Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf extract on human colon cancer HCT116 cell line

Purpose: To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line.Methods: M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified by thin layer chromatography (TLC), proton nuclear magnetic resonance (1H NMR) and mass spectrometry (MS). The growth inhibitory activity and mechanism of action of the extracts in HCT116 colon cancer cells were investigated by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blotting.Results: Successive fractions from M. oleifera leaf crude extracts by column  chromatography were combined into four pooled batches (MOL1 - MOL4) according to their absorbance at 260 nm and TLC pattern. MOL2 and MOL3 contain astragalin and isoquercetin, respectively. The results from MTT assay indicated that cell proliferation was significantly (p < 0.05) inhibited in a concentration-dependent fashion, especially by MOL2, MOL3 and MOL4. MOL2 and MOL3 exhibited a stronger cell growth  inhibition than their major ingredients. The anti-proliferative activity of MOL2 - MOL4 in HCT116 colon cancer cells was  mediated by downregulation of ERK1/2 phosphorylation.Conclusion: M. oleifera leaf extract has a strong anti-proliferative activity which is exerted by decreasing ERK1/2 phosphorylation. Thus, the extract has a potential for use in cancer chemoprevention.Keywords: Moringa oleifera, Anti-proliferation, Colon cancer, AKT, ERK1/2 phosphorylation, Chemopreventio

Time-efficient combined morphologic and quantitative joint MRI based on clinical image contrasts -- An exploratory in-situ study of standardized cartilage defects

OBJECTIVES: Quantitative MRI techniques such as T2 and T1$\rho$ mapping are beneficial in evaluating cartilage and meniscus. We aimed to evaluate the MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with IntUitive RElaxometry) sequences that provide morphologic images with clinical turbo spin-echo (TSE) contrasts and additional parameter maps versus reference TSE sequences in an in-situ model of human cartilage defects. MATERIALS AND METHODS: Prospectively, standardized cartilage defects of 8mm, 5mm, and 3mm diameter were created in the lateral femora of 10 human cadaveric knee specimens (81$\pm$10 years, nine male/one female). Using a clinical 3T MRI scanner and knee coil, MIXTURE sequences combining (i) proton-density weighted fat-saturated (PD-w FS) images and T2 maps and (ii) T1-weighted images and T1$\rho$ maps were acquired before and after defect creation, alongside the corresponding 2D TSE and 3D TSE reference sequences. Defect delineability, bone texture, and cartilage relaxation times were quantified. Inter-sequence comparisons were made using appropriate parametric and non-parametric tests. RESULTS: Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences. After defect creation, relaxation times increased significantly in the central femur (for T2) and all regions combined (for T1$\rho$). CONCLUSION: MIXTURE sequences permit time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1$\rho$ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defect delineability and bone texture, were comparable between MIXTURE and corresponding reference sequences.Comment: 12 pages (main body), 3 tables, 6 figure

Two for One -- Combined Morphologic and Quantitative Knee Joint MRI Using a Versatile Turbo Spin-Echo Platform

Introduction: Quantitative MRI techniques such as T2 and T1\r{ho} mapping are beneficial in evaluating knee joint pathologies; however, long acquisition times limit their clinical adoption. MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with IntUitive RElaxometry) provides a versatile turbo spin-echo (TSE) sequence platform for simultaneous morphologic and quantitative joint imaging yet lacks comparative evaluation in basic and translational research contexts. Methods: Two MIXTURE sequences were designed along clinical requirements: (i) MIX1, combining proton density (PD)-weighted fat-saturated (FS) images and quantitative T2 mapping (acquisition time: 4:59 min), and (ii) MIX2, combining T1-weighted images with quantitative T1\r{ho} mapping (6:38 min). MIXTURE sequences and their reference 2D and 3D TSE counterparts were acquired from ten human cadaveric knee joints using a clinical 3T MRI scanner and knee coil. Contrast, contrast-to-noise ratios, and coefficients of variation were comparatively evaluated using parametric tests. Clinical radiologists (n=3) assessed diagnostic quality as a function of sequence and anatomic structure using 5-point Likert scales and ordinal regression. The significance level was set to {\alpha}=0.01. Results: MIX1 and MIX2 had at least equal diagnostic quality compared to the 2D and 3D TSE sequences of the same image weighting. Contrast, contrast-to-noise ratios, and coefficients of variation were largely similar for the PD-weighted FS and T1-weighted images. Discussion: In clinically feasible scan times, the MIXTURE sequence platform yields (i) morphologic images of diagnostic quality and adjustable TSE-based contrasts and (ii) quantitative parameter mapping with additional insights on soft tissue composition and ultrastructure.Comment: 13 pages (main text), 7 figures, 3 table

Differentiation of Brain Metastases and Gliomas Based on Color Map of Phase Difference Enhanced Imaging

Background and objective: Phase difference enhanced imaging (PADRE), a new phase-related MRI technique, can enhance both paramagnetic and diamagnetic substances, and select which phases to be enhanced. Utilizing these characteristics, we developed color map of PADRE (Color PADRE), which enables simultaneous visualization of myelin-rich structures and veins. Our aim was to determine whether Color PADRE is sufficient to delineate the characteristics of non-gadolinium-enhancing T2-hyperintense regions related with metastatic tumors (MTs), diffuse astrocytomas (DAs) and glioblastomas (GBs), and whether it can contribute to the differentiation of MTs from GBs.Methods: Color PADRE images of 11 patients with MTs, nine with DAs and 17 with GBs were created by combining tissue-enhanced, vessel-enhanced and magnitude images of PADRE, and then retrospectively reviewed. First, predominant visibility of superficial white matter and deep medullary veins within non-gadolinium-enhancing T2-hyperintense regions were compared among the three groups. Then, the discriminatory power to differentiate MTs from GBs was assessed using receiver operating characteristic analysis.Results: The degree of visibility of superficial white matter was significantly better in MTs than in GBs (p = 0.017), better in GBs than in DAs (p = 0.014), and better in MTs than in DAs (p = 0.0021). On the contrary, the difference in the visibility of deep medullary veins was not significant (p = 0.065). The area under the receiver operating characteristic curve to discriminate MTs from GBs was 0.76 with a sensitivity of 80% and specificity of 64%.Conclusion: Visibility of superficial white matter on Color PADRE reflects inferred differences in the proportion of vasogenic edema and tumoral infiltration within non-gadolinium-enhancing T2-hyperintense regions of MTs, DAs and GBs. Evaluation of peritumoral areas on Color PADRE can help to distinguish MTs from GBs