Clinical Science (London, England : 1979)最新文献_第3页

Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics. 慢性阻塞性肺疾病和动脉粥样硬化:常见机制和新疗法。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2022-03-31 DOI: 10.1042/CS20210835

Kurt Brassington, Stavros Selemidis, Steven Bozinovski, Ross Vlahos

{"title":"Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics.","authors":"Kurt Brassington, Stavros Selemidis, Steven Bozinovski, Ross Vlahos","doi":"10.1042/CS20210835","DOIUrl":"https://doi.org/10.1042/CS20210835","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) and atherosclerosis are chronic irreversible diseases, that share a number of common causative factors including cigarette smoking. Atherosclerosis drastically impairs blood flow and oxygen availability to tissues, leading to life-threatening outcomes including myocardial infarction (MI) and stroke. Patients with COPD are most likely to die as a result of a cardiovascular event, with 30% of all COPD-related deaths being attributed to cardiovascular disease (CVD). Both atherosclerosis and COPD involve significant local (i.e. lung, vasculature) and systemic inflammation and oxidative stress, of which current pharmacological treatments have limited efficacy, hence the urgency for the development of novel life-saving therapeutics. Currently these diseases must be treated individually, with no therapies available that can effectively reduce the likelihood of comorbid CVD other than cessation of cigarette smoking. In this review, the important mechanisms that drive atherosclerosis and CVD in people with COPD are explained and we propose that modulation of both the oxidative stress and the inflammatory burden will provide a novel therapeutic strategy to treat both the pulmonary and systemic manifestations related to these diseases.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"405-423"},"PeriodicalIF":6.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40315819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

The insecticide β-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype. 杀虫剂β-氟氯菊酯通过与NaV1.5相互作用诱导急性心律失常心脏毒性，雷诺嗪可逆转该表型。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2022-03-18 DOI: 10.1042/CS20211151

Maria Vitoria da Silva, Artur Santos-Miranda, Julliane V Joviano-Santos, Diego Santos Souza, Leisiane Pereira Marques, Jaqueline Oliveira Sarmento, Samuel Santos Beserra, Danilo Roman-Campos

{"title":"The insecticide β-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype.","authors":"Maria Vitoria da Silva, Artur Santos-Miranda, Julliane V Joviano-Santos, Diego Santos Souza, Leisiane Pereira Marques, Jaqueline Oliveira Sarmento, Samuel Santos Beserra, Danilo Roman-Campos","doi":"10.1042/CS20211151","DOIUrl":"https://doi.org/10.1042/CS20211151","url":null,"abstract":"β-Cyfluthrin, a class II Pyrethroid, is an insecticide used worldwide in agriculture, horticulture (field and protected crops), viticulture, and domestic applications. β-Cyfluthrin may impair the function of biological systems; however, little information is available about its potential cardiotoxic effect. Here, we explored the acute toxicity of β-Cyfluthrin in isolated heart preparations and its cellular basis, using isolated cardiomyocytes. Moreover, β-Cyfluthrin effects on the sodium current, especially late sodium current (INa-L), were investigated using human embryonic kidney cells (HEK-293) cells transiently expressing human NaV1.5 channels. We report that β-Cyfluthrin raised INa-L in a dose-dependent manner. β-Cyfluthrin prolonged the repolarization of the action potential (AP) and triggered oscillations on its duration. Cardiomyocytes contraction and calcium dynamics were disrupted by the pesticide with a marked incidence of non-electronic-stimulated contractions. The antiarrhythmic drug Ranolazine was able to reverse most of the phenotypes observed in isolated cells. Lastly, ventricular premature beats (VPBs) and long QT intervals were found during β-Cyfluthrin exposure, and Ranolazine was able to attenuate them. Overall, we demonstrated that β-Cyfluthrin can cause significant cardiac alterations and Ranolazine ameliorated the phenotype. Understanding the insecticides' impacts upon electromechanical properties of the heart is important for the development of therapeutic approaches to treat cases of pesticides intoxication.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"329-343"},"PeriodicalIF":6.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39639665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection. 红细胞增加内源性鞘氨醇1-磷酸水平作为对SARS-CoV-2感染的适应性反应。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-12-22 DOI: 10.1042/CS20210666

Martin Sebastian Winkler, Ralf Alexander Claus, Mareike Schilder, Stefan Pöhlmann, Sina M Coldewey, Julian Grundmann, Torben Fricke, Onnen Moerer, Konrad Meissner, Michael Bauer, Heike Hofmann-Winkler, Markus H Gräler

{"title":"Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection.","authors":"Martin Sebastian Winkler, Ralf Alexander Claus, Mareike Schilder, Stefan Pöhlmann, Sina M Coldewey, Julian Grundmann, Torben Fricke, Onnen Moerer, Konrad Meissner, Michael Bauer, Heike Hofmann-Winkler, Markus H Gräler","doi":"10.1042/CS20210666","DOIUrl":"https://doi.org/10.1042/CS20210666","url":null,"abstract":"Abstract Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2781-2791"},"PeriodicalIF":6.0,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/eb/cs-135-cs20210666.PMC8696489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39701666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Sex differences in white adipose tissue expansion: emerging molecular mechanisms. 白色脂肪组织扩张的性别差异:新兴的分子机制。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-12-22 DOI: 10.1042/CS20210086

Simon T Bond, Anna C Calkin, Brian G Drew

{"title":"Sex differences in white adipose tissue expansion: emerging molecular mechanisms.","authors":"Simon T Bond, Anna C Calkin, Brian G Drew","doi":"10.1042/CS20210086","DOIUrl":"https://doi.org/10.1042/CS20210086","url":null,"abstract":"The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2691-2708"},"PeriodicalIF":6.0,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39602613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Correction: Alamandine attenuates hepatic fibrosis by regulating autophagy induced by NOX4-dependent ROS. 更正：Alamandine通过调节nox4依赖性ROS诱导的自噬来减轻肝纤维化。

Clinical Science (London, England : 1979) Pub Date : 2021-12-22 DOI: 10.1042/CS-2019-1235_COR

引用次数: 0

Contribution of dipeptidyl peptidase 4 to non-typeable Haemophilus influenzae-induced lung inflammation in COPD. 二肽基肽酶4在非分型流感嗜血杆菌引起的慢性阻塞性肺病肺部炎症中的作用

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-09-17 DOI: 10.1042/CS20210099

Sudhir Kotnala, Yerin Kim, Charu Rajput, Hymavathi Reddyvari, Sudhir Bolla, Nathaniel T Marchetti, Beata Kosmider, Karim Bahmed, Umadevi S Sajjan

{"title":"Contribution of dipeptidyl peptidase 4 to non-typeable Haemophilus influenzae-induced lung inflammation in COPD.","authors":"Sudhir Kotnala, Yerin Kim, Charu Rajput, Hymavathi Reddyvari, Sudhir Bolla, Nathaniel T Marchetti, Beata Kosmider, Karim Bahmed, Umadevi S Sajjan","doi":"10.1042/CS20210099","DOIUrl":"https://doi.org/10.1042/CS20210099","url":null,"abstract":"Dipeptidyl peptidase 4 (DPP4) expression is increased in the lungs of chronic obstructive pulmonary disease (COPD). DPP4 is known to be associated with inflammation in various organs, including LPS-induced acute lung inflammation. Since non-typeable Haemophilus influenzae (NTHi) causes acute exacerbations in COPD patients, we examined the contribution of DPP4 in NTHi-induced lung inflammation in COPD. Pulmonary macrophages isolated from COPD patients showed higher expression of DPP4 than the macrophages isolated from normal subjects. In response to NTHi infection, COPD, but not normal macrophages show a further increase in the expression of DPP4. COPD macrophages also showed higher expression of IL-1β, and CCL3 responses to NTHi than normal, and treatment with DPP4 inhibitor, diprotin A attenuated this response. To examine the contribution of DPP4 in NTHi-induced lung inflammation, COPD mice were infected with NTHi, treated with diprotin A or PBS intraperitoneally, and examined for DPP4 expression, lung inflammation, and cytokine expression. Mice with COPD phenotype showed increased expression of DPP4, which increased further following NTHi infection. DPP4 expression was primarily observed in the infiltrated inflammatory cells. NTHi-infected COPD mice also showed sustained neutrophilic lung inflammation and expression of CCL3, and this was inhibited by DPP4 inhibitor. These observations indicate that enhanced expression of DPP4 in pulmonary macrophages may contribute to sustained lung inflammation in COPD following NTHi infection. Therefore, inhibition of DPP4 may reduce the severity of NTHi-induced lung inflammation in COPD.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2067-2083"},"PeriodicalIF":6.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39321608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice. 胎盘特异性Slc38a2/SNAT2敲低导致小鼠胎儿生长受限。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-09-17 DOI: 10.1042/CS20210575

Owen R Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V Anthony, Thomas L Brown, Sara L Hillman, Rebecca Spencer, Anna L David, Fredrick J Rosario, Theresa L Powell, Thomas Jansson

{"title":"Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.","authors":"Owen R Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V Anthony, Thomas L Brown, Sara L Hillman, Rebecca Spencer, Anna L David, Fredrick J Rosario, Theresa L Powell, Thomas Jansson","doi":"10.1042/CS20210575","DOIUrl":"https://doi.org/10.1042/CS20210575","url":null,"abstract":"Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2049-2066"},"PeriodicalIF":6.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39322303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Allosteric activation of PP2A inhibits experimental abdominal aortic aneurysm. PP2A的变构活化抑制实验性腹主动脉瘤。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-09-17 DOI: 10.1042/CS20210315

Xianming Zhou, Chao Zhang, Fei Xie, Wei Wei, Rui Li, Qian Xu, Yu Wang, Philip A Klenotic, Goutham Narla, Nianguo Dong, Zhiyong Lin

{"title":"Allosteric activation of PP2A inhibits experimental abdominal aortic aneurysm.","authors":"Xianming Zhou, Chao Zhang, Fei Xie, Wei Wei, Rui Li, Qian Xu, Yu Wang, Philip A Klenotic, Goutham Narla, Nianguo Dong, Zhiyong Lin","doi":"10.1042/CS20210315","DOIUrl":"https://doi.org/10.1042/CS20210315","url":null,"abstract":"Although extremely important, the molecular mechanisms that govern aortic aneurysm (AA) formation and progression are still poorly understood. This deficit represents a critical roadblock toward the development of effective pharmaceutical therapies for the treatment of AA. While dysregulation of protein phosphatase 2A (PP2A) is thought to play a role in cardiovascular disease, its role in aortic aneurysm is unknown. The objective of the present study is to test the hypothesis that PP2A regulates abdominal aortic aneurysm (AAA) progression in a murine model. In an angiotensin II-induced AAA murine model, the PP2A inhibitor, LB-100, markedly accelerated AAA progression as demonstrated by increased abdominal aortic dilation and mortality. AAA progression was associated with elevated inflammation and extracellular matrix fragmentation, concomitant with increases in both metalloproteinase activity and reactive oxygen species production. Conversely, administration of a novel class of small molecule activators of PP2A (SMAPs) resulted in an antithetical effect. SMAPs effectively reduced AAA incidence along with the corresponding pathologies that were increased with LB-100 treatment. Mechanistically, modulation of PP2A activities in vivo functioned in part via alteration of the ERK1/2 and NFκB signaling pathways, known regulators of AAA progression. These studies, for the first time, demonstrate a role of PP2A in AAA etiology and demonstrate that PP2A activation may represent a novel strategy for the treatment of abdominal aortic aneurysms.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2085-2097"},"PeriodicalIF":6.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612712/pdf/nihms-1756972.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39319066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Maternal intermittent fasting during pregnancy: a translational research challenge for an important clinical scenario. 妊娠期间产妇间歇性禁食:一个重要临床场景的转化研究挑战。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-09-17 DOI: 10.1042/CS20210578

Dominique Darmaun

{"title":"Maternal intermittent fasting during pregnancy: a translational research challenge for an important clinical scenario.","authors":"Dominique Darmaun","doi":"10.1042/CS20210578","DOIUrl":"https://doi.org/10.1042/CS20210578","url":null,"abstract":"In volume 135, issue 11 of Clinical Science, Alkhalefah et al. report that, in pregnant rats, repeated, cyclic fasting, mimicking the fasting experienced by observant Muslim pregnant women during Ramadan, alters placental amino acid transport and increases the incidence of low birth weight. Though Muslim women are exempt, many observe Ramadan: >500 million fetuses worldwide may be exposed to Ramadan fasting in each generation, and low birth weight increases the risk of developing chronic disease in the future adult. Several mechanisms, including altered circadian rhythm, maternal stress, undernutrition or compensatory overeating at the breaking of fast, could, in theory, impact fetal growth during Ramadan. Limitations of the experimental model obviously prevent direct extrapolation to humans. Whether Ramadan fasting indeed affect fetal growth therefore remains unclear, as there is no clear-cut evidence from epidemiological studies. The paper illustrates the need to design further case-controlled studies in large cohorts of women who fasted at various stages of pregnancy, compared to appropriately matched women who did not fast, as well as more experimental studies focused on this issue of public health relevance.","PeriodicalId":519494,"journal":{"name":"Clinical Science (London, England : 1979)","volume":" ","pages":"2099-2102"},"PeriodicalIF":6.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39374053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxytocin: much more than childbirth and milk letdown. 催产素:比分娩和分泌乳汁更重要。

IF 6

Clinical Science (London, England : 1979) Pub Date : 2021-09-17 DOI: 10.1042/CS20210180

Morley D Hollenberg

引用次数: 0