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Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.
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Envejecimiento , Apoptosis , Homeostasis , Células Madre Mesenquimatosas , Mitocondrias , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Envejecimiento/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteoporosis/metabolismo , Huesos/metabolismo , Fenotipo , Ratones Endogámicos C57BL , Humanos , Ratones Endogámicos MRL lpr , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Estaurosporina/farmacología , MasculinoRESUMEN
Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind-driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low-humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s-1 wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long-term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.
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Pancreatic adenocarcinoma characterized by a mere 10% 5-year survival rate, poses a formidable challenge due to its specific anatomical location, making tumor tissue acquisition difficult. This limitation underscores the critical need for novel biomarkers to stratify this patient population. Accordingly, this study aimed to construct a prognosis prediction model centered on S100 family members. Leveraging six S100 genes and their corresponding coefficients, an S100 score was calculated to predict survival outcomes. The present study provided comprehensive internal and external validation along with power evaluation results, substantiating the efficacy of the proposed model. Additionally, the study explored the S100-driven potential mechanisms underlying malignant progression. By comparing immune cell infiltration proportions in distinct patient groups with varying prognoses, the research identified differences driven by S100 expression. Furthermore, the analysis explored significant ligand-receptor pairs between malignant cells and immune cells influenced by S100 genes, uncovering crucial insights. Notably, the study identified a novel biomarker capable of predicting the sensitivity of neoadjuvant chemotherapy, offering promising avenues for further research and clinical application.
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Adenocarcinoma , Biomarcadores de Tumor , Neoplasias Pancreáticas , Proteínas S100 , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/genética , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Pronóstico , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/genética , Masculino , Femenino , Persona de Mediana Edad , AncianoRESUMEN
Electrostatic generators show great potential for powering widely distributed electronic devices in Internet of Things (IoT) applications. However, a critical issue limiting such generators is their high impedance mismatch when coupled to electronics, which results in very low energy utilization efficiency. Here, we present a high-performance energy management unit (EMU) based on a spark-switch tube and a buck converter with an RF inductor. By optimizing the elements and parameters of the EMU, a maximum direct current output power of 79.2 mW m-2 rps-1 was reached for a rotary electret generator with the EMU, achieving 1.2 times greater power output than without the EMU. Furthermore, the maximum power of the contact-separated triboelectric nanogenerator with an EMU is 1.5 times that without the EMU. This excellent performance is attributed to the various optimizations, including utilizing an ultralow-loss spark-switch tube with a proper breakdown voltage, adding a matched input capacitor to enhance available charge, and incorporating an RF inductor to facilitate the high-speed energy transfer process. Based on this extremely efficient EMU, a compact self-powered wireless temperature sensor node was demonstrated to acquire and transmit data every 3.5 s under a slight wind speed of 0.5 m/s. This work greatly promotes the utilization of electrostatic nanogenerators in practical applications, particularly in IoT nodes.
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Extracellular vesicles (EVs) are lipid bilayer nanovesicles released from living or apoptotic cells that can transport DNA, RNA, protein, and lipid cargo. EVs play critical roles in cell-cell communication and tissue homeostasis, and have numerous therapeutic uses including serving as carriers for nanodrug delivery. There are multiple ways to load EVs with nanodrugs, such as electroporation, extrusion, and ultrasound. However, these approaches may have limited drug-loading rates, poor EV membrane stability, and high cost for large-scale production. Here, it is shown that apoptotic mesenchymal stem cells (MSCs) can encapsulate exogenously added nanoparticles into apoptotic vesicles (apoVs) with a high loading efficiency. When nano-bortezomib is incorporated into apoVs in culture-expanded apoptotic MSCs, nano-bortezomib-apoVs show a synergistic combination effect of bortezomib and apoVs to ameliorate multiple myeloma (MM) in a mouse model, along with significantly reduced side effects of nano-bortezomib. Moreover, it is shown that Rab7 regulates the nanoparticle encapsulation efficiency in apoptotic MSCs and that activation of Rab7 can increase nanoparticle-apoV production. In this study, a previously unknown mechanism to naturally synthesize nano-bortezomib-apoVs to improve MM therapy is revealed.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Mieloma Múltiple , Animales , Ratones , Bortezomib/farmacología , Bortezomib/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/metabolismo , Vesículas Extracelulares/metabolismo , Comunicación CelularRESUMEN
There is a growing but unmet need for point-of-care detection of prostate-specific antigen (PSA) in body fluid which may facilitate early diagnosis and therapy of prostate cancer in a cost-effective and user-friendly way. Low sensitivity and narrow detection range limits applications of point-of-care testing in practice. Here, an immunosensor is first presented based on shrink polymer and integrated into a miniaturized electrochemical platform for detecting PSA in clinical samples. The sensing electrode was prepared by sputtering a gold film on shrink polymer, followed by heating to shrink the electrode to a small size with wrinkles from nano-scale to micro-scale. These wrinkles can be directly regulated by the thickness of the gold film with high specific areas for enhancement of antigen-antibody binding (3.9 times). A distinct difference between electrochemical active surface area (EASA) and response to PSA of shrink electrodes was observed and discussed. The electrode was treated with air plasma and modified with self-assembled graphene to further enhance the sensor's sensitivity (10.4 times). The shrink sensor with gold 200 nm thick integrated into the portable system was validated by a label-free immunoassay for detection of PSA in 20 µL serum within 35 mins. It exhibited a limit of detection of 0.38 fg/mL, the lowest among label-free PSA sensors, and a wide linear response from 10 fg/mL to 1000 ng/mL. Moreover, the sensor demonstrated reliable assay results in clinical serums, comparable to the commercial chemiluminescence instrument, confirming its feasibility for clinical diagnosis.
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Técnicas Biosensibles , Nanopartículas del Metal , Masculino , Humanos , Antígeno Prostático Específico , Polímeros , Sistemas de Atención de Punto , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Electrodos , Oro , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
High-quality cutaneous wound healing is associated with rapid wound closure and a comfortable healing process. Currently, exosomes derived from mesenchymal stem cells displayed a prominent therapeutic effect on skin wound closure. But the therapeutic approaches for wound itching are very limited in clinical. Stem cells from human exfoliated deciduous teeth (SHED) may offer a unique exosome resource for cell-free therapeutics in potential clinical applications. Here, we investigated the common mechanisms underlying wound closure and unpleasant sensation of itching, focusing on the contribution of the SHED-derived exosome to immune response and wound itching during healing. The effects of SHED-derived exosomes on inflammatory wound healing were examined using lipopolysaccharide (LPS)-induced wounds in a mouse model. We found prolonged inflammation and distinct itch responses in skin wound tissue during LPS-induced wound healing. SHED-derived exosomes facilitated LPS-induced wound closure and relieved wound itching. Therefore, they are ideal for the treatment of wound healing. Macrophages in skin wound tissues are responsible for autophagy during wound healing. Macrophage autophagy also regulates cell proliferation, migration, and neuronal signal transduction in vitro. SHED-derived exosomes containing miR-1246 enhanced autophagy by regulating macrophage function through the AKT, ERK1/2, and STAT3 signaling pathways. Thus, SHED-derived exosomes promote wound healing with less itching in an LPS-induced wound model by stimulating macrophage autophagy, which has implications for the treatment of inflammatory wound healing.
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Exosomas , Animales , Autofagia , Exosomas/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Ratones , Prurito/metabolismo , Cicatrización de HeridasRESUMEN
Mesenchymal stem cell (MSC) therapy can attenuate organ damage and reduce mortality in sepsis; however, the detailed mechanism is not fully elucidated. In this study, it is shown that MSC-derived apoptotic vesicles (apoVs) can ameliorate multiple organ dysfunction and improve survival in septic mice. Mechanistically, it is found that tail vein-infused apoVs mainly accumulate in the bone marrow of septic mice via electrostatic charge interactions with positively charged neutrophil extracellular traps (NETs). Moreover, apoVs switch neutrophils NETosis to apoptosis via the apoV-Fas ligand (FasL)-activated Fas pathway. In summary, these findings uncover a previously unknown role of apoVs in sepsis treatment and an electrostatic charge-directed target therapeutic mechanism, suggesting that cell death is associated with disease development and therapy.
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Neutrófilos , Sepsis , Animales , Apoptosis/fisiología , Ratones , Sepsis/terapia , Electricidad Estática , Distribución TisularRESUMEN
BACKGROUND: Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs). METHODS: Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality, the Zung's Self-rating Depression Scale (SDS) to measure depressive symptom, and the Work Stress Scale to measure job stress. The CLOCK gene rs12649507 polymorphism was genotyped in 289 blood samples. RESULTS: There were positive inter-correlations between job stress, PSQI and SDS (almost ps < 0.05). GG homozygotes of the SNP had higher PSQI and its sleep duration and daytime dysfunction scores than AA homozygotes (all Bonferroni corrected ps0.05). The SNP had no main effect on the SDS and did not interact with job stress to affect SDS, PSQI and its dimensions (all ps > 0.05). Interestingly, after controlling for job stress and covariates, the significant effect size of the SNP on the SDS mediated by the PSQI was 0.68 (95% CI [0.24, 1.35]). LIMITATIONS: Some limitations included single professional background, cross-sectional study design, small sample size and potential confounding factors, which could be amended by future research. CONCLUSIONS: Non-clinical Chinese carrying CLOCK gene rs12649507 G-allele may lead to poor sleep quality and further depression symptoms.
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Depresión , Trastornos del Sueño-Vigilia , China , Estudios Transversales , Depresión/genética , Humanos , Polimorfismo Genético , Sueño , Calidad del Sueño , Trastornos del Sueño-Vigilia/genéticaRESUMEN
Electrostatic generators as a kind of effective energy harvesters have attracted intensive attention. However, the output of the generators is highly dependent on the charge density. Here, we demonstrate an all-in-one rotary electrostatic nanogenerator based on the charge pumping and voltage multiplying strategy (CV-ESG), which achieves high output power in SF6 atmosphere. CV-ESG integrates a pumping electret generator, a main generator, and a voltage multiplying and stabilization circuit on a pair of rotator and stator. We analyze the breakdown effect and its influence on the insulating layer covered on the electrodes through experiments. The breakdown voltage is high in SF6 atmosphere, and the maximum average power of CV-ESG in SF6 is 37.29 mW at 750 rpm, which is 3.29 times that in air. There is no surface friction in CV-ESG, which avoids abrasion and reduces friction damping. And the pumping generator is integrated with the main generator, making CV-ESG compact and easy to assemble. This work provides the design strategy for a high-power rotary electrostatic generator with good performance.
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Apoptosis is critical for maintaining bodily homeostasis and produces a large number of apoptotic extracellular vesicles (apoEVs). Several types of cancer cells display reduced expression of Fas on the cell surface and are thus capable of escaping Fas ligand-induced apoptosis. However, it is unknown whether normal cell-derived apoEVs can regulate tumor growth. In this study, we show that apoEVs can induce multiple myeloma (MM) cell apoptosis and inhibit MM cell growth. Systemic infusion of mesenchymal stem cell (MSC)-derived apoEVs significantly prolongs the lifespan of MM mice. Mechanistically, apoEVs directly contact MM cells to facilitate Fas trafficking from the cytoplasm to the cell membrane by evoking Ca2+ influx and elevation of cytosolic Ca2+. Subsequently, apoEVs use their Fas ligand to activate the Fas pathway in MM cells, leading to the initiation of apoptosis. This study identifies the role of apoEVs in inducing MM apoptosis and suggests a potential for apoEVs to treat MM.
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Vesículas Extracelulares , Mieloma Múltiple , Animales , Apoptosis , Ratones , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
BACKGROUND: During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing. RESULTS: Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation. CONCLUSION: Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.
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Antioxidantes/farmacología , Ácidos Cumáricos/farmacología , Hidrogeles/farmacología , Indoles/farmacología , Isoflavonas/farmacología , Polímeros/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/química , Vendajes , Ácidos Cumáricos/química , Liberación de Fármacos , Humanos , Hidrogeles/química , Indoles/química , Isoflavonas/química , Ratones , Nanopartículas/química , Ligamento Periodontal , Polietilenglicoles , Polímeros/química , Especies Reactivas de Oxígeno , Piel/efectos de los fármacos , Células MadreRESUMEN
Peptide-based materials hold great promise for various biomedical applications and have drawn increasing attention over the past five years. Despite the progress in fabrication and handling peptide materials in vitro, manipulating assemblies of peptides in living cells (or animals) is still in its infancy. In this contributing review, recent work is summarized using endogenous triggers to construct functional assemblies of peptides in vivo. After introducing the triggers for inducing peptide assemblies, the recent progress is highlighted of the in situ construction of assemblies for biomedical applications with emphasis on cancer therapy. Finally, a brief perspective is provided to discuss the future promises and challenges of this emerging area of supramolecular chemistry.
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Hidrogeles , Neoplasias , Animales , Neoplasias/terapia , PéptidosRESUMEN
Human periodontal ligament stem cells (hPDLSCs) can undergo osteogenic differentiation under induction conditions. Cyclic tensile stress (CTS) can stimulate stem cell osteogenic differentiation. The present study explored the mechanism of CTS in hPDLSC osteogenic differentiation. The hPDLSCs of the 4th passage were selected. hPDLSCs were subjected to CTS with deformation of 10% elongation at 0.5 Hz for 1, 4, 8, 12 and 24 h. ALP activity and staining, ARS staining and detection of expressions of osteogenesis-related genes (RUNX2, OPN, Sp7 and OCN) were used to assess hPDLSC osteogenic differentiation ability. microRNA (miR)-129-5p and BMP2 expression and p-Smad1/5 level were detected under CTS stimulation. The binding relationship between miR-129-5p and BMP2 was predicted and verified. The osteogenic differentiation ability of CTS-treated hPDLSCs was evaluated after intervention of miR-129-5p and BMP2. CTS induced hPDLSC osteogenic differentiation, as manifested by increased ALP activities, osteogenesis-related gene expressions and mineralized nodules, together with positive ALP staining. CTS inhibited miR-129-5p expression, and promoted BMP2 expression and p-Smad1/5 level in hPDLSCs. miR-129-5p targeted BMP2. Overexpressed miR-129-5p or silenced BMP2 prevented hPDLSC osteogenic differentiation ability. We demonstrated that CTS inhibited miR-129-5p expression, and then activated the BMP2/Smad pathway, thereby showing stimulative effects on hPDLSC osteogenic differentiation.
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MicroARNs , Osteogénesis , Diferenciación Celular , Células Cultivadas , Humanos , Ligamento Periodontal , Células MadreRESUMEN
AIMS: Human periodontal ligament stem cells (hPDLSCs) tether the teeth to the surrounding bone and are considered as major functional stem cells responsible for regeneration of the alveolar bone and periodontal ligament tissue. However, the outcome of stem cell regenerative therapy is affected by the survival rate and their differentiation potential of transplanted cells. This is primarily because of local oxidative stress and chronic inflammation at the transplantation site. Therefore, our study aimed to explore whether a natural antioxidant, curcumin could increase the tissue regeneration ability of transplanted hPDLSCs. MAIN METHODS: A hydrogen peroxide environment and a rat cranial bone defect model were built to mimic the oxidative stress conditions in vitro and in vivo, respectively. We evaluated the effect of curcumin on oxidative status, apoptosis, mitochondrial function and osteogenic differentiation of H2O2-stimulated hPDLSCs in vitro. We also measured the effect of curcumin on cell viability and bone repair ability of transplanted hPDLSCs in vivo. KEY FINDINGS: Our data showed that curcumin enhanced cell proliferation, reduced the reactive oxygen species (ROS) levels and apoptosis, maintained the standard mitochondrial structure and function, and promoted osteogenic differentiation of H2O2-stimulated hPDLSCs. The extracellular regulated protein kinases 1/2 (Erk1/2) signaling pathway was determined to be involved in the osteogenic differentiation of the H2O2-stimulated hPDLSCs. Moreover, curcumin enhanced the viability and the bone repair ability of hPDLSCs in vivo. SIGNIFICANCE: Curcumin reduced apoptosis and promoted osteogenesis of the hPDLSCs under oxidative stress, and might therefore have a potential clinical use with respect to tissue regeneration.
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Curcumina/farmacología , Ligamento Periodontal/metabolismo , Trasplante de Células Madre/métodos , Animales , Apoptosis/efectos de los fármacos , Huesos/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Curcumina/metabolismo , Femenino , Humanos , Ligamentos/metabolismo , Masculino , Diente Molar/metabolismo , Osteogénesis/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas Sprague-Dawley , Células Madre/citología , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Adulto JovenRESUMEN
Job stress and the Circadian Locomotor Output Cycles Kaput (CLOCK) gene could affect circadian rhythm and sleep quality. The main aim of our present study was to investigate the association of job stress, CLOCK gene polymorphism and their interaction with sleep quality in a non-clinical Chinese Han population, which has not been reported to date. Using a cross-sectional design, 450 subjects were recruited in Beijing. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and job stress was measured with the Work Stress Scale. CLOCK gene rs11932595 polymorphism was genotyped in 297 blood samples. Correlation analysis showed a close but different association of high job stress with the PSQI and its components. Analysis of variance showed significant main effects of the CLOCK gene rs11932595 polymorphism. G-allele carriers had a higher score in the PSQI, sleep duration, sleep latency and sleep disturbances. Further interaction analyses showed an ordinal interaction on sleep duration, and a disordinal interaction on daytime dysfunction. Specifically, G-allele carriers had poorer sleep duration than AA homozygotes when in high job stress, while the two subgroups displayed similar sleep duration when in low job stress, conforming to the diathesis-stress model. In comparison to G-allele carriers, AA homozygotes experienced less daytime dysfunction when in low job stress whereas more daytime dysfunction when in high job stress, fitting with the differential susceptibility model. As genetic links have been revealed, our investigation might be conducive for elucidating aetiological factors for sleep quality and targets for implementing interventions to attain good sleep quality.
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Proteínas CLOCK/genética , Ritmo Circadiano/genética , Estrés Laboral/psicología , Polimorfismo Genético/genética , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Adulto , Estudios Transversales , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) have a limited self-renewal ability, impaired multi-differentiation potential, and undetermined cell senescence during in vitro series expansion. To address this concern, we investigated the effects of the microenvironment provided by stem cells from human exfoliated deciduous teeth (SHED) in maintaining the stemness of human bone marrow mesenchymal stem cells (hBMSCs) and identified the key factors and possible mechanisms responsible for maintaining the stemness of MSCs during long-term expansion in vitro. METHODS: The passage 3 (P3) to passage 8 (P8) hBMSCs were cultured in the conditioned medium from SHED (SHED-CM). The percentage of senescent cells was evaluated by ß-galactosidase staining. In addition, the osteogenic differentiation potential was analyzed by reverse transcription quantitative PCR (RT-qPCR), Western blot, alizarin red, and alkaline phosphatase (ALP) staining. Furthermore, RT-qPCR results identified hepatocyte growth factor (HGF) and stem cell factor (SCF) as key factors. Thus, the effects of HGF and SCF on mitochondrial function were assessed by measuring the ROS and mitochondrial membrane potential levels. Finally, selected mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways were investigated to determine the effects of HGF and SCF in preserving the mitochondrial function of hBMSCs during long-term expansion. RESULTS: SHED-CM had significantly enhanced the cell proliferation, reduced the senescent cells, and maintained the osteogenesis and pro-angiogenic capacity in P8 hBMSCs during long-term expansion. In addition, hBMSCs treated with 100 ng/ml HGF and 10 ng/ml SCF had reduced ROS levels and preserved mitochondrial membrane potential compared with P8 hBMSCs during long-term expansion. Furthermore, HGF and SCF upregulated the expression of mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways, possibly contributing to the maintenance of hBMSCs stemness by preserving mitochondrial function. CONCLUSION: Both HGF and SCF are key factors in maintaining the stemness of hBMSCs by preserving mitochondrial function through the expression of proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways. This study provides new insights into the anti-senescence capability of HGF and SCF, as well as new evidence for their potential application in optimizing the long-term culture of MSCs.
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Factor de Crecimiento de Hepatocito , Células Madre Mesenquimatosas , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/metabolismo , Osteogénesis , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3 , Factor de Células Madre/genética , Factor de Células Madre/metabolismoRESUMEN
BACKGROUND: Accelerated proliferation of human periodontal ligament stem cells (PDLSCs) is present in periodontitis. It is known that fibroblast growth factor 2 (FGF2) regulates the proliferation of PDLSCs, while the function of FGF2 in myogenic cell differentiation is mediated by Linc-RNA Activator of Myogenesis (Linc-RAM) lncRNA. Therefore, Linc-RAM lncRNA may also participate in periodontitis. METHODS: This study included 28 patients with periodontitis (patient group) and 22 patients without periodontitis but received orthodontic treatment (control group) in the stomatological hospital of Sun Yat-Sen university. Gingival biopsies were obtained from participants. RT-qPCR, cell transfection, cell proliferation assay and western blot were carrying out to analyze the samples. RESULTS: We found that FGF2 mRNA was upregulated, while Linc-RAM was downregulated in PDLSCs derived from periodontitis-affected teeth than in healthy teeth. FGF2 mRNA and Linc-RAM were inversely correlated in both types of PDLSCs. FGF2 overexpression led to inhibited Linc-RAM expression in PDLSCs derived from periodontitis-affected teeth and promoted the proliferation of PDLSCs. Linc-RAM overexpression failed to significantly affect FGF2 expression but attenuated the enhancing effects of FGF2 overexpression on the proliferation of PDLSCs. CONCLUSIONS: Therefore, downregulation of Linc-RAM lncRNA may participate in FGF-2 mediated- proliferation of human PDLSCs.
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Factor 2 de Crecimiento de Fibroblastos , Ligamento Periodontal , ARN Largo no Codificante , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Regulación hacia Abajo , Humanos , Desarrollo de Músculos , Proteínas Musculares , Osteogénesis , Células MadreRESUMEN
Periodontitis is a chronic disease that includes the pathologic loss of periodontal tissue and alveolar bone. The inflammatory environment in periodontitis impairs the osteogenic differentiation potential and depresses the regeneration capacity of human periodontal ligament stem cells (hPDLSCs). Since Forkhead box protein O1 (FoxO1) plays an important role in redox balance and bone formation, we investigated the role of FoxO1 in oxidative stress resistance and osteogenic differentiation in an inflammatory environment by overexpressing FoxO1 in hPDLSCs. First, we found that FoxO1 overexpression reduced reactive oxygen species (ROS) accumulation, decreased malondialdehyde (MDA) levels, and elevated antioxidant potential under oxidative condition. Next, the overexpression of FoxO1 protected hPDLSCs against oxidative damage, which involved stabilization of the mitochondrial membrane potential. Third, overexpressed FoxO1 promoted extracellular matrix (ECM) mineralization and increased the expression of the osteogenic markers Runx2 and SP7 in the inflammatory environment. These results indicated that FoxO1 overexpression in hPDLSCs has an anti-inflammatory effect, increases antioxidative capacity, and positively regulates osteogenesis in a mimicked inflammatory environment.