Neuroprotective agents effective against radiation damage of central nervous system

Ionizing radiation caused by medical treatments,nuclear events or even space flights can irreversibly damage structure and function of brain cells.That can result in serious brain damage,with memory and behavior disorders,or even fatal oncologic or neurodegenerative illnesses.Currently used treatments and drugs are mostly targeting biochemical processes of cell apoptosis,radiation toxicity,neuroinflammation,and conditions such as cognitive-behavioral disturbances or others that result from the radiation insult.With most drugs,the side effects and potential toxicity are also to be considered.Therefore,many agents have not been approved for clinical use yet.In this review,we focus on the latest and most effective agents that have been used in animal and also in the human research,and clinical treatments.They could have the potential therapeutical use in cases of radiation damage of central nervous system,and also in prevention considering their radioprotecting effect of nervous tissue.

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.

The diffusion and concentration effects of formamide on a TiO₂surface in the presence of a water solvent

The formamide-titanium oxide interaction mechanism is a research target of great importance for understanding the elementary events of the origin of life: the synthesis of nucleoside bases and formation of biological molecules needed for life. Titanium oxide (TiO2) can act as a strongly adsorbing surface or a catalytic material. In the present study, a comparative molecular dynamics analysis performed to clarify the adsorbing and diffusion properties of liquid formamide on a TiO2 surface in the presence of water molecules. The structural features of the formamide concentration effect (the accumulation of molecules) on a TiO2 surface in the presence and absence of water solvent are cleared up. Modification of the formamide diffusion abilities mediated by a water solvent is observed to correlate with the formamide-water concentration distribution on the surface.

Molecular dynamics simulations of a DNA photolyase protein: High-mobility and conformational changes of the FAD molecule at low temperatures

A molecular dynamics (MD) simulation is performed on a DNA photolyase to study the conformational behavior of the photoactive cofactor flavin adenine dinucleotide (FAD) inside the enzyme pocket. A DNA photolyase is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane pyrimidine dimer in damaged DNA. In this work, the FAD conformational and dynamic changes were studied within the total complex structure of a DNA photolyase protein (containing FADH–, MTHF, and DNA molecules) embedded in a water solvent. We aimed to compare the conformational changes of the FAD cofactor and other constituent fragments of the molecular system under consideration. The obtained results were discussed to gain insight into the light-driven mechanism of DNA repair by a DNA photolyase enzyme—based on the enzyme structure, the FAD mobility, and conformation shape.

Molecular Dynamics Simulations of the DNA-CNT Interaction Process: Hybrid Quantum Chemistry Potential and Classical Trajectory Approach

In this work the quantum chemistry Tersoff potential in combination with classical trajectory calculations was used to investigate the interaction of the DNA molecule with a carbon nanotube (CNT). The so-called hybrid approach—the classical and quantum-chemical modeling, where the force fields and interaction between particles are based on a definite (but not unique) description method, has been outlined in some detail. In such approach the molecules are described as a set of spheres and springs, thereby the spheres imitate classical particles and the spring the interaction force fields provided by quantum chemistry laws. The Tersoff potential in hybrid molecular dynamics (MD) simulations correctly describes the nature of covalent bonding. The aim of the present work was to estimate the dynamical and structural behavior of the DNA-CNT system at ambient temperature conditions. The dynamical configurations were built up for the DNA molecule interacting with the CNT. The analysis of generated МD configurations for the DNA-CNT complex was carried out. For the DNA-CNT system the observations reveal an encapsulation-like behavior of the DNA chain inside the CNT chain. The discussions were made on possible use of the DNA-CNT complex as a candidate material in drug delivery and related systems.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.

Radiomic analysis based on multi-phase magnetic resonance imaging to predict preoperatively microvascular invasion in hepatocellular carcinoma

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy.In terms of recent studies,microvascular invasion(MVI)is one of the potential predictors of recurrence.Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning.AIM To develop a radiomic analysis model based on pre-operative magnetic resonance imaging(MRI)data to predict MVI in HCC.METHODS A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation,among whom 73 were found to have MVI and 40 were not.All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy.We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI,namely,the regions of interest.Quantitative analyses included most discriminant factors(MDFs)developed using linear discriminant analysis algorithm and histogram analysis with MaZda software.Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis.Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic(ROC)curve analysis.Five-fold cross-validation was also applied via R software.RESULTS The area under the ROC curve(AUC)of the MDF(0.77-0.85)outperformed that of histogram parameters(0.51-0.74).After multivariate analysis,MDF values of the arterial and portal venous phase,and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI(P<0.05).The AUC value of the model was 0.939[95%confidence interval(CI):0.893-0.984,standard error:0.023].The result of internal five-fold cross-validation(AUC:0.912,95%CI:0.841-0.959,standard error:0.0298)also showed favorable predictive efficacy.CONCLUSION Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.

Exosomal circular RNAs inglioma:coexistenceof opportunitiesand challenges forapplication

Glioma is the most common primary tumor in the central nervous system.With the help of intercellular communication,glioma cells have the ability to survive in the tumor microenvironment(TME)and make it more suitable.

Glioblastoma vaccine tumor therapy research progress

Glioblastoma(GBM)is the most common primary malignancy of the central nervous system in adults.The prognosis for late-stage glioblastoma(World Health Organization grade IV astrocytic glioma)is very poor.Novel treatment options are sought after and evaluated by clinicians and researchers,and remarkable advances have been made in surgical techniques,radiotherapy,and chemotherapy.However,the treatment of glioblastoma remains extremely difficult and it can extend the lives of patients by only a few months.There has been notable progress in the field of immunotherapy,particularly with the use of tumor vaccines,for treating glioblastoma;especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines.However,the results of the current clinical trials for vaccination are not satisfactory.This article reviews the progress in the development of vaccines for glioblastoma.

KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma

Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been studied.In this study,we find that lysine-specific demethylase 2 b(KDM2 B)is highly expressed in HSA cell lines compared with normal canine endothelial cells.Silencing of KDM2 B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage.Similarly,doxycycline-induced KDM2 B silencing in tumor xenografts results in decreased tumor sizes compared with the control.Furthermore,KDM2 B is also highly expressed in clinical cases of HSA.We hypothesize that pharmacological KDM2 B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA.We treat HSA cells with GSK-J4,a histone demethylase inhibitor,and find that GSK-J4 treatment also induces apoptosis and cell death.In addition,GSK-J4 treatment decreases tumor size.Therefore,we demonstrate that KDM2 B acts as an oncogene in HSA by enhancing the DNA damage response.Moreover,we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.