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  1. Article ; Online: Pb-Induced Eryptosis May Provoke Thrombosis Prior to Hemolysis

    Qiushuo Jin / Chunyang Yao / Yiying Bian / Jingbo Pi

    International Journal of Molecular Sciences, Vol 23, Iss 7008, p

    2022  Volume 7008

    Abstract: Lead (Pb) is a common metal, which can be toxic to the human body via the pollution of water or food, and can cause anemia and other diseases. However, what happens before hemolysis and anemia caused by Pb poisoning is unclear. Here, we demonstrated Pb ... ...

    Abstract Lead (Pb) is a common metal, which can be toxic to the human body via the pollution of water or food, and can cause anemia and other diseases. However, what happens before hemolysis and anemia caused by Pb poisoning is unclear. Here, we demonstrated Pb can cause procoagulant activity of erythroid cells leading to thrombosis before hemolysis. In freshly isolated human erythroid cells, we observed that Pb resulted in hemolysis in both concentration- and time-dependent manners, but that no lysis occurred in Pb-exposed erythroid cells (≤20 μM for 1 h). Pb treatment did not cause shape changes at up to 0.5 h incubation but at 1 h incubation echinocyte and echino-spherocyte shape changes were observed, indicating that Pb can exaggerate a concentration- and time-dependent trend of shape changes in erythroid cells. After Pb treatment, ROS-independent eryptosis was shown with no increase of reactive oxygen species (ROS), but with an increase of [Ca 2+ ] i and caspase 3 activity. With a thrombosis mouse model, we observed increased thrombus by Pb treatment (0 or 25 mg/kg). In brief, prior to hemolysis, we demonstrated Pb can cause ROS-independent but [Ca 2+ ] i -dependent eryptosis, which might provoke thrombosis.
    Keywords lead (Pb) ; ROS-independent ; intracellular calcium level ; eryptosis ; shape changes ; venous thrombosis mice model ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 333
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation

    Thien Ngo / Keunyoung Kim / Yiying Bian / Hakjun Noh / Kyung-Min Lim / Jin-Ho Chung / Ok-Nam Bae

    International Journal of Molecular Sciences, Vol 20, Iss 20, p

    2019  Volume 5040

    Abstract: Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts ...

    Abstract Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.
    Keywords paeoniflorin ; paeonia suffruticosa ; shear stress ; antiplatelet ; antithrombotic ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 630
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The roles of NFE2L1 in adipocytes

    Suping Ren / Yiying Bian / Yongyong Hou / Zhendi Wang / Zhuo Zuo / Zhiyuan Liu / Yue Teng / Jingqi Fu / Huihui Wang / Yuanyuan Xu / Qiang Zhang / Yanyan Chen / Jingbo Pi

    Redox Biology, Vol 44, Iss , Pp 102015- (2021)

    Structural and mechanistic insight from cell and mouse models

    2021  

    Abstract: Adipocytes play pivotal roles in maintaining energy homeostasis by storing lipids in adipose tissue (AT), regulating the flux of lipids between AT and the circulation in response to the body's energy requirements and secreting a variety of hormones, ... ...

    Abstract Adipocytes play pivotal roles in maintaining energy homeostasis by storing lipids in adipose tissue (AT), regulating the flux of lipids between AT and the circulation in response to the body's energy requirements and secreting a variety of hormones, cytokines and other factors. Proper AT development and function ensure overall metabolic health. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as NRF1) belongs to the CNC-bZIP family and plays critical roles in regulating a wide range of essential cellular functions and varies stress responses in many cells and tissues. Human and rodent Nfe2l1 genes can be transcribed into multiple splice variants resulting in various protein isoforms, which may be further modified by a variety of post-translational mechanisms. While the long isoforms of NFE2L1 have been established as master regulators of cellular adaptive antioxidant response and proteasome homeostasis, the exact tissue distribution and physiological function of NFE2L1 isoforms, the short isoforms in particular, are still under intense investigation. With regard to key roles of NFE2L1 in adipocytes, emerging data indicates that deficiency of Nfe2l1 results in aberrant adipogenesis and impaired AT functioning. Intriguingly, a single nucleotide polymorphism (SNP) of the human NFE2L1 gene is associated with obesity. In this review, we summarize the most significant findings regarding the specific roles of the multiple isoforms of NFE2L1 in AT formation and function. We highlight that NFE2L1 plays a fundamental regulatory role in the expression of multiple genes that are crucial to AT metabolism and function and thus could be an important target to improve disease states involving aberrant adipose plasticity and lipid homeostasis.
    Keywords NFE2L1 ; Adipose ; Adipocytes ; Adipogenesis ; Energy metabolism ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: CNC-bZIP protein NFE2L1 regulates osteoclast differentiation in antioxidant-dependent and independent manners

    Zhiyuan Liu / Huihui Wang / Yongyong Hou / Yang Yang / Jingkun Jia / Jinzhi Wu / Zhuo Zuo / Tianchang Gao / Suping Ren / Yiying Bian / Shengnan Liu / Jingqi Fu / Yongxin Sun / Jiliang Li / Masayuki Yamamoto / Qiang Zhang / Yuanyuan Xu / Jingbo Pi

    Redox Biology, Vol 48, Iss , Pp 102180- (2021)

    2021  

    Abstract: Fine-tuning of osteoclast differentiation (OD) and bone remodeling is crucial for bone homeostasis. Dissecting the mechanisms regulating osteoclastogenesis is fundamental to understanding the pathogenesis of various bone disorders including osteoporosis ... ...

    Abstract Fine-tuning of osteoclast differentiation (OD) and bone remodeling is crucial for bone homeostasis. Dissecting the mechanisms regulating osteoclastogenesis is fundamental to understanding the pathogenesis of various bone disorders including osteoporosis and arthritis. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as NRF1), which belongs to the CNC-bZIP family of transcription factors, orchestrates a variety of physiological processes and stress responses. While Nfe2l1 gene may be transcribed into multiple alternatively spliced isoforms, the biological function of the different isoforms of NFE2L1 in bone metabolism, osteoclastogenesis in particular, has not been reported. Here we demonstrate that knockout of all isoforms of Nfe2l1 transcripts specifically in the myeloid lineage in mice [Nfe2l1(M)-KO] results in increased activity of osteoclasts, decreased bone mass and worsening of osteoporosis induced by ovariectomy and aging. In comparison, LysM-Cre-mediated Nfe2l1 deletion has no significant effect on the osteoblast and osteocytes. Mechanistic investigations using bone marrow cells and RAW 264.7 cells revealed that deficiency of Nfe2l1 leads to accelerated and elevated OD, which is attributed, at least in part, to enhanced accumulation of ROS in the early stage of OD and expression of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1α (Nfatc1/α). In addition, NFE2L1 regulates the transcription of multiple antioxidant genes and Nfatc1/α and OD in an isoform-specific manner. While long isoforms of NFE2L1 function as accelerators of induction of Nfatc1/α and antioxidant genes and OD, the short isoform NFE2L1-453 serves as a brake that keeps the long isoforms’ accelerator effects in check. These findings provide a novel insight into the regulatory roles of NFE2L1 in osteoclastogenesis and highlight that NFE2L1 is essential in regulating bone remodeling and thus may be a valuable therapeutic target for bone disorders.
    Keywords NFE2L1 ; ROS ; NFATc1 ; Osteoclast ; Osteoporosis ; Osteoclastogenesis ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Thermoresponsive ophthalmic poloxamer/tween/carbopol in situ gels of a poorly water-soluble drug fluconazole: preparation and in vitro-in vivo evaluation.

    Lihong, Wang / Xin, Che / Yongxue, Guo / Yiying, Bian / Gang, Cheng

    Drug development and industrial pharmacy

    2014  Volume 40, Issue 10, Page(s) 1402–1410

    Abstract: The purpose of the present study was to optimize the formulations of the thermoresponsive ophthalmic in situ gels of a poorly water-soluble drug fluconazole (FLU) and evaluate the in vitro and in vivo properties of the formulations. The thermoresponsive ... ...

    Abstract The purpose of the present study was to optimize the formulations of the thermoresponsive ophthalmic in situ gels of a poorly water-soluble drug fluconazole (FLU) and evaluate the in vitro and in vivo properties of the formulations. The thermoresponsive ophthalmic FLU in situ gels were prepared by mixing FLU, Poloxamer407, Tween80, benzalkonium chloride and carbopol934 in borate buffer solution. The in vivo eye irritation tests and ophthalmic absorption were carried out in rabbits. The formulation compositions influenced the physicochemical properties of FLU in situ gels. The amount of poloxamer407 in the formulation was the main factor that affected the sol-gel transition temperature of the products. Tween80 not only improved the solubility of the FLU but also affected the products' sol-gel transition temperature. In this study, sol-gel transition temperature was not affected by carbopol934. However, carbopol934 affected pH value, transparency and gelling capacity of the products. The product of the optimized formulation was a pseudoplastic fluid and its sol-gel transition temperature was 30.6 ± 1.2 °C. The autoclaving test showed that the sol-gel transition temperature, the flow ability and the flow behavior of the test samples did not change obviously after autoclaving sterilization at 121 °C and 15 psi for 20 min, thus the autoclaving was an acceptable sterilization method for this preparation. The thermoresponsive ophthalmic FLU in situ gels' in vivo ophthalmic absorption was superior to the conventional FLU eye drop. In conclusion, the thermoresponsive ophthalmic FLU in situ gel is a better alternative than the FLU eye drop.
    MeSH term(s) Acrylates/chemistry ; Administration, Ophthalmic ; Animals ; Antifungal Agents/administration & dosage ; Antifungal Agents/chemistry ; Antifungal Agents/pharmacokinetics ; Benzalkonium Compounds/chemistry ; Chemistry, Pharmaceutical ; Excipients/chemistry ; Female ; Fluconazole/administration & dosage ; Fluconazole/chemistry ; Fluconazole/pharmacokinetics ; Gels ; Hydrogen-Ion Concentration ; Male ; Ophthalmic Solutions ; Poloxamer/chemistry ; Polysorbates/chemistry ; Rabbits ; Solubility ; Sterilization ; Temperature ; Transition Temperature
    Chemical Substances Acrylates ; Antifungal Agents ; Benzalkonium Compounds ; Excipients ; Gels ; Ophthalmic Solutions ; Polysorbates ; carbopol 934P ; Poloxamer (106392-12-5) ; Fluconazole (8VZV102JFY)
    Language English
    Publishing date 2014-10
    Publishing country England
    Document type Comparative Study ; Journal Article
    ZDB-ID 751874-2
    ISSN 1520-5762 ; 0363-9045
    ISSN (online) 1520-5762
    ISSN 0363-9045
    DOI 10.3109/03639045.2013.828221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effect of radiochemotherapy on the cognitive function and diffusion tensor and perfusion weighted imaging for high-grade gliomas

    Yiying Bian / Li Meng / Jianghua Peng / Junfeng Li / Rui Wei / Lei Huo / Huan Yang / Ying Wang / Jun Fu / Liangfang Shen / Jidong Hong

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    A prospective study

    2019  Volume 10

    Abstract: Abstract This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 ( ... ...

    Abstract Abstract This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 (ERP-P300), and specific MRI parameters were compared, and the associations between specific MRI parameters and different doses of radiation were determined for before and up to 12 months after radiotherapy. There were no significant differences in MMSE, MoCA, or ERP-P300 before and after radiotherapy. Compared with pre-radiochemotherapy, fractional anisotropy (FA) in the contralateral hippocampus decreased at 6 and 9 months after radiotherapy. FA in the ipsilateral hippocampus before radiochemotherapy decreased compared with 6 months after radiotherapy. Compared to the end of radiotherapy, as well as 3- and 6-months post-radiotherapy, the regional cerebral blood volume (rCBV) in the genu of the corpus was significantly lower at 12 months post-radiotherapy. Some MRI parameters in different regions of the brain were negatively correlated with the mean and maximum dose. There was no significant effect of radiochemotherapy on the neurocognitive functioning of patients with HGGs found before radiochemotherapy until 12 months after radiotherapy. The radiation-induced FA decrease in the bilateral hippocampus preceded cognitive dysfunction, and DTI of the hippocampus may provide a useful biomarker for predicting radiation-induced neurocognitive impairment in patients with HGGs.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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