Neurological disorders including neurodegenerative diseases,brain tumors,and stroke are the second leading cause of death and the greatest cause of disability worldwide.However,it remains challenging to achieve effect...Neurological disorders including neurodegenerative diseases,brain tumors,and stroke are the second leading cause of death and the greatest cause of disability worldwide.However,it remains challenging to achieve effective drug delivery to the central nervous system for treatments of neurological diseases due to the blood-brain barrier(BBB).The function of the BBB is regulated by the physiological interactions between various types of cells in the neurovascular unit(NVU).In the NVU,the brain vasculature of the BBB is surrounded by brain pericytes,brain astrocytes,neurons,and microglia(Figure 1).Moreover,the NVU at the levels of arteries and veins includes contractile smooth muscle cells(Schaeffer and Iadecola,2021).展开更多
Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals ind...Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million animals.Beyond ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug exposure.While animal testing has been the traditional method for assessing the safety and efficacy of drugs.展开更多
We have studied the redox potentials and electronic properties of C60 and C59N using density functional theory method. It is found that doping C60 with one nitrogen atom results in a slight increase in redox potential...We have studied the redox potentials and electronic properties of C60 and C59N using density functional theory method. It is found that doping C60 with one nitrogen atom results in a slight increase in redox potential. Next, we have also studied C59N functionalized with various redox-active oxygen containing functional groups and strongly electron withdrawing functional groups. It is found that the intrinsic electronic structure of the molecule is the major determinant of the redox potential. Our DFT calculations show that the electron affinity to redox potential of functionalized C59N is correlated with the LUMO of the systems very well. This is the first systematic study on the redox properties and electronic structures of N-doped C60 systems.展开更多
In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discuss...In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas poly-unsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well understood. Recently, it has been demonstrated by lipidomics and associated molecular techniques, that activation and metabolic channeling of long-chain fatty acids are important mechanisms to modify colorectal carcinogenesis. In this Editorial, an overview about the present concept of long-chain fatty acids and its derivatives in colorectal carcinogenesis as well as technical algorithms in lipid analysis is given.展开更多
Plant cell culture in bioreactors is an enabling tool for large scale production of clonal elite plants in agriculture, horticulture, forestry, pharmaceutical sectors, and for biofuel production. Advantages of bioreac...Plant cell culture in bioreactors is an enabling tool for large scale production of clonal elite plants in agriculture, horticulture, forestry, pharmaceutical sectors, and for biofuel production. Advantages of bioreactors for plant cell culture have resulted in various types of bioreactors differing in design, operating technologies, instrumentations, and construction of culture vessels. In this review, different types of bioreactors for clonal propagation of plants and secondary metabolites production are discussed. Mechanical and biochemical parameters associated with bioreactor design, such as aeration, flow rate, mixing, dissolved oxygen, composition of built-up gas in the headspace, and pH of the medium, are pivotal for cell morphology, growth, and development of cells within tissues, embryos, and organs. The differences in such parameters for different bioreactor designs are described here, and correlated to the plant materials that have been successfully cultured in different types of bioreactors.展开更多
High-density lipoprotein （HDL） serves as a natural nanoparticle with compositional and functional heterogeneity and contributes to the maintenance of lipid metabolism and various biological functions. HDL also trans...High-density lipoprotein （HDL） serves as a natural nanoparticle with compositional and functional heterogeneity and contributes to the maintenance of lipid metabolism and various biological functions. HDL also transports endogenous microRNAs, vitamins, hormones, and proteins through blood and interstitial fluids to various organs. These unique and diverse features of HDL have encouraged its applications for the transport of therapeutics and diagnostic reagents in the last decade. In this review, we describe the heterogeneous characteristics and biological functions of HDL and highlight HDL mimetic approaches, including apolipoprotein mimetic peptides and reconstituted HDL nanoparticles. Given the potential of HDL as a nanocarrier delivering various therapeutic agents, we discuss the current representative studies of HDL mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases and analyze the current challenges and future perspective.展开更多
This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current...This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20%to 40%of the cases,and the incidence of CvST has increased since the outbreak of the coronavirus disease 2019 pandemic.Compared with conventional anticoagulant or thrombolytic drugs,sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves.However,previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes(e.g.,recanalization within 30 min)in treating large,completely occluded veins or arteries.Here,we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wavematter interaction-induced shear stress to enhance the lytic rate substantially.Our in vitro experiment showed that the lytic rate was increased by at least 64.3%compared with the nonvortex endovascular ultrasound treatment.A 3.1-g,7.5-cm-long,completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot invitro.Furthermore,we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins.This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.展开更多
基金supported by a 2-Year Research Grant of Pusan National University(to SIA).
文摘Neurological disorders including neurodegenerative diseases,brain tumors,and stroke are the second leading cause of death and the greatest cause of disability worldwide.However,it remains challenging to achieve effective drug delivery to the central nervous system for treatments of neurological diseases due to the blood-brain barrier(BBB).The function of the BBB is regulated by the physiological interactions between various types of cells in the neurovascular unit(NVU).In the NVU,the brain vasculature of the BBB is surrounded by brain pericytes,brain astrocytes,neurons,and microglia(Figure 1).Moreover,the NVU at the levels of arteries and veins includes contractile smooth muscle cells(Schaeffer and Iadecola,2021).
文摘Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million animals.Beyond ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug exposure.While animal testing has been the traditional method for assessing the safety and efficacy of drugs.
文摘We have studied the redox potentials and electronic properties of C60 and C59N using density functional theory method. It is found that doping C60 with one nitrogen atom results in a slight increase in redox potential. Next, we have also studied C59N functionalized with various redox-active oxygen containing functional groups and strongly electron withdrawing functional groups. It is found that the intrinsic electronic structure of the molecule is the major determinant of the redox potential. Our DFT calculations show that the electron affinity to redox potential of functionalized C59N is correlated with the LUMO of the systems very well. This is the first systematic study on the redox properties and electronic structures of N-doped C60 systems.
文摘In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas poly-unsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well understood. Recently, it has been demonstrated by lipidomics and associated molecular techniques, that activation and metabolic channeling of long-chain fatty acids are important mechanisms to modify colorectal carcinogenesis. In this Editorial, an overview about the present concept of long-chain fatty acids and its derivatives in colorectal carcinogenesis as well as technical algorithms in lipid analysis is given.
文摘Plant cell culture in bioreactors is an enabling tool for large scale production of clonal elite plants in agriculture, horticulture, forestry, pharmaceutical sectors, and for biofuel production. Advantages of bioreactors for plant cell culture have resulted in various types of bioreactors differing in design, operating technologies, instrumentations, and construction of culture vessels. In this review, different types of bioreactors for clonal propagation of plants and secondary metabolites production are discussed. Mechanical and biochemical parameters associated with bioreactor design, such as aeration, flow rate, mixing, dissolved oxygen, composition of built-up gas in the headspace, and pH of the medium, are pivotal for cell morphology, growth, and development of cells within tissues, embryos, and organs. The differences in such parameters for different bioreactor designs are described here, and correlated to the plant materials that have been successfully cultured in different types of bioreactors.
文摘High-density lipoprotein （HDL） serves as a natural nanoparticle with compositional and functional heterogeneity and contributes to the maintenance of lipid metabolism and various biological functions. HDL also transports endogenous microRNAs, vitamins, hormones, and proteins through blood and interstitial fluids to various organs. These unique and diverse features of HDL have encouraged its applications for the transport of therapeutics and diagnostic reagents in the last decade. In this review, we describe the heterogeneous characteristics and biological functions of HDL and highlight HDL mimetic approaches, including apolipoprotein mimetic peptides and reconstituted HDL nanoparticles. Given the potential of HDL as a nanocarrier delivering various therapeutic agents, we discuss the current representative studies of HDL mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases and analyze the current challenges and future perspective.
基金support from the National Institutes of Health(grant numbers R01HL141967,R41HL154735,and R21EB027304)support from the National Science Foundation(grant number CMMI-2142555)。
文摘This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20%to 40%of the cases,and the incidence of CvST has increased since the outbreak of the coronavirus disease 2019 pandemic.Compared with conventional anticoagulant or thrombolytic drugs,sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves.However,previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes(e.g.,recanalization within 30 min)in treating large,completely occluded veins or arteries.Here,we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wavematter interaction-induced shear stress to enhance the lytic rate substantially.Our in vitro experiment showed that the lytic rate was increased by at least 64.3%compared with the nonvortex endovascular ultrasound treatment.A 3.1-g,7.5-cm-long,completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot invitro.Furthermore,we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins.This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.
