Metformin ,Prostate cancer ,Endocrinology ,Oncology ,Apoptosis ,Internal medicine ,Unfolded protein response ,medicine ,Cancer research ,biology.protein ,Neuronatin ,Carcinogenesis ,business ,Calreticulin ,medicine.drug - Abstract
Previous studies showed that metformin is associated with lower risk of tumorigenesis for several cancer types including prostate cancer. However, the molecular basis of anti-tumor effect induced by this biguanide agent is still unclear. In this study, we identified miR-708-5p as a novel downstream effector of metformin in prostate cancer. By increasing the expression of miR-708-5p, metformin suppresses the expression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) and subsequently induces apoptosis of prostate cancer cells through ER stress pathway. Notably, down-regulated NNAT is associated with down-regulated intracellular calcium level and induces malformation of endoplasmic reticulum-ribosome structure which is revealed by electronic microscopy. Furthermore, western blot shows that the unfolded-protein response (UPR) proteins including CHOP, p-eIF2α, Calreticulin, GRP78 and ATP2A1, all of which are also considered as the ER stress markers, were up-regulated by metformin and miR-708-5p. Importantly, an increased apoptosis of prostate cancer cells is also observed when miR-708-5p mimic or NNAT siRNA was introduced. In summary, our findings clearly reveals that metformin stimulates miR-708-5p to target on NNAT mediated response to ER stress and apoptosis. This novel regulatory mechanism of metformin in prostate cancer cells not only advances our knowledge on the molecular mechanism of metformin in cancer progression, but also provide a promising therapeutic target for prostate cancer treatment. Citation Format: Jian Yang, Juncheng Wei, Yushi Wu, Zhilin Wang, Yuqi Guo, Xin Li. Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3814. doi:10.1158/1538-7445.AM2015-3814
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- 2015
45. Social and psychological factors of the suicidal tendencies of Chinese medical students
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Aiming Zheng and Zhilin Wang
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medicine.medical_specialty ,Social Psychology ,education ,Short Report ,Alternative medicine ,Behavioural sciences ,Psychosomatic medicine ,Psychological factors ,Psychiatry and Mental health ,Social factors ,Chinese medical students ,SUICIDAL TENDENCY ,medicine ,Suicidal tendency ,Psychiatry ,China ,Psychology ,Psychology(all) ,Biological Psychiatry ,General Psychology ,Clinical psychology - Abstract
Background Over the past few decades, concern about suicide by college students has been on the rise worldwide, in general and in China particularly. The main objective of this study is to investigate the effects of social and psychological factors on the suicidal tendencies of Chinese medical students. Findings Of the 540 students surveyed, 48 had a suicidal tendency to some extent. The highest rate of suicide was observed for fourth-year students, followed by the fifth-year, first-year, third-year, and second-year students. Female students and students not satisfied with their major had a higher rate of suicidal tendency. However, mature coping strategies had a protective effect on suicide. The stepwise regression analysis shows that academic burden, grade, and introversion/extraversion are the most significant risk factors for the suicidal tendency of Chinese medical students. Conclusion Suicide is affected by demographic risk factors as well as psychological factors. Our results lend support to a multi-factorial approach to the understanding and prevention of suicide by college students.
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- 2014
46. Dichloridobis[2-(2-chloroethyl)-1,2,3,4-tetrahydropyrazino[1,2-a]benzimidazole-κN]cobalt(II)
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Yao Zhao, Zhilin Wang, Zhong Zhang, and Zhirong Geng
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Metal-Organic Papers ,Benzimidazole ,biology ,Chemistry ,Hydrogen bond ,Ligand ,chemistry.chemical_element ,General Chemistry ,Condensed Matter Physics ,Bioinformatics ,biology.organism_classification ,Chloride ,lcsh:Chemistry ,chemistry.chemical_compound ,Crystallography ,lcsh:QD1-999 ,medicine ,Side chain ,Tetra ,General Materials Science ,Cobalt ,medicine.drug ,Coordination geometry - Abstract
In the title compound, [CoCl(2)(C(12)H(14)ClN(3))(2)], the central Co(II) ion lies on a twofold rotation axis and adopts a distorted tetra-hedral coordination geometry defined by two N atoms from two 2-(2-chloro-ethyl)-1,2,3,4-tetra-hydro-pyrazino[1,2-a]benzimidazole ligands and two chloride anions. The Cl atom located in the side chain of the ligand is involved in inter-molecular C-H⋯Cl hydrogen bonding, which links neutral complex units into a one-dimensional right-handed helical chain running along a crystallographic 4(1) axis. Such hydrogen-bonded helical chains are connected to each other to form a homochiral three-dimensional supra-molecular network. One C atom of the 2-chloro-ethyl chain is disordered over two positions, with site-occupancy factors of 0.52 and 0.48.
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- 2008
47. Azole derivatives as novel non-iron-chelating inhibitors of prolyl hydroxylase 3 for HIF-1 activation
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Zhilin Wang, Xiaoyan Ma, Xiaoxin Wang, Zhirong Geng, Jing Cao, Xiaobo Wang, and Zhong Zhang
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Pharmacology ,chemistry.chemical_classification ,medicine.diagnostic_test ,biology ,Proteolysis ,Organic Chemistry ,Pharmaceutical Science ,Active site ,Trypsin ,Biochemistry ,Hydroxylation ,chemistry.chemical_compound ,Enzyme ,chemistry ,Docking (molecular) ,Drug Discovery ,medicine ,biology.protein ,Molecular Medicine ,Azole ,medicine.drug ,Calcium signaling - Abstract
Prolyl hydroxylase 3 (PHD3) controls hypoxia-inducible factor-1 (HIF-1) degradation by oxygen dependent hydroxylation. PHD3 inhibitors are potential targets for HIF-1α activation, thereby treating a number of HIF-related diseases. We herein rationally designed a novel scaffold for PHD3 inactivation under the guidance of enzyme–ligand docking simulation studies. The potent inhibitors were able to non-covalently bind to the active site of PHD3, and to stabilize the core domain resisting to trypsin proteolysis. The conformational changes of the protein occurred concomitant with inhibitor binding, which thus deactivated the enzyme. The up-regulated levels of HIF-1α protein and downstream genes (glucose transporter-1 (GLUT-1) and vascular endothelial growth factor (VEGF)) suggest that the PHD inhibitors manage to mimic the cellular signalling effects of hypoxia. Interestingly, unlike available PHD inhibitors, the iron-chelating motif is not found in all azole compounds, among which we identified a unique compound 1-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-1H-benzo[d][1,2,3]triazole (BEBT) as the most effective inhibitor. BEBT binds to the enzyme with the lowest predicted binding energy, and activates HIF activity most significantly in cellular systems. This novel non-iron-chelating inhibitor offers a new target for the drug design towards hypoxia-related diseases therapy with possibly minimized iron-relating side effects.
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- 2013
48. A potent antitumor Zn2+ tetraazamacrocycle complex targeting DNA: the fluorescent recognition, interaction and apoptosis studies
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Jinghan Wen, Zhirong Geng, Xiaoyan Ma, Chengying Li, and Zhilin Wang
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Models, Molecular ,Macrocyclic Compounds ,Molecular Conformation ,Antineoplastic Agents ,Apoptosis ,Catalysis ,HeLa ,chemistry.chemical_compound ,Organometallic Compounds ,Materials Chemistry ,medicine ,Humans ,Cytotoxicity ,Cisplatin ,biology ,Metals and Alloys ,DNA ,General Chemistry ,biology.organism_classification ,Molecular biology ,Fluorescence ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Zinc ,Spectrometry, Fluorescence ,chemistry ,Ceramics and Composites ,Cancer cell lines ,HeLa Cells ,medicine.drug - Abstract
A Zn(2+) tetraazamacrocycle complex (2) bearing three naphthalene moieties has been prepared. Complex 2 recognizes, binds and causes damage to DNA, and shows considerable cytotoxicity against human cervical (HeLa), breast (MCF-7) and lung (NCI-H157) cancer cell lines with a different apoptotic pathway from that of cisplatin.
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- 2011
49. miR-320a affects spinal cord edema through negatively regulating aquaporin-1 of blood–spinal cord barrier during bimodal stage after ischemia reperfusion injury in rats
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Zhilin Wang, Wen-Fei Tan, Hong Ma, Xi-Jia Sun, Xiao-Qian Li, Bo Fang, and Zai-Li Zhang
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0301 basic medicine ,medicine.medical_specialty ,Cord ,Ischemia ,Blood–spinal cord barrier ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,Edema ,medicine ,Microglia ,business.industry ,General Neuroscience ,Aquaporin ,medicine.disease ,Spinal cord ,Extravasation ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Anesthesia ,Aquaporin 1 ,medicine.symptom ,business ,Reperfusion injury ,030217 neurology & neurosurgery ,Ischemia reperfusion injury ,Research Article - Abstract
Background Spinal cord edema is a serious complication and pathophysiological change after ischemia reperfusion (IR) injury. It has been demonstrated closely associated with bimodal disruption of blood–spinal cord barrier (BSCB) in our previous work. Aquaporin (AQP)1 plays important but contradictory roles in water homeostasis. Recently, microRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, whether miRs are able to protect against dimodal disruption of BSCB by regulating perivascular AQP1 remains to be elucidated. Results Spinal water content and EB extravasation were suggested as a bimodal distribution in directly proportion to AQP1, since all maximal changes were detected at 12 and 48 h after reperfusion. Further TEM and double immunofluorescence showed that former disruption of BSCB at 12 h was attributed to cytotoxic edema by up-regulated AQP1 expressions in astrocytes, whereas the latter at 48 h was mixed with vasogenic edema with both endothelial cells and astrocytes involvement. Microarray analysis revealed that at 12 h post-injury, ten miRs were upregulated (>2.0 fold) and seven miRs were downregulated (1 in spinal cord after IR in vitro. In vivo, compared to rats in IR and negative control group, intrathecal infusion of miR-320a mimic attenuated IR-induced lower limb motor function deficits and BSCB dysfunction as decreased EB extravasation and spinal water content through down-regulating AQP1 expressions, whereas pretreated with miR-320a AMO reversed above effects. Conclusion These findings indicate miR-320a directly and functionally affects spinal cord edema through negatively regulating AQP1 of BSCB after IR.
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50. MiR-27a ameliorates inflammatory damage to the blood-spinal cord barrier after spinal cord ischemia: reperfusion injury in rats by downregulating TICAM-2 of the TLR4 signaling pathway
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Bo Fang, Wen-Fei Tan, Hong Ma, Huang-Wei Lv, Zhilin Wang, and Xiao-Qian Li
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Male ,Time Factors ,Cord ,Immunology ,Oligonucleotides ,Ischemia ,Down-Regulation ,Inflammation ,Toll-like receptor adaptor molecule 2 ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Downregulation and upregulation ,medicine ,Animals ,Blood-spinal cord barrier ,Receptor ,Adaptor Proteins, Signal Transducing ,Spinal Cord Ischemia ,business.industry ,Research ,General Neuroscience ,Toll-like receptor 4 ,Microarray Analysis ,medicine.disease ,Spinal cord ,Rats ,MicroRNAs ,Disease Models, Animal ,medicine.anatomical_structure ,Spinal Cord ,Neurology ,Reperfusion Injury ,Anti-miR oligonucleotides ,TLR4 ,Cancer research ,Cytokines ,medicine.symptom ,business ,MiR mimics ,Reperfusion injury ,Ischemia reperfusion injury - Abstract
Background Spinal cord ischemia reperfusion (IR) injury causes inflammation and subsequently increases blood-spinal cord barrier leakage and Toll-like receptor 4 (TLR4) pathway activation. MicroRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, their roles during IR injury are poorly understood. We investigated miRs involvement, particularly miR-27a, in TLR4 pathway-mediated inflammatory responses after IR. Method We used a genomics approach to examine changed miRs of rats that had undergone 14 minutes of ischemia, followed by 24 or 72 hours of reperfusion. Quantitative RT-PCR was used to identify and confirm the miRs involved in regulating TLR4 pathway activation. We scanned miR databases for potential miR targets and confirmed these targets by quantitative RT-PCR. The miR mimic and anti-miR oligonucleotides (AMOs) were intrathecally injected at 12-hour intervals beginning three days before the ischemia. The effects of miRs on the TLR4 pathway and downstream cytokines were analyzed by PCR, western blotting, and ELISA. Double immunofluorescence staining was perfumed to determine the relationship between the targets and TLR4. Blood-spinal cord barrier (BSCB) permeability was examined using Evans blue (EB) dye. Results A microarray analysis revealed that at 24 hours post-injury, three miRs were upregulated (>2.0 fold) and 15 miRs were downregulated (
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