Pub Date : 2024-10-22DOI: 10.1007/s11033-024-09998-1
Vishnu Adith Janarathanam, Praveen Kumar Issac, Ieshita Pan, Nagalakshmi Kamaraj, Sabah Ansar, Yedluri Anil Kumar, Ajay Guru
Background: An excessive amount of reactive oxygen species triggers oxidative stress, leading to an imbalance in cellular homeostasis. Antioxidant therapy is an effective tool for lowering the oxidative stress and associated ailments. Recently, green nano-based drug formulations have demonstrated promising antioxidant activity and neutralizing oxidative stress. In this study, a tannin molecule Hamamelitannin (HAM), was utilized to synthesize zinc oxide nanoparticles HAM-ZnO NPs, to mitigate oxidative stress and associated ailments .
Methodology: The HAM-ZnO NPs were synthesized and characterized by XRD, SEM, and FTIR. The antioxidant potentials of HAM-ZnO NPs were analyzed by in vitro antioxidant assays. Zebrafish embryos and larvae were used as in-vivo models to assess the toxicity and antioxidant protective mechanism. Hydrogen peroxide (1mM) was employed to induce oxidative stress and treated with HAM-ZnO NPs to study the cognitive impairment and antioxidant enzyme levels. Levels of reactive oxygen species and cell death due to oxidative stress induction were studied by 2',7'-dichlorodihydrofluorescein diacetate and Acridine orange staining methods. Additionally, expression of Antioxidant genes such as SOD, CAT, GPx, and GSR were studied. .
Results: HAM-ZnO NPs exhibited a spherical morphology and size ranges between 48 and 53 nm. In vitro antioxidant studies revealed the antioxidant properties of HAM-ZnO NPs. Furthermore, in vivo studies indicated that HAM-ZnO NPs don't possess any cytotoxic effects in zebrafish larvae at concentrations between (5-25 µg/ml), The study also observed that HAM-ZnO NPs significantly reduced Hydrogen Peroxide-induced stress and increased antioxidant activity in zebrafish larvae. Also, the antioxidant gene expression was upregulated in the HAM-ZnO NPs zebrafish larvae.
Conclusion: Findings in this study showed that HAM-ZnO NPs might be a potential intervention for diseases linked to oxidative stress.
{"title":"Investigating antioxidant effects of hamamelitannin-conjugated zinc oxide nanoparticles on oxidative stress-Induced neurotoxicity in zebrafish larvae model.","authors":"Vishnu Adith Janarathanam, Praveen Kumar Issac, Ieshita Pan, Nagalakshmi Kamaraj, Sabah Ansar, Yedluri Anil Kumar, Ajay Guru","doi":"10.1007/s11033-024-09998-1","DOIUrl":"https://doi.org/10.1007/s11033-024-09998-1","url":null,"abstract":"<p><strong>Background: </strong>An excessive amount of reactive oxygen species triggers oxidative stress, leading to an imbalance in cellular homeostasis. Antioxidant therapy is an effective tool for lowering the oxidative stress and associated ailments. Recently, green nano-based drug formulations have demonstrated promising antioxidant activity and neutralizing oxidative stress. In this study, a tannin molecule Hamamelitannin (HAM), was utilized to synthesize zinc oxide nanoparticles HAM-ZnO NPs, to mitigate oxidative stress and associated ailments .</p><p><strong>Methodology: </strong>The HAM-ZnO NPs were synthesized and characterized by XRD, SEM, and FTIR. The antioxidant potentials of HAM-ZnO NPs were analyzed by in vitro antioxidant assays. Zebrafish embryos and larvae were used as in-vivo models to assess the toxicity and antioxidant protective mechanism. Hydrogen peroxide (1mM) was employed to induce oxidative stress and treated with HAM-ZnO NPs to study the cognitive impairment and antioxidant enzyme levels. Levels of reactive oxygen species and cell death due to oxidative stress induction were studied by 2',7'-dichlorodihydrofluorescein diacetate and Acridine orange staining methods. Additionally, expression of Antioxidant genes such as SOD, CAT, GPx, and GSR were studied. .</p><p><strong>Results: </strong>HAM-ZnO NPs exhibited a spherical morphology and size ranges between 48 and 53 nm. In vitro antioxidant studies revealed the antioxidant properties of HAM-ZnO NPs. Furthermore, in vivo studies indicated that HAM-ZnO NPs don't possess any cytotoxic effects in zebrafish larvae at concentrations between (5-25 µg/ml), The study also observed that HAM-ZnO NPs significantly reduced Hydrogen Peroxide-induced stress and increased antioxidant activity in zebrafish larvae. Also, the antioxidant gene expression was upregulated in the HAM-ZnO NPs zebrafish larvae.</p><p><strong>Conclusion: </strong>Findings in this study showed that HAM-ZnO NPs might be a potential intervention for diseases linked to oxidative stress.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470187","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 : 2024-10-22DOI: 10.1007/s11033-024-10012-x
Chaohu Chen, Pan Li, Guangrui Fan, Enguang Yang, Suoshi Jing, Yibo Shi, Yuwen Gong, Luyang Zhang, Zhiping Wang
As an AAA + ATPase, thyroid hormone receptor interacting protein 13 (TRIP13) primarily functions in DNA double-strand break repair, chromosome recombination, and cell cycle checkpoint regulation; aberrant expression of TRIP13 can result in chromosomal instability (CIN). According to recent research, TRIP13 is aberrantly expressed in a variety of cancers, and a patient's poor prognosis and tumor stage are strongly correlated with high expression of TRIP13. Tumor cell and subcutaneous xenograft growth can be markedly inhibited by TRIP13 knockdown or TRIP13 inhibitor administration. In the initiation and advancement of human malignancies, TRIP13 seems to function as an oncogene. Based on available data, TRIP13 may function as a biological target and biomarker for cancer. The creation of inhibitors that specifically target TRIP13 may present novel approaches to treating cancer.
{"title":"Role of TRIP13 in human cancer development.","authors":"Chaohu Chen, Pan Li, Guangrui Fan, Enguang Yang, Suoshi Jing, Yibo Shi, Yuwen Gong, Luyang Zhang, Zhiping Wang","doi":"10.1007/s11033-024-10012-x","DOIUrl":"https://doi.org/10.1007/s11033-024-10012-x","url":null,"abstract":"<p><p>As an AAA + ATPase, thyroid hormone receptor interacting protein 13 (TRIP13) primarily functions in DNA double-strand break repair, chromosome recombination, and cell cycle checkpoint regulation; aberrant expression of TRIP13 can result in chromosomal instability (CIN). According to recent research, TRIP13 is aberrantly expressed in a variety of cancers, and a patient's poor prognosis and tumor stage are strongly correlated with high expression of TRIP13. Tumor cell and subcutaneous xenograft growth can be markedly inhibited by TRIP13 knockdown or TRIP13 inhibitor administration. In the initiation and advancement of human malignancies, TRIP13 seems to function as an oncogene. Based on available data, TRIP13 may function as a biological target and biomarker for cancer. The creation of inhibitors that specifically target TRIP13 may present novel approaches to treating cancer.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470204","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}
{"title":"Correction: Value of miR-31 and mir-150-3p as diagnostic and prognostic biomarkers for breast cancer.","authors":"Elif Erturk, Ferda Ari, Omer Enes Onur, Sehsuvar Mustafa Gokgoz, Sahsine Tolunay","doi":"10.1007/s11033-024-10010-z","DOIUrl":"https://doi.org/10.1007/s11033-024-10010-z","url":null,"abstract":"","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470162","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 : 2024-10-21DOI: 10.1007/s11033-024-09990-9
Muhammet Yusuf Tepebasi, Esma Selcuk, Rumeysa Taner, Serife Tasan, Halil Asci, Ali Baran Gunes, Berkehan Sarisahin, Bunyamin Aydın
Background: Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 inhibitor and is used in the treatment of diabetes. In this study, we aimed to investigate the effect of DPG on cardiotoxicity caused by systemic inflammation via endoplasmic reticulum (ER) stress and autophagy.
Methods and results: Four groups of thirty-two Wistar Albino rats were created: Control (1 ml oral physiological saline for five days and intraperitoneal saline on the 5th day), LPS (1 ml oral physiological saline for five days and intraperitoneal 5 mg/kg of LPS on the 5th day), LPS + DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of LPS intraperitoneally on the 5th day), and DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of SF intraperitoneally on the 5th day). Histopathological and immunohistochemical analyses were performed on heart and aorta tissues. ER stress and autophagy gene markers in heart tissues were evaluated by RT-qPCR. Oxidative stress in heart tissues and serum cardiac enzymes were analyzed by spectrophotometric method. The heart and aortic tissues of the LPS group showed increased expressions of Tumor Necrosis Factor-α (TNF-α) and Caspase-3 (Cas-3), along with mild hyperemia, slight inflammatory cell infiltrations, and myocardial cell damage. The heart tissues also showed genetically increased expressions of include binding immunoglobulin protein (BiP/ GRP78), protein kinase RNA-like ER Kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factors 4 (ATF-4), activating transcription factors 4 (ATF6), C/EBP homologous protein (CHOP), and BECLIN 1. Furthermore, Creatine kinase-MB (CK-MB) and Lactate dehydrogenase (LDH) levels in blood tissue significantly increased, according to biochemical analysis. With DPG therapy, all of these findings were reversed.
Conclusion: In conclusion, DPG protects against the cardiotoxic effect of systemic inflammation with its antioxidant and anti-inflammatory properties by regulating ER stress and autophagy pathways.
{"title":"Potential ameliorative effect of Dapagliflozin on systemic inflammation-induced cardiovascular injury via endoplasmic reticulum stress and autophagy pathway.","authors":"Muhammet Yusuf Tepebasi, Esma Selcuk, Rumeysa Taner, Serife Tasan, Halil Asci, Ali Baran Gunes, Berkehan Sarisahin, Bunyamin Aydın","doi":"10.1007/s11033-024-09990-9","DOIUrl":"https://doi.org/10.1007/s11033-024-09990-9","url":null,"abstract":"<p><strong>Background: </strong>Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 inhibitor and is used in the treatment of diabetes. In this study, we aimed to investigate the effect of DPG on cardiotoxicity caused by systemic inflammation via endoplasmic reticulum (ER) stress and autophagy.</p><p><strong>Methods and results: </strong>Four groups of thirty-two Wistar Albino rats were created: Control (1 ml oral physiological saline for five days and intraperitoneal saline on the 5th day), LPS (1 ml oral physiological saline for five days and intraperitoneal 5 mg/kg of LPS on the 5th day), LPS + DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of LPS intraperitoneally on the 5th day), and DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of SF intraperitoneally on the 5th day). Histopathological and immunohistochemical analyses were performed on heart and aorta tissues. ER stress and autophagy gene markers in heart tissues were evaluated by RT-qPCR. Oxidative stress in heart tissues and serum cardiac enzymes were analyzed by spectrophotometric method. The heart and aortic tissues of the LPS group showed increased expressions of Tumor Necrosis Factor-α (TNF-α) and Caspase-3 (Cas-3), along with mild hyperemia, slight inflammatory cell infiltrations, and myocardial cell damage. The heart tissues also showed genetically increased expressions of include binding immunoglobulin protein (BiP/ GRP78), protein kinase RNA-like ER Kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factors 4 (ATF-4), activating transcription factors 4 (ATF6), C/EBP homologous protein (CHOP), and BECLIN 1. Furthermore, Creatine kinase-MB (CK-MB) and Lactate dehydrogenase (LDH) levels in blood tissue significantly increased, according to biochemical analysis. With DPG therapy, all of these findings were reversed.</p><p><strong>Conclusion: </strong>In conclusion, DPG protects against the cardiotoxic effect of systemic inflammation with its antioxidant and anti-inflammatory properties by regulating ER stress and autophagy pathways.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470199","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}
Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.
{"title":"Potential hypothesis for the increased risk of Parkinson´s disease following COVID-19.","authors":"Raffaella Mormile, Cristina Mormile, Carmine Picone","doi":"10.1007/s11033-024-10021-w","DOIUrl":"https://doi.org/10.1007/s11033-024-10021-w","url":null,"abstract":"<p><p>Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470200","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 : 2024-10-21DOI: 10.1007/s11033-024-10004-x
Raja Ben Ahmed, Łukasz Gajda, Piotr Świątek
Background: We hereby report the first occurrence of Helobdella octatestisaca in North Africa, specifically in Tunisia, as a likely introduced species from the Neotropical Region. Historically, leeches bearing a prominent chitinous scute on their dorsal surface were commonly diagnosed as H. stagnalis. Most probably, H. octatestisaca had previously been misidentified as H. stagnalis in Tunisia.
Methods and results: The identification was primarily based on morphological evidence, supplemented by genetic data obtained from COI DNA barcoding. The morphology of the examined specimens was consistent with the original species description, notably characterized by the presence of four pairs of testisacs. To support our findings, we conducted a phylogenetic analysis using the Maximum Likelihood method based on COI alignment constructed with the newly obtained sequence from Tunisian specimens and complete or nearly complete 'Folmer fragment' sequences of congeners sourced from the GenBank database.
Conclusions: This study highlights the first identification of H. octatestisaca in North Africa and suggests that previous records of H. stagnalis in Tunisia likely misidentified this species.
背景:我们在此报告首次在北非(特别是突尼斯)发现八角蛭(Helobdella octatestisaca),它很可能是从新热带地区引入的物种。在历史上,背上有明显壳质鳞片的水蛭通常被诊断为 H. stagnalis。在突尼斯,很可能曾将 H. octatestisaca 误认为 H. stagnalis:鉴定主要基于形态学证据,并辅以 COI DNA 条形码获得的遗传数据。受检标本的形态与原始物种描述一致,主要特征是有四对睾丸。为了支持我们的研究结果,我们使用最大似然法进行了系统发育分析,该方法基于从突尼斯标本中新获得的 COI 序列和从 GenBank 数据库中获得的同系物完整或接近完整的 "Folmer 片段 "序列:本研究首次在北非鉴定出 H. octatestisaca,并表明突尼斯以前的 H. stagnalis 记录可能误认了该物种。
{"title":"Morphological data and DNA barcoding reveal the presence of the alien freshwater leech Helobdella octatestisaca (Hirudinida: Glossiphoniformes) in North Africa (Tunisia).","authors":"Raja Ben Ahmed, Łukasz Gajda, Piotr Świątek","doi":"10.1007/s11033-024-10004-x","DOIUrl":"https://doi.org/10.1007/s11033-024-10004-x","url":null,"abstract":"<p><strong>Background: </strong>We hereby report the first occurrence of Helobdella octatestisaca in North Africa, specifically in Tunisia, as a likely introduced species from the Neotropical Region. Historically, leeches bearing a prominent chitinous scute on their dorsal surface were commonly diagnosed as H. stagnalis. Most probably, H. octatestisaca had previously been misidentified as H. stagnalis in Tunisia.</p><p><strong>Methods and results: </strong>The identification was primarily based on morphological evidence, supplemented by genetic data obtained from COI DNA barcoding. The morphology of the examined specimens was consistent with the original species description, notably characterized by the presence of four pairs of testisacs. To support our findings, we conducted a phylogenetic analysis using the Maximum Likelihood method based on COI alignment constructed with the newly obtained sequence from Tunisian specimens and complete or nearly complete 'Folmer fragment' sequences of congeners sourced from the GenBank database.</p><p><strong>Conclusions: </strong>This study highlights the first identification of H. octatestisaca in North Africa and suggests that previous records of H. stagnalis in Tunisia likely misidentified this species.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470197","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 : 2024-10-21DOI: 10.1007/s11033-024-10003-y
Undral Munkhsaikhan, Karima Ait-Aissa, Amal M Sahyoun, Ehsanul Hoque Apu, Ammaar H Abidi, Adam Kassan, Modar Kassan
Dyslipidemia is the most significant risk factor for cardiovascular diseases (CVDs) Secondary dyslipidemia: its treatments and association with atherosclerosis. Glob Health Med, Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies. The current treatment strategies for managing dyslipidemia focus on reducing low-density lipoprotein cholesterol (LDL-C) to minimize the risks of atherosclerosis and myocardial infarction (MI). Homozygous Familial Hypercholesterolemia (HoFH) is an inherited autosomal dominant disease caused by a mutation in the LDL receptor (LDLr), which can lead to extremely high levels of LDL-C The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr(-/-) Mice with Obesity, The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity. Although statin therapy has been the primary treatment for dyslipidemia, HoFH patients do not respond well to statins, requiring alternative therapies. Microsomal triglyceride transfer protein (MTP) inhibition has emerged as a potential therapeutic target for treating HoFH. MTP is primarily responsible for transferring triglyceride and other lipids into apolipoprotein B (ApoB) during the assembly of very low-density lipoprotein (VLDL) particles in the liver. Lomitapide, an inhibitor of MTP, has been approved for treatingof HoFH adults. Unlike statins, lomitapide does not act on the LDLr to reduce cholesterol. Instead, lomitapide lowers the levels of ApoB-containing proteins, primarily VLDL, eventually decreasing LDL-C levels. Studies have shown that lomitapide can reduce LDL-C levels by more than 50% in patients with HoFH who have failed to respond adequately to other treatments. Lowering LDL-C levels is important for preventing atherosclerosis, reducing cardiovascular risk, improving endothelial function, and promoting overall cardiovascular health, especially for patients with HoFH Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. This review paper focuses on research findings regarding the therapeutic benefits of lomitapide, highlighting its effectiveness in lowering cholesterol levels and reducing the risk of CVDs The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity.
血脂异常是心血管疾病(CVDs)最重要的风险因素 继发性血脂异常:其治疗方法及其与动脉粥样硬化的关系。全球健康医学》(Glob Health Med),《沙格列扎治疗血脂异常的疗效和安全性》(Saroglitazar for the management of dyslipidemia):对干预性研究的系统回顾和荟萃分析。目前控制血脂异常的治疗策略主要是降低低密度脂蛋白胆固醇(LDL-C),以尽量减少动脉粥样硬化和心肌梗死(MI)的风险。洛米他匹对 LDLr(-/-)肥胖小鼠心血管系统的有益影响,微粒体甘油三酯转移蛋白抑制剂洛米他匹可改善肥胖小鼠的血管功能。虽然他汀类药物治疗一直是血脂异常的主要治疗方法,但HoFH患者对他汀类药物反应不佳,需要替代疗法。抑制微粒体甘油三酯转移蛋白(MTP)已成为治疗HoFH的潜在治疗靶点。微粒体甘油三酯转移蛋白主要负责在肝脏组装极低密度脂蛋白(VLDL)颗粒的过程中将甘油三酯和其他脂类转移到载脂蛋白 B(ApoB)中。洛米他匹是一种 MTP 抑制剂,已被批准用于治疗 HoFH 成人。与他汀类药物不同,洛米他匹不作用于 LDLr 以降低胆固醇。相反,洛米他匹降低含载脂蛋白 B 蛋白(主要是 VLDL)的水平,最终降低 LDL-C 水平。研究表明,对于其他治疗方法无效的 HoFH 患者,洛米他匹可将低密度脂蛋白胆固醇水平降低 50%以上。降低低密度脂蛋白胆固醇水平对于预防动脉粥样硬化、降低心血管风险、改善内皮功能和促进整体心血管健康非常重要,尤其是对于HoFH患者。微粒体甘油三酯转移蛋白抑制剂洛米他匹能改善肥胖症小鼠的血管功能。
{"title":"Lomitapide: navigating cardiovascular challenges with innovative therapies.","authors":"Undral Munkhsaikhan, Karima Ait-Aissa, Amal M Sahyoun, Ehsanul Hoque Apu, Ammaar H Abidi, Adam Kassan, Modar Kassan","doi":"10.1007/s11033-024-10003-y","DOIUrl":"https://doi.org/10.1007/s11033-024-10003-y","url":null,"abstract":"<p><p>Dyslipidemia is the most significant risk factor for cardiovascular diseases (CVDs) Secondary dyslipidemia: its treatments and association with atherosclerosis. Glob Health Med, Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies. The current treatment strategies for managing dyslipidemia focus on reducing low-density lipoprotein cholesterol (LDL-C) to minimize the risks of atherosclerosis and myocardial infarction (MI). Homozygous Familial Hypercholesterolemia (HoFH) is an inherited autosomal dominant disease caused by a mutation in the LDL receptor (LDLr), which can lead to extremely high levels of LDL-C The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr(-/-) Mice with Obesity, The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity. Although statin therapy has been the primary treatment for dyslipidemia, HoFH patients do not respond well to statins, requiring alternative therapies. Microsomal triglyceride transfer protein (MTP) inhibition has emerged as a potential therapeutic target for treating HoFH. MTP is primarily responsible for transferring triglyceride and other lipids into apolipoprotein B (ApoB) during the assembly of very low-density lipoprotein (VLDL) particles in the liver. Lomitapide, an inhibitor of MTP, has been approved for treatingof HoFH adults. Unlike statins, lomitapide does not act on the LDLr to reduce cholesterol. Instead, lomitapide lowers the levels of ApoB-containing proteins, primarily VLDL, eventually decreasing LDL-C levels. Studies have shown that lomitapide can reduce LDL-C levels by more than 50% in patients with HoFH who have failed to respond adequately to other treatments. Lowering LDL-C levels is important for preventing atherosclerosis, reducing cardiovascular risk, improving endothelial function, and promoting overall cardiovascular health, especially for patients with HoFH Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. This review paper focuses on research findings regarding the therapeutic benefits of lomitapide, highlighting its effectiveness in lowering cholesterol levels and reducing the risk of CVDs The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470194","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: Doublesex and mab-3 related transcription factor (DMRT) 1, commonly found in all vertebrates, regulates the transcription of genes involved in the masculinization and maintenance of gonadal somatic cells and/or germline cell development. DMRT1 has a DNA-binding domain called the DM domain and a transcription regulatory region. Unlike the former, there is little knowledge about the latter transcription regulatory region. This study aimed to identify the transcription activation regions of DMRT1 from four species: humans and mice (mammals), leopard geckos (reptiles), and medaka (teleost fish), adding perspectives on evolutionary conservation and diversity.
Methods and results: For each species, several expression plasmids of deletion mutants were constructed, and the resultant plasmid and a DMRT1-driven luciferase reporter were co-transfected into cultured cells to measure transactivation ability. The key point of this analysis is that the transactivation ability was normalized by quantifying the expression levels of DMRT1 variants using the HiBiT tag. As a result, two to three transactivation regions were suggested to exist in the C-terminal region of the DM domain in all four species. Among seven regions in DMRT1, the fourth region from the N-terminus contributed to transactivation common to the four species, and the sixth and seventh regions on the C-terminal side differed depending on the species.
Conclusions: These findings indicated that the regions involved in the transactivation ability of DMRT1 could subtly change during evolution, indicating diversity in transactivation domains.
{"title":"Diversity of transactivation regions of DMRT1 in vertebrates.","authors":"Naoki Ishikawa, Kazuko Fujitani, Norihito Okano, Shun Hayashi, Nene Sakabe, Shiori Inazumi, Honoka Okuyama, Kota Seki, Kosuke Suda, Daisuke Tsukamoto, Takuya Matsuo, Kei Tamura, Michihiko Ito","doi":"10.1007/s11033-024-10006-9","DOIUrl":"https://doi.org/10.1007/s11033-024-10006-9","url":null,"abstract":"<p><strong>Background: </strong>Doublesex and mab-3 related transcription factor (DMRT) 1, commonly found in all vertebrates, regulates the transcription of genes involved in the masculinization and maintenance of gonadal somatic cells and/or germline cell development. DMRT1 has a DNA-binding domain called the DM domain and a transcription regulatory region. Unlike the former, there is little knowledge about the latter transcription regulatory region. This study aimed to identify the transcription activation regions of DMRT1 from four species: humans and mice (mammals), leopard geckos (reptiles), and medaka (teleost fish), adding perspectives on evolutionary conservation and diversity.</p><p><strong>Methods and results: </strong>For each species, several expression plasmids of deletion mutants were constructed, and the resultant plasmid and a DMRT1-driven luciferase reporter were co-transfected into cultured cells to measure transactivation ability. The key point of this analysis is that the transactivation ability was normalized by quantifying the expression levels of DMRT1 variants using the HiBiT tag. As a result, two to three transactivation regions were suggested to exist in the C-terminal region of the DM domain in all four species. Among seven regions in DMRT1, the fourth region from the N-terminus contributed to transactivation common to the four species, and the sixth and seventh regions on the C-terminal side differed depending on the species.</p><p><strong>Conclusions: </strong>These findings indicated that the regions involved in the transactivation ability of DMRT1 could subtly change during evolution, indicating diversity in transactivation domains.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470165","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 : 2024-10-21DOI: 10.1007/s11033-024-10017-6
Mahtab Kalani, Fatemeh Mirzaei, Haniyeh Keyghobadi, Gholamhossein Keighobadi, Atefeh Raoofat, Mehdi Kalani, Ali Moravej
Background: Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines.
Methods: Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR.
Results: The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine.
Conclusion: Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines.
{"title":"Comparing the distribution of common human papillomavirus genotypes among the population of Fars province in southwest Iran with the genotypes included in the available HPV vaccines.","authors":"Mahtab Kalani, Fatemeh Mirzaei, Haniyeh Keyghobadi, Gholamhossein Keighobadi, Atefeh Raoofat, Mehdi Kalani, Ali Moravej","doi":"10.1007/s11033-024-10017-6","DOIUrl":"https://doi.org/10.1007/s11033-024-10017-6","url":null,"abstract":"<p><strong>Background: </strong>Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines.</p><p><strong>Methods: </strong>Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR.</p><p><strong>Results: </strong>The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine.</p><p><strong>Conclusion: </strong>Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470161","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: India's oilseed economy falls short of self-sufficiency and is supplemented by huge imports every year. Increasing national productivity of the major oilseeds is confronted with yield losses due to diverse biotic and abiotic stresses. The productivity of Indian mustard (Brassica juncea Linnaeus), belonging to the family Brassicaceae, is significantly reduced due to damage caused by mustard aphids (Lipaphis erysimi Kaltenbach, Hemiptera: Aphididae). Rapid colonization by the nymphs makes it difficult to protect the crop through agrochemicals. Aphids release effector molecules to modulate the host-defence responses. Glucosinolates (GSLs) extensively found in Brassicaceae family, are hydrolysed by myrosinase into toxic compounds that deter herbivore insects.
Methods: Here, we investigated the differential activation of the glucosinolate-myrosinase pathway in mustard manifesting susceptibility and resistance to different aphid species. Mustard plants were challenged by two different aphid species mustard aphid and cowpea aphid (Aphis craccivora Koch, Hemiptera: Aphididae) leading to complete host-susceptibility in one case and resistance in the other, respectively. Differential regulation of the GSL biosynthetic pathway and myrosinase activity was assessed by gene expression study and ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC- QToF-ESL-MS).
Results: Gene expression study identified selective transcriptional attenuation of the key GSL biosynthetic and myrosinase gene in mustard when challenged with mustard aphid. In contrary, the activation of GSL biosynthetic genes in conjunction with myrosinase at the transcriptional level was profound in mustard, when challenged with cowpea aphid. UPLC-MS analysis showed higher turnover in the hydrolysis of glucosinolates by myrosinase which led to concomitant generation of glucose as byproduct in response to cowpea aphid in mustard plants.
Conclusion: GSL-myrosinase pathway is specifically attenuated by the successful aphid species in mustard and thus plays a pivotal role in determining the outcome of the B. juncea-aphid interaction. The results open up a new genetic modification strategy for developing resistance against aphids.
{"title":"Differential regulation of glucosinolate-myrosinase mediated defense determines host-aphid interaction in Indian mustard Brassica juncea L.","authors":"Ashakiran Loitongbam, Naresh Kumar Samal, Nikhil Ram Kumar, Satish Kumar, Muthuganeshan Annamalai, Aditi Kundu, Sabtharishi Subramanian, Ramcharan Bhattacharya","doi":"10.1007/s11033-024-10002-z","DOIUrl":"https://doi.org/10.1007/s11033-024-10002-z","url":null,"abstract":"<p><strong>Background: </strong>India's oilseed economy falls short of self-sufficiency and is supplemented by huge imports every year. Increasing national productivity of the major oilseeds is confronted with yield losses due to diverse biotic and abiotic stresses. The productivity of Indian mustard (Brassica juncea Linnaeus), belonging to the family Brassicaceae, is significantly reduced due to damage caused by mustard aphids (Lipaphis erysimi Kaltenbach, Hemiptera: Aphididae). Rapid colonization by the nymphs makes it difficult to protect the crop through agrochemicals. Aphids release effector molecules to modulate the host-defence responses. Glucosinolates (GSLs) extensively found in Brassicaceae family, are hydrolysed by myrosinase into toxic compounds that deter herbivore insects.</p><p><strong>Methods: </strong>Here, we investigated the differential activation of the glucosinolate-myrosinase pathway in mustard manifesting susceptibility and resistance to different aphid species. Mustard plants were challenged by two different aphid species mustard aphid and cowpea aphid (Aphis craccivora Koch, Hemiptera: Aphididae) leading to complete host-susceptibility in one case and resistance in the other, respectively. Differential regulation of the GSL biosynthetic pathway and myrosinase activity was assessed by gene expression study and ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC- QToF-ESL-MS).</p><p><strong>Results: </strong>Gene expression study identified selective transcriptional attenuation of the key GSL biosynthetic and myrosinase gene in mustard when challenged with mustard aphid. In contrary, the activation of GSL biosynthetic genes in conjunction with myrosinase at the transcriptional level was profound in mustard, when challenged with cowpea aphid. UPLC-MS analysis showed higher turnover in the hydrolysis of glucosinolates by myrosinase which led to concomitant generation of glucose as byproduct in response to cowpea aphid in mustard plants.</p><p><strong>Conclusion: </strong>GSL-myrosinase pathway is specifically attenuated by the successful aphid species in mustard and thus plays a pivotal role in determining the outcome of the B. juncea-aphid interaction. The results open up a new genetic modification strategy for developing resistance against aphids.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470164","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}