{"title":"Yin and Yang of Gut Microbiota in Cocaine Abuse.","authors":"Simone Baldi, Elisabetta Gerace, Guido Mannaioni, Amedeo Amedei","doi":"10.31083/j.fbl2906215","DOIUrl":"10.31083/j.fbl2906215","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473233","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}
Xiuling Xu, Feifei Wu, Qiang Zhang, Shasha Xu, Xunxun Ying, Xiaohong Fang, Ruolang Pan, Yang Jin
Background: Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized.
Methods: In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed.
Results: The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells.
Conclusions: Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.
背景:尽管脐带间充质干细胞(UCMSC)输注已被认为是治疗急性肺损伤(ALI)的一种有前景的策略,但UCMSC移植的参数,如输注途径和剂量,仍需进一步优化:在这项研究中,我们利用大鼠模型比较了通过静脉注射和气管内灌注移植的 UCMSCs 对脂多糖诱导的 ALI 的治疗效果。移植后,对血清中的炎症因子水平、支气管肺泡灌洗液(BALF)中的中性粒细胞、白细胞总数和淋巴细胞水平以及肺损伤水平进行了分析:结果:结果表明,通过动脉血气、肺组织病理学、支气管肺泡灌洗液(BALF)内容物和炎症因子水平的分析,通过静脉和气管内途径给药的 UCMSCs 均能有效缓解 ALI。比较发现,气管内灌注 UCMSCs 可降低 BALF 中的淋巴细胞和总蛋白水平,而静脉注射干细胞的大鼠血清中肿瘤坏死因子 α(TNF-α)和白细胞介素 1β(IL-1β)的水平降低幅度更大:我们的研究结果提供了令人信服的证据,表明 UCMSC 治疗通过不同给药途径介导的 ALI 具有疗效,从而为进一步的临床研究提供了可靠的理论依据。此外,这些研究结果还表明,使用两种评估的给药途径进行 UCMSC 移植所获得的疗效是通过不同的机制介导的,这可能归因于不同的细胞或分子靶点。
{"title":"Comparative Effects of Umbilical Cord Mesenchymal Stem Cell Treatment via Different Routes on Lipopolysaccharide-Induced Acute Lung Injury.","authors":"Xiuling Xu, Feifei Wu, Qiang Zhang, Shasha Xu, Xunxun Ying, Xiaohong Fang, Ruolang Pan, Yang Jin","doi":"10.31083/j.fbl2906217","DOIUrl":"https://doi.org/10.31083/j.fbl2906217","url":null,"abstract":"<p><strong>Background: </strong>Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized.</p><p><strong>Methods: </strong>In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed.</p><p><strong>Results: </strong>The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells.</p><p><strong>Conclusions: </strong>Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473147","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}
Moran Wang, Chaofan Wang, Jun Deng, Huafang Wang, Chunyan Sun, Shanshan Luo, Yu Hu
The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.
随着免疫疗法的出现,多发性骨髓瘤(MM)的治疗方案发生了重大转变。目前,以肿瘤抗原为重点的新型疗法推动了多发性骨髓瘤研究的进展。双特异性抗体(bsAbs)利用生物工程技术的革命性进步,体现了第二代基于抗体的肿瘤疗法。最近对复发/难治性 MM 病例进行的 bsAbs 研究显示,其疗效显著,安全性可接受。elranatamab和teclistamab的获批标志着bsAbs治疗MM的下一步发展。这篇综述文章探讨了应用 bsAbs 治疗耐药 MM 的抗原靶向、疗效、安全性和策略,重点是临床试验和真实世界的数据。
{"title":"Bispecific Antibodies for Multiple Myeloma: Recent Advancements and Strategies for Increasing Their Efficacy.","authors":"Moran Wang, Chaofan Wang, Jun Deng, Huafang Wang, Chunyan Sun, Shanshan Luo, Yu Hu","doi":"10.31083/j.fbl2906216","DOIUrl":"https://doi.org/10.31083/j.fbl2906216","url":null,"abstract":"<p><p>The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473145","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}
Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.
多囊卵巢综合征(PCOS)是一种普遍存在的生殖、内分泌和代谢疾病,影响着全球 5-18% 的女性,而且发病率还在不断上升。高雄激素血症和胰岛素抵抗是导致多囊卵巢综合征的两个关键病理生理因素,这两个因素会导致多种健康问题,如月经不调、肥胖、糖脂平衡失调、不孕、精神障碍、心脑血管疾病等。尽管相关研究仍在进行,但多囊卵巢综合征的起源和发病机制仍难以捉摸;临床上也需要为患有多囊卵巢综合征的妇女提供更简单、更有效、更持久和更全面的治疗方法。肠道-脂肪轴是新陈代谢、内分泌功能和免疫反应的重要调节途径,近年来在 2 型糖尿病和非酒精性脂肪肝等代谢性疾病的病因和治疗研究中受到了广泛关注。对多囊卵巢综合征的最新研究发现,肠道微生物群的同质性和系统发育多样性发生了显著变化。利用粪便微生物群移植进行的动物研究证实,肠道微生物群在调节多囊卵巢综合征患者的胰岛素敏感性和性激素平衡方面具有重要作用。此外,研究还表明,多囊卵巢综合症患者棕色脂肪组织(BAT)的体积和/或活性下降,这种变化会改变脂肪因子的释放,导致胰岛素抵抗和高雄激素血症,从而加重多囊卵巢综合症的发展。鉴于棕色脂肪组织在增加能量消耗和缓解代谢参数方面的功能,激活棕色脂肪组织或诱导白色脂肪组织棕色化已成为治疗多囊卵巢综合征的可能方法。最近的研究表明,肠道微生物群可通过短链脂肪酸和胆汁酸等代谢物以及肠脑轴影响 BAT 的生成和活性。基础和临床研究均表明,寒冷暴露、健康节食、二甲双胍、减肥手术、胰高血糖素样肽 1 受体激动剂和褪黑素可通过影响肠道微生物群来调节 BAT 的活性,显示出巨大的临床潜力。然而,要为多囊卵巢综合症开发出更有效、更舒适、更安全的定制疗法,还需要对肠道-BAT 轴的调节机制进行更多的研究。
{"title":"Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers.","authors":"Yanhui Li, Yuqing Fang, Hongbo Wang, Hangke Zhang","doi":"10.31083/j.fbl2906208","DOIUrl":"https://doi.org/10.31083/j.fbl2906208","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473144","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}
Guangshuai Li, Ji Feng, Shengbin Huang, Qingchang Li
Background: Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
Methods: The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
Results: PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
Conclusion: PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
{"title":"LncRNA-PVT1 Inhibits Ferroptosis through Activating STAT3/GPX4 Axis to Promote Osteosarcoma Progression.","authors":"Guangshuai Li, Ji Feng, Shengbin Huang, Qingchang Li","doi":"10.31083/j.fbl2906207","DOIUrl":"10.31083/j.fbl2906207","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.</p><p><strong>Methods: </strong>The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).</p><p><strong>Results: </strong>PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.</p><p><strong>Conclusion: </strong>PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473170","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}
Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.
表观遗传学指的是基因表达和功能的遗传变化,这些变化会影响与染色质相关的核过程,但不会改变 DNA 序列。这些表观遗传模式作为遗传性状,是错综复杂地调节基因表达和遗传的重要生物机制。近年来,化学标记和单细胞分辨率绘图策略的应用极大地促进了核酸的大规模表观遗传修饰。值得注意的是,表观遗传修饰可诱导遗传表型变化、调控细胞分化、影响细胞特异性基因表达、亲代印记基因、激活 X 染色体以及稳定基因组结构。鉴于表观遗传修饰的可逆性和易受环境因素影响的特点,表观遗传修饰在疾病诊断中的地位日益突出,对临床医学研究产生了重大影响。最近的研究发现,表观遗传修饰与代谢性心血管疾病(包括先天性心脏病、心力衰竭、心肌病、高血压和动脉粥样硬化)的发病机制密切相关。在这篇综述中,我们概述了在心血管疾病方面的表观遗传学研究进展,包括其发病机制、预防、诊断和治疗。此外,我们还阐述了核酸表观遗传修饰在临床医学和生物医学应用中的潜在前景。
{"title":"Mechanisms and Advances of Epigenetic Regulation in Cardiovascular Disease.","authors":"Xiaojun Wang, Xusheng Teng, Chao Luo, Laifa Kong","doi":"10.31083/j.fbl2906205","DOIUrl":"https://doi.org/10.31083/j.fbl2906205","url":null,"abstract":"<p><p>Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473212","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}
Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to "see" light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called "photoneuroendocrinology", which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light's beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin's photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin's unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.
{"title":"Molecular Pathways Regulating Circadian Rhythm and Associated Diseases.","authors":"Min Ding, Hang Zhou, Yu-Mei Li, Yun-Wen Zheng","doi":"10.31083/j.fbl2906206","DOIUrl":"https://doi.org/10.31083/j.fbl2906206","url":null,"abstract":"<p><p>Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to \"see\" light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called \"photoneuroendocrinology\", which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light's beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin's photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin's unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473214","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}
Mudagadde G Deeksha, Suresh M Nebapure, Doddachowdappa Sagar, Ramcharan Bhattacharya, Anil Dahuja, Sabtharishi Subramanian
Background: Phosphine resistance in Tribolium castaneum challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in Indian Tribolium castaneum populations.
Methods: Seven field populations of T. castaneum were compared with Lab- susceptible population for their resistance to phosphine. The levels of cytochrome P450 enzyme and expression of certain CYP346 family genes were tracked in these populations.
Results: The highly resistant Patiala population showed significantly increased CYP450 activity (11.26 ± 0.14 nmol/min/mg protein, 7.41-fold higher) compared to the lab-susceptible population (1.52 ± 0.09 nmol/min/mg protein) when assayed using 8 mM p-nitroanisole as the substrate. The mRNA expression was measured relative to the standard gene RPS18 and revealed significant upregulation of CYP346B1 and CYP346B3 in highly resistant populations Moga and Patiala (CYP346B1: 12.09 ± 2.19 to 21.74 ± 3.82; CYP346B3: 59.097 ± 10.265 to 50.148 ± 8.272). Patiala's CYP346B1 exhibited an impressive 685.76-fold change, and Moga's CYP346B3 showed a 361.893-fold change compared to lab-susceptible. Linear regression confirmed robust fits for each gene (R2: 0.693 to 0.756). Principal component analysis (PCA) demonstrated a strong positive correlation between CYP346 genes expression; and cytochrome P450 activity. Patiala, Moga, and Hapur populations showed conformity, associating higher resistance with increased P450 activity and CYP346 gene expression. Cluster analysis highlighted a potential correlation between CYP346B1, CYP346B2, and CYP346B3 and P450 activity, with Patiala and Moga clustering together.
Conclusions: Variability in CYP346B1 and CYP346B3 in strong resistance populations may contribute to adaptation and resistance mechanisms. The study provides insights into specific CYP346 family genes associated with phosphine resistance, emphasizing the intricate interaction between CYP450 detoxifying enzymes, CYP346 family genes, and resistance mechanisms. The upregulation of CYP346 genes suggests a survival advantage for T. castaneum against phosphine, diminishing phosphine's efficacy as a pest control measure.
{"title":"Revealing the Role of CYP346 Family Genes on Phosphine Resistance in Indian Populations of <i>Tribolium castaneum</i>.","authors":"Mudagadde G Deeksha, Suresh M Nebapure, Doddachowdappa Sagar, Ramcharan Bhattacharya, Anil Dahuja, Sabtharishi Subramanian","doi":"10.31083/j.fbl2906203","DOIUrl":"10.31083/j.fbl2906203","url":null,"abstract":"<p><strong>Background: </strong>Phosphine resistance in <i>Tribolium castaneum</i> challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in Indian Tribolium castaneum populations.</p><p><strong>Methods: </strong>Seven field populations of <i>T. castaneum</i> were compared with Lab- susceptible population for their resistance to phosphine. The levels of cytochrome P450 enzyme and expression of certain CYP346 family genes were tracked in these populations.</p><p><strong>Results: </strong>The highly resistant Patiala population showed significantly increased CYP450 activity (11.26 ± 0.14 nmol/min/mg protein, 7.41-fold higher) compared to the lab-susceptible population (1.52 ± 0.09 nmol/min/mg protein) when assayed using 8 mM p-nitroanisole as the substrate. The mRNA expression was measured relative to the standard gene <i>RPS18</i> and revealed significant upregulation of <i>CYP346B1</i> and <i>CYP346B3</i> in highly resistant populations Moga and Patiala (<i>CYP346B1</i>: 12.09 ± 2.19 to 21.74 ± 3.82; <i>CYP346B3</i>: 59.097 ± 10.265 to 50.148 ± 8.272). Patiala's <i>CYP346B1</i> exhibited an impressive 685.76-fold change, and Moga's <i>CYP346B3</i> showed a 361.893-fold change compared to lab-susceptible. Linear regression confirmed robust fits for each gene (R2: 0.693 to 0.756). Principal component analysis (PCA) demonstrated a strong positive correlation between <i>CYP346</i> genes expression; and cytochrome P450 activity. Patiala, Moga, and Hapur populations showed conformity, associating higher resistance with increased P450 activity and CYP346 gene expression. Cluster analysis highlighted a potential correlation between <i>CYP346B1</i>, <i>CYP346B2</i>, and <i>CYP346B3</i> and P450 activity, with Patiala and Moga clustering together.</p><p><strong>Conclusions: </strong>Variability in <i>CYP346B1</i> and <i>CYP346B3</i> in strong resistance populations may contribute to adaptation and resistance mechanisms. The study provides insights into specific CYP346 family genes associated with phosphine resistance, emphasizing the intricate interaction between CYP450 detoxifying enzymes, CYP346 family genes, and resistance mechanisms. The upregulation of <i>CYP346</i> genes suggests a survival advantage for <i>T. castaneum</i> against phosphine, diminishing phosphine's efficacy as a pest control measure.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473227","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: Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of DEPDC1B has been reported to occur in various tumor types. However, the functional implications of this alteration in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we investigated the role and clinical significance of DEPDC1B in LUAD.
Methods: The expression of DEPDC1B in LUAD and its relationship with prognosis were systematically evaluated in several publically available datasets. The effects of DEPDC1B knockdown on the proliferation and motility of LUAD cells were assessed using the JULI Stage Real-time Cell History Recorder, while the effect of knockdown on the cell cycle was studied by flow cytometry. Furthermore, RNA-Sequencing (RNA-Seq) analysis was conducted to identify the downstream target genes and pathways regulated by DEPDC1B. Correlations between the expression of DEPDC1B and immune cell infiltration, immunotherapy resistance, and chemoresistance were also examined. Additionally, molecular biological methods were used to explore the regulatory mechanism of B-Myb on DEPDC1B expression.
Results: DEPDC1B was found to be upregulated in LUAD patients and this was associated with poor clinical outcomes. Knockdown of DEPDC1B inhibited cell growth, migration and motility, as well as cell cycle progression. Knockdown also resulted in the down-regulation of several downstream genes, including NID1, FN1, and EGFR, as well as the inactivation of multiple critical pathways, such as the ERK and PI3K-AKT pathways. Analysis of the tumor immuno-environment in LUAD revealed that high DEPDC1B expression was associated with an abundance of activated CD4+ memory T cells, M0 macrophages, M1 macrophages, and CD8+ T cells. Moreover, these tumors responded poorly to immunotherapy. Analysis of chemo-drug sensitivity showed that LUADs with high DEPDC1B expression were more responsive to frontline chemotherapeutic drugs such as Vinorelbine, Cisplatin, and Etoposide. Additionally, mechanistic investigations revealed that DEPDC1B is a direct target gene of B-Myb, and that its knockdown attenuated the proliferation and motility effects of B-Myb.
Conclusions: In summary, our findings indicate that DEPDC1B is a critical regulator during the malignant progression of LUAD. DEPDC1B could therefore be a promising prognostic marker and therapeutic target in LUAD diagnosis and treatment.
{"title":"DEPDC1B is a Novel Direct Target of B-Myb and Contributes to Malignant Progression and Immune Infiltration in Lung Adenocarcinoma.","authors":"Xiaofeng Zuo, Dongyu Wang, Chuntao Tao, Xuanqi Dou, Zongrong Zhao, Jinlu Zhang, Shiyi Huang, Yue Li, Xia Zhang, Youquan Bu, Yitao Wang","doi":"10.31083/j.fbl2906204","DOIUrl":"10.31083/j.fbl2906204","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of DEPDC1B has been reported to occur in various tumor types. However, the functional implications of this alteration in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we investigated the role and clinical significance of DEPDC1B in LUAD.</p><p><strong>Methods: </strong>The expression of DEPDC1B in LUAD and its relationship with prognosis were systematically evaluated in several publically available datasets. The effects of DEPDC1B knockdown on the proliferation and motility of LUAD cells were assessed using the JULI Stage Real-time Cell History Recorder, while the effect of knockdown on the cell cycle was studied by flow cytometry. Furthermore, RNA-Sequencing (RNA-Seq) analysis was conducted to identify the downstream target genes and pathways regulated by DEPDC1B. Correlations between the expression of DEPDC1B and immune cell infiltration, immunotherapy resistance, and chemoresistance were also examined. Additionally, molecular biological methods were used to explore the regulatory mechanism of B-Myb on DEPDC1B expression.</p><p><strong>Results: </strong>DEPDC1B was found to be upregulated in LUAD patients and this was associated with poor clinical outcomes. Knockdown of <i>DEPDC1B</i> inhibited cell growth, migration and motility, as well as cell cycle progression. Knockdown also resulted in the down-regulation of several downstream genes, including <i>NID1</i>, <i>FN1</i>, and <i>EGFR</i>, as well as the inactivation of multiple critical pathways, such as the ERK and PI3K-AKT pathways. Analysis of the tumor immuno-environment in LUAD revealed that high DEPDC1B expression was associated with an abundance of activated CD4+ memory T cells, M0 macrophages, M1 macrophages, and CD8+ T cells. Moreover, these tumors responded poorly to immunotherapy. Analysis of chemo-drug sensitivity showed that LUADs with high DEPDC1B expression were more responsive to frontline chemotherapeutic drugs such as Vinorelbine, Cisplatin, and Etoposide. Additionally, mechanistic investigations revealed that DEPDC1B is a direct target gene of B-Myb, and that its knockdown attenuated the proliferation and motility effects of B-Myb.</p><p><strong>Conclusions: </strong>In summary, our findings indicate that DEPDC1B is a critical regulator during the malignant progression of LUAD. DEPDC1B could therefore be a promising prognostic marker and therapeutic target in LUAD diagnosis and treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473150","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: The antibiotic resistance of microorganisms is escalating rapidly. Infections caused by opportunistic pathogens in immunocompromised individuals have prompted researchers to seek for potent and safe antibacterial agents. The purpose of this investigation was to explore the suppression of virulence gene expression, specifically the pga operon genes responsible in biofilm formation in Acinetobacter baumannii, through the utilization of metabolites obtained from probiotic bacteria.
Methods: To assess the antimicrobial properties, standard strains of five probiotic bacteria were tested against a standard strain of multidrug-resistant (MDR) A. baumannii employing the agar gel diffusion technique. Following the identification of the most potent probiotic strain (Bacillus licheniformis), the existence of its LanA and LanM genes was confirmed using the polymerase chain reaction (PCR) test. High-performance liquid chromatography (HPLC) and fourier-transform infrared spectroscopy (FTIR) techniques were employed to identify the intended metabolite, which was found to be a lipopeptide nature. The minimum inhibitory concentration (MIC) values and anti-biofilm activity of the targeted metabolite were determined using a dilution method in 96-well microplates and field emission scanning electron microscopy (FE-SEM). Real-time PCR (qPCR) was utilized for comparing the expression of pga operon genes, including pgaABCD, in A. baumannii pre- and post-exposure to the derived lipopeptide.
Results: The MIC results indicated that the probiotic product inhibited the growth of A. baumannii at concentrations lower than those needed for conventional antibiotics. Furthermore, it was observed that the desired genes' expression decreased due to the effect of this substance.
Conclusions: This research concludes that the B. licheniformis probiotic product could be a viable alternative for combating drug resistance in A. baumannii.
{"title":"Enhancing the Antibacterial Impact of Lipopeptide Extracted from <i>Bacillus licheniformis</i> as a Probiotic against MDR <i>Acinetobacter baumannii</i>.","authors":"Mahdi Hosseini Bafghi, Farangis Ghanipour, Razieh Nazari, Seyed Soheil Aghaei, Parvaneh Jafari","doi":"10.31083/j.fbl2905171","DOIUrl":"https://doi.org/10.31083/j.fbl2905171","url":null,"abstract":"<p><strong>Background: </strong>The antibiotic resistance of microorganisms is escalating rapidly. Infections caused by opportunistic pathogens in immunocompromised individuals have prompted researchers to seek for potent and safe antibacterial agents. The purpose of this investigation was to explore the suppression of virulence gene expression, specifically the <i>pga</i> operon genes responsible in biofilm formation in <i>Acinetobacter baumannii</i>, through the utilization of metabolites obtained from probiotic bacteria.</p><p><strong>Methods: </strong>To assess the antimicrobial properties, standard strains of five probiotic bacteria were tested against a standard strain of multidrug-resistant (MDR) <i>A. baumannii</i> employing the agar gel diffusion technique. Following the identification of the most potent probiotic strain (<i>Bacillus licheniformis</i>), the existence of its <i>LanA</i> and <i>LanM</i> genes was confirmed using the polymerase chain reaction (PCR) test. High-performance liquid chromatography (HPLC) and fourier-transform infrared spectroscopy (FTIR) techniques were employed to identify the intended metabolite, which was found to be a lipopeptide nature. The minimum inhibitory concentration (MIC) values and anti-biofilm activity of the targeted metabolite were determined using a dilution method in 96-well microplates and field emission scanning electron microscopy (FE-SEM). Real-time PCR (qPCR) was utilized for comparing the expression of <i>pga</i> operon genes, including <i>pgaABCD</i>, in <i>A. baumannii</i> pre- and post-exposure to the derived lipopeptide.</p><p><strong>Results: </strong>The MIC results indicated that the probiotic product inhibited the growth of <i>A. baumannii</i> at concentrations lower than those needed for conventional antibiotics. Furthermore, it was observed that the desired genes' expression decreased due to the effect of this substance.</p><p><strong>Conclusions: </strong>This research concludes that the <i>B. licheniformis</i> probiotic product could be a viable alternative for combating drug resistance in <i>A. baumannii</i>.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176336","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}