Pub Date : 2024-07-31DOI: 10.2174/0118761429305367240725112731
Sharmeen Fayyaz, Atia tul-Wahab, Bushra Taj, M. Iqbal Choudhary
Objectives: Increasing ratio of bone fragility, and susceptibility to fractures constitutes a major health problem worldwide. Therefore, we aimed to identify new compounds with a potential to increase proliferation and differentiation of osteoblasts. Methods: Cellular and molecular assays, such as ALP activity, alizarin staining, and flow cytometry were employed to check the effect of TMF on osteogenesis. Moreover, gene expression analysis of certain important genes and transcriptional factors was also performed. Results: Our findings report for the first time that 7,3′,4′-trimethoxyflavone is capable of enhancing proliferation, and differentiation in osteoblast cells. Results from flow cytometry analysis also indicated that TMF increases the number of cells in S-phase. Furthermore, treatment with TMF altered the expression of osteogenic genes, OCN and Axin-2 indicating possible activation of Wnt signaling pathway. Conclusion: Taken together, this study identified that 7,3′,4′-trimethoxyflavone has the potential to enhance osteoblast proliferation and differentiation, possibly due to the activation of Wnt/β-catenin pathway. Thus, demonstrating TMF as naturally occurring agent to promote osteogenesis and prevention of bone fragility, and related disorders.
目的：骨脆性和骨折易感性的比例不断增加是全球范围内的一个主要健康问题。因此，我们旨在找出具有增加成骨细胞增殖和分化潜力的新化合物。研究方法采用 ALP 活性、茜素染色和流式细胞术等细胞和分子检测方法来检验 TMF 对成骨作用的影响。此外，还对某些重要基因和转录因子进行了基因表达分析。结果我们的研究结果首次报道了 7,3′,4′-三甲氧基黄酮能够促进成骨细胞的增殖和分化。流式细胞仪分析的结果也表明，TMF 能增加处于 S 期的细胞数量。此外，TMF 还能改变成骨基因 OCN 和 Axin-2 的表达，这表明 Wnt 信号通路可能被激活。结论综上所述，本研究发现 7,3′,4′-三甲氧基黄酮具有促进成骨细胞增殖和分化的潜力，这可能是由于激活了 Wnt/β-catenin 通路。因此，TMF 是促进成骨和预防骨质脆弱及相关疾病的天然药物。
{"title":"Positive Regulation of Osteoblast Proliferation and Differentiation in MC3T3- E1 Cells by 7,3′,4′-Trimethoxyflavone","authors":"Sharmeen Fayyaz, Atia tul-Wahab, Bushra Taj, M. Iqbal Choudhary","doi":"10.2174/0118761429305367240725112731","DOIUrl":"https://doi.org/10.2174/0118761429305367240725112731","url":null,"abstract":"Objectives: Increasing ratio of bone fragility, and susceptibility to fractures constitutes a major health problem worldwide. Therefore, we aimed to identify new compounds with a potential to increase proliferation and differentiation of osteoblasts. Methods: Cellular and molecular assays, such as ALP activity, alizarin staining, and flow cytometry were employed to check the effect of TMF on osteogenesis. Moreover, gene expression analysis of certain important genes and transcriptional factors was also performed. Results: Our findings report for the first time that 7,3′,4′-trimethoxyflavone is capable of enhancing proliferation, and differentiation in osteoblast cells. Results from flow cytometry analysis also indicated that TMF increases the number of cells in S-phase. Furthermore, treatment with TMF altered the expression of osteogenic genes, OCN and Axin-2 indicating possible activation of Wnt signaling pathway. Conclusion: Taken together, this study identified that 7,3′,4′-trimethoxyflavone has the potential to enhance osteoblast proliferation and differentiation, possibly due to the activation of Wnt/β-catenin pathway. Thus, demonstrating TMF as naturally occurring agent to promote osteogenesis and prevention of bone fragility, and related disorders.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.2174/187446721701240419165931
Li Yuan, Liang Zeng, Feng Ye, Kai Chen, Zhengrong Chen, Liping Li
An error occurred in the funding details of the manuscript titled I“MPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway”, 2024; 17: e18761429257350 [1]. <p> Original: <p> This work was funded by grants from the National Natural Science Foundation of China (No. 81802346). <p> Corrected: This work was funded by grants from the Basic Research Program of Guangzhou Science and Technology Program Project No. 202201010947. <p> The original article can be found online at https://benthamscience.com/article/138645
原标题为《MPDH2 Positively Impacts the Proliferation Potentials of Hepatoblastoma Cells by Activating JunB Signaling Pathway》，2024; 17: e18761429257350 [1]的稿件的经费细节出现错误：本研究得到了广州市科技计划基础研究项目（编号：202201010947）的资助。<p> 原文可在 https://benthamscience.com/article/138645 上查阅。
{"title":"Corrigendum to: IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway","authors":"Li Yuan, Liang Zeng, Feng Ye, Kai Chen, Zhengrong Chen, Liping Li","doi":"10.2174/187446721701240419165931","DOIUrl":"https://doi.org/10.2174/187446721701240419165931","url":null,"abstract":"An error occurred in the funding details of the manuscript titled I“MPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway”, 2024; 17: e18761429257350 [1]. <p> Original: <p> This work was funded by grants from the National Natural Science Foundation of China (No. 81802346). <p> Corrected: This work was funded by grants from the Basic Research Program of Guangzhou Science and Technology Program Project No. 202201010947. <p> The original article can be found online at https://benthamscience.com/article/138645","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nasopharyngeal cancer is a rare cancer with unique ethnic and geographic distribution. Since nasopharyngeal cancer often originates from the pharyngeal crypt, early symptoms are not obvious. They are difficult to detect in time, and the disease is usually diagnosed and treated only when it has progressed to an advanced-stage. Since angiogenesis is essential for the growth and invasion of solid tumors, antiangiogenic therapy has become a common treatment strategy for many solid tumors, and it has also achieved remarkable results in the treatment of nasopharyngeal carcinoma, which is prone to recurrence and distant metastasis. In this paper, we review the latest research progress of antiangiogenic drugs for nasopharyngeal carcinoma and their antiangiogenic mechanism of action and further propose some promising antiangiogenic therapeutic targets.
{"title":"Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma.","authors":"Yunzhi Zhu, Yi Hu, Chengsheng Yang, Shipu Huang, Jianping Wen, Weiguo Huang, Shengjun Xiao","doi":"10.2174/0118761429290933240408071812","DOIUrl":"https://doi.org/10.2174/0118761429290933240408071812","url":null,"abstract":"Nasopharyngeal cancer is a rare cancer with unique ethnic and geographic distribution. Since nasopharyngeal cancer often originates from the pharyngeal crypt, early symptoms are not obvious. They are difficult to detect in time, and the disease is usually diagnosed and treated only when it has progressed to an advanced-stage. Since angiogenesis is essential for the growth and invasion of solid tumors, antiangiogenic therapy has become a common treatment strategy for many solid tumors, and it has also achieved remarkable results in the treatment of nasopharyngeal carcinoma, which is prone to recurrence and distant metastasis. In this paper, we review the latest research progress of antiangiogenic drugs for nasopharyngeal carcinoma and their antiangiogenic mechanism of action and further propose some promising antiangiogenic therapeutic targets.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-05DOI: 10.2174/0118761429264553231204115314
Natalia Nazarenko, Jiyoung Seo, Sanjana Nagraj, Leonidas Palaiodimos, Damianos G. Kokkinidis
:: Globally, there remains an unwavering increase in the incidence of cvd - from 271 million in 1990 to 523 million in 2019. Among the several modifiable and non-modifiable risk factors of heart disease, dyslipidemia is an important and prevalent risk factor mediated by both genetics and lifestyle factors. Hence, lowering lipid levels, specifically, ldl-c levels (low-density lipoprotein cholesterol), is a key strategy in decreasing the risk of cardiovascular disease. A reduction of 20 mg/dl in ldl-c levels has been found to prevent 2-3 cases of coronary artery disease (cad) for every 1000 individuals. Studies have also found reductions in ldl-c levels to be associated with a mortality benefit. However, ldl-c levels reduction may not eliminate the risk of significant cardiovascular events.
{"title":"RNA Interference-based Therapies for the Reduction of Cardiovascular Risk","authors":"Natalia Nazarenko, Jiyoung Seo, Sanjana Nagraj, Leonidas Palaiodimos, Damianos G. Kokkinidis","doi":"10.2174/0118761429264553231204115314","DOIUrl":"https://doi.org/10.2174/0118761429264553231204115314","url":null,"abstract":":: Globally, there remains an unwavering increase in the incidence of cvd - from 271 million in 1990 to 523 million in 2019. Among the several modifiable and non-modifiable risk factors of heart disease, dyslipidemia is an important and prevalent risk factor mediated by both genetics and lifestyle factors. Hence, lowering lipid levels, specifically, ldl-c levels (low-density lipoprotein cholesterol), is a key strategy in decreasing the risk of cardiovascular disease. A reduction of 20 mg/dl in ldl-c levels has been found to prevent 2-3 cases of coronary artery disease (cad) for every 1000 individuals. Studies have also found reductions in ldl-c levels to be associated with a mortality benefit. However, ldl-c levels reduction may not eliminate the risk of significant cardiovascular events.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140045625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.2174/0118761429257350231212093136
Li Yuan, Liang Zeng, Feng Ye, Kai Chen, Zhengrong Chen, Liping Li
Background: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB). Methods: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB. Results: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB. Conclusion: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.
{"title":"IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway","authors":"Li Yuan, Liang Zeng, Feng Ye, Kai Chen, Zhengrong Chen, Liping Li","doi":"10.2174/0118761429257350231212093136","DOIUrl":"https://doi.org/10.2174/0118761429257350231212093136","url":null,"abstract":"Background: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB). Methods: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB. Results: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB. Conclusion: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139949549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.2174/0118761429246578231130064830
Ali Mohammad Pourbagher-Shahri, Tahereh Farkhondeh, Amir Masoud Jafari-Nozad, Majid Darroudi, Kobra Naseri, Masoumeh Amirian, Saeed Samarghandian
:: Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.
::缺血再灌注损伤（IRI）是一种自相矛盾的现象，消除损伤源会造成额外的损伤。缺血会减少 ATP 生成和细胞内 pH 值，从而减少氧化反应，增加乳酸释放，激活无氧代谢。再灌注可恢复有氧呼吸并增加 ROS 的产生，导致跨膜转运功能失调、蛋白酶激活、DNA 溶解和蛋白质变性，从而导致细胞凋亡。Nrf2 是一种调节细胞炎症和氧化反应的转录因子。它被氧化剂和电介质激活，增强解毒酶的表达，维持氧化还原平衡。它还能激活 ARE，从而激活多个 ARE 调控基因，这些基因通过表现出对氧化剂和电介质的抵抗力而有利于细胞存活。Nrf2 通过产生第二阶段和抗氧化防御酶（包括 HO-1、NQO-1、谷氨酰半胱氨酸合成酶和谷胱甘肽合成的限速酶）来调节抗氧化防御系统。Nrf2 保护线粒体免受损伤，并在压力条件下支持线粒体功能。白藜芦醇是一种以芪为基础的化合物，对人体健康有多种益处，包括抗氧化、抗癌、抗肿瘤和雌激素/抗雌激素。白藜芦醇可通过包括 Nrf2/ARE 通路在内的几种信号通路防止 IRI。在此，我们回顾了有关白藜芦醇通过调节 Nrf2 信号通路防止 IRI 的机制的研究。
{"title":"Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury","authors":"Ali Mohammad Pourbagher-Shahri, Tahereh Farkhondeh, Amir Masoud Jafari-Nozad, Majid Darroudi, Kobra Naseri, Masoumeh Amirian, Saeed Samarghandian","doi":"10.2174/0118761429246578231130064830","DOIUrl":"https://doi.org/10.2174/0118761429246578231130064830","url":null,"abstract":":: Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139763786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.2174/0118761429269383231119062233
Asmat Ullah, Anum Razzaq, Mohammad Y. Alfaifi, Serag Eldin I. Elbehairi, Farid Menaa, Najeeb Ullah, Somia Shehzadi, Touseef Nawaz, Haroon Iqbal
Background:: Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes. Aims:: Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration. Objective:: This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299. Methods:: MTT assay to determine the IC50, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein. Results:: Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation. Conclusion:: Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.
背景：：肺癌（LC）发病率在全球范围内不断上升，已成为癌症相关死亡的主要原因。肺癌会导致多阶段的癌变，遗传和表观遗传变化会逐渐增加。研究目的桑吉纳林（Sang）通过刺激活性氧（ROS）、阻碍Bcl2、增强Bax和其他凋亡相关蛋白Caspase-3、-9和-PARP来介导LCC株的抗癌作用，进而抑制LCC的侵袭和迁移。研究目的本研究旨在探讨人 LC 细胞（LCC）H522 和 H1299 的凋亡率和 Sang 的作用机制。方法通过 MTT 试验测定 IC50、细胞形态学和集落形成试验来显示桑吉纳林对 LC 细胞株的影响。此外，还进行了划痕试验和透孔试验以检测迁移情况。还进行了 Western 印迹和 qPCR 分析，以显示其对目标蛋白和基因的影响。酶联免疫吸附试验（ELISA）显示了三基萘林处理后对血管内皮生长因子（VEGF）的影响。免疫荧光检查目标蛋白的互锁情况。结果Sang 能明显抑制 LCC 株系的生长，且具有时间和剂量依赖性。流式细胞术检查和Annexin-V标记确定桑增加了凋亡细胞的百分比。用 Sang 处理的 H522 和 H1299 LCC 株表现出明显的细胞凋亡特征，包括形态变化和 DNA 断裂。结论Sang 对 LCC 株具有抗癌潜力，可诱导细胞凋亡，阻碍 LCC 的侵袭和迁移，是一种在肺癌治疗中很有前景的抗癌天然药物。
{"title":"Sanguinarine Attenuates Lung Cancer Progression via Oxidative Stress-induced Cell Apoptosis","authors":"Asmat Ullah, Anum Razzaq, Mohammad Y. Alfaifi, Serag Eldin I. Elbehairi, Farid Menaa, Najeeb Ullah, Somia Shehzadi, Touseef Nawaz, Haroon Iqbal","doi":"10.2174/0118761429269383231119062233","DOIUrl":"https://doi.org/10.2174/0118761429269383231119062233","url":null,"abstract":"Background:: Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes. Aims:: Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration. Objective:: This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299. Methods:: MTT assay to determine the IC50, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein. Results:: Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation. Conclusion:: Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139763862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background:: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. Objective:: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. Methods:: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. Results:: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. Conclusion:: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.
{"title":"Impact of Nicosulfuron on Sperm Quality: Insights into Testicular Cell Apoptosis and NF-κB Signaling Pathway in Mice Testes","authors":"Jianqiu Han, Chen Zhao, Qing Shen, Yalei Qi, Yanjia Zhang, Faisal Raza, Yongmei Li, Hajra Zafar, Tengfei Liu, Juan Tan, Honghui Han, Xueyun Ma","doi":"10.2174/0118761429282063231119180457","DOIUrl":"https://doi.org/10.2174/0118761429282063231119180457","url":null,"abstract":"Background:: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. Objective:: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. Methods:: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. Results:: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. Conclusion:: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139763953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.2174/0118761429274883231129103220
Liqi Li, Yunyun Li, Xiaoshu Zhou
:: Guanine nucleotide exchange factor H1 (GEF-H1) is a unique protein modulated by the GDP/GTP exchange. As a regulator of the Rho-GTPase family, GEF-H1 can be activated through a microtubule-depended mechanism and phosphorylation regulation, enabling it to perform various pivotal biological functions across multiple cellular activities. These include the regulation of Rho-GTPase, cytoskeleton formation, cellular barrier, cell cycle, mitosis, cell differentiation, and vesicle trafficking. Recent studies have revealed its crucial effect on the tumor microenvironment (TME) components, promoting tumor initiation and progress. Consequently, an in-depth exploration of GEF-H1’s biological roles and association with tumors holds promise for its potential as a valuable molecular target in tumor treatment.
{"title":"Advancements in the Research of GEF-H1: Biological Functions and Tumor Associations","authors":"Liqi Li, Yunyun Li, Xiaoshu Zhou","doi":"10.2174/0118761429274883231129103220","DOIUrl":"https://doi.org/10.2174/0118761429274883231129103220","url":null,"abstract":":: Guanine nucleotide exchange factor H1 (GEF-H1) is a unique protein modulated by the GDP/GTP exchange. As a regulator of the Rho-GTPase family, GEF-H1 can be activated through a microtubule-depended mechanism and phosphorylation regulation, enabling it to perform various pivotal biological functions across multiple cellular activities. These include the regulation of Rho-GTPase, cytoskeleton formation, cellular barrier, cell cycle, mitosis, cell differentiation, and vesicle trafficking. Recent studies have revealed its crucial effect on the tumor microenvironment (TME) components, promoting tumor initiation and progress. Consequently, an in-depth exploration of GEF-H1’s biological roles and association with tumors holds promise for its potential as a valuable molecular target in tumor treatment.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139763951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Cardiovascular diseases [CVD] are the number one reason for morbidity and mortality in the modern world, and their incidence is increasing at an incredible pace. Increasing evidence has shown the significant functions of microRNAs in the cardiovascular system and has highlighted their potential application as a new era of diagnostic and therapeutic targets for CVD that can improve the prognosis and life expectancy of patients. Among more than 2,000 microRNAs, microRNA-21 [miR-21] is highly expressed in human hearts and has earned the interest of researchers as a potential biomarker in a wide range of common heart conditions. Here, we summarized recent research progress regarding the significant role of miR-21 in CVD, focusing on cardiotoxicity, heart arrhythmias, cardiomyopathies, and hypertension. Several signaling pathways [TGF-β1/Smad2 signaling, FGFR1/FGF21/PPARγ, NF-κB/miR-21/SMAD7, miR-21/SPRY1/ERK/mTOR …] and molecular targets [BTG2, PDCD4, PTEN, STAT3…] were reported to be controlled, at least partially, by miR-21 and are linked to CVD pathogenesis. Most investigations highlighted miR-21 cardioprotective functions in heart injury, while some other studies showed that this miR is elevated in the serum/tissue of patients, promoting fibrosis and cardiac dysfunction. This dual role can be explained by the fact that miR-21 has multiple regulatory functions depending on the microenvironment, downstream signaling, and target genes, which indicates that cell-type-specific investigations should receive more attention. With further investigations, miR-21 can be considered a novel tailored therapy with favorable outcomes.
{"title":"A Review of the Dual Role of MicroRNA-21 in Cardiovascular Diseases: Risk Factor or a Potential Therapeutic Target","authors":"Amir Masoud Jafari-Nozad, Negin Rostami, Melika Esmaeili, Haniye Vahdati, Serajoddin Hosseini, Tahereh Farkhondeh, Saeed Samarghandian","doi":"10.2174/0118761429287057240116040703","DOIUrl":"https://doi.org/10.2174/0118761429287057240116040703","url":null,"abstract":": Cardiovascular diseases [CVD] are the number one reason for morbidity and mortality in the modern world, and their incidence is increasing at an incredible pace. Increasing evidence has shown the significant functions of microRNAs in the cardiovascular system and has highlighted their potential application as a new era of diagnostic and therapeutic targets for CVD that can improve the prognosis and life expectancy of patients. Among more than 2,000 microRNAs, microRNA-21 [miR-21] is highly expressed in human hearts and has earned the interest of researchers as a potential biomarker in a wide range of common heart conditions. Here, we summarized recent research progress regarding the significant role of miR-21 in CVD, focusing on cardiotoxicity, heart arrhythmias, cardiomyopathies, and hypertension. Several signaling pathways [TGF-β1/Smad2 signaling, FGFR1/FGF21/PPARγ, NF-κB/miR-21/SMAD7, miR-21/SPRY1/ERK/mTOR …] and molecular targets [BTG2, PDCD4, PTEN, STAT3…] were reported to be controlled, at least partially, by miR-21 and are linked to CVD pathogenesis. Most investigations highlighted miR-21 cardioprotective functions in heart injury, while some other studies showed that this miR is elevated in the serum/tissue of patients, promoting fibrosis and cardiac dysfunction. This dual role can be explained by the fact that miR-21 has multiple regulatory functions depending on the microenvironment, downstream signaling, and target genes, which indicates that cell-type-specific investigations should receive more attention. With further investigations, miR-21 can be considered a novel tailored therapy with favorable outcomes.","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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