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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis
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作者 Conglin Wang Fangyuan Cheng +9 位作者 Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong Ge Dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei 《Neural Regeneration Research》 SCIE CAS 2025年第2期518-532,共15页
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)... Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes. 展开更多
关键词 AKT ASTROCYTE blood-brain barrier cerebral edema EXOSOMES human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells NEUROINFLAMMATION PI3K
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Vertical human-induced vibration of pedestrian bridge 被引量:1
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作者 丁建明 陈娟婷 +1 位作者 王葆茜 徐秀丽 《Journal of Southeast University(English Edition)》 EI CAS 2010年第4期582-585,共4页
The double degrees-of-freedom(DOFs)parallel model is adopted to analyze static vertical human-induced vibration with the finite element analysis(FEA)method.In the first-order symmetric vibration mode,the periods o... The double degrees-of-freedom(DOFs)parallel model is adopted to analyze static vertical human-induced vibration with the finite element analysis(FEA)method.In the first-order symmetric vibration mode,the periods of the spring-mass model gradually decrease with the increase in K1 and K2,but they are always greater than the period of the add-on mass model.Meanwhile,the periods of the spring-mass model decrease with the decrease in m1 and m2,but they are always greater than the period of the hollow bridge model.Since the human's two degrees-of-freedom vibrate in the same direction as that of the bridge mid-span,the existence of human's rigidity leads to the reduction in the rigidity of the spring-mass model.In the second-order symmetric vibration mode,the changes of rigidity K2 and mass m2 result in the disappearance or occurrence of some vibration modes.It can be concluded that compared with the spring-mass model,the results of the add-on mass model lean to lack of safety to the structure;besides,the DOF with a smaller ratio of mass to rigidity plays the chief role in the vibration of the structure. 展开更多
关键词 human-induced vibration spring-mass model double degrees-of-freedom(DOFs)parallel model
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Integrated Organ-on-a-chip with Human-induced Pluripotent Stem Cells Directional Differentiation for 3D Skin Model Generation
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作者 LUO Zhang GONG Chaihong +4 位作者 MAO Xiaowei WANG Zhe LIU Zhifan BEN Yali ZHANG Weiying 《Journal of Wuhan University of Technology(Materials Science)》 SCIE EI CAS 2022年第6期1271-1278,共8页
Keratinocytes and fibroblasts,derived from hiPSCs,were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid)(PLGA)nanofibers and a human skin-on-a-chip device.... Keratinocytes and fibroblasts,derived from hiPSCs,were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid)(PLGA)nanofibers and a human skin-on-a-chip device.Unlike the conventional culture dish method,two different epidermal cells are successfully adhered to the front and back sides of the patch,which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin.As expected,the differentiated hiPSCs show the expression of keratinocyte-and fibroblast-specific proteins on the patch,and the layering is found between these two kinds of cells,indicating that this approach creates a powerful in vitro system for modeling skin development and diseases. 展开更多
关键词 organ-on-a-chip human-induced pluripotent stem cells 3D skin model direction differentiation
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Human-induced pluripotent stem cell-atrial-specific cardiomyocytes and atrial fibrillation
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作者 Wattana Leowattana Tawithep Leowattana Pathomthep Leowattana 《World Journal of Clinical Cases》 SCIE 2022年第27期9588-9601,共14页
Patient-specific human-induced pluripotent stem cell-derived atrial cardiomyocytes(hiPSC-aCMs) may be produced,genome-edited,and differentiated into multiple cell types for regenerative medicine,disease modeling,drug ... Patient-specific human-induced pluripotent stem cell-derived atrial cardiomyocytes(hiPSC-aCMs) may be produced,genome-edited,and differentiated into multiple cell types for regenerative medicine,disease modeling,drug testing,toxicity screening,and three-dimensional tissue fabrication.There is presently no complete model of atrial fibrillation(AF) available for studying human pharmacological responses and evaluating the toxicity of potential medication candidates.It has been demonstrated that hiPSC-aCMs can replicate the electrophysiological disease phenotype and genotype of AF.The hiPSC-aCMs,however,are immature and do not reflect the maturity of a CMs in the native myocardium.Numerous laboratories utilize a variety of methodologies and procedures to improve and promote a CM maturation,including electrical stimulation,culture duration,biophysical signals,and changes in metabolic variables.This review covers the current methods being explored for use in the maturation of patient-specific hiPSC-aCMs and their application towards a personalized approach to the pharmacologic therapy of AF. 展开更多
关键词 Atrial fibrillation human-induced pluripotent stem cell-derived atrial cardiomyocytes Disease modeling Maturation Pharmacologic response Personalized medicine
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The Physical Principles Elucidate Numerous Atmospheric Behaviors and Human-Induced Climatic Consequences
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作者 Ernani Sartori 《Open Journal of Applied Sciences》 2012年第4期302-318,共17页
The principles that govern the operation of an open and a closed evaporator are relevant for the understanding of the open and “closed” Earth’s atmospheric behaviors, and are thus described. In these greenhouses, t... The principles that govern the operation of an open and a closed evaporator are relevant for the understanding of the open and “closed” Earth’s atmospheric behaviors, and are thus described. In these greenhouses, the water is included, otherwise the heat and mass balances do not match. It is incorrect to consider the radiation as the only energy transfer factor for an atmospheric warming. Demonstrations show that when the greenhouse effect and the cloud cover increase, the evaporation and the wind naturally decrease. Researchers did not understand why reductions in surface solar radiation and pan evaporation have been simultaneous with increased air temperature, cloudiness and precipitation for the last decades. It is an error to state that the evaporation increases based solely on the water and/or air temperatures increase. Also, researchers did not comprehend why in the last 50 years the clouds and the precipitation increased while the evaporation decreased and they named such understanding as the “evaporation paradox”, while others “found” “the cause” violating the laws of thermodynamics, but more precipitation is naturally conciliatory with less evaporation. The same principle that increases the formation of clouds may cause less rainfall. Several measurements confirm the working principles of greenhouses described in this paper. The hydrological cycle is analyzed and it was also put in form of equation, which analyses have never been done before. The human influence alters the velocity of the natural cycles as well as the atmospheric heat and mass balances, and the evaporation has not been the only source for the cloud formation. It is demonstrated that the Earth’s greenhouse effect has increased in some places and this proof is not based only on temperatures. 展开更多
关键词 Evaporation Clouds Air Water Temperature PARADOX Hydrological Cycle Precipitation Rain Drought Global Warming Radiation Convection Aerosols Greenhouse Effect Wind PARTICULATES Atmosphere Climate human-induced
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Investigations on serviceability control of long-span structures under human-induced excitation 被引量:3
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作者 Chen Xin Ding Youliang +2 位作者 Li Ai-qun Zhang Zhiqiang Sun Peng 《Earthquake Engineering and Engineering Vibration》 SCIE EI CSCD 2012年第1期57-71,共15页
The increasing strength of new structural materials and the span of new structures, accompanied by aesthetic requirements for greater slenderness, are resulting in more applications of long-span structures. In this pa... The increasing strength of new structural materials and the span of new structures, accompanied by aesthetic requirements for greater slenderness, are resulting in more applications of long-span structures. In this paper, serviceability control technology and its design theory are studied. First, a novel tuned mass damper (TMD) with controllable stiffness is developed. Second, methods for modeling human-induced loads are proposed, including standing up, walking, jumping and running, and an analysis method for long-span floor response is proposed based on a finite element model. Third, a design method for long-span floors installed with a multiple TMD (MTMD) system considering human comfort is introduced, largely based on a study of existing literature. Finally, a design, analysis and field test is conducted using several large scale buildings in China including the Beijing Olympic Park National Conference Center, Changsha New Railway Station and the Xi'an Northern Railway Station. The analytical and field test results show that the MTMD system designed using the proposed method is capable of effectively mitigating the vertical vibration of long-span floor structures. The study presented in this paper provides an important reference for the analysis of vibration serviceability of similar long-span floors and design of control system for these structures. 展开更多
关键词 long-span floor vibration control TMD human-inducing loads vibration serviceability
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The impact of human-induced turbulence on indoor thermal environment and pollutant diffusion
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作者 Yu Zhao Chang Xiong +2 位作者 Zhiwen Luo Tareq Hussein Tianyi Zhao 《Building Simulation》 2025年第3期473-497,共25页
Turbulence induced by human movement is thought to affect the dispersion of pollutants in indoor environments.In this study,eight classical crowd scenarios were numerically simulated to investigate the effects of huma... Turbulence induced by human movement is thought to affect the dispersion of pollutants in indoor environments.In this study,eight classical crowd scenarios were numerically simulated to investigate the effects of human movement on indoor air pollution in different scenarios.High-level simulations were performed into human movement,respiration,and heat dissipation,and differential analyses of the simulation results for different flow scenarios were conducted to investigate the interactions between individuals.Research has shown that people walking create significant wake currents within approximately 1.1 m on either side of their path and within 3–4 m behind them.When two pedestrians crossed paths,the wind speed increased significantly to 1.87 m/s compared with a single person walking at 1 m/s.The greatest mutual interference in pollutant distribution occurs when two individual cross paths are perpendicular,with a critical interference distance threshold of 2.87 m.Carbon dioxide concentrations fluctuate,surpassing 1,000 ppm within ten minutes at a density of 1.52 persons per square meter.Additionally,the dispersion of aerosol particles is significantly influenced by the relative direction of movement between individuals and pollutant sources.Calculated“safe distance”to avoid inhalation of exhaled aerosols in short flow exposure scenarios is at least 3.4 m.The personnel wake disturbance intensity was defined based on the rate of change in the velocity amplitude in the personnel wake region,the wake deformation rate,and the dissipation time.These insights can guide improvements in indoor air quality and health risk reduction in densely populated spaces. 展开更多
关键词 human-induced turbulence wind-heat environment carbon dioxide aerosol particles computational fluid dynamics(CFD) pollutant dispersion
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MiR-21-5p-enriched exosomes from hiPSC-derived cardiomyocytes exhibit superior cardiac repair efficacy compared to hiPSC-derived exosomes in a murine MI model
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作者 Jing-Jun Jin Rong-Hua Liu +6 位作者 Jin-Yan Chen Kun Wang Jun-Yong Han Dao-Shun Nie Yu-Qing Gong Bin Lin Guo-Xing Weng 《World Journal of Stem Cells》 2025年第3期81-101,共21页
BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives... BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives offer promising therapeutic options;however,challenges such as low retention,engraftment issues,and tumorigenic risks hinder their clinical utility.Recent focus has shifted to exosomes(exos)-nanoscale vesicles that facilitate intercellular communication-as a safer and more versatile alternative.Understanding the specific mechanisms and comparative efficacy of exos from hiPSCs vs hiPSC-derived cardiomyocytes(hiPSC-CMs)is crucial for advancing cardiac repair therapies.AIM To evaluate and compare the therapeutic efficacy of exos secreted by hiPSCs and hiPSC-CMs in cardiac repair,and to elucidate the role of microRNA 21-5p(miR-21-5p)in the observed effects.METHODS We differentiated hiPSCs into CMs using small molecule methods and characterized the cells and their exos.RESULTS Our findings indicate that hiPSC-CMs and their exos enhanced cardiac function,reduced infarct size,and decreased myocardial fibrosis in a murine myocardial infarction model.Notably,hiPSC-CM exos outperformed hiPSC-CM cell therapy,showing improved ejection fraction and reduced apoptosis.We identified miR-21-5p,a microRNA in hiPSC-CM exos,as crucial for CM survival.Exos with miR-21-5p were absorbed by AC16 cells,suggesting a mechanism for their cytoprotective effects.CONCLUSION Overall,hiPSC-CM exos could serve as a potent therapeutic agent for myocardial repair,laying the groundwork for future research into exos as a treatment for ischemic heart disease. 展开更多
关键词 human-induced pluripotent stem cells human-induced pluripotent stem cell-derived cardiomyocytes Myocardial infarction EXOSOMES MicroRNA 21-5p Apoptosis
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Effects of climate change and human activities on grassland productivity:A case study of the Qinghai Lake Basin,China
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作者 ZHANG Jinlong MA Xiaofang +6 位作者 QI Yuan YANG Rui LI Long ZHANG Juan MA Chao WANG Lu WANG Hongwei 《Journal of Arid Land》 2025年第7期997-1013,共17页
Grassland is a key component of the ecosystem in the Qinghai Lake Basin,China.Understanding the effects of climate change and human activities on grassland productivity significantly improves ecological conservation a... Grassland is a key component of the ecosystem in the Qinghai Lake Basin,China.Understanding the effects of climate change and human activities on grassland productivity significantly improves ecological conservation and promotes sustainable vegetation growth in this area.Based on the net primary productivity(NPP)products of MOD17A3HGF(a moderate-resolution imaging spectroradiometer(MODIS)product that provides annual NPP at 500 m resolution)and meteorological data,we analyzed the spatial and temporal evolution of grassland NPP and its interaction with climate factors in the Qinghai Lake Basin from 2001 to 2022 via partial correlation and trend analysis methods.We also used the deflecting trend residual method and scenario analysis method to quantitatively assess the relative contributions of climatic factors and human activities to grassland NPP.The results revealed that:(1)during the past 22 a,grassland NPP increased considerably,with a gradient change from the northwest to the southeast of the study area;(2)sunshine duration,precipitation,and temperature positively influenced grassland NPP,with sunshine duration exerting a stronger effect on grassland NPP than precipitation and temperature;and(3)98.47%of the grassland in the study area was restored,with an average contribution of 65.00%from human activities and 35.00%from climatic alterations.Compared with climate change,human-induced factors had a greater effect on grassland NPP in this area.The results of the study not only provide important scientific support for ecological restoration and sustainable development of the basin but also offer new ideas for research on similar ecologically fragile areas. 展开更多
关键词 ecological conservation human-induced factors net primary productivity PRECIPITATION TEMPERATURE
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Soil Drainage as an Active Agent of Recent Soil Evolution: A Review 被引量:3
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作者 D. MONTAGNE S. CORNU +1 位作者 L. LE FORESTIER I. COUSIN 《Pedosphere》 SCIE CAS CSCD 2009年第1期1-13,共13页
While research on pedogenesis mainly focuses on long-term soil formation and most often neglects recent soil evolution in response to human practices or climate changes, this article reviews the impact of artificial s... While research on pedogenesis mainly focuses on long-term soil formation and most often neglects recent soil evolution in response to human practices or climate changes, this article reviews the impact of artificial subsurface drainage on soil evolution. Artificial drainage is considered as an example of the impact of recent changes in water fluxes on soil evolution over time scales of decades to a century. Results from various classical studies on artificial drainage including hydrological and environmental studies are reviewed and collated with rare studies dealing explicitly with soil morphology changes, in response to artificial drainage. We deduce that soil should react to the perturbations associated with subsurface drainage over time scales that do not exceeding a few decades. Subsurface drainage decreases the intensity of erosion and must i) increase the intensity of the lixiviation and eluviation processes, ii) affect iron and manganese dynamics, and iii) induce heterogeneities in soil evolution at the ten meter scale. Such recent soil evolutions can no longer be neglected as they are mostly irreversible and will probably have unknown, but expectable, feedbacks on crucial soil functions such as the sequestration of soil organic matter or the water available capacity. 展开更多
关键词 CULTIVATION human-induced soil evolution PEDOGENESIS soil processes subsurface drainage
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Influence of anthropogenic activities on landslide susceptibility:A case study in Solan district,Himachal Pradesh,India 被引量:1
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作者 Sangeeta S.K.SINGH 《Journal of Mountain Science》 SCIE CSCD 2023年第2期429-447,共19页
Landslides in the Himalayan region are primarily controlled by natural parameters,including rainfall,seismic activity,and anthropogenic parameters,such as the construction of large-scale projects like road development... Landslides in the Himalayan region are primarily controlled by natural parameters,including rainfall,seismic activity,and anthropogenic parameters,such as the construction of large-scale projects like road development,tunneling and hydroelectric power projects and climate change.The parameters which are more crucial among these are a matter of scientific study and analysis.This research,taking Solan district,Himachal Pradesh,India,as the study area,aims to assess the impact of anthropogenic activities on landslide susceptibility at a regional scale.Landslide distribution was characterized into two groups,namely Rainfall-Induced Landslide(RIL)and Human-Induced Landslide(HIL)based on triggering factors.Multiple data such as slope angle,aspect,profile curvature,distance to drainage,distance to lineament,lithology,distance to road,normalized difference vegetation index(NDVI)and land use land cover(LULC)have been considered for delineating the landslide susceptibility zonation(LSZ)map.The effect of anthropogenic activities on landslide occurrences has been examined through the distribution of landslides along national highways and land use land cover changes(LULCC).Two sets of LSZ maps with a LULC of time interval covering five years(2017&2021)were prepared to compare the temporal progression of LULC and landslide susceptibility during the five years.The results indicated the significant impact of anthropogenic activities on the landslide susceptibility.LSZ map of the year 2021 shows that 23%area falls into high and very high susceptible classes and 48%area falls into very low and low susceptibility classes.Compared to LSZ map of 2017,high and very high susceptible classes have been increased by 15%,whereas very low and low susceptible classes have been reduced by 7%.The present case study will help to understand the potential driving parameters responsible for HIL and also suggest the inclusion of LULC in landslide susceptibility analysis.The study will demonstrate new opportunities for research that could help decision-makers prepare for future disasters,both in the Indian Himalayan region and other areas. 展开更多
关键词 LANDSLIDE ANTHROPOGENIC human-induced Landslide(HIL) Rainfall-Induced Landslide(RIL)
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The road to opportunities: landscape change promotes body-size divergence in a highly mobile species
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作者 Carlos CAMACHO Pedro SAEZ +3 位作者 Sonia SANCHEZ Sebastian PALACIOS Carlos MOLINA Jaime POTTI 《Current Zoology》 SCIE CAS CSCD 2016年第1期7-14,共8页
Landscape change provides a suitable framework for investigating population-level responses to novel ecological pressures. However, relatively little attention has been paid to examine the poten- tial influence of lan... Landscape change provides a suitable framework for investigating population-level responses to novel ecological pressures. However, relatively little attention has been paid to examine the poten- tial influence of landscape change on the geographic scale of population differentiation. Here, we tested for morphological differentiation of red-necked nightjars Caprimulgus ruficollis breeding in a managed property and a natural reserve situated less than 10 km apart. At both sites, we also esti- mated site fidelity over 5 years and quantified the potential foraging opportunities for nightjars. Breeding birds in the managed habitat were significantly larger in size--as indexed by keel length--than those in the natural one. However, there were no significant differences in wing or tail length. Immigration from neighboring areas was almost negligible and, furthermore, no individual (out of 1130 captures overall) exchanged habitats between years, indicating strong site fidelity. Food supply for nightjars was equally abundant in both habitats, but the availability of foraging sites was remarkably higher in the managed property. As a result, nightjars--particularly fledg- lings-in the latter habitat benefited from increased foraging opportunities in relation to those in the natural site. It seems likely that the fine-scale variation in nightjar morphology reflects a pheno- typic response to unequal local conditions, since non-random dispersal or differential mortality had been determined not to be influential. High site fidelity appears to contribute to the mainten- ance of body-size differences between the two habitats. Results from this nightjar population high- light the potential of human-induced landscape change to promote population-level responses at exceedingly small geographic scales. 展开更多
关键词 human-induced environmental change morphology phenotypic divergence PHILOPATRY population differentiation.
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Dynamic characteristics of the coupled system of footbridge and human
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作者 牛少华 高世桥 +2 位作者 王栋 KASPERSKI M AGU E 《Journal of Beijing Institute of Technology》 EI CAS 2013年第3期285-290,共6页
The influence of human body on dynamic characteristics of footbridge was analyzed. A re- alistic footbridge was measured during a mass event. A simulation experiment system including a simple beam as object and a shak... The influence of human body on dynamic characteristics of footbridge was analyzed. A re- alistic footbridge was measured during a mass event. A simulation experiment system including a simple beam as object and a shaker as back ground excitation was built. The acceleration responses of beam were measured when person in static and active stated stood on the beam. The dynamic pa- rameters of the structure were identified by the time-domain approach and verified by theoretical and laboratory tests. The results showed that for the human-structure coupled system, nature frequency of the structure decreased and damping increased. Moreover, the increase of damping with passive person was bigger than that with active person. 展开更多
关键词 human-induced loads dynamic parameters human-structure interaction coupled sys-tem linear-sweep
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Depletion of Forest Resources and Wildlife Population with Habitat Complexity: A Mathematical Model
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作者 Rachana Pathak 《Open Journal of Ecology》 2018年第11期579-589,共11页
Nowadays, management and regulation of natural resources like agriculture, fisheries, forestry and wildlife is one of the popular topics in research. The evolution of humankind is largely dependent on the quality of t... Nowadays, management and regulation of natural resources like agriculture, fisheries, forestry and wildlife is one of the popular topics in research. The evolution of humankind is largely dependent on the quality of the environment and the resources it provides;but numerous human-induced factors, and climate change may drastically alter the conditions of human sustainability. This paper deals with effect of numerous human-induced activities on the depletion of forestry resources and wildlife population with habitat complexity. A nonlinear mathematical model is proposed and analyzed. In modeling process, we assume that the growth rate of wildlife population wholly depends on forestry biomass. It is depleted by human-induced activities. Local stability analysis of the mathematical model along with the persistence of the system is checked by using theory of nonlinear ordinary differential equations and Butler-McGhee lemma. Analytical results obtained are justified numerically through numerical simulation. Important parameters are investigated and variation of variables with change in these parameters is determined. 展开更多
关键词 FORESTRY BIOMASS Depletion WILDLIFE POPULATION human-induced ACTIVITIES Stability PERSISTENCE
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Skin organoid transplantation promotes tissue repair with scarless in frostbite 被引量:2
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作者 Wenwen Wang Pu Liu +6 位作者 Wendi Zhu Tianwei Li Ying Wang Yujie Wang Jun Li Jie Ma Ling Leng 《Protein & Cell》 2025年第4期239-258,共20页
Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to s... Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell(hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix(ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite. 展开更多
关键词 skin frostbite frostbite treatment human-induced pluripotent stem cell skin organoids single-cell transcriptomics
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