ABSTRACT
Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO3-x is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO3-x nanoreactors exhibit strong absorption of X-ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme-mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst-like activity and are sensitive to H2O2 in the tumor microenvironment (TME) under near infrared-II (NIR-II) light stimulation. They efficiently catalyze the conversion of H2O2 to O2, thereby ameliorating hypoxia, inhibiting the expression of HIF-1α, and enhancing RT-induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high H2O2 levels in TME, the Ir@WO3-x nanoreactor also exerts peroxidase-like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS-dependent death signaling. Furthermore, Ir@WO3-x can serve as a high-quality computed tomography contrast agent due to its high X-ray attenuation coefficient and generation of pronounced tumor-tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities.
ABSTRACT
Seed vigour, including rapid, uniform germination and robust seedling establishment under various field conditions, is becoming an increasingly essential agronomic trait for achieving high yield in crops. However, little is known about this important seed quality trait. In this study, we performed a genome-wide association study to identify a key transcription factor ZmRap2.7, which regulates seed vigour through transcriptionally repressing expressions of three ABA signalling genes ZmPYL3, ZmPP2C and ZmABI5 and two phosphatidylethanolamine-binding genes ZCN9 and ZCN10. In addition, ZCN9 and ZCN10 proteins could interact with ZmPYL3, ZmPP2C and ZmABI5 proteins, and loss-of-function of ZmRap2.7 and overexpression of ZCN9 and ZCN10 reduced ABA sensitivity and seed vigour, suggesting a complex regulatory network for regulation of ABA signalling mediated seed vigour. Finally, we showed that four SNPs in ZmRap2.7 coding region influenced its transcriptionally binding activity to the downstream gene promoters. Together with previously identified functional variants within and surrounding ZmRap2.7, we concluded that the distinct allelic variations of ZmRap2.7 were obtained independently during maize domestication and improvement, and responded separately for the diversities of seed vigour, flowering time and brace root development. These results provide novel genes, a new regulatory network and an evolutional mechanism for understanding the molecular mechanism of seed vigour.
ABSTRACT
Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.
Subject(s)
Apoptosis , Copper , Reactive Oxygen Species , Ruthenium , Copper/chemistry , Copper/pharmacology , Humans , Reactive Oxygen Species/metabolism , Animals , Ruthenium/chemistry , Ruthenium/pharmacology , Apoptosis/drug effects , Mice , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/therapy , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Ligands , Ferroptosis/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacologyABSTRACT
AIM: To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction (SMILE) with different myopic diopters. METHODS: Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study. Patients were allocated into three groups based on the preoperative spherical equivalent (SE): low myopia (SE≥-3.00 D), moderate myopia (-3.00 D>SE>-6.00 D) and high myopia (SE≤-6.00 D). Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times (1wk, 1, 3, 6mo, and 1y). Posterior mean elevation (PME) at 25 predetermined points of 3 concentric circles (2-, 4-, and 6-mm diameter) above the best fit sphere was analyzed. RESULTS: All surgeries were completed uneventfully and no ectasia was found through the observation. The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively (1mo: P=0.017; 3mo: P=0.018). The effect of time on ΔPME was statistically significant (2-mm ring: P=0.001; 4-mm ring: P<0.001; 6-mm ring: P<0.001). The effect of different corneal locations on ΔPME was significant except 1wk postoperatively (1mo: P=0.000; 3mo: P=0.000; 6mo: P=0.001; 1y: P=0.001). Posterior corneal stability was linearly correlated with SE, central corneal thickness, ablation depth, residual bed thickness, percent ablation depth and percent stromal bed thickness. CONCLUSION: The posterior corneal surface changes dynamically after SMILE. No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery. SMILE has good stability, accuracy, safety and predictability.
ABSTRACT
The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.
Subject(s)
Facial Nerve Injuries , Tissue Engineering , Humans , Tissue Engineering/methods , Facial Nerve Injuries/therapy , Porosity , Prostheses and Implants , Polymers , Nerve Regeneration , Tissue ScaffoldsABSTRACT
For the drawbacks of phase change materials such as poor shape stability and weak solar-thermal conversion ability, a rotunda-shaped carboxymethylcellulose/carbon nanotube aerogel (CA) with three-dimensional network was constructed by freeze casting with a special mold, and then impregnated with polyethylene glycol (PEG) in this work. The PEG/CA had an enthalpy of 183.21â J/g, and a thermal conductivity of 0.324â W m-1 K-1, which was 57 % higher than the pure PEG. The ability of PEG/CA to convert solar energy to thermal energy was a positive correlation between the inclusion of CNTs and the composite material's thermal conductivity. Under simulated sunlight, its solar-thermal conversion efficiency reaches 94.41 %, and after 10â min of irradiation, the surface temperature can reach 65 °C and the internal temperature can reach 44.67 °C. This rotunda-shaped PEG/CA is promising for the efficient use of renewable solar energy due to its strong solar-thermal conversion and thermal storage capabilities.
ABSTRACT
Tumor recurrence and wound healing represent significant burdens for tumor patients after the surgical removal of melanomas. Wound dressings with wound healing and anticancer therapeutic abilities could help to solve these issues. Thus, a hybrid hydrogel made of polyvinyl alcohol (PVA) and polyethylene imine (PEI) was prepared by cross-linking imine bond and boronic acid bond. This hydrogel was loaded with ruthenium nanorods (Ru NRs) and glucose oxidase (GOx) and named as nanocomposite hydrogel (Ru/GOx@Hydrogel), exhibiting remarkable photothermal/photodynamic/starvation antitumor therapy and wound repair abilities. Ru NRs are bifunctional phototherapeutic agents that simultaneously exhibit intrinsic photothermal and photodynamic functions. Three-dimensional composite hydrogel loaded with GOx can also consume glucose in the presence of O2 during tumor starvation therapy. Near-infrared (NIR) light-triggered hyperthermia can not only promote the consumption of glucose, but also facilitate the ablation of residual cancer cells. The antitumor effect of the Ru/GOx@Hydrogel resulted in significant improvements, compared to those observed with either phototherapy or starvation therapy alone. Additionally, the postoperative wound was substantially healed after treatment with Ru/GOx@Hydrogel and NIR irradiation. Therefore, the Ru/GOx@Hydrogel can be used as a multi-stimulus-responsive nanoplatform that could facilitate on-demand controlled drug release, and be used as a promising postoperative adjuvant in combination therapy.
Subject(s)
Hyperthermia, Induced , Nanotubes , Neoplasms , Ruthenium , Humans , Glucose Oxidase , Ruthenium/pharmacology , Polyethyleneimine , Polyvinyl Alcohol , Hydrogels/chemistry , Neoplasms/therapy , GlucoseABSTRACT
Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH2. Three compounds of Zeaxanthin (q = 0), Troglitazone (q = 0), and Sequinavir (q = +1 e) are singled out as potential inhibitors; Zeaxanthin can only be hit via USRCAT. These drugs displayed a stronger binding strength compared to the reported potent inhibitor CVT-10216. Sarizotan (q = +1 e) and Netarsudil (q = 0/+1 e) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. This likely left a space for substrate binding, and thus they were not ideal inhibitors. The MM-PBSA results indicate that the selected negatively charged compounds from the similarity search and Vina scoring are thermodynamically unfavorable, mainly due to electrostatic repulsion with the receptor (q = -6 e for ALDH2). The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.
Subject(s)
Drug Repositioning , Molecular Dynamics Simulation , Molecular Docking Simulation , Ligands , ZeaxanthinsABSTRACT
Human carbonic anhydrases (hCAs) have enzymatic activities for reversible hydration of CO2 and are acknowledged as promising targets for the treatment of various diseases. Using molecular docking and molecular dynamics simulation approaches, we hit three compounds of methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z for short), cyclothiazide, and 2,3,5,6-tetrafluoro-4-piperidin-1-ylbenzenesulfonamide (3UG for short) from the existing hCA I inhibitors and word-approved drugs. As a Zn2+-dependent metallo-enzyme, the influence of Zn2+ ion models on the stability of metal-binding sites during MD simulations was addressed as well. MM-PBSA analysis predicted a strong binding affinity of -18, -16, and -14 kcal/mol, respectively, for these compounds, and identified key protein residues for binding. The sulfonamide moiety bound to the Zn2+ ion appeared as an essential component of hCA I inhibitors. Vina software predicted a relatively large (unreasonable) Zn2+-sulfonamide distance, although the relative binding strength was reproduced with good accuracy. The selected compounds displayed potent inhibition against other hCA isoforms of II, XIII, and XIV. This work is valuable for molecular modeling of hCAs and further design of potent inhibitors.
Subject(s)
Carbonic Anhydrase I , Carbonic Anhydrases , Humans , Drug Repositioning , Molecular Docking Simulation , Sulfanilamide , Sulfonamides/pharmacologyABSTRACT
Gasdermin (GSDM) family, the key executioners of pyroptosis, play crucial roles in anti-pathogen and anti-tumor immunities, although little is known about the expression of GSDM in lung diseases at single-cell resolution, especially in lung epithelial cells. We comprehensively investigated the transcriptomic profiles of GSDM members in various lung tissues from healthy subjects or patients with different lung diseases at single cell level, e.g., chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung adenocarcinoma (LUAD), or systemic sclerosis (SSC). The expression of GSDM members varied among pulmonary cell types (immune cells, structural cells, and especially epithelial cells) and even across lung diseases. Regarding disease-associated specificities, we found that GSDMC or GSDMD altered significantly in ciliated epithelia of COPD or LUAD, GSDMD in mucous, club, and basal cells of LUAD and GSDMC in mucous epithelia of para-tumor tissue, as compared with the corresponding epithelia of other diseases. The phenomic specificity of GSDM in lung cancer subtypes was noticed by comparing with 15 non-pulmonary cancers and para-cancer samples. GSDM family gene expression changes were also observed in different lung epithelial cell lines (e.g., HBE, A549, H1299, SPC-1, or H460) in responses to external challenges, including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and AR2 inhibitor at various doses or durations. GSDMA is rarely expressed in those cell lines, while GSDMB and GSDMC are significantly upregulated in human lung epithelia. Our data indicated that the heterogeneity of GSDM member expression exists at different cells, pathologic conditions, challenges, probably dependent upon cell biological phenomes, functions, and behaviors, upon cellular responses to external changes, and the nature and severity of lung disease. Thus, the deep exploration of GSDM phenomes may provide new insights into understanding the single-cell roles in the tissue, regulatory roles of the GSDM family in the pathogenesis, and potential values of biomarker identification and development.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Neoplasm Proteins/metabolism , Transcriptome/genetics , Epithelial Cells/metabolism , Lung Neoplasms/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Biomarkers, Tumor/genetics , Pore Forming Cytotoxic Proteins/geneticsABSTRACT
Maize (Zea mays) kernel size is an important factor determining grain yield; although numerous genes regulate kernel development, the roles of RNA polymerases in this process are largely unclear. Here, we characterized the defective kernel 701 (dek701) mutant that displays delayed endosperm development but normal vegetative growth and flowering transition, compared to its wild type. We cloned Dek701, which encoded ZmRPABC5b, a common subunit to RNA polymerases I, II and III. Loss-of-function mutation of Dek701 impaired the function of all three RNA polymerases and altered the transcription of genes related to RNA biosynthesis, phytohormone response and starch accumulation. Consistent with this observation, loss-of-function mutation of Dek701 affected cell proliferation and phytohormone homeostasis in maize endosperm. Dek701 was transcriptionally regulated in the endosperm by the transcription factor Opaque2 through binding to the GCN4 motif within the Dek701 promoter, which was subjected to strong artificial selection during maize domestication. Further investigation revealed that DEK701 interacts with the other common RNA polymerase subunit ZmRPABC2. The results of this study provide substantial insight into the Opaque2-ZmRPABC5b transcriptional regulatory network as a central hub for regulating endosperm development in maize.
Subject(s)
DNA-Directed RNA Polymerases , Endosperm , Zea mays , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/metabolism , Endosperm/genetics , Endosperm/growth & development , Gene Expression Regulation, Plant , Plant Growth Regulators/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Zea mays/genetics , Zea mays/metabolismABSTRACT
Barley malt is produced through a malting process; it begins with steeping followed by germination and kilning, in which dramatic changes happen for a large number of physiological and biochemical traits in barley seeds. The objectives of this study were to comprehensively investigate the phenotypic changes during malting, and identify the key regulators that modulate the expression of genes associated with malt quality traits. The results showed that there was a significant positive correlation between gibberellic acid (GA) content and the activities of some hydrolytic enzymes, including α-amylases, ß-amylases, and limit dextrinase (LD), and a significant negative correlation between GA and ß-glucan content. Starch content had little change, but starch granules were pitted severely during malting. Weighted gene coexpression analysis (WGCNA) identified the genes associated with the greatest changes of the examined malt traits during malting. The correlation analysis and protein-protein interaction (PPI) analysis detected several key transcriptional factor (TF) regulating genes associated with malt quality. These genes and TFs regulating malting traits are potentially useful in barley breeding for malt quality improvement.
Subject(s)
Hordeum , Hordeum/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Breeding , Germination , Seedlings , Starch/metabolismABSTRACT
The African swine fever virus (ASFV) is a highly infectious viral pathogen that presents a major threat to the global pig industry. No effective vaccine is available for the virus. The p54 protein, a major structural component of ASFV, is involved in virus adsorption and entry to target cells and also plays a key role in ASFV vaccine development and disease prevention. Here, we generated species-specific monoclonal antibodies (mAbs), namely 7G10A7F7, 6E8G8E1, 6C3A6D12, and 8D10C12C8 (subtype IgG1/kappa type), against the ASFV p54 protein and characterized the specificity of these mAbs. Peptide scanning techniques were used to determine the epitopes that are recognized by the mAbs, which defined a new B-cell epitope, TMSAIENLR. Amino acid sequence comparison showed that this epitope is conserved among all reference ASFV strains from different regions of China, including the widely prevalent, highly pathogenic strain Georgia 2007/1 (NC_044959.2). This study reveals important signposts for the design and development of ASFV vaccines and also provides critical information for the functional studies of the p54 protein via deletion analysis.
Subject(s)
African Swine Fever Virus , African Swine Fever , Swine , Animals , Epitopes, B-Lymphocyte , Antibodies, Monoclonal , Viral ProteinsABSTRACT
Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.
ABSTRACT
Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.
Subject(s)
Hepatitis B , Nucleic Acids , Humans , RNA, Small Interfering/genetics , Genetic Therapy/methods , Hepatitis B/drug therapy , Half-Life , Genetic VectorsABSTRACT
Hypoxia, as a main feature of the tumor microenvironment, has greatly limited the efficacy of photodynamic therapy (PDT), as well as its clinical application. Here, a multifunctional composite nanoplatform, the peptide/Ce6/MnO2 nanocomposite (RKCM), has been constructed to alleviate tumor hypoxia and increase the efficacy of PDT using rationally designed peptide fibrils to encapsulate chlorin e6 (Ce6) inside and to mineralize MnO2 nanoparticles on the surface. As a result, RKCM significantly improved the PDT efficacy by increasing reactive oxygen species (ROS) generation, decreasing tumor cell viability, and inhibiting tumor growth and metastasis. Besides, decreased HIF-1α expression and increased immune-activated cell infiltration were also observed in RKCM/laser treatment xenograft. Mechanically, (1) Ce6 can induce singlet oxygen (1O2) generation under laser irradiation to give photodynamic therapy (PDT); (2) MnO2 can react with H2O2 in situ to supply additional O2 to alleviate tumor hypoxia; and (3) the released Mn2+ ions can induce a Fenton-like reaction to generate â¢OH for chemical dynamic therapy (CDT). Moreover, RKCM/laser treatment also presented with an abscopal effect to block the occurrence of lung metastasis by remolding the pre-metastasis immune microenvironment. With these several aspects working together, the peptide/Ce6/MnO2 nanoplatform can achieve highly efficient tumor therapy. Such a strategy based on peptide self-assembly provides a promising way to rationally design a cancer-responsive multifunctional nanoplatform for highly efficient combined cancer therapy by alleviating hypoxia and improving the immune microenvironment.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Cell Line, Tumor , Manganese Compounds/pharmacology , Hydrogen Peroxide/pharmacology , Oxides/pharmacology , Nanoparticles/therapeutic use , Hypoxia/drug therapy , Peptides/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Tumor Microenvironment , Neoplasms/drug therapyABSTRACT
BACKGROUND: As photosensitizer and photocatalyst, titanium dioxide (TiO2) can produce a photodynamic reaction for antibacterial treatment. This study aims to explore a Titanium dioxide/nano-hydroxyapatite (TiO2-HAP) composite combined with the dental curing lamp (385-515 nm) in clinical which could inhibit the dental plaque biofilm formed by Streptococcus mutans (S. mutans) and promote the enamel surface remineralization simultaneously. METHODS: X-ray Diffraction (XRD) and high resolution transmission electron microscope (HRTEM) were used to detect the characterization of TiO2-HAP composite nanomaterials. Photodynamic properties of TiO2-HAP were detected by Diffuse reflectance spectrum (DRS) and fluorescence spectroscopy. Bacterial growth was measured by reading the absorbance of bacterial cultures and confocal microscope was used to observe the biofilm removal ability of nanomaterials. The ability of TiO2-HAP to promote enamel remineralization was measured by Scanning electron microscope (SEM). RESULTS: The OD 600 of S. mutans was 0.76 in the control group and 0.13 in group of TiO2-HAP with exposure to light-emitting diode (LED) (150 mW/cm2) for 5 min, suggesting its sustained antibacterial potency and inhibition of the metabolic activity of dental plaque microcosm biofilm. Also, the release of calcium and phosphorus ions in TiO2-HAP can promote enamel mineralization simultaneously. After 15 days of remineralization, the Ca/P ratio of demineralized enamel surface increased from 1.28 to 1.67, which was similar to that of normal enamel. CONCLUSIONS: The TiO2-HAP exhibit a promising anti-bacterial activity and remineralization capacity which can prevent the occurrence of caries to the greatest extent and promote the biomimetic mineralization of dental tissues.
Subject(s)
Dental Caries , Dental Plaque , Nanostructures , Photochemotherapy , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Streptococcus mutans , Tooth Remineralization/methods , Anti-Bacterial Agents/pharmacology , Biofilms , Dental Caries/drug therapyABSTRACT
N-acetyltransferase 10 (NAT10), a nuclear acetyltransferase and a member of the GNAT family, plays critical roles in RNA stability and translation processes as well as cell proliferation. Little is known about regulatory effects of NAT10 in lung epithelial cell proliferation. We firstly investigated NTA10 mRNA expression in alveolar epithelial types I and II, basal, ciliated, club, and goblet/mucous epithelia from heathy and patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung adenocarcinoma, para-tumor tissue, and systemic sclerosis, respectively. We selected A549 cells for representative of alveolar epithelia or H1299 and H460 cells as airway epithelia with different genetic backgrounds and studied dynamic responses of NAT10-down-regulated epithelia to high temperature, lipopolysaccharide, cigarette smoking extract (CSE), drugs, radiation, and phosphoinositide 3-kinase (PI3K) inhibitors at various doses. We also compared transcriptomic profiles between alveolar and airway epithelia, between cells with or without NAT10 down-regulation, between early and late stages, and between challenges. The present study demonstrated that NAT10 expression increased in human lung epithelia and varied among epithelial types, challenges, and diseases. Knockdown of NAT10 altered epithelial mitochondrial functions, dynamic responses to LPS, CSE, or PI3K inhibitors, and transcriptomic phenomes. NAT10 regulates biological phenomes, and behaviors are more complex and are dependent upon multiple signal pathways. Thus, NAT10-associated signal pathways can be a new alternative for understanding the disease and developing new biomarkers and targets.
Subject(s)
Epithelial Cells , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/metabolism , Epithelial Cells/metabolism , Lung/metabolism , Acetyltransferases/metabolism , Acetyltransferases/pharmacology , A549 Cells , N-Terminal Acetyltransferases/metabolismABSTRACT
Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH-responsive i-motif DNA-mediated strategy to tailor the programmable behaviors of erbium-based rare-earth nanoparticles (ErNPs) decorated copper doped metal-organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i-motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near-infrared (NIR) photon-activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications.
ABSTRACT
Mitochondria play a critical role in cell growth and metabolism. And mitochondrial dysfunction is closely related to various diseases, such as cancers, and neurodegenerative and cardiovascular diseases. Therefore, it is of vital importance to monitor mitochondrial dynamics and function. One of the most widely used methods is to use nanotechnology-mediated mitochondria targeting and imaging. It has gained increasing attention in the past few years because of the flexibility, versatility and effectiveness of nanotechnology. In the past few years, researchers have implemented various types of design and construction of the mitochondrial structure dependent nanoprobes following assorted nanotechnology pathways. This review presents an overview on the recent development of mitochondrial structure dependent target imaging probes and classifies it into two main sections: mitochondrial membrane targeting and mitochondrial microenvironment targeting. Also, the significant impact of previous research as well as the application and perspectives will be demonstrated.