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Report on the annual meeting of the ECCR 24th-25th November 2023. ECCR 年会报告 2023 年 11 月 24-25 日。
IF 6 2区 医学
Clinical science Pub Date : 2024-03-01 DOI: 10.1042/CS2023ECCR001-MR
Carmine Savoia
{"title":"Report on the annual meeting of the ECCR 24th-25th November 2023.","authors":"Carmine Savoia","doi":"10.1042/CS2023ECCR001-MR","DOIUrl":"10.1042/CS2023ECCR001-MR","url":null,"abstract":"","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"137 S1","pages":"1"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease. NaHCO3 负荷会导致慢性肾病大鼠的动脉压升高和肾脏损伤。
IF 6 2区 医学
Clinical science Pub Date : 2024-02-21 DOI: 10.1042/CS20231709
Elinor C Mannon, P Robinson Muller, Jingping Sun, Weston B Bush, Alex Coleman, Hiram Ocasio, Aaron J Polichnowski, Michael W Brands, Paul M O'Connor
{"title":"NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease.","authors":"Elinor C Mannon, P Robinson Muller, Jingping Sun, Weston B Bush, Alex Coleman, Hiram Ocasio, Aaron J Polichnowski, Michael W Brands, Paul M O'Connor","doi":"10.1042/CS20231709","DOIUrl":"10.1042/CS20231709","url":null,"abstract":"<p><p>Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"189-203"},"PeriodicalIF":6.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
COVID-19 and abnormal uterine bleeding: potential associations and mechanisms. COVID-19 与异常子宫出血:潜在关联与机制。
IF 6 2区 医学
Clinical science Pub Date : 2024-02-21 DOI: 10.1042/CS20220280
Jacqueline A Maybin, Marianne Watters, Bethan Rowley, Catherine A Walker, Gemma C Sharp, Alexandra Alvergne
{"title":"COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.","authors":"Jacqueline A Maybin, Marianne Watters, Bethan Rowley, Catherine A Walker, Gemma C Sharp, Alexandra Alvergne","doi":"10.1042/CS20220280","DOIUrl":"10.1042/CS20220280","url":null,"abstract":"<p><p>The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 4","pages":"153-171"},"PeriodicalIF":6.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex differences in physiological response to increased neuronal excitability in a knockin mouse model of pediatric epilepsy. 小儿癫痫基因敲入小鼠模型中神经元兴奋性增高的生理反应的性别差异。
IF 6 2区 医学
Clinical science Pub Date : 2024-02-21 DOI: 10.1042/CS20231572
Michael F Hammer, Collin T Krzyzaniak, Erfan Bahramnejad, Kiran J Smelser, Joshua B Hack, Joseph C Watkins, Patrick T Ronaldson
{"title":"Sex differences in physiological response to increased neuronal excitability in a knockin mouse model of pediatric epilepsy.","authors":"Michael F Hammer, Collin T Krzyzaniak, Erfan Bahramnejad, Kiran J Smelser, Joshua B Hack, Joseph C Watkins, Patrick T Ronaldson","doi":"10.1042/CS20231572","DOIUrl":"10.1042/CS20231572","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a common neurological disease; however, few if any of the currently marketed antiseizure medications prevent or cure epilepsy. Discovery of pathological processes in the early stages of epileptogenesis has been challenging given the common use of preclinical models that induce seizures in physiologically normal animals. Moreover, despite known sex dimorphism in neurological diseases, females are rarely included in preclinical epilepsy models.</p><p><strong>Methods: </strong>We characterized sex differences in mice carrying a pathogenic knockin variant (p.N1768D) in the Scn8a gene that causes spontaneous tonic-clonic seizures (TCs) at ∼3 months of age and found that heterozygous females are more resilient than males in mortality and morbidity. To investigate the cellular mechanisms that underlie female resilience, we utilized blood-brain barrier (BBB) and hippocampal transcriptomic analyses in heterozygous mice before seizure onset (pre-TC) and in mice that experienced ∼20 TCs (post-TC).</p><p><strong>Results: </strong>In the pre-TC latent phase, both sexes exhibited leaky BBB; however, patterns of gene expression were sexually dimorphic. Females exhibited enhanced oxidative phosphorylation and protein biogenesis, while males activated gliosis and CREB signaling. After seizure onset (chronic phase), females exhibited a metabolic switch to lipid metabolism, while males exhibited increased gliosis and BBB dysfunction and a strong activation of neuroinflammatory pathways.</p><p><strong>Conclusion: </strong>The results underscore the central role of oxidative stress and BBB permeability in the early stages of epileptogenesis, as well as sex dimorphism in response to increasing neuronal hyperexcitability. Our results also highlight the need to include both sexes in preclinical studies to effectively translate results of drug efficacy studies.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"205-223"},"PeriodicalIF":6.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Excessive hypercholesterolemia in pregnancy impairs rat uterine artery function via activation of Toll-like receptor 4. 妊娠期过高胆固醇血症通过激活 Toll 样受体 4 损害大鼠子宫动脉功能
IF 6 2区 医学
Clinical science Pub Date : 2024-02-21 DOI: 10.1042/CS20231442
Amanda A de Oliveira, Emma Elder, Floor Spaans, Murilo E Graton, Anita Quon, Raven Kirschenman, Amy L Wooldridge, Christy-Lynn M Cooke, Sandra T Davidge
{"title":"Excessive hypercholesterolemia in pregnancy impairs rat uterine artery function via activation of Toll-like receptor 4.","authors":"Amanda A de Oliveira, Emma Elder, Floor Spaans, Murilo E Graton, Anita Quon, Raven Kirschenman, Amy L Wooldridge, Christy-Lynn M Cooke, Sandra T Davidge","doi":"10.1042/CS20231442","DOIUrl":"10.1042/CS20231442","url":null,"abstract":"<p><p>Hypercholesterolemia in pregnancy is a physiological process required for normal fetal development. In contrast, excessive pregnancy-specific hypercholesterolemia increases the risk of complications, such as preeclampsia. However, the underlying mechanisms are unclear. Toll-like receptor 4 (TLR4) is a membrane receptor modulated by high cholesterol levels, leading to endothelial dysfunction; but whether excessive hypercholesterolemia in pregnancy activates TLR4 is not known. We hypothesized that a high cholesterol diet (HCD) during pregnancy increases TLR4 activity in uterine arteries, leading to uterine artery dysfunction. Sprague Dawley rats were fed a control diet (n=12) or HCD (n=12) during pregnancy (gestational day 6-20). Vascular function was assessed in main uterine arteries using wire myography (vasodilation to methacholine and vasoconstriction to phenylephrine; with and without inhibitors for mechanistic pathways) and pressure myography (biomechanical properties). Exposure to a HCD during pregnancy increased maternal blood pressure, induced proteinuria, and reduced the fetal-to-placental weight ratio for both sexes. Excessive hypercholesterolemia in pregnancy also impaired vasodilation to methacholine in uterine arteries, whereby at higher doses, methacholine caused vasoconstriction instead of vasodilation in only the HCD group, which was prevented by inhibition of TLR4 or prostaglandin H synthase 1. Endothelial nitric oxide synthase expression and nitric oxide levels were reduced in HCD compared with control dams. Vasoconstriction to phenylephrine and biomechanical properties were similar between groups. In summary, excessive hypercholesterolemia in pregnancy impairs uterine artery function, with TLR4 activation as a key mechanism. Thus, TLR4 may be a target for therapy development to prevent adverse perinatal outcomes in complicated pregnancies.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"137-151"},"PeriodicalIF":6.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice. 同时针对热量摄入和热量效率对节食诱导肥胖小鼠的有益影响
IF 6 2区 医学
Clinical science Pub Date : 2024-02-21 DOI: 10.1042/CS20231016
Sing-Young Chen, Aiden J Telfser, Ellen M Olzomer, Calum S Vancuylenberg, Mingyan Zhou, Martina Beretta, Catherine Li, Stephanie J Alexopoulos, Nigel Turner, Frances L Byrne, Webster L Santos, Kyle L Hoehn
{"title":"Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice.","authors":"Sing-Young Chen, Aiden J Telfser, Ellen M Olzomer, Calum S Vancuylenberg, Mingyan Zhou, Martina Beretta, Catherine Li, Stephanie J Alexopoulos, Nigel Turner, Frances L Byrne, Webster L Santos, Kyle L Hoehn","doi":"10.1042/CS20231016","DOIUrl":"10.1042/CS20231016","url":null,"abstract":"<p><p>Semaglutide is an anti-diabetes and weight loss drug that decreases food intake, slows gastric emptying, and increases insulin secretion. Patients begin treatment with low-dose semaglutide and increase dosage over time as efficacy plateaus. With increasing dosage, there is also greater incidence of gastrointestinal side effects. One reason for the plateau in semaglutide efficacy despite continued low food intake is due to compensatory actions whereby the body becomes more metabolically efficient to defend against further weight loss. Mitochondrial uncoupler drugs decrease metabolic efficiency, therefore we sought to investigate the combination therapy of semaglutide with the mitochondrial uncoupler BAM15 in diet-induced obese mice. Mice were fed high-fat western diet (WD) and stratified into six treatment groups including WD control, BAM15, low-dose semaglutide without or with BAM15, and high-dose semaglutide without or with BAM15. Combining BAM15 with either semaglutide dose decreased body fat and liver triglycerides, which was not achieved by any monotherapy, while high-dose semaglutide with BAM15 had the greatest effect on glucose homeostasis. This study demonstrates a novel approach to improve weight loss without loss of lean mass and improve glucose control by simultaneously targeting energy intake and energy efficiency. Such a combination may decrease the need for semaglutide dose escalation and hence minimize potential gastrointestinal side effects.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"173-187"},"PeriodicalIF":6.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physiological response to fetal intravenous lipid emulsion. 胎儿静脉注射脂质乳剂的生理反应。
IF 6 2区 医学
Clinical science Pub Date : 2024-02-07 DOI: 10.1042/CS20231419
Brian D Piccolo, Athena Chen, Samantha Louey, Kent L R Thornburg, Sonnet S Jonker
{"title":"Physiological response to fetal intravenous lipid emulsion.","authors":"Brian D Piccolo, Athena Chen, Samantha Louey, Kent L R Thornburg, Sonnet S Jonker","doi":"10.1042/CS20231419","DOIUrl":"10.1042/CS20231419","url":null,"abstract":"<p><p>In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In the present study, we determined fetal physiological responses to intravenous lipid emulsion. Fetal sheep were given intravenous Intralipid 20® (n = 4 females, 7 males) or Lactated Ringer's Solution (n = 7 females, 4 males) between 125 ± 1 and 133 ± 1 d of gestation (term = 147 d). Manufacturer's recommendation for premature human infants was followed: 0.5-1 g/kg/d initial rate, increased by 0.5-1 to 3 g/kg/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. Intravenous Intralipid did not alter hemodynamic or most blood parameters. Compared with controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5 ± 0.3 vs. 3.9 ± 0.2 g/dL), albumin (P = 0.031; 2.2 ± 0.1 vs. 2.4 ± 0.2 g/dL), and bilirubin (P<0.001; conjugated: 0.2 ± 0.1 vs. 0.6 ± 0.2 mg/dL; unconjugated: 0.2 ± 0.1 vs. 1.1 ± 0.4 mg/dL). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66 ± 24 vs. 46 ± 24 ng/mL). Compared with control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"117-134"},"PeriodicalIF":6.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-γ axis. 间歇性短时再氧通过 NOX4/H2O2/PPAR-γ 轴缓解高海拔肺动脉高压。
IF 6.7 2区 医学
Clinical science Pub Date : 2024-02-07 DOI: 10.1042/CS20231508
Shaohua Li, Qiang Lyu, Qixin Shi, Yungang Bai, Xinling Ren, Jin Ma
{"title":"Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-γ axis.","authors":"Shaohua Li, Qiang Lyu, Qixin Shi, Yungang Bai, Xinling Ren, Jin Ma","doi":"10.1042/CS20231508","DOIUrl":"10.1042/CS20231508","url":null,"abstract":"<p><p>High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease that can lead to right heart failure. Intermittent short-duration reoxygenation at high altitude is effective in alleviating HAPH; however, the underlying mechanisms are unclear. In the present study, a simulated 5,000-m hypoxia rat model and hypoxic cultured pulmonary artery smooth muscle cells (PASMCs) were used to evaluate the effect and mechanisms of intermittent short-duration reoxygenation. The results showed that intermittent 3-h/per day reoxygenation (I3) effectively attenuated chronic hypoxia-induced pulmonary hypertension and reduced the content of H2O2 and the expression of NADPH oxidase 4 (NOX4) in lung tissues. In combination with I3, while the NOX inhibitor apocynin did not further alleviate HAPH, the mitochondrial antioxidant MitoQ did. Furthermore, in PASMCs, I3 attenuated hypoxia-induced PASMCs proliferation and reversed the activated HIF-1α/NOX4/PPAR-γ axis under hypoxia. Targeting this axis offset the protective effect of I3 on hypoxia-induced PASMCs proliferation. The present study is novel in revealing a new mechanism for preventing HAPH and provides insights into the optimization of intermittent short-duration reoxygenation.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"103-115"},"PeriodicalIF":6.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Umbilical cord mesenchymal stem cells from gestational diabetes show impaired ability to up-regulate paracellular permeability from sub-endothelial niche. 妊娠期糖尿病患者的脐带间充质干细胞上调血管内皮下壁龛旁通透性的能力受损
IF 6 2区 医学
Clinical science Pub Date : 2024-01-24 DOI: 10.1042/CS20230657
Samar Salem, Lopa Leach
{"title":"Umbilical cord mesenchymal stem cells from gestational diabetes show impaired ability to up-regulate paracellular permeability from sub-endothelial niche.","authors":"Samar Salem, Lopa Leach","doi":"10.1042/CS20230657","DOIUrl":"10.1042/CS20230657","url":null,"abstract":"<p><p>In vitro studies have shown that Wharton's jelly mesenchymal stem cells (WJ-MSCs) can cross umbilical and uterine endothelial barriers and up-regulate endothelial junctional integrity from sub-endothelial niches. This pericytic behaviour may be lost in pregnancies complicated by gestational diabetes (GDM), where increased vascular permeability and junctional disruption are reported. The aim of the present study was to investigate whether WJ-MSCs isolated from GDM pregnancies displayed any changes in morphology, proliferation, VEGF-A secretion, and their ability to influence paracellular junctional composition and permeability. WJ-MSCs were isolated from human umbilical cords from normal pregnancies (nWJ-MSCs, n=13) and those complicated by GDM (gWJ-MSCs), either diet-controlled (d-GDM, n=13) or metformin-treated (m-GDM, n=9). We recorded that 4-fold more WJ-MSCs migrated from m-GDM, and 2.5-fold from d-GDM cord samples compared with the normal pregnancy. gWJ-MSCs showed a less predominance of spindle-shaped morphology and secreted 3.8-fold more VEGF-A compared with nWJ-MSCs. The number of cells expressing CD105 (Endoglin) was higher in gWJ-MSCs compared with nWJ-MSCs (17%) at P-2. The tracer leakage after 24 h across the HUVEC + gWJ-MSCs bilayer was 22.13% and 11.2% higher in the m-GDM and d-GDM, respectively, HUVEC + nWJ-MSCs. Transfection studies with siRNAs that target Endoglin were performed in n-WJ-MSCs; transfected cells were co-cultured with HUVEC followed by permeability studies and VE-cadherin analyses. Loss of Endoglin also led to increased VEGF-A secretion, increased permeability and affected endothelial stabilization. These results reinforce the pericytic role of nWJ-MSCs to promote vascular repair and the deficient ability of gWJ-MSCs to maintain endothelial barrier integrity.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"87-102"},"PeriodicalIF":6.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration. 与口服给药相比,鼻饲蛋白质给药能增强胰岛素血症和氨基酸血症,但不能增强全身蛋白质周转或肌肉蛋白质合成。
IF 6 2区 医学
Clinical science Pub Date : 2024-01-10 DOI: 10.1042/CS20231126
George F Pavis, Doaa R Abdelrahman, Andrew J Murton, Benjamin T Wall, Francis B Stephens, Marlou L Dirks
{"title":"Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration.","authors":"George F Pavis, Doaa R Abdelrahman, Andrew J Murton, Benjamin T Wall, Francis B Stephens, Marlou L Dirks","doi":"10.1042/CS20231126","DOIUrl":"10.1042/CS20231126","url":null,"abstract":"<p><p>Nasogastric feeding of protein-rich liquids is a nutritional support therapy that attenuates muscle mass loss. However, whether administration via a nasogastric tube per se augments whole-body or muscle protein anabolism compared with oral administration is unknown. Healthy participants were administered a protein-rich drink (225 ml containing 21 g protein) orally (ORAL; n=13; age 21 ± 1 year; BMI 22.2 ± 0.6 kg·m-2) or via a nasogastric tube (NG; n=13; age 21 ± 1 yr; BMI 23.9 ± 0.9 kg·m-2) in a parallel group design, balanced for sex. L-[ring-2H5]-phenylalanine and L-[3,3-2H2]-tyrosine were infused to measure postabsorptive and postprandial whole-body protein turnover. Skeletal muscle biopsies were collected at -120, 0, 120 and 300 min relative to drink administration to quantify temporal myofibrillar fractional synthetic rates (myoFSR). Drink administration increased serum insulin and plasma amino acid concentrations, and to a greater extent and duration in NG versus ORAL (all interactions P<0.05). Drink administration increased whole-body protein synthesis (P<0.01), suppressed protein breakdown (P<0.001), and created positive net protein balance (P<0.001), but to a similar degree in ORAL and NG (interactions P>0.05). Drink administration increased myoFSR from the postabsorptive state (P<0.01), regardless of route of administration in ORAL and in NG (interaction P>0.05). Nasogastric bolus administration of a protein-rich drink induces insulinaemia and aminoacidaemia to a greater extent than oral administration, but the postprandial increase in whole-body protein turnover and muscle protein synthesis was equivalent between administration routes. Nasogastric administration is a potent intervention to increase postprandial amino acid availability. Future work should assess its utility in overcoming impaired sensitivity to protein feeding, such as that seen in ageing, disuse, and critical care.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"43-60"},"PeriodicalIF":6.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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