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In situ monitoring of tissue regeneration progression is of primary importance to basic medical research and clinical transformation. Despite significant progress in the field of tissue engineering and regenerative medicine, few technologies have been established to in situ inspect the regenerative process. Here, we present an integrated second near-infrared (NIR-II, 1000-1700 nm) window in vivo imaging strategy based on 3D-printed bioactive glass scaffolds doped with NIR-II ratiometric lanthanide-dye hybrid nanoprobes, allowing for in situ monitoring of the early inflammation, angiogenesis, and implant degradation during mouse skull repair. The functional bioactive glass scaffolds contribute to more effective bone regeneration because of their excellent angiogenic and osteogenic activities. The reliability of ratiometric fluorescence imaging, coupled with low autofluoresence in the NIR-II window, facilitates the accuracy of in vivo inflammation detection and high-resolution visualization of neovascularization and implant degradation in deep tissue.
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Elementos de la Serie de los Lantanoides , Animales , Regeneración Ósea , Ratones , Imagen Óptica/métodos , Reproducibilidad de los Resultados , Ingeniería de TejidosRESUMEN
Recent studies have shown that Fc-Fcγ receptor (FcγR) interactions are required for in vivo protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for in vivo protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating FcγRs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind FcγR. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and in vivo protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains in vivo; however, 100F4/IgG2a, but not 100F4/D265A, showed in vivo protection. Thus, we conclude that Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific.IMPORTANCE Abs play an important role in immune protection against influenza virus infection. Fc-FcγR interactions are required for in vivo protection by broadly neutralizing antistem, but not by virus strain-specific, anti-receptor binding site (RBS), Abs. Whether such interactions are necessary for protection by Abs that recognize epitopes outside RBS is not fully understood. In the present study, we investigated in vivo protection mechanisms against three H5 strains by two pan-H5 Abs, 65C6 and 100F4. We show that although these two Abs have similar neutralizing, binding, and ADCC activities against all three H5 strains in vitro, they have divergent requirements for Fc-FcγR interactions to protect against the three H5 strains in vivo The Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6. Thus, we conclude that Fc-FcγR interactions for in vivo protection by pan-H5 Abs is not strain specific, but epitope specific.
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Anticuerpos Antivirales/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Fragmentos Fc de Inmunoglobulinas/metabolismo , Subtipo H5N1 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Receptores de IgG/metabolismo , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/administración & dosificación , Anticuerpos Antivirales/química , Anticuerpos Antivirales/genética , Citotoxicidad Celular Dependiente de Anticuerpos , Epítopos/inmunología , Células HEK293 , Humanos , Inmunoglobulina G/inmunología , Ratones , Pruebas de Neutralización , Infecciones por Orthomyxoviridae/inmunología , Unión Proteica , Proteínas Recombinantes de Fusión/inmunología , Acoplamiento ViralRESUMEN
Sodium-ion batteries (SIBs) have caught considerable attention in last few years owing to the abundance of sodium in comparison to lithium. The commercial graphite anode is demonstrated unsuitable as an anode material for SIBs due to the larger radius of Na+ ions, whereas the transition metal dichalcogenides (TMDs) show great potential as anodes for SIBs because of their high achievable capacity. The sluggish kinetics, large volume expansion, and aggregation of those materials however results in severe decay of the electrochemical performance. In this work, a flower-like MoSe2 /C composite is synthesized with ethylenediamine and cassava starch (denoted as MoSe2 /Ccas ) and designed based on these principles: 1)â expand the d-spacing of (0 0 2) planes of MoSe2 to enhance the kinetics for the intercalation-deintercalation of Na+ ions and 2)â embed MoSe2 into the carbon matrix to enhance the conductivity and restrict the volume expansion and aggregation of MoSe2 . As a result, MoSe2 /Ccas exhibits superior cycle performance and rate capability for sodium storage. It shows durable long-life cycle capability with a reversible capacity of 360â mAh g-1 after 350â cycles at 0.5â Ag-1 . At the current density of 4â Ag-1 , the reversible capacity is still maintained at 266â mAh g-1 .
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A facile and scalable method is realized for the inâ situ synthesis of N/S co-doped 3 D porous carbon nanosheet networks (NSPCNNs) as anode materials for sodium-ion batteries. During the synthesis, NaCl is used as a template to prepare porous carbon nanosheet networks. In the resultant architecture, the unique 3 D porous architecture ensures a large specific surface area and fast diffusion paths of both electrons and ions. In addition, the import of N/S produces abundant defects, increased interlayer spacings, more active sites, and high electronic conductivity. The obtained products deliver a high specific capacity and excellent long-term cycling performance, specifically, a capacity of 336.2â mA h g-1 at 0.05â A g-1 , remaining as large as 214.9â mA h g-1 after 2000 charge/discharge cycles at 0.5â A g-1 . This material has great prospects for future applications of scalable, low-cost, and environmentally friendly sodium-ion batteries.
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Allograft rejection has been an obstacle for long-term survival of patients for many years. Current strategies for transplant rejection are not as optimal as we expected, especially for long-term treatments. Trichinella spiralis, a nematode parasitized in mammalian muscle and as an invader, maintains harmonious with host in the long term by evading host immune attack. To determine whether T. spiralis infection impacts on allograft rejection, we performed mice cardiac allograft transplantation model by using BALB/c (H-2(b)) mice as donors and C57BL/6 (H-2(b)) mice orally infected with 300 muscle larvae for 28 days as recipients. Graft survival was monitored by daily palpation of the abdomen; histologic change was observed by H&E stain; and CD4(+), CD8(+), CD4(+)IFN-γ(+), and CD4(+)IL-17(+) T cells and regulatory T cells were examined with the use of flow cytometry. Serum cytokine levels were measured by Luminex. Finally, we found that mean survival time of cardiac allografts in T. spiralis group was 23.40 ± 1.99 days, while the vehicle control group was 10.60 ± 0.75 days. Furthermore, we observed alleviated histological changes in the heart allograft, decreased corresponding CD8(+) T cells, suppressed Th1 and Th17 responses, and increased regulatory T cell frequency in a murine cardiac transplantation model at day 7 post-transplantation in experimental group. These data suggest that T. spiralis infection resulted in prolonged allograft survival following murine cardiac transplantation, with suppressed Th1/Th17 responses and augmented regulatory T cells.
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Rechazo de Injerto/prevención & control , Supervivencia de Injerto/fisiología , Trasplante de Corazón/normas , Trichinella spiralis/fisiología , Triquinelosis/inmunología , Aloinjertos , Animales , Linfocitos T CD8-positivos/inmunología , Citocinas/sangre , Citometría de Flujo , Humanos , Interferón gamma/inmunología , Interleucina-17/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Trasplante de Piel/normas , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th17/inmunología , Factores de Tiempo , Trasplante Heterotópico , Trasplante HomólogoRESUMEN
Since 1996, highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with virus-like particle induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and postattachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , ADN Viral/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Animales , Anticuerpos Neutralizantes/genética , Linfocitos T CD8-positivos/inmunología , ADN Viral/inmunología , Femenino , Vacunas contra la Influenza/inmunología , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Vacunación/métodosRESUMEN
The rapid spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral treatment. Previously, we developed human monoclonal antibodies 65C6 and 100F4 that neutralize almost all (sub)clades of HPAI H5N1. The conserved 65C6 epitope was mapped to the globular head of HA. However, neither the 100F4 epitope nor the neutralization mechanism by these antibodies was known. In this study, we determined the 100F4 epitope and unraveled a neutralization mechanism by antibodies 65C6 and 100F4.
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Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Epítopos/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Mapeo Epitopo , Humanos , Subtipo H5N1 del Virus de la Influenza A/inmunologíaRESUMEN
Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Epítopos/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Secuencia de Aminoácidos , Animales , Secuencia Conservada , Mapeo Epitopo , Epítopos/química , Epítopos/genética , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H5N1 del Virus de la Influenza A/química , Subtipo H5N1 del Virus de la Influenza A/genética , Virus de la Influenza A/química , Virus de la Influenza A/genética , Virus de la Influenza A/inmunología , Gripe Humana/virología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Pruebas de NeutralizaciónRESUMEN
Chronic low back pain (LBP) caused by intervertebral disc (IVD) degradation is a serious socioeconomic burden that can cause severe disabilities. Addressing the underlying pathogenic mechanisms of IVD degeneration may inspire novel therapeutic strategy for LBP. Herein, hypoxic preconditioning improves both the biological function of MSCs in hostile microenvironments and enhances the production of small extracellular vesicles (sEVs) with desirable therapeutic functions. In vitro results reveal that hypoxic preconditional engineering sEVs (HP-sEVs) alleviate the inflammatory microenvironments of IVD degradation, enhance the proliferation of nucleus pulposus (NP) cells, and promote proteoglycan synthesis and collagen formation. Transcriptomic sequencing reveales the excellent therapeutic effects of HP-sEVs in promoting extracellular matrix regeneration through the delivery of microRNA(miR)-7-5p, which further suppresses p65 production and thus the inhibition of Cxcl2 production. Moreover, in vivo results further confirm the robust therapeutic role of HP-sEVs in promoting IVD regeneration through the same mechanism mediated by miR-7-5p delivery. In conclusion, this study provides a novel therapeutic strategy for treating IVD degradation and is thus valuable for understanding the mechanism-of-action of HP-sEVs in IVD regeneration associated with chronic lower back pain.
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Vesículas Extracelulares , Degeneración del Disco Intervertebral , Disco Intervertebral , MicroARNs , Humanos , Vesículas Extracelulares/metabolismo , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , FN-kappa B/farmacología , FN-kappa B/uso terapéutico , Regeneración , Quimiocina CXCL2/metabolismoRESUMEN
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.
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Background: The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods: To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the effect and potential mechanism of sEVs on the effects of osteogenesis and angiogenesis. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs (BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results: hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion: This finding illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.
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Exosomas , MicroARNs , Humanos , Osteogénesis , Hidrogeles/farmacología , Andamios del Tejido , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración Ósea , Exosomas/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p<0.0001) but lower specificity (35.71 vs. 89.28%; p<0.0001). Among the 48 kinds of pathogens detected, the Torque teno virus 22 (15/122) was the most common, followed by Primate erythroparvovirus 1 (13/122). The top four bacteria included Klebsiella pneumoniae (n = 8), Enterococcus faecium (n = 5), Stenotrophomonas maltophilia (n = 4), and Escherichia coli (n = 4). Aspergillus fumigatus was the most common fungus. The bronchoalveolar lavage fluid (BALF) exhibited the highest proportion of positive findings among sample types, with viral, fungal, and bacterial mixed infection being the most common (n = 6, 19.35%). Besides, using mNGS for early diagnosis of infection after liver transplantation may effectively prolong patient survival. This is the first study to explore the application value of mNGS and its comparison with traditional culture in pneumonia and other infections in post-liver transplantation patients. The simultaneous application of these two methods suggested that the Torque teno virus 22, Klebsiella pneumoniae, and the Aspergillus fumigatus are the most common pathogens of viruses, bacteria, and fungi after LT, suggesting that these pathogens may be associated with postoperative pathogen infection and patient prognosis. The mNGS technique showed distinct advantages in detecting mixed, viral, and parasitic infections in this patient population. Further studies are warranted to systematically elucidate the dynamic evolution and molecular characteristics of infection after liver transplantation.
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The extrusion 3D printing of hydrogels has evolved as a promising approach that can be applied for specific tissue repair. However, the printing process of hydrogel scaffolds with high shape fidelity is inseparable from the complex crosslinking strategy, which significantly increases the difficulty and complexity of printing. The aim of this study was to develop a printable hydrogel that can extrude at room temperature and print scaffolds with high shape fidelity without any auxiliary crosslinking during the printing process. To this end, a novel formulation consisting of a Laponite suspension with a high solid concentration and a gelatine methacrylate (GelMA) nanocomposite hydrogel was developed. A homogeneously dispersed high-concentration (up to 20% w/v) Laponite suspension was obtained by stirring at 0 °C. The addition of Laponite with high concentration improved the rheological properties, the degradation stability, and the mechanical strength of the hydrogel. The formulation of 15% (w/v) GelMA and 8% (w/v) Laponite nanocomposite hydrogel exhibited desirable printability and biocompatibility. The GelMA/Laponite hydrogels significantly promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. Both desirable printability under mild conditions and cyto-compatibility enable composite hydrogel a potential candidate as biomaterial inks to be applied for bone tissue regeneration.
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Regeneración Ósea/efectos de los fármacos , Arcilla/química , Células Madre Mesenquimatosas/química , Nanogeles/química , Impresión Tridimensional , Desarrollo Óseo/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/fisiología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Gelatina/química , Humanos , Ensayo de Materiales , Metacrilatos/química , Osteogénesis/efectos de los fármacos , Reología , Silicatos/química , Silicatos/farmacologíaRESUMEN
The increasing incidence of hepatocellular carcinoma (HCC) is a major challenge worldwide. In the past few years, an increasing number of studies have suggested that circular RNAs (circRNAs) play an important role in the development of human tumors, including HCC, but our understanding of their function is still limited. In this study, we investigated differences in the expression of circRNA MAN2B2 (circMAN2B2) in hepatocellular tissues and paired normal tissues. We found that knockdown of circMAN2B2 expression in the HCC cell lines Hep-G2 and Huh-7 significantly inhibited cell proliferation by sponging (miRNA) miR-217 and inhibiting its function. Through a series of experiments, we also demonstrated that miR-217 functioned as a tumor suppressor molecule in HCC cells and regulated the expression of mitogen-activated protein kinase 1 (MAPK1). Restoration of MAPK1 rescued repression of cell proliferation induced by circMAN2B2 knockdown. In summary, our study indicated that circMAN2B2 acted as an onco-miRNA in HCC by sponging miRNA-217 to promote MAPK1 expression.
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Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.
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The grain structure and surface morphology of bio-implants act as a pivotal part in altering cell behavior. Titanium alloy bone screws, as common implants, are prone to screws loosening and complications threat in the physiological environment due to their inferior anti-wear and surface inertia. Manufacturing bone screws with high wear resistance and ideal biocompatibility has always been a challenge. In this study, a series of overlapping morphologies inspired by the hierarchical structure of fish scales and micro bulges of shrimp were structured on Ti-6Al-4V implant by laser texturing. The results indicate that the textured patterns could improve cell attachment, proliferation, and osteogenic differentiation. The short-term response of human bone marrow-derived mesenchymal stem cells (hBMSCs) on the textured surface are more sensitive to the microstructure than the surface roughness, wettability, grain size and surface chemical elements of the textured surfaces. More importantly, the friction-increasing and friction-reducing type overlapping structures exhibit excellent friction stability at different stages of modified simulated body fluid (m-SBF) soaking. The overlapping structure (Micro-smooth stacked ring: MSSR) is more beneficial to promote the formation of apatite. Deposited spherical-like apatite particles can act as a "lubricant" on the MSSR surface during the friction process to alleviate the adhesion wear of the surface. Meanwhile, apatite particles participate in the formation of friction film, which plays an effective role in reducing friction and antiwear in corrosion solution (m-SBF) for a long time. These features show that the combination of soaking treatment in m-SBF solution with laser-textured MSSR structure is expected to be an efficient and environmentally friendly strategy to prolong the service life of bone screws and reducing the complications of mildly osteoporotic implants.
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Osteogénesis , Titanio , Aleaciones , Animales , Fricción , Humanos , Rayos Láser , Propiedades de SuperficieRESUMEN
The lubrication states between the friction pairs in lubrications have an important effect on its tribological behavior. Therefore, the aim of this complementary data article is to identify the corresponding lubrication states between bone and Ti-6Al-4V interface in three biolubricants in reciprocation sliding by the Stribeck theory. Among that, three biolubricated film thicknesses at the stroke center and stroke end were separately calculated using the elastohydrodynamic theory. The current data are considered as a complementary for the main work "Tribological behavior of Ti-6Al-4V against cortical bone in different biolubricants" (Wang et al., 2018).
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Titanium alloys (Ti-6Al-4V) are promising materials as bone implants in clinical surgeries owing to their excellent performances. However, wear debris caused by the tribological behavior of the cortical bone and titanium alloy interface were found to be paramount for implant stability. The contact environment between the cortical bone and Ti-6Al-4V in vivo has been considered to affect the tribological behavior. Currently, the tribological behaviors of bone and Ti-6Al-4V in different biolubricants remain elusive. Therefore, in this work, the tribological behaviors of Ti-6Al-4V plates sliding against bovine cortical bone were investigated in dry sliding and in biolubricants of physiological saline (PS), simulated body fluids (SBF), and fetal bovine serum (FBS). Results show that the friction coefficient and wear rate of the bovine cortical bone and Ti-6Al-4V interface exhibit the same sequence as follows: FBS > SBF > PS > dry sliding. These results are attributed to bone hardness variation and corrosion of different biolubricants. Meanwhile, the effects of normal load and velocity on the tribological behavior of bone and Ti-6Al-4V interface were also investigated in dry sliding and three different biolubricants. Results show that as the normal load is increased and the sliding velocity is decreased, the friction coefficient decreases in dry condition, adhering to the Hertz contact theory. However, according to the boundary lubrication theory, the friction coefficient in three biolubricants correlates positively to the normal load and negatively to the sliding velocity. Moreover, the wear rates of the bone samples increase with the increase in normal load and sliding velocity under dry and biolubrication conditions. Finally, the characterization results indicate that the wear mechanisms of the cortical bone and Ti-6Al-4V interface in dry friction are primarily adhesive and abrasive wear. Further, corrosive wear occurs in biolubrications, apart from adhesive and abrasive wear.
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Materiales Biocompatibles/farmacología , Hueso Cortical/efectos de los fármacos , Lubricantes/farmacología , Titanio/farmacología , Aleaciones , Animales , Materiales Biocompatibles/química , Bovinos , Corrosión , Electroquímica , Fricción , Dureza/efectos de los fármacos , Lubricantes/química , Fenómenos Mecánicos , Propiedades de Superficie , Titanio/químicaRESUMEN
BACKGROUND: The correlation between single nucleotide polymorphism (SNP) rs12807809 in Neurogranin (NRGN) gene and Schizophrenia (SCZ) was investigated by several studies, whereas the results were conflicting. Thus, we performed the present meta-analysis to combine and analyze the available studies in order to provide a more accurate result on the association of rs12807809 polymorphism in NRGN gene and SCZ vulnerability. METHODS: A comprehensive retrieval in PubMed, EMBASE, Web of Science, Cochrane Library and Wanfang was performed for relevant studies on the relationship of rs12807809 polymorphism and SCZ. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant and recessive model to appraise the association. RESULTS: The meta-analysis included 8 studies containing 12552 SCZ cases and 34783 controls. The results showed a statistically significant correlation between SCZ and rs12807809 polymorphism in overall population in allelic model (ORâ=â1.10, 95%CI 1.04-1.17). However, subgroup analysis indicated the association only existed in Caucasians but not Asian. CONCLUSION: The results of present meta-analysis suggested significant association between SNP rs12807809 in NRGN gene and SCZ susceptibility in Caucasians but not Asians.
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Neurogranina/genética , Esquizofrenia/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Rapid and effective osseointegration, as a critical factor in affecting the success rate of titanium (Ti) implants in orthopedic applications, is significantly affected by their surface microstructure and chemical composition. In this work, surface microgrooved Ti-6Al-4V alloys with graphene oxide coating (Ti-G-GO) were fabricated by a combination of laser processing and chemical assembly techniques. The osteogenic capability in vitro and new bone formation in vivo of the implants were systematically investigated, and biomechanical pull-out tests of the screws were also performed. First, in vitro studies indicated that the optimal microgroove width of the titanium alloy surface was 45 µm (Ti-G), and the optimum GO concentration was 1 mg/mL. Furthermore, the effects of the surface microstructure and GO coating on the in vitro bioactivity were investigated through culturing bone marrow mesenchymal stem cells (BMSCs) on the surface of titanium alloy plates. The results showed that the BMSCs cultured on the Ti-G-GO group exhibited the best adhesion, proliferation, and differentiation, compared with that on the Ti-G and Ti groups. Micro-computed tomography evaluation, histological analysis, and pull-out testing demonstrated that both Ti-G and Ti-G-GO implants had the higher osseointegration than the untreated Ti implant. Moreover, the osteogenic capability of the Ti-G-GO group appeared to be superior to that of the Ti-G group, which could be attributed to the improvement of surface wettability and apatite formation by the GO coatings. These results suggest that the combination of the microgroove structure and GO coatings exhibits considerable potential for enhancing the surface bioactivation of materials, and the combination modification is expected to be used on engineered titanium alloy surfaces to enhance osseointegration for orthopedic applications.