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  1. Article ; Online: Patient experiences of an online consultation system: a qualitative study in English primary care post-COVID-19.

    Moschogianis, Susan / Darley, Sarah / Coulson, Tessa / Peek, Niels / Cheraghi-Sohi, Sudeh / Brown, Benjamin C

    The British journal of general practice : the journal of the Royal College of General Practitioners

    2024  

    Abstract: Background: Online consultation systems (OCSs) allow patients to contact their healthcare teams online. Since 2020 they have been rapidly rolled out in primary care following policy initiatives and the COVID-19 pandemic. In-depth research of patients' ... ...

    Abstract Background: Online consultation systems (OCSs) allow patients to contact their healthcare teams online. Since 2020 they have been rapidly rolled out in primary care following policy initiatives and the COVID-19 pandemic. In-depth research of patients' experiences using OCSs is lacking.
    Aim: Explore patients' experiences of using an OCS.
    Design and setting: Qualitative study in English GP practices using the Patchs OCS (www.Patchs.ai) from March 2020 to July 2022.
    Method: Thematic analysis of 25 patient interviews and 21 467 written comments from 11 851 patients who used the OCS from nine and 240 GP practices, respectively.
    Results: Patients cited benefits of using the OCS as speed, flexibility, and efficiency. Nevertheless, some patients desired a return to traditional consultation methods. GP practices often did not clearly advertise the OCS or use it as patients expected, which caused frustration. Patients reported advantages of having a written record of consultations and the opportunity to communicate detailed queries in free text. Views differed on how the OCS influenced clinical safety and discussions of sensitive topics. Patients who struggled to communicate in traditional consultations often preferred using the OCS, and male patients reported being more likely to use it.
    Conclusion: Globally, this is the largest in-depth study of patient experiences of an OCS. It contributes new knowledge that the patient experience of using OCSs can be influenced by previously unreported patient characteristics and the conditions they consult about. Further, it contributes recommendations on the design and implementation of the OCS in practice.
    Language English
    Publishing date 2024-03-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 1043148-2
    ISSN 1478-5242 ; 0035-8797 ; 0960-1643
    ISSN (online) 1478-5242
    ISSN 0035-8797 ; 0960-1643
    DOI 10.3399/BJGP.2023.0076
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  2. Article ; Online: Understanding How the Design and Implementation of Online Consultations Affect Primary Care Quality: Systematic Review of Evidence With Recommendations for Designers, Providers, and Researchers.

    Darley, Sarah / Coulson, Tessa / Peek, Niels / Moschogianis, Susan / van der Veer, Sabine N / Wong, David C / Brown, Benjamin C

    Journal of medical Internet research

    2022  Volume 24, Issue 10, Page(s) e37436

    Abstract: Background: Online consultations (OCs) allow patients to contact their care providers on the web. Worldwide, OCs have been rolled out in primary care rapidly owing to policy initiatives and COVID-19. There is a lack of evidence regarding how OC design ... ...

    Abstract Background: Online consultations (OCs) allow patients to contact their care providers on the web. Worldwide, OCs have been rolled out in primary care rapidly owing to policy initiatives and COVID-19. There is a lack of evidence regarding how OC design and implementation influence care quality.
    Objective: We aimed to synthesize research on the impacts of OCs on primary care quality, and how these are influenced by system design and implementation.
    Methods: We searched databases from January 2010 to February 2022. We included quantitative and qualitative studies of real-world OC use in primary care. Quantitative data were transformed into qualitative themes. We used thematic synthesis informed by the Institute of Medicine domains of health care quality, and framework analysis informed by the nonadoption, abandonment, scale-up, spread, and sustainability framework. Strength of evidence was judged using the GRADE-CERQual approach.
    Results: We synthesized 63 studies from 9 countries covering 31 OC systems, 14 (22%) of which used artificial intelligence; 41% (26/63) of studies were published from 2020 onward, and 17% (11/63) were published after the COVID-19 pandemic. There was no quantitative evidence for negative impacts of OCs on patient safety, and qualitative studies suggested varied perceptions of their safety. Some participants believed OCs improved safety, particularly when patients could describe their queries using free text. Staff workload decreased when sufficient resources were allocated to implement OCs and patients used them for simple problems or could describe their queries using free text. Staff workload increased when OCs were not integrated with other software or organizational workflows and patients used them for complex queries. OC systems that required patients to describe their queries using multiple-choice questionnaires increased workload for patients and staff. Health costs decreased when patients used OCs for simple queries and increased when patients used them for complex queries. Patients using OCs were more likely to be female, younger, and native speakers, with higher socioeconomic status. OCs increased primary care access for patients with mental health conditions, verbal communication difficulties, and barriers to attending in-person appointments. Access also increased by providing a timely response to patients' queries. Patient satisfaction increased when using OCs owing to better primary care access, although it decreased when using multiple-choice questionnaire formats.
    Conclusions: This is the first theoretically informed synthesis of research on OCs in primary care and includes studies conducted during the COVID-19 pandemic. It contributes new knowledge that, in addition to having positive impacts on care quality such as increased access, OCs also have negative impacts such as increased workload. Negative impacts can be mitigated through appropriate OC system design (eg, free text format), incorporation of advanced technologies (eg, artificial intelligence), and integration into technical infrastructure (eg, software) and organizational workflows (eg, timely responses).
    Trial registration: PROSPERO CRD42020191802; https://tinyurl.com/2p84ezjy.
    MeSH term(s) United States ; Humans ; Female ; Male ; COVID-19 ; Pandemics ; Artificial Intelligence ; Referral and Consultation ; Quality of Health Care
    Language English
    Publishing date 2022-10-24
    Publishing country Canada
    Document type Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028830-X
    ISSN 1438-8871 ; 1439-4456
    ISSN (online) 1438-8871
    ISSN 1439-4456
    DOI 10.2196/37436
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  3. Article ; Online: Erythrocyte ENT1-AMPD3 Axis is an Essential Purinergic Hypoxia Sensor and Energy Regulator Combating CKD in a Mouse Model.

    Chen, Changhan / Xie, TingTing / Zhang, Yujin / Wang, Yiyan / Yu, Fang / Lin, Lizhen / Zhang, Weiru / Brown, Benjamin C / Zhang, Xin / Kellems, Rodney E / D'Alessandro, Angelo / Xia, Yang

    Journal of the American Society of Nephrology : JASN

    2023  Volume 34, Issue 10, Page(s) 1647–1671

    Abstract: Significance statement: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated ... ...

    Abstract Significance statement: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated in a mouse model that erythrocyte ENT1-AMPD3 is a master energy regulator of the intracellular purinergic hypoxic compensatory response that promotes rapid energy supply from extracellular adenosine, eAMPK-dependent metabolic reprogramming, and O 2 delivery, which combat renal hypoxia and progression of CKD. ENT1-AMPD3-AMPK-BPGM comprise a group of circulating erythroid-specific biomarkers, providing early diagnostic and novel therapeutic targets for CKD.
    Background: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear.
    Methods: Mice with an erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 ( eEnt1-/- ) and a global deficiency in AMP deaminase 3 ( Ampd3-/- ) were generated to define their function in two independent CKD models, including angiotensin II (Ang II) infusion and unilateral ureteral obstruction (UUO). Unbiased metabolomics, isotopic adenosine flux, and various biochemical and cell culture analyses coupled with genetic studies were performed. Translational studies in patients with CKD and cultured human erythrocytes examined the role of ENT1 and AMPD3 in erythrocyte function and metabolism.
    Results: eEnt1-/- mice display severe renal hypoxia, kidney damage, and fibrosis in both CKD models. The loss of eENT1-mediated adenosine uptake reduces intracellular AMP and thus abolishes the activation of AMPK α and bisphosphoglycerate mutase (BPGM). This results in reduced 2,3-bisphosphoglycerate and glutathione, leading to overwhelming oxidative stress in eEnt1-/- mice. Excess reactive oxygen species (ROS) activates AMPD3, resulting in metabolic reprogramming and reduced O 2 delivery, leading to severe renal hypoxia in eEnt1-/- mice. By contrast, genetic ablation of AMPD3 preserves the erythrocyte adenine nucleotide pool, inducing AMPK-BPGM activation, O 2 delivery, and antioxidative stress capacity, which protect against Ang II-induced renal hypoxia, damage, and CKD progression. Translational studies recapitulated the findings in mice.
    Conclusion: eENT1-AMPD3, two highly enriched erythrocyte purinergic components that sense hypoxia, promote eAMPK-BPGM-dependent metabolic reprogramming, O 2 delivery, energy supply, and antioxidative stress capacity, which mitigates renal hypoxia and CKD progression.
    MeSH term(s) Humans ; Mice ; Animals ; AMP-Activated Protein Kinases/metabolism ; Hypoxia/metabolism ; Adenosine/metabolism ; Erythrocytes/metabolism ; Renal Insufficiency, Chronic/metabolism ; AMP Deaminase/genetics ; AMP Deaminase/metabolism
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Adenosine (K72T3FS567) ; AMPD3 protein, mouse (EC 3.5.4.6) ; AMP Deaminase (EC 3.5.4.6)
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.0000000000000195
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  4. Article ; Online: Protein-L-isoaspartate O-methyltransferase is required for <i>in vivo</i> control of oxidative damage in red blood cells.

    D'Alessandro, Angelo / Hay, Ariel / Dzieciatkowska, Monika / Brown, Benjamin C / Morrison, Evan J / Hansen, Kirk C / Zimring, James C

    Haematologica

    2021  Volume 106, Issue 10, Page(s) 2726–2739

    Abstract: Red blood cells have the special challenge of a large amount of reactive oxygen species (from their substantial iron load and Fenton reactions) combined with the inability to synthesize new gene products. Considerable progress has been made in ... ...

    Abstract Red blood cells have the special challenge of a large amount of reactive oxygen species (from their substantial iron load and Fenton reactions) combined with the inability to synthesize new gene products. Considerable progress has been made in elucidating the multiple pathways by which red blood cells neutralize reactive oxygen species via NADPH driven redox reactions. However, far less is known about how red blood cells repair the inevitable damage that does occur when reactive oxygen species break through anti-oxidant defenses. When structural and functional proteins become oxidized, the only remedy available to red blood cells is direct repair of the damaged molecules, as red blood cells cannot synthesize new proteins. Amongst the most common amino acid targets of oxidative damage is the conversion of asparagine and aspartate side chains into a succinimidyl group through deamidation or dehydration, respectively. Red blood cells express an L-Isoaspartyl methyltransferase (PIMT, gene name PCMT1) that can convert succinimidyl groups back to an aspartate. Herein, we report that deletion of PCMT1 significantly alters red blood cell metabolism in a healthy state, but does not impair the circulatory lifespan of red blood cells. Through a combination of genetic ablation, bone marrow transplantation and oxidant stimulation with phenylhydrazine in vivo or blood storage ex vivo, we use omics approaches to show that, when animals are exposed to oxidative stress, red blood cells from PCMT1 knockout undergo significant metabolic reprogramming and increased hemolysis. This is the first report of an essential role of PCMT1 for normal RBC circulation during oxidative stress.
    MeSH term(s) Animals ; Erythrocytes/metabolism ; Isoaspartic Acid/metabolism ; Oxidative Stress ; Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics ; Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism ; Reactive Oxygen Species
    Chemical Substances Isoaspartic Acid ; Reactive Oxygen Species ; Protein D-Aspartate-L-Isoaspartate Methyltransferase (EC 2.1.1.77)
    Language English
    Publishing date 2021-10-01
    Publishing country Italy
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2020.266676
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  5. Article ; Online: Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis.

    Xu, Ping / Chen, Changhan / Zhang, Yujin / Dzieciatkowska, Monika / Brown, Benjamin C / Zhang, Weiru / Xie, Tingting / Abdulmalik, Osheiza / Song, Anren / Tong, Chao / Qi, Hongbo / Roach, Robert / Kellems, Rodney E / D'Alessandro, Angelo / Xia, Yang

    Cell metabolism

    2022  Volume 34, Issue 2, Page(s) 299–316.e6

    Abstract: Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen ( ... ...

    Abstract Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen (O
    MeSH term(s) Animals ; Carnitine/metabolism ; Erythrocytes/metabolism ; Erythrocytes/pathology ; Homeostasis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mice ; Oxygen/metabolism ; Renal Insufficiency, Chronic/pathology ; Solute Carrier Family 22 Member 5/metabolism ; Transglutaminases/metabolism
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; SLC22A5 protein, human ; Solute Carrier Family 22 Member 5 ; Transglutaminases (EC 2.3.2.13) ; Carnitine (S7UI8SM58A) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2021.12.019
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  6. Article: 13

    Renuse, Santosh / Benson, Linda M / Vanderboom, Patrick M / Ruchi, F N U / Yadav, Yogesh R / Johnson, Kenneth L / Brown, Benjamin C / Peterson, Jane A / Basu, Rita / McCormick, Daniel J / Pandey, Akhilesh / Basu, Ananda

    Clinical proteomics

    2022  Volume 19, Issue 1, Page(s) 16

    Abstract: Background: Glucagon serves as an important regulatory hormone for regulating blood glucose concentration with tight feedback control exerted by insulin and glucose. There are critical gaps in our understanding of glucagon kinetics, pancreatic α cell ... ...

    Abstract Background: Glucagon serves as an important regulatory hormone for regulating blood glucose concentration with tight feedback control exerted by insulin and glucose. There are critical gaps in our understanding of glucagon kinetics, pancreatic α cell function and intra-islet feedback network that are disrupted in type 1 diabetes. This is important for translational research applications of evolving dual-hormone (insulin + glucagon) closed-loop artificial pancreas algorithms and their usage in type 1 diabetes. Thus, it is important to accurately measure glucagon kinetics in vivo and to develop robust models of glucose-insulin-glucagon interplay that could inform next generation of artificial pancreas algorithms.
    Methods: Here, we describe the administration of novel
    Results: The limit of quantitation was found to be 1.56 pg/ml using stable isotope-labeled glucagon as an internal standard. Intra and inter-assay variability was < 6% and < 16%, respectively, for FF glucagon while it was < 5% and < 23%, respectively, for FFLA glucagon. Further, we carried out a novel isotope dilution technique using glucagon tracers for studying glucagon kinetics in type 1 diabetes.
    Conclusions: The methods described in this study for simultaneous detection and quantitation of glucagon tracers have clinical utility for investigating glucagon kinetics in vivo in humans.
    Language English
    Publishing date 2022-05-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2205154-5
    ISSN 1542-6416
    ISSN 1542-6416
    DOI 10.1186/s12014-022-09344-2
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  7. Article ; Online: Supporting patients. The future is already here.

    Brown, Benjamin C / Hannan, Amir

    BMJ (Clinical research ed.)

    2011  Volume 342, Page(s) d2702

    MeSH term(s) Access to Information ; England ; Humans ; Internet/utilization ; Medical Records ; Patient Participation ; Physician-Patient Relations
    Language English
    Publishing date 2011-05-03
    Publishing country England
    Document type Letter
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj.d2702
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  8. Article ; Online: Best practice guidance for antibiotic audit and feedback interventions in primary care: a modified Delphi study from the Joint Programming Initiative on Antimicrobial resistance: Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN).

    Schwartz, Kevin L / Xu, Alice X T / Alderson, Sarah / Bjerrum, Lars / Brehaut, Jamie / Brown, Benjamin C / Bucher, Heiner C / De Sutter, An / Francis, Nick / Grimshaw, Jeremy / Gunnarsson, Ronny / Hoye, Sigurd / Ivers, Noah / Lecky, Donna M / Lindbæk, Morten / Linder, Jeffrey A / Little, Paul / Michalsen, Benedikte Olsen / O'Connor, Denise /
    Pulcini, Celine / Sundvall, Pär-Daniel / Lundgren, Pia Touboul / Verbakel, Jan Y / Verheij, Theo J

    Antimicrobial resistance and infection control

    2023  Volume 12, Issue 1, Page(s) 72

    Abstract: Background: Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and ... ...

    Abstract Background: Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A&F may impact its effectiveness. There are no best practice guidelines for peer comparison A&F in antibiotic prescribing in primary care.
    Objective: To develop best practice guidelines for peer comparison A&F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network.
    Methods: We used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A&F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement.
    Results: The final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5).
    Conclusion: We report an expert-derived best practice recommendations for designing and evaluating peer comparison A&F for antibiotic prescribing in primary care. These 13 statements can be used by A&F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care.
    MeSH term(s) Humans ; Feedback ; Anti-Bacterial Agents/therapeutic use ; Delphi Technique ; Drug Resistance, Bacterial ; Primary Health Care
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2023-07-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2666706-X
    ISSN 2047-2994 ; 2047-2994
    ISSN (online) 2047-2994
    ISSN 2047-2994
    DOI 10.1186/s13756-023-01279-z
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  9. Article ; Online: Maternal erythrocyte ENT1-mediated AMPK activation counteracts placental hypoxia and supports fetal growth.

    Sayama, Seisuke / Song, Anren / Brown, Benjamin C / Couturier, Jacob / Cai, Xiaoli / Xu, Ping / Chen, Changhan / Zheng, Yangxi / Iriyama, Takayuki / Sibai, Baha / Longo, Monica / Kellems, Rodney E / D'Alessandro, Angelo / Xia, Yang

    JCI insight

    2020  Volume 5, Issue 10

    Abstract: Insufficient O2 supply is frequently associated with fetal growth restriction (FGR), a leading cause of perinatal mortality and morbidity. Although the erythrocyte is the most abundant and only cell type to deliver O2 in our body, its function and ... ...

    Abstract Insufficient O2 supply is frequently associated with fetal growth restriction (FGR), a leading cause of perinatal mortality and morbidity. Although the erythrocyte is the most abundant and only cell type to deliver O2 in our body, its function and regulatory mechanism in FGR remain unknown. Here, we report that genetic ablation of mouse erythrocyte equilibrative nucleoside transporter 1 (eENT1) in dams, but not placentas or fetuses, results in FGR. Unbiased high-throughput metabolic profiling coupled with in vitro and in vivo flux analyses with isotopically labeled tracers led us to discover that maternal eENT1-dependent adenosine uptake is critical in activating AMPK by controlling the AMP/ATP ratio and its downstream target, bisphosphoglycerate mutase (BPGM); in turn, BPGM mediates 2,3-BPG production, which enhances O2 delivery to maintain placental oxygenation. Mechanistically and functionally, we revealed that genetic ablation of maternal eENT1 increases placental HIF-1α; preferentially reduces placental large neutral aa transporter 1 (LAT1) expression, activity, and aa supply; and induces FGR. Translationally, we revealed that elevated HIF-1α directly reduces LAT1 gene expression in cultured human trophoblasts. We demonstrate the importance and molecular insight of maternal eENT1 in fetal growth and open up potentially new diagnostic and therapeutic possibilities for FGR.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Enzyme Activation ; Equilibrative Nucleoside Transporter 1/metabolism ; Erythrocytes/metabolism ; Female ; Fetal Development ; Fetus/metabolism ; Hypoxia/metabolism ; Mice ; Mice, Knockout ; Placenta/metabolism ; Pregnancy
    Chemical Substances Equilibrative Nucleoside Transporter 1 ; SLC29A1 protein, mouse ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2020-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.130205
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  10. Article ; Online: Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies.

    Xie, Tingting / Chen, Changhan / Peng, Zhangzhe / Brown, Benjamin C / Reisz, Julie A / Xu, Ping / Zhou, Zhen / Song, Anren / Zhang, Yujin / Bogdanov, Mikhail V / Kellems, Rodney E / D'Alessandro, Angelo / Zhang, Weiru / Xia, Yang

    Circulation research

    2020  Volume 127, Issue 3, Page(s) 360–375

    Abstract: Rationale: Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O: Objective: To investigate the function and metabolic basis of erythrocyte S1P in CKD with a goal to explore ...

    Abstract Rationale: Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O
    Objective: To investigate the function and metabolic basis of erythrocyte S1P in CKD with a goal to explore potential therapeutics.
    Methods and results: Using erythrocyte-specific SphK1 (sphingosine kinase 1; the only enzyme to produce S1P in erythrocytes) knockout mice (
    Conclusions: Our study elucidates the beneficial role of eSphk1-S1P in hypertensive CKD by channeling glucose metabolism toward Rapoport-Luebering shunt and inducing 2,3-bisphosphoglycerate production and O
    MeSH term(s) Adult ; Animals ; Case-Control Studies ; Cell Hypoxia ; Cellular Reprogramming ; Disease Models, Animal ; Energy Metabolism ; Erythrocytes/enzymology ; Erythrocytes/metabolism ; Female ; Fibrosis ; Humans ; Hypertension/complications ; Kidney/metabolism ; Kidney/pathology ; Male ; Metabolome ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Renal Insufficiency, Chronic/blood ; Renal Insufficiency, Chronic/enzymology ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/pathology
    Chemical Substances Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; Sphk1 protein, mouse (EC 2.7.1.-)
    Language English
    Publishing date 2020-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.119.316298
    Database MEDical Literature Analysis and Retrieval System OnLINE

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