Betulinic acid inhibits glioma cell viability by downregulation of NF-κB and enhancement of apoptosis

Purpose: To determine the inhibitory potential of betulinic acid on pro-survival signaling pathway in glioblastoma.Methods: Changes in viabilities of glioma cells and primary astrocytes were measured using 3-(4, 5dimethylthiazol-2-yl)-2,  5-diphenyltetrazolium bromide (MTT) assay. Apoptotic changes were analyzed using Hoechst 33342 staining and Annexin V-FITC/PI kits. Western blotting was used for assaying the protein expressions of various pro-apoptotic and anti-apoptotic factors.Results: The proliferative potential of U87MG and A172 cells were significantly reduced on treatment with betulinic acid in a concentration- and time-dependent manner. Treatment with betulinic acid at a dose of 8.75 µg/mL increased apoptosis in U87MG and A172 cells to 41.8 ± 0.5 and 48.8 ± 0.5%, respectively (p < 0.05). Betulinic acid significantly decreased intracellular levels of NFκB p65 andsuppressed levels of survivin, XIAP and Bcl-2 in U87MG and A172 cells (p < 0.05). However, betulinic acid significantly increased the levels of Bax and activated caspase-9 and caspase-3 in U87MG and A172 cells (p < 0.05).Conclusion: Betulinic acid inhibited the proliferation of U87MG and A172 glioblastoma cells and mediated their apoptosis. There is need for in vivo studies for validation of the therapeutic potential of betulinic acid as an anti-glioblastoma drug. Keywords: Glioblastoma, Betulinic acid, Proliferation, Apoptosis, Chemotherapy, Intracranial malignanc

Early on-treatment plasma interleukin-18 as a promising indicator for long-term virological response in patients with HIV-1 infection

Background and aimsIt is necessary to identify simple biomarkers that can efficiently predict the efficacy of long-term antiretroviral therapy (ART) against human immunodeficiency virus (HIV), especially in underdeveloped countries. We characterized the dynamic changes in plasma interleukin-18 (IL-18) and assessed its performance as a predictor of long-term virological response.MethodsThis was a retrospective cohort study of HIV-1-infected patients enrolled in a randomized controlled trial with a follow-up of 144  weeks of ART. Enzyme-linked immunosorbent assay was performed to evaluate plasma IL-18. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144.ResultsAmong the 173 enrolled patients, the long-term virological response rate was 93.1%. Patients with a long-term virological response had significantly lower levels of week 24 IL-18 than non-responders. We defined 64  pg./mL, with a maximum sum of sensitivity and specificity, as the optimal cutoff value of week 24 IL-18 level to predict long-term virological response. After adjusting for age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotype and treatment strategy, we found that lower week 24 IL-18 level (≤64 vs. >64 pg./mL, a OR 19.10, 95% CI: 2.36–154.80) was the only independent predictor of long-term virological response.ConclusionEarly on-treatment plasma IL-18 could act as a promising indicator for long-term virological response in patients with HIV-1 infection. Chronic immune activation and inflammation may represent a potential mechanism; further validation is necessary

Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ

Mitochondrial production of ROS (reactive oxygen species) is thought to be associated with the cellular damage resulting from chronic exposure to high glucose in long-term diabetic patients. We hypothesized that a mitochondria-targeted antioxidant would prevent kidney damage in the Ins2+/−AkitaJ mouse model (Akita mice) of Type 1 diabetes. To test this we orally administered a mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways were determined by immunohistochemical analysis, and mitochondria were isolated from the kidney for functional assessment. MitoQ treatment improved tubular and glomerular function in the Ins2+/−AkitaJ mice. MitoQ did not have a significant effect on plasma creatinine levels, but decreased urinary albumin levels to the same level as non-diabetic controls. Consistent with previous studies, renal mitochondrial function showed no significant change between any of the diabetic or wild-type groups. Importantly, interstitial fibrosis and glomerular damage were significantly reduced in the treated animals. The pro-fibrotic transcription factors phospho-Smad2/3 and β-catenin showed a nuclear accumulation in the Ins2+/−AkitaJ mice, which was prevented by MitoQ treatment. These results support the hypothesis that mitochondrially targeted therapies may be beneficial in the treatment of diabetic nephropathy. They also highlight a relatively unexplored aspect of mitochondrial ROS signalling in the control of fibrosis

Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation

The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported.The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo.These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional food for the prevention and treatment of inflammatory diseases

Quantitative 3D Association of Geological Factors and Geophysical Fields with Mineralization and Its Significance for Ore Prediction: An Example from Anqing Orefield, China

Quantitative 3D spatial association of geological factors and geophysical fields with orebodies is critical for ore prediction. The Anqing orefield, a principal Cu–Fe orefield in China, is closely associated with the Yueshan intrusion. By compiling the data from drilling and tunnelling exploration, Controlled Source Audiofrequency Magnetotelluric (CSAMT) surveying and the computational modelling of magmatic intrusion’s cooling process, we constructed models of the Yueshan intrusion, ore-favourable carbonate formation, orebodies, resistivity field and volume strain field. These models are used as evidential factors to analyse their spatial association with mineralization by the weights-of-evidence (WofE) method. The location of orebodies is closely related to the shape of the contact zone of the Yueshan intrusion. The spaces with the distance ≤200 m to the concaves that were selected by minimum principal curvature (|Kmin| ≥ 0.0025) from contact zones, are very favourable for localization of orebodies. Most orebodies are not located in the spaces of the lowest resistivity, suggesting that the lowest resistivity cannot be used as an indicator for mineralization. The spaces with higher positive volumetric strain have higher positive weights with orebodies, implying that the mineralization is positively related to the positive volumetric strain. The spaces of all evidential factors that had positive correlation with mineralization were integrated to create a 3D prospectivity map by calculating posterior probability. Five areas with higher posterior probability, indicating higher prospectivity potential, are selected as targets for future exploration

Mineralogical Characteristics and Isothermal Oxidation Kinetics of Ironsand Pellets

An in-depth understanding of mineralogical characteristics and the oxidation behaviors of ironsand is of great significance to make the best of ironsand and develop Ti-containing pellets. This paper quantitatively characterized the mineralogical characteristics of the ironsand from East Java in Indonesia through X-ray diffraction (XRD-Rietveld) and scanning electron microscope (SEM-EDS). The results indicated that the mineral composition of the ironsand was magnetite (22.7%), titanomagnetite (40.9%), enstatite (17.1%), hematite⁻ilmenite solid solution (14.5%), and magnesium iron aluminum silicon oxide (5.8%). The microstructure characterization of pellets after oxidation showed that the porosity of the pellets decreased from 20.7% to 11.7% with temperatures ranging from 1073 to 1473 K. Moreover, the activation energies of ironsand pellets were calculated by using model-function method. The calculated data of different mechanism functions indicated that the chemical reaction mechanism for the early stage of the oxidation fit A2 (random nucleation and nuclei growth) well, the chemical reaction mechanism for the post-oxidation at 1073⁻1273 K fit F1 (chemical reaction) well, and the chemical reaction mechanism for the post-oxidation at 1373 and 1473 K fit D4 (diffusion) well. The reaction mechanism and the limited link was finally discussed based on the kinetic analysis and the mineralogical characteristics

Formation of the [M+NH₄]⁺ ions of some mono-and di-saccharides in fast atom bombardment mass spectrometry

812-814In positive-ion fast atom bombardment (FAB) mas spectrometry, the abundance of [M+H]+ ion of mono- and di-saccharides is too low to allow determination of their molecular weights. However, when mono- and di-saccharides are mixed with an appropriate amount of NH4Cl, a highly abundant peak [M+NH4]+ appears in FAB mass spectra. From the adduct ion [M+NH4(the molecular weights of mono - and di-saccharides can be determined definitively. Here, twelve monosaccharides and six disaccharides have been studied

SSNet: A Novel Transformer and CNN Hybrid Network for Remote Sensing Semantic Segmentation

There are still various challenges in remote sensing semantic segmentation due to objects diversity and complexity. Transformer-based models have significant advantages in capturing global feature dependencies for segmentation. However, it unfortunately ignores local feature details. On the other hand, convolutional neural network (CNN), with a different interaction mechanism from transformer-based models, captures more small-scale local features instead of global features. In this article, a new semantic segmentation net framework named SSNet is proposed, which incorporates an encoder–decoder structure, optimizing the advantages of both local and global features. In addition, we build feature fuse module and feature inject module to largely fuse these two-style features. The former module captures the dependencies between different positions and channels to extract multiscale features, which promotes the segmentation precision on similar objects. The latter module condenses the global information in transformer and injects it into CNN to obtain a broad global field of view, in which the depthwise strip convolution improves the segmentation accuracy on tiny objects. A CNN-based decoder progressively recovers the feature map size, and a block called atrous spatial pyramid pooling is adopted in decoder to obtain a multiscale context. The skip connection is established between the decoder and the encoder, which retains important feature information of the shallow layer network and is conducive to achieving flow of multiscale features. To evaluate our model, we compare it with current state-of-the-art models on WHDLD and Potsdam datasets. The experimental results indicate that our proposed model achieves more precise semantic segmentation

The interaction of nanoparticulate Fe2O3 in the sintering process: A molecular dynamics simulation

In this paper, molecular dynamics (MD) simulations have been used to investigate the sintering process of nanoparticulate Fe2O3 at 300 K and 1300 K. The main growth mechanism of the sintering neck is the surface atom diffusion with the diffusion coefficient of O (D-o = 0.00417 nm(2)/ps) and Fe (D-Fe =0.00333 nm(2)/ps), respectively. It is proposed to evaluate the sintering degree by the effective sintering area (A(e)) and the effective sintering volume (V-e). The migration mechanism of the atom at different stages is further explored by the atomic displacement vector diagram. The evolution of crystal structure has also been observed by the common neighbor analysis. The crystal structure gradually changed from HCP and BCC structures to amorphous structures with a proportion of 66%. (C) 2020 Elsevier B.V. All rights reserved

Sintering neck growth mechanism of Fe nanoparticles: a molecular dynamics simulation

In this paper, the sintering neck growth mechanism of Fe nanoparticles is studied by molecular dynamics method. The accuracy of the EAM potential function is verified. The relationship between the sintering temperature of the nanoparticles and the particle size has been investigated. The sintering temperature of the particles is linearly positively correlated with the size. The whole sintering process can be divided into three stages: the initial sintering, the stable growth and the sudden increase. The atoms are divided into surface atoms and internal atoms depending on the recognition method. By calculating the mean square displacement of the particles and observing the vector displacement of the atoms, the growth mechanisms of the sintering neck at different stages have been analyzed. Similarly, the evolution of crystal structure during sintering is captured by structure analysis. These simulation results firstly reveal the rule of atomic migration and the growth mechanism of the sintering neck