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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    

Progress of three-dimensional macroporous bioactive glass for bone regeneration

Lijun JI, Yunfeng SI, Ailing LI, Wenjun WANG, Dong QIU, Aiping ZHU

《化学科学与工程前沿(英文)》 2012年 第6卷 第4期   页码 470-483 doi: 10.1007/s11705-012-1217-1

摘要: Bioactive glasses (BGs) are ideal materials for macroporous scaffolds due to their excellent osteoconductive, osteoinductive, biocompatible and biodegradable properties, and their high bone bonding rates. Macroporous scaffolds made from BGs are in high demand for bone regeneration because they can stimulate vascularized bone ingrowth and they enhance bonding between scaffolds and surrounding tissues. Engineering BG/biopolymers (BP) composites or hybrids may be a good way to prepare macroporous scaffolds with excellent properties. This paper summarizes the progress in the past few years in preparing three-dimensional macroporous BG and BG/BP scaffolds for bone regeneration. Since the brittleness of BGs is a major problem in developing macroporous scaffolds and this limits their use in load bearing applications, the mechanical properties of macroporous scaffolds are particularly emphasized in this review.

关键词: bioactive glass     biopolymer     bone regeneration     macroporous scaffolds     tissue engineering    

Development and clinical trial of a novel bioactive bone cement

LEONG John, LI Zhaoyang, LU William

《医学前沿(英文)》 2008年 第2卷 第2期   页码 117-126 doi: 10.1007/s11684-008-0022-1

摘要: Strontium (Sr) and related compounds have become more attractive in the prevention and treatment of osteoporosis. Previously, we developed a novel bioactive bone cement which is mainly composed of strontium-containing hydroxyapatite (Sr-HA) filler and bisphenol A diglycidylether dimethacrylate (Bis-GMA) resin. This bone cement is superior to conventional polymethylmethacrylate (PMMA) bone cement in bioactivity, biocompatibility, and osseointegration. It also has shown sufficient mechanical strength properties for its use in percutaneous vertebroplasty (PVP) and total hip replacement (THR). In this paper, we review the and clinical evidence for the effectiveness of this bioactive bone cement.

关键词: bioactivity     effectiveness     strontium-containing hydroxyapatite     osseointegration     sufficient mechanical    

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    

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    

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿(英文)》 2021年 第15卷 第2期   页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要: The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词: bioactive hyaluronan     lipopolysaccharide     inflammatory cytokines     TLR4     human macrophages    

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    

AGRONOMIC AND ENVIRONMENTAL BENEFITS OF REINTRODUCING HERB- AND LEGUME-RICH MULTISPECIES LEYS INTO ARABLE ROTATIONS: A REVIEW

《农业科学与工程前沿(英文)》 2022年 第9卷 第2期   页码 245-271 doi: 10.15302/J-FASE-2021439

摘要:

Agricultural intensification and the subsequent decline of mixed farming systems has led to an increase in continuous cropping with only a few fallow or break years, undermining global soil health. Arable-ley rotations incorporating temporary pastures (leys) lasting 1–4 years may alleviate soil degradation by building soil fertility and improving soil structure. However, the majority of previous research on arable-ley rotations has utilized either grass or grass-clover leys within ungrazed systems. Multispecies leys, containing a mix of grasses, legumes, and herbs, are rapidly gaining popularity due to their promotion in agri-environment schemes and potential to deliver greater ecosystem services than conventional grass or grass-clover leys. Livestock grazing in arable-ley rotations may increase the economic resilience of these systems, despite limited research of the effects of multispecies leys on ruminant health and greenhouse gas emissions. This review aims to evaluate previous research on multispecies leys, highlighting areas for future research and the potential benefits and disbenefits on soil quality and livestock productivity. The botanical composition of multispecies leys is crucial, as legumes, deep rooted perennial plants (e.g., Onobrychis viciifolia and Cichorium intybus) and herbs (e.g., Plantago lanceolata) can increase soil carbon, improve soil structure, reduce nitrogen fertilizer requirements, and promote the recovery of soil fauna (e.g., earthworms) in degraded arable soils while delivering additional environmental benefits (e.g., biological nitrification inhibition and enteric methane reduction). Multispecies leys have the potential to deliver biologically driven regenerative agriculture, but more long-term research is needed to underpin evidence-based policy and farmer guidance.

关键词: bioactive forages / integrated crop-livestock systems / nitrogen cycling / plant secondary metabolites / soil carbon / soil quality    

中药生物活性成分对糖脂代谢紊乱疾病的治疗作用和机制 Review

张莹, 鞠佳明, 焦磊, 杨宝峰

《工程(英文)》 2023年 第29卷 第10期   页码 73-82 doi: 10.1016/j.eng.2023.03.004

摘要:

胆固醇和葡萄糖稳态异常在心血管疾病、脑血管疾病、中枢神经系统疾病和癌症等多种疾病的发生发展中起着至关重要的作用。 越来越多的研究表明,体内脂肪堆积过多与2型糖尿病或胰岛素抵抗有关,高胆固醇和高血糖将加重上述疾病的发展进程。因此,稳定患者的血脂和血糖水平是改善心脑血管和中枢神经系统疾病患者症状的主要策略。中药(CHM)在中国已有两千多年的历史,建立了独特的中医理论,积累了丰富的临床经验。此外,中药在国内外广泛应用于心脑血管疾病的治疗和预防,具有防治高脂血症、糖尿病和高血压等疾病的优势。然而,中药在西方国家的使用仍然相当有限,部分原因是对其多种复杂成分的了解不完整,药理机制不确定。本文就中药生物活性成分及其制剂治疗高脂血症和高血糖症的作用、分子机制和临床研究进展进行综述和讨论。

关键词: Chinese herbal medicines     Hyperlipidemia     Hyperglycemia     Cardiovascular and cerebrovascular diseases    

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

《医学前沿(英文)》 2020年 第14卷 第6期   页码 726-745 doi: 10.1007/s11684-020-0746-0

摘要: Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词: CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

基于整合临床和动物实验的小分子筛选平台揭示经典方剂茵陈蒿汤治疗黄疸证显效状态下的活性化合物及潜在作用靶点 Article

熊辉, 张爱华, 郭雅静, 周小航, 孙晖, 杨乐, 方衡, 闫广利, 王喜军

《工程(英文)》 2021年 第7卷 第9期   页码 1293-1305 doi: 10.1016/j.eng.2020.12.016

摘要:

中药方剂化学组成高度复杂,其药理作用具有多成分、多靶点的特点,使得阐明其生物活性化合物极具挑战性。茵陈蒿汤被广泛用于治疗黄疸相关疾病。尽管近年来茵陈蒿汤的药效及活性成分被不断证实,但仍然缺乏对其效应成分、效应机制和功能靶点的深入系统分析,尤其是临床研究方面。本研究建立了一个整合临床和动物实验平台用于发现茵陈蒿汤的活性化合物和潜在靶点。首先采用基于超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-ToF-MS)技术的代谢组学方法结合中药血清药物化学方法揭示茵陈蒿汤的血清代谢谱和化学成分谱。此外,通过网络药理学和智能途径分析平台构建化合物-靶标-通路关联网络。最终发现茵陈蒿汤中8 个活性小分子与5 个核心靶点极度相关,并通过酶联免疫吸附测定实验进行生物学验证。结果表明茵陈蒿汤通过靶向胆固醇7α-羟化酶(CYP7A1)、多药耐药相关蛋白2(ABCC2)、多药耐药相关蛋白3(ABCC3)、尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT1A1)和法尼醇X受体(FXR)来调节包括初级胆汁酸生物合成、卟啉和叶绿素代谢以及胆汁分泌在内的代谢通路,从而发挥利胆退黄的作用。该整合策略可以成功地用于中药方剂活性小分子及其作用靶点的发现。

关键词: 有效性     活性化合物     小分子     靶点     中药     代谢组学    

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

Progress of three-dimensional macroporous bioactive glass for bone regeneration

Lijun JI, Yunfeng SI, Ailing LI, Wenjun WANG, Dong QIU, Aiping ZHU

期刊论文

Development and clinical trial of a novel bioactive bone cement

LEONG John, LI Zhaoyang, LU William

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

Chemical transdifferentiation: closer to regenerative medicine

null

期刊论文

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

期刊论文

Emerging immunological strategies: recent advances and future directions

期刊论文

AGRONOMIC AND ENVIRONMENTAL BENEFITS OF REINTRODUCING HERB- AND LEGUME-RICH MULTISPECIES LEYS INTO ARABLE ROTATIONS: A REVIEW

期刊论文

中药生物活性成分对糖脂代谢紊乱疾病的治疗作用和机制

张莹, 鞠佳明, 焦磊, 杨宝峰

期刊论文

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

期刊论文

基于整合临床和动物实验的小分子筛选平台揭示经典方剂茵陈蒿汤治疗黄疸证显效状态下的活性化合物及潜在作用靶点

熊辉, 张爱华, 郭雅静, 周小航, 孙晖, 杨乐, 方衡, 闫广利, 王喜军

期刊论文