Rogério F. Marcos Eber, Chaves V. Hellíada, Pinto R. Isabela, de Sousa A. Nayara, Ribeiro A. Kátia, Monteiro M. Dina Andressa, E. S. R. Antonio Alfredo, Arriaga C. Ângela Martha, Teixeira S. Maria Valdeline, Pimenta T. A. Antônia, Jorge B. Roberta Jeane, Braz B. Helyson Lucas, Pinto T. Vicente de Paulo, de Moraes Amaral Maria Elisabete, Girão C. C. Virgínia, Bezerra Mirna Marques
Background: This study aimed to predict the pharmacokinetic and toxicological properties of lead flavonoids from the roots of T. egregia [praecansone A (1) and pongachalcone (2)], and to assess the gastroprotective effects and possible underlying mechanisms of the root extract in mice.Methods: Quantitative and qualitative data for in silico absorption, distribution, metabolism, and excretion (ADME) analyses of the two flavonoids were acquired from the SwissADME database. Toxicity assessment was performed with the ProTox-II server. To evaluate the putative interactions of both flavonoids with opioid receptors and NO protein, we acquired structures of the targets (μ, κ, and δ-opioid receptors, and iNOS) in Homo sapiens from https://www.rcsb.org/. For docking studies, AutoDock 4.2 was used for ligand and target arrangement, and AutoDock Vina was used for calculations. For in vivo assays, mice were pretreated (per os) with T. egregia (2, 20, or 200 mg/kg). After 60 min, 99.9% ethanol (0.2 mL) was injected (per os). At 30 min after ethanol injection, the mice were euthanized, and the gastric damage, gastric levels of hemoglobin, glutathione content, and activity of superoxide dismutase and catalase were evaluated. To elucidate T. egregia mechanisms, we used misoprostol, a prostaglandin analog; indomethacin, an inhibitor of prostaglandin synthesis; L-arginine, an NO precursor; L-NAME, an antagonist of NO synthase; naloxone, an opioid antagonist; and morphine, an opioid agonist.Results: In silico results showed that flavonoids (1) and (2) had favorable ADME properties and toxicity profiles, and exhibited satisfactory binding energies data (below −6.0 kcal/mol) when docked into their targets (μ, κ, and δ-opioid receptors, and iNOS). T. egregia decreased the ethanol-induced gastric damage and hemoglobin levels, and increased the glutathione content, and activity of superoxide dismutase and catalase. Naloxone and L-NAME, but not indomethacin, prevented T. egregia’s effects, thus suggesting that opioid receptors and NO are involved in T. egregia’s efficacy.Conclusions: Flavonoids (1) and (2) exhibited favorable pharmacokinetic properties, showing high lethal dose, 50% (LD50; 3,800 and 2,500 mg/kg, respectively) values. Neither flavonoid was found to be hepatotoxic, carcinogenic, or cytotoxic to human cells. In vivo assays indicated that T. egregia ameliorated oxidative stress levels, and its mechanism is at least partially based on opioid receptors and NO. T. egregia may therefore be considered as a new gastroprotective strategy.
{"title":"ADME-Tox Prediction and Molecular Docking Studies of Two Lead Flavonoids From the Roots of Tephrosia Egregia Sandw and the Gastroprotective Effects of Its Root Extract in Mice","authors":"Rogério F. Marcos Eber, Chaves V. Hellíada, Pinto R. Isabela, de Sousa A. Nayara, Ribeiro A. Kátia, Monteiro M. Dina Andressa, E. S. R. Antonio Alfredo, Arriaga C. Ângela Martha, Teixeira S. Maria Valdeline, Pimenta T. A. Antônia, Jorge B. Roberta Jeane, Braz B. Helyson Lucas, Pinto T. Vicente de Paulo, de Moraes Amaral Maria Elisabete, Girão C. C. Virgínia, Bezerra Mirna Marques","doi":"10.15212/bioi-2021-0035","DOIUrl":"https://doi.org/10.15212/bioi-2021-0035","url":null,"abstract":"Background: This study aimed to predict the pharmacokinetic and toxicological properties of lead flavonoids from the roots of T. egregia [praecansone A (1) and pongachalcone (2)], and to assess the gastroprotective effects and possible underlying mechanisms of the root extract in mice.Methods: Quantitative and qualitative data for in silico absorption, distribution, metabolism, and excretion (ADME) analyses of the two flavonoids were acquired from the SwissADME database. Toxicity assessment was performed with the ProTox-II server. To evaluate the putative interactions of both flavonoids with opioid receptors and NO protein, we acquired structures of the targets (μ, κ, and δ-opioid receptors, and iNOS) in Homo sapiens from https://www.rcsb.org/. For docking studies, AutoDock 4.2 was used for ligand and target arrangement, and AutoDock Vina was used for calculations. For in vivo assays, mice were pretreated (per os) with T. egregia (2, 20, or 200 mg/kg). After 60 min, 99.9% ethanol (0.2 mL) was injected (per os). At 30 min after ethanol injection, the mice were euthanized, and the gastric damage, gastric levels of hemoglobin, glutathione content, and activity of superoxide dismutase and catalase were evaluated. To elucidate T. egregia mechanisms, we used misoprostol, a prostaglandin analog; indomethacin, an inhibitor of prostaglandin synthesis; L-arginine, an NO precursor; L-NAME, an antagonist of NO synthase; naloxone, an opioid antagonist; and morphine, an opioid agonist.Results: In silico results showed that flavonoids (1) and (2) had favorable ADME properties and toxicity profiles, and exhibited satisfactory binding energies data (below −6.0 kcal/mol) when docked into their targets (μ, κ, and δ-opioid receptors, and iNOS). T. egregia decreased the ethanol-induced gastric damage and hemoglobin levels, and increased the glutathione content, and activity of superoxide dismutase and catalase. Naloxone and L-NAME, but not indomethacin, prevented T. egregia’s effects, thus suggesting that opioid receptors and NO are involved in T. egregia’s efficacy.Conclusions: Flavonoids (1) and (2) exhibited favorable pharmacokinetic properties, showing high lethal dose, 50% (LD50; 3,800 and 2,500 mg/kg, respectively) values. Neither flavonoid was found to be hepatotoxic, carcinogenic, or cytotoxic to human cells. In vivo assays indicated that T. egregia ameliorated oxidative stress levels, and its mechanism is at least partially based on opioid receptors and NO. T. egregia may therefore be considered as a new gastroprotective strategy.","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130949714","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}
{"title":"Voice Series: Interview with Professor Dr. Kun Qian, School of Medical Technology, Beijing Institute of Technology, China","authors":"Phei Er Saw","doi":"10.15212/bioi-2023-0009","DOIUrl":"https://doi.org/10.15212/bioi-2023-0009","url":null,"abstract":"<jats:p>\u0000 \u0000 </jats:p>","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121548545","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}
{"title":"SORTing the Fate of Nanodelivery Systems","authors":"P. Saw, Na Kong","doi":"10.15212/BIOI-2021-0005","DOIUrl":"https://doi.org/10.15212/BIOI-2021-0005","url":null,"abstract":"<jats:p>\u0000 \u0000 </jats:p>","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123090634","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}
Background: A two-dimensional (2D) ultrasound examination is the primary technique for follicle monitoring, but 2D ultrasound follicle monitoring has significant inter- and intra-observer variability in the measurement of follicle diameter. The aim of this study was to propose a novel deep learning-based automated model for accurate 2D ultrasound follicle monitoring and validate the reliability and repeatability in clinical practice.Methods: A prospective trial including 300 infertile women undergoing ovulation induction (single follicle cycles) or controlled ovarian hyperstimulation (multiple follicle cycles) was conducted in the reproductive center. After 2D ultrasound image acquisition, the mean diameter of each targeted follicle was measured using an automated model, experts, and a novice. Designating the expert assessment as the gold standard, the reliability and repeatability of the automated model for single and multiple follicle cycles were evaluated using the intraclass correlation coefficient and Bland-Altman plots.Results: A total of 228 and 1065 follicles from single and multiple follicle cycles, respectively, were included. The accurate recognition rate of follicle boundaries using the automated model was 0.931. The inter-observer variability of follicle mean diameter measurements in single and multiple follicle cycles were 0.970 and 0.984 for the automated model and experts, and 0.965 and 0.978 for a novice and experts, respectively. Bland-Altman plots showed that 95% limits of agreement for follicle diameter measurement between the automated model and experts (−2.02 to 2.39 mm and −0.68 to 1.50 mm) was lower than a novice and experts (−1.69 to 2.74 mm and −0.58 to 1.73 mm) for both single and multiple follicle cycles. The intraclass correlation (ICC) of follicle diameters ≥10 mm calculated by the automated model was significantly higher than follicle diameters <10 mm in multiple follicle cycles (0.834 vs. 0.609). There were no significant differences between the two groups in single follicle cycles (0.967 vs. 0.970).Conclusion: A deep learning-based automated model provides an accurate and fast approach for novices to improve the reliability and receptivity of 2D ultrasound follicle monitoring, especially in multiple follicle cycles and for follicles with a mean diameter ≥ 10 mm.
背景:二维(2D)超声检查是卵泡监测的主要技术，但二维超声卵泡监测在测量卵泡直径时具有显着的观察者之间和内部差异。本研究的目的是提出一种新的基于深度学习的二维超声卵泡精确监测自动化模型，并在临床实践中验证其可靠性和可重复性。方法:在生殖中心对300名接受促排卵(单卵泡周期)或控制卵巢过度刺激(多卵泡周期)治疗的不孕症妇女进行前瞻性试验。在二维超声图像采集后，使用自动模型，专家和新手测量每个目标卵泡的平均直径。以专家评价为金标准，采用类内相关系数和Bland-Altman图评价单、多卵泡周期自动模型的可靠性和可重复性。结果:共纳入单个和多个卵泡周期的228和1065个卵泡。自动模型对毛囊边界的准确识别率为0.931。单个和多个卵泡周期的平均直径测量值，自动模型和专家的观察者间变异率分别为0.970和0.984，新手和专家的观察者间变异率分别为0.965和0.978。Bland-Altman图显示，对于单个和多个卵泡周期，自动模型和专家(- 2.02至2.39 mm和- 0.68至1.50 mm)之间卵泡直径测量的95%一致性界限低于新手和专家(- 1.69至2.74 mm和- 0.58至1.73 mm)。在多个卵泡周期中，自动模型计算的≥10 mm卵泡直径的类内相关性(ICC)显著高于<10 mm的卵泡直径(0.834 vs. 0.609)。单卵泡周期两组间差异无统计学意义(0.967 vs 0.970)。结论:基于深度学习的自动模型为新手提高二维超声卵泡监测的可靠性和接受度提供了一种准确、快速的方法，特别是在多个卵泡周期和平均直径≥10 mm的卵泡监测中。
{"title":"Deep Learning Based Two-Dimensional Ultrasound for Follicle Monitoring in Infertility Patients","authors":"Xiaowen Liang, Fengyi Zeng, Haoming Li, Yuewei Li, Yan Lin, Kuan Cai, Dong Ni, Zhiyi Chen","doi":"10.15212/bioi-2022-0024","DOIUrl":"https://doi.org/10.15212/bioi-2022-0024","url":null,"abstract":"\u0000 Background: A two-dimensional (2D) ultrasound examination is the primary technique for follicle monitoring, but 2D ultrasound follicle monitoring has significant inter- and intra-observer variability in the measurement of follicle diameter. The aim of this study was to propose a novel deep learning-based automated model for accurate 2D ultrasound follicle monitoring and validate the reliability and repeatability in clinical practice.Methods: A prospective trial including 300 infertile women undergoing ovulation induction (single follicle cycles) or controlled ovarian hyperstimulation (multiple follicle cycles) was conducted in the reproductive center. After 2D ultrasound image acquisition, the mean diameter of each targeted follicle was measured using an automated model, experts, and a novice. Designating the expert assessment as the gold standard, the reliability and repeatability of the automated model for single and multiple follicle cycles were evaluated using the intraclass correlation coefficient and Bland-Altman plots.Results: A total of 228 and 1065 follicles from single and multiple follicle cycles, respectively, were included. The accurate recognition rate of follicle boundaries using the automated model was 0.931. The inter-observer variability of follicle mean diameter measurements in single and multiple follicle cycles were 0.970 and 0.984 for the automated model and experts, and 0.965 and 0.978 for a novice and experts, respectively. Bland-Altman plots showed that 95% limits of agreement for follicle diameter measurement between the automated model and experts (−2.02 to 2.39 mm and −0.68 to 1.50 mm) was lower than a novice and experts (−1.69 to 2.74 mm and −0.58 to 1.73 mm) for both single and multiple follicle cycles. The intraclass correlation (ICC) of follicle diameters ≥10 mm calculated by the automated model was significantly higher than follicle diameters <10 mm in multiple follicle cycles (0.834 vs. 0.609). There were no significant differences between the two groups in single follicle cycles (0.967 vs. 0.970).Conclusion: A deep learning-based automated model provides an accurate and fast approach for novices to improve the reliability and receptivity of 2D ultrasound follicle monitoring, especially in multiple follicle cycles and for follicles with a mean diameter ≥ 10 mm.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114238323","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}
{"title":"Unlocking the Signal Transduction between Glioma-initiating Cells of Tumor Edge","authors":"Zihan Wang, Jing Huang, S. Qu","doi":"10.15212/BIOI-2021-0010","DOIUrl":"https://doi.org/10.15212/BIOI-2021-0010","url":null,"abstract":"<jats:p>\u0000 \u0000 </jats:p>","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129702999","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}
Background: Orthodontic relapse is fairly common; however, the mechanisms between relapse and the dental arch form remain unclear. The purpose of our study was to establish three-dimensional (3D) finite element models of different dental arch forms after orthodontic treatment and to analyze the states of different arches applied with various sagittal forces.Methods: By calculating the equations of different dental arch forms and combining them with a full maxillary arch (14 teeth), 3D finite element models of square, oval, and tapered dental arches were established; they were designed to be subjected to anterior lingual, posterior mesial, and combined forces, respectively.Results: The von Mises stress and displacement of teeth under different forces were calculated for each loading scenario. Under the different forcing scenarios, all incisors had irregularity trends, and the inclination and intrusion of the canines were increased, and the premolars had a tendency to buccal or lingual crown tipping or even intrusion in our study. The tapered arch was the most stable and had the smallest displacement and von Mises stress, followed by the ovoid arch; the most unstable arch was the square arch.Conclusions: To achieve a stable orthodontic effect, a tapered or ovoid arch, rather than a square arch, should be chosen as the final outcome of treatment.
{"title":"Finite Element Analysis of Orthodontic Relapse in Different Maxillary Arch Form","authors":"Yuanyuan Li, MD, Yiting Shao, MD, Yansong Yu, MD, Yushan Ye, MD, Yingjuan Lu, PhD, Shaohai Chang, MD","doi":"10.15212/bioi-2021-0012","DOIUrl":"https://doi.org/10.15212/bioi-2021-0012","url":null,"abstract":"\u0000 Background: Orthodontic relapse is fairly common; however, the mechanisms between relapse and the dental arch form remain unclear. The purpose of our study was to establish three-dimensional (3D) finite element models of different dental arch forms after orthodontic treatment and to analyze the states of different arches applied with various sagittal forces.Methods: By calculating the equations of different dental arch forms and combining them with a full maxillary arch (14 teeth), 3D finite element models of square, oval, and tapered dental arches were established; they were designed to be subjected to anterior lingual, posterior mesial, and combined forces, respectively.Results: The von Mises stress and displacement of teeth under different forces were calculated for each loading scenario. Under the different forcing scenarios, all incisors had irregularity trends, and the inclination and intrusion of the canines were increased, and the premolars had a tendency to buccal or lingual crown tipping or even intrusion in our study. The tapered arch was the most stable and had the smallest displacement and von Mises stress, followed by the ovoid arch; the most unstable arch was the square arch.Conclusions: To achieve a stable orthodontic effect, a tapered or ovoid arch, rather than a square arch, should be chosen as the final outcome of treatment.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126897707","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}
M. Amir, Amir Gafoor, Z. Iqbal, Shehriyar Ashraf, Salma Zeb
Background: We herein report our experience of optimized utilization of tocilizumab for patients with coronavirus disease 2019 (COVID-19) in a limited-resource tertiary care hospital.Methods: This single-center, single-arm, open-label, interventional study was conducted to determine the effect of tocilizumab on the mortality of patients with COVID-19.Results: Fifty-nine patients were administered tocilizumab. Patients who received invasive respiratory support were identified to have a higher risk of mortality than those who received oxygen support.Conclusion: Our study showed that the maximum benefit of tocilizumab was observed as a prophylactic treatment of cytokine syndrome in patients with COVID-19, particularly those with moderate to severe symptoms who are not receiving invasive respiratory support.TOCIPAK https://ensaiosclinicos.gov.br/rg/RBR-25rtydq; REBEC Number 11773
{"title":"Compassionate Use of Tocilizumab in Patients with Coronavirus Disease 2019 in a Low-resource Country, Pakistan: A Pilot Study","authors":"M. Amir, Amir Gafoor, Z. Iqbal, Shehriyar Ashraf, Salma Zeb","doi":"10.15212/bioi-2021-0019","DOIUrl":"https://doi.org/10.15212/bioi-2021-0019","url":null,"abstract":"\u0000 Background: We herein report our experience of optimized utilization of tocilizumab for patients with coronavirus disease 2019 (COVID-19) in a limited-resource tertiary care hospital.Methods: This single-center, single-arm, open-label, interventional study was conducted to determine the effect of tocilizumab on the mortality of patients with COVID-19.Results: Fifty-nine patients were administered tocilizumab. Patients who received invasive respiratory support were identified to have a higher risk of mortality than those who received oxygen support.Conclusion: Our study showed that the maximum benefit of tocilizumab was observed as a prophylactic treatment of cytokine syndrome in patients with COVID-19, particularly those with moderate to severe symptoms who are not receiving invasive respiratory support.TOCIPAK https://ensaiosclinicos.gov.br/rg/RBR-25rtydq; REBEC Number 11773\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128495358","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}
Shishi He, Xiaoyun Xiao, R. Lei, Jiewen Chen, Hongyan Huang, Ailifeire Yilihamu, M. Guo, Cui Tan, Xun Li, Zilin Zhuang, Phei Er Saw, Yan Nie
Breast phyllodes tumors (PTs) are biphasic, with epithelial and stromal components. Although the PT incidence is low (approximately 1% of all breast tumors), its clinical outcomes are unpredictable, and malignant PTs often progress rapidly. No effective treatment is currently available, thus resulting a high mortality rate from malignant PTs. PT cell lines must be established to facilitate the study of PTs. Herein, we established six PT cell lines through continuous passage or cell immortalization. We characterized these PT cell lines through in vitro functional assays, malignant PT marker detection and short tandem repeat identification. Benign PT cell lines (SYSH-BPT-01 and SYSH-BPT-02) were transfected with human papillomavirus 16 E6/E7, and two malignant PT cell lines (SYSH-MPT-01 and SYSH-MPT-02) were transfected with Simian virus 40 large T antigen. Two malignant PT cell lines (SYSH-MPT-03 and SYSH-MPT-04) were established through continuous passage. All malignant PT cell lines showed greater proliferation, colony formation, migration, invasion and collagen contraction ability than the benign PT cell lines. Moreover, the expression levels of malignant PT markers (α-smooth muscle actin and fibroblast activation protein) and short tandem repeat identification indicated that each PT cell line was identical to the parental primary cells. We successfully established PT cell lines that preserved the features of primary cells. These cell lines may serve as ideal experimental models for studying the function of breast PTs, thus opening new possibilities for PT drug screening and therapeutic target validation.
{"title":"Establishment of Breast Phyllodes Tumor Cell Lines Preserving the Features of Phyllodes Tumors","authors":"Shishi He, Xiaoyun Xiao, R. Lei, Jiewen Chen, Hongyan Huang, Ailifeire Yilihamu, M. Guo, Cui Tan, Xun Li, Zilin Zhuang, Phei Er Saw, Yan Nie","doi":"10.15212/bioi-2022-0025","DOIUrl":"https://doi.org/10.15212/bioi-2022-0025","url":null,"abstract":"\u0000 Breast phyllodes tumors (PTs) are biphasic, with epithelial and stromal components. Although the PT incidence is low (approximately 1% of all breast tumors), its clinical outcomes are unpredictable, and malignant PTs often progress rapidly. No effective treatment is currently available, thus resulting a high mortality rate from malignant PTs. PT cell lines must be established to facilitate the study of PTs. Herein, we established six PT cell lines through continuous passage or cell immortalization. We characterized these PT cell lines through in vitro functional assays, malignant PT marker detection and short tandem repeat identification. Benign PT cell lines (SYSH-BPT-01 and SYSH-BPT-02) were transfected with human papillomavirus 16 E6/E7, and two malignant PT cell lines (SYSH-MPT-01 and SYSH-MPT-02) were transfected with Simian virus 40 large T antigen. Two malignant PT cell lines (SYSH-MPT-03 and SYSH-MPT-04) were established through continuous passage. All malignant PT cell lines showed greater proliferation, colony formation, migration, invasion and collagen contraction ability than the benign PT cell lines. Moreover, the expression levels of malignant PT markers (α-smooth muscle actin and fibroblast activation protein) and short tandem repeat identification indicated that each PT cell line was identical to the parental primary cells. We successfully established PT cell lines that preserved the features of primary cells. These cell lines may serve as ideal experimental models for studying the function of breast PTs, thus opening new possibilities for PT drug screening and therapeutic target validation.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"140 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124420122","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}
Large-animal models show greater advantages than rodents in recapitulating human genetic diseases, primarily because of their higher similarity to humans in terms of anatomy, physiology and genetics. Notably, as genome-editing technologies have rapidly improved, particularly transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9) systems, their application in biomedical research has accelerated. A variety of genetically modified large-animal models, including non-human primates, pigs, dogs, bovines and sheep, have been produced to recapitulate human inherited disorders, thus providing novel biological and translational insights. Here, we review recent progress in the generation of large-animal models over the past 5 years and summarize their use in studying human genetic diseases, focusing on the nervous system, cardiovascular and metabolic systems, the immune system, xenotransplantation, the reproductive system and embryonic development.
{"title":"Recent advances in genetically modified large-animal models of human diseases","authors":"Jing Zhang, Xiaoyue Sun, Chunwei Cao","doi":"10.15212/bioi-2022-0018","DOIUrl":"https://doi.org/10.15212/bioi-2022-0018","url":null,"abstract":"\u0000 Large-animal models show greater advantages than rodents in recapitulating human genetic diseases, primarily because of their higher similarity to humans in terms of anatomy, physiology and genetics. Notably, as genome-editing technologies have rapidly improved, particularly transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9) systems, their application in biomedical research has accelerated. A variety of genetically modified large-animal models, including non-human primates, pigs, dogs, bovines and sheep, have been produced to recapitulate human inherited disorders, thus providing novel biological and translational insights. Here, we review recent progress in the generation of large-animal models over the past 5 years and summarize their use in studying human genetic diseases, focusing on the nervous system, cardiovascular and metabolic systems, the immune system, xenotransplantation, the reproductive system and embryonic development.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133632644","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}
Transcription factors are key components in gene expression and are associated with various diseases. Transcription factors maintain the stability of gene transcription and cell function. Among the transcription factors, the Runt-related transcription factor (RUNX) family regulates growth and development in a tissue-specific manner and is involved in tumorigenesis. The function of an important member of the RUNX family, RUNX3, was shown to be closely related to its subcellular localization. Normally, RUNX3 promotes or represses gene transcription in the nucleus; however, when RUNX3 is restricted in the cytoplasm, RUNX3 fails to function and only has a minor effect o gene expression. Hence, the risk of tumorigenesis cannot simply be equated with the level of RUNX3 expression, which makes the diagnosis and treatment of cancer more complicated. The cytoplasmic localization of RUNX3 has been shown to be associated with a variety of tumors. Herein we have summarized the current information on RUNX3 mis-localization and RUNX3 promotion of tumorigenesis, thus providing new insight for future investigations to elucidate the mechanisms by which RUNX3 regulates tumorigenesis.
{"title":"RUNX3: A Location-oriented Genome Coordinator","authors":"Tianshu Xu, Yancan Liang, Zhiquan Huang, Zixian Huang","doi":"10.15212/bioi-2023-0003","DOIUrl":"https://doi.org/10.15212/bioi-2023-0003","url":null,"abstract":"\u0000 Transcription factors are key components in gene expression and are associated with various diseases. Transcription factors maintain the stability of gene transcription and cell function. Among the transcription factors, the Runt-related transcription factor (RUNX) family regulates growth and development in a tissue-specific manner and is involved in tumorigenesis. The function of an important member of the RUNX family, RUNX3, was shown to be closely related to its subcellular localization. Normally, RUNX3 promotes or represses gene transcription in the nucleus; however, when RUNX3 is restricted in the cytoplasm, RUNX3 fails to function and only has a minor effect o gene expression. Hence, the risk of tumorigenesis cannot simply be equated with the level of RUNX3 expression, which makes the diagnosis and treatment of cancer more complicated. The cytoplasmic localization of RUNX3 has been shown to be associated with a variety of tumors. Herein we have summarized the current information on RUNX3 mis-localization and RUNX3 promotion of tumorigenesis, thus providing new insight for future investigations to elucidate the mechanisms by which RUNX3 regulates tumorigenesis.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115873192","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}
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