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11.
Nianxiu Duan Junjun Li Sha Song Feng Wang Yiwei Yang Di Nie Caifen Wang Yingjie Sheng Yali Tao Jie Gao Can Xu Yan Wei Yong Gan 《Advanced functional materials》2021,31(46):2100605
Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy. 相似文献
12.
Dr. Ying Wang Prof. Dr. Andrew Ewing 《Chembiochem : a European journal of chemical biology》2021,22(5):807-813
Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types. 相似文献
13.
Alison Jee Samantha Christine Sernoskie Jack Uetrecht 《International journal of molecular sciences》2021,22(6)
Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses. 相似文献
14.
Caifang Gao Mu-Pai Lee Mengjiao Li Ko-Chun Lee Feng-Shou Yang Che-Yi Lin Kenji Watanabe Takashi Taniguchi Po-Wen Chiu Chen-Hsin Lien Wen-Wei Wu Shu-Ping Lin Wenwu Li Yen-Fu Lin Junhao Chu 《Advanced functional materials》2021,31(5):2005182
The human brain is often likened to an incredibly complex and intricate computer, rather than electrical devices, consisting of billions of neuronal cells connected by synapses. Different brain circuits are responsible for coordinating and performing specific functions. The reward pathway of the synaptic plasticity in the brain is strongly related to the features of both drug addiction and relief. In the current study, a synaptic device based on layered hafnium disulfide (HfS2) is developed for the first time, to emulate the behavioral mechanisms of drug dosage modulation for neuroplasticity. A strong gate-dependent persistent photocurrent is observed, arising from the modulation of substrate-trapping events. By controlling the polarity of gate voltage, the basic functions of biological synapses are realized under a range of light spiking conditions. Furthermore, under the control of detrapping/trapping events at the HfS2/SiO2 interface, positive/negative correlations of the An/A1 index, which significantly reflected the weight change of synaptic plasticity, are realized under the same stimulation conditions for the emulation of the drug-related addition/relief behaviors in the brain. The findings provide a new advance for mimicking human brain plasticity. 相似文献
15.
《Ceramics International》2022,48(22):33361-33372
Calcium phosphate cements (CPCs) have been increasingly used as synthetic bone substitutes for repair and regeneration of bone defects given their biocompatibility, resemblance to bone and malleability. Moreover, their use as local antibiotic delivery systems is of main interest against bone infections, avoiding the adverse effects of high dosages of conventional therapy. The main goals of this work were to improve the properties of a commercial CPC (Neocement®), turning it injectable, and to provide it with a new functionality as a drug delivery system able to ensure a sustained release of an antibiotic commonly used in orthopaedics (gentamicin sulphate, GS). For this, the influence of the liquid phase amount (%LP) and type of polymer contained in the formulation (chitosan, Chi, or hydroxypropyl methylcellulose, HPMC) on the basic properties of the material was evaluated. It was found that the formulation containing 42%LP + HPMC+1.87% wt GS was the best one. It showed suitable setting and mechanical properties, and injectability around 87% (much superior to the original Neocement®, with 31%). It ensured a sustained release of GS for at least 14 days, at antibacterial levels. The antibiotic released is highly effective against S. epidermidis, but also presents some antibacterial activity against S. aureus. The CPC revealed to be non-cytotoxic. Moreover, it demonstrated good flowability and connectivity with human cadaveric trabecular bone. 相似文献
16.
A comparative study on pyrolysis reactivity and gas release characteristics of biomass and coal using TG-MS analysis 总被引:1,自引:0,他引:1
Juntao Wei Xia Liu Qinghua Guo Xueli Chen 《Energy Sources, Part A: Recovery, Utilization, and Environmental Effects》2018,40(17):2063-2069
Pyrolysis reactivity and gas release characteristics of biomass and coals were comparatively investigated using TG-MS. In addition, chemical compositions and structures of tested samples were determined to correlate pyrolysis gas release characteristic. It was found that pyrolysis reactivity and gaseous product release were hardly varied with pyrolysis heating rate. Furthermore, pyrolysis rates of two biomass samples were greater than those of coals, which were mainly attributed to the chemical compositions and the gaseous product evolution process. The result also showed that gaseous product release during pyrolysis process was related to the presence of different functional groups in samples. 相似文献
17.
Dr. Christine Brotschi Dr. Martin H. Bolli Dr. John Gatfield Dr. Bibia Heidmann Dr. Francois Jenck Dr. Catherine Roch Dr. Thierry Sifferlen Dr. Alexander Treiber Dr. Jodi T. Williams Dr. Christoph Boss 《ChemMedChem》2020,15(5):430-448
The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 . 相似文献
18.
彭家寅 《计算机工程与应用》2020,56(12):93-97
目的是利用高维量子纠缠态为量子信道,讨论未知单粒子态的受控隐形传输问题。以三维量子纠缠态为信道,提出一个二维任意单粒子态的受控隐形传输协议。提出了以任意[d]-维量子纠缠态为量子信道,[t]-维任意单粒子态的隐形传输协议[(t相似文献
19.
Hollow mesoporous silica nanoparticles (HMSNs) have become an attractive drug carrier because of their unique characteristics including stable physicochemical properties, large specific surface area and facile functionalization, especially made into intelligent drug delivery systems (DDSs) for cancer therapy. HMSNs are employed to transport traditional anti-tumor drugs, which can solve the problems of drugs with instability, poor solubility and lack of recognition, etc., while significantly improving the anti-tumor effect. And an unexpected good result will be obtained by combining functional molecules and metal species with HMSNs for cancer diagnosis and treatment. Actually, HMSNs-based DDSs have developed relatively mature in recent years. This review briefly describes how to successfully prepare an ordinary HMSNs-based DDS, as well as its degradation, different stimuli-responses, targets and combination therapy. These versatile intelligent nanoparticles show great potential in clinical aspects. 相似文献
20.
Riham Gharib Jouda Mediouni Ben Jema Catherine Charcosset Sophie Fourmentin Hlne Greige‐Gerges 《European Journal of Lipid Science and Technology》2020,122(5)
Eucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention. Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release. 相似文献