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Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcription factor ATF7 in innate immunological memory. ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages by recruiting the histone H3K9 dimethyltransferase G9a. Treatment with lipopolysaccharide, which mimics bacterial infection, induced phosphorylation of ATF7 via the kinase p38, which led to the release of ATF7 from chromatin and a decrease in repressive histone H3K9me2 marks. A partially disrupted chromatin structure and increased basal expression of target genes were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.
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Factores de Transcripción Activadores/metabolismo , Epigénesis Genética/inmunología , Memoria Inmunológica/genética , Memoria Inmunológica/inmunología , Macrófagos/inmunología , Factores de Transcripción Activadores/genética , Animales , Epigénesis Genética/efectos de los fármacos , Lipopolisacáridos/farmacología , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is mainly inhibited during short term abscisic acid (ABA) treatment, and dynamically changed in prolonged treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 could prevent the nuclear localization of ZmCPK2 through phosphorylation of ZmCPK2T60. ZmCPK2 interacts with and phosphorylates and activates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded directly by ZmCPK17 that inhibits ZmCPK2, thereby promoting plant adaptation to water deficit.
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Ácido Abscísico , Calcio , Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Proteínas Quinasas , Zea mays , Zea mays/efectos de los fármacos , Zea mays/metabolismo , Zea mays/genética , Zea mays/fisiología , Calcio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Fosforilación , Proteínas Quinasas/metabolismo , Plantas Modificadas Genéticamente , Estrés Fisiológico/efectos de los fármacos , Unión Proteica/efectos de los fármacosRESUMEN
The phytohormone abscisic acid (ABA) and the Polycomb group proteins have key roles in regulating plant growth and development; however, their interplay and underlying mechanisms are not fully understood. Here, we identified an Arabidopsis (Arabidopsis thaliana) nodulin homeobox (AtNDX) protein as a negative regulator in the ABA signaling pathway. AtNDX mutants are hypersensitive to ABA, as measured by inhibition of seed germination and root growth, and the expression of AtNDX is downregulated by ABA. AtNDX interacts with the Polycomb Repressive Complex1 (PRC1) core components AtRING1A and AtRING1B in vitro and in vivo, and together, they negatively regulate the expression levels of some ABA-responsive genes. We identified ABA-INSENSITIVE (ABI4) as a direct target of AtNDX. AtNDX directly binds the downstream region of ABI4 and deleting this region increases the ABA sensitivity of primary root growth. Furthermore, ABI4 mutations rescue the ABA-hypersensitive phenotypes of ndx mutants and ABI4-overexpressing plants are hypersensitive to ABA in primary root growth. Thus, our work reveals the critical functions of AtNDX and PRC1 in some ABA-mediated processes and their regulation of ABI4.
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Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Plantas/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Transducción de Señal , Ácido Abscísico/farmacología , Arabidopsis/efectos de los fármacos , Proteínas de Arabidopsis/genética , Secuencia de Bases , Proteínas Portadoras/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Germinación/efectos de los fármacos , Proteínas de Homeodominio/genética , Modelos Biológicos , Mutación/genética , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Complejo Represivo Polycomb 1/genética , Unión Proteica/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Transducción de Señal/efectos de los fármacosRESUMEN
Asherman's syndrome (AS) occurs as a consequence of severe damage to the endometrial basalis, usually leading to menstrual abnormalities, infertility, and recurrent miscarriage in women. Currently, human endometrium-derived adventitial cells (En-ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En-ADV spheroid-loaded hierarchical microneedles (MN/En-ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En-ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN/En-ADV, the repaired uteri show well-defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN/En-ADV can be an ideal candidate for versatile in situ tissue regeneration.
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Antiinfecciosos , Ginatresia , Regeneración , Útero , Animales , Antiinfecciosos/farmacología , Endometrio/crecimiento & desarrollo , Femenino , Gelatina , Ginatresia/terapia , Humanos , Metacrilatos , Ratas , Útero/crecimiento & desarrolloRESUMEN
Drug metabolism in the intestine is considered to substantially contribute to the overall first-pass metabolism, which has been neglected for a long time. It is highly desirable to develop a reliable model to evaluate drug metabolism in the intestine in vitro. In this work, we made the first attempt to develop a biomimetic human gut-on-a-chip for modeling drug metabolism in intestine. In this chip, constant flow, together with porous nitrocellulose membrane and collagen I, mimics an in vivo-like intestinal microenvironment. The Caco-2 cells grown in the chip formed a compact intestinal epithelial layer with continuous expression of the tight junction protein, ZO-1. Furthermore, higher gene expression of villin, sucrase-isomaltase, and alkaline phosphatase demonstrated that cells in the biomimetic human gut-on-a-chip device were more mature with near-physiological functions compared to the control on planar substrate. In particular, cellular metabolic activity was assessed on different substrates, indicating higher metabolic efficiency of ifosfamide and verapamil in the biomimetic human gut-on-a-chip model. Taken together, our results suggested that this biomimetic human gut-on-a-chip promoted the differentiation of intestinal cells with enhanced functionality by creating a biomimetic 3D microenvironment in vitro. It might offer a bioactive, low-cost, and flexible in vitro platform for studies on intestinal metabolism as well as preclinical drug development.
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Mucosa Intestinal/metabolismo , Dispositivos Laboratorio en un Chip , Preparaciones Farmacéuticas/metabolismo , Biomimética , Células CACO-2 , Expresión Génica , Humanos , Ifosfamida/metabolismo , Verapamilo/metabolismoRESUMEN
Multiple hormones, including abscisic acid (ABA) and auxin, regulate cell division and differentiation of Arabidopsis root meristems. AUXIN RESPONSE FACTOR 2 (ARF2) functions as a negative regulator of ABA responses, as seed germination and primary root growth of arf2 mutants are hypersensitive to ABA. In this study, we found that ABA treatment reduced the expression levels of the PIN-FORMEDs (PIN) auxin efflux carriers, PIN1, PIN3, PIN4, and PIN7, to a greater extent in the root meristems of arf2-101 mutant than in the wild type. Also, arf2-101 pin1 and arf2-101 pin4 double mutants show less ABA-induced inhibition of root meristem activity than the arf2-101 mutants. Furthermore, ARF2 positively mediates the transcripts of transcription factor PLETHORA 1 (PLT1) gene but negatively mediates PLT2 at protein level in root meristems. Using a dexamethasone (DEX)-inducible transgenic line, Pro35S:PLT2-GR, we showed that PLT2 greatly promotes cell division and completely inhibits cell differentiation in root meristems of the arf2-101 mutant once PLT2 is induced by DEX, which can be partially reversed by ABA treatment, suggesting that ABA regulates root meristem activity in both ARF2-dependent and independent pathways. Our results uncover a complex regulatory architecture in which ARF2 coordinates with PLTs and PINs to orchestrate ABA-mediated regulation of root meristem activity in Arabidopsis.
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Ácido Abscísico/farmacología , Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Meristema/crecimiento & desarrollo , Proteínas Represoras/metabolismo , Arabidopsis/citología , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Proteínas Fluorescentes Verdes/metabolismo , Meristema/citología , Meristema/efectos de los fármacos , Meristema/metabolismo , Mutación/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Acute lung injury (ALI) is a lethal disease with high mortality rate, and its physiologically relevant models that could mimic human disease processes are urgently needed to study pathophysiology and predict drug efficacy. Here, this work presents a novel lipopolysaccharide (LPS) based ALI model on a microfluidic chip that reconstitutes an air-liquid interface lined by human alveolar epithelium and microvascular endothelium for screening the therapeutic effects of mesenchymal stem cells (MSC) derived extracellular vesicles (MSC-EVs) to the biomimetic ALI. The air-liquid interface is established by coculture of alveolar epithelium and microvascular endothelium on the opposite sides of the porous membrane. The functionalized architecture is characterized by integrate cell layers and suitable permeability. Using this biomimetic microsystem, LPS based ALI model is established, which exhibits the disrupted alveolar-capillary barrier, reduced transepithelial/transendothelial electrical resistance (TEER), and impaired expression of junction proteins. As a reliable disease model, this work examines the effects of MSC-EVs, and the data indicate the therapeutic potential of EVs for severe ALI. MSC-EVs can alleviate barrier disruption by restoring both the epithelial and endothelial barrier integrity. They hope this study can become a unique approach to study human pathophysiology of ALI and advance drug development.
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Lesión Pulmonar Aguda , Células Madre Mesenquimatosas , Animales , Humanos , Lipopolisacáridos , Modelos Animales de Enfermedad , Lesión Pulmonar Aguda/metabolismo , Dispositivos Laboratorio en un ChipRESUMEN
Aging is an inevitable and complex biological process involving multi-factorial mechanisms. Mitochondrial dysfunction is a critical factor in the aging process, characterized by a decline in mitochondrial quality and activity, leading to aging and aging-related diseases. Therefore, mitochondria have become an attractive target in anti-aging therapies. Several senolytic drugs targeting mitochondria and antioxidant agents have been used in anti-aging research in the past few years. However, these strategies may cause adverse effects with long-term medication. In this extensive review, we propose "mitochondrial transplantation," which transfers healthy mitochondria from donor cells to recipient cells to replace damaged or dysfunctional mitochondria, as a new alternative strategy for treating mitochondrial dysfunction and aging-associated diseases. In this review, we introduce the contemporary landscape of mitochondrial transplantation, then discuss intensely the successful applications of mitochondrial transplantation therapy in aging diseases such as neurodegenerative diseases, cardiovascular aging, and reproductive aging, highlighting its translational potential. Finally, we summarize and prospect the challenges and opportunities mitochondrial transplantation faces in anti-aging therapy.
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Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have shown applied values in the recovery of ovarian function. Here, a novel exosome-encapsulated microcarrier prepared by microfluidic technology for ovarian repair after chemotherapy damage is presented. The exosomes derived from lipopolysaccharide (LPS)-preconditioned hUC-MSCs are encapsulated with hyaluronic acid methacryloyl (HAMA) via microfluidic electrospray, which is named HAMA/MSC-Exos. Attributing to the biocompatibility and semipermeable property of HAMA, the encapsulated exosomes show great viability and controllable release behavior from HAMA. It is demonstrated that in situ transplantation of HAMA/MSC-Exos can rescue ovarian functions of cyclophosphamide-induced ovarian failure in mice by increasing ovarian volume, improving the number of antral follicles and restoring fertility. It is believed that the transplantation of HAMA/MSC-Exos will provide a new concept for the treatment of POF in clinical practice.
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Exosomas , Células Madre Mesenquimatosas , Humanos , Animales , Ratones , Ácido Hialurónico/farmacología , Lipopolisacáridos/farmacología , MicrofluídicaRESUMEN
The placenta is an essential organ that maintains the health of both the fetus and its mother. Understanding the development of human placenta has been hindered by the limitations of existing animal models and monolayer cell cultures. Models that can recapitulate the essential aspects of human placental multicellular components and vasculature are still lacking. Herein, we presented a new strategy to establish placenta-like organoids with vascular-like structures from human-induced pluripotent stem cells in a defined three-dimensional (3D) culture system. The resulting placenta-like tissue resembles first-trimester human placental development in terms of complex placental components and secretory function. The multicellular tissue was characterized by the inclusion of trophoblasts (cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, and other endogenous vascular cells), which were identified by immunofluorescence, flow cytometry analyses, real-time quantitative reverse transcription polymerase chain reaction and single-cell RNA-seq. Moreover, the 3D tissue was able to secrete the placenta-specific hormone human chorionic gonadotropin ß (hCG-ß) and vascular endothelial growth factor A (VEGFA). The tissue responded to the inflammatory factor tumor necrosis factor-α (TNF-α) and VEGF receptor inhibitors. This new model system can represent the major features of placental cellular components, and function, which have not been realized in 2D monolayer cultures. The developed tissue system might open new avenues for studying normal early human placental development and its disease states.
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Brain assembloids offer a highly promising strategy to model human brain development and disease, and advance potential studies in regenerative medicine, therapeutic screening, and drug discovery, while it is challenging to produce uniform brain organoids and assemble them flexibly by conventional methods. Here, a multidisciplinary engineered strategy to generate human brain assembloids with desired patterning based on microfluidic technology is presented. By encapsulating human induced pluripotent stem cells in microcapsules via microfluidic electrospray, brain region-specific organoids are efficiently formed, which are then introduced into a microfluidic chip consisting of a bottom layer with a micropillar array and a movable upper layer with a complementary microhole array. These brain organoids can settle into microholes and fuse into brain assembloids. As varied organoid microcapsules with designed 1D sequences or 2D arrays can be assembled into the vertical microholes, large coding amounts of fused brain assembloids with desired patterning can be produced. It is found that brain assembloids composed of cortical, hippocampal, and thalamic organoids can grow and function well, characterized with active neural migration and interaction. These features indicate that the suggested flexible, scalable, and controlled microfluidic systems are remarkably potential in wide applications of brain assembloids in neurological and biomedical fields.
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Células Madre Pluripotentes Inducidas , Microfluídica , Humanos , Cápsulas , Encéfalo , OrganoidesRESUMEN
As a promising new micro-physiological system, organ-on-a-chip has been widely utilized for in vitro pharmaceutical study and tissues engineering based on the three-dimensional constructions of tissues/organs and delicate replication of in vivo-like microenvironment. To better observe the biological processes, a variety of sensors have been integrated to realize in-situ, real-time, and sensitive monitoring of critical signals for organs development and disease modeling. Herein, we discuss the recent research advances made with respect to sensors-integrated organ-on-a-chip in this overall review. Firstly, we briefly explore the underlying fabrication procedures of sensors within microfluidic platforms and several classifications of sensory principles. Then, emphasis is put on the highlighted applications of different types of organ-on-a-chip incorporated with various sensors. Last but not least, perspective on the remaining challenges and future development of sensors-integrated organ-on-a-chip are presented.
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Alveolar microenvironmental models are important for studying the basic biology of the alveolus, therapeutic trials, and drug testing. However, a few systems can fully reproduce the in vivo alveolar microenvironment including dynamic stretching and the cell-cell interface. Here, a novel biomimetic alveolus-on-a-chip microsystem is presented suitable for visualizing physiological breathing for simulating the 3D architecture and function of human pulmonary alveoli. This biomimetic microsystem contains an inverse opal structured polyurethane membrane that achieves real-time observation of mechanical stretching. In this microsystem, the alveolar-capillary barrier is created by alveolar type 2 (ATII) cells cocultured with vascular endothelial cells (ECs) on this membrane. Based on this microsystem, the phenomena of flattening and the tendency of differentiation in ATII cells are observed. The synergistic effects of mechanical stretching and ECs on the proliferation of ATII cells are also observed during the repair process following lung injury. These features indicate the potential of this novel biomimetic microsystem for exploring the mechanisms of lung diseases, which can provide future guidance concerning drug targets for clinical therapies.
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Biomimética , Células Endoteliales , Humanos , Alveolos Pulmonares/fisiología , Pulmón , Técnicas de CocultivoRESUMEN
Cortical organoids represent cutting-edge models for mimic human brain development during the early and even middle stage of pregnancy, while they often fail to recreate the complex microenvironmental factors, such as physiological hypoxia. Herein, to recapitulate fetal brain development, we propose a novel cortical organoid-on-a-chip with physiological hypoxia and further explore the effects of tanshinone IIA (Tan IIA) in neural differentiation. The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.
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Excessive bone resorption due to increased inflammatory factors is a common feature of inflammatory lytic bone diseases. This group of diseases is effectively treated with drugs. In recent years, many studies have reported that traditional Chinese medicine herbs have substantial effects on inflammation, osteoclast differentiation and maturation, and bone destruction. Herein, we investigated the effects of osthole (OST) on lipopolysaccharide- (LPS-) induced macrophage polarization, inflammatory responses, and osteolysis. In vitro, we used immunofluorescence and quantitative real-time polymerase chain reaction assays to confirm whether bone marrow-derived macrophages showed an increased expression of inflammatory factors, such as interleukin-6, iNOS, CCR7, and CD86, in the presence of LPS. However, we found that such expression was suppressed and that the M2 macrophage expression increased in the presence of OST. OST reduced LPS- and RANKL-induced intracellular reactive oxygen species production in the bone marrow-derived macrophages. Further, it potently suppressed osteoclast differentiation and osteoclast-specific gene expression by suppressing the P38/MAPK and NF-κB pathways. Consistent with the in vitro observations, OST greatly ameliorated LPS-induced bone resorption and modulated the ratio of macrophages at the site of osteolysis. Taken together, OST has great potential for use in the management of osteolytic diseases.
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Resorción Ósea , Osteólisis , Animales , Ratones , Osteólisis/tratamiento farmacológico , Lipopolisacáridos/efectos adversos , Macrófagos/metabolismo , Osteoclastos/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Cráneo/metabolismo , FN-kappa B/metabolismo , Ligando RANK/metabolismo , Diferenciación Celular , Osteogénesis , Ratones Endogámicos C57BLRESUMEN
CDA-II (cell differentiation agent II), isolated from healthy human urine, is a DNA methyltransferase inhibitor. Previous studies indicated that CDA-II played important roles in the regulation of cell growth and certain differentiation processes. However, it has not been determined whether CDA-II affects skeletal myogenesis. In this study, we investigated effects of CDA-II treatment on skeletal muscle progenitor cell differentiation, migration and proliferation. We found that CDA-II blocked differentiation of murine myoblasts C2C12 in a dose-dependent manner. CDA-II repressed expression of muscle transcription factors, such as Myogenin and Mef2c, and structural proteins, such as myosin heavy chain (Myh3), light chain (Mylpf) and MCK. Moreover, CDA-II inhibited C1C12 cell migration and proliferation. Thus, our data provide the first evidence that CDA-II inhibits growth and differentiation of muscle progenitor cells, suggesting that the use of CDA-II might affect skeletal muscle functions.
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Diferenciación Celular/efectos de los fármacos , Metilasas de Modificación del ADN/antagonistas & inhibidores , Desarrollo de Músculos/efectos de los fármacos , Mioblastos Esqueléticos/efectos de los fármacos , Mioblastos/efectos de los fármacos , Péptidos/farmacología , Fenilacetatos/farmacología , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Factores de Transcripción MEF2 , Ratones , Desarrollo de Músculos/genética , Mioblastos/citología , Mioblastos/inmunología , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/enzimología , Factores Reguladores Miogénicos/antagonistas & inhibidores , Miogenina/antagonistas & inhibidores , Cadenas Pesadas de Miosina/antagonistas & inhibidoresRESUMEN
With the popularity of Internet technology, reading has developed in the direction of digitalization and mobileization. And entering the metaverse era, both the subject and object of reading may be redefined, presenting a new developmental pattern. This process brings a crisis to reading, such as the fragmentation of reading, the obstruction of reading needs, and the replacement of classical reading. However, reading is still an important way for college students to acquire new knowledge, broaden their horizons and improve their skills. The existence of reading crises inevitably affects the academic achievement of college students. Therefore, from the perspective of university management, this paper conducts regression analysis on 1,155 effective samples of colleges and universities in Anhui Province, extracts the factors that affect college students' reading engagement, and further explores the relationship between college students' reading engagement and academic achievement. The study concluded that: (1) in terms of family reading culture, students who grow up in families with good family reading culture perform better in reading engagement. The amount of family books, family reading education and family reading atmosphere all have significant positive effects on reading time and reflective reading strategies of college students. (2) In the cultivation of reading habits in colleges and universities, the course-driven mechanism and the atmosphere stimulating mechanism have a significant positive effect on students' reading time. The course-driven mechanism, resource supporting mechanism and atmosphere stimulating mechanism have a significant positive effect on the critical reading strategy of college students. (3) In terms of reading time, it is only found that the reading time spent on paper books has a significant positive effect on college students' academic achievement and professional quality. (4) In terms of reading strategies, the replicative reading strategy only has a significant positive effect on the improvement of college students' academic achievement and professional quality. The critical reading strategy has a significant positive effect on the professional quality, general ability and career planning ability of college students.
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Skin flap transplantations are common methods for covering and repairing tissue defects in surgery, while the survival rates of these skin flaps are still low due to the vascular crisis and necrosis. To improve this situation, herein a novel biohybrid scaffold is proposed by integrating the advantages of anisotropic fish scales and mesenchymal stem cells (MSCs) for skin flap regeneration. The fish scale scaffold is obtained through its decellularization and decalcification processes, which reserved intact collagen, glycosaminoglycan, and other endogenous growth factors for MSCs and human vascular endothelial cells proliferation. As the scaffold maintains intrinsic anisotropic structures on both surfaces, the proliferative cells can be elongated along the aligned structures on the fish scale, which endow them the capacity to differentiate into multiple directions. Based on these features, it is demonstrated from an in vivo experiment that the MSCs-loading fish scale scaffolds can effectively convert the activated inflammatory macrophages into anti-inflammatory properties, reduce the inflammation around the flap, and improve the survival rate. These results indicate that the MSCs-loading fish scale scaffold is suitable and has the potential for skin flap regeneration and functional recovery.
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Células Madre Mesenquimatosas , Ingeniería de Tejidos , Andamios del Tejido , Animales , Colágeno , Células Endoteliales/metabolismo , Proteínas de Peces/química , Humanos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Cicatrización de HeridasRESUMEN
Infertility is a rising global health issue with a far-reaching impact on the socioeconomic livelihoods. As there are highly complex causes of male and female infertility, it is highly desired to promote and maintain reproductive health by the integration of advanced technologies. Biomedical engineering, a mature technology applied in the fields of biology and health care, has emerged as a powerful tool in the diagnosis and treatment of infertility. Nowadays, various promising biomedical engineering approaches are under investigation to address human infertility. Biomedical engineering approaches can not only improve our fundamental understanding of sperm and follicle development in bioengineered devices combined with microfabrication, biomaterials, and relevant cells, but also be applied to repair uterine, ovary, and cervicovaginal tissues and restore tissue function. Here, we introduce the infertility in male and female and provide a comprehensive summary of the various promising biomedical engineering technologies and their applications in reproductive medicine. Also, the challenges and prospects of biomedical engineering technologies for clinical transformation are discussed. We believe that this review will promote communications between engineers, biologists, and clinicians and potentially contribute to the clinical transformation of these innovative research works in the immediate future.
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Non-obstructive coronary artery disease (CAD), which is defined as coronary stenosis <50%, has been increasingly recognized as an emerging entity in clinical practice. Vasomotion abnormality and coronary microvascular dysfunction are two major mechanisms contributing to the occur of angina with non-obstructive CAD. Although routine coronary functional assessment is limited due to several disadvantages, functional evaluation can help to understand the pathophysiological mechanism and/or to exclude specific etiologies. In this review, we summarized the potential mechanisms involved in ischemia with non-obstructive coronary arteries (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA), the two major form of non-obstructive CAD. Additionally, we reviewed currently available functional assessment indices and their use in non-obstructive CAD. Furthermore, we speculated that novel technique combined anatomic and physiologic parameters might provide more individualized therapeutic choice for patients with non-obstructive CAD.