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BACKGROUND: Insulin has been known to regulate bone metabolism, yet its specific molecular mechanisms during the proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) remain poorly understood. This study aimed to explore the effects of insulin on the bone formation capability of human DPSCs and to elucidate the underlying mechanisms. METHODS: Cell proliferation was assessed using a CCK-8 assay. Cell phenotype was analyzed by flow cytometry. Colony-forming unit-fibroblast ability and multilineage differentiation potential were evaluated using Toluidine blue, Oil red O, Alizarin red, and Alcian blue staining. Gene and protein expressions were quantified by real-time quantitative polymerase chain reaction and Western blotting, respectively. Bone metabolism and biochemical markers were analyzed using electrochemical luminescence and chemical colorimetry. Cell adhesion and growth on nano-hydroxyapatite/collagen (nHAC) were observed with a scanning electron microscope. Bone regeneration was assessed using micro-CT, fluorescent labeling, immunohistochemical and hematoxylin and eosin staining. RESULTS: Insulin enhanced the proliferation of human DPSCs as well as promoted mineralized matrix formation in a concentration-dependent manner. 10- 6 M insulin significantly up-regulated osteogenic differentiation-related genes and proteins markedly increased the secretion of bone metabolism and biochemical markers, and obviously stimulated mineralized matrix formation. However, it also significantly inhibited the expression of genes and proteins of receptors and receptor substrates associated with insulin/insulin-like growth factor-1 signaling (IIS) pathway, obviously reduced the expression of the phosphorylated PI3K and the ratios of the phosphorylated PI3K/total PI3K, and notably increased the expression of the total PI3K, phosphorylated AKT, total AKT and mTOR. The inhibitor LY294002 attenuated the responsiveness of 10- 6 M insulin to IIS/PI3K/AKT/mTOR pathway axis, suppressing the promoting effect of insulin on cell proliferation, osteogenic differentiation and bone formation. Implantation of 10- 6 M insulin treated DPSCs into the backs of severe combined immunodeficient mice and the rabbit jawbone defects resulted in enhanced bone formation. CONCLUSIONS: Insulin induces insulin resistance in human DPSCs and effectively promotes their proliferation, osteogenic differentiation and bone formation capability through gradually inducing the down-regulation of IIS/PI3K/AKT/mTOR pathway axis under insulin resistant states.
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Diferenciación Celular , Proliferación Celular , Pulpa Dental , Insulina , Osteogénesis , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Células Madre , Serina-Treonina Quinasas TOR , Pulpa Dental/citología , Pulpa Dental/metabolismo , Humanos , Osteogénesis/efectos de los fármacos , Insulina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Madre/metabolismo , Células Madre/citología , Células Madre/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proliferación Celular/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones , Animales , Durapatita/farmacología , Células Cultivadas , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , ColágenoRESUMEN
Wound dressing diligently facilitate healing by fostering hemostasis, immunoregulation, the angiogenesis, and collagen deposition. Our methodology entails fabricating chitosan-taurine nanoparticles (CS-Tau) through an ionic gelation method. The morphology of CS-Tau was observed utilizing Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Dynamic Light Scattering (DLS). The nanoparticles are subsequently incorporated into carboxymethyl chitosan hydrogels for crosslinking by EDC-NHS, yielding hydrogel dressings (CMCS-CS-Tau) designed to extend the duration of taurine release. In vitro investigations confirmed that these innovative compound dressings displayed superior biodegradation, biocompatibility, cytocompatibility, and non-toxicity, in addition to possessing anti-inflammatory properties, and stimulating the proliferation and mobility of human umbilical vein endothelial cells (HUVECs). Experiments conducted on mice models with full-thickness skin removal demonstrated that CMCS-CS-Tau efficaciously aided in wound healing by spurring angiogenesis, and encouraging collagen deposition. CMCS-CS-Tau can also minimize inflammation and promote collagen deposition in chronic diabetic wound. Hence, CMCS-CS-Tau promotes both acute and chronic diabetic wound healing. Furthermore, the sustained release mechanism of CMCS-CS-Tau on taurine reveals promising potential for extending its clinical utility in relation to various biological effects of taurine.
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Quitosano , Células Endoteliales de la Vena Umbilical Humana , Hidrogeles , Nanopartículas , Taurina , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Nanopartículas/química , Humanos , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Taurina/análogos & derivados , Taurina/química , Taurina/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Masculino , Reactivos de Enlaces Cruzados/químicaRESUMEN
Burkitt's lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. Although the outcomes of patients with BL have greatly improved, options for patients with relapsed and refractory BL are limited. Therefore, there is an urgent need to improve BL therapeutics and to develop novel drugs with reduced toxicity. In this study, we demonstrated that enolase 1 (ENO1) is a potential novel drug target for BL treatment. We determined that ENO1 was aberrantly upregulated in BL, which was closely related to its invasiveness and poor clinical outcomes. Furthermore, using RNA interference, we demonstrated that ENO1 depletion significantly inhibited cell proliferation and invasion both in vitro and in vivo. Mechanistically, we established that ENO1 knockdown suppressed the PI3K-AKT and epithelial-mesenchymal transition (EMT) signaling pathways by reducing plasminogen (PLG) recruitment, plasmin (PL) generation, and TGF-ß1 activation. Addition of activated TGF-ß1 protein to the culture medium of shENO1 cells reversed the inhibitory effects on cell proliferation and invasion, as well as those on the PI3K-AKT and EMT signaling pathways. Notably, our research led to the discovery of a novel ENO1-PLG interaction inhibitor, Ciwujianoside E (L-06). L-06 effectively disrupts the interaction between ENO1 and PLG, consequently reducing PL generation and suppressing TGF-ß1 activation. In both in vitro and in vivo experiments, L-06 exerted impressive antitumor effects. In summary, our study elucidated the critical role of ENO1 in BL cell proliferation and invasion and introduced a novel ENO1 inhibitor, which holds promise for improving the treatment of patients with BL in the future.
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Linfoma de Burkitt , Proliferación Celular , Proteínas de Unión al ADN , Transición Epitelial-Mesenquimal , Invasividad Neoplásica , Fosfopiruvato Hidratasa , Plasminógeno , Factor de Crecimiento Transformador beta1 , Proteínas Supresoras de Tumor , Fosfopiruvato Hidratasa/metabolismo , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Animales , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/patología , Linfoma de Burkitt/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Plasminógeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Ratones Desnudos , Femenino , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Biomarcadores de TumorRESUMEN
The development of a thermoplastic, biodegradable composite material to replace conventional polymers derived from petroleum was the main area of concentration. Herein, a method for preparing antibacterial, UV-blocking and degradable CNF/Lignin/PBAT composite films (CLP) using cellulose nanofibrils (CNF), lignin, and Poly (butylene adipate-terephthalate) (PBAT) as raw materials by solution casting method was described. With the adding of PBAT, the thermal stability, thermoplastic, mechanical properties were enhanced by improving the compatibility between components. The maximum tensile strength of CLP could reach 189.72 MPa, which increased 25.5 % compared to CNF/Lignin film. The average initial decomposition temperature could reach 321 °C, which was much higher than that of CNF and lignin. At the same time, its good heat-sealing performance made it suitable for practical use. Meanwhile, the composite films had excellent UV resistance and could block over 95 % of UV light. The antibacterial results indicated that the films had a good inhibitory effect on E. coli and S. aureus, with a maximum inhibitory ring diameter of 5.56 and 6.36 mm. In addition, the composite film also had excellent barrier capability to liquid and gas. The prepared film had potential to produce flexible packing, industrial compositing and biomedical fields.
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Antibacterianos , Biomasa , Celulosa , Escherichia coli , Lignina , Poliésteres , Staphylococcus aureus , Rayos Ultravioleta , Antibacterianos/química , Antibacterianos/farmacología , Lignina/química , Escherichia coli/efectos de los fármacos , Celulosa/química , Poliésteres/química , Staphylococcus aureus/efectos de los fármacos , Resistencia a la Tracción , Nanofibras/química , Temperatura , Pruebas de Sensibilidad MicrobianaRESUMEN
This research presents a new approach to facilely fabricating a multifunctional film using polyvinyl alcohol (PVA) as the base material. The film is modified chemically to incorporate various desirable properties such as high transparency, UV-shielding, antibacterial activity, and fluorescence. The fabrication process of this film is straightforward and efficient. The modified film showed exceptional UV-blocking capability, effectively blocking 100% of UV radiation. It also exhibits strong antibacterial properties. Additionally, the film emitted bright blue fluorescence, which can be useful in various optical and sensing applications. Despite the chemical modification, the film retained the excellent properties of PVA, including high transparency (90%) at 550 nm and good mechanical strength. Furthermore, it demonstrated remarkable stability even under harsh conditions such as exposure to long-term UV radiation, extreme temperatures (-40 or 120 °C), or immersion in different solvents. Overall, this work showcases a promising strategy to develop versatile, structurally stable, transparent, and flexible polymer films with multiple functionalities. These films have potential applications in various fields that require protection, such as packaging materials, biomedical devices, and optical components.
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Antibacterianos , Alcohol Polivinílico , Rayos Ultravioleta , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Alcohol Polivinílico/química , Fluorescencia , Polímeros/química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacosRESUMEN
Multiple myeloma (MM) is a distinguished hematologic malignancy, with existing studies elucidating its interaction with neutrophil extracellular traps (NETs), which may potentially facilitate tumor growth. However, systematic investigations into the role of NETs in MM remain limited. Utilizing the single-cell dataset GSE223060, we discerned active NET cell subgroups, namely neutrophils, monocytes, and macrophages. A transcriptional trajectory was subsequently constructed to comprehend the progression of MM. Following this, an analysis of cellular communication in MM was conducted with a particular emphasis on neutrophils, revealing an augmentation in interactions albeit with diminished strength, alongside abnormal communication links between neutrophils and NK cells within MM samples. Through the intersection of differentially expressed genes (DEGs) between NET active/inactive cells and MM versus healthy samples, a total of 316 genes were identified. This led to the development of a 13-gene risk model for prognostic prediction based on overall survival, utilizing transcriptomics dataset GSE136337. The high-risk group manifested altered immune infiltration and heightened sensitivity to chemotherapy. A constructed nomogram for predicting survival probabilities demonstrated encouraging AUCs for 1, 3, and 5-year survival predictions. Collectively, our findings unveil a novel NET-related prognostic signature for MM, thereby providing a potential avenue for therapeutic exploration.
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Trampas Extracelulares , Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Microambiente Tumoral/genética , Pronóstico , NeutrófilosRESUMEN
An electrocatalyst of single-atomic Mn sites with MnP nanoparticles (NPs) on N, P co-doped carbon substrate was constructed to enhance the catalytic activity of oxygen reduction reaction (ORR) through one-pot in situ doping-phosphatization strategy. The optimized MnSA-MnP-980â catalyst exhibits an excellent ORR activity in KOH electrolyte with a half-wave potential (E1/2) of 0.88 V (vs. RHE), and the ORR current density of MnSA-MnP-980â maintained 97.9 % for over 25000 s chronoamperometric i-t measurement. When using as the cathode, the MnSA-MnP-980â displays a peak power density of 51 mW cm-2 in Zinc-Air batteries, which observably outperformed commercial Pt/C (20 wt%). The X-ray photoelectron spectroscopy reveal that the doped P atoms with a strong electron-donating effectively enhances electron cloud density of Mn SAs sites, facilitating the adsorption of O2 molecules. Meanwhile, the introduction of MnP NPs can regulate the electronic structure of Mn SAs sites, making Mn SAs active sites exist in a low oxidation state and are less positively charged, which can supply electrons for ORR process to narrow the adsorption energy barrier of ORR intermediates. This work constructs novel active sites with excellent ORR properties and provides valuable reference for the development of practical application.
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Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia. SIGNIFICANCE: Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.
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Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Leucemia Mieloide Aguda , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteómica , Proliferación Celular , Neoplasias Pulmonares/metabolismo , Leucemia Mieloide Aguda/genética , Células Progenitoras Mieloides , Receptores ErbB/metabolismo , Antígenos CD34/metabolismo , Células Madre Neoplásicas/metabolismoRESUMEN
The inherent highly hydrophilic feature of cellulose-based paper hinders its application in many fields. Herein, a cellulose-based hydrophobic paper was fabricated based on surface chemical modification. Firstly, the hydrophobic acrylate components were bonded to the cellulose acetoacetate (CAA) fibers to obtain CAA graft acrylate (CAA-X) fibers through Michael addition reaction. Subsequently, CAA-X fibers were processed into paper via wet papermaking technology. The resulting paper exhibited good hydrophobic performance (water contact angle was up to 135°) with an air permeability of 24.8 µm/Pa·s. The hydrophobicity of paper was very stable and remained even after treating with different solvents. Moreover, the hydrophobic properties of this paper could be adjusted by changing the type of acrylate component. It should be noted that the surface modification strategy has no obvious effects on the whiteness (79.8%), writing, and printing properties of the cellulose fibers. Thus, it is a simple, benign, and efficient strategy for the construction of cellulose-based hydrophobic paper, which has great potential to be used in paper tableware, oil-water separation, watercolor protection, and food packaging fields.
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Celulosa , Agua , Celulosa/química , Interacciones Hidrofóbicas e Hidrofílicas , Agua/química , Solventes , Acrilatos/químicaRESUMEN
Smart-response materials with ultralong room-temperature phosphorescence (RTP) are highly desirable, but they have rarely been described, especially those originating from sustainable polymers. Herein, a variety of cellulose derivatives with 1,4-dihydropyridine (DHP) rings are synthesized through the Hantzsch reaction, giving impressive RTP with a long lifetime of up to 1251 ms. Specifically, the introduction of acetoacetyl groups and DHP rings promotes the spin-orbit coupling and intersystem crossing process; and multiple interactions between cellulose induce clustering and inhibit the nonradiative transitions, boosting long-live RTP. Furthermore, the resulting transparent and flexible cellulose films also exhibit excitation-dependent and color-tunable afterglows by introducing different extended aromatic groups. More interestingly, the RTP performance of these films is sensitive to water and can be repeated in response to wet/dry stimuli. Inspired by these advantages, the RTP cellulose demonstrates advanced applications in information encryption and anti-counterfeiting. This work not only enriches the photophysical properties of cellulose but also provides a versatile platform for the development of sustainable afterglows.
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The alveolar bone marrow mesenchymal stem cells (ABM-MSCs) play an important role in oral bone healing and regeneration. Insulin is considered to improve impaired oral bones due to local factors, systemic factors and pathological conditions. However, the effect of insulin on bone formation ability of ABM-MSCs still needs to be elucidated. The aim of this study was to determine the responsiveness of rat ABM-MSCs to insulin and to explore the underlying mechanism. We found that insulin promoted ABM-MSCs proliferation in a concentration-dependent manner, in which 10-6 M insulin exerted the most significant effect. 10-6 M insulin significantly promoted the type I collagen (COL-1) synthesis, alkaline phosphatase (ALP) activity, osteocalcin (OCN) expression, and mineralized matrix formation in ABM-MSCs, significantly enhanced the gene and protein expressions of intracellular COL-1, ALP, and OCN. Acute insulin stimulation significantly promoted insulin receptor (IR) phosphorylation, IR substrate-1 (IRS-1) protein expression, and mammalian target of rapamycin (mTOR) phosphorylation, but chronic insulin stimulation decreased these values, while inhibitor NT219 could attenuate these responses. When seeded on ß-tricalcium phosphate (ß-TCP), ABM-MSCs adhered and grew well, during the 28-day culture period, ABM-MSCs+ß-TCP +10-6 M insulin group showed significantly higher extracellular total COL-1 amino-terminus prolongation peptide content, ALP activity, OCN secretion, and Ca and P concentration. When implanted subcutaneously in severe combined immunodeficient mice for 1 month, the ABM-MSCs+ß-TCP +10-6 M insulin group obtained the most bone formation and blood vessels. These results showed that insulin promoted the proliferation and osteogenic differentiation of ABM-MSCs in vitro, and enhance osteogenesis and angiogenesis of ABM-MSCs in vivo. Inhibition studies demonstrated that the insulin-induced osteogenic differentiation of ABM-MSCs was dependent of insulin/mTOR signaling. It suggests that insulin has a direct anabolic effect on ABM-MSCs.
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Células Madre Mesenquimatosas , Osteogénesis , Ratones , Ratas , Animales , Insulina/farmacología , Insulina/metabolismo , Diferenciación Celular , Colágeno/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Células de la Médula Ósea , Células Cultivadas , Fosfatasa Alcalina/metabolismo , Mamíferos/metabolismoRESUMEN
The anti-PD-L1 immunotherapy has shown promise in treating cancer. However, certain patients with metastatic cancer have low response and high relapse rates. A main reason is systemic immunosuppression caused by exosomal PD-L1, which can circulate in the body and inhibit T cell functions. Here, we show that Golgi apparatus-Pd-l1-/- exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1. The GENPs can accumulate in tumors through homotypic targeting and effectively deliver retinoic acid, inducing disorganization of the Golgi apparatus and a sequence of intracellular events including alteration of endoplasmic reticulum (ER)-to-Golgi trafficking and subsequent ER stress, which finally disrupts the PD-L1 production and the release of exosomes. Furthermore, GENPs could mimic exosomes to access draining lymph nodes. The membrane antigen of PD-l1-/- exosome on GENPs can activate T cells through a vaccine-like effect, strongly promoting systemic immune responses. By combining GENPs with anti-PD-L1 treatment in the sprayable in situ hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.
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Exosomas , Melanoma , Animales , Ratones , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Inmunoterapia , Linfocitos T , Terapia de Inmunosupresión , Aparato de Golgi , Exosomas/metabolismoRESUMEN
Hexagonal boron nitride (BN) is an attractive filler candidate for thermal interface materials, but the thermal conductivity enhancement is limited by the anisotropic thermal conductivity of BN and disordered thermal pathways in the polymer matrix. Herein, a facile and economic ice template method is proposed, wherein BN modified by tannic acid (BN-TA) directly self-assemble to form vertically aligned nacre-mimetic scaffold without additional binders and post-treatment. The effects of the BN slurry concentration and the ratio of BN/TA on three-dimensional (3D) skeleton morphology are fully investigated. The corresponding polydimethylsiloxane (PDMS) composite via vacuum-impregnation achieves a high through-plane thermal conductivity of 3.8 W/mK at a low filler loading of 18.7 vol%, which is 2433% and 100% higher than that of pristine PDMS and the PDMS composite with randomly distributed BN-TA, respectively. The finite element analysis results theoretically demonstrate the superiority of the highly longitudinally ordered 3D BN-TA skeleton in axial heat transfer. Additionally, 3D BN-TA/PDMS exhibits excellent practical heat dissipation capability, lower thermal expansion coefficient, and enhanced mechanical properties. This strategy offers an anticipated perspective for developing high-performance thermal interface materials to address the thermal challenges of modern electronics.
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Transition metal phosphide (TMP) emerges as a promising electrocatalyst for overall water splitting (OWS). However, conventional TMP materials require exogenous metal ions to participate in coordination reactions, which usually suffer from active site blocking, pronounced intrinsic impedance, and inevitable catalyst shedding at high current density. Herein, a novel in-situ construction strategy has been developed to grow N-doped carbon (NC) enwrapped Co/CoP nanosheets directly onto Co foam (abbreviated as CoF) through a three-step transformation of Co to Co(OH)2 to Co-Metal-Organic Framework (Co-MOF) to Co/CoP/NC. In the entire preparation process, Co metal is only provided by the CoF substrate without external metal sources. Such in-situ construction yields tight contact at the interface of the heterogeneous catalyst, leading to much-reduced impedance and boundary vacancy, while the porous nitrogen-doped carbon backbone further endows the catalyst with the exposure of massive active sites, promotes mass transfer, and possesses high electrical conductivity. The Co/CoP/NC/CoF requires overpotentials of only 64 mV/263 mV@10 mA cm-2 and 414 mV/481 mV@400 mA cm-2 for both HER/OER in 1.0 M KOH, respectively. Remarkably, it reveals excellent OWS catalytic activity with a cell voltage of 1.56 V@10 mA cm-2 and 1.88 V@200 mA cm-2. This strategy of in-situ interface engineering transformation provides new ideas for direct device processing and construction of highly-efficient transition-metal-based OWS electrode materials.
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Patients with diabetic osteoporosis (DOP) often suffer from poor osseointegration of artificial implants, which is a challenge that affects implant outcomes. The osteogenic differentiation ability of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is the key to implant osseointegration. Studies have shown that the microenvironment of hyperglycemia affects the osteogenic differentiation of mesenchymal stem cells (MSC), but the mechanism is still unclear. Therefore, the aim of this study was to isolate and culture JBMMSCs from surgically derived bone fragments from DOP patients and control patients to investigate the differences in their osteogenic differentiation ability and to elucidate its mechanisms. The results showed that the osteogenic ability of hJBMMSCs was significantly decreased in the DOP environment. Mechanism study showed that the expression of senescence marker gene P53 was significantly increased in DOP hJBMMSCs compared to control hJBMMSCs according to RNA-sequencing result. Further, DOP hJBMMSCs were found to display significant senescence using ß-galactosidase staining, mitochondrial membrane potential and ROS assay, qRT-PCR and WB analysis. Overexpression of P53 in hJBMMSCs, knockdown of P53 in DOP hJBMMSCs, and knockdown followed by overexpression of P53 significantly affected the osteogenic differentiation ability of hJBMMSCs. These results suggest that MSC senescence is an important reason for decreasing osteogenic capacity in DOP patients. P53 is a key target in regulating hJBMMSCs aging, and knocking down P53 can effectively restore the osteogenic differentiation ability of DOP hJBMMSCs and promote osteosynthesis in DOP dental implants. It provided a new idea to elucidate the pathogenesis and treatment of diabetic bone metabolic diseases.
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OBJECTIVES: This study is aimed at assessing the Cone-beam computed tomographic (CBCT) characteristics of temporomandibular joints (TMJ) in degenerative temporomandibular joint disease (DJD) patients with chewing side preference (CSP). MATERIALS AND METHODS: CBCT images of 98 patients with DJD (67 with CSP and 31 without CSP) and 22 asymptomatic participants without DJD were measured retrospectively to compare the osteoarthritic changes and the morphology of TMJ. Quantitative analysis of the TMJ radiographic images was performed to present a comparison between the three inter-group groups and between the two sides of the joints. RESULTS: The frequencies of the articular flattening and surface erosion occur more often in the preferred side joints of DJD patients with CSP than the contralateral side. In addition, the horizontal angle of condyle, the depth of glenoid fossa (DGF), and the inclination of articular eminence (IAE) were larger in DJD patients with CSP than that in asymptomatic participants (p<0.05). Also, the condylar anteroposterior dimension of preferred side joints was significantly less than that of non-preferred side (p=0.026), while the width of condyles (p=0.041) and IAE (p=0.045) was greater. CONCLUSIONS: DJD patients with CSP appear to have a higher prevalence of osteoarthritic changes, with the morphological changes such as flat condyle, deep glenoid fossa, and steep articular eminence, which might be considered the characteristic imaging features. CLINICAL RELEVANCE: This study found that CSP is a predisposing factor for the development of DJD, and attention should be paid to the existence of CSP in DJD patients during the clinical practice.
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Cóndilo Mandibular , Trastornos de la Articulación Temporomandibular , Humanos , Estudios Retrospectivos , Masticación , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/diagnóstico por imagen , Tomografía Computarizada de Haz CónicoRESUMEN
Transition metal selenides (TMSes) with cubic pyrite-type crystal structure have been widely explored as electrocatalysts for oxygen evolution reaction (OER), but the insufficient hydrogen evolution reaction (HER) performance hinders the application of overall water splitting. Herein, we designed and prepared a Mo doped NiSe2-CoSe2 heterostructure aerogel as bifunctional electrocatalyst via facile spontaneous gelation and selenium vapor deposition. The active sites on the heterointerface possessed desirable Gibbs free energy of hydrogen adsorption, leading to better HER performance than single NiSe2 or CoSe2. Moreover, systematically experimental research and density functional theory (DFT) calculations revealed that fine regulated Mo doping improved the electropositivity of heterostructure, promoting the nucleophilic adsorption of water molecule. Benefit from those improvements, the optimal Mo doped NiSe2-CoSe2 aerogel exhibited an extremely low overpotential of 57 mV at the current density of 10 mA·cm-2 for HER with a small Tafel slope value of 38 mV·dec-1. Meanwhile, Mo doping provided higher electron transfer efficiency and better adsorptive property toward reaction intermediate in anodic reaction, resulting in low overpotential of 270 mV at the current density of 100 mA·cm-2 for OER with good electrocatalytic stability. This work provides an anticipated perspective of rational combination of metal doping and heterostructure for advanced electrocatalysts.
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The regulation of the multi-dimensional interface plays an important role in optimizing the electron transport and gas mass transfer during catalysis, which is conducive to promoting the electrocatalytic process. Herein, a self-supporting electrode has been developed with the multistage interface within 3D Ni2P@C nanospheres/nanoflowers arrays derived from metal-organic frameworks (MOFs) as template skeletons and precursors. The constructed nanosphere interface protrudes outward to optimize the contact with the electrolyte while the nanoflower lamellar connection promotes rapid electron transfer and exposes more active sites, and accelerates the gas diffusion with the abundant interspace channels. According to theoretical calculation, the synergistic effect between Ni2P and C is conducive to the optimal adsorption and desorption of H*, thus contributing to the improvement of catalytic kinetics. With the optimized growth times assembled onto nickel foam substrates, the Ni2P@C-12 h requires overpotentials of only 69 mV and 205 mV to drive the current density of 10 mA cm-2 towards hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. And it reveals an ultralow cell voltage of 1.55 V at 10 mA cm-2 to achieve overall water splitting (OWS). In addition, the stability of the Ni2P@C/NF electrocatalyst emerges as prominent long-term stability, which is attributed to the carbonaceous nanosphere anchors on the substrate to minimize the possibility of oxidation of the catalyst surface. This strategy of in situ growth of MOF-derived phosphates provides a general idea for interfacial engineering modification of OWS electrode materials.
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BACKGROUND: Dental pulp stem cells (DPSCs) refer to a type of stem cells, which is characterized by great differentiation potential and is easy to obtain. DPSCs are able to be employed for treating immune diseases and tissue regeneration. However, the differentiation ability exhibited by aging DPSCs is reduced, thereby limiting the application. As speculated by the microarray analysis, different expressions of miRNAs might be involved in DPSC senescence, whereas comprehensive transcriptome level detection has been rare. OBJECTIVE AND METHODS: To gain insights into the molecular mechanisms involved, RNA-sequencing, pathway enrichment and Gene Ontology Analysis were conducted on aging and young DPSCs. RESULTS: In this study, the differences in long non-coding RNA (lncRNA) and messenger RNA (mRNA expressions) of the aging and young DPSCs were demonstrated, and the vital factors and the relevant pathways were speculated. On the whole, 18950 mRNAs and 21854 lncRNAs were detected, among which 14 mRNAs and 7 lncRNAs were differentially expressed. Furthermore, hsa-miR-6724-5p may be a vital node in the aging process of DPSCs, and its target genes was involved in the dopaminergic synapse. CONCLUSION: In brief, the aging of DPSCs was significantly dependent of differentially expressed genes (DEGs) which is related to dopaminergic synapse. However, the specific function and internal relationship of the DEGs should be verified in depth.
Asunto(s)
MicroARNs , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Pulpa Dental , Proliferación Celular/genética , Diferenciación Celular , MicroARNs/genética , MicroARNs/metabolismo , Células Madre/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células CultivadasRESUMEN
Novel phase change materials composed of polyethylene glycol (PEG), cellulose nanofibers (CNFs) and carbon nanotubes (CNTs) were developed by an efficient and environment friendly strategy. The CNFs were modified and cross-linked by chitosan to form three-dimensional network structure, which provides strong support for the resulting CNF/CNT/PEG composites. The structure and properties of CNF/CNT/PEG composites were characterized using scanning electron microscopy, spectrums, and differential scanning calorimeter. They exhibit high latent heat (158.3 J/g), low heat loss (0.75%) and excellent photo-thermal conversion (energy storage efficiency 85.6%), electro-thermal conversion (energy storage efficiency 92.3%) properties. Due to their excellent performances, CNF/CNT/PEG composites have great potential to be used as thermal management materials.