Brazilian Journal of Medical and Biological Research最新文献_第2页

Acute effects of energy drink consumption on microvascular reactivity in young male volunteers at rest: a randomized trial. 饮用能量饮料对年轻男性志愿者休息时微血管反应性的急性影响：随机试验。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-23 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13624

L Skaf-Gonçalves, D Peçanha, D Kasal, E Tibirica

{"title":"Acute effects of energy drink consumption on microvascular reactivity in young male volunteers at rest: a randomized trial.","authors":"L Skaf-Gonçalves, D Peçanha, D Kasal, E Tibirica","doi":"10.1590/1414-431X2024e13624","DOIUrl":"10.1590/1414-431X2024e13624","url":null,"abstract":"Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The role and mechanisms of cordycepin in inhibiting cancer cells. 虫草素抑制癌细胞的作用和机制

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-23 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13889

Gong Yu, Jiahua Peng, Lu Li, Wenbin Yu, Bin He, Bin Xie

引用次数: 0

Selective inhibition of interleukin 6 receptor decreased inflammatory cytokines and increased proteases in an experimental model of critical calvarial defect. 选择性抑制白细胞介素 6 受体可减少临界腓骨缺损实验模型中的炎症细胞因子并增加蛋白酶。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13913

R C O Melo, A A Martins, G H A Vieira, R V S Andrade, D N A Silva, J Chalmers, T M Silveira, F Q Pirih, V S Araújo, J S P Silva, M L D S Lopes, R F C Leitão, R F Araújo Júnior, I L G Silva, L J T Silva, E G Barbosa, A A Araújo

{"title":"Selective inhibition of interleukin 6 receptor decreased inflammatory cytokines and increased proteases in an experimental model of critical calvarial defect.","authors":"R C O Melo, A A Martins, G H A Vieira, R V S Andrade, D N A Silva, J Chalmers, T M Silveira, F Q Pirih, V S Araújo, J S P Silva, M L D S Lopes, R F C Leitão, R F Araújo Júnior, I L G Silva, L J T Silva, E G Barbosa, A A Araújo","doi":"10.1590/1414-431X2024e13913","DOIUrl":"10.1590/1414-431X2024e13913","url":null,"abstract":"Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Which detergent is most suitable for the generation of an acellular pancreas bioscaffold? 哪种洗涤剂最适合生成无细胞胰腺生物支架？

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13107

M C Mantovani, N R Damaceno-Rodrigues, G T S Ronatty, R S Segovia, C A Pantanali, V Rocha-Santos, E G Caldini, M C Sogayar

{"title":"Which detergent is most suitable for the generation of an acellular pancreas bioscaffold?","authors":"M C Mantovani, N R Damaceno-Rodrigues, G T S Ronatty, R S Segovia, C A Pantanali, V Rocha-Santos, E G Caldini, M C Sogayar","doi":"10.1590/1414-431X2024e13107","DOIUrl":"10.1590/1414-431X2024e13107","url":null,"abstract":"Pancreatic bioengineering is a potential therapeutic alternative for type 1 diabetes (T1D) in which the pancreas is decellularized, generating an acellular extracellular matrix (ECM) scaffold, which may be reconstituted by recellularization with several cell types to generate a bioartificial pancreas. No consensus for an ideal pancreatic decellularization protocol exists. Therefore, we aimed to determine the best-suited detergent by comparing sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and Triton X-100 at different concentrations. Murine (n=12) and human pancreatic tissue from adult brain-dead donors (n=06) was harvested in accordance with Institutional Ethical Committee of the University of São Paulo Medical School (CEP-FMUSP) and decellularized under different detergent conditions. DNA content, histological analysis, and transmission and scanning electron microscopy were assessed. The most adequate condition for pancreatic decellularization was found to be 4% SDC, displaying: a) effective cell removal; b) maintenance of extracellular matrix architecture; c) proteoglycans, glycosaminoglycans (GAGs), and collagen fibers preservation. This protocol was extrapolated and successfully applied to human pancreas decellularization. The acellular ECM scaffold generated was recelullarized using human pancreatic islets primary clusters. 3D clusters were generated using 0.5×104 cells and then placed on top of acellular pancreatic slices (25 and 50 μm thickness). These clusters tended to connect to the acellular matrix, with visible cells located in the periphery of the clusters interacting with the ECM network of the bioscaffold slices and continued to produce insulin. This study provided evidence on how to improve and accelerate the pancreas decellularization process, while maintaining its architecture and extracellular structure, aiming at pancreatic bioengineering.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition. 抑制 GSK3B 可通过调节 PI3K/Akt 信号通路和上皮细胞向间质转化，减少宫颈癌细胞的增殖和迁移。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13796

Yanhong Zheng, Yang Yang, Weiyan Zhu, Ruhao Liu, Aodong Liu, Runfeng Zhang, Weixing Lei, Shifeng Huang, Yongzhu Liu, Qinglan Hu

{"title":"GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.","authors":"Yanhong Zheng, Yang Yang, Weiyan Zhu, Ruhao Liu, Aodong Liu, Runfeng Zhang, Weixing Lei, Shifeng Huang, Yongzhu Liu, Qinglan Hu","doi":"10.1590/1414-431X2024e13796","DOIUrl":"10.1590/1414-431X2024e13796","url":null,"abstract":"Previous studies show that glycogen synthase kinase 3β (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT).","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Synergy between isobavachalcone and doxorubicin suppressed the progression of anaplastic thyroid cancer through ferroptosis activation. 异巴夏尔酮与多柔比星的协同作用通过激活铁突变抑制了无性甲状腺癌的进展。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13679

Shuai Lin, Hui Cai, Xuemei Song

{"title":"Synergy between isobavachalcone and doxorubicin suppressed the progression of anaplastic thyroid cancer through ferroptosis activation.","authors":"Shuai Lin, Hui Cai, Xuemei Song","doi":"10.1590/1414-431X2024e13679","DOIUrl":"10.1590/1414-431X2024e13679","url":null,"abstract":"The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer. SNORA5A 通过 TRAF3IP3 调节乳腺癌中肿瘤相关巨噬细胞 M1/M2 的表型。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13809

Yiqi Zhang, Ang Zheng, Yue Shi, Heng Lu

{"title":"SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer.","authors":"Yiqi Zhang, Ang Zheng, Yue Shi, Heng Lu","doi":"10.1590/1414-431X2024e13809","DOIUrl":"10.1590/1414-431X2024e13809","url":null,"abstract":"Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database. 从 FDA 不良事件报告系统 (FAERS) 数据库中对环孢素进行真实世界比例失调分析。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13392

Shichao Cui, Li Li, Wensheng Liu, Bin Zhao, Xingming Zhong

{"title":"A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database.","authors":"Shichao Cui, Li Li, Wensheng Liu, Bin Zhao, Xingming Zhong","doi":"10.1590/1414-431X2024e13392","DOIUrl":"10.1590/1414-431X2024e13392","url":null,"abstract":"Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Experimental study of local anesthetic and antiarrhythmic activities of fluorinated ethynylpiperidine derivatives. 氟化乙炔基哌啶衍生物局部麻醉和抗心律失常活性的实验研究。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13429

E M Satbayeva, S S Zhumakova, M D Khaiitova, U S Kemelbekov, F M Tursunkhodzhaeva, A A Azamatov, Sh N Tursymbek, V Kh Sabirov, T S Nurgozhin, V K Yu, T M Seilkhanov

{"title":"Experimental study of local anesthetic and antiarrhythmic activities of fluorinated ethynylpiperidine derivatives.","authors":"E M Satbayeva, S S Zhumakova, M D Khaiitova, U S Kemelbekov, F M Tursunkhodzhaeva, A A Azamatov, Sh N Tursymbek, V Kh Sabirov, T S Nurgozhin, V K Yu, T M Seilkhanov","doi":"10.1590/1414-431X2024e13429","DOIUrl":"10.1590/1414-431X2024e13429","url":null,"abstract":"The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Nav1.4 and Nav1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice. 中等强度的持续训练可降低血脂异常载脂蛋白 CIII 转基因小鼠的甘油三酯血症并改善耗氧量。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.1590/1414-431X2024e13202

N R Teixeira Junior, D R Jimenes, C Schultz, D L Almeida, P C F Mathias, J A Berti

{"title":"Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.","authors":"N R Teixeira Junior, D R Jimenes, C Schultz, D L Almeida, P C F Mathias, J A Berti","doi":"10.1590/1414-431X2024e13202","DOIUrl":"10.1590/1414-431X2024e13202","url":null,"abstract":"This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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