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  1. Article: Autophagy in neural stem cells and glia for brain health and diseases.

    Nagayach, Aarti / Wang, Chenran

    Neural regeneration research

    2023  Volume 19, Issue 4, Page(s) 729–736

    Abstract: Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation, maturation, and survival. Autophagy facilities the ... ...

    Abstract Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation, maturation, and survival. Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells. Autophagy arbitrates structural and functional remodeling during the cell differentiation process. Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases. Only recently, studies have begun to shed light on autophagy regulation in glia (microglia, astrocyte, and oligodendrocyte) in the brain. Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development, synaptic function, brain metabolism, cellular debris clearing, and restoration of damaged or injured tissues. Thus, this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions, neurodevelopmental disorders, and neurodegenerative diseases. This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.
    Language English
    Publishing date 2023-10-16
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.382227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Functional Analysis of a Novel Immortalized Murine Microglia Cell Line in 3D Spheroid Model.

    Angst, Gabrielle / Tang, Xin / Wang, Chenran

    Neurochemical research

    2023  Volume 48, Issue 9, Page(s) 2857–2869

    Abstract: Microglia are the residential immune cells of central nervous system and they are crucial for brain development and homeostasis, as well as the progression of inflammatory brain diseases. To study microglia's physiological and pathological functions, one ...

    Abstract Microglia are the residential immune cells of central nervous system and they are crucial for brain development and homeostasis, as well as the progression of inflammatory brain diseases. To study microglia's physiological and pathological functions, one of the most widely used models is primary microglia culture from neonatal rodents. However, primary microglia culture is time consuming and needs a great number of animals. In our microglia culture, we found a strain of spontaneously immortalized microglia that continued to divide without any known genetic intervention. We confirmed the immortalization of these cells for uninterrupted thirty passages and we named them as immortalized microglia like-1 cells (iMG-1). The iMG-1 cells kept their microglia morphology, and they expressed macrophage/microglia-specific proteins of CD11b, CD68, P2RY12, and IBA1 in vitro. iMG-1 cells were responsive to inflammatory stimulations with lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (pIpC), triggering increased mRNA/protein levels of IL1-β, IL-6, TNF-α, and interferons. LPS and pIpC treated iMG-1 cells also significantly increased their accumulation of lipid droplets (LDs). We also generated a 3D spheroid model using immortalized neural progenitor cells and iMG-1 cells with defined percentages to study neuroinflammation. The iMG-1 cells distributed evenly in spheroids, and they regulated the basal mRNA levels of cytokines of neural progenitors in 3D spheroid. iMG-1 cells were responsive to LPS by increased expression of IL-6 and IL1-β in spheroids. Together, this study indicated the reliability of iMG-1 which could be readily available to study the physiological and pathological functions of microglia.
    MeSH term(s) Mice ; Animals ; Microglia/metabolism ; Lipopolysaccharides/pharmacology ; Interleukin-6/metabolism ; Reproducibility of Results ; Cell Line ; RNA, Messenger/metabolism
    Chemical Substances Lipopolysaccharides ; Interleukin-6 ; RNA, Messenger
    Language English
    Publishing date 2023-05-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-023-03952-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Trend and Cause of Mortality Burden in Infancy - China, 1990-2019.

    Wang, Chenran / Xu, Tao

    China CDC weekly

    2021  Volume 3, Issue 16, Page(s) 340–345

    Language English
    Publishing date 2021-09-14
    Publishing country China
    Document type Journal Article
    ISSN 2096-7071
    ISSN (online) 2096-7071
    DOI 10.46234/ccdcw2021.091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease.

    Tang, Xin / Walter, Ellen / Wohleb, Eric / Fan, Yanbo / Wang, Chenran

    Autophagy

    2023  Volume 20, Issue 4, Page(s) 847–862

    Abstract: Macroautophagy/autophagy is the intracellular degradation process of cytoplasmic content and damaged organelles. Autophagy is strongly associated with the progression of Alzheimer disease (AD). Microglia are brain-resident macrophages, and recent studies ...

    Abstract Macroautophagy/autophagy is the intracellular degradation process of cytoplasmic content and damaged organelles. Autophagy is strongly associated with the progression of Alzheimer disease (AD). Microglia are brain-resident macrophages, and recent studies indicate that autophagy in microglia protects neurons from neurodegeneration. Postnatal neurogenesis, the generation of new neurons from adult neural stem cells (NSCs), is impaired in AD patients as well as in AD animal models. However, the extent to which microglial autophagy influences adult NSCs and neurogenesis in AD animal models has not been studied. Here, we showed that conditional knock out (cKO) of
    MeSH term(s) Animals ; Neurogenesis ; Microglia/metabolism ; Microglia/pathology ; Autophagy-Related Protein 5/metabolism ; Autophagy-Related Protein 5/genetics ; Alzheimer Disease/pathology ; Alzheimer Disease/metabolism ; Hippocampus/metabolism ; Hippocampus/pathology ; Autophagy/physiology ; Mice, Knockout ; Female ; Mice ; Neural Stem Cells/metabolism ; Dentate Gyrus/metabolism ; Dentate Gyrus/pathology ; Male ; Disease Models, Animal ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors ; Doublecortin Protein ; Autophagy-Related Proteins/metabolism
    Chemical Substances Autophagy-Related Protein 5 ; Atg5 protein, mouse ; Rb1cc1 protein, mouse ; Dcx protein, mouse ; Csf1r protein, mouse ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; Doublecortin Protein ; Autophagy-Related Proteins
    Language English
    Publishing date 2023-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2023.2277634
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Reducing Neonatal Mortality with a Three-Stage Neonatal Resuscitation Training Programme - China, 2004-2021.

    Wang, Chenran / Yue, Qing / Xu, Tao

    China CDC weekly

    2022  Volume 4, Issue 36, Page(s) 807–810

    Abstract: Neonatal asphyxia is a leading cause of neonatal death that is largely preventable with neonatal resuscitation techniques. In July 2004, China launched a 15-year, three-stage Neonatal Resuscitation Programme (NRP) with stages in 2004-2009, 2011-2016, and ...

    Abstract Neonatal asphyxia is a leading cause of neonatal death that is largely preventable with neonatal resuscitation techniques. In July 2004, China launched a 15-year, three-stage Neonatal Resuscitation Programme (NRP) with stages in 2004-2009, 2011-2016, and 2017-2021 ( 1). The objective of China's NRP was to ensure the presence of at least one trained attendant proficient in neonatal resuscitation at every delivery. With consistent effort, both incidence and mortality from neonatal asphyxia decreased remarkably during 2003-2020: incidence decreased from 6.32% to 1.42% and mortality decreased from 0.76‰ to 0.19‰ ( 1- 2). China's empirical experience shows that widespread promotion of high-quality neonatal resuscitation techniques can reduce preventable neonatal deaths and provide important insight into "ending preventable deaths in newborns by 2030," as proposed in the United Nations Sustainable Development Goal's third target ( 3).
    Language English
    Publishing date 2022-10-15
    Publishing country China
    Document type Systematic Review
    ISSN 2096-7071
    ISSN (online) 2096-7071
    DOI 10.46234/ccdcw2022.168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A unified framework on defining depth for point process using function smoothing

    Xu, Zishen / Wang, Chenran / Wu, Wei

    Computational statistics & data analysis. 2022 June 09,

    2022  

    Abstract: The notion of statistical depth has been extensively studied in multivariate and functional data over the past few decades. In contrast, the depth on temporal point process is still under-explored. The problem is challenging because a point process has ... ...

    Abstract The notion of statistical depth has been extensively studied in multivariate and functional data over the past few decades. In contrast, the depth on temporal point process is still under-explored. The problem is challenging because a point process has two types of randomness: 1) the number of events in a process, and 2) the distribution of these events. Recent studies proposed depths in a weighted product of two terms, describing the above two types of randomness, respectively. Under a new framework through a smoothing procedure, these two randomnesses can be unified. Basically, the point process observations are transformed into functions using conventional kernel smoothing methods, and then the well-known functional h-depth and its modified, center-based version are adopted to describe the center-outward rank in the original data. To do so, a proper metric is defined on the point processes with smoothed functions. Then an efficient algorithm is provided to estimate the defined “center”. The mathematical properties of the newly defined depths are explored and the asymptotic theories are studied. Simulation results show that the proposed depths can properly rank point process observations. Finally, the new methods are demonstrated in a classification task using a real neuronal spike train dataset.
    Keywords algorithms ; data analysis ; data collection ; neurons ; statistics
    Language English
    Dates of publication 2022-0609
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 1478763-5
    ISSN 0167-9473
    ISSN 0167-9473
    DOI 10.1016/j.csda.2022.107545
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats.

    Wang, Chenran / Sun, Shen / Jiao, Jing / Yu, Xinhua / Huang, Shaoqiang

    BMC anesthesiology

    2022  Volume 22, Issue 1, Page(s) 19

    Abstract: Background: Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of ... ...

    Abstract Background: Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics.
    Methods: Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg
    Results: All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4-20.7] versus 7.2 [5.9-8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0-29.1] versus 11.3 [10.7-13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9-11.7] versus 5.6 [4.5-7.0], p = 0.060).
    Conclusions: Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.
    MeSH term(s) Anesthetics, Local/adverse effects ; Animals ; Benzamides/pharmacology ; Bupivacaine/adverse effects ; Cardiotoxicity/prevention & control ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Piperazines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/agonists
    Chemical Substances Anesthetics, Local ; Benzamides ; Piperazines ; Receptors, Opioid ; BW 373U86 (150428-54-9) ; Bupivacaine (Y8335394RO)
    Language English
    Publishing date 2022-01-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091252-3
    ISSN 1471-2253 ; 1471-2253
    ISSN (online) 1471-2253
    ISSN 1471-2253
    DOI 10.1186/s12871-022-01568-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Effects of nalbuphine on the cardiotoxicity of ropivacaine in rats.

    Wang, Chenran / Sun, Shen / Jiao, Jing / Yu, Xinhua / Huang, Shaoqiang

    Fundamental & clinical pharmacology

    2022  Volume 36, Issue 5, Page(s) 811–817

    Abstract: When combined with nalbuphine, local anesthetics show a longer duration of nerve block without increasing complications. However, no evidence is available concerning the effect of nalbuphine on the cardiotoxicity of local anesthetics. The objective of ... ...

    Abstract When combined with nalbuphine, local anesthetics show a longer duration of nerve block without increasing complications. However, no evidence is available concerning the effect of nalbuphine on the cardiotoxicity of local anesthetics. The objective of this work is to investigate whether nalbuphine pretreatment can increase the lethal dose threshold of ropivacaine in rats. Anesthetized Sprague Dawley rats were pretreated with different doses of nalbuphine (0.4, 0.8, 1.5, 3.0, 5.0 mg/kg) or NS (normal saline, negative control) or 30% LE (lipid emulsion, positive control) 2 ml/kg/min for 5 min (n = 6). Then 0.5% ropivacaine was infused at a rate of 2.5 mg/kg/min until asystole occurs. Time of arrhythmia, 50% mean arterial pressure- and 50% heart rate-reduction, and asystole were recorded, and ropivacaine doses were calculated. Nalbuphine (0.4-5.0 mg/kg) did not affect ropivacaine-induced arrhythmia, 50% mean arterial pressure-reduction and 50% heart rate-reduction, and asystole in rats compared with NS pre-treatment. The asystole dose threshold (in milligrams per kilogram) of group LE was higher than that of group NS (NS 28.25(6.32) vs. LE, 41.58(10.65); P = 0.04; 95% confidence interval 0.23 to 26.45), while thresholds of arrhythmia, 50% mean arterial pressure-reduction, and 50% heart rate-reduction were not affected by LE. Nalbuphine doses of 0.4-5.0 mg/kg pretreatment did not increase the threshold of ropivacaine cardiotoxicity compared with NS control; 30% LE increases the lethal dose threshold of ropivacaine in rats.
    MeSH term(s) Amides/toxicity ; Anesthetics, Local/toxicity ; Animals ; Arrhythmias, Cardiac/chemically induced ; Bupivacaine ; Cardiotoxicity/etiology ; Heart Arrest/chemically induced ; Nalbuphine/toxicity ; Rats ; Rats, Sprague-Dawley ; Ropivacaine/toxicity
    Chemical Substances Amides ; Anesthetics, Local ; Ropivacaine (7IO5LYA57N) ; Nalbuphine (L2T84IQI2K) ; Bupivacaine (Y8335394RO)
    Language English
    Publishing date 2022-04-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 639134-5
    ISSN 1472-8206 ; 0767-3981
    ISSN (online) 1472-8206
    ISSN 0767-3981
    DOI 10.1111/fcp.12778
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification.

    Huang, Yan / Wang, Jianhui / Liu, Feng / Wang, Chenran / Xiao, Zhiyong / Zhou, Wenxia

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1134176

    Abstract: A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. Our ...

    Abstract A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress.
    Language English
    Publishing date 2023-04-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1134176
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Role of FIP200 in inflammatory processes beyond its canonical autophagy function.

    Yeo, Syn Kok / Wang, Chenran / Guan, Jun-Lin

    Biochemical Society transactions

    2020  Volume 48, Issue 4, Page(s) 1599–1607

    Abstract: FIP200 (RB1CC1) is a critical regulator of canonical macroautophagy and has also emerged as a crucial regulator of selective autophagy as well as inflammatory processes. The illumination of FIP200's role in autophagy at the molecular level has been ... ...

    Abstract FIP200 (RB1CC1) is a critical regulator of canonical macroautophagy and has also emerged as a crucial regulator of selective autophagy as well as inflammatory processes. The illumination of FIP200's role in autophagy at the molecular level has been accompanied by studies demonstrating the importance of its autophagy function in physiological processes in mammals and pathological contexts such as cancer. However, there is an increasing appreciation that most, if not all of the autophagy genes, also play a role in other processes such as LC3-associated phagocytosis, vesicle trafficking and protein secretion. Consequently, this has led to efforts in generating specific mutants of autophagy genes that are more amenable to dissecting their autophagy versus non-autophagy functions. In this aspect, we have generated a FIP200 knock-in mouse allele that is defective for canonical macroautophagy. This has revealed a canonical-autophagy-independent function of FIP200 that is responsible for limiting pro-inflammatory signaling. In this review, we will discuss FIP200's role in this process, the implications with regards to cancer immunotherapy and highlight key prospective avenues to specifically dissect the distinct functions of FIP200.
    MeSH term(s) Alleles ; Animals ; Autophagy/physiology ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/physiology ; Immunotherapy ; Inflammation/metabolism ; Inflammation/physiopathology ; Mice ; Mice, Transgenic ; Neoplasms/therapy ; Signal Transduction
    Chemical Substances Autophagy-Related Proteins ; Rb1cc1 protein, mouse
    Language English
    Publishing date 2020-04-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20191156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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