380 results on '"Yumei Wu"'
Search Results
102. A partnership of the lipid scramblase XK and of the lipid transfer protein VPS13A at the plasma membrane
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Andrés Guillén Samander, Yumei Wu, S. Sebastian Pineda, Francisco J. García, Julia N. Eisen, Marianna Leonzino, Berrak Uğur, Manolis Kellis, Myriam Heiman, and Pietro De Camilli
- Abstract
Chorea-acanthocytosis and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an ER-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.
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- 2022
103. 3D FIBSEM CLEM v1
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Pietro De Camilli and Yumei Wu
- Abstract
This protocol details the procedure of Correlative Light Microscopy and Electron Microscopy (CLEM) with 3D Focus Ion Beam Scanning Electron Microscopy (FIBSEM) technique in Zeiss Crossbeam 550 FIBSEM system.
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- 2022
104. 2D TEM CLEM (Correlative Light Microscopy and Electron Microscopy) v1
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Pietro De Camilli and Yumei Wu
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This protocol details the general procedure of Correlative Light Microscopy and Electron Microscopy (CLEM) with conventional chemical fixation and 2D Transmission Electron Microscopy (TEM) imaging.
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- 2022
105. Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
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Xin Yi Ng, Yumei Wu, Youneng Lin, Sidra Mohamed Yaqoob, Lois E. Greene, Pietro De Camilli, and Mian Cao
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Cellular and Molecular Neuroscience ,Neurology ,Neurology (clinical) - Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by defective dopaminergic (DAergic) input to the striatum. Mutations in two genes encoding synaptically enriched clathrin-uncoating factors, synaptojanin 1 (SJ1) and auxilin, have been implicated in atypical Parkinsonism. SJ1 knock-in (SJ1-KIRQ) mice carrying a disease-linked mutation display neurological manifestations reminiscent of Parkinsonism. Here we report that auxilin knockout (Aux-KO) mice display dystrophic changes of a subset of nigrostriatal DAergic terminals similar to those of SJ1-KIRQ mice. Furthermore, Aux-KO/SJ1-KIRQ double mutant mice have shorter lifespan and more severe synaptic defects than single mutant mice. These include increase in dystrophic striatal nerve terminals positive for DAergic markers and for the PD risk protein SV2C, as well as adaptive changes in striatal interneurons. The synergistic effect of the two mutations demonstrates a special lability of DAergic neurons to defects in clathrin uncoating, with implications for PD pathogenesis in at least some forms of this condition.
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- 2022
106. Heat Stress and SCA48 Mutations Reveal the Metamorphic Structure and Function of the Ubiquitin Ligase CHIP
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Ran Ming, Jamie B. Scaglione, Adam J. Kanack, Erik Soderblom, Anna Umano, Kanesha L. Travis, Yumei Wu, Oliver J. Newsom, Matthew G. Thompson, and K. Matthew Scaglione
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
107. Absence of Sac2/INPP5F enhances the phenotype of a Parkinson’s disease mutation of synaptojanin 1
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Yumei Wu, Mian Cao, Daehun Park, and Pietro De Camilli
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medicine.medical_specialty ,Parkinson's disease ,Dopamine ,INPP5F ,Phosphatase ,Endocytic cycle ,Biology ,Mice ,Internal medicine ,medicine ,endocytosis ,Animals ,Humans ,Synaptic vesicle recycling ,synaptojanin 1 ,Gene ,Sac2 ,Mice, Knockout ,Nerve Endings ,Multidisciplinary ,Inositol Polyphosphate 5-Phosphatases ,Dopaminergic ,PI4P ,Parkinson Disease ,Biological Sciences ,medicine.disease ,Molecular biology ,Phenotype ,Mice, Inbred C57BL ,Endocrinology ,Mutation ,Synapses ,Knockout mouse ,Neuroscience ,Genome-Wide Association Study - Abstract
Significance Extensive genetic studies have identified numerous genes whose mutations results on Parkinson’s disease (PD), including synaptojanin 1 (SJ1/Park20), a nerve terminal enriched protein that includes an inositol 4-phosphatase domain (Sac domain). In addition, many PD candidate genes have been identified by genome-wide association studies, but for most of these genes, the link to PD remains hypothetical. One such gene is Sac2/INPP5F, which, interestingly, also includes an inositol 4-phosphatase domain. While Sac2KO mice do not show obvious defects, we show a striking synthetic effect in mice of the KO of Sac2 and the Sac domain mutation of SJ1 found in PD patients. These findings support a synergistic role of SJ1 and Sac2 on a PI4P pool whose dysfunction results in PD., Numerous genes whose mutations cause, or increase the risk of, Parkinson’s disease (PD) have been identified. An inactivating mutation (R258Q) in the Sac inositol phosphatase domain of synaptojanin 1 (SJ1/PARK20), a phosphoinositide phosphatase implicated in synaptic vesicle recycling, results in PD. The gene encoding Sac2/INPP5F, another Sac domain-containing protein, is located within a PD risk locus identified by genome-wide association studies. Knock-In mice carrying the SJ1 patient mutation (SJ1RQKI) exhibit PD features, while Sac2 knockout mice (Sac2KO) do not have obvious neurologic defects. We report a “synthetic” effect of the SJ1 mutation and the KO of Sac2 in mice. Most mice with both mutations died perinatally. The occasional survivors had stunted growth, died within 3 wk, and showed abnormalities of striatal dopaminergic nerve terminals at an earlier stage than SJ1RQKI mice. The abnormal accumulation of endocytic factors observed at synapses of cultured SJ1RQKI neurons was more severe in double-mutant neurons. Our results suggest that SJ1 and Sac2 have partially overlapping functions and are consistent with a potential role of Sac2 as a PD risk gene.
- Published
- 2020
108. The Potential Vertical Distribution of Bigeye Tuna (Thunnus obesus) and Its Influence on the Spatial Distribution of CPUEs in the Tropical Atlantic Ocean
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Liming Song, Wei Fan, Zhang Bianbian, Yumei Wu, Yu Zhang, Heng Zhang, Yang Dai, Shengmao Zhang, and Shenglong Yang
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Stock assessment ,biology ,Buoy ,Bigeye tuna ,Ocean Engineering ,Pelagic zone ,04 agricultural and veterinary sciences ,Catch per unit effort ,Oceanography ,biology.organism_classification ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Environmental science ,Thermocline ,Thunnus ,Argo - Abstract
Understanding the potential vertical distribution of bigeye tuna (Thunnus obesus) is necessary to understand the catch rate fluctuations and the stock assessment of bigeye tuna. To characterize the potential vertical distribution of this fish while foraging and determine the influences of the distribution on longline efficiency in the tropical Atlantic Ocean, the catch per unit effort (CPUE) data were compiled from the International Commission for the Conservation of Atlantic Tunas and the Argo buoy data were downloaded from the Argo data center. The raw Argo buoy data were processed by data mining methods. The CPUE was standardized by support vector machine before analysis. We assumed the depths with the upper and lower limits of the optimum water temperatures of 15°C and 9°C as the preferred swimming depth, while the lower limit of the temperature (12°C) associated with the highest hooking rate as the preferred foraging depth (D12) of bigeye tuna during the daytime in the Atlantic Ocean. The preferred swimming depth and foraging depth range in the daytime were assessed by plotting the isobath based on Argo buoy data. The preferred swimming depth and vertical structure of the water column were identified to investigate the spatial effects on the CPUE by using a generalized additive model (GAM). The empirical cumulative distribution function was used to assess the relationship between the spatial distribution of CPUE and the depth of 12°C isolines and thermocline. The results indicate that 1) the preferred swimming depth of bigeye tuna in the tropical Atlantic is from 100 m to 400 m and displays spatial variation; 2) the preferred foraging depth of bigeye tuna is between 190 and 300 m and below the thermocline; 3) the number of CPUEs peaks at a relative depth of 30-50 m (difference between the 12°C isolines and the lower boundary of the thermocline); and 4) most CPUEs are within the lower depth boundary of the thermocline levels (LDBT) which is from 160 m to 230 m. GAM analysis indicates that the general relationship between the nominal CPUE and LDBT is characterized by a dome shape and peaks at approximately 190 m. The oceanographic features influence the habitat of tropical pelagic fish and fisheries. Argo buoy data can be an important tool to describe the habitat of oceanic fish. Our results provide new insights into how oceanographic features influence the habitat of tropical pelagic fish and fisheries and how fisheries exploit these fish using a new tool (Argo profile data).
- Published
- 2020
109. ErCas12a CRISPR-MAD7 for Model Generation in Human Cells, Mice, and Rats
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John A. Schiel, Zhenyi Liu, Angela Bartels, Guojun Zhao, Žaklina Strezoska, Elena Maksimova, Anja van Brabant Smith, Emily M. Anderson, Joe Warren, Yumei Wu, Kevin P. Forbes, and Chris E. Lowe
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CRISPR-Associated Proteins ,Mice ,Bacterial Proteins ,Dna genetics ,Genome editing ,Genetics ,Animals ,Humans ,CRISPR ,Clustered Regularly Interspaced Short Palindromic Repeats ,Eubacterium rectale ,Research Articles ,Gene Editing ,Nuclease ,Endodeoxyribonucleases ,Genome ,biology ,Eubacterium ,Cas9 ,RNA ,DNA ,Endonucleases ,HCT116 Cells ,Molecular biology ,Rats ,biology.protein ,CRISPR-Cas Systems ,RNA, Guide, Kinetoplastida ,Biotechnology - Abstract
MAD7 is an engineered class 2 type V-A CRISPR-Cas (Cas12a/Cpf1) system isolated from Eubacterium rectale. Analogous to Cas9, it is an RNA-guided nuclease with demonstrated gene editing activity in Escherichia coli and yeast cells. Here, we report that MAD7 is capable of generating indels and fluorescent gene tagging of endogenous genes in human HCT116 and U2OS cancer cell lines, respectively. In addition, MAD7 is highly proficient in generating indels, small DNA insertions (23 bases), and larger integrations ranging from 1 to 14 kb in size in mouse and rat embryos, resulting in live-born transgenic animals. Due to the different protospacer adjacent motif requirement, small-guide RNA, and highly efficient targeted gene disruption and insertions, MAD7 can expand the CRISPR toolbox for genome enginnering across different systems and model organisms.
- Published
- 2020
110. Properties and proximity proteomics of synaptopodin provide insight into the molecular organization of the spine apparatus of dendritic spines
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Hanieh Falahati, Yumei Wu, Vanessa Feuerer, and Pietro De Camilli
- Abstract
SUMMARYThe spine apparatus is a specialization of the neuronal ER in dendritic spines consisting of stacks of interconnected cisterns separated by a dense matrix. Synaptopodin, a specific actin binding protein of the spine apparatus, is essential for its formation, but the underlying mechanisms remain unknown. We show that synaptopodin, when expressed in fibroblasts, forms actin-rich structures with connections to the ER, and that an ER-tethered synaptopodin assembles into liquid condensates. We also identified protein neighbors of synaptopodin in spines by in vivo proximity biotinylation. We validated a small subset of such proteins and showed that they co-assemble with synaptopodin in living cells. One of them is Pdlim7, an actin binding protein not previously identified in spines, and we show its precise colocalization with synaptopodin. We suggest that the matrix of the spine apparatus has the property of a liquid protein condensate generated by a multiplicity of low affinity interactions.Graphical abstract
- Published
- 2021
111. SHIP164 is a Chorein Motif Containing Lipid Transport Protein that Controls Membrane Dynamics and Traffic at the Endosome-Golgi Interface
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Michael G. Hanna, Patreece Suen, Karin M. Reinisch, Yumei Wu, and Pietro De Camilli
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symbols.namesake ,Membrane ,Lipid Chemistry ,Endosome ,Chemistry ,Vesicle ,Endocytic cycle ,Organelle ,symbols ,Biophysics ,Golgi apparatus ,Lipid Transport - Abstract
Cellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred in bulk from one membrane to another at membrane contact sites, and thus independently of vesicular traffic. Here we show that SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with these proteins and is localized on a subpopulation of vesicle clusters in the early endocytic pathway whose membrane cargo includes the cation-independent mannose-6-phosphate receptor (MPR) and ATG9. Loss of SHIP164 disrupts retrograde traffic of these organelles to the Golgi complex. Our findings raise the possibility that bulk transfer of lipids to endocytic membranes may play a role in their traffic.
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- 2021
112. English Classroom Face-to-face and Online Discussion Based on Information Technology
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Yumei Wu
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- 2021
113. Inhibition of GPR17 with cangrelor improves cognitive impairment and synaptic deficits induced by Aβ
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ShiYu, Jin, Xin, Wang, XiaoTong, Xiang, YuMei, Wu, Jie, Hu, YueYue, Li, Yue, Lin Dong, YueQiang, Tan, and Xian, Wu
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Mice, Inbred ICR ,Amyloid beta-Peptides ,NF-E2-Related Factor 2 ,NF-kappa B ,Membrane Proteins ,Nerve Tissue Proteins ,Adenosine Monophosphate ,Peptide Fragments ,Receptors, G-Protein-Coupled ,Mice ,Electrical Synapses ,Alzheimer Disease ,Animals ,Humans ,Cognitive Dysfunction ,Heme Oxygenase-1 ,Platelet Aggregation Inhibitors ,Signal Transduction - Abstract
The accumulation of amyloid beta (Aβ) in the brain is thought to be associated with cognitive deficits in Alzheimer's disease (AD). However, current methods to combat Aβ neurotoxicity are still lacking. G protein-coupled receptor 17 (GPR17) has become a target for treating inflammation in brain diseases, but it is unclear whether it has a role in AD. Here, we investigated the effects of cangrelor, a GPR17 antagonist, on neurotoxicity and memory impairment induced by intracerebroventricular (i.c.v.) injection of Aβ
- Published
- 2021
114. Dynamin deficiency causes insulin secretion failure and hyperglycemia
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Fan Fan, Dan Nerad, Xuelin Lou, Adam Rizk, Natalia A. Tamarina, Manami Hara, Chen Ji, and Yumei Wu
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Blood Glucose ,Dynamins ,Male ,medicine.medical_treatment ,Endocytic cycle ,Mice, Transgenic ,Nerve Tissue Proteins ,Endocytosis ,Exocytosis ,Dynamin II ,Membrane fission ,GTP-Binding Proteins ,Insulin-Secreting Cells ,Insulin Secretion ,medicine ,Animals ,Calcium Signaling ,Dynamin ,Mice, Knockout ,Multidisciplinary ,Chemistry ,Insulin ,Biological Sciences ,Cell biology ,Dense Core Vesicles ,DNM3 ,Hyperglycemia ,Female ,Intracellular - Abstract
Pancreatic β cells operate with a high rate of membrane recycling for insulin secretion, yet endocytosis in these cells is not fully understood. We investigate this process in mature mouse β cells by genetically deleting dynamin GTPase, the membrane fission machinery essential for clathrin-mediated endocytosis. Unexpectedly, the mice lacking all three dynamin genes (DNM1, DNM2, DNM3) in their β cells are viable, and their β cells still contain numerous insulin granules. Endocytosis in these β cells is severely impaired, resulting in abnormal endocytic intermediates on the plasma membrane. Although insulin granules are abundant, their release upon glucose stimulation is blunted in both the first and second phases, leading to hyperglycemia and glucose intolerance in mice. Dynamin triple deletion impairs insulin granule exocytosis and decreases intracellular Ca(2+) responses and granule docking. The docking defect is correlated with reduced expression of Munc13-1 and RIM1 and reorganization of cortical F-actin in β cells. Collectively, these findings uncover the role of dynamin in dense-core vesicle endocytosis and secretory capacity. Insulin secretion deficiency in the absence of dynamin-mediated endocytosis highlights the risk of impaired membrane trafficking in endocrine failure and diabetes pathogenesis.
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- 2021
115. Protective Effects and Network Analysis of Ginsenoside Rb1 Against Cerebral Ischemia Injury: A Pharmacological Review
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Song Zhang, Tianbao Xiao, Yumei Wu, Weijie Xie, Yibo Cao, Xinyue Wang, and Dongsheng Yang
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0301 basic medicine ,Drug ,antioxidant ,media_common.quotation_subject ,Excitotoxicity ,Ischemia ,Traditional Chinese medicine ,RM1-950 ,Review ,medicine.disease_cause ,Bioinformatics ,Neuroprotection ,03 medical and health sciences ,Ginseng ,0302 clinical medicine ,antiapoptosis ,In vivo ,ginsenoside Rb1 ,Medicine ,Pharmacology (medical) ,media_common ,anti-inflammatory ,Pharmacology ,business.industry ,ischemia stroke ,medicine.disease ,ischemia and reperfusion injury ,Clinical trial ,030104 developmental biology ,Therapeutics. Pharmacology ,business ,030217 neurology & neurosurgery - Abstract
Ischemic stroke is a leading cause of death and disability worldwide. Currently, only a limited number of drugs are available for treating ischemic stroke. Hence, studies aiming to explore and develop other potential strategies and agents for preventing and treating ischemic stroke are urgently needed. Ginseng Rb1 (GRb1), a saponin from natural active ingredients derived from traditional Chinese medicine (TCM), exerts neuroprotective effects on the central nervous system (CNS). We conducted this review to explore and summarize the protective effects and mechanisms of GRb1 on cerebral ischemic injury, providing a valuable reference and insights for developing new agents to treat ischemic stroke. Our summarized results indicate that GRb1 exerts significant neuroprotective effects on cerebral ischemic injury both in vivo and in vitro, and these network actions and underlying mechanisms are mediated by antioxidant, anti-inflammatory, and antiapoptotic activities and involve the inhibition of excitotoxicity and Ca2+ influx, preservation of blood–brain barrier (BBB) integrity, and maintenance of energy metabolism. These findings indicate the potential of GRb1 as a candidate drug for treating ischemic stroke. Further studies, in particular clinical trials, will be important to confirm its therapeutic value in a clinical setting.
- Published
- 2021
116. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines.
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Falahat, Hanieh, Yumei Wu, Feuerer, Vanessa, Simon, Hans-Georg, and De Camilli, Pietro
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DENDRITIC spines , *PROTEOMICS , *CARRIER proteins , *ENDOPLASMIC reticulum , *SPINE diseases - Abstract
The spine apparatus is a specialized compartment of the neuronal smooth endoplasmic reticulum (ER) located in a subset of dendritic spines. It consists of stacks of ER cisterns that are interconnected by an unknown dense matrix and are continuous with each other and with the ER of the dendritic shaft. While this organelle was first observed over 60 y ago, its molecular organization remains a mystery. Here, we performed in vivo proximity proteomics to gain some insight into its molecular components. To do so, we used the only known spine apparatus–specific protein, synaptopodin, to target a biotinylating enzyme to this organelle. We validated the specific localization in dendritic spines of a small subset of proteins identified by this approach, and we further showed their colocalization with synaptopodin when expressed in nonneuronal cells. One such protein is Pdlim7, an actin binding protein not previously identified in spines. Pdlim7, which we found to interact with synaptopodin through multiple domains, also colocalizes with synaptopodin on the cisternal organelle, a peculiar stack of ER cisterns resembling the spine apparatus and found at axon initial segments of a subset of neurons. Moreover, Pdlim7 has an expression pattern similar to that of synaptopodin in the brain, highlighting a functional partnership between the two proteins. The components of the spine apparatus identified in this work will help elucidate mechanisms in the biogenesis and maintenance of this enigmatic structure with implications for the function of dendritic spines in physiology and disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
117. Bayesian theory based software reliability demonstration test method for safety critical software.
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Yumei Wu, Risheng Yang, Haifeng Li 0013, and Minyan Lu
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- 2014
- Full Text
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118. Activation of GPR55 attenuates cognitive impairment, oxidative stress, neuroinflammation, and synaptic dysfunction in a streptozotocin-induced Alzheimer's mouse model
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XiaoTong Xiang, Xin Wang, YuMei Wu, Jie Hu, YueYue Li, ShiYu Jin, and Xian Wu
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Pharmacology ,Clinical Biochemistry ,Toxicology ,Biochemistry ,Streptozocin ,Behavioral Neuroscience ,Disease Models, Animal ,Mice ,Oxidative Stress ,Neuroprotective Agents ,Alzheimer Disease ,Synapses ,Acetylcholinesterase ,Animals ,Aspartic Acid Endopeptidases ,Cannabidiol ,Cognitive Dysfunction ,Amyloid Precursor Protein Secretases ,Maze Learning ,Receptors, Cannabinoid ,Biological Psychiatry - Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cascading changes in cognition and behavior. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for the treatment of diabetes, but its function in AD is unclear. The objective of this study was to investigate the neuroprotective effects of O-1602, a GPR55 agonist, on the streptozotocin (STZ)-induced AD mouse model. A single intracerebroventricular (i.c.v.) injection of STZ into the brains of mice significantly induced cognitive impairment. In contrast, O-1602 (2.0 or 4.0 μg/mouse, i.c.v.) can improve the cognitive dysfunction caused by STZ in the Morris water maze (MWM) and novel object recognition (NOR) tests. Importantly, O-1602 treatment reversed STZ-induced GPR55 down-regulation, reduced the activity of β-secretase 1 (BACE1) and the level of Aβ
- Published
- 2021
119. Successful Treatment of Recalcitrant Psoriasis by Scopolamine and Propofol: A Report of Two Cases
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Buwei Yu, Yumei Wu, and Qifang Li
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business.industry ,Psoriasis ,Anesthesia ,medicine ,Scopolamine ,General Medicine ,medicine.disease ,Propofol ,business ,medicine.drug - Published
- 2020
120. Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
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Zhidong Liu, Yumei Wu, Yuanyuan Liu, Peng Lu, Jian Yang, Jiawei Li, Zhe Ma, Bing Zhang, Xinyue Li, and Dereje Kebebe
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Stereochemistry ,Cell ,Biophysics ,Pharmaceutical Science ,Bioengineering ,Peptide ,02 engineering and technology ,Conjugated system ,010402 general chemistry ,01 natural sciences ,Biomaterials ,chemistry.chemical_compound ,Drug Discovery ,Zeta potential ,medicine ,Peptide bond ,Cytotoxicity ,chemistry.chemical_classification ,Organic Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Monomer ,medicine.anatomical_structure ,chemistry ,Gambogic acid ,0210 nano-technology - Abstract
Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity. Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice. Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 µg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK)2] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK)2]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC. Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK)2]-GA-NLC in breast cancer therapy.
- Published
- 2019
121. Dynamic instability of clathrin assembly provides proofreading control for endocytosis
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Yumei Wu, Jeffery Yong, Yang Yang, Min Wu, Antonio Martinez-Sanchez, Yan Chen, Rubén Fernández-Busnadiego, and Pietro De Camilli
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Swine ,Coated vesicle ,macromolecular substances ,Auxilin ,Endocytosis ,Clathrin ,Clathrin coat ,03 medical and health sciences ,0302 clinical medicine ,Report ,Animals ,Research Articles ,030304 developmental biology ,0303 health sciences ,biology ,Extramural ,Cell Biology ,Receptor-mediated endocytosis ,Cell biology ,biology.protein ,Proofreading ,030217 neurology & neurosurgery - Abstract
Chen et al. reconstitute endocytosis in a cell-free system and show that cargo sorting requires the dynamic dissociation of clathrin during the growth phase of the clathrin-coated pit formation., Clathrin-mediated endocytosis depends on the formation of functional clathrin-coated pits that recruit cargos and mediate the uptake of those cargos into the cell. However, it remains unclear whether the cargos in the growing clathrin-coated pits are actively monitored by the coat assembly machinery. Using a cell-free reconstitution system, we report that clathrin coat formation and cargo sorting can be uncoupled, indicating that a checkpoint is required for functional cargo incorporation. We demonstrate that the ATPase Hsc70 and a dynamic exchange of clathrin during assembly are required for this checkpoint. In the absence of Hsc70 function, clathrin assembles into pits but fails to enrich cargo. Using single-molecule imaging, we further show that uncoating takes place throughout the lifetime of the growing clathrin-coated pits. Our results suggest that the dynamic exchange of clathrin, at the cost of the reduced overall assembly rates, primarily serves as a proofreading mechanism for quality control of endocytosis.
- Published
- 2019
122. Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry
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Jiawei Li, Bing Zhang, Yumei Wu, Pan Guo, Jiaxin Pi, Jun Lu, Zhidong Liu, Lili Fan, Dongli Qi, Nan Li, and Bo-ying Liu
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Tight junctions associated proteins ,Membrane permeability ,Pharmaceutical Science ,Western blot ,02 engineering and technology ,Labrasol ,010402 general chemistry ,01 natural sciences ,Cornea ,medicine ,Transdermal ,Ussing chamber ,Pharmacology ,medicine.diagnostic_test ,Chemistry ,lcsh:RM1-950 ,Penetration (firestop) ,Permeation ,021001 nanoscience & nanotechnology ,Immunohistochemistry ,0104 chemical sciences ,medicine.anatomical_structure ,lcsh:Therapeutics. Pharmacology ,Paracellular transport ,Biophysics ,0210 nano-technology ,Enhanced corneal permeation ,Research Article - Abstract
Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as F-actin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively., Graphical abstract Image, graphical abstract
- Published
- 2019
123. Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment
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Zhidong Liu, Yumei Wu, Yuqi Fan, Bing Zhang, Zhe Ma, Jiaxin Pi, Peng Lu, and Dereje Kebebe
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Tumor targeting ,Combination therapy ,Combined use ,Biophysics ,Pharmaceutical Science ,Design elements and principles ,Antineoplastic Agents ,Bioengineering ,Nanotechnology ,Review ,codelivery ,02 engineering and technology ,Traditional Chinese medicine ,010402 general chemistry ,01 natural sciences ,combination therapy ,Biomaterials ,Drug Delivery Systems ,Neoplasms ,Drug Discovery ,cancer ,Humans ,Medicine ,Molecular Targeted Therapy ,Medicine, Chinese Traditional ,Therapeutic strategy ,tumor targeting ,business.industry ,Organic Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,TCM ,nanotargeted drug-delivery system ,Drug release ,Drug Therapy, Combination ,Nanocarriers ,0210 nano-technology ,business ,Drugs, Chinese Herbal - Abstract
Cancer is a major public health problem, and is now the world’s leading cause of death. Traditional Chinese medicine (TCM)-combination therapy is a new treatment approach and a vital therapeutic strategy for cancer, as it exhibits promising antitumor potential. Nano-targeted drug-delivery systems have remarkable advantages and allow the development of TCM-combination therapies by systematically controlling drug release and delivering drugs to solid tumors. In this review, the anticancer activity of TCM compounds is introduced. The combined use of TCM for antitumor treatment is analyzed and summarized. These combination therapies, using a single nanocarrier system, namely codelivery, are analyzed, issues that require attention are determined, and future perspectives are identified. We carried out a systematic review of >280 studies published in PubMed since 1985 (no patents involved), in order to provide a few basic considerations in terms of the design principles and management of targeted nanotechnology-based TCM-combination therapies.
- Published
- 2019
124. Lipid transporter TMEM24/C2CD2L is a Ca 2+ -regulated component of ER–plasma membrane contacts in mammalian neurons
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Yiying Cai, Pietro De Camilli, Andrés Guillén-Samander, Yumei Wu, Mirko Messa, Elizabeth Wen Sun, and Xin Bian
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Primary Cell Culture ,Phospholipid ,Endoplasmic Reticulum ,Cell Line ,Mice ,Synaptotagmins ,chemistry.chemical_compound ,Animals ,Humans ,Calcium Signaling ,Phosphorylation ,Phospholipids ,Ion channel ,Lipid Transport ,Mammals ,Neurons ,Multidisciplinary ,Endoplasmic reticulum ,Cell Membrane ,Membrane Proteins ,Transporter ,Lipids ,Potassium channel ,Cell biology ,Cytosol ,PNAS Plus ,chemistry ,Calcium ,Calcium Channels ,Plant lipid transfer proteins - Abstract
Close appositions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are a general feature of all cells and are abundant in neurons. A function of these appositions is lipid transport between the two adjacent bilayers via tethering proteins that also contain lipid transport modules. However, little is known about the properties and dynamics of these proteins in neurons. Here we focused on TMEM24/C2CD2L, an ER-localized SMP domain containing phospholipid transporter expressed at high levels in the brain, previously shown to be a component of ER–PM contacts in pancreatic β-cells. TMEM24 is enriched in neurons versus glial cells and its levels increase in parallel with neuronal differentiation. It populates ER–PM contacts in resting neurons, but elevations of cytosolic Ca(2+) mediated by experimental manipulations or spontaneous activity induce its transient redistribution throughout the entire ER. Dissociation of TMEM24 from the plasma membrane is mediated by phosphorylation of an array of sites in the C-terminal region of the protein. These sites are only partially conserved in C2CD2, the paralogue of TMEM24 primarily expressed in nonneuronal tissues, which correspondingly display a much lower sensitivity to Ca(2+) elevations. ER–PM contacts in neurons are also sites where Kv2 (the major delayed rectifier K(+) channels in brain) and other PM and ER ion channels are concentrated, raising the possibility of a regulatory feedback mechanism between neuronal excitability and lipid exchange between the ER and the PM.
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- 2019
125. Research progress of in-situ gelling ophthalmic drug delivery system
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Dereje Kebebe, Yumei Wu, Jun Lu, Jiawei Li, Jing Ren, Yuanyuan Liu, Zhidong Liu, Xinyue Li, Bing Zhang, and Shouying Du
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Drug ,medicine.medical_specialty ,Bioavailability ,genetic structures ,media_common.quotation_subject ,Pharmaceutical Science ,02 engineering and technology ,Review Article ,010402 general chemistry ,Corneal retention ,01 natural sciences ,Social burden ,Ocular ,Ophthalmic drug ,Global health ,Medicine ,Intensive care medicine ,Polymer ,media_common ,Pharmacology ,business.industry ,lcsh:RM1-950 ,021001 nanoscience & nanotechnology ,eye diseases ,0104 chemical sciences ,In-situ gel ,Posterior segment of eyeball ,lcsh:Therapeutics. Pharmacology ,Drug delivery ,Delivery system ,sense organs ,0210 nano-technology ,business - Abstract
Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (, Graphical abstract Image, graphical abstract
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- 2019
126. Multimodal Imaging of Synaptic Vesicles with a Single Probe
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Yumei Wu, Travis J. Gould, David Zenisek, Stephen M. Strittmatter, Joerg Bewersdorf, Michael J. Mlodzianoski, Seong An, Pietro De Camilli, and Massimiliano Stagi
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Multimodal imaging ,Modality (human–computer interaction) ,Computer science ,Vesicle ,Temporal resolution ,Microscopy ,Biophysics ,Synaptic vesicle recycling ,Synaptic vesicle ,C2 domain - Abstract
A complete understanding of synaptic vesicle recycling requires the use of multiple microscopy methods to obtain complementary information. However, many currently available probes are limited to a specific microscopy modality, which necessitates the use of multiple probes and labeling paradigms. Given the complexity of vesicle populations and recycling pathways, having new single vesicle probes that could be used for multiple microscopy techniques would complement existing sets of tools for studying vesicle function. Here we present a novel probe based on the membrane-binding C2 domain of cytosolic phospholipase A2 (cPLA2) that fulfills this need. By conjugating the C2 domain with different detectable tags, we demonstrate that a single, modular probe can allow synaptic vesicles to be imaged at multiple levels of spatial and temporal resolution.
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- 2021
127. Chemical Composition, Protective Effects, and Mechanisms of Volatile Oil from Fructus Gleditsiae Abnormalis with Nasal Administration against Ischemic Injury in HFD and MCAO-Induced Rats
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Dereje Kebebe, Nana Dong, Xiaolan Chen, Jing Wan, Wei Han, Bili Deng, Chengyue Luo, and Yumei Wu
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Article Subject ,business.industry ,Cerebral infarction ,Ischemia ,Blood stasis ,Pharmacology ,medicine.disease ,medicine.disease_cause ,Neuroprotection ,Other systems of medicine ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,medicine ,Hemorheology ,Paeonol ,business ,Stroke ,RZ201-999 ,Oxidative stress ,Research Article - Abstract
Fructus Gleditsiae Abnormalis (FGA) has been used as a traditional Chinese medicine (TCM) for the treatment of stroke caused by phlegm and blood stasis. However, its substance basis and mechanism of action are currently unknown. This study is aimed to analyze the constituents of the volatile oil in FGA (VOFGA) using gas chromatography coupled with mass spectrometry (GC-MS) and explore the underlying effects and mechanisms of VOFGA in the prevention and treatment of ischemia stroke. An in vivo ischemia model was constructed by combination treatment of high-fat diet (HFD) and middle cerebral artery occlusion (MCAO) method. After administration, the cerebral infarction volume, the brain water content, hemorheology, blood lipids, inflammatory factors, oxidative stress indicators, Bax, Bcl-2, and cleaved caspase-3 and histological examination (HE) were determined and observed to explore the underlying effects and mechanisms of VOFGA against ischemia stroke. The results showed that forty components were determined after analyzed by GC-MS, and the percentage content of palmitate, paeonol, violetone, linalool, salpinol, citral, and methyleugenol were 4.69%, 5.2%, 3.56%, 3.31%, 2.42%, 2.65%, and 1.67%, respectively. The high dose of VOFGA could inhibit neurological damage; reduce the cerebral infarction volume and brain water content; improve whole blood viscosity and red blood cell aggregation index at various shear rates; reduce the levels of TG, TC, LDL-C, TNF-α, IL-1β, MDA, and NO; increase the contents of HDL-C, IL-10, and SOD; downregulate the expressions of Bax and cleaved caspase-3 in the ischemic regions; and upregulate the expressions of Bcl-2. These effects implied that VOFGA may exert neuroprotective effects via inhibiting ischemia-triggered oxidative damage-regulating blood lipid factors and reducing the production of proinflammatory mediators against cerebral I/R injury and neuronal apoptosis. The VOFGA presents a potential treatment value for cerebral ischemic stroke, and it may offer insights into discovering new active compounds for the treatment of ischemic stroke.
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- 2021
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128. A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane.
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Guillén-Samander, Andrés, Yumei Wu, Pineda, S. Sebastian, García, Francisco J., Eisen, Julia N., Leonzino, Marianna, Ugur, Berrak, Kellis, Manolis, Heiman, Myriam, and De Camilli, Pietro
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LIPID transfer protein , *CELL membranes , *BLOOD proteins , *INTRACELLULAR membranes , *LIPIDS , *ANIMAL products - Abstract
Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an endoplasmic reticulum (ER)-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK, and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration. [ABSTRACT FROM AUTHOR]
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- 2022
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129. Activation of GPR55 attenuates cognitive impairment and neurotoxicity in a mouse model of Alzheimer's disease induced by Aβ
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XiaoTong, Xiang, Xin, Wang, ShiYu, Jin, Jie, Hu, YuMei, Wu, YueYue, Li, and Xian, Wu
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Memory Disorders ,Amyloid beta-Peptides ,Brain ,Apoptosis ,Hippocampus ,Peptide Fragments ,Disease Models, Animal ,Mice ,Infusions, Intraventricular ,Alzheimer Disease ,Animals ,Cannabidiol ,Cognitive Dysfunction ,Neurotoxicity Syndromes ,Amyloid Precursor Protein Secretases ,Receptors, Cannabinoid - Abstract
The accumulation of amyloid-β (Aβ) peptides in the brain is considered to be the initial event in the Alzheimer's disease (AD). Neurotoxicity mediated by Aβ has been demonstrated to damage the cognitive function. In the present study, we sought to determine the effects of O-1602, a specific G-protein coupled receptor 55 (GPR55) agonist, on the impairment of learning and memory induced by intracerebroventricular (i.c.v.) of Aβ
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- 2020
130. Activation of GPR55 attenuates cognitive impairment and neurotoxicity in a mouse model of Alzheimer's disease induced by Aβ1–42 through inhibiting RhoA/ROCK2 pathway
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XiaoTong Xiang, Jie Hu, YuMei Wu, Xin Wang, ShiYu Jin, Xian Wu, and YueYue Li
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Pharmacology ,RHOA ,biology ,Chemistry ,Neurotoxicity ,Hippocampus ,Morris water navigation task ,medicine.disease ,Superoxide dismutase ,Synaptophysin ,biology.protein ,medicine ,Memory impairment ,Receptor ,Biological Psychiatry - Abstract
The accumulation of amyloid-β (Aβ) peptides in the brain is considered to be the initial event in the Alzheimer's disease (AD). Neurotoxicity mediated by Aβ has been demonstrated to damage the cognitive function. In the present study, we sought to determine the effects of O-1602, a specific G-protein coupled receptor 55 (GPR55) agonist, on the impairment of learning and memory induced by intracerebroventricular (i.c.v.) of Aβ1–42 (400 pmol/mouse) in mice. Our results showed that i.c.v. injection of aggregated Aβ1–42 into the brain of mice resulted in cognitive impairment and neurotoxicity. In contrast, O-1602 (2.0 or 4.0 μg/mouse, i.c.v.) can improve memory impairment induced by Aβ1–42 in the Morris water maze (MWM), and novel object recognition (NOR) tests. Besides, we found that O-1602 reduced the activity of β-secretase 1 (BACE1) and the level of soluble Aβ1–42 in the hippocampus and frontal cortex. Importantly, O-1602 treatment reversed Aβ1–42-induced GPR55 down-regulation, decreased pro-inflammatory cytokines, and the level of malondialdehyde (MDA), increased the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as well as suppressed apoptosis as indicated by decreased TUNEL-positive cells, and increased the ratio of Bcl-2/Bax. O-1602 treatment also pronouncedly ameliorated synaptic dysfunction by promoting the upregulation of PSD-95 and synaptophysin (SYN) proteins. Moreover, O-1602 concurrently down regulated the protein levels of RhoA, and ROCK2, the critical proteins in the RhoA/ROCK2 pathway. This study indicates that O-1602 may reverse Aβ1–42-induced cognitive impairment and neurotoxicity in mice by inhibiting RhoA/ROCK2 pathway. Taken together, these findings suggest that GPR55 could be a novel and promising target for the treatment of AD.
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- 2022
131. Establishment and verification of the nomogram that predicts the 3-year recurrence risk of epithelial ovarian carcinoma
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Xiaobing Jiao, Lirong Zhu, Hongyan Guo, and Yumei Wu
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Background As we all know, patients with epithelial ovarian carcinomahave poor prognosis and high recurrence rate. It is critical and challenging to screen out the patients with high risk of recurrence. At present, there are some models predicting the overall survival of epithelial ovarian carcinoma, however, thereis no widely accepted tool or applicable model predicting the recurrence risk of epithelial ovarian carcinomapatients. The objective of this study was to establish and verify a nomogram to predict the recurrence risk of EOC.Results The nomogram for 3-year recurrence risk was established with FIGO stage, histological grade, histological type, lymph node metastasis status and serum CA125 level at diagnosis. The total score can be obtained by adding the grading values of these factors together. In the external validation, the AUC (C statistics) was 0.803 [95%CI, 0.738-0.867] and the Chi-square value is 11.04 (P=0.135>0.05). With the threshold value of 198, the sensitivity, specificity, positive predictive value, negative predictive value and correct index of the monogram were 75.7%, 77.0%, 83.2%, 67.9%, and 0.52 respectively.Conclusions We established and validated a nomogram to predict 3-year recurrence risk of patients with EOC who achieved clinical complete remission after cytoreductive surgery and chemotherapy. This nomogram with good discrimination and calibration might be useful for screening out the patients with high risk of recurrence.
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- 2020
132. Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells
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Pietro De Camilli, Goeun Kim, Sangeun Lee, Yumei Wu, Seonyoung Jeong, Sunghoe Chang, Dragomir Milovanovic, and Daehun Park
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0301 basic medicine ,General Physics and Astronomy ,Supramolecular assembly ,Mice ,0302 clinical medicine ,Cytosol ,Chlorocebus aethiops ,Synaptic vesicle exocytosis ,Cells, Cultured ,Neurons ,Multidisciplinary ,biology ,Chemistry ,Vesicle ,Synapsin ,Endocytosis ,metabolism [Neurons] ,COS Cells ,ddc:500 ,Synaptic Vesicles ,metabolism [Fibroblasts] ,Science ,Static Electricity ,Synaptophysin ,ultrastructure [Fibroblasts] ,Neurotransmission ,Synaptic vesicle ,General Biochemistry, Genetics and Molecular Biology ,Article ,ultrastructure [Synaptic Vesicles] ,03 medical and health sciences ,Animals ,Humans ,metabolism [Synapsins] ,metabolism [Synaptic Vesicles] ,Intrinsically disordered proteins ,metabolism [Synaptophysin] ,metabolism [Calcium-Calmodulin-Dependent Protein Kinase Type 2] ,General Chemistry ,Fibroblasts ,Synapsins ,Microvesicles ,Cellular neuroscience ,030104 developmental biology ,nervous system ,Membrane protein ,biology.protein ,Biophysics ,metabolism [Cytosol] ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,030217 neurology & neurosurgery - Abstract
Clusters of tightly packed synaptic vesicles (SVs) are a defining feature of nerve terminals. While SVs are mobile within the clusters, the clusters have no boundaries consistent with a liquid phase. We previously found that purified synapsin, a peripheral SV protein, can assemble into liquid condensates and trap liposomes into them. How this finding relates to the physiological formation of SV clusters in living cells remains unclear. Here, we report that synapsin alone, when expressed in fibroblasts, has a diffuse cytosolic distribution. However, when expressed together with synaptophysin, an integral SV membrane protein previously shown to be localized on small synaptic-like microvesicles when expressed in non-neuronal cells, is sufficient to organize such vesicles in clusters highly reminiscent of SV clusters and with liquid-like properties. This minimal reconstitution system can be a powerful model to gain mechanistic insight into the assembly of structures which are of fundamental importance in synaptic transmission., Synaptic vesicle clusters were proposed to represent phase separated condensates. Here, the authors show that only two proteins, synapsin and synaptophysin, are sufficient to make vesicle clusters in fibroblasts which are similar to those found at synapses in morphology and liquid-like properties.
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- 2020
133. Laparoscopic Versus Open Abdominal Radical Hysterectomy for Patients with Endometrial Cancer Involving Cervix
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Ming Wang, Ziyi Zhao, Xiaohong Xu, Jinwei Miao, Weimin Kong, Wei Duan, Li Su, Ziran Yin, and Yumei Wu
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BACKGROUND: Data on the survival outcome between laparoscopic and open abdominal radical hysterectomy is limited in patients with endometrial cancer involving cervix.METHODS: We performed a retrospective 1:1 matched observational study in patients who had their cervix involved by endometrial cancer during the 2010–2018 period in Beijing Obstetrics and Gynecology Hospital in China. All enrolled patients underwent cancer-directed radical hysterectomy through laparoscopic approach or open abdominal surgery and followed until 3 years after the surgery. The primary outcome was the rates of disease-free survival and overall survival.RESULTS: A total of 142 patients were included in the study, 54 patients received laparoscopic surgery and 54 of the remaining 88 patients who received open surgery were selected as control. Overall, the median follow-up duration was 54.22 ± 31.14 months (95%CI: 48.71–59.89 months). There was no difference on the baseline information between two groups, including ages, rates of histologic subtypes, rates of deep myometrial invasion, rates of lymph-node involvement, and postoperative stage. There was no significant difference between the three-year disease-free rates between two groups (3-year rate, 94.3% vs. 92.2%; hazard ratio, 1.36; 95% CI, 0.40 to 4.61). The 3-years rate of overall survival in patients of the laparoscopic group was comparable to patients in the open surgery group (3-year rate, 89.87% vs. 92.14%; hazard ratio for death from any cause, 1.87; 95% CI, 0.60 to5.86).CONCLUSIONS: This study revealed that laparoscopic approach surgery was not associated with shorter disease-free survival and overall survival than open abdominal radical hysterectomy in patients with endometrial cancer involving cervix.
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- 2020
134. Survey of human and bovine tuberculosis infection on dairy farms in southwestern China
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Wei Hou, Yan Liu, Shu Zhang, Zhengyuan Rao, Xiulan Yang, Aiguo Yang, Yumei Wu, Liang Zhang, Li Guo, and Chuang Chen
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Veterinary medicine ,Geography ,Bovine tuberculosis ,China - Abstract
Background Tuberculosis is a zoonotic chronic infectious disease that can be transmitted through respiratory secretions, causing simultaneous infection in both people and cattle. The aim of our study was to identify the co-infections of Mycobacterium tuberculosis between human and cattle in dairy farms in Sichuan Province, southwest China.Results We selected 6 large-scale dairy farms and 5 small-scale dairy farms in Sichuan Province, southwest China, as research sites. A total of 378 dairy farm workers (except one pregnant woman)were screened for tuberculosis symptoms and examined by X-ray radiographs. One worker was diagnosed with tuberculosis, but the sputum culture result was negative, and no strain was obtained. The purified protein derivative (PPD) skin tests of 10224 dairy cows showed that 99 cows were positive, with a positive rate of 9.7‰. The Oesophageal-Pharyngeal (OP) secretions of PPD-positive cows were cultured, and 21 strains were obtained. After amplifying and sequencing the 16SrDNA, hsp65 and rpoB genes and the ITS region, sequence alignment in BLAST showed that these strains were nontuberculous mycobacteria (NTM)(18 Mycobacterium nonchromogenicum , 1 Mycobacterium hiberniae , 1 Mycobacterium arupense and 1 Mycobacterium chitae ).Conclusion This study indicated that PPD-positive cows on dairy farms were infected with NTM rather than Mycobacterium bovis . Cross-infection of tuberculosis between humans and cows on dairy farms has been controlled.
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- 2020
135. Singularities of plane gravitational waves in Einstein’s general relativity
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Guoliang Lü, Bowen Li, Anzhong Wang, Jared Fier, Yumei Wu, Zhaojun Wang, and Tongzheng Wang
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Physics ,Physics and Astronomy (miscellaneous) ,010308 nuclear & particles physics ,Gravitational wave ,General relativity ,Plane (geometry) ,Null (mathematics) ,Graviton ,01 natural sciences ,General Relativity and Quantum Cosmology ,Differential geometry ,Schwarzschild coordinates ,0103 physical sciences ,Gravitational singularity ,010303 astronomy & astrophysics ,Mathematical physics - Abstract
Similar to the Schwarzschild coordinates for spherical black holes, the Baldwin, Jeffery and Rosen (BJR) coordinates for plane gravitational waves are often singular, and extensions beyond such singularities are necessary, before studying asymptotic properties of such spacetimes at the null infinity of the plane, on which the gravitational waves propagate. The latter is closely related to the studies of memory effects and soft graviton theorems. In this paper, we point out that in the BJR coordinates all the spacetimes are singular physically at the focused point $$u = u_s$$, except for the two cases: (1) $$\alpha =1/2, \; \forall \; \chi _n$$; and (2) $$\alpha =1, \; \chi _i = 0\; (i = 1, 2, 3)$$, where $$\chi _n$$ are the coefficients in the expansion $$\chi \equiv \left[ {\text{ det }}\left( g_{ab}\right) \right] ^{1/4} = \left( u- u_s\right) ^{\alpha }\sum _{n = 0}^{\infty }\chi _n \left( u - u_s\right) ^n$$ with $$\chi _0 \not = 0$$, the constant $$\alpha \in (0, 1]$$ characterizes the strength of the singularities, and $$g_{ab}$$ denotes the reduced metric on the two-dimensional plane orthogonal to the propagation direction of the wave. Therefore, the hypersurfaces $$u= u_s$$ already represent the boundaries of such spacetimes, and the null infinity does not belong to them. As a result, they cannot be used to study properties of plane gravitational waves at null infinities, including memory effects and soft graviton theorems.
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- 2020
136. α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons
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Jeremy H. Herskowitz, Benjamin W. Henderson, Jada H. Vaden, Laura A. Volpicelli-Daley, Gokulakrishna Banumurthy, Linda Overstreet-Wadiche, Yumei Wu, John W. Mclean, Jessica M. Froula, and Jose Carlos Gonzalez
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0301 basic medicine ,Patch-Clamp Techniques ,Dendritic spine ,Physiology ,Calcium imaging ,Tetrodotoxin ,Hippocampal formation ,Hippocampus ,Dendritic spines ,lcsh:RC346-429 ,Pathology and Forensic Medicine ,GABA Antagonists ,Synapse ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Transduction, Genetic ,Postsynaptic potential ,medicine ,Animals ,Picrotoxin ,Cells, Cultured ,lcsh:Neurology. Diseases of the nervous system ,Fibril ,Neurons ,Synucleinopathies ,α-Synuclein ,Lewy body ,Chemistry ,Research ,Synaptic Potentials ,medicine.disease ,Endotoxins ,Mice, Inbred C57BL ,030104 developmental biology ,Lewy neurite ,nervous system ,Phosphopyruvate Hydratase ,alpha-Synuclein ,Excitatory postsynaptic potential ,Parkinson’s disease ,Calcium ,Neurology (clinical) ,Neuron death ,Neuroscience ,030217 neurology & neurosurgery ,Sodium Channel Blockers - Abstract
Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death. Electronic supplementary material The online version of this article (10.1186/s40478-018-0537-x) contains supplementary material, which is available to authorized users.
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- 2018
137. A reliability analysis method of network structure reconfiguration for phased mission system
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Yumei Wu, Jingxiu Yao, and Bin Liu
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Computer Networks and Communications ,Computer science ,Survivability ,Network structure ,Control reconfiguration ,020206 networking & telecommunications ,02 engineering and technology ,Construct (python library) ,Reliability engineering ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,Software ,Reliability (statistics) ,Analysis method - Abstract
The analytical hierarchy method for phased mission system is presented to construct the time super-network model. The means of network structure reconfiguration are analyzed to improve the reliability including survivability and the invulnerability of the time super-network model for phased mission system. The effects of the reliability of the time super-network by applying network structure reconfiguration are compared. Experiment results show that the survivability and the invulnerability of the network increase as the increasing of the connectivity between new functional unit and others.
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- 2018
138. Inhibition of GPR17 with cangrelor improves cognitive impairment and synaptic deficits induced by Aβ1–42 through Nrf2/HO-1 and NF-κB signaling pathway in mice
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Yue Lin Dong, YueYue Li, YueQiang Tan, ShiYu Jin, Xian Wu, YuMei Wu, Xin Wang, XiaoTong Xiang, and Jie Hu
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Pharmacology ,Microglia ,biology ,Chemistry ,Amyloid beta ,Immunology ,Neurotoxicity ,Hippocampus ,medicine.disease_cause ,medicine.disease ,Heme oxygenase ,chemistry.chemical_compound ,medicine.anatomical_structure ,Cangrelor ,medicine ,biology.protein ,Immunology and Allergy ,Neuroinflammation ,Oxidative stress - Abstract
The accumulation of amyloid beta (Aβ) in the brain is thought to be associated with cognitive deficits in Alzheimer's disease (AD). However, current methods to combat Aβ neurotoxicity are still lacking. G protein-coupled receptor 17 (GPR17) has become a target for treating inflammation in brain diseases, but it is unclear whether it has a role in AD. Here, we investigated the effects of cangrelor, a GPR17 antagonist, on neurotoxicity and memory impairment induced by intracerebroventricular (i.c.v.) injection of Aβ1–42 in mice. The behavior results showed that cangrelor (2.0 or 4.0 μg/mouse, i.c.v.) treatment reversed the deficits in memory and learning ability induced by Aβ1–42 in mice. Importantly, we demonstrated for the first time that GPR17 expression in the hippocampus and frontal cortex is increased in response to Aβ1–42 exposures. We also found that cangrelor treatment reduced the activity of β-secretase 1 (BACE1) and the levels of soluble Aβ1–42 in the hippocampus and frontal cortex. Meanwhile, cangrelor treatment suppressed oxidative stress induced by Aβ1–42, as proved by reduced production of malondialdehyde (MDA), and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), and promoted the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Furthermore, cangrelor also suppressed Aβ1–42-induced neuroinflammation, characterized by suppressed activation of microglia, decreased the levels of pro-inflammatory cytokines, and nuclear translocation of NF-κB p65, as well as ameliorated synaptic deficits by promoting the upregulation of synaptic proteins, and increasing the number of Golgi-Cox stained dendritic spines. These results suggest that cangrelor may reverse Aβ1–42-induced cognition deficits via inhibiting oxidative stress, neuroinflammation, and synaptic dysfunction mediated by Nrf2/HO-1 and NF-κB signaling.
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- 2021
139. Measurement and decomposition of energy efficiency of Northeast China—based on super efficiency DEA model and Malmquist index
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Xiaojun Ma, Yan Liu, Mengchen Zheng, Yumei Wu, Yifan Li, Chaochao Cheng, Xiaoxue Wei, Yuanbo Yu, Zhaonan Liu, and Yudong Li
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China ,020209 energy ,Health, Toxicology and Mutagenesis ,02 engineering and technology ,General Medicine ,Models, Theoretical ,010501 environmental sciences ,Environment Problem ,Efficiency, Organizational ,01 natural sciences ,Pollution ,Super efficiency ,Socioeconomic Factors ,0202 electrical engineering, electronic engineering, information engineering ,Decomposition (computer science) ,Econometrics ,Environmental Chemistry ,Tobit model ,Total factor productivity ,Malmquist index ,0105 earth and related environmental sciences ,Mathematics ,Efficient energy use - Abstract
Nowadays, environment problem has become the international hot issue. Experts and scholars pay more and more attention to the energy efficiency. Unlike most studies, which analyze the changes of TFEE in inter-provincial or regional cities, TFEE is calculated with the ratio of target energy value and actual energy input based on data in cities of prefecture levels, which would be more accurate. Many researches regard TFP as TFEE to do analysis from the provincial perspective. This paper is intended to calculate more reliably by super efficiency DEA, observe the changes of TFEE, and analyze its relation with TFP, and it proves that TFP is not equal to TFEE. Additionally, the internal influences of the TFEE are obtained via the Malmquist index decomposition. The external influences of the TFFE are analyzed afterward based on the Tobit models. Analysis results demonstrate that Heilongjiang has the highest TFEE followed by Jilin, and Liaoning has the lowest TFEE. Eventually, some policy suggestions are proposed for the influences of energy efficiency and study results.
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- 2017
140. Increasing efficacy and reducing systemic absorption of brimonidine tartrate ophthalmic gels in rabbits
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Yumei Wu, Zhidong Liu, Pan Guo, Nan Li, Jiaxin Pi, Xiaochen Pang, Dongli Qi, and Jiawei Li
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Intraocular pressure ,Acrylic Resins ,Biological Availability ,Pharmaceutical Science ,Administration, Ophthalmic ,Lactose ,Methylcellulose ,Pharmacology ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Brimonidine Tartrate ,Animals ,Medicine ,Intraocular Pressure ,business.industry ,Systemic absorption ,General Medicine ,Absorption, Physiological ,Ophthalmic solutions ,030221 ophthalmology & optometry ,Uplc ms ms ,Rabbits ,Delivery system ,Ophthalmic Solutions ,business ,Gels ,Biological availability - Abstract
Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC
- Published
- 2017
141. Quantification of Nineteen Bioactive Components in the Ancient Classical Chinese Medicine Formula of Wen-Dan Decoction and Its Commercial Preparations by UHPLC-QQQ-MS/MS
- Author
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Dongli Qi, Zhidong Liu, Deng Xiuping, Zhe Ma, Dereje Kebebe, Zhifeng Xue, Peng Lu, Nan Li, Jiaxin Pi, Yumei Wu, Bing Zhang, and Pan Guo
- Subjects
Calibration curve ,Formic acid ,Phytochemicals ,Pharmaceutical Science ,Decoction ,01 natural sciences ,Dosage form ,Article ,Wen-Dan Decoction ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,Limit of Detection ,Tandem Mass Spectrometry ,Drug Discovery ,Cluster Analysis ,Physical and Theoretical Chemistry ,Medicine, Chinese Traditional ,Chromatography, High Pressure Liquid ,Chromatography ,quantitative analysis ,Elution ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Selected reaction monitoring ,commercial preparations ,Reference Standards ,0104 chemical sciences ,Triple quadrupole mass spectrometer ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Molecular Medicine ,UHPLC-QQQ-MS/MS ,Quantitative analysis (chemistry) ,Drugs, Chinese Herbal - Abstract
A UHPLC-QQQ-MS/MS method was developed to quantify the significant constituents in Wen-Dan Decoction (WDD), a traditional Chinese medicine. Analysis of 19 compounds was conducted on an ACQUITY UPLC®, BEH C18 Column (2.1 ×, 50 mm, 1.7 &mu, m) using elution with a gradient elution of acetonitrile and 0.05% (v/v) formic acid in water. A triple quadrupole mass spectrometer was operated in negative ionization mode and positive ionization mode by multiple reaction monitoring (MRM), respectively. All calibration curves showed acceptable linearity (r &ge, 0.9950). The RSDs of intra- and inter-day precisions of low, mid and high concentrations were &le, 8.88%. The repeatabilities (RSDs &le, 7.17%) and stabilities (RSD &le, 4.79%) of the samples were qualified. The recoveries were found in the range of 93.07 ±, 3.86 to 103.98 ±, 2.98% with the RSD varying between 1.30 and 7.86%. The final rapid, sensitive, precise, accurate and reliable UHPLC-QQQ-MS/MS method was used for the simultaneous quantification of 19 constituents in WDD and its commercial preparations. The strategy of combining the contents of the 19 chemicals in a daily dose of the WDD preparations with the hierarchical cluster analysis and the 3D principal component analysis was employed to effectively distinguish the WDD preparations provided by the different suppliers, which represents a contribution to the evaluation and control of the quality of WDD (or other decoctions consisting of the same herbs) and the preparations of WDD in other dosage forms such as tablets and granules.
- Published
- 2019
142. Drosophilafemale-specific brain neuron elicits persistent position- and direction-selective male-like social behaviors
- Author
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Bidaye Ss, Yumei Wu, and Mahringer D
- Subjects
endocrine system ,Lineage (genetic) ,Biology ,Neurotransmission ,medicine.anatomical_structure ,medicine ,Biological neural network ,Neuron ,Mating ,Neuroscience ,Function (biology) ,Acetylcholine ,Social behavior ,medicine.drug - Abstract
SummaryLatent neural circuitry in the female brain encoding male-like mating behaviors has been revealed in both mice and flies. InDrosophila, a key component of this circuitry consists of thedoublesex-expressing pC1 neurons, which were deemed to exist in both sexes and function based on the amount of cells being activated. Here, we identify pC1-alpha, a female-specific subtype of pC1, as responsible for inducing persistent male-like social behaviors in females. We demonstrate that activation of a single pC1-alpha neuron is sufficient for such induction in a position- and direction-selective manner, and activity of pC1-alpha neurons as a whole is indispensable for maintaining normal sexual receptivity. These dual functions of pC1-alpha may require different neurotransmission, with acetylcholine specifically required for the former but not the latter. Our findings suggest that pC1-alpha may be the female counterpart of male P1 due to their shared similarities in morphology, lineage, and social promoting function.
- Published
- 2019
143. Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
- Author
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Dereje, Kebebe, Yumei, Wu, Bing, Zhang, Jian, Yang, Yuanyuan, Liu, Xinyue, Li, Zhe, Ma, Peng, Lu, Zhidong, Liu, and Jiawei, Li
- Subjects
Drug Carriers ,Mice, Inbred BALB C ,Cell Survival ,Xanthones ,Gambogic acid ,nanostructured lipid carriers ,Mice, Nude ,Breast Neoplasms ,Lipids ,Nanostructures ,c(RGD) peptides ,Drug Delivery Systems ,breast cancer ,Cell Line, Tumor ,Animals ,Humans ,Female ,Tissue Distribution ,cell uptake ,Particle Size ,Protein Multimerization ,Oligopeptides ,Original Research ,antitumor - Abstract
Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity. Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice. Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 µg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK)2] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK)2]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC. Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK)2]-GA-NLC in breast cancer therapy.
- Published
- 2019
144. Application Value of Bedside Ultrasound in the Positioning of PICC Tips in Preterm Infants
- Author
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Yuting Jiao, Yumei Wu, and Zhi Yang
- Subjects
medicine.medical_specialty ,business.industry ,Ultrasound ,Significant difference ,Color doppler ultrasound ,Gold standard (test) ,Peripherally inserted central catheter ,Environmental sciences ,Catheter ,Ultrasound guidance ,medicine ,Bedside ultrasound ,GE1-350 ,Radiology ,business - Abstract
Objective To investigate the application value of bedside ultrasound in the localization of the tip of a Peripherally Inserted Central Catheter (PICC) in preterm infants. Methods 52 preterm infants underwent bedside ultrasound and bedside X-ray examination. Observing the position of the catheter tip, and using the bedside X-ray positioning as the gold standard. Statistics of the incidence of PICC tip normal position and ectopic position showed by bedside ultrasound, and comparing the difference between the results of bedside ultrasound and bedside X-ray. Calculating the accuracy, sensitivity, and specificity of ultrasound in diagnosing the tip position, and the length of the inlet and withdrawal tubes of the ectopic catheter was observed and calculated by ultrasound and down-regulated to the appropriate position under ultrasound guidance. Results The display rate of catheter tip by bedside color Doppler ultrasound was 98.0%, and the accuracy rate of tip position was 90.2%. There was no significant difference compared with bedside X-ray (P = 0.375), and the tip position of the two examination methods was highly consistent (Kappa = 0.769, P
- Published
- 2021
145. MiR-27b is epigenetically downregulated in tamoxifen resistant breast cancer cells due to promoter methylation and regulates tamoxifen sensitivity by targeting HMGB3
- Author
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Xiunan Li, Xin Tang, Yumei Wu, and Aihui Liu
- Subjects
0301 basic medicine ,Antineoplastic Agents, Hormonal ,Cell Survival ,Biophysics ,Down-Regulation ,Breast Neoplasms ,Biology ,Biochemistry ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Western blot ,Cell Line, Tumor ,HMGB3 Protein ,medicine ,Humans ,Gene silencing ,Luciferase ,Promoter Regions, Genetic ,skin and connective tissue diseases ,Molecular Biology ,Demethylation ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Promoter ,Cell Biology ,Methylation ,DNA Methylation ,Molecular biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Tamoxifen ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Cancer research ,medicine.drug - Abstract
MiR-27b downregulation is significantly associated with tamoxifen resistance in breast cancer cells. However, how it is downregulated in tamoxifen resistant (TamR) breast cancer cells and its downstream regulation were not clear. By performing MSP assay and QRT-PCR analysis with the use of 5-AZA-dC, a DNA methyltransferase inhibitor, we observed that TamR MCF-7 cells had significantly higher levels of methylation in the miR-27b promoter region than tamoxifen sensitive MCF-7 (TamS) cells and demethylation restored miR-27b expression. Re-expression of miR-27b sensitized TamR MCF-7 cells to tamoxifen, inhibited invasion and reversed epithelial-mesenchymal transition (EMT)-like properties. By using bioinformatics analysis and following dual luciferase and western blot analysis, this study confirmed a direct regulation of miR-27b on HMGB3 expression by binding to the 3′UTR. In addition, this study also found that silencing of HMGB3 indeed partially phenocopied the effects of miR-27b in reducing tamoxifen resistance and cell invasion and in reversing EMT-like properties. Therefore, we infer that HMGB3 is a functional target of miR-27b in modulation of tamoxifen resistance and EMT.
- Published
- 2016
146. Dynamin Function in Exocytosis and Endocytosis Coupling of Dense-Core Vesicles in Pancreatic Beta Cells
- Author
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Yumei Wu, Louis H. Philipson, Pietro De Camilli, Natalia A. Tamarina, Jenifer Wendlick, Shawn M. Ferguson, Fan Fan, and Xuelin Lou
- Subjects
Coupling (electronics) ,Chemistry ,Pancreatic beta Cells ,Biophysics ,Dense Core Vesicles ,Endocytosis ,Exocytosis ,Function (biology) ,Dynamin - Published
- 2020
147. Brain targeting of Baicalin and Salvianolic acid B combination by OX26 functionalized nanostructured lipid carriers
- Author
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Yumei Wu, Zhifeng Xue, Zhidong Liu, Jiawei Li, Jiaxin Pi, Shouying Du, Dereje Kebebe, Xinyue Li, and Xunan Song
- Subjects
Male ,Microdialysis ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Transferrin receptor ,02 engineering and technology ,Pharmacology ,030226 pharmacology & pharmacy ,Permeability ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,In vivo ,Receptors, Transferrin ,parasitic diseases ,medicine ,Animals ,Humans ,Tissue Distribution ,Benzofurans ,Flavonoids ,Drug Carriers ,Chemistry ,Antibodies, Monoclonal ,Brain ,021001 nanoscience & nanotechnology ,Lipids ,In vitro ,Disease Models, Animal ,Drug Combinations ,Drug Liberation ,medicine.anatomical_structure ,Reperfusion Injury ,Pharmacodynamics ,Nanoparticles ,Administration, Intravenous ,Neuron ,0210 nano-technology ,Baicalin ,Drugs, Chinese Herbal - Abstract
In order to deliver Salvianolic acid B (Sal B) and Baicalin (BA) to the brain tissue to repair neuron damage and improve cerebral ischemia-reperfusion injury (IRI), in our previous study, a nanostructured lipid carrier (NLC) containing BA and Sal B, and modified by the transferrin receptor monoclonal antibody OX26 (OX26-BA/Sal B-NLC) was constructed. The present study is to evaluate its in vitro release behavior, in vitro and in vivo targeting ability, in vitro pharmacodynamics and brain pharmacokinetics. The results showed that the release mechanism of the formulation was in line with the Weibull model release equation. The in-vitro and in-vivo targeting ability study exhibited that OX26 modified formulations was obviously higher than that of non-modified and solution groups. The results of in vitro preliminary study to investigate the protective effect of OX26-BA/Sal B-NLC on oxygen-glucose deprivation/reperfusion injured cells showed that it could decrease the injury. Furthermore, the results of brain microdialysis study showed that the OX26-modified preparation group could significantly increase the content of BA in the brain. In the solution group and the unmodified group, Sal B can only be detected at few time points, while OX26-modified BA/Sal B-NLC could be detected within 4 h. These results indicating that OX26-modified NLC can promote the brain delivery of Sal B and BA combination.
- Published
- 2019
148. Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers
- Author
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Yuanyuan Liu, Zhidong Liu, Yumei Wu, Maikhone Vilakhamxay, Dereje Kebebe, and Jiawei Li
- Subjects
0301 basic medicine ,Tumor targeting ,Cell ,Biophysics ,Pharmaceutical Science ,Bioengineering ,Peptide ,02 engineering and technology ,Cell-Penetrating Peptides ,Review ,Biomaterials ,03 medical and health sciences ,Drug Delivery Systems ,Neoplasms ,Drug Discovery ,Medicine ,Animals ,Humans ,cancer ,Cytotoxicity ,chemistry.chemical_classification ,Drug Carriers ,nanocarriers ,business.industry ,herb-based drug ,tumor targeting ,Organic Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,Antineoplastic Agents, Phytogenic ,targeting drug delivery ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Drug delivery ,Cancer research ,Cell-penetrating peptide ,Nanoparticles ,Nanocarriers ,0210 nano-technology ,Drug carrier ,business ,cell-penetrating peptide - Abstract
Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.
- Published
- 2018
149. Additional file 4: of Îą-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons
- Author
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Froula, Jessica, Henderson, Benjamin, Gonzalez, Jose, Vaden, Jada, Mclean, John, Yumei Wu, Gokulakrishna Banumurthy, Overstreet-Wadiche, Linda, Herskowitz, Jeremy, and Volpicelli-Daley, Laura
- Abstract
Figure S4. The length of the active zone and number of synaptic vesicles normalized to active zone length were quantified using transmission electron microscopy images. Only asymmetric synapses were quantified. (PDF 188 kb)
- Published
- 2018
- Full Text
- View/download PDF
150. Additional file 3: of α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons
- Author
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Froula, Jessica, Henderson, Benjamin, Gonzalez, Jose, Vaden, Jada, Mclean, John, Yumei Wu, Gokulakrishna Banumurthy, Overstreet-Wadiche, Linda, Herskowitz, Jeremy, and Volpicelli-Daley, Laura
- Subjects
nervous system - Abstract
Figure S3. A. Neurons were exposed to fibrils or PBS as a control and were sequentially extracted in 1% Tx-100 followed by 2%SDS. Lysates were subjected to SDS-PAGE on a 4–20% gel and immunoblots were performed with antibodies to p-α-syn, total α-syn or Tuj1 as a loading control. B. Neurons were exposed to fibrils and either fixed with 4% paraformaldehyde (left panel) or 4% paraformaldehyde with 1% Tx-100 (right panel). Immunofluorescence was performed with an antibody to p-α-syn. C. Confocal image of a dense spherical inclusion labeled using an antibody to p-α-syn. Hoechst shows the presence of nuclei, although the nucleus juxtaposed to the inclusion appears fainter compared to the healthier nuclei nearby. D. Examples of aggregates that appear morphologically similar to Lewy neurites. Scale bar = 100 μm. (PDF 919 kb)
- Published
- 2018
- Full Text
- View/download PDF
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