Revealing the intrinsic peroxidase-like catalytic mechanism of O-doped CoS2 nanoparticles.

CoS2 nanoparticles (NPs) have shown promise as potential peroxidase (POD)-like catalysts, but the catalytic molecular mechanisms are largely unknown. Moreover, no study has adequately explored the influence of O-doping induced by the inevitable oxidation of CoS2 on their POD-like activity. Here, O-doped CoS2 NPs were prepared by a one-step method, and their intrinsic POD-like catalytic mechanism was investigated with a combined experimental and theoretical approach. The hydroxyl radical (˙OH) and the superoxide radical (O2˙-) have been found to play significant roles in the POD-like activity, and ˙OH is the major radical. The O-doping could reduce the transition-state energy barrier of H2O2 dissociation, thus promoting the decomposition of H2O2 to ˙OH and inducing the formation of O2˙-. Therefore, O-doping is an effective method for enhancing the catalytic activity of CoS2 NPs. Furthermore, due to the excellent oxidation property of ˙OH and O2˙-, this nanozyme exhibited efficient catalytic activity towards the degradation of organic dyes with H2O2. This manuscript provides a new inspiration for designing more promising anion-defective transition-metal sulfide nanozymes for different applications.

Nanozymes in the Treatment of Diseases Caused by Excessive Reactive Oxygen Specie.

Excessive reactive oxygen species (ROS) may generate deleterious effects on biomolecules, such as DNA damage, protein oxidation and lipid peroxidation, causing cell and tissue damage and eventually leading to the pathogenesis of diseases, such as neurodegenerative diseases, ischemia/reperfusion ((I/R)) injury, and inflammatory diseases. Therefore, the modulation of ROS can be an efficient means to relieve the aforementioned diseases. Several studies have verified that antioxidants such as Mitoquinone (a mitochondrial-targeted coenzyme Q10 derivative) can scavenge ROS and attenuate related diseases. Nanozymes, defined as nanomaterials with intrinsic enzyme-like properties that also possess antioxidant properties, are hence expected to be promising alternatives for the treatment of ROS-related diseases. This review introduces the types of nanozymes with inherent antioxidant activities, elaborates on various strategies (eg, controlling the size or shape of nanozymes, regulating the composition of nanozymes and environmental factors) for modulating their catalytic activities, and summarizes their performances in treating ROS-induced diseases.

CREB1-induced miR-1204 promoted malignant phenotype of glioblastoma through targeting NR3C2.

BACKGROUND: Glioblastoma (GBM) is a subclass of brain malignancy with unsatisfactory prognosis. MicroRNAs (miRNAs) are a group of non-coding RNAs (ncRNAs) that exert key function on tumorigenesis and tumor development. PURPOSES: The purpose of this work was to unravel the biological behavior and mechanism of miR-1204 in GBM. METHODS: Expressions of miR-1204, NR3C2 and CREB1 were detected by RT-qPCR and western blot. Proliferation and apoptosis of GBM cells were detected by CCK-8, colony formation, caspase-3 activity and TUNEL assays. Molecular interplays were examined by ChIP, RIP, and luciferase reporter assays. RESULTS: MiR-1204 level was elevated in GBM cell lines. Functionally, miR-1204 aggravated cell proliferation whereas suppressed cell apoptosis in GBM cells. Mechanistically, cAMP Responsive Element Binding Protein 1 (CREB1) bound to the promoter of miR-1204 and activated the transcription of miR-1204. Furthermore, miR-1204 targeted and inhibited Nuclear receptor subfamily 3 group C member 2 (NR3C2), a tumor suppressor gene in GBM cells. Rescue assays indicated that NR3C2 participated in the regulation of miR-1204 on the malignant phenotype of GBM cells. CONCLUSIONS: We observed for the first time that CREB1-induced miR-1204 promoted malignant phenotype of GBM through targeting NR3C2, indicating that miR-1204 acted as a novel oncogenic miRNA in GBM.

A convenient detection system consisting of efficient Au@PtRu nanozymes and alcohol oxidase for highly sensitive alcohol biosensing.

Effective alcohol detection represents a substantial concern not only in the context of personal and automobile safety but also in clinical settings as alcohol is a contributing factor in a wide range of health complications including various types of liver cirrhoses, strokes, and cardiovascular diseases. Recently, many kinds of nanomaterials with enzyme-like properties have been widely used as biosensors. Herein, we have developed a convenient detection method that combines Au@PtRu nanozymes and alcohol oxidase (AOx). We found that the Au@PtRu nanorods exhibited peroxidase-like catalytic activity that was much higher than the catalytic activities of the Au and Au@Pt nanorods. The Au@PtRu nanorod-catalyzed generation of hydroxyl radicals in the presence of H2O2 was used to develop an alcohol sensor by monitoring the H2O2 formed by the oxidation of alcohol to acetaldehyde in the presence of AOx. When coupled with AOx, alcohol was detected down to 23.8 µM in a buffer solution for biological assays. Notably, alcohol was successfully detected in mouse blood samples with results comparable to that from commercial alcohol meters. These results highlight the potential of the Au@PtRu nanorods with peroxidase-like activity for alcohol detection, which opens up a new avenue for nanozyme development for biomedical applications.

In Vitro and In Vivo Toxicity of Black Phosphorus Nanosheets.

As a new kind of two-dimensional nanomaterial, black phosphorus (BP) nanosheets have attracted significant interests in diverse bioapplications due to their unique structure and physicochemical properties. Despite BP nanosheets' advantages in cancer diagnosis and therapy applications, their biosafety issues are still unclear. Herein, we report a systematic study on the In Vitro and In Vivo toxicity of BP nanosheets. In Vitro experiments showed that BP nanosheets decrease the viability of human bronchial epithelial cells in a time- and dose-dependent manner. The mechanism study showed that BP nanosheets interfere with mitochondrial membrane potential, leading to an increase in intracellular ROS. These responses further initiated the activation of the caspase-3 and ultimately dictated cells to undergo apoptosis. Then, the In Vivo experiments of BP nanosheets revealed that single injection of BP nanosheets does not cause toxicity to mice in a short period of time, whereas multiple injections of BP nanosheets exert adverse effects on liver and renal function of mice. Interestingly, the liver and renal function of the mice returned to normal after a recovery period. Our findings provide insights into the rational design of BP nanosheets and guide their applications in biomedical fields.

O-Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies.

Multivalent carbohydrate-lectin interactions play a crucial role in bacterial infection. Biomimicry of multivalent glycosystems represents a major strategy in the repression of bacterial growth. In this study, a new kind of glycopeptide (Naphthyl-Phe-Phe-Ser-Tyr, NMY) scaffold with mannose modification is designed and synthesized, which is able to perform supramolecular self-assembly with the assistance of catalytic enzyme, and present multiple mannose ligands on its self-assembled structure to target mannose-binding proteins. Relying on multivalent carbohydrate-lectin interactions, the glycopeptide hydrogel is able to bind Escherichia coli (E. coli) in high specificity, and result in bacterial adhesion, membrane disruption and subsequent cell death. In vivo wound healing assays reveal that this glycopeptide hydrogel exhibits considerable potentials for promoting wound healing and preventing E. coli infection in a full-thickness skin defect mouse model. Therefore, through a specific mannose-lectin interaction, a biocompatible hydrogel with inherent antibacterial activity against E. coli is achieved without the need to resort to antibiotic or antimicrobial agent treatment, highlighting the potential role of sugar-coated nanomaterials in wound healing and control of bacterial pathogenesis.

Fabrication of Hybrid Hydrogels from Silk Fibroin and Tannic Acid with Enhanced Gelation and Antibacterial Activities.

The development of silk fibroin hydrogels with a suitable gelation rate and mechanical strength, as well as multifunctional properties including injectability, antibacterial activity, and adhesiveness, is of importance for wound healing and skin infection treatment, yet their design remains challenging. Herein, a multifunctional hydrogel from silk fibroin and tannic acid is developed, relying on the favorable interactions between them. The hybrid hydrogel (SF-TA) exhibits numerous advantages, such as short gelation time, low gelation concentrations, good adhesiveness, and shear-thinning and self-recovery properties. Moreover, the incorporation of tannic acid endows the hybrid hydrogel with remarkable bioactivity, including antimicrobial and antioxidant activities, beneficial to improving wound healing. In vivo experiments verify that the designed hybrid hydrogel can significantly accelerate the wound healing process in a full-thickness skin defect model on mice.

Cell division cycle associated 7 like predicts unfavorable prognosis and promotes invasion in glioma.

BACKGROUND: Cell division cycle associated 7 like (CDCA7L) belongs to the JPO protein family, which is recently identified as a target gene of c-Myc and is frequently dysregulated in multiple cancers. This study aimed to explore the clinicpathological value and biological role of CDCA7L in glioma. METHODS: CDCA7L expression in glioma patients was determined using the Oncomine database, and the prognostic role of CDCA7L expression was assessed in a retrospective cohort study. Moreover, the relationship of CDCA7L expression with the clinicopathological characteristics in glioma patients, including age, gender, tumor size, cystic change, Karnofsky performance scale (KPS) score, tumor location, extent of resection, WHO grade, adjuvant therapy and tumor recurrence, was analyzed in this study. In addition, the CDCA7L small interfering (si) RNA was constructed and transfected into the glioma U251 cells, so as to examine the role of CDCA7L in glioma patients. Besides, the changes in U251 cell invasion after transfection with CDCA7L siRNA were also monitored through Transwell assay. RESULTS: Our results suggested that CDCA7L expression was up-regulated in different glioma types, including glioblastoma, oligodendroglioma, diffuse astrocytoma and anaplastic astrocytoma. Moreover, the current retrospective cohort study indicated that high CDCA7L expression was associated with tumor size, WHO grade, adjuvant therapy and recurrence, as well as the poor overall survival (OS) and recurrence-free survival (RFS) in glioma patients. Lastly, CDCA7L expression was knocked down using CDCA7L siRNA, which could block the invasion abilities of glioma U251 cells. CONCLUSIONS: CDCA7L is highly expressed in human glioma tissues and a high CDCA7L expression level predicts the dismal prognosis for glioma patients. Moreover, CDCA7L can promote glioma invasion, which can serve as an independent potential prognostic biomarker for glioma patients.