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Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

《化学科学与工程前沿(英文)》 2022年 第16卷 第1期   页码 4-33 doi: 10.1007/s11705-021-2041-2

摘要: The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases, such as cancer and neurodegenerative and cardiovascular diseases. Therefore, the simultaneous, accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases. Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and due to its excellent performances, including high sensitivity and selectivity, noninvasive properties, real-time and high spatial temporal resolution. Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems. Hence, in this review, we focus on summarizing the design strategies, classifications, and bioimaging applications of dual-response fluorescent probes over the past decade. Furthermore, future research directions in this field are proposed.

关键词: bioactive molecules     fluorescent probes     in living cells and in vivo     review    

Chemical transdifferentiation: closer to regenerative medicine

null

《医学前沿(英文)》 2016年 第10卷 第2期   页码 152-165 doi: 10.1007/s11684-016-0445-z

摘要:

Cell transdifferentiation, which directly switches one type of differentiated cells into another cell type, is more advantageous than cell reprogramming to generate pluripotent cells and differentiate them into functional cells. This process is crucial in regenerative medicine. However, the cell-converting strategies, which mainly depend on the virus-mediated expression of exogenous genes, have clinical safety concerns. Small molecules with compelling advantages are a potential alternative in manipulating cell fate conversion. In this review, we briefly retrospect the nature of cell transdifferentiation and summarize the current developments in the research of small molecules in promoting cell conversion. Particularly, we focus on the complete chemical compound-induced cell transdifferentiation, which is closer to the clinical translation in cell therapy. Despite these achievements, the mechanisms underpinning chemical transdifferentiation remain largely unknown. More importantly, identifying drugs that induce resident cell conversion in vivo to repair damaged tissue remains to be the end-goal in current regenerative medicine.

关键词: cell therapy     cell transdifferentiation     chemical compounds     small molecules     tissue regeneration    

Emerging immunological strategies: recent advances and future directions

《医学前沿(英文)》 2021年 第15卷 第6期   页码 805-828 doi: 10.1007/s11684-021-0886-x

摘要: Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

关键词: cancer immunotherapy     bispecific antibodies     small molecules     chimeric antigen receptor T therapy     cancer vaccines    

NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

《医学前沿(英文)》 2009年 第3卷 第1期   页码 1-7 doi: 10.1007/s11684-009-0018-5

摘要: Reactive oxygen species (ROS) are small molecule metabolites of oxygen that are prone to participate in redox reactions their high reactivity. Intracellular ROS could be generated in reduced nicotinamide-adenine dinucleotidephosphate (NADPH) oxidase-dependent and/or NADPH oxidase-independent manners. Physiologically, ROS are involved in many signaling cascades that contribute to normal processes. One classical example is that ROS derived from the NADPH oxidase and released in neurotrophils are able to digest invading bacteria. Excessive ROS, however, contribute to pathogenesis of various human diseases including cancer, aging, dimentia and hypertension. As signaling messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumor growth, invasion or metastasis. The present review summarizes recent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor growth, invasion and metastasis, and focuses on the role of the NADPH oxidase-derived ROS in cancer pathogenesis.

关键词: free radicals     tumor     phox     cell proliferation     cancer therapy    

Polymorphism of pharmaceutical molecules: perspectives on nucleation

Jie LU, Zhen LI, Xiaolin JIANG,

《化学科学与工程前沿(英文)》 2010年 第4卷 第1期   页码 37-44 doi: 10.1007/s11705-009-0294-2

摘要: Polymorphism is a widespread phenomenon observed in more than half of all drug substances. Various polymorphs frequently possess different physical, chemical, mechanical and thermal properties that can profoundly affect the bioavailability, stability and other performance characteristics of the drug. Accordingly, the elucidation of the relationship between the particular polymorph of a pharmaceutical molecule and its functional properties is crucial to select the most suitable polymorph of the pharmaceutical molecule for development into a drug product. This review briefly introduces recent advances in the discovery and control of the polymorphs of pharmaceutical molecules, in terms of the enhancement of the selective nucleation of a particular polymorph. In the light of this, some cases discussed in the following is to be considered controversial.

关键词: development     Polymorphism     elucidation     controversial     relationship    

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 108-111 doi: 10.1007/s11684-014-0344-0

摘要:

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54-year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour (GIST) of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient’s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

关键词: gastrointestinal stromal tumour     hemoperitoneum     small bowel GIST     small bowel neoplasm     imatinib    

Simulation and experimental improvement on a small-scale Stirling thermo-acoustic engine

Mao CHEN,Yonglin JU

《能源前沿(英文)》 2016年 第10卷 第1期   页码 37-45 doi: 10.1007/s11708-015-0390-6

摘要: Compared with the traditional engines, the thermo-acoustic engines are relatively new and can act as the linear compressors for refrigerators. Many institutes have shown great interest in this kind of machine for its absence of moving mechanical part. In this paper, the influence of the dimensions of the main parts of the small-scale Stirling thermo-acoustic engine was numerically simulated using a computer code called DeltaEC. The resonator and the resonator cavity were found to be the most convenient and effective in improving the performance of the engine. Based on the numerical simulation, a small-scale Stirling thermo-acoustic engine were constructed and experimentally investigated. Currently, with a resonator length of only 1 m, the working frequency of the engine was decreased to 90 Hz and the onset temperature difference was decreased to 198.2 K.

关键词: thermo-acoustic Stirling engine     small-scale     simulation     experiment    

Discovery of small molecule degraders for modulating cell cycle

《医学前沿(英文)》 2023年 第17卷 第5期   页码 823-854 doi: 10.1007/s11684-023-1027-5

摘要: The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

关键词: PROTAC     molecular glue     degrader     cell cycle     CDK     cyclin    

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

《医学前沿(英文)》 2013年 第7卷 第2期   页码 157-171 doi: 10.1007/s11684-013-0272-4

摘要:

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

关键词: non-small-cell lung cancer     molecular typing     individualized medicine     molecular-targeted therapy     gene expression profiling    

Gut microbiota and its implications in small bowel transplantation

null

《医学前沿(英文)》 2018年 第12卷 第3期   页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要:

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词: gut microbiota     small bowel transplantation     acute rejection     chronic rejection     mucosal immunity     biomarker     microbiota-targeted therapy    

Fine-tuning cell organelle dynamics during mitosis by small GTPases

《医学前沿(英文)》 2022年 第16卷 第3期   页码 339-357 doi: 10.1007/s11684-022-0926-1

摘要: During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer’s disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

关键词: small GTPase     cell organelle     mitosis    

Performance prediction of switched reluctance generator with time average and small signal models

Jyoti KOUJALAGI, B. UMAMAHESWARI, R. ARUMUGAM

《能源前沿(英文)》 2013年 第7卷 第1期   页码 56-68 doi: 10.1007/s11708-012-0216-8

摘要: This paper presents the complete mathematical model and predicts the performance of switched reluctance generator with time average and small signal models. The complete mathematical model is developed in three stages. First, a switching model is developed based on quasi-linear inductance profile. Next, based on the switching behaviour, a time average model is obtained to measure the difference between the excitation and generation time in each switching cycle. Finally, to track control voltage and current wave shapes, a small signal model is designed. The effectiveness of the complete multilevel model combining electrical machine, power converter, load and control with programming language is demonstrated through simulations. A PI controller is used for controlling the voltage of the generator. The results presented show that the controller exhibits accurate tracking control of load voltage under different operating conditions. This demonstrates that the proposed model is able to perform an accurate control of the generated output voltage even in transient situations. The simulation is performed to choose the control parameters and study the performance of switched reluctance generator prior to its actual implementation. Initial experimental results are presented using NI-Data acquisition card to control the output power according to load requirements.

关键词: generator     reluctance     switching model     small signal model     time average model    

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿(英文)》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要: With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词: non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell

《医学前沿(英文)》 2022年 第16卷 第4期   页码 610-617 doi: 10.1007/s11684-021-0827-8

摘要: Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B+PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B+PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P <0.001). The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group (27.3% vs. 10.8%, respectively; P=0.204). Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

关键词: bevacizumab     elderly patient     advanced non-small-cell lung cancer     overall survival     toxicity    

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

《医学前沿(英文)》 2022年 第16卷 第2期   页码 176-184 doi: 10.1007/s11684-021-0885-y

摘要: Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

关键词: small noncoding RNAs     epigenetic inheritance     paternal intergenerational inherence     extracellular vesicles    

标题 作者 时间 类型 操作

Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

期刊论文

Chemical transdifferentiation: closer to regenerative medicine

null

期刊论文

Emerging immunological strategies: recent advances and future directions

期刊论文

NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

期刊论文

Polymorphism of pharmaceutical molecules: perspectives on nucleation

Jie LU, Zhen LI, Xiaolin JIANG,

期刊论文

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

期刊论文

Simulation and experimental improvement on a small-scale Stirling thermo-acoustic engine

Mao CHEN,Yonglin JU

期刊论文

Discovery of small molecule degraders for modulating cell cycle

期刊论文

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

期刊论文

Gut microbiota and its implications in small bowel transplantation

null

期刊论文

Fine-tuning cell organelle dynamics during mitosis by small GTPases

期刊论文

Performance prediction of switched reluctance generator with time average and small signal models

Jyoti KOUJALAGI, B. UMAMAHESWARI, R. ARUMUGAM

期刊论文

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell

期刊论文

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

期刊论文