scholarly journals Synergistic Effects of Resveratrol and Temozolomide Against Glioblastoma Cells: Underlying Mechanism and Therapeutic Implications

2020 ◽  
Vol Volume 12 ◽  
pp. 8341-8354
Author(s):  
Yusi Liu ◽  
Xue Song ◽  
Moli Wu ◽  
Jiao Wu ◽  
Jia Liu
Keyword(s):  
Synergistic Effects ◽  
Underlying Mechanism ◽  
Glioblastoma Cells ◽  
Therapeutic Implications

A Theoretical Perspective of the Structure and Thermodynamics of Secondary Organic Aerosols from Toluene: Molecular Hierarchical Synergistic Effects

2022 ◽  
Author(s):  
Xianli Duan ◽  
Xianyu Song ◽  
Shi Ruifang ◽  
Wang Xuan ◽  
Suhang Chen ◽  
...  
Keyword(s):  
Liquid Fuel ◽  
Secondary Organic Aerosols ◽  
Secondary Organic Aerosol ◽  
Synergistic Effects ◽  
Theoretical Perspective ◽  
Organic Aerosols ◽  
Organic Aerosol ◽  
Underlying Mechanism ◽  
Important Constituent

Toluene is an important constituent of liquid fuel, and it contributes to the formation of secondary organic aerosol (SOA) under photochemical conditions. However, the underlying mechanism of toluene SOA is...

scholarly journals Capsosiphon fulvescens Glycoproteins Enhance Probiotics-Induced Cognitive Improvement in Aged Rats

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 837 ◽  
Author(s):  
Jeong Hwan Oh ◽  
Taek-Jeong Nam ◽  
Youn Hee Choi
Keyword(s):  
Dorsal Hippocampus ◽  
Synergistic Effects ◽  
Elongation Factor ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Aged Rats ◽  
Bdnf Expression ◽  
Cognitive Improvement ◽  
Capsosiphon Fulvescens ◽  
Eef2 Kinase

Aging-induced cognitive dysfunction can be regulated by probiotics through bidirectional communication with the brain. This study aimed to investigate whether Capsosiphon fulvescens glycoproteins (Cf-hGP) enhanced probiotic-induced improvement of memory in aged rats and the underlying mechanism in the dorsal hippocampus. Cf-hGP were isolated using lectin resin. Cf-hGP (15 mg/kg/day) and/or Lactobacillus plantarum (L. plantarum) (109 CFU/rat/day) were orally administered once a day for 4 weeks. Co-treatment with Cf-hGP and L. plantarum synergistically improved spatial memory in aged rats, which was overturned by functional blocks of brain-derived neurotrophic factor (BDNF) signaling. Increases in BDNF expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation were accompanied by mono- and/or co-administration in the dorsal hippocampus, while c-Jun N-terminal kinase (JNK) phosphorylation and glucose-regulated protein 78 expression were decreased. These synergistic effects were downregulated by blocks of BDNF/Nrf2-mediated signaling. In particular, co-treatment, not mono-treatment, reduced phosphorylation of eukaryotic elongation factor 2 (eEF2) regulated by eEF2 kinase and protein phosphatase 2A. Additionally, co-treatment downregulated the interaction between eEF2 kinase and JNK. These data demonstrated that cognitive impairment in aged rats was synergistically diminished by co-treatment with Cf-hGP and L. plantarum through BDNF-mediated regulation of Nrf2 and eEF2 signaling pathways in the dorsal hippocampus.

scholarly journals The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5881
Author(s):  
Nak Yoon Sung ◽  
Deok Jeong ◽  
Youn Young Shim ◽  
Zubair Ahmed Ratan ◽  
Young-Jin Jang ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Biological Activities ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Flaxseed Oil ◽  
C6 Cells ◽  
Glioblastoma Cells ◽  
Downstream Effector ◽  
Anti Cancer ◽  
Induced Apoptosis

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1–9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

scholarly journals KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Seon Rang Woo ◽  
Yunhee Ham ◽  
Wonyoung Kang ◽  
Heekyoung Yang ◽  
Sujong Kim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Line ◽  
Synergistic Effects ◽  
Resistant Cell Line ◽  
Therapeutic Effects ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Cytotoxic Treatment ◽  
Xenograft Models

Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy. Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies. We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma. Although KML001 alone showed little effects onin vitrosurvival of glioblastoma cells, cell death byin vitrotemozolomide treatment or irradiation was synergistically potentiated by combination with KML001. Since phosphorylatedγ-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis. Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG. In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly. These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.

scholarly journals Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhang’an Dai ◽  
Lin Cai ◽  
Yingyu Chen ◽  
Silu Wang ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Herbal Extract ◽  
Extracellular Matrix Protein ◽  
Glioblastoma Cells ◽  
Primary Glioblastoma ◽  
Proliferation And Invasion

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

scholarly journals Kokumi Taste Active Peptides Modulate Salt and Umami Taste

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1198 ◽  
Author(s):  
Mee-Ra Rhyu ◽  
Ah-Young Song ◽  
Eun-Young Kim ◽  
Hee-Jin Son ◽  
Yiseul Kim ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Human Subjects ◽  
Underlying Mechanism ◽  
Soy Sauce ◽  
Na Channel ◽  
Taste Intensity ◽  
Maximum Increase ◽  
Salt Taste ◽  
Umami Taste ◽  
Peptide Fraction

Kokumi taste substances exemplified by γ-glutamyl peptides and Maillard Peptides modulate salt and umami tastes. However, the underlying mechanism for their action has not been delineated. Here, we investigated the effects of a kokumi taste active and inactive peptide fraction (500–10,000 Da) isolated from mature (FIIm) and immature (FIIim) Ganjang, a typical Korean soy sauce, on salt and umami taste responses in humans and rodents. Only FIIm (0.1–1.0%) produced a biphasic effect in rat chorda tympani (CT) taste nerve responses to lingual stimulation with 100 mM NaCl + 5 μM benzamil, a specific epithelial Na+ channel blocker. Both elevated temperature (42 °C) and FIIm produced synergistic effects on the NaCl + benzamil CT response. At 0.5% FIIm produced the maximum increase in rat CT response to NaCl + benzamil, and enhanced salt taste intensity in human subjects. At 2.5% FIIm enhanced rat CT response to glutamate that was equivalent to the enhancement observed with 1 mM IMP. In human subjects, 0.3% FIIm produced enhancement of umami taste. These results suggest that FIIm modulates amiloride-insensitive salt taste and umami taste at different concentration ranges in rats and humans.

scholarly journals Antifungal Triazoles and Polymorphonuclear Leukocytes Synergize To Cause Increased Hyphal Damage to Scedosporium prolificans and Scedosporium apiospermum

2002 ◽  
Vol 46 (7) ◽  
pp. 2234-2237 ◽  
Author(s):  
Cristina Gil-Lamaignere ◽  
Emmanuel Roilides ◽  
Juan Mosquera ◽  
Avgi Maloukou ◽  
Thomas J. Walsh
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Fungal Pathogens ◽  
Colorimetric Assay ◽  
Synergistic Effects ◽  
Scedosporium Apiospermum ◽  
Pseudallescheria Boydii ◽  
Antifungal Activities ◽  
Therapeutic Implications ◽  
Scedosporium Prolificans ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii) cause pulmonary and disseminated infections refractory to most currently used antifungal agents in immunocompromised patients. We therefore investigated the potential antifungal activities of the triazoles itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) in combination with human polymorphonuclear leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide) sodium salt was used for the measurement of hyphal damage as an indicator of antifungal activity. We found that the newer triazoles VRC and PSC displayed synergistic effects with PMNs against S. prolificans hyphae after 24 h (P < 0.05), whereas the effect of ITC in combination with PMNs was additive (P < 0.01). All three triazoles displayed additive antifungal activities in combination with PMNs against S. apiospermum hyphae (P < 0.05). The synergistic or additive effects that these triazoles exhibited, combined with the antifungal activities of human PMNs, may have important therapeutic implications for the management of infections due to S. prolificans and S. apiospermum.

Anti-Inflammatory Effects of Boldine and Reticuline Isolated from Litsea cubeba through JAK2/STAT3 and NF-κB Signaling Pathways

Planta Medica ◽  
2017 ◽  
Vol 84 (01) ◽  
pp. 20-25 ◽  
Author(s):  
Xinyao Yang ◽  
Xiaoli Gao ◽  
Yuan Cao ◽  
Qiang Guo ◽  
Shanshan Li ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Underlying Mechanism ◽  
Janus Kinase ◽  
Inflammatory Activity ◽  
Intragastric Administration ◽  
Litsea Cubeba ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Rat Paw

AbstractThe anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies. Boldine, reticuline, and their combination notably inhibited mRNA expressions of TNF-α, and IL-6 and reduced the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Beyond that, their combination also can reduce the phosphorylation levels of p65 and IκBα in the pathological tissues of animals, as observed by real-time PCR and western blot analyses, respectively. These findings indicate for the first time that boldine and reticuline have not only anti-inflammatory activity but also potential synergistic effects in vivo. The underlying mechanism may relate to the inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which may be a consequence of JAK2/STAT3 and NF-κB pathway involvements. This study provides useful data for further exploration and application of boldine and reticuline as potential anti-inflammatory medicines.

scholarly journals GTP-dependent formation of straight oligomers leads to nucleation of microtubules

2020 ◽  
Author(s):  
Rie Ayukawa ◽  
Seigo Iwata ◽  
Hiroshi Imai ◽  
Shinji Kamimura ◽  
Masahito Hayashi ◽  
...  
Keyword(s):  
High Efficiency ◽  
Early Stage ◽  
Synergistic Effects ◽  
Underlying Mechanism ◽  
Small Shift ◽  
Spontaneous Nucleation ◽  
Cellular Factors ◽  
Stochastic Events ◽  
A Minor

AbstractMicrotubule (MT) nucleation is essential for cellular activities, but its mechanism is not known because of the difficulty involved in capturing rare stochastic events in the early stage of polymerization. In cells, MTs are nucleated at tubulin concentrations significantly lower than those required for spontaneous nucleation in vitro. The high efficiency of nucleation is due to the synergistic effects of various cellular factors, but the underlying mechanism has not been clarified yet. Here, combining negative stain electron microscopy and kinetic analysis, we demonstrate that the formation of single-stranded straight oligomers with critical size is essential for nucleation in vitro. While the single-stranded oligomers of GTP-tubulin that form prior to MT nucleation show variable curvatures including a few straight oligomers, only curved oligomers are observed among the GDP-bound counterparts. The Y222F mutation in β-tubulin increases the proportion of straight oligomers and drastically accelerates MT nucleation. Our results support a model in which GTP binding causes a small shift in the distribution of oligomer curvature, generating a minor population of straight oligomers compatible with lateral association and further growth to MTs. Our study suggests that cellular factors involved in nucleation promote it via stabilization of straight oligomers.

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