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result(s) for
"MDA"
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A Triple Combination of Metformin, Acetylsalicylic Acid, and Oseltamivir Phosphate Impacts Tumour Spheroid Viability and Upends Chemoresistance in Triple-Negative Breast Cancer
by
Qorri, Bessi
,
Harless, William
,
Szewczuk, Myron R
in
Aldehyde Dehydrogenase 1 Family - antagonists & inhibitors
,
Aldehyde Dehydrogenase 1 Family - metabolism
,
Antineoplastic Agents - pharmacology
2020
Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen. Also, the development of chemoresistance is a common clinical challenge with breast cancer. Higher doses and additional drug agents can produce additional adverse effects leading to a more aggressive malignancy. Acetylsalicylic acid (ASA), metformin (Met), and oseltamivir phosphate (OP) were investigated for their efficacy to sensitize MDA-MB-231 triple-negative breast cancer and its tamoxifen (Tmx) resistant variant (MDA-MB-231-TmxR) together in combination with Tmx treatment.
Microscopic imaging, the formation of 3D multicellular tumour spheroids, immunocytochemistry, flow cytometry, Annexin V Assay, Caspase 3/7 Apoptosis Assay, tube formation assay and analysis, and WST-1 cell viability assay evaluated the formation of MCTS, morphologic changes, cell viability, apoptosis activity and the expression levels of ALDH1A1, CD44 and CD24 on the cell surface, MDA-MB231 triple-negative breast cancer, tamoxifen (Tmx) resistant variant (MDA-MB-231-TmxR).
The results using a triple combination of ASA, Met and OP on MDA-MB-231 and MDA-MB-231-TmxR cells and their matrix-free 3D multicellular tumour spheroids (MCTS) formed by using the cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP)) peptide method demonstrate a consistent and significant decrease in cell and tumour spheroid viability and volume with increased apoptotic activity, and increased sensitivity to Tmx therapy. Tmx treatment of MDA-MB-231 cells in combination with ASA, Met and OP markedly reduced the CD44/CD24 ratio by 6.5-fold compared to the untreated control group. Tmx treatment of MDA-MB-231-TmxR cells in combination with ASA, Met and OP markedly reduced the ALDH1A1 by 134-fold compared to the same treatment for the parental cell line. Also, the triple combination treatment of ASA, Met, and OP inhibited vasculogenic endothelial cell tube formation and induced endothelial cell apoptosis.
For the first time, the findings demonstrate that repurposing ASA, Met, and OP provides a novel and promising targeted multimodal approach in the treatment of triple-negative breast cancer and its chemoresistant variant.
Journal Article
miRNA regulation, antitumor activity, and molecular modeling by Naproxen-1,2,4-triazole compound in human Breast cancer
2026
In this study, a new 1,2,4-triazole ring that has a 2-fluorophenyl ring was synthesized using (S)-Naproxen as the starting molecule. The target compound was characterized using spectroscopic methods such as FT-IR, 1H-NMR, 13C-NMR, and HR-MS. In molecular modeling studies, compound (4a) was used to control for the Bcl-2 apoptotic marker. The main aim was to show that the MDA-MB-231 cell line developed growth inhibition in a dose-dependent manner after compound treatment. The results showed that compound (4a) inhibited the motility of MDA-MB-231 cells. Compound (4a) at 75, 150, and 300 µM concentrations significantly reduced the viability of MDA-MB-231 cells compared to the control group. IC50 value of the compound (4a) for 48 h was 57.6 µM. In our study, for the first time, miR-133a-5p was significantly up-regulated in MDA-MB-231 breast cancer cells treated with compound (4a) at different concentrations compared to the control group. As such, miR-133a-5p could play an essential role in tumorigenesis by targeting Bcl-2 in MDA-MB-231 and may be a biomarker for therapeutic targets in breast cancer treatment.
Journal Article
The Role of Natural Low Molecular Weight Dicarbonyls in Atherogenesis and Diabetogenesis
by
Lankin, Vadim Z.
,
Tikhaze, Alla K.
,
Sharapov, Mars G.
in
antioxidant enzymes
,
Antioxidants
,
apoptosis
2024
This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not “oxidized” (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.
Journal Article
Sanguinarine Inhibition of TNF-α-Induced CCL2, IKBKE/NF-κB/ERK1/2 Signaling Pathway, and Cell Migration in Human Triple-Negative Breast Cancer Cells
by
Zarmouh, Najla O.
,
Messeha, Samia S.
,
Antonie, Lovely
in
Angiogenesis
,
Breast cancer
,
Cancer therapies
2022
Angiogenesis is a process that drives breast cancer (BC) progression and metastasis, which is linked to the altered inflammatory process, particularly in triple-negative breast cancer (TNBC). In targeting inflammatory angiogenesis, natural compounds are a promising option for managing BC. Thus, this study was designed to determine the natural alkaloid sanguinarine (SANG) potential for its antiangiogenic and antimetastatic properties in triple-negative breast cancer (TNBC) cells. The cytotoxic effect of SANG was examined in MDA-MB-231 and MDA-MB-468 cell models at a low molecular level. In this study, SANG remarkably inhibited the inflammatory mediator chemokine CCL2 in MDA-MB-231 and MDA-MB-468 cells. Furthermore, qRT-PCR confirmed with Western analysis studies showed that mRNA CCL2 repression was concurrent with reducing its main regulator IKBKE and NF-κB signaling pathway proteins in both TNBC cell lines. The total ERK1/2 protein was inhibited in the more responsive MDA-MB-231 cells. SANG exhibited a higher potential to inhibit cell migration in MDA-MB-231 cells compared to MDA-MB-468 cells. Data obtained in this study suggest a unique antiangiogenic and antimetastatic effect of SANG in the MDA-MB-231 cell model. These effects are related to the compound’s ability to inhibit the angiogenic CCL2 and impact the ERK1/2 pathway. Therefore, SANG use may be recommended as a component of the therapeutic strategy for TNBC.
Journal Article
Fucoxanthin inhibits tumour‐related lymphangiogenesis and growth of breast cancer
2019
Tumour lymphangiogenesis plays an important role in promoting the growth and lymphatic metastasis of tumours. The process is associated with cell proliferation, migration and tube‐like structure formation in lymphatic endothelial cells (LEC), but no antilymphangiogenic agent is currently used in clinical practice. Fucoxanthin is a material found in brown algae that holds promise in the context of drug development. Fucoxanthin is a carotenoid with variety of pharmacological functions, including antitumour and anti‐inflammatory effects. The ability of fucoxanthin to inhibit lymphangiogenesis remains unclear. The results of experiments performed as part of this study show that fucoxanthin, extracted from Undaria pinnatifida (Wakame), inhibits proliferation, migration and formation of tube‐like structures in human LEC (HLEC). In this study, fucoxanthin also suppressed the malignant phenotype in human breast cancer MDA‐MB‐231 cells and decreased tumour‐induced lymphangiogenesis when used in combination with a conditional medium culture system. Fucoxanthin significantly decreased levels of vascular endothelial growth factor (VEGF)‐C, VEGF receptor‐3, nuclear factor kappa B, phospho‐Akt and phospho‐PI3K in HLEC. Fucoxanthin also decreased micro‐lymphatic vascular density (micro‐LVD) in a MDA‐MB‐231 nude mouse model of breast cancer. These findings suggest that fucoxanthin inhibits tumour‐induced lymphangiogenesis in vitro and in vivo, highlighting its potential use as an antilymphangiogenic agent for antitumour metastatic comprehensive therapy in patients with breast cancer.
Journal Article
Weighted gene coexpression network analysis-based identification of key modules and hub genes associated with drought sensitivity in rice
2020
Background
Drought stress is an adverse factor with deleterious effects on several aspects of rice growth. However, the mechanism underlying drought resistance in rice remains unclear. To understand the molecular mechanism of the drought response in rice, drought-sensitive CSSL (Chromosome Single-substitution Segment Line) PY6 was used to map QTLs of sensitive phenotypes and to reveal the impact of the QTLs on transcriptional profiling.
Results
The QTL
dss-1
was mapped onto the short arm of chromosome 1 of rice. According to transcriptomic analysis, the identified differentially expressed genes (DEGs) exhibited a downregulated pattern and were mainly enriched in photosynthesis-related GO terms, indicating that photosynthesis was greatly inhibited under drought. Further, according to weighted gene coexpression network analysis (WGCNA), specific gene modules (designating a group of genes with a similar expression pattern) were strongly correlated with H
2
O
2
(4 modules) and MDA (3 modules), respectively. Likewise, GO analysis revealed that the photosynthesis-related GO terms were consistently overrepresented in H
2
O
2
-correlated modules. Functional annotation of the differentially expressed hub genes (DEHGs) in the H
2
O
2
and MDA-correlated modules revealed cross-talk between abiotic and biotic stress responses for these genes, which were annotated as encoding WRKYs and PR family proteins, were notably differentially expressed between PY6 and PR403.
Conclusions
We speculated that drought-induced photosynthetic inhibition leads to H
2
O
2
and MDA accumulation, which can then trigger the reprogramming of the rice transcriptome, including the hub genes involved in ROS scavenging, to prevent oxidative stress damage. Our results shed light on and provide deep insight into the drought resistance mechanism in rice.
Journal Article
Chemical Profiling and Bioactivity Assessment of Helichrysum italicum (Roth) G. Don. Essential Oil: Exploring Pure Compounds and Synergistic Combinations
2023
Helichrysum italicum (Roth) G. Don., immortelle, is a plant species used in ethnomedicine and the food industry as a spice added to food, beverages, and bakery products. It has been shown to possess various biological activities, such as antioxidant and antibacterial activity, making it useful as a natural preservative. We investigated the phytochemical profile and biological activity of H. italicum essential oils from wild-grown plant material collected from natural habitats in the Republic of Croatia and Bosnia and Herzegovina. Using high-resolution scanning electron microscopy (SEM), a visual investigation of plant organs (stem, leaf, and flower) was performed, confirming the presence of essential oil reservoirs on the surface of all examined plant organs. Essential oils were isolated by hydrodistillation in the Clevenger apparatus. The chemical composition of the essential oils was determined using the GC-MS analytical technique. Cytotoxic activity tests were performed in vitro on three cell lines: skin (fibroblast), lung, and breast cancer. Using statistical tools, the synergistic and selective effects of H. italicum essential oil on healthy and tumor cells were correlated to chemical composition and cytotoxic activity. The synergistic and antagonistic effects of H. italicum essential oil’s individual components were simulated by testing pure compounds and their mixture of cytotoxic activity on fibroblasts and breast cancer cells. The results confirm that essential oil’s biological activity is much greater than the sum of the effects of its components. The present data are novel contributions to the body of knowledge on the biological activity of this species used in the food industry.
Journal Article
3-NAntC: A Potent Crotoxin B-Derived Peptide against the Triple-Negative MDA-MB-231 Breast Cancer Cell Line
2024
Breast cancer stands as the most prevalent type of tumor and a significant contributor to cancer-related deaths. Among its various subtypes, triple-negative breast cancer (TNBC) presents the worst prognosis due to its aggressive nature and the absence of effective treatments. Crotoxin, a protein found in the venom of Crotalus genus snakes, has demonstrated notable antitumor activity against aggressive solid tumors. However, its application has been hindered by substantial toxicity in humans. In efforts to address this challenge, Crotoxin B-derived peptides were synthesized and evaluated in vitro for their antitumor potential, leading to the discovery of 3-NAntC. Treatment with 3-NAntC at 1 µg/mL for 72 h notably reduced the viability of MDA-MB-231 cells to 49.0 ± 17.5% (p < 0.0001), while exhibiting minimal impact on the viability of HMEC cells (98.2 ± 13.8%) under the same conditions. Notably, 3-NAntC displayed superior antitumoral activity in vitro compared to cisplatin and exhibited a similar effect to doxorubicin. Further investigation revealed that 3-NAntC decreased the proliferation of MDA-MB-231 cells and induced G2/M phase arrest. It primarily prompted optimal cell death by apoptosis, with a lower incidence of the less desirable cell death by necrosis in comparison to doxorubicin. Additionally, 3-NAntC demonstrated low LDH release, and its cytotoxicity remained unaffected by the autophagy inhibitor 3-MA. In an in vivo zebrafish model, 3-NAntC exhibited excellent tolerability, showing no lethal effects and a low rate of malformations at high doses of up to 75 mg/mL. Overall, 3-NAntC emerges as a novel synthetic peptide with promising antitumor effects in vitro against TNBC cells and low toxicity in vivo.
Journal Article
Corrigendum to: A Study on IIIA Group Metals (B or Ga or Tl) Doped Mo2C-HZSM-5 Catalysts for Methane Dehydroaromatization
2026
CORRIGENDUM TO:Pasupulety, N., Alamoudi, M. A., Al-Zahrani, A. A. (2025). A Study on IIIA Group Metals (B or Ga or Tl) Doped Mo2C-HZSM-5 Catalysts for Methane Dehydroaromatization. Bulletin of Chemical Reaction Engineering & Catalysis, 20(4), 631-639. DOI: https://doi.org/10.9767/bcrec.20477This article has been corrected by Authors as follow:Corrections to References cited were done by Authors for improving validity, i.e. [12], [19-20], [22-23], [25-31], [33], [35-38], to the article DOI: 10.9767/bcrec.20477.Copyright © 2026 by Authors, Published by BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Journal Article
Development and Evaluation of a Novel Relatively Low-Cost Method to Derive HIV-1 Integration Sites and Proviral Sequences
by
Mullins, James I.
,
Hardy, Samantha R.
,
McLaughlin, Sherry
in
Antiretroviral therapy
,
DNA, Viral - genetics
,
Genomes
2026
In people taking antiretroviral therapy (ART) for HIV infection, the methods to characterize latent and active HIV reservoirs remain costly and labor-intensive. Our objective was to develop a relatively low-cost technique to amplify and sequence the proviruses that persist during ART along with the site in the human genome where each provirus is integrated. We developed a novel HIV-specific Multiple Displacement Amplification (HIV-MDA) assay that specifically amplifies HIV-1 proviruses and their associated integration site. Upon comparison of our HIV-MDA to an established commercial kit designed to amplify cellular DNA, we found that the HIV-MDA (1) typically yielded a greater number of HIV integration site (HIV IS) sequences per 150,000 cells analyzed; (2) improved rates of proviral DNA amplification; and (3) amplified HIV IS at a fraction of the cost (13.6 times less expensive). Thus, the HIV-MDA method appears to be a more sensitive and cost-effective approach to sequencing HIV IS and the associated proviruses compared to a commercial kit.
Journal Article