ABSTRACT
The various applications of bearing-only sensor networks for detection and localization are becoming increasingly widespread and important. The array layout of the bearing-only sensor network seriously impacts the detection performance. This paper proposes a multi-strategy fusion improved adaptive mayfly algorithm (MIAMA) in a bearing-only sensor network to perform layout planning on the geometric configuration of the optimal detection. Firstly, the system model of a bearing-only sensor network was constructed, and the observability of the system was analyzed based on the Cramer-Rao Lower Bound and Fisher Information Matrix. Then, in view of the limitations of the traditional mayfly algorithm, which has a single initial population and no adaptability and poor global search capabilities, multi-strategy fusion improvements were carried out by introducing Tent chaos mapping, the adaptive inertia weight factor, and Random Opposition-based Learning. Finally, three simulation experiments were conducted. Through comparison with the Particle Swarm Optimization (PSO) algorithm, Mayfly Algorithm (MA), and Genetic Algorithm (GA), the effectiveness and superiority of the proposed MIAMA were validated.
ABSTRACT
A novel sustained chlorine-releasing polydimethylsiloxane/Ca(ClO)2 (PDMS/Ca(ClO)2) material was fabricated by encapsulating Ca(ClO)2 in a PDMS matrix due to its high hydrophobicity and high chemical stability, which showed immediate-responsive and long-lasting antibacterial capabilities in aqueous conditions. Free chlorine could be released from the PDMS/Ca(ClO)2 after immersion in water for 2 min and could also be sustainedly released for 2 weeks, while the released concentration is negatively related to the duration time and positively with the initial Ca(ClO)2 contents. Additionally, Ca(ClO)2 powder as a filler significantly affects the crosslinking and pore size of PDMS. The PDMS/Ca(ClO)2 materials exhibited enduring antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in both planktonic and multispecies-biofilm status. It is expected that this PDMS/Ca(ClO)2 material and its similar composite would be promising candidates for wide sustainable disinfection applications in biomedical and industrial fields.
ABSTRACT
RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKß and IκBα are decreased. Moreover, the level of GSK3ß is increased, whereas the levels of Wnt3a, ß-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/ß-catenin signaling pathways in colonic cells.
Subject(s)
Colitis , NF-kappa B , Animals , Mice , beta Catenin/genetics , beta Catenin/metabolism , Colitis/genetics , Mice, Knockout , NF-kappa B/metabolism , Wnt Signaling PathwayABSTRACT
Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.
Subject(s)
Genetic Therapy , Nucleic Acids , Humans , Nucleic Acids/administration & dosage , Genetic Therapy/methods , Transfection/methods , Administration, Inhalation , Lung Diseases/therapy , Lung Diseases/genetics , Gene Transfer Techniques , Lung/metabolism , AnimalsABSTRACT
The problem of state estimation based on bearing-only sensors is increasingly important while existing research on distributed filtering solutions is rather limited. Therefore, this paper proposed the novel distributed cubature information filtering (DCIF) method for addressing the state estimation challenge in bearing-only sensor networks. Firstly, the system model of the bearing-only sensor network was constructed, and the observability of the system was analyzed. The sensor nodes are paired to measure relative angle information. Subsequently, the coordinated consistency theory is employed to achieve a unified state estimation of the maneuvering target. The DCIF method enhances the observability of the system, addressing the issues of large accuracy errors and divergence in traditional nonlinear filtering algorithms. Building upon the theoretical proof of consistency convergence in DCIF, four simulation experiments were conducted for comparison. These experiments validate the effectiveness and superiority of the DCIF method in bearing-only sensor networks.
ABSTRACT
Polyphenolic compound-modified hydrogel wound dressings with excellent wet tissue adhesion, antimicrobial properties, stretchability, and full-thickness skin healing properties are still extremely rare so far. Polyphenolic compounds such as tannic acid or dopamine can improve the antibacterial and bioadhesive properties of hydrogels, and are also polymerization inhibitors for free radical polymerization. In this study, polyacrylic acid (PAA) aqueous solution was first synthesized, and then antibacterial PAA-TA hydrogel was prepared by mixing it with tannic acid (TA) and the crosslinker 1,6-hexanediol bis(2-methyl-1-propionic acid azide) (HBMAP). This method avoids the hindrance of the phenolic hydroxyl groups in TA on acrylic acid polymerization, and we were able to obtain a series of TA hydrogels (in the range of 0-15 wt.%. We applied these PAA-TA hydrogels to wound dressings and found that they had excellent adhesion to biological tissues, and the tensile strength and elongation at break of PAA-TA hydrogels with 15 wt.%TA content were as high as 1.72 MPa and 1446.3% in tensile strength evaluation. In addition, microbiological analysis showed that wound dressings had significant antimicrobial activity against Staphylococcus aureus and Escherichia coli. In vitro wound healing experiments confirmed that the wound dressing was biocompatible and could significantly promote the healing of full-thickness skin defects in the guinea pig model. Our work describes an injectable, self-healing, antimicrobial hydrogel that may have promising clinical applications as a wound dressing material.
Subject(s)
Acrylic Resins , Anti-Infective Agents , Hydrogels , Polyphenols , Animals , Guinea Pigs , Anti-Bacterial Agents/pharmacology , Bandages , Escherichia coliABSTRACT
Objective: This study aimed to elucidate the prognostic implications of deviant expressions of long non-coding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL), microRNA-363-3p (miR-363-3p), and ADAM metallopeptidase domain 10 (ADAM10) in patients diagnosed with ovarian serous cystadenocarcinoma (OSC). Methods: To predict and refine the targeted miRNAs and downstream target genes for PURPL, we utilized open medical databases. Through the employment of real-time RT-PCR, we conducted tissue analysis to discern the expressions of PURPL, miR-363-3p, and ADAM10 in both OSC and control tissues. The pathological correlations in the clinic and the prognostic implications of deviant expressions of PURPL, miR-363-3p, and ADAM10 in OSC patients were analyzed independently. Results: Database inquiries revealed that PURPL might target miR-363-3p, and in turn, miR-363-3p could target ADAM10. Differential expression of PURPL, miR-363-3p, and ADAM10 was observed between OSC and paired tissues. The premature version of miR-363-3p, miR-363, correlated with overall survival (OS), while ADAM10 corresponded with progression-free survival (PFS) in ovarian cancer patients. Tissue detection displayed significantly elevated expressions of PURPL and ADAM10, and conspicuously diminished expressions of miR-363-3p in OSC tissues compared to the control tissues (P<0.05). A negative correlation was observed between the expressions of PURPL and miR-363-3p, and miR-363-3p and ADAM10, while a positive correlation was found between PURPL and ADAM10 in different ovarian tissues (P<0.05). In OSC tissues, upregulation of PURPL was associated with an advanced clinical stage, TP53 mutation, and lymph node metastasis (P<0.05), downregulation of miR-363-3p was associated with a more advanced clinical stage and lymph node metastasis (P<0.05), and overexpression of ADAM10 correlated with a more advanced FIGO stage. High expressions of PURPL and ADAM10, and low expression of miR-363-3p, were linked with poor PFS and OS in OSC patients, respectively (P<0.05). In addition, OSC patients with elevated PURPL and reduced miR-363-3p, patients with elevated PURPL and ADAM10, and patients with reduced miR-363-3p and elevated ADAM10 also demonstrated worse PFS and OS, respectively (P<0.05). Conclusions: The anomalous expressions of PURPL, miR-363-3p, and ADAM10 might contribute to the pathogenesis of OSC via up-down stream regulation, and these abnormal expressions could serve as potential prognostic indicators for OSC patients.
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WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.
Subject(s)
Ovarian Neoplasms , Tumor Necrosis Factor-alpha , Female , Humans , Prognosis , Cell Communication , ChromatinABSTRACT
The effective treatment for periodontitis is to completely and sustainedly eradicate the bacterial pathogens from the complex periodontal pockets. Local sustained-release antibiotics as a complementary treatment after scaling and root planning can sustainedly combat bacterial pathogens in the periodontal pockets to help treat the disease, but the increasing concern of bacterial resistance limits its future use. Here, we reported a local antibacterial system based on microsized multifunctional Ag-TiO2-x encapsulated in alginate (ATA) microspheres. We confirmed that ATA displayed strong photothermally enhanced dual enzyme-mimicking (peroxidase-like and catalase-like) activities and weak photocatalytic activity under 808 nm near-infrared (NIR) irradiation, which could boost the generation of reactive oxygen species (ROS) and O2 in the presence of low-level H2O2. As a result, the ATA/H2O2/NIR system exhibited efficient antibacterial activity against Porphyromonas gingivalis and Streptococcus gordonii in both planktonic and biofilm forms. With the help of ROS, ATA could release Ag+ in concentrations sufficient to inhibit periodontal pathogens as well. Moreover, the in situ-generated oxygen was supposed to alleviate the local hypoxic environment and would help downregulate the lipopolysaccharide-mediated inflammatory response of periodontal stem cells. The in vivo rat periodontitis treatment results demonstrated that the ATA/H2O2/NIR system reduced the bacterial load, relieved inflammation, and improved tissue healing. Our work developed a new local prolonged bactericidal and oxygenation system for enhanced periodontitis. Avoiding the usage of antibiotics and nanomaterials, this strategy showed great promise in adjunctive periodontitis treatment and also in other biomedical applications.
Subject(s)
Alginates , Periodontitis , Rats , Animals , Alginates/pharmacology , Periodontal Pocket/drug therapy , Reactive Oxygen Species/pharmacology , Hydrogen Peroxide/pharmacology , Microspheres , Periodontitis/drug therapy , Periodontitis/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Porphyromonas gingivalisABSTRACT
Acute leukemia is a type of blood cancer with a high mortality rate. Current therapeutic methods include bone marrow transplantation, supportive therapy, and chemotherapy. Although a satisfactory remission of the disease can be achieved, the risk of recurrence is still high. Therefore, novel treatments are demanding. Chimeric antigen receptor-T (CAR-T) therapy has emerged as a promising approach to treating and curing acute leukemia. To harness the therapeutic potential of CAR-T cell therapy for blood diseases, reliable cell morphological identification is crucial. Nevertheless, the identification of CAR-T cells is a big challenge posed by their phenotypic similarity with other blood cells. To address this substantial clinical challenge, herein we first construct a CAR-T dataset with 500 original microscopy images after staining. Following that, we create a novel integrated model called RCMNet (ResNet18 with Convolutional Block Attention Module and Multi-Head Self-Attention) that combines the convolutional neural network (CNN) and Transformer. The model shows 99.63% top-1 accuracy on the public dataset. Compared with previous reports, our model obtains satisfactory results for image classification. Although testing on the CAR-T cell dataset, a decent performance is observed, which is attributed to the limited size of the dataset. Transfer learning is adapted for RCMNet and a maximum of 83.36% accuracy is achieved, which is higher than that of other state-of-the-art models. This study evaluates the effectiveness of RCMNet on a big public dataset and translates it to a clinical dataset for diagnostic applications.
Subject(s)
Deep Learning , Leukemia , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/therapeutic use , Immunotherapy, Adoptive/methods , T-Lymphocytes , Leukemia/therapy , Leukemia/drug therapyABSTRACT
Golgi protein 73 (also known as GP73 or GOLPH2) is a transmembrane glycoprotein present in the Golgi apparatus. In diseased states, GP73 is expressed by hepatocytes rather than by bile duct epithelial cells. Many studies have reported that serum GP73 (sGP73) is a marker for hepatocellular carcinoma (HCC). For HCC diagnosis, the sensitivities of sGP73 were higher than that of other markers but the specificities were lower. Considering that the concentration of GP73 is consistent with the stage of liver fibrosis and cirrhosis, some studies have implied that GP73 may be a marker for liver fibrosis and cirrhosis. Increased sGP73 levels may result from hepatic inflammatory activity. During liver inflammation, GP73 facilitates liver tissue regeneration. By summarizing the studies on GP73 in liver diseases, we wish to focus on the mechanism of GP73 in diseases.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Biomarkers, Tumor , Carcinoma, Hepatocellular/pathology , Humans , Liver Cirrhosis/diagnosis , Liver Neoplasms/pathology , Membrane ProteinsABSTRACT
INTRODUCTION: During cell-free regenerative endodontic therapy, both stem cells from apical papilla (SCAPs) and periodontal ligament cells (PDLCs) are possible cell sources because of their proximity. Nonetheless, the regenerative ability of PDLCs and SCAPs under the induction of concentrated growth factors (CGFs) remains unclear. METHODS: PDLCs and SCAPs were treated with various concentrations of CGF-conditioned medium (CCM). The effects of CCM with or without Porphyromonas gingivalis lipopolysaccharide (LPS) on cell migration, odonto/osteogenic differentiation, and the expression of inflammatory cytokines were assessed. Dentin matrix transplants composed of PDLCs or SCAPs cell sheets coupled with CGF were put subcutaneously in immunocompromised mice for 8 weeks to explore their regenerative characteristics in vivo. RESULTS: CCM dose dependently enhanced the migration, proliferation, and odonto/osteogenic differentiation of PDLCs and SCAPs. CCM alleviated LPS-inhibited odonto/osteogenic differentiation of PDLCs and SCAPs as well as the LPS-induced up-regulation of inflammatory cytokines. In vivo, the newly regenerated tissue and microvessels formed by PDLCs and SCAPs were significantly increased under the induction of CGF. SCAPs mainly regenerated pulp/dentinlike tissues and a large number of microvessels, whereas PDLCs mainly formed bone/cementumlike structures. CONCLUSIONS: Overall, PDLCs excelled in cell proliferation, migration, and osteogenic differentiation, whereas SCAPs outperformed PDLCs in terms of angiogenic and odontogenic differentiation. The biological differences between PDLCs and SCAPs provided a possible theoretical basis for the formation of bone/cementum/periodontal ligament-like tissues after cell-free regenerative endodontic therapy.
Subject(s)
Dental Papilla , Osteogenesis , Animals , Cell Differentiation , Cell Proliferation , Cells, Cultured , Cytokines/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/pharmacology , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Mice , Periodontal Ligament , Stem Cells/physiologyABSTRACT
Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was â¼359 µm, and that of GelMA cores was â¼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. STATEMENT OF SIGNIFICANCE: Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo. This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.
Subject(s)
Alginates , Gelatin , Alginates/pharmacology , Capsules , Gelatin/chemistry , Gelatin/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , MethacrylatesABSTRACT
RATIONALE: Nicotine use disorder can alter synaptic plasticity correlated with learning and memory process. G protein-coupled receptor 55 (GPR55), a novel cannabinoid receptor, which is highly expressed in the central nervous system, plays a prominent role in learning and memory. However, the role of GPR55 in nicotine use disorder remains unclear. METHODS: In this study, we used the conditioned place preference (CPP) paradigm, a standard and well-established model for evaluating the rewarding effect of drug abuse, to investigate nicotine use disorder behavior in mice. After behavioral tests, the effect of GPR55 on nicotine response was evaluated using Western blotting, immunofluorescence staining, whole-cell patch-clamp recordings, and ELISA. RESULTS: GPR55 activation significantly reduced nicotine-CPP behavior by decreasing the spontaneous excitatory postsynaptic currents frequency in the nucleus accumbens (NAc) and the release of dopamine in serum. Furthermore, we found that the inhibition effects of nicotine response were mediated by phosphorylation of AMPAR. The PI3K-Akt signaling was involved in nicotine-CPP via GPR55 activation. CONCLUSION: Our findings showed that GPR55 in the NAc plays a specific role in blocking nicotine-CPP behavior and might be a potential target for the treatment of nicotine use disorder.
Subject(s)
Cannabinoids , Tobacco Use Disorder , Animals , Mice , Nucleus Accumbens , Phosphatidylinositol 3-Kinases , Phosphorylation , Receptors, Cannabinoid , RewardABSTRACT
AIMS: We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms. BACKGROUND: The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors. METHODS: Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments. RESULTS: The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth. CONCLUSION: Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.
ABSTRACT
Rapid angiogenesis is one of the challenges in endodontic regeneration. Recently, tailored polymeric microsphere system that loaded pro-angiogenic growth factors (GFs) is promising in facilitating vascularization in dental pulp regeneration. In addition, the synergistic effect of multiple GFs is considered more beneficial, but combination usage of them is rather complex and costly. Herein, we aimed to incorporate human platelet lysate (PL), a natural-derived pool of multiple GFs, into gelatin methacrylate (GelMA) microsphere system (GP), which was further modified by Laponite (GPL), a nanoclay with efficient drug delivery ability. These hybrid microspheres were successfully fabricated by electrostatic microdroplet technique with suitable size range (180â¼380 µm). After incorporation of the PL and Laponite with GelMA, the Young's modulus of the hybrid hydrogel increased up to about 3-fold and the swelling and degradation rate decreased simultaneously. The PL-derived GFs continued to release up to 28 days from both the GP and GPL microspheres, while the latter released relatively more slowly. What's more, the released GFs could effectively induce tubule formation of human umbilical endothelial cells (HUVECs) and also promote human dental pulp stem cells (hDPSCs) migration. Additionally, the PL component in the GelMA microspheres significantly improved the proliferation, spreading, and odontogenic differentiation of the encapsulated hDPSCs. As further verified by the subcutaneous implantation results, both of the GP and GPL groups enhanced microvascular formation and pulp-like tissue regeneration. This work demonstrated that PL-incorporating GelMA microsphere system was a promising functional vehicle for promoting vascularized endodontic regeneration. STATEMENT OF SIGNIFICANCE: Polymeric microsphere system loaded with pro-angiogenic growth factors (GFs) shows great promise for regeneration of vascularized dental pulp. Herein, we prepared a functional GelMA microsphere system incorporated with human platelet lysates (PL) and nanoclay Laponite by the electrostatic microdroplet method. The results demonstrated that the GelMA/PL/Laponite microspheres significantly improved the spreading, proliferation, and odontogenic differentiation of the encapsulated hDPSCs compared with pure GelMA microspheres. Moreover, they also enhanced microvascular formation and pulp-like tissue regeneration in vivo. This hybrid microsphere system has great potential to accelerate microvessel formation in regenerated dental pulp and other tissues.
Subject(s)
Gelatin , Methacrylates , Cell Proliferation , Dental Pulp , Endothelial Cells , Humans , Hydrogels , Microspheres , RegenerationABSTRACT
CircRNA LNPEP has been shown to promote the development of hepatocellular carcinoma, but its function in ovarian cancer (OC) remains unclear. The Kaplan-Meier method was used to analyze the clinical significance of circLNPEP expression in OC patients. The stability of circLNPEP was detected by actinomycin D and RNase R treatment. The correlations between miR-876-3p and two genes (circLNPEP and WNT5A) were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assay. Expressions of circLNPEP, miR-876-3p, and WNT5A were determined by qRT-PCR and western blot. The effect of circLNPEP/miR-876-3p/WNT5A axis on viability, proliferation, migration, and invasion, and angiogenesis of cells was determined by cell function experiment and rescue experiment. Xenograft tumor mice were constructed for in vivo verification. Expressions of apoptosis, epithelial mesenchymal transition (EMT)-related genes, and CD34 were determined by qRT-PCR, western blot and immunohistochemistry. High level of circLNPEP was related to poor prognosis in OC. CircLNPEP was highly expressed in OC tissues and cell lines, mainly distributed in the cytoplasm, while miR-876-3p was the opposite. MiR-876-3p targeted and negatively correlated with circLNPEP and WNT5A. Sh-circLNPEP repressed cell viability, proliferation, migration, invasion, angiogenesis, and EMT but promoted apoptosis, which were related to its regulation of expression of EMT- and apoptosis-related genes, WNT5A, and CD34. The regulatory effect of sh-circLNPEP can be reversed by miR-876-3p inhibitor, and that of miR-876-3p inhibitor can be reversed by sh-WNT5A. CircLNPEP promoted cancer cell proliferation, EMT and angiogenesis, and inhibited apoptosis by regulating miR-876-3p/WNT5A axis.