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Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 404-418 doi: 10.1007/s11684-014-0379-2

摘要：

microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-cell communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.

关键词： microRNA     cardiovascular disease     biomarkers     therapeutic target    

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Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

null

《医学前沿（英文）》 2012年 第6卷 第1期   页码 35-40 doi: 10.1007/s11684-012-0171-0

摘要：

Inflammation is important in the pathogenesis and development of cardiovascular diseases. Recent studies show that vagus nerve stimulation inhibits pro-inflammatory cytokine production through “the cholinergic anti-inflammatory pathway,” more specifically via the α7 nicotinic acetylcholine receptor (α7nAChR). In the current study, the role of the cholinergic anti-inflammatory pathway during septic shock, hypertension, and myocardial infarction is reviewed, and its possible clinical implications in cardiovascular diseases are discussed.

关键词： α7 nicotinic acetylcholine receptor     cardiovascular diseases     baroreflex sensitivity    

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Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

《化学科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 275-286 doi: 10.1007/s11705-011-1203-z

摘要： Polymer-based conjugates are an interesting option and challenge for the design of nano-sized drug-delivery systems, as they require advanced conjugation chemistry and precise engineering. In the case of nucleic acid therapy, non-viral carriers face several biological barriers during the delivery process, namely 1) protection of the cargo from extracellular degradation, 2) avoidance of non-specific interactions with non-targeted tissues, 3) efficient entry into the target cells, 4) intracellular trafficking to the site of action and 5) cargo release. To take on these obstacles, multifunctional conjugates can act as “smart polymers” with microenvironment-sensing dynamics to facilitate the separate delivery steps. Synthesis of defined polymer architectures with precise functionalization enables structure-activity relationships to be investigated and the integration of key functions for efficient delivery. Thus bioresponsive polymer conjugates, which are equipped with molecular devices responding to the certain microenvironments within the delivery pathway (e.g. pH, redox potential, enzymes) can be assembled. This review focuses on the modular engineering and conjugation of multifunctional polymeric structures for the utilization as “tailor-made” nucleic acid carriers.

关键词： conjugate     DNA     gene transfer     polymer     RNA     targeting    

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Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutictarget

《医学前沿（英文）》 2022年 第16卷 第5期   页码 723-735 doi: 10.1007/s11684-021-0905-y

摘要： Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca2+-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.

关键词： amyotrophic lateral sclerosis     coronin-1a     autophagy     pathogenesis    

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Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 24-32 doi: 10.1007/s11684-014-0312-8

摘要：

In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivoinvestigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

关键词： osteopontin (OPN)     hepatocellular carcinoma     metastasis     prognosis     therapeutic target     biomarker     genetic polymorphism    

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Barriers to advancing nanotechnology to better improve and translate nanomedicines

Yuwei WANG,David W. Grainger

《化学科学与工程前沿（英文）》 2014年 第8卷 第3期   页码 265-275 doi: 10.1007/s11705-014-1442-x

摘要： Engineered nanomaterials and nanotechnologies promise many benefits to enhance both and performance. This is now manifest in the increasing number of reported biomedical products under development and testing that contain nanotechnologies as their distinguishing performance—enhancing components. In many cases, nano-sized materials are selected to provide a specific functional aspect that contributes to improved medical performance, either or . Nanoparticles are most commonly exploited in diverse roles in topical lotions and creams, solubilization aids, for and diagnostic and targeting agents in nanomedicines and theranostics. Despite fundamental scientific excitement and many claims to nanotechnology-based improvements in new biomedical applications, several fundamental and long-standing challenges remain to be addressed using nanomedicines to make clinically important progress. This review addresses several issues that must be fairly and objectively reported and then overcome to provide truly credible performance for nanomedicines.

关键词： nanotechnology     nanomedicine     drug delivery     therapeutic     target delivery    

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pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker and implicates potential therapeutic

《医学前沿（英文）》 2022年 第16卷 第3期   页码 378-388 doi: 10.1007/s11684-021-0840-y

摘要： Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.

关键词： severe Mycoplasma pneumoniae pneumonia     children     proteomics     Fc fragment of the IgG-binding protein     mechanistic target of rapamycin kinase inhibitor    

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Brown and beige fat: the metabolic function, induction, and therapeutic potential

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 162-172 doi: 10.1007/s11684-015-0382-2

摘要：

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.

关键词： brown adipocyte     beige adipocyte     metabolism     obesity    

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Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Wen-Qiang CHEN MD, Yun ZHANG MD, PhD, FACC,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 36-42 doi: 10.1007/s11684-010-0020-y

摘要： Vulnerable atherosclerotic plaque rupture leading to thrombosis is the major cause of acute coronary syndrome (ACS). Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable plaque. In our laboratory, we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture. Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity, proliferation-apoptosis, oxidative stress and biomechanics aspects. Imaging markers and biomarkers were used to detect vulnerable plaques, including high frequency duplex ultrasound, intravascular ultrasound (IVUS), intravascular ultrasound elastography, magnetic resonance imaging (MRI) and inflammatory markers. Effective gene and drug strategies to treat vulnerable plaques were explored.

关键词： vulnerable plaque     animal models     mechani-sm     detection     treatment    

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Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

《医学前沿（英文）》 2020年 第14卷 第2期   页码 117-125 doi: 10.1007/s11684-020-0773-x

摘要： Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

关键词： COVID-19     SARS-CoV-2     pathogenesis     evidence-based medicine     control and therapeutic strategies    

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Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 134-138 doi: 10.1007/s11684-015-0396-9

摘要：

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

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Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 46-56 doi: 10.1007/s11684-015-0375-1

摘要：

Sickle cell disease (SCD) is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso-occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 (Nrf2) controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.

关键词： oxidative stress     Nrf2     triterpenoids     sickle cell disease     vaso-occlusion     CDDO-Me    

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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Base editors: development and applications in biomedicine

《医学前沿（英文）》 2023年 第17卷 第3期   页码 359-387 doi: 10.1007/s11684-023-1013-y

摘要： Base editor (BE) is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase, enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break (DSB) or requiring donor DNA templates in living cells. Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems, such as CRISPR/Cas9, as the DSB induced by Cas9 will cause severe damage to the genome. Thus, base editors have important applications in the field of biomedicine, including gene function investigation, directed protein evolution, genetic lineage tracing, disease modeling, and gene therapy. Since the development of the two main base editors, cytosine base editors (CBEs) and adenine base editors (ABEs), scientists have developed more than 100 optimized base editors with improved editing efficiency, precision, specificity, targeting scope, and capacity to be delivered in vivo, greatly enhancing their application potential in biomedicine. Here, we review the recent development of base editors, summarize their applications in the biomedical field, and discuss future perspectives and challenges for therapeutic applications.

关键词： base editing     CBE     ABE     ADAR     DdCBE     disease model     therapeutic application    

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Multi-target combinatory strategy to overcome tumor immune escape

《医学前沿（英文）》 2022年 第16卷 第2期   页码 208-215 doi: 10.1007/s11684-022-0922-5

摘要： Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.

关键词： immune checkpoints     multi-target     immune escape     immune-related adverse events     combination therapy    

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标题 作者 时间 类型 操作

Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets

null

期刊论文

Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

null

期刊论文

Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

期刊论文

Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutictarget

期刊论文

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

期刊论文

Barriers to advancing nanotechnology to better improve and translate nanomedicines

Yuwei WANG,David W. Grainger

期刊论文

pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker and implicates potential therapeutic

期刊论文

Brown and beige fat: the metabolic function, induction, and therapeutic potential

null

期刊论文

Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Wen-Qiang CHEN MD, Yun ZHANG MD, PhD, FACC,

期刊论文

Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

期刊论文

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

期刊论文

Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

期刊论文

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

期刊论文

Base editors: development and applications in biomedicine

期刊论文

Multi-target combinatory strategy to overcome tumor immune escape

期刊论文