Shi-Rui Bai, Qi Zhao, Hui-Jie Jia, Fei He, Xiao-Bo Wang
{"title":"Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.","authors":"Shi-Rui Bai, Qi Zhao, Hui-Jie Jia, Fei He, Xiao-Bo Wang","doi":"10.1139/cjpp-2023-0432","DOIUrl":"10.1139/cjpp-2023-0432","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-β-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080854","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}
{"title":"Retraction: Endothelin axis induces metalloproteinase activation and invasiveness in human lymphatic endothelial cells.","authors":"","doi":"10.1139/cjpp-2024-0264","DOIUrl":"10.1139/cjpp-2024-0264","url":null,"abstract":"","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035334","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}
Shekoofeh Saboktakin Rizi, Evan Wiens, Jennifer Hunt, Robin Ducas
{"title":"Correction: Cardiac physiology and pathophysiology in pregnancy.","authors":"Shekoofeh Saboktakin Rizi, Evan Wiens, Jennifer Hunt, Robin Ducas","doi":"10.1139/cjpp-2024-0319","DOIUrl":"10.1139/cjpp-2024-0319","url":null,"abstract":"","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406158","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}
Wanderson Gabriel Gomes de Melo, Dayseanny de Oliveira Bezerra, Elis Rosélia Dutra de Freitas Siqueira Silva, Camile Benício Campêlo, Maria Acelina Martins de Carvalho, Napoleão Martins Argôlo Neto
{"title":"Behavioral dynamics of medicinal signaling cells from porcine bone marrow in long-term culture.","authors":"Wanderson Gabriel Gomes de Melo, Dayseanny de Oliveira Bezerra, Elis Rosélia Dutra de Freitas Siqueira Silva, Camile Benício Campêlo, Maria Acelina Martins de Carvalho, Napoleão Martins Argôlo Neto","doi":"10.1139/cjpp-2023-0458","DOIUrl":"10.1139/cjpp-2023-0458","url":null,"abstract":"<p><p>Medicinal signaling cells (MSC) hold promise for regenerative medicine due to their ability to repair damaged tissues. However, their effectiveness can be affected by how long they are cultured in the lab. This study investigated how passage number influences key properties for regenerative medicine of pig bone marrow MSC. The medicinal signiling cells derived from pig bone marrow (BM-MSC) were cultured in D-MEM High Glucose supplemented with 15% foetal bovine serum until the 25th passage and assessed their growth, viability, ability to differentiate into different cell types (plasticity), and cell cycle activity. Our findings showed that while the cells remained viable until the 25th passage, their ability to grow and differentiate declined after the 5th passage. Additionally, cells in later passages spent more time in a resting phase, suggesting reduced activity. In conclusion, the number of passages is a critical factor for maintaining ideal MSC characteristics. From the 9th passage BM-MSC exhibit decline in proliferation, differentiation potential, and cell cycle activity. Given this, it is possible to suggest that the use of 5th passage cells is the most suitable for therapeutic applications.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072109","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}
Jocelyn M Delgado Spicuzza, Jigar Gosalia, Matthew Studinski, Chenée Armando, Elmira Alipour, Daniel B Kim-Shapiro, Michael Flanagan, Yasina B Somani, David N Proctor
{"title":"The acute effects of dietary nitrate supplementation on postmenopausal endothelial resistance to ischemia reperfusion injury: a randomized, placebo-controlled, double blind, crossover clinical trial.","authors":"Jocelyn M Delgado Spicuzza, Jigar Gosalia, Matthew Studinski, Chenée Armando, Elmira Alipour, Daniel B Kim-Shapiro, Michael Flanagan, Yasina B Somani, David N Proctor","doi":"10.1139/cjpp-2024-0061","DOIUrl":"10.1139/cjpp-2024-0061","url":null,"abstract":"<p><p>Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO<sub>3</sub> <sup>-</sup>)-nitrite (NO<sub>2</sub> <sup>-</sup>)-nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BR<sub>nitrate</sub> 600 mg NO<sub>3</sub> <sup>-</sup>/140 mL, BR<sub>placebo</sub> ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia-reperfusion (IR) injury to a greater extent in early-postmenopausal (1-6 years following their final menstrual period (FMP), <i>n</i> = 12) compared to late-postmenopausal (6+ years after FMP, <i>n</i> = 12) women. Analyses with general linear models revealed a significant (<i>p</i> < 0.05) time<sup>*</sup>treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BR<sub>placebo</sub> (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, <i>p</i> < 0.001) and was lower than post-IR with BR<sub>nitrate</sub> (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, <i>p</i> = 0.014). A single dose of BR<sub>nitrate</sub> significantly increased resting macrovascular function in the late postmenopausal group only (<i>p</i> = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431518","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}
{"title":"Expression of concern: Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53.","authors":"","doi":"10.1139/cjpp-2024-0220","DOIUrl":"10.1139/cjpp-2024-0220","url":null,"abstract":"","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726948","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}
Laurentiu Braescu, Adrian Sturza, Raluca Sosdean, Oana Maria Aburel, Mihai Andrei Lazar, Danina Muntean, Constantin Tudor Luca, Daniel Miron Brie, Horea Feier, Simina Crisan, Cristian Mornos
{"title":"Echocardiographic assessment of epicardial adipose tissue thickness as independent predictor in coronary artery disease.","authors":"Laurentiu Braescu, Adrian Sturza, Raluca Sosdean, Oana Maria Aburel, Mihai Andrei Lazar, Danina Muntean, Constantin Tudor Luca, Daniel Miron Brie, Horea Feier, Simina Crisan, Cristian Mornos","doi":"10.1139/cjpp-2024-0188","DOIUrl":"10.1139/cjpp-2024-0188","url":null,"abstract":"<p><p>This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery<i>.</i> EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, <i>p</i> = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H<sub>2</sub>O<sub>2</sub>/g tisssue/h vs. 15.7 ± 1.55 nmol H<sub>2</sub>O<sub>2</sub>/g tisssue/h, <i>p</i> < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124913","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}
{"title":"Retraction: β-arrestin-1 mediates the endothelin-1-induced activation of Akt and integrin-linked kinase.","authors":"","doi":"10.1139/cjpp-2024-0265","DOIUrl":"10.1139/cjpp-2024-0265","url":null,"abstract":"","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035335","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}
{"title":"Agonists, inverse agonists, and antagonists as therapeutic approaches to manipulate retinoic acid-related orphan receptors.","authors":"Darya Nematisouldaragh, Huong Nguyen, Inna Rabinovich-Nikitin","doi":"10.1139/cjpp-2024-0099","DOIUrl":"10.1139/cjpp-2024-0099","url":null,"abstract":"<p><p>Retinoic acid-related orphan receptors (RORs) serve as transcription factors that play a pivotal role in a myriad of physiological processes within the body. Their involvement extends to critical biological processes that confer protective effects in the heart, immune system, and nervous system, as well as contributing to the mitigation of several aggressive cancer types. These protective functions are attributed to ROR's regulation of key proteins and the management of various cellular processes, including autophagy, mitophagy, inflammation, oxidative stress, and glucose metabolism, highlighting the emerging need for pharmacological approaches to modulate ROR expression. Thus, the modulation of RORs is a rapidly growing area of research aimed not only at comprehending these receptors, but also at manipulating them to attain the desired physiological response. Despite the presence of natural ROR ligands, the development of synthetic agonists with high selectivity for these receptors holds substantial therapeutic potential. The exploration and advancement of such compounds can effectively target diseases associated with ROR dysregulation, thereby providing avenues for therapeutic interventions. Herein, we provide a comprehensive examination of the multifaceted role of ROR in diverse physiological and pathophysiological conditions, accompanied by an in-depth exploration of a spectrum of ROR agonists, inverse agonists, and antagonists.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903907","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}
{"title":"Pharmacological Interactions of Jadomycin B with Topoisomerase Poisons in MDA-MB-231 Human Breast Cancer Cells.","authors":"Brendan T McKeown, Kerry B Goralski","doi":"10.1139/cjpp-2024-0232","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0232","url":null,"abstract":"<p><p>Jadomycin B, a natural product isolated from <i>Streptomyces venezuelae</i>, exerts an anti-cancer effect on human triple negative breast cancer cells <i>in vitro</i> and has anti-tumoral effects <i>in vivo</i> in animal models of breast cancer. One proposed mechanism for this anti-cancer effect is through interaction with topoisomerase 2 (TOP2). Based on the previously described interactions between jadomycin B and TOP2 we hypothesized that jadomycin B will act additively with TOP2 poisons and produce a similar functional outcome in eliciting cell cycle arrest. Combined treatments of jadomycin B and the TOP2 poisons doxorubicin or mitoxantrone produced moderately synergistic to additive cytotoxicity (combination index values ranging from 0.72-0.94) in MDA-MB-231 cells. In comparison, combined mitoxantrone and doxorubicin produced additive cytotoxicity (combination index values 0.96-1.11). Jadomycin B combined with the proteosome inhibitor MG132 had additive cytotoxicity (combination index values 0.76-1.18). In contrast, mitoxantrone or doxorubicin cytotoxicity was antagonized by MG132 (combination index values 1.21-2.31). Jadomycin B treatment arrested cells in S-phase (P = 0.0024) as opposed to mitoxantrone which caused G<sub>2</sub>/M-phase arrest (P < 0.0001). In conclusion, jadomycin B interacts differently than known TOP2 poisons in combination, supporting a novel pharmacological mechanism(s) of action for jadomycin B cytotoxicity.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557251","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}