Clinical and Experimental Pharmacology and Physiology最新文献_第7页

Effect of BTP2 on agonist-induced vasoconstriction in the mouse aorta in vitro. BTP2对激动剂诱导的小鼠主动脉血管收缩的影响。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2021-05-01 Epub Date: 2021-02-09 DOI: 10.1111/1440-1681.13469

Meng-Yuan Zhou, Li Zhang, Dan-Lin Zheng, Ying-Yu Lai, Pei-Ming Liu, Lin Liu, Su-Juan Kuang, Hui Yang, Fang Rao, Huang Long, Chun-Yu Deng

{"title":"Effect of BTP2 on agonist-induced vasoconstriction in the mouse aorta in vitro.","authors":"Meng-Yuan Zhou, Li Zhang, Dan-Lin Zheng, Ying-Yu Lai, Pei-Ming Liu, Lin Liu, Su-Juan Kuang, Hui Yang, Fang Rao, Huang Long, Chun-Yu Deng","doi":"10.1111/1440-1681.13469","DOIUrl":"https://doi.org/10.1111/1440-1681.13469","url":null,"abstract":"BTP2 is a potent inhibitor of store-operated Ca2+ entry (SOCE), which plays a vital role in vasoconstriction. However, the direct effect of BTP2 on the contractile response remains unclear. Here, we investigated the effects and mechanisms of action of BTP2 in the mouse aorta. Isometric tension was measured using a Multi Myograph System with two stainless steel wires. Ca2+ transient was recorded by confocal laser scanning microscope. The results showed that BTP2 markedly suppressed vasoconstriction mediated by SOCE and Ca2+ influx mediated by SOCE. The cumulative concentration of BTP2 had no effect on the baseline of mouse aortic rings, whereas it increased vasoconstriction stimulated by 3 μmol/L Phenylephrine. BTP2 (1 μmol/L) significantly increased vasoconstriction induced by 3 μmol/L Phe or cumulative concentration. BTP2 also promoted noradrenaline-induced aortic contraction. However, Phe- and noradrenaline-induced contraction was not affected by 0.3 or 3 μmol/L BTP2, and BTP2 at 10 μmol/L significantly suppressed aortic contraction. BTP2 inhibited 5-HT-evoked contraction in a concentration-dependent manner. BTP2 at higher concentrations (>3 μmol/L) inhibited CaCl2 -induced and 60 mmol/L K+ -induced contraction with progressive reduction of maximal contraction in a concentration-dependent manner. These results suggest that 1 μmol/L BTP2 increases contraction evoked by α1 adrenoreceptor activation. BTP2 at higher concentrations may inhibit Cav1.2 channels.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"726-734"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25354663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

An MSC bone-homing compound, Rab001, increases bone mass and reduces the incidence of osteonecrosis in a glucocorticoid-induced osteonecrosis mouse model. 一种MSC骨归巢化合物Rab001在糖皮质激素诱导的骨坏死小鼠模型中增加骨量并减少骨坏死的发生率。

IF 2.5 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2021-05-01 Epub Date: 2020-12-15 DOI: 10.1111/1440-1681.13441

Min Jiang, Lixian Liu, Xuexiang Xiang, Runmin Liang, Xuelian Qin, Jinmin Zhao, Qingjun Wei

{"title":"An MSC bone-homing compound, Rab001, increases bone mass and reduces the incidence of osteonecrosis in a glucocorticoid-induced osteonecrosis mouse model.","authors":"Min Jiang, Lixian Liu, Xuexiang Xiang, Runmin Liang, Xuelian Qin, Jinmin Zhao, Qingjun Wei","doi":"10.1111/1440-1681.13441","DOIUrl":"10.1111/1440-1681.13441","url":null,"abstract":"Currently, there are no effective medications to either prevent or slow the progression of atraumatic osteonecrosis (ON). The objective of this study is to determine the effects of bone-targeted delivery of mesenchymal stem cells on the prevalence of ON in a glucocorticoid (GC)-induced mouse model. Eight-week-old male BALB/c mice were randomized into groups that received placebo (PL), prednisolone (GC), or concurrent treatments with GC + mesenchymal stromal cells (MSCs), Rab001 or GC + Rab001 + MSCs. Human parathyroid hormone (hPTH) was used as a positive control for bone anabolism. Mice were killed after 30 days, and quantitative measurements of bone mass, bone strength, prevalent ON at the distal femoral epiphysis (DFE) were performed. Angiogenesis was accessed by RNA-Seq, the circulating angiogenic markers, as well as by immunohistochemical staining. We have showed that a novel agent, Rab001 that can noncovalently bind to mesenchymal stem cells (MSC) and direct them to the bone, prevents the incidence of glucocorticoid-induced osteonecrosis in the mouse. In contrast, PTH, a bone anabolic treatment, preserves bone mass but sustains higher ON incidence than Rab001+/- MSC-treated mice. The results of these experiments reveal that glucocorticoids increase the prevalence of ON, and agents that prevent loss of bone vascularity appear to prevent the development of ON. This intervention might be useful in patients with early stages of atraumatic ON.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"770-781"},"PeriodicalIF":2.5,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38710419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Increased lipoxygenase and decreased cytochrome P450s metabolites correlated with the incidence of diabetic nephropathy: Potential role of eicosanoids from metabolomics in type 2 diabetic patients. 脂氧合酶升高和细胞色素p450代谢物降低与糖尿病肾病发病率相关:代谢组学研究显示类二十烷类化合物在2型糖尿病患者中的潜在作用

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2021-05-01 Epub Date: 2021-02-19 DOI: 10.1111/1440-1681.13471

Liyuan Peng, Bei Sun, Yajin Liu, Jing Huang, Guangzhi Chen, Xu Zhang, Chen Chen, Daowen Wang, Gang Wang

{"title":"Increased lipoxygenase and decreased cytochrome P450s metabolites correlated with the incidence of diabetic nephropathy: Potential role of eicosanoids from metabolomics in type 2 diabetic patients.","authors":"Liyuan Peng, Bei Sun, Yajin Liu, Jing Huang, Guangzhi Chen, Xu Zhang, Chen Chen, Daowen Wang, Gang Wang","doi":"10.1111/1440-1681.13471","DOIUrl":"https://doi.org/10.1111/1440-1681.13471","url":null,"abstract":"Diabetic nephropathy (DN) is the major cause of chronic kidney disease and end-stage renal disease. Previous studies have demonstrated that long-chain omega-3 polyunsaturated fatty acids (PUFAs) might have therapeutic potential in reducing proteinuria in DN. However, the local level of eicosanoids derived from PUFAs in the plasma of DN patients remains unclear. This work aims to study the eicosanoid profile difference in plasma of DN patients and type 2 diabetes (T2D) without DN. A total of 27 T2D patients with similar diabetic duration were recruited and divided into T2D+DN group and T2D+NDN (non-DN) group based on urinary albumin excretion (UAE) detection. Using LC-MS/MS-based metabolomics, DN patients showed increased level of lipoxygenase (LOX) metabolites (5-HETE and LTB4) and decreased levels of eicosanoids derived according to the cytochrome P450s (CYP450) metabolic pathway (5,6-DHET; 14,15-DHET and 9,10-diHOME). Receiver operating characteristics and logistic regression analysis revealed increased level LOX metabolites and decreased level of CYP450 metabolites were significantly correlated with the incidence of DN in T2D patients. LOX and CYP450 metabolites correlated with DN incidence in T2D patients, which might be treatment targets for DN in T2D patients.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"679-685"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25384262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

Effects of obesity and diabesity on heart rhythm in the Zucker rat. 肥胖和糖尿病对Zucker大鼠心律的影响。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2021-05-01 Epub Date: 2021-02-20 DOI: 10.1111/1440-1681.13473

Ahmed Sultan, Michael Jacobson, Ernest Adeghate, Abderrahim Oulhaj, Mohamed Shafiullah, Anwar Qureshi, Frank Christopher Howarth

{"title":"Effects of obesity and diabesity on heart rhythm in the Zucker rat.","authors":"Ahmed Sultan, Michael Jacobson, Ernest Adeghate, Abderrahim Oulhaj, Mohamed Shafiullah, Anwar Qureshi, Frank Christopher Howarth","doi":"10.1111/1440-1681.13473","DOIUrl":"https://doi.org/10.1111/1440-1681.13473","url":null,"abstract":"Obesity and type 2 diabetes mellitus are risk factors for hypertension, coronary heart disease, cardiac arrhythmias including atrial fibrillation, heart failure and sudden cardiac death. The effects of obesity and diabesity on heart rhythm were investigated in the Zucker diabetic fatty (ZDF) and Zucker fatty (ZF) compared to the Zucker lean (ZL) control rat. In vivo biotelemetry techniques were used to assess the electrocardiogram and other cardiac and metabolic parameters. ZDF rats were characterized by age-dependent elevations in fasting and non-fasting blood glucose, glucose intolerance and weight gain and ZF rats were characterized by smaller elevations in fasting and non-fasting blood glucose and greater weight gain compared to ZL rats. Heart rate (HR) was progressively reduced in ZDF, ZF and ZL rats. At 195 days (6.5 months) of age there were significant differences in HR between ZDF (265 ± 8 bpm, n = 10), ZF (336 ± 9 bpm, n = 10) and ZL (336 ± 10 bpm, n = 10) rats and significant differences in HRV between ZDF (22 ± 1 bpm, n = 10), ZF (27 ± 1 bpm, n = 10) and ZL (31 ± 1 bpm, n = 10) rats. Power spectral analysis revealed no significant (P > 0.05) differences in HRV at low frequencies, reduced HRV at high frequencies and increased sympathovagal balance in ZDF compared to ZF and ZL rats. HR was reduced by ageing and additionally reduced by diabesity in the absence of changes in physical activity and body temperature. Reductions in HRV associated with altered sympathovagal drive might partly underlie disturbed HR in the ZDF rat. Possible explanations for reduced HR and future mechanistic studies are discussed.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"735-747"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25386066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 6

Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53-dependent and -independent mechanisms in telomerase deficient mice. 端粒酶缺陷小鼠肺泡干细胞通过p53依赖和不依赖机制发生衰老、凋亡和分化。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2021-05-01 Epub Date: 2021-02-25 DOI: 10.1111/1440-1681.13472

Kexiong Zhang, Lihui Wang, Hao Chen, Yao Shi, Yingying Liu, Jun Liu, Xiaojing Hong, Jun-Ping Liu

{"title":"Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53-dependent and -independent mechanisms in telomerase deficient mice.","authors":"Kexiong Zhang, Lihui Wang, Hao Chen, Yao Shi, Yingying Liu, Jun Liu, Xiaojing Hong, Jun-Ping Liu","doi":"10.1111/1440-1681.13472","DOIUrl":"https://doi.org/10.1111/1440-1681.13472","url":null,"abstract":"Pulmonary senescence and fibrosis occur with deoxyribonucleic acid (DNA) damage response in the lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that pulmonary alveolar epithelial type 2 cells (AEC2) (alveolar stem cells) undergo not only replicative senescence, but also apoptosis and differentiation in association with increased innate immune natural killer (NK) cells in telomerase knockout (KO) mice. Telomerase ribonucleic acid (RNA) component (TERC) deficiency results in increased senescence-associated heterochromatin foci marker HP1γ, p21, p16 and apoptosis-associated cleaved caspase-3 in AEC2. However, p53 deficiency in the Trp53-/- allele of the late generation of TERC KO mice attenuates the increased senescent and apoptotic markers significantly. Moreover, p53 deficiency has no significant effect on the increased gene expression of T1α (a marker of terminal differentiated alveolar epithelial type 1 cells [AEC1]) in AEC2 of the late generation of TERC KO mice. Collectively, our findings suggest that pulmonary senescence takes place in deficiency of telomerase RNA component with the alveolar stem cells undergoing p53-dependent senescence and apoptosis as well as p53-independent differentiation.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"651-659"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25414046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor-CaMK II-c-Myc pathway. 氯胺酮通过阻断NMDA受体- camk II-c-Myc通路抑制结直肠癌细胞的有氧糖酵解。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-22 DOI: 10.1111/1440-1681.13248

Jianjun Hu, Wenming Duan, Yahua Liu

{"title":"Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor-CaMK II-c-Myc pathway.","authors":"Jianjun Hu, Wenming Duan, Yahua Liu","doi":"10.1111/1440-1681.13248","DOIUrl":"https://doi.org/10.1111/1440-1681.13248","url":null,"abstract":"Aerobic glycolysis plays a crucial role in cancer progression. Ketamine is often used for cancer pain relief in clinical settings. Moreover, ketamine inhibits proliferation and induces apoptosis in many cancer cell types. However, the anti-tumour mechanism of ketamine is still poorly understood. In the present study, we survey whether and how ketamine inhibits aerobic glycolysis in colon cancer cells. Glycolysis of colon cancer cells was determined by detecting the extracellular acidification rate in HT29 and SW480 cells. Quantitative real-time PCR was employed to determine mRNA expression. Calcium levels were detected with a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was employed to assess glycolysis in the tumours of the xenograft model. Ketamine treatment inhibited colon cancer cell viability and migration in HT29 and SW480 cells. Moreover, ketamine decreased aerobic glycolysis and decreased the expression of glycolysis-related proteins in HT29 and SW480 cells. MicroPET/CT demonstrated that ketamine decreased 18F-FDG uptake in the xenograft model. In addition, ketamine inhibited c-Myc expression and CaMK II phosphorylation and decreased calcium levels. Further, dizocilpine (an NMDAR inhibitor), and KN93 (a CaMK II inhibitor), decreased CaMK II phosphorylation, c-Myc expression, and cancer cell glycolysis; these results were similar to those with ketamine treatment. Furthermore, the anti-tumour effect of ketamine was counteracted by rapastinel (an NMDAR activator). Ketamine inhibited aerobic glycolysis in colon cancer cells probably by blocking the NMDA receptor-CaMK II-c-Myc pathway, thus attenuating colon cancer cell viability and migration.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"848-856"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37501619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 14

Inhibitory effect of gallic acid on voltage-gated Na⁺ channels in rat cardiomyocytes. 没食子酸对大鼠心肌细胞电压门控Na+通道的抑制作用。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-02-06 DOI: 10.1111/1440-1681.13254

Ya-Ya Du, Li Zou, Xiu-Xiu Wang, Le-Yao Dai, Xin-Nan Ling, Zheng-Xin Xu

{"title":"Inhibitory effect of gallic acid on voltage-gated Na+ channels in rat cardiomyocytes.","authors":"Ya-Ya Du, Li Zou, Xiu-Xiu Wang, Le-Yao Dai, Xin-Nan Ling, Zheng-Xin Xu","doi":"10.1111/1440-1681.13254","DOIUrl":"https://doi.org/10.1111/1440-1681.13254","url":null,"abstract":"Gallic acid (GA) has a protective effect on the cardiovascular system. To study its cardiac electrophysiological effects, voltage-gated Na+ channel currents (INa ) were recorded in rat cardiomyocytes using whole-cell patch clamp techniques. Moreover, the effects of GA on aconitine-induced arrhythmias were assessed using electrocardiograms in vivo. We found that the current-voltage characteristic curve (I-V curve) of INa significantly shifted in the presence of 1, 3, and 10 μmol/L of GA. The peak sodium current density (INa -Peak) was reduced from -84.02 ± 5.68 pA/pF to -65.78 ± 3.96 pA/pF with 1 μmol/L, -54.45 ± 5.18 pA/pF with 3 μmol/L, and -44.20 ± 4.35 pA/pF with 10 μmol/L, respectively. GA shifted the steady-state activation curve of INa and recovery curve to the right and the steady-state inactivation curve to the left. The observed inhibitory effect was comparable to that of amiodarone. GA pre-treatment significantly prolonged the onset of fatal ventricular fibrillation. Our results indicated that GA inhibited INa in rat ventricular myocytes and aconitine-induced arrhythmias in vivo. These results suggest the potential of GA for development as a novel anti-arrhythmic therapeutic.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"771-779"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37531905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 5

Molecular insight into the selective binding between human telomere G-quadruplex and a negatively charged stabilizer. 人类端粒g -四重体与负电荷稳定剂之间选择性结合的分子洞察。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-24 DOI: 10.1111/1440-1681.13249

Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, Jun-Ping Liu

{"title":"Molecular insight into the selective binding between human telomere G-quadruplex and a negatively charged stabilizer.","authors":"Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, Jun-Ping Liu","doi":"10.1111/1440-1681.13249","DOIUrl":"https://doi.org/10.1111/1440-1681.13249","url":null,"abstract":"The single-strand human telomere overhang forms intramolecular high-order structures named G-quadruplex (G4) under physiological conditions. Telomere G4 stabilization prevents telomere lengthening by telomerase in cancer cells representing a promising strategy in cancer therapy. Using molecular docking and molecular dynamics (MD) simulations, specific binding of the anionic phthalocyanine 3,4',4'',4'''-tetrasulfonic acid (APC) to the human hybrid (3 + 1) G4s was investigated at the atomic level. We found that APC preferred the end-stacking binding with the telomere hybrid type II (hybrid-II) G4 as compared to the groove binding with the hybrid type I (hybrid-I) G4 remarkable stabilizing effect and more favourable binding free energies. Analysis of non-covalent interaction and decomposition of the binding free energy revealed that van der Waals interaction played a leading role in the binding of APC and telomere hybrid G4s. These findings provide evidence for the first time to shed light on the designs of selective telomere G4 stabilizers.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"892-902"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37506304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 7

Perinatal taurine exerts a hypotensive effect in male spontaneously hypertensive rats and down-regulates endothelial oxide nitric synthase in the aortic arch. 围产期牛磺酸对雄性自发性高血压大鼠有降压作用，可下调主动脉弓内皮细胞一氧化氮合酶。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-02-05 DOI: 10.1111/1440-1681.13260

Melisa F Mensegue, Adriana L Burgueño, Mariana L Tellechea

{"title":"Perinatal taurine exerts a hypotensive effect in male spontaneously hypertensive rats and down-regulates endothelial oxide nitric synthase in the aortic arch.","authors":"Melisa F Mensegue, Adriana L Burgueño, Mariana L Tellechea","doi":"10.1111/1440-1681.13260","DOIUrl":"https://doi.org/10.1111/1440-1681.13260","url":null,"abstract":"Essential hypertension is considered to be a result of the interaction between genetic and environmental factors, including perinatal factors. Different advantageous perinatal factors proved to have beneficial long-lasting effects against an abnormal genetic background. Taurine is a ubiquitous sulphur-containing amino acid present in foods such as seafood. The antihypertensive effects of taurine have been reported in experimental studies and in human hypertension. We aimed to investigate the effects of perinatal treatment with taurine in spontaneously hypertensive rats (SHR), a known model of genetic hypertension. Female SHR were administered with taurine (3 g/L) during gestation and lactation (SHR-TAU). Untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. Long-lasting effects in offspring were investigated. Addition of taurine to the mother's drinking water reduced blood pressure in adult offspring. No differences were observed in cardiac hypertrophy. Findings on morphometric evaluations suggest that perinatal treatment with taurine would be partially effective in improving structural alterations of the aorta. Modifications in gene expression of Bcl-2 family members and upregulation of endothelial nitric oxide synthase in the aorta of 22-week-old male offspring were found. No differences were observed on relative telomere length in different cardiovascular tissues between SHR and SHR-TAU. Altogether results suggest that taurine programming, albeit sex specific, is associated with gene expression changes which ultimately may lead to improvement of aortic remodelling and enhanced endothelial function because of augmented nitric oxide (NO) production.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"780-789"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37559317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Cancer stemness contributes to cluster formation of colon cancer cells and high metastatic potentials. 癌症的干细胞性有助于结肠癌细胞的聚集形成和高转移潜力。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-23 DOI: 10.1111/1440-1681.13247

Joanna Kapeleris, Hong Zou, Yan Qi, Yushu Gu, Jingyun Li, Jennifer Schoning, Michael J Monteiro, Wenyi Gu

{"title":"Cancer stemness contributes to cluster formation of colon cancer cells and high metastatic potentials.","authors":"Joanna Kapeleris, Hong Zou, Yan Qi, Yushu Gu, Jingyun Li, Jennifer Schoning, Michael J Monteiro, Wenyi Gu","doi":"10.1111/1440-1681.13247","DOIUrl":"https://doi.org/10.1111/1440-1681.13247","url":null,"abstract":"The ability of cancer cells to form clusters is a characteristic feature in the development of metastatic tumours with drug resistance. Several studies demonstrated that clusters of circulating tumour cells (CTCs) have a greater metastatic potential to establish new tumours at secondary sites than single CTCs. However, the mechanism of cluster formation is not well understood. In this study, we investigated whether cancer stemness would contribute to cluster formation. We used a tumour sphere culture method to enrich cancer stem cells (CSCs) from colon cancer cells and found that during the second generation of sphere culture, clusters (between 3 and 5 cells) formed within the first 24 hours, whereas the rest remained as single cells. The clusters were analysed for stemness and metastatic potential, including gene expressions for cancer stemness (CD133 and Lgr5), epithelial-mesenchymal transition (E-cadherin and TGF-β 1-3) and hypoxia-induced factors (HIF-1α and HIF-2α). The results showed that the clusters expressed higher levels of these genes and colon CSC surface markers (including CD24, CD44 and CD133) than the single cells. Among these markers, CD24 seemed the major contributor linking the cells into the clusters. These clusters also showed a stronger ability to both form colonies and migrate. Our data collectively suggest that colon cancer stemness contributes to cluster formation and that clustered cells exhibit a great metastatic potential. Our study thus provides a method to study the CTC clusters and derive insight into oncogenesis and metastasis.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"838-847"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37497179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 17