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Head and neck epithelial tissue tumors may be identified as head and neck squamous cell carcinoma (HNSC). Numerous malignancies are encouraged by dysregulation of the FGF19-ß-Klotho (KLB) axis in the tumor microenvironment. Using protein databases and RT-qPCR, we examined KLB expression in HNSC. In HNSC, higher KLB expression was linked to longer survival times and better prognoses. Furthermore, variations in drug susceptibility and immunological infiltration were noted according to KLB expression levels. These results underscore the importance of KLB in the course and management of HNSC by indicating that it may function as a possible prognostic marker and influence immunological and therapeutic responses in these individuals. Further study on HNSC is necessary to investigate KLB's potential as a therapeutic target and prognostic indicator.
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Neoplasias de Cabeza y Cuello , Proteínas Klotho , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Proteínas Klotho/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Masculino , Persona de Mediana Edad , Anciano , Regulación Neoplásica de la Expresión Génica , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologíaRESUMEN
Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.
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Background: Telerehabilitation provide distant physical rehabilitation services and help overcome the barriers associated with face-to-face interventions for hip fractures. This study aims to analyse the progress of the application of telerehabilitation in hip fracture and reveal its research profile, hotspots and development trends. Methods: The articles and reviews related to telerehabilitation in hip fracture were retrieved from 1992 to 2024. A bibliometric visualization and comparative analysis of countries, institutions, journals, authors, references and keywords were conducted using Java-based CiteSpace and VOSviewer. Results: A total of 79 documents were obtained. Spain was the most academically influential country. The University of Granada was the most prolific institution. The author Ariza-vega P listed first in terms of publications and citations. Most publications were published in high academic impact journals. The major frontier keywords were "older adults," "functional recovery," "reliability," "mortality," "rehabilitation," "mobility" and "quality of life." The most popular keywords from 2020 to 2024 were "geriatric medicine," "family caregiver" and "digital health." Conclusions: The historical and prospective perspective in telerehabilitation following hip fracture were presented. A primary focus in the early years was the impact of telerehabilitation on functional independence for hip fracture patients. Future outcomes are expected to include patient satisfaction, health-related quality of life and psychiatric symptoms. Exercise was also designed to eliminate travel burdens and strengthen self-efficacy, and improve the physical and psychosocial function of hip fracture patients. This work will provide a fundamental reference as well as a directional guide for future research.
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CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.
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Cromatina , Desarrollo Embrionario , Animales , Ratones , Sitios de Unión , Blastocisto/metabolismo , Cromatina/metabolismo , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Mamíferos , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Cigoto/metabolismoRESUMEN
Objectives: To examine the 16-year developmental history, research hotspots, and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics. Methods: The literature on zinc-based biodegradable metallic materials in WoSCC was searched. Historical characteristics, the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite. Results: Over the past 16 years, the field of zinc-based biodegradable metal materials has remained in a hotspot stage, with extensive scientific collaboration. In addition, there are 45 subject categories and 51 keywords in different research periods, and 80 papers experience citation bursts. Keyword clustering anchored 3 emerging research subfields, namely, #1 plastic deformation #4 additive manufacturing #5 surface modification. The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property, microstructure, corrosion behavior, etc., and emerging keywords are additive manufacturing, surface modification, dynamic recrystallization, etc. The most recent research on reference clustering has six subfields. Namely, #0 microstructure, #2 sem, #3 additive manufacturing, #4 laser powder bed fusion, #5 implant, and #7 Zn-1Mg. Conclusion: The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials, which can help researchers identify hot spots and explore new research directions in the field.
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Mechanobiology focuses on a series of important physiopathological processes, such as how cells perceive different mechanomechanical stimuli, the process of intracellular mechanotransduction, and how mechanical signals determine the behavior and fate of cells. From the initial stage of embryogenesis, to developmental biology and regenerative medicine, or even through the whole life process, mechanical signaling cascades and cellular mechanical responses in mechanobiology are of great significance in biomedical research. In recent years, research in the field of mechanobiology has undergone remarkable development. Several scientific consortia around the world have been analyzing mechanobiological processes from different perspectives, aiming to gain insights into the regulatory mechanisms by which mechanical factors affect cell fate determination. In this article, we summarized and reviewed the topics that have attracted more research interests in recent years in the field of mechanobiology, for example, arterial blood vessels, stem cell, and ion channel. We also discussed the potential trends that may emerge, such as nuclear deformation, fibrous extracellular matrix, tumor mechanobiology, cellular mechanotransduction, and piezo ion channels. In addition, we put forward new ideas concerning the limitations of mechanism research and the importance of big data analysis and mining in this field, thereby providing objective support and a systematic framework for grasping the hot research topics and exploring new research directions in the field of mechanobiology.
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Mecanotransducción Celular , Transducción de Señal , Mecanotransducción Celular/fisiología , Canales Iónicos/metabolismo , Matriz Extracelular/metabolismo , BiofisicaRESUMEN
Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide. Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells, and it plays an important role in gene regulation of pro-inflammatory, pro-thrombotic, pro-oxidative stress, and cell permeability. Many important endothelial cell mechanosensitive genes have been discovered, including KLK10, CCN gene family, NRP2, YAP, TAZ, HIF-1α, NF-κB, FOS, JUN, TFEB, KLF2/KLF4, NRF2, and ID1. Some of them have been intensively studied, whereas the relevant regulatory mechanism of other genes remains unclear. Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease. Thus, this article reviews the mechanosensitive genes affecting vascular endothelial cells, including classical pathways and some newly screened genes, and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights for anti-atherosclerosis.
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The utilization of nanomaterials in the biosensor field has garnered substantial attention in recent years. Initially, the emphasis was on enhancing the sensor current rather than material interactions. However, carbon nanotubes (CNTs) have gained prominence in glucose sensors due to their high aspect ratio, remarkable chemical stability, and notable optical and electronic attributes. The diverse nanostructures and metal surface designs of CNTs, coupled with their exceptional physical and chemical properties, have led to diverse applications in electrochemical glucose sensor research. Substantial progress has been achieved, particularly in constructing flexible interfaces based on CNTs. This review focuses on CNT-based sensor design, manufacturing advancements, material synergy effects, and minimally invasive/noninvasive glucose monitoring devices. The review also discusses the trend toward simultaneous detection of multiple markers in glucose sensors and the pivotal role played by CNTs in this trend. Furthermore, the latest applications of CNTs in electrochemical glucose sensors are explored, accompanied by an overview of the current status, challenges, and future prospects of CNT-based sensors and their potential applications.
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Nanoestructuras , Nanotubos de Carbono , Glucemia , Automonitorización de la Glucosa Sanguínea , Conductividad EléctricaRESUMEN
Osteoporosis is a metabolic bone disease that affects hundreds of millions of people worldwide and is characterized by excessive loss of bone protein and mineral content. The incidence and mortality of osteoporosis increase with age, creating a significant medical and economic burden globally. The importance of cholesterol levels has been reported in the development of diseases including osteoporosis. It is important to note that key enzymes and molecules involved in cholesterol homeostasis are closely related to bone formation. Excessive cholesterol may cause osteoporosis, cholesterol and its metabolites affect bone homeostasis by regulating the proliferation and stimulation of osteoblasts and osteoclasts. Therefore, antagonism of elevated cholesterol levels may be a potential strategy to prevent osteoporosis. There is sufficient evidence to support the use of bisphosphonates and statin drugs for osteoporosis in the clinic. Therefore, in view of the aggravation of the aging problem, we summarize the intracellular mechanism of cholesterol homeostasis and its relationship with osteoporosis (including cholesterol and cholesterol oxidation products (COPs) in osteoporosis). Furthermore, the current clinical cholesterol-lowering drugs for osteoporosis were also summarized, as are new and promising therapies (cell-based therapies (e.g., stem cells) and biomaterial-delivered target drug therapies for osteoporosis as well).
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Osteoporosis , Humanos , Osteoporosis/tratamiento farmacológico , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Huesos , HomeostasisRESUMEN
INTRODUCTION: Previous studies have demonstrated the beneficial effects of treadmill exercise (EX) on osteoporosis, and of hyperbaric oxygen (HBO) on osteoblast and osteoclast formation in vitro. We investigated the effects of HBO and the combination of HBO and EX on osteoporosis in ovariectomized rats. METHODS: Forty 3-month-old female Sprague-Dawley rats were randomly divided into 5 groups (n = 8): a sham control group (Control); an ovariectomy group; an ovariectomy with treadmill exercise treatment group; an ovariectomy with HBO treatment group; and an ovariectomy with HBO treatment combined with treadmill exercise group. The HBO exposures were 203 kPa, 85-90% O2, 90 min and the exercise regimen was 20 m·min⻹, 40 min·day¹, 5° slope. Both treatments were administered once daily, five days a week for 12 weeks until the rats were sacrificed. RESULTS: All three treatments (HBO, exercise, and both combined) significantly promoted the expression of the osteoblast-related gene and oxidative metabolism-related gene (PGC-1α). They also exerted significant inhibitory effects on the osteoclast-related mRNA expression (RANKL) and bone resorption marker CTX-I. Additionally, exercise and the combination exercise-HBO treatment increased serum superoxide dysmutase (SOD) and sclerostin expression. No significant between-group difference was observed. CONCLUSIONS: Hyperbaric oxygen, exercise, and the combination ameliorated bone microarchitecture deterioration and ovariectomy-induced bone loss in rats, and these inhibitory effects may be associated with the increased SOD and up-regulated PGC-1α.
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Oxigenoterapia Hiperbárica , Osteoporosis , Condicionamiento Físico Animal , Ratas , Femenino , Animales , Ratas Sprague-Dawley , Osteoporosis/prevención & control , Superóxido DismutasaRESUMEN
Nanoparticles (NPs) hold tremendous targeting potential in cardiovascular disease and regenerative medicine, and exciting clinical applications are coming into light. Vascular endothelial cells (ECs) exposure to different magnitudes and patterns of shear stress (SS) generated by blood flow could engulf NPs in the blood. However, an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies. Here, the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted. The mechanism of SS affecting NP uptake through regulating the cellular ROS level, endothelial glycocalyx and membrane fluidity is summarized, and the molecules containing clathrin and caveolin in the engulfment process are elucidated. SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine. This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
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Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence (ECL) immunoassays, but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development. In this study, we synthesized a series of gold nanoparticles (AuNPs)/reduced graphene oxide (Au/rGO) composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)32+)'s multisignal luminescence. With the increase in the diameter of AuNPs (3 to 30 nm), their ability to promote Ru(bpy)32+'s anodic ECL was first impaired and then strengthened, and cathodic ECL was first enhanced and then weakened. Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)32+'s cathodic and anodic luminescence, respectively. Notably, the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)32+ co-reactants. Moreover, we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)32+'s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution. This method avoids signal cross talk between luminophores and their respective co-reactants, which achieved a good linear range of 10-7 to 10-1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen. This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)32+, broadening its application in biomaterial detection. Furthermore, the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)32+ could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)32+ luminescence enhancers or applications of Au/rGOs to other luminophores. This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.
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The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenâ ¡A in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.
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Campos Electromagnéticos , Exosomas , Células Madre Mesenquimatosas , Animales , Ratas , Apoptosis , Condrocitos , Exosomas/metabolismo , Exosomas/fisiología , Células Madre Mesenquimatosas/metabolismoRESUMEN
Purpose: This review aims to explore the history, research hotspots, and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics. Methods: Publications on DES were retrieved from WoSCC. The bibliometric tools including CiteSpace and HistCite were used to identify the historical features, the evolution of active topics, and emerging trends on the DES field. Results: In the last 20 years, the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations. In addition, active topics emerge in different periods, as evidenced by a total of 41 disciplines, 511 keywords, and 1377 papers with citation bursts. Keyword clustering anchored five emerging research subfields, namely #0 dual antiplatelet therapy, #3 drug-coated balloon, #4 bifurcation, 5# rotational atherectomy, and 6# quantitative flow ratio. The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis, restenosis, etc., and the emerging keywords are paclitaxel eluting balloon, coated balloon, drug-eluting balloon, etc. There are 7 recent research subfields anchored by reference clustering, namely #2 dual antiplatelet therapy, #4 drug-coated balloon, #5 peripheral artery disease, #8 fractional flow reserve, #10 bioresorbable vascular scaffold, # 13 intravascular ultrasound, #14 biodegradable polymer. Conclusion: The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.
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BACKGROUND: The intra-articular injection of mesenchymal stem cell (MSC)-derived exosomes has already been proved to reverse osteoarthritic cartilage degeneration. Pulsed electromagnetic field (PEMF) has been found to regulate the biogenic function of MSCs. However, the effect of PEMF on MSC-derived exosomes has not yet been characterized. The aim of this study was to elucidate the regulatory role of different frequencies of PEMF in promoting the osteoarthritic cartilage regeneration of MSC-derived exosomes. METHODS: The adipose tissue-derived MSCs (AMSCs) were extracted from the epididymal fat of healthy rats and further exposed to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. The chondrocytes were treated with interlukin-1ß (IL-1ß) and the regenerative effect of co-culturing with PEMF-exposed AMSC-derived exosomes was assessed via Western blot, quantitative polymerase chain reaction, and ELISA assays. A rat model of osteoarthritis was established by anterior cruciate ligament transection (ACLT) surgery and received 4 times intra-articular injection of PEMF-exposed AMSC-derived exosomes once a week. After 8 weeks, the knee joint specimens of rats were collected for micro-computed tomography and histologic analyses. RESULTS: PEMF-exposed AMSC-derived exosomes could be endocytosed with IL-1ß-induced chondrocytes. Compared with the AMSC-derived exosomes alone, the PEMF-exposed AMSC-derived exosomes substantially suppressed the inflammation and extracellular matrix degeneration of IL-1ß-induced chondrocytes as shown by higher expression of transcripts and proteins of COL2A1, SOX9, and ACAN and lower expression of MMP13 and caspase-1. Of these, the 75-Hz PEMF presented a more significant inhibitive effect than the 15-Hz and 45-Hz PEMFs. Furthermore, the intra-articular injection of 75-Hz PEMF-exposed exosomes could obviously increase the number of tibial epiphyseal trabeculae, lead to a remarkable decrease in Osteoarthritis Research Society International score, and upregulate the COL2A1 and ACAN protein level of the degenerated cartilage. CONCLUSION: The present study demonstrated that PEMF stimulation could effectively promote the regeneration effects of AMSC-derived exosomes on osteoarthritic cartilage. Compared with other frequency parameters, the PEMF at a frequency of 75 Hz showed a superior positive effect on AMSC-derived exosomes in suppressing the IL-1ß-induced chondrocyte inflammation and extracellular matrix catabolism, as well as the osteoarthritic cartilage degeneration.
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Enfermedades de los Cartílagos , Cartílago Articular , Células Madre Mesenquimatosas , Osteoartritis , Ratas , Animales , Cartílago Articular/patología , Campos Electromagnéticos , Microtomografía por Rayos X , Osteoartritis/metabolismo , Células Madre Mesenquimatosas/metabolismo , Enfermedades de los Cartílagos/patología , Inflamación/metabolismoRESUMEN
Glucocorticoids induce cellular senescence, including of stem/progenitor cells in the bone marrow of growing long bone, which leads to bone loss in glucocorticoid-induced osteoporosis. There is no specific drug available to treat this disease. Clearance of senescent cells has been reported to be an effective therapy for osteoporosis. LepR+ cells in the bone marrow are the key kind of stem/progenitor cells conducive to bone remodeling in adulthood. Here, we show that glucocorticoids induce cellular senescence, demonstrated by increased activity of senescence-associated ß-galactosidase (SA-ßGal+) cells and simultaneous upregulation of coimmunofluorescence staining of p16INK4a with LepR in longitudinal femoral sections. We applied pulsed electromagnetic fields (PEMFs), which alleviated bone loss in glucocorticoid-induced osteoporosis mice. We found the increased accumulation of senescent LepR+ cells in the bone marrow of adult mice after glucocorticoid treatment, and this could be counteracted by PEMFs. Moreover, PEMFs maintained type H vessel formation and osteogenesis. This process was modulated by the polycomb histone methyltransferase enhancer of zeste homolog 2 (EZH2) and its trimethylation of histone H3 on lysine 27 (H3K27me3). These results provide evidence that PEMFs alleviate bone loss induced by glucocorticoids by eliminating senescent cells, maintaining angiogenesis-osteogenesis coupling, and shedding light on the mechanisms, providing a potential method to treat glucocorticoid-induced osteoporosis.
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Células Madre Mesenquimatosas , Osteoporosis , Animales , Médula Ósea , Campos Electromagnéticos , Glucocorticoides/farmacología , Ratones , Osteoporosis/inducido químicamenteRESUMEN
Key transcription factors (TFs) play critical roles in zygotic genome activation (ZGA) during early embryogenesis, whereas genome-wide occupancies of only a few factors have been profiled during ZGA due to the limitation of cell numbers or the lack of high-quality antibodies. Here, we present FitCUT&RUN, a modified CUT&RUN method, in which an Fc fragment of immunoglobulin G is used for tagging, to profile TF occupancy in an antibody-free manner and demonstrate its reliability and robustness using as few as 5000 K562 cells. We applied FitCUT&RUN to zebrafish undergoing embryogenesis to generate reliable occupancy profiles of three known activators of zebrafish ZGA: Nanog, Pou5f3, and Sox19b. By profiling the time-series occupancy of Nanog during zebrafish ZGA, we observed a clear trend toward a gradual increase in Nanog occupancy and found that Nanog occupancy prior to the major phase of ZGA is important for the activation of some early transcribed genes.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Reproducibilidad de los Resultados , Factores de Transcripción SOX/genética , Factores de Transcripción/genética , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Cigoto/metabolismoRESUMEN
The growth of blood vessels and osteogenesis are coupled in bone tissue. A specialized subset of CD31hiEndomucinhi (CD31hiEmcnhi) vascular endothelium in bone has been identified to positively regulate bone formation. Pulsed electromagnetic field (PEMF) can promote the facture healing and reverse the loss of bone mass. However, the underlying mechanisms mediating in the positive effects of PEMF on bone mass accrual remain unclear. In the ovariectomized (OVX) osteoporotic mouse model, PEMF with specific parameters was administrated after 12 weeks of surgery and continued for 8 weeks. µCT analysis, quantitative PCR and Elisa assays were used to assess the PEMF-induced the osteogenesis, while immunostaining and flow cytometry were used to evaluate the abundance of CD31hiEmcnhi endothelium in the metaphysis near the growth plate. Administration of PEMF substantially countered OVX-induced bone loss as shown by greater trabecular bone, higher expression of Osterix, PDGFB and Col-1a1 transcripts, and modulation of bone anabolic and catabolic activity. The PEMF-induced osteogenesis was coupled by the expansion of CD31hiEmcnhi endothelium as demonstrated by CD31 and Endomucin double-positive immunostaining and flow cytometry. Concurrently, the higher level of HIF-α was found in PEMF-treated mice than in vehicle controls. Notably, inhibition of HIF-1α considerably reduced PEMF-induced osteogenesis, and led to a remarkable decrease of CD31hiEmcnhi vessels in the PEMF-treated OVX mice. The present study demonstrated the PEMF-induced coupling promotion of osteogenesis and CD31hiEmcnhi endothelial cells in a mouse model of postmenopausal osteoporosis. This coupling effect might be mediated in HIF-1α signaling in CD31hiEmcnhi endothelium. These findings open up new directions of al that might enable therapeutic improvement of osteogenesis in patients with osteoporosis.
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Osteogénesis , Osteoporosis , Animales , Campos Electromagnéticos , Células Endoteliales/metabolismo , Femenino , Humanos , Ratones , Osteoporosis/etiología , Osteoporosis/metabolismo , OvariectomíaRESUMEN
Doxorubicin (DOX) stimulates the generation of reactive oxygen species, thereby impairing mitochondrial functions. Angiotensin-converting enzyme inhibitors (ACEIs) have been identified to exhibit protective effects on cardiovascular diseases. The present study aimed to test the hypothesis that an ACEI benazepril hydrochloride (HCl) may protect against DOX-induced cardiotoxicity. The DOX injury model was established using rat embryonic cardiac myoblast cells (H9c2 cell line) treated with DOX in vitro. H9c2 cells were treated with benazepril-HCl, DOX or a mixture of DOX and benazepril-HCl to measure the activities of myocardial enzymes including lactate dehydrogenase (LDH), superoxide dismutase, catalase and glutathione peroxidase, in addition to the concentration of malondialdehyde in the culture medium. Cells without any treatment were used as a control. DOX treatment increased the levels of activity of myocardial enzymes in H9c2 cells compared with those in the untreated control cells. Additionally, co-treatment with benazepril-HCl significantly reduced the levels of apoptosis occurring due to DOX-mediated cellular damage. The mechanistic experiment revealed that pretreatment with benazepril-HCl counteracted the DOX-induced oxidative stress and suppressed the activation of apoptosis via the PI3K/Akt signaling pathway. By contrast, an Akt inhibitor (MK2206) inhibited the protective effects of benazepril-HCl against DOX-induced H9c2 cell injury, as revealed by increased LDH release in H9c2 cells. These results suggested that benazepril-HCl may potentially be administered as an adjuvant for DOX in long-term clinical use.