Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of ne...Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.展开更多
The modern transportation system is increasingly developed during recent years.It is an effective solution to set the noise barriers to reduce the traffic noise pollution caused by different kinds of transportation sy...The modern transportation system is increasingly developed during recent years.It is an effective solution to set the noise barriers to reduce the traffic noise pollution caused by different kinds of transportation systems.Many deficiencies on concrete noise barriers and metal noise barriers with rivet structure can be eliminated by a new kind of noise barrier with no-riveted structure.The mechanical performance examination and acoustic performance test are conducted on the new-designed noise barrier with no-riveted structure.The results indicate that the maximum stress is 1.74 MPa and the maximum deformation is 1.04 mm with load acting on the unit plate.The noise reduction coefficient of this kind of no-riveted noise barrier unit plate is 0.75 and its noise insulation is 40 dB,which were conform to or superior to the standard requirements.Therefore,this new designed noise barrier meets the field application requirements of mechanical and acoustic performance,which demonstrates the noise barriers can be widely promoted.展开更多
To date,the United States(U.S.)has been the most heavily impacted country by the coronavirus disease 2019(COVID-19).By November 30,2020,when this paper was written,13.5 million cases were reported in the U.S.with over...To date,the United States(U.S.)has been the most heavily impacted country by the coronavirus disease 2019(COVID-19).By November 30,2020,when this paper was written,13.5 million cases were reported in the U.S.with over 268000 deaths.Historically,vaccines have been one of the most effective and efficient technical tools for controlling a communicable disease.While the development of these vaccines has certainly been a challenge,it could be more challenging to achieve robust vaccine uptake because of many barriers.In this review,we focused on two types of barriers documented from long-term experience in the U.S.:structural and attitudinal.Structural barriers are systemic issues that impact one's ability to access a service,and they include time,transportation,cost,and clinic or outlet location;while attitudinal barriers are beliefs or perceptions that impact the willingness of at-risk individuals to seek out and/or accept a service.In the context of vaccination they include beliefs about the communicable disease,beliefs about vaccines,fear,and trust in healthcare and governmental agencies.Of the attitudinal barriers,public trust is a barrier that is of particular importance.In addition to affecting reception of vaccines,it may exacerbate disparities and reduce the likelihood of success of a vaccination program.Recommendations are made to overcome attitudinal barriers to help improve the effectiveness of vaccination programs for COVID-19 control in the U.S.,such as building public support through bipartisan endorsements and leveraging social media platforms to promote vaccination.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the...BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments,both structural and functionally.The literature still lacks consensus on the best conditions to mimic the blood-brain barrier(BBB)for drug screening and other personalized therapies.The development of models based on BBB-on-achip using iPSCs is promising and is a potential alternative to the use of animals in research.AIM To analyze the literature for BBB models on-a-chip involving iPSCs,describe the microdevices,the BBB in vitro construction,and applications.METHODS We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices.Thirty articles were identified,wherein only 14 articles were finally selected according to the inclusion and exclusion criteria.Data compiled from the selected articles were organized into four topics:(1)Microfluidic devices design and fabrication;(2)characteristics of the iPSCs used in the BBB model and their differentiation conditions;(3)BBB-on-a-chip reconstruction process;and(4)applications of BBB microfluidic three-dimensional models using iPSCs.RESULTS This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research.Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups.Conventional polydimethylsiloxane was the most used material to fabricate in-house chips(57%),whereas few studies(14.3%)adopted polymethylmethacrylate.Half the models were constructed using a porous membrane made of diverse materials to separate the channels.iPSC sources were divergent among the studies,but the main line used was IMR90-C4 from human fetal lung fibroblast(41.2%).The cells were differentiated through diverse and complex processes either to endothelial or neural cells,wherein only one study promoted differentiation inside the chip.The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen Ⅳ(39.3%),followed by cell seeding in single cultures(36%)or co-cultures(64%)under controlled conditions,aimed at developing an in vitro BBB that mimics the human BBB for future applications.CONCLUSION This review evidenced technological advances in the construction of BBB models using iPSCs.Nonetheless,a definitive BBB-on-a-chip has not yet been achieved,hindering the applicability of the models.展开更多
Based on the waterflooding development in carbonate reservoirs in the Middle East,in order to solve the problem of the poor development effects caused by commingled injection and production,taking the thick bioclastic...Based on the waterflooding development in carbonate reservoirs in the Middle East,in order to solve the problem of the poor development effects caused by commingled injection and production,taking the thick bioclastic limestone reservoirs of Cretaceous in Iran-Iraq as an example,this paper proposes a balanced waterflooding development technology for thick and complex carbonate reservoirs.This technology includes the fine division of development units by concealed baffles and barriers,the combination of multi well type and multi well pattern,and the construction of balanced water injection and recovery system.Thick carbonate reservoirs in Iran-Iraq are characterized by extremely vertical heterogeneity,development of multi-genesis ultra-high permeability zones,and highly concealed baffles and barriers.Based on the technologies of identification,characterization,and sealing evaluation for concealed baffles and barriers,the balanced waterflooding development technology is proposed,and three types of balanced waterflooding development modes/techniques are formed,namely,conventional stratigraphic framework,fine stratigraphic framework,and deepened stratigraphic framework.Numerical simulations show that this technology is able to realize a fine and efficient waterflooding development to recover,in a balanced manner,the reserves of thick and complex carbonate reservoirs in Iran and Iraq.The proposed technology provides a reference for the development optimization of similar reservoirs.展开更多
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an...Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.展开更多
The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-sp...The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies.Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with plateletderived growth factor(80μg/kg)at the injury site.Our results showed that after platelet-derived growth factor administration,spinal cord injury,neuronal apoptosis,and blood-spinal cord barrier permeability were reduced,excessive astrocyte proliferation and the autophagyrelated apoptosis signaling pathway were inhibited,collagen synthesis was increased,and mouse locomotor function was improved.In vitro,human umbilical vein endothelial cells were established by exposure to 200μM H2O2.At 2 hours prior to injury,in vitro cell models were treated with 5 ng/mL platelet-derived growth factor.Our results showed that expression of blood-spinal cord barrier-related proteins,including Occludin,Claudin 5,andβ-catenin,was significantly decreased and autophagy was significantly reduced.Additionally,the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine,an autophagy inhibitor,for 3 successive days prior to spinal cord injury.Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy,improve the function of the blood-spinal cord barrier,and promote the recovery of locomotor function post-spinal cord injury.Approval for animal experiments was obtained from the Animal Ethics Committee,Wenzhou Medical University,China(approval No.wydw2018-0043)in July 2018.展开更多
Background: The volunteer role has been cited as an important in supporting healthcare organizations in diverse areas such as contributing to research, health professional’s education, health care delivery, health po...Background: The volunteer role has been cited as an important in supporting healthcare organizations in diverse areas such as contributing to research, health professional’s education, health care delivery, health policy development and patient administration. Proper motivation of volunteers is required for sustaining volunteer performance, while encumbrances to optimal engagement in health systems need to be addressed. This study aimed to investigate the main factors that motivate volunteers to participate in the UAE healthcare system, along with exploring the barriers and challenges being faced. Methods: This study was designed as a quantitative cross-sectional study in United Arab Emirates (UAE). A purposive sample of the Adult citizens and residents using purposive sampling directed at all major health volunteer recruitment agencies in UAE, who have volunteered at least once in the health system over the preceding 12 months. Participants Adult UAE residents were selected by a purposive sampling method from February to April 2017. Data were collected through electronic questionnaires using modified Volunteer Motivation Inventory (VMI). Data were analyzed from 667 adults’ residents who were reported to volunteer at least once in healthcare opportunities. Results: About 53% (n = 290) of the volunteers in this sample were full time employed individuals. Almost 63% (n = 422) were female. Overall, assessed self-reported motivations of volunteer participants were high. The main motivation for volunteering in healthcare opportunities in the UAE was Understanding dimension (Mean = 4.68), followed by self-esteem dimension (Mean = 4.60). Eight elements of volunteer motivation showed no statistically significant differences between male and female respondents. Organization/system barriers dimension was the highest among respondents (Mean = 2.9), followed by individual barriers (Mean = 2.6), interpersonal (Mean = 2.06) and contextual (Mean = 2.04). Conclusion: UAE health sector volunteers who participated in this study appeared to be highly motivated. The main motivation factor was understanding dimension which allowed volunteers in healthcare to gain a new perspective on things, through practical training and learning new things, dealing with different groups in the health sector, for example doctors, nursing, patients. What makes the health sector volunteer understand them self and the world around them. Therefore the organization should focus on volunteer motivation to ensure future intensions of them. The four main barriers to volunteer were Individual barriers, Interpersonal barriers, contextual barriers and organizations system barriers. Concerted efforts are needed to raise awareness about available volunteer opportunities, and optimally align the motivations of volunteers with organizational objectives in the UAE health sector.展开更多
In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in t...In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system.Since then,the neurovascular unit has attracted increasing interest from research teams,who have contributed greatly to the prevention,treatment,and prognosis of stroke and neurodegenerative diseases.However,additional research is needed to establish an efficient,low-cost,and low-energy in vitro model of the neurovascular unit,as well as enable noninvasive observation of neurovascular units in vivo and in vitro.In this review,we first summarize the composition of neurovascular units,then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models,and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.展开更多
Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic te...Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.展开更多
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
基金supported by the National Natural Science Foundation of China(No.82160237)the Key Research and Development Program in Hainan Province(No.ZDYF2023SHFZ104)Natural Science Foundation of Hainan Province(No.822MS210).
文摘Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.
基金supported by the National Natural Science Foundation of China (No. 51768014).
文摘The modern transportation system is increasingly developed during recent years.It is an effective solution to set the noise barriers to reduce the traffic noise pollution caused by different kinds of transportation systems.Many deficiencies on concrete noise barriers and metal noise barriers with rivet structure can be eliminated by a new kind of noise barrier with no-riveted structure.The mechanical performance examination and acoustic performance test are conducted on the new-designed noise barrier with no-riveted structure.The results indicate that the maximum stress is 1.74 MPa and the maximum deformation is 1.04 mm with load acting on the unit plate.The noise reduction coefficient of this kind of no-riveted noise barrier unit plate is 0.75 and its noise insulation is 40 dB,which were conform to or superior to the standard requirements.Therefore,this new designed noise barrier meets the field application requirements of mechanical and acoustic performance,which demonstrates the noise barriers can be widely promoted.
基金This article was supported by U.S.National Institute on Alcohol Abuse and Alcoholism Grant T32AA025877.
文摘To date,the United States(U.S.)has been the most heavily impacted country by the coronavirus disease 2019(COVID-19).By November 30,2020,when this paper was written,13.5 million cases were reported in the U.S.with over 268000 deaths.Historically,vaccines have been one of the most effective and efficient technical tools for controlling a communicable disease.While the development of these vaccines has certainly been a challenge,it could be more challenging to achieve robust vaccine uptake because of many barriers.In this review,we focused on two types of barriers documented from long-term experience in the U.S.:structural and attitudinal.Structural barriers are systemic issues that impact one's ability to access a service,and they include time,transportation,cost,and clinic or outlet location;while attitudinal barriers are beliefs or perceptions that impact the willingness of at-risk individuals to seek out and/or accept a service.In the context of vaccination they include beliefs about the communicable disease,beliefs about vaccines,fear,and trust in healthcare and governmental agencies.Of the attitudinal barriers,public trust is a barrier that is of particular importance.In addition to affecting reception of vaccines,it may exacerbate disparities and reduce the likelihood of success of a vaccination program.Recommendations are made to overcome attitudinal barriers to help improve the effectiveness of vaccination programs for COVID-19 control in the U.S.,such as building public support through bipartisan endorsements and leveraging social media platforms to promote vaccination.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.
基金CNPq,Nos.308901/2020-7 and 400856/2016-6FAPESP,Nos.2019/21070-3,2017/17868-4,and 2016/21470-3+1 种基金SisNANO 2.0/MCTIC,No.442539/2019-3the National Institute of Science and Technology Complex Fluids,INCT-FCx.
文摘BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments,both structural and functionally.The literature still lacks consensus on the best conditions to mimic the blood-brain barrier(BBB)for drug screening and other personalized therapies.The development of models based on BBB-on-achip using iPSCs is promising and is a potential alternative to the use of animals in research.AIM To analyze the literature for BBB models on-a-chip involving iPSCs,describe the microdevices,the BBB in vitro construction,and applications.METHODS We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices.Thirty articles were identified,wherein only 14 articles were finally selected according to the inclusion and exclusion criteria.Data compiled from the selected articles were organized into four topics:(1)Microfluidic devices design and fabrication;(2)characteristics of the iPSCs used in the BBB model and their differentiation conditions;(3)BBB-on-a-chip reconstruction process;and(4)applications of BBB microfluidic three-dimensional models using iPSCs.RESULTS This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research.Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups.Conventional polydimethylsiloxane was the most used material to fabricate in-house chips(57%),whereas few studies(14.3%)adopted polymethylmethacrylate.Half the models were constructed using a porous membrane made of diverse materials to separate the channels.iPSC sources were divergent among the studies,but the main line used was IMR90-C4 from human fetal lung fibroblast(41.2%).The cells were differentiated through diverse and complex processes either to endothelial or neural cells,wherein only one study promoted differentiation inside the chip.The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen Ⅳ(39.3%),followed by cell seeding in single cultures(36%)or co-cultures(64%)under controlled conditions,aimed at developing an in vitro BBB that mimics the human BBB for future applications.CONCLUSION This review evidenced technological advances in the construction of BBB models using iPSCs.Nonetheless,a definitive BBB-on-a-chip has not yet been achieved,hindering the applicability of the models.
基金Supported by the Major Science and Technology Project of CNPC(2023ZZ19-01).
文摘Based on the waterflooding development in carbonate reservoirs in the Middle East,in order to solve the problem of the poor development effects caused by commingled injection and production,taking the thick bioclastic limestone reservoirs of Cretaceous in Iran-Iraq as an example,this paper proposes a balanced waterflooding development technology for thick and complex carbonate reservoirs.This technology includes the fine division of development units by concealed baffles and barriers,the combination of multi well type and multi well pattern,and the construction of balanced water injection and recovery system.Thick carbonate reservoirs in Iran-Iraq are characterized by extremely vertical heterogeneity,development of multi-genesis ultra-high permeability zones,and highly concealed baffles and barriers.Based on the technologies of identification,characterization,and sealing evaluation for concealed baffles and barriers,the balanced waterflooding development technology is proposed,and three types of balanced waterflooding development modes/techniques are formed,namely,conventional stratigraphic framework,fine stratigraphic framework,and deepened stratigraphic framework.Numerical simulations show that this technology is able to realize a fine and efficient waterflooding development to recover,in a balanced manner,the reserves of thick and complex carbonate reservoirs in Iran and Iraq.The proposed technology provides a reference for the development optimization of similar reservoirs.
基金supported by the National Natural Science Foundation of China,No.81430102(to QGW)
文摘Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.
基金This study was partly supported by research grants from the National Natural Science Foundation of China,Nos.81802251(to KX),81772450(to HYZ)and 81801233(to YQW)the Natural Science Foundation of Zhejiang Province of China,Nos.LQ18H150003(to KX),LY19H150001(to DQC),LQ18H090011(to YQW)and LQ20C200015(to HJ)the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences,No.YKFJ3-011(to KX).
文摘The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies.Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with plateletderived growth factor(80μg/kg)at the injury site.Our results showed that after platelet-derived growth factor administration,spinal cord injury,neuronal apoptosis,and blood-spinal cord barrier permeability were reduced,excessive astrocyte proliferation and the autophagyrelated apoptosis signaling pathway were inhibited,collagen synthesis was increased,and mouse locomotor function was improved.In vitro,human umbilical vein endothelial cells were established by exposure to 200μM H2O2.At 2 hours prior to injury,in vitro cell models were treated with 5 ng/mL platelet-derived growth factor.Our results showed that expression of blood-spinal cord barrier-related proteins,including Occludin,Claudin 5,andβ-catenin,was significantly decreased and autophagy was significantly reduced.Additionally,the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine,an autophagy inhibitor,for 3 successive days prior to spinal cord injury.Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy,improve the function of the blood-spinal cord barrier,and promote the recovery of locomotor function post-spinal cord injury.Approval for animal experiments was obtained from the Animal Ethics Committee,Wenzhou Medical University,China(approval No.wydw2018-0043)in July 2018.
文摘Background: The volunteer role has been cited as an important in supporting healthcare organizations in diverse areas such as contributing to research, health professional’s education, health care delivery, health policy development and patient administration. Proper motivation of volunteers is required for sustaining volunteer performance, while encumbrances to optimal engagement in health systems need to be addressed. This study aimed to investigate the main factors that motivate volunteers to participate in the UAE healthcare system, along with exploring the barriers and challenges being faced. Methods: This study was designed as a quantitative cross-sectional study in United Arab Emirates (UAE). A purposive sample of the Adult citizens and residents using purposive sampling directed at all major health volunteer recruitment agencies in UAE, who have volunteered at least once in the health system over the preceding 12 months. Participants Adult UAE residents were selected by a purposive sampling method from February to April 2017. Data were collected through electronic questionnaires using modified Volunteer Motivation Inventory (VMI). Data were analyzed from 667 adults’ residents who were reported to volunteer at least once in healthcare opportunities. Results: About 53% (n = 290) of the volunteers in this sample were full time employed individuals. Almost 63% (n = 422) were female. Overall, assessed self-reported motivations of volunteer participants were high. The main motivation for volunteering in healthcare opportunities in the UAE was Understanding dimension (Mean = 4.68), followed by self-esteem dimension (Mean = 4.60). Eight elements of volunteer motivation showed no statistically significant differences between male and female respondents. Organization/system barriers dimension was the highest among respondents (Mean = 2.9), followed by individual barriers (Mean = 2.6), interpersonal (Mean = 2.06) and contextual (Mean = 2.04). Conclusion: UAE health sector volunteers who participated in this study appeared to be highly motivated. The main motivation factor was understanding dimension which allowed volunteers in healthcare to gain a new perspective on things, through practical training and learning new things, dealing with different groups in the health sector, for example doctors, nursing, patients. What makes the health sector volunteer understand them self and the world around them. Therefore the organization should focus on volunteer motivation to ensure future intensions of them. The four main barriers to volunteer were Individual barriers, Interpersonal barriers, contextual barriers and organizations system barriers. Concerted efforts are needed to raise awareness about available volunteer opportunities, and optimally align the motivations of volunteers with organizational objectives in the UAE health sector.
基金financially supported by the National Natural Science Foundation of China,Nos.82104412(to TD),81873023(to JW)Natural Science Basic Research Program of Shaanxi Province of China,No.2020JQ-865(to TD)+1 种基金Education Department of Shaanxi Province of China,No.20JK0597(to TD)the Subject Innovation Team of Shaanxi University of Chinese Medicine of China,No.2019-QN02(to PW).
文摘In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system.Since then,the neurovascular unit has attracted increasing interest from research teams,who have contributed greatly to the prevention,treatment,and prognosis of stroke and neurodegenerative diseases.However,additional research is needed to establish an efficient,low-cost,and low-energy in vitro model of the neurovascular unit,as well as enable noninvasive observation of neurovascular units in vivo and in vitro.In this review,we first summarize the composition of neurovascular units,then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models,and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.
基金supported by the Stem Cell Clinical Research Project of China,No.CMR-20161129-1003Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031the Dalian Innovation Technology Foundation of China,No.2018J11CY025(all to JL).
文摘Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.