ABSTRACT
Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal-organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn-MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn-MOF and the unique optical features of DUCNPs granted the DUCNP@Mn-MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn-MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn-MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn-MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors.
Subject(s)
Antineoplastic Agents , Metal-Organic Frameworks , Nanoparticles , Neoplasms , Animals , Mice , Drug Delivery Systems , Metal-Organic Frameworks/chemistry , Neoplasms/drug therapy , Nanoparticles/chemistry , Tumor MicroenvironmentABSTRACT
IFN-ß promoter stimulator-1 (IPS-1)- and stimulator of IFN genes (STING)-mediated type I IFNs play a critical role in antiviral responses. Myxovirus resistance (Mx) proteins are pivotal components of the antiviral effectors induced by IFNs in many species. An unprecedented expansion of Mx genes has occurred in fish. However, the functions and mechanisms of Mx family members remain largely unknown in fish. In this study, we found that grass carp (Ctenopharyngodon idella) MxG, a teleost-specific Mx protein, is induced by IFNs and viruses, and it negatively regulates both IPS-1- and STING-mediated antiviral responses to facilitate grass carp reovirus, spring viremia of carp virus, and cyprinid herpesvirus-2 replication. MxG binds and degrades IPS-1 via the proteasomal pathway and STING through the lysosomal pathway, thereby negatively regulating IFN1 antiviral responses and NF-κB proinflammatory cytokines. MxG also suppresses the phosphorylation of STING IFN regulatory factor 3/7, and it subsequently downregulates IFN1 and NF-κB1 at the promoter, transcription, and protein levels. GTPase and GTPase effector domains of MxG contribute to the negative regulatory function. On the contrary, MxG knockdown weakens virus replication and cytopathic effect. Therefore, MxG can be an ISG molecule induced by IFNs and viruses, and degrade IPS-1 and STING proteins in a negative feedback manner to maintain homeostasis and avoid excessive immune responses after virus infection. To our knowledge, this is the first identification of a negative regulator in the Mx family, and our findings clarify a novel mechanism by which the IFN response is regulated.
Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Antiviral Restriction Factors/immunology , Lysosomes/immunology , Membrane Proteins/immunology , Myxovirus Resistance Proteins/immunology , Proteasome Endopeptidase Complex/immunology , Animals , Carps/immunology , Cells, Cultured , Myxovirus Resistance Proteins/geneticsABSTRACT
Generating strong adhesion by engineered proteins has the potential for high technical applications. Current studies of adhesive proteins are primarily limited to marine organisms, e.g., mussel adhesive proteins. Here, we present a modular engineering strategy to generate a type of exotic protein adhesives with super strong adhesion behaviors. In the protein complexes, the lanmodulin (LanM) underwent α-helical conformational transition induced by lanthanides, thereby enhancing the stacking density and molecular interactions of adhesive protein. The resulting adhesives exhibited outstanding lap-shear strength of ≈31.7â MPa, surpassing many supramolecular and polymer adhesives. The extreme temperature (-196 to 200 °C) resistance capacity and underwater adhesion performance can significantly broaden their practical application scenarios. Ex vivo and in vivo experiments further demonstrated the persistent adhesion performance for surgical sealing and healing applications.
ABSTRACT
Synergistic therapy for malignant tumors has been developed in the past. However, several disadvantages that are associated with the applied inorganic nanoagents cannot be avoided, including intrinsic systemic toxicity, immunosuppression, and low therapeutic efficiency. Herein, a biocompatible, multifunctional, inorganic nanoagent that simultaneously integrates chemodynamic, starvation, and photothermal therapies is developed. This nanoagent effectively converts endogenous H2 O2 into highly toxic hydroxyl radicals via the Fenton reaction. Self-reinforced cancer therapy is achieved via the scavenging of intracellular glutathione and glucose. The encapsulation of nanoagent by erythrocytes drastically reduces its immune recognition by macrophages. Thus, an augmented anti-tumor immune response is realized. Moreover, in contrast to traditional inorganic chemodynamic nanomaterials, the nanoagent has outstanding photothermal efficiency. Therefore, the present system exhibits an effective tumor therapeutic outcome. This work may facilitate a new pathway for the development of highly efficacious synergetic therapies.
Subject(s)
Nanostructures , Neoplasms , Cell Line, Tumor , Glutathione/metabolism , Humans , Hydroxyl Radical , Neoplasms/drug therapyABSTRACT
Degradable bioplastics have attracted growing interest worldwide. However, it is challenging to develop bioplastics with a simple processing procedure, strong mechanical performance, good biocompatibility, and adjustable physicochemical properties. Herein, we introduced structural proteins as building blocks and developed a simple environmentally friendly approach to fabricate diverse protein-based plastics. A cost-effective and high-level production approach was developed through batch fermentation of Escherichia coli to produce the biomaterials. These bioplastics possess super plasticity, biocompatibility, biodegradability, and high resistance to organic solvents. Their structural and mechanical properties can be precisely controlled. Besides, high density information storage and hemostatic applications were realized in the bioplastic system. The customizable bioplastics have great potential for applications in numerous fields and are capable to scale up to the industrial level.
Subject(s)
Plastics , Proteins , Fermentation , Information Storage and Retrieval , Plastics/chemistry , SolventsABSTRACT
Chondroitinases, catalyzing the degradation of chondroitin sulfate (CS) into oligosaccharides, not only play a crucial role in understanding the structure and function of CS, but also have been reported as a potential candidate drug for the treatment of high CS-related diseases. Here, a marine bacterium Vibrio hyugaensis LWW-1 was isolated, and its genome was sequenced and annotated. A chondroitinase, VhChlABC, was found to belong to the second subfamily of polysaccharide lyase (PL) family 8. VhChlABC was recombinant expressed and characterized. It could specifically degrade CS-A, CS-B, and CS-C, and reached the maximum activity at pH 7.0 and 40 °C in the presence of 0.25 M NaCl. VhChlABC showed high stability within 8 h under 37 °C and within 2 h under 40 °C. VhChlABC was stable in a wide range of pH (5.0~10.6) at 4 °C. Unlike most chondroitinases, VhChlABC showed high surfactant tolerance, which might provide a good tool for removing extracellular CS proteoglycans (CSPGs) of lung cancer under the stress of pulmonary surfactant. VhChlABC completely degraded CS to disaccharide by the exolytic mode. This research expanded the research and application system of chondroitinases.
Subject(s)
Chondroitinases and Chondroitin Lyases/chemistry , Surface-Active Agents/chemistry , Vibrio , Animals , Aquatic OrganismsABSTRACT
Hydrogels enable a variety of applications due to their dynamic networks, structural flexibility, and tailorable functionality. However, their mechanical performances are limited, specifically in the context of cellular mechanobiology. It is also difficult to fabricate robust gel networks with a long-term durability. Thus, a new generation of soft materials showing outstanding mechanical behavior for mechanobiology applications is highly desirable. We combined synthetic biology and supramolecular assembly to prepare elastin-like protein (ELP) organogel fibers with extraordinary mechanical properties. The mechanical performance and stability of the assembled anisotropic proteins are superior to other organo-/hydrogel systems. Bone-derived mesenchymal cells were introduced into the organofiber system for stem-cell lineage differentiation. This approach demonstrates the feasibility of mechanically strong and anisotropic organonetworks for mechanobiology applications and holds great potential for tissue-regeneration translations.
Subject(s)
Hydrogels/metabolism , Mesenchymal Stem Cells/metabolism , Anisotropy , Biophysics , Cell Differentiation , Humans , Hydrogels/chemistry , Mesenchymal Stem Cells/chemistry , Mesenchymal Stem Cells/cytology , Tissue EngineeringABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder and the primary cause of age-related dementia. The etiology of AD is complex and has not been completely elucidated. Herein, we report that treatment with elastin-like polypeptides (ELPs), a component of the brain extracellular matrix (ECM), significantly increased the levels of AD-related amyloid-ß peptides (Aß) both inâ vitro and inâ vivo. Regarding the molecular mechanism(s), the upregulation of Aß levels was related to increased proteolytic processing of the amyloid precursor protein. Furthermore, nesting tests demonstrated that the ELP-treated animals showed significant neurobehavioral deficits with cognitive impairment. These results suggest that the elastin is associated with AD-related pathological and behavioral changes. This finding presents a new aspect for Alzheimer's amyloidosis event and provides a great promise in developing ELP-based model systems to better understand the pathogenesis of AD.
Subject(s)
Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Elastin/metabolism , Peptides/metabolism , Humans , Up-RegulationABSTRACT
Pex11p plays a crucial role in peroxisome fission. Previously, it was shown that a conserved N-terminal amphipathic helix in Pex11p, termed Pex11-Amph, was necessary for peroxisomal fission in vivo while in vitro studies revealed that this region alone was sufficient to bring about tubulation of liposomes with a lipid consistency resembling the peroxisomal membrane. However, molecular details of how Pex11-Amph remodels the peroxisomal membrane remain unknown. Here we have combined in silico, in vitro and in vivo approaches to gain insights into the molecular mechanisms underlying Pex11-Amph activity. Using molecular dynamics simulations, we observe that Pex11-Amph peptides form linear aggregates on a model membrane. Furthermore, we identify mutations that disrupted this aggregation in silico, which also abolished the peptide's ability to remodel liposomes in vitro, establishing that Pex11p oligomerisation plays a direct role in membrane remodelling. In vivo studies revealed that these mutations resulted in a strong reduction in Pex11 protein levels, indicating that these residues are important for Pex11p function. Taken together, our data demonstrate the power of combining in silico techniques with experimental approaches to investigate the molecular mechanisms underlying Pex11p-dependent membrane remodelling.
Subject(s)
Cell Membrane/chemistry , Fungal Proteins/chemistry , Membrane Proteins/chemistry , Penicillium chrysogenum/enzymology , Peroxins/chemistry , Amino Acid Substitution , Fungal Proteins/genetics , Fungal Proteins/physiology , Membrane Proteins/genetics , Membrane Proteins/physiology , Models, Molecular , Molecular Dynamics Simulation , Mutation, Missense , Penicillium chrysogenum/genetics , Peptide Fragments/chemistry , Peroxins/genetics , Peroxins/physiology , Peroxisomes/chemistry , Protein Aggregates , Protein ConformationABSTRACT
BACKGROUND Ovarian cancer is a common type of malignant neoplasm. Its prognosis is poor because the disease is not well understood. Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), localized in peroxisomes, might be a regulatory factor in lipometabolism. However, the role of HSDL2 in ovarian cancer progression remains unknown. MATERIAL AND METHODS HSDL2 expression was detected by qPCR and immunohistochemistry in ovarian tumor samples and qPCR in human ovarian cancer cell lines. Cell proliferation was measured by Celigo and MTT assay. Cell cycle distribution and apoptosis were determined using flow cytometry. Giemsa staining was used for analyzing colony formation. Cell motility was performed using Transwell migration and invasion assays. Tumorigenesis in nude mice was also detected. RESULTS HSDL2 expression was upregulated in human ovarian cancer samples and in 3 human ovarian cancer cell lines: SKOV3, HO8910, and OVCAR-3. Higher expression of HSDL2 in ovarian tumor samples was associated with more progressed tumors (P=0.03) and lymphatic metastases (P=0.03). HSDL2 down-regulation by lentiviral-mediated HSDL2 knockdown suppressed cell proliferation, colony formation, and cell motility, while it promoted cell apoptosis and resulted in cell cycle arrest at the G0/G1 phase in human ovarian cancer cell lines OVCAR-3 and SKOV3. HSDL2 knockdown also inhibited tumorigenesis in mouse models. CONCLUSIONS This study shows that HSDL2 upregulation is associated with ovarian cancer progression. HSDL2 knockdown inhibited cell proliferation, colony formation, motility, and tumorigenesis. It induced apoptosis and cell cycle arrest and might therefore serve as a potential target for ovarian cancer therapy.
Subject(s)
Hydroxysteroid Dehydrogenases/metabolism , Ovarian Neoplasms/enzymology , Adult , Aged , Animals , Apoptosis/physiology , Carcinogenesis , Cell Cycle Checkpoints/physiology , Cell Line, Tumor , Cell Proliferation/physiology , Disease Progression , Down-Regulation , Female , HEK293 Cells , Heterografts , Humans , Hydroxysteroid Dehydrogenases/genetics , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Prognosis , Transcriptome , Up-RegulationABSTRACT
Chinese jujube (Ziziphus jujuba Mill.) fruit are much admired for their unique flavor and high nutritional value. This study tracks changes in skin color and antioxidant activity over six stages (S1 S6) of fruit development in two cultivars of jujube, 'Junzao' and the color mutant 'Tailihong'. The study records the changing levels of chlorophylls, carotenoids, anthocyanins, and phenolic compounds during fruit development. Contents of chlorophylls, ß-carotenes and anthocyanins decreased throughout the developmental stages in two jujube cultivars, while lutein contents decreased at first and then increased to a maximum at S6. The levels of total phenolics, total flavonoids, total flavanols, total anthocyanins, procyanidin B1, procyanidin B2, procyanidin B3, (+)-catechin, quercetin, and ferulic acid are significantly higher in 'Tailihong' than in 'Junzao' before the onset ripening (before S3). However, after S3 the level differences of these components in the two cultivars are not significant. In both cultivars, antioxidant activity reduces gradually throughout fruit development. Our findings indicate how the skin color of jujube fruit during maturation is due to changes in the levels of flavonoids, carotenoids, and anthocyanins. The color changes are also associated with changes in antioxidant activity.
Subject(s)
Antioxidants/metabolism , Phenols/metabolism , Ziziphus/chemistry , Anthocyanins/metabolism , Biflavonoids/metabolism , Carotenoids/metabolism , Catechin/metabolism , Coumaric Acids/metabolism , Proanthocyanidins/metabolism , Quercetin/metabolismABSTRACT
Complexation of biomacromolecules (e.g., nucleic acids, proteins, or viruses) with surfactants containing flexible alkyl tails, followed by dehydration, is shown to be a simple generic method for the production of thermotropic liquid crystals. The anhydrous smectic phases that result exhibit biomacromolecular sublayers intercalated between aliphatic hydrocarbon sublayers at or near room temperature. Both this and low transition temperatures to other phases enable the study and application of thermotropic liquid crystal phase behavior without thermal degradation of the biomolecular components.
Subject(s)
DNA/chemistry , Liquid Crystals/chemistry , Phase TransitionABSTRACT
ADAR (adenosine deaminases acting on RNA)-mediated adenosine-to-inosine (A-to-I) editing to double-stranded RNA (dsRNA) is a critical arm of the antiviral response. The present study focused on the structural and functional characterizations of grass carp (Ctenopharyngodon idella) ADAR2 (CiADAR2) gene. The complete genomic sequence of CiADAR2 is 150,458 bp in length, containing 12 exons and 11 introns. The open reading frame (ORF) of 2100 bp encodes a polypeptide of 699 amino acids (aa) which contains three highly conservative domains - two N-terminal dsRNA binding domains (dsRBDs) and one C-terminal deaminase domain. The predicted crystal structure of CiADAR2 deaminase domain suggested a catalytic center form in the enzyme active site. CiADAR2 mRNA was ubiquitously expressed in the fifteen tested tissues, and was induced post GCRV challenge in spleen and head kidney and C. idella kidney (CIK) cells. The ex vivo expression of CiADAR2 protein was verified by the Flag (tag)-based western blot assay. Antiviral activity assay of CiADAR2 was manifested by the delayed appearance of cytopathic effect (CPE) and inhibition of GCRV yield at 48 h post infection. Furthermore, in CiADAR2 overexpression cells, mRNA expression levels of CiIFN1, CiTLR7 and CiTLR8 were facilitated at different time points after GCRV infection, comparing to those in control group. Taken together, it was indicated that ADAR2 was an antiviral cytokine against GCRV and anti-GCRV function mechanism might involve in the TLR7/8-regulated IFN-signaling. These findings suggested that CiADAR2 was a novel member engaging in antiviral innate immune defense in C. idella, which laid a foundation for the further mechanism research of ADAR2 in fishes.
Subject(s)
Adenosine Deaminase/genetics , Carps , Fish Diseases/genetics , Fish Proteins/genetics , Immunity, Innate , Reoviridae Infections/veterinary , Adenosine Deaminase/metabolism , Animals , Fish Diseases/immunology , Fish Diseases/virology , Fish Proteins/metabolism , Gene Expression Regulation , Protein Structure, Tertiary , RNA, Double-Stranded/genetics , RNA, Double-Stranded/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reoviridae/physiology , Reoviridae Infections/genetics , Reoviridae Infections/immunology , Reoviridae Infections/virology , Sequence Analysis, DNA/veterinaryABSTRACT
As DNA exhibits persistent structures with dimensions that exceed the range of their intermolecular forces, solid-state DNA undergoes thermal degradation at elevated temperatures. Therefore, the realization of solvent-free DNA fluids, including liquid crystals and liquids, still remains a significant challenge. To address this intriguing issue, we demonstrate that combining DNA with suitable cationic surfactants, followed by dehydration, can be a simple generic scheme for producing these solvent-free DNA fluid systems. In the anhydrous smectic liquid crystalline phase, DNA sublayers are intercalated between aliphatic hydrocarbon sublayers. The lengths of the DNA and surfactant are found to be extremely important in tuning the physical properties of the fluids. Stable liquid-crystalline and liquid phases are obtained in the -20 °C to 200 °C temperature range without thermal degradation of the DNA. Thus, a new type of DNA-based soft biomaterial has been achieved, which will promote the study and application of DNA in a much broader context.
Subject(s)
Crystallization/methods , DNA/chemistry , Liquid Crystals/chemistry , Surface PropertiesABSTRACT
Mesenchymal stem cells (MSCs), also called multipotent mesenchymal stromal cells, exist in almost all tissues and are a key cell source for tissue repair and regeneration. Under pathological conditions, such as tissue injury, these cells are mobilized towards the site of damage. Tissue damage is usually accompanied by proinflammatory factors, produced by both innate and adaptive immune responses, to which MSCs are known to respond. Indeed, recent studies have shown that there are bidirectional interactions between MSCs and inflammatory cells, which determine the outcome of MSC-mediated tissue repair processes. Although many details of these interactions remain to be elucidated, we provide here a synthesis of the current status of this newly emerging and rapidly advancing field.
Subject(s)
Mesenchymal Stem Cells/immunology , Adaptive Immunity , Animals , Chronic Disease , Humans , Immunity, Innate , Inflammation/immunologyABSTRACT
Toll-like receptor 8 (TLR8), a prototypical intracellular member of TLR family, is generally linked closely to antiviral innate immune through recognizing viral nucleic acid. In this study, 5'-flanking region of Ctenopharyngodon idella TLR8 (CiTLR8), 671bp in length, was amplified and eight SNPs containing one SNP in the intron, three SNPs in the coding region (CDS) and four SNPs in the 3'-untranslated region (UTR) were identified and characterized. Of which 4062 A/T was significantly associated with the susceptibility/resistance to GCRV both in genotype and allele (P < 0.05), while 4168 C/T was extremely significantly associated with that (P < 0.01) according to the case (susceptibility)-control (resistance) analysis. Following the verification experiment, further analyses of mRNA expression, linkage disequilibrium (LD), haplotype and microRNA (miRNA) target site indicated that 4062 A/T and 4168 C/T in 3'-UTR might affect the miRNA regulation, while the exertion of antiviral effects of 4062 A/T might rely on its interaction with other SNPs. Additionally, the high-density of SNPs in 3'-UTR might reflect the specific biological functions of 3'-UTR. And also, the mutation of 747 A/G in intron changing the potential transcriptional factor-binding sites (TFBS) nearby might affect the expression of CiTLR8 transcriptionally or post-transcriptionally. Moreover, as predicted, the A/G transition of the only non-synonymous SNP (3846 A/G) in CDS causing threonine/alanine variation, could shorten the length of the α-helix and ultimately affect the integrity of the Toll-IL-1 receptor (TIR) domain. The functional mechanism of 3846 A/G might also involve a threonine phosphorylation signaling. This study may broaden the knowledge of TLR polymorphisms, lay the foundation for further functional research of CiTLR8 and provide potential markers as well as theoretical basis for resistance molecular breeding of grass carp against GCRV.
Subject(s)
Carps , Fish Diseases/genetics , Fish Proteins/genetics , Haplotypes , Polymorphism, Single Nucleotide , Reoviridae Infections/veterinary , Toll-Like Receptor 8/genetics , Animals , Cloning, Molecular , DNA, Complementary/genetics , DNA, Complementary/metabolism , Fish Diseases/immunology , Fish Diseases/virology , Fish Proteins/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Random Allocation , Real-Time Polymerase Chain Reaction/veterinary , Reoviridae/physiology , Reoviridae Infections/genetics , Reoviridae Infections/immunology , Reoviridae Infections/virology , Toll-Like Receptor 8/metabolismABSTRACT
As an intracellular pattern recognition receptor (PRR), laboratory of genetics and physiology 2 (LGP2) plays a pivotal role in detecting nucleic acids of invading pathogens and simultaneously modulating signaling by retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in type I interferon (IFN-I) pathway. Nevertheless, the underlying antiviral transcription mechanism of LGP2 remains obscure. The present study attempted to reveal the methylation levels of CiLGP2 (Ctenopharyngodon idella LGP2) in muscle and spleen of grass carp and their association with the resistance against grass carp reovirus (GCRV). By prediction, the CpG island was 133 bp in length in 5'-flanking region, containing six candidate CpG loci, whose methylation statuses were investigated by virtue of the bisulfite sequencing PCR (BSP) among muscle and spleen tissues in 120 individuals that were divided into resistant/susceptible groups after a challenge experiment, and the association analysis was performed with Chi-square test. Quantitative real-time RT-PCR (qRT-PCR) was employed to ascertain the interrelation between methylation status and transcription of CiLGP2. The CpG sites at -1394, -1366, -1331 and -1314 nt were identified as hypermethylated, inversely unmethylated at -1350 CpG site. The -1411 CpG site presented six methylation patterns as well as one mentionable type of mutation triggered by spontaneous deamination. Although there was no statistically significant difference on DNA methylation with resistance against GCRV at -1411 CpG site, the methylation levels were significantly lower in spleen than those in muscle, accompanied by higher mRNA expression of CiLGP2 in spleen. Notably, DNA methylation may be conceivably serve as an essential regulatory factor for CiLGP2 antiviral transcription in spleen. This research first demonstrated the relationship between DNA methylation and LGP2 gene expression, preliminary revealed the underlying transcription mechanism of CiLGP2 against GCRV as well as provided potential references and laid a theoretical foundation for viral recognition and regulation research of LGP2 in vertebrates.
Subject(s)
Carps , DNA Methylation , Dinucleoside Phosphates/genetics , Fish Diseases/genetics , Fish Proteins/genetics , Reoviridae Infections/veterinary , Reoviridae/physiology , 5' Flanking Region , Animals , Base Sequence , Dinucleoside Phosphates/metabolism , Disease Susceptibility/veterinary , Disease Susceptibility/virology , Fish Diseases/virology , Fish Proteins/metabolism , Molecular Sequence Data , Muscle, Skeletal/metabolism , Muscle, Skeletal/virology , Polymerase Chain Reaction/veterinary , Reoviridae Infections/genetics , Reoviridae Infections/virology , Spleen/metabolism , Spleen/virology , Transcription, GeneticABSTRACT
PURPOSE: To study the relationship between the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) and the osteogenic activity and oxygen level of alveolar bone. METHODS: The alveolar bones of 56 patients with chronic periodontitis who received dental treatment from March 2021 to March 2023 were collected as the experimental (periodontitis) group, and the healthy alveolar bones of 53 patients who received dental treatment during the same period were selected as the control group. The osteoblasts were cultured by tissue block culture, and modified Kaplow's alkaline phosphatase (ALP) staining was used to identify the cells. COX-2, PGE2 and osteoclastogenesis inhibitory factor (OPG) receptor activator of nuclear factor-κb ligand (RANKL) and other indicators were determined by ELISA. PGE2, COX-2, OPG, internal oxygen level, ALP, RANKL and their correlation were compared between the two groups. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: PGE2, COX-2 and RANKL in periodontitis group were significantly higher than those in the control group, but OPG, internal oxygen level and ALP were significantly lower than those in the control group (Pï¼0.05). PGE2 and COX2 were highly positively correlated with OPG, internal oxygen level and ALP, but were highly positively correlated with RANKL(Pï¼0.05). CONCLUSIONS: The expression of PGE2 and COX-2 is highly negatively correlated with ALP and oxygen levels. Clinical treatment may consider increasing oxygen levels, increasing oxygen partial pressure, and regulating ALP levels by drugs, so as to change the inflammatory condition of periodontitis or other dental diseases.
Subject(s)
Dinoprostone , Periodontitis , Humans , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Dinoprostone/pharmacology , Osteoblasts/metabolism , Osteogenesis , Osteoprotegerin/metabolism , RANK Ligand/metabolismABSTRACT
The utilization of bioderived flame retardants in biodegradable poly (lactic acid) (PLA) has profound practical implications for extending the widespread application of PLA composites and protecting the environment. Nevertheless, there are still certain challenges that require prompt attention, especially the ineffectiveness of bio-based flame retardants and their deterioration of the mechanical properties of PLA. This work introduced triglycidyl isocyanurate (TGIC), which has multiple epoxy functions, into the self-assembly process of phytic acid (PA) and chitosan (CS). The epoxy-modified bioderived flame retardant PA@CS-TGIC (PCT) was well dispersed in the PLA matrix and had a strong interfacial adhesion, while also TGIC had a synergistic char-forming effect. By compounding epoxy-modified ammonium polyphosphate (MAPP), 3%PCT/MAPP-PLA composites may reach a LOI value of 28.8 % and UL-94 V-0 rating. Simultaneously, the melting droplets had been considerably reduced. Tensile strength of the 3%PCT/MAPP-PLA composites was 67.0 MPa, 10.8 % higher than that of pure PLA. This work paves a new avenue for the development of PLA composites with robust mechanical and flame retardant properties.
Subject(s)
Flame Retardants , Polyesters , Polyesters/chemistry , Tensile Strength , Chitosan/chemistry , Phytic Acid/chemistry , Triazines/chemistryABSTRACT
In high molecular weight poly(L-lactic acid)/poly(D-lactic acid) (HMW PLLA/PDLA) blends, the construction of exclusive stereocomplex crystals (SC) with high crystallinity and strong melt memory remains a great challenge. In the present study, various norbornene dicarboxylate complexes (TMXNa, Mg, Al, or Ca) were employed as the stereo-selective nucleating agents (NAs), and their effect on the crystallization characteristics, rheological behavior, and heat resistance of PLLA/PDLA blends were thoroughly studied. Strikingly, TMX-Al facilitated the construction of exclusive SC with over 50 % crystallinity and excellent melt memory. The dense SC crystals network structure boosted the heat resistance of L/D-xAl blends with a VST as high as 145 °C. The strengthened intermolecular interaction fostered the generation of pre-ordered structure in the melt and enhanced chain interdiffusion, which contributed to intermolecular nucleation and SC crystallization in L/D-xAl blend. This study opens up a new avenue for melt processing and application development of SC-PLA materials.