Effect of doramectin on programmed cell death pathway in glioma cells

Purpose Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. Methods In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. Results We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. Conclusion Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy (AU)

Effect of doramectin on programmed cell death pathway in glioma cells.

PURPOSE: Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. METHODS: In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. RESULTS: We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. CONCLUSION: Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.

Colorimetric sensing of glucose and GSH using core-shell Cu/Au nanoparticles with peroxidase mimicking activity.

The catalytic properties of bimetallic nanoparticles have been widely studied by researchers in many fields. In this paper, core-shell Cu/Au nanoparticles (Cu/Au NPs) were synthesized by a simple and mild one-pot method, and their peroxidase activity was proved by catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with color change to blue. The change of solution color and absorbance strongly depends on the concentration of H2O2, so it can be used for direct detection of H2O2 and indirect detection of glucose. What's more, GSH can efficiently react with the hydroxyl radicals from H2O2 catalyzed by core-shell Cu/Au NPs to inhibit the production of ox-TMB. Thus, the concentration of GSH can be determined by the decrease in the absorbance of the solution at 652 nm. The results showed that our proposed strategy had good detection range and detection limit for the detection of glucose and GSH. This method has been used in the detection of practical samples and has great application potential in environmental monitoring and clinical diagnosis.

Cu2+ modified Zr-based metal organic framework-CTAB-graphene for sensitive electrochemical detection of sunset yellow.

A sensitive electrochemical sensor for sunset yellow (SY) was constructed based on cetyltrimethylammonium bromide (CTAB) functionalized graphene (Gr) and Cu/Zr-MOF electrode modified materials. The CTAB-Gr-Cu/Zr-MOF composites were synthesized by using a mild method and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and EDX spectrum. The combination of Cu/Zr-MOF and graphene exhibited synergetic effect of the strong accumulation efficiency, fast electron transfer rate and more sensing sites towards the oxidation of SY. The new modified materials remarkably increased the electrochemical response of SY to 6.53-fold when comparing with bare electrode. Under the optimized conditions, the oxidation peak currents of SY had a linear relationship with its concentration in a wide range from 0.10 to 8.00 µM and 40.00-1000.00 µM, and the limit of detection was 6.68 nM (S/N = 3). The electrochemical method shows high sensitivity, stability, reproducibility and is successfully applied in the determination of SY in soft drinks.

Polyoxometalates-graphene nanocomposites modified electrode for electro-sensing detection of Sudan I in food.

Sudan I, a lipophilic azo dye -dye, is desirable and urgent to be accurate detected due to its increasing levels and high toxicity in food and environmental monitoring and analysis. Herein, a sensitive electrochemical sensor for Sudan I was established based on a new K10P2W18Fe4(H2O)2O68 functionalized carbon nanomaterials (Fe4P2W18-GNPS). The electrode modified nanocomposite, Fe4P2W18-GNPS, was successfully fabricated and characterized by FTIR, SEM and UV-vis. The effective combination of Fe4P2W18 and graphene exhibited high electrocatalytic activity towards the oxidation of Sudan I, promote charge transfer, and more sensing sites. Under optimized experimental conditions, the proposed differential pulse voltammetry (DPV) showed excellent analytical performances for Sudan I with the limit of detection (LOD) of 5 nM (S/N = 3), the sensitivity of 13.10 µA·µM-1cm-2 at the 0.005-2 µM and 0.39 µA·µM-1cm-2 at 10-200 µM. The stability and reproducibility make the electrochemical sensor suitable for detecting the Sudan I in food.

Recent Advances in Polyoxometalates with Enzyme-like Characteristics for Analytical Applications.

Artificial enzymes based on inorganic solids with both enzyme-mimetic activities and the special material features has been a promising candidate to overcome many deleterious effects of native enzymes in analytical applications. Polyoxometalates (POMs) are an importance class of molecular metal-oxygen anionic clusters. Their outstanding physicochemical properties, versatility and potential applications in energy conversion, magnetism, catalysis, molecular electronics and biomedicine have long been studied. However, the analytical applications of them is limited. Recently, the intrinsic enzymatic activities of POMs have also been found and become an area of growing interest. In this review, along with other reports, we aimed to classify the enzymatic activity of POMs, summarize the construction of POMs-based enzymes, and survey their recent advances in analytical fields. Finally, the current challenges and trends of the polyoxometalates with enzymatic activity in future chemo-/bio-sensing applications are briefly discussed.

A Multifunctional Janus Electrospun Nanofiber Dressing with Biofluid Draining, Monitoring, and Antibacterial Properties for Wound Healing.

Wound healing greatly affects patients' health and produces medical burden. Therefore, we developed a multifunctional electrospun nanofiber dressing, which can inhibit methicillin-resistant Staphylococcus aureus (MRSA), drain excessive biofluid to promote wound healing, and simultaneously monitor wound pH level. The polyoxometalate (α-K6P2W18O62·14H2O, P2W18) and oxacillin (OXA) are encapsulated in hydrophobic polylactide (PLA) nanofiber to synergistically inhibit MRSA. The phenol red (PSP) is encapsulated in hydrophilic polyacrylonitrile (PAN) nanofiber to sensitively indicate wound pH in situ. The PSP/PAN nanofiber is directly electrospun on the patterning OXA/P2W18/PLA nanofiber layer to form a Janus dressing. By taking advantage of the wettability difference between the two layers, the excess biofluid can be drained away from the wound. In addition, the Janus dressing exhibits good biocompatibility and accelerates wound healing via its antimicrobial activity and skin repairing function. This multifunctional Janus electrospun nanofiber dressing would be beneficial for wound management and treatment.

Multienzymatic Antioxidant Activity of Manganese-Based Nanoparticles for Protection against Oxidative Cell Damage.

Oxidative stress is related to many diseases, but available clinical treatment methods are currently limited. Exploitation of enzyme-mimicking nanomaterials (nanozymes) is a promising way for scavenging reactive oxygen species (ROS) and treatment of ROS-related diseases. Herein, the catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) mimicking activities are expressed by MnO2 nanoparticles (MnO2-BSA NPs) coated with BSA. Effective •OH removal activity is also expressed by MnO2-BSA NPs at neutral pH. Apoptosis inhibition and ROS scavenging capabilities of MnO2-BSA NPs are evident on the H2O2-exposed BEAS-2B cells line. Western blot analysis indicates that MnO2-BSA NPs inhibit H2O2-induced apoptosis by mediating the expression of apoptosis-related proteins.

Vancomycin recognition and induced-aggregation of the Au nanoparticles through freeze-thaw for foodborne pathogen Staphylococcus aureus detection.

Infectious diseases caused by foodborne pathogens have become a serious public health problem. It is urgent to develop simple, rapid, and visual methods for pathogen detection. Herein, gold nanoparticles (AuNPs), aptamer and vancomycin (Van) based dual-recognition molecules and magnetic enrichment were combined to realize visual detection of Staphylococcus aureus (S. aureus). Initially, S. aureus was bounded to aptamer coupled Fe3O4 with high affinity and selectivity, which can achieve the separation and enrichment of S. aureus in complex sample matrix. Subsequently, the second recognition molecule, Van, was conjugated to S. aureus -Apt - Fe3O4. Finally, the unbound Van supernatant was dropped in AuNPs solution that induced the aggregation of the AuNPs through freeze-thaw. Firstly, it was found that AuNPs were stable in the presence of Van after a freeze-thaw cycle. A facile visual colorimetric detection of S. aureus was constructed with the linear range from 101 to 104 CFU/mL and the limit of detection (LOD) of 0.2 CFU/mL. By altering the aptamer, this method can be extended to the other Gram-positive bacteria. The proposed method has great potential applications in monitoring food contamination and infectious diseases.

A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy.

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.

In Vitro Antifungal Activity and Mechanism of Ag3PW12O40 Composites against Candida Species.

Fungal infections pose a serious threat to human health. Polyoxometalates (POMs) are metal-oxygen clusters with potential application in the control of microbial infections. Herein, the Ag3PW12O40 composites have been synthesized and verified by Fourier transform infrared (FT-IR) spectrum, transmission electron microscopy (TEM), scanning electron microscope (SEM), elemental analysis, and X-ray diffraction (XRD). The antifungal activities of Ag3PW12O40 were screened in 19 Candida species strains through the determination of minimum inhibitory concentration (MIC) by the microdilution checkerboard technique. The minimum inhibitory concentration (MIC50) values of Ag3PW12O40 are 2~32 µg/mL to the Candida species. The MIC80 value of Ag3PW12O40 to resistant clinical isolates C. albicans HL963 is 8 µg/mL, which is lower than the positive control, fluconazole (FLC). The mechanism against C. albicans HL963 results show that Ag3PW12O40 can decrease the ergosterol content. The expressions of ERG1, ERG7, and ERG11, which impact on the synthesis of ergosterol, are all prominently upregulated by Ag3PW12O40. It indicates that Ag3PW12O40 is a candidate in the development of new antifungal agents.

Anisotropic active ligandations in siRNA-Loaded hybrid nanodiscs lead to distinct carcinostatic outcomes by regulating nano-bio interactions.

Active targeting modification is one of the foremost nanomedicine strategies for the efficacy improvement. Compared to the homogeneous ligandation on spherical nanocarriers, non-spherical nanomedicines usually make the ligand modification more complicated. The modified ligands always exhibit anisotropy and heterogeneity. However, there is very little systematic study on these diversified anisotropic modifications. The efficacy difference and underlying mechanism were still unclear. Here, we separately fabricated hybrid nanodiscs (NDs) conjugated with cRGD on the edge and plane surfaces to engineer two anisotropic targeting nanocarriers (E-cRGD-NDs and P-cRGD-NDs, respectively) for gene delivery. The ligand anisotropy endowed NDs with diversified cellular interactions, and caused different efficacies between E-cRGD-NDs and P-cRGD-NDs. Of note, E-cRGD-NDs showed significant superiority in siRNA loading, cellular uptake, silence efficiency, protein expression and even in vivo efficacy. The mechanism investigation revealed the functional anisotropy specifically for E-cRGD-NDs. The edge modification of cRGD efficiently separated the targeting and siRNA loading domains, maximizing their respective functions. These findings reflected the unique effect of ligand anisotropy, also provided a new strategy for the targeting screening of extensive nanomedicines.