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#33080566   2020/10/03 To Up

Effect of the isoflavone corylin from cullen corylifolium on colorectal cancer growth, by targeting the STAT3 signaling pathway.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Corylin is an isoflavone extracted from Cullen corylifolium (L.) Medik., which is widely used anti-inflammatory and anticancer in Asian countries. Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and development of CRC.
Lehe Yang, Yulei Yao, Ying Bai, Dandan Zheng, Feng Zhou, Luye Chen, Wanle Hu, Youqun Xiang, Haiyang Zhao, Zhiguo Liu, Liangxing Wang, Xiaoying Huang, Chengguang Zhao

2673 related Products with: Effect of the isoflavone corylin from cullen corylifolium on colorectal cancer growth, by targeting the STAT3 signaling pathway.

2 Pieces/Boxmin 2 cartons2 Pieces/Box100.00 ul200 units12 Pieces/Box1500 Units

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#33080494   2020/10/08 To Up

Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy.

PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as H NMR, C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC of 5.827 ± 0.46 µM, but significantly inhibited the Wnt/β-catenin pathway with IC1286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.
Tarek S Ibrahim, Mohamed M Hawwas, Ehab S Taher, Nabil A Alhakamy, Mohamed A Alfaleh, Mohamed Elagawany, Bahaa Elgendy, Gamal M Zayed, Mamdouh F A Mohamed, Zakaria K Abdel-Samii, Yaseen A M M Elshaier

2229 related Products with: Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy.

100ul25 mg100 mg100ug 25 MG10 mg2.5 mg10 plates200ul100ug25 mg

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#33080468   2020/10/17 To Up

D-Carvone inhibit cerebral ischemia/reperfusion induced inflammatory response TLR4/NLRP3 signaling pathway.

To explore the present treatment strategies for ischemic stroke lowered by ischemia-reperfusion (I/R) injury, to hypothesize the effect of d-Carvone on cerebral I/R brain injury induced neuroinflammation through oxidative stress markers mechanism via NRLP3 and TLR4 marker expressions in rat model. The rats were divided into four groups: Sham, I/R vehicle, I/R + D-carvone (10 mg/kg/bw), I/R + D-carvone (20 mg/kg/bw). Supplementation of d-carvone at dose of 10 and 20 m/kg/bw increased the water content, reduced infract volume, attenuated neurological score depicts, furthermore it had antioxidative, anti-inflammatory, and anti-apoptotic effects against cerebral I/R brain injury. In the brain tissues decreased proinflammatory cytokines IL-1β and TNF-α reduced interleukins IL-6, IL-4, IL-10 & VEGF dose dependently, and mRNA expressions of NLRP3, caspase -1, TNF-α, ASC, IL-1β and TLR3 down regulated in cerebral I/R induced rats. Finally d- carvone can successfully improve the cerebral I/R induced rats neuroinflammation, in the hippocampus and cortical areas of the brain finally reduces cerebral I/R induced injury. These results were hypothesized that d-carvone contributed to cerebral stroke associated with the TLR3, giving an excellent therapeutic approach for cerebral I/R brain injury.
Mengyuan Dai, Lixiu Wu, Kunqiang Yu, Ri Xu, Yanbin Wei, Arunachalam Chinnathambi, Tahani Awad Alahmadi, Minya Zhou

2996 related Products with: D-Carvone inhibit cerebral ischemia/reperfusion induced inflammatory response TLR4/NLRP3 signaling pathway.

Inhibitors1 mg2 Pieces/Box7 inhibitors1.5x10(6) cells2 Pieces/Box11 inhibitors2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box

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#33080445   2020/10/14 To Up

Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions.

Glioblastoma (GBM) is the most common malignant primary brain tumour originating in the CNS. Median patient survival is <15 months with standard treatment which consists of surgery alongside radiation therapy and temozolomide chemotherapy. However, because of the aggressive nature of GBM, and the significant toxicity of these adjuvant therapies, long-term therapeutic effects are unsatisfactory. Thus, there is urgency to identify new drug targets for GBM. Recent evidence shows that the transient receptor potential melastatin 7 (TRPM7) cation channel is aberrantly upregulated in GBM and its inhibition leads to reduction of GBM cellular functions. This suggests that TRPM7 may be a potential drug target for GBM treatment. In this study, we assessed the effects of the specific TRPM7 antagonist waixenicin A on human GBM cell lines U87 or U251 both in vitro and in vivo. First, we demonstrated in vitro that application of waixenicin A reduced TRPM7 protein expression and inhibited the TRPM7-like currents in GBM cells. We also observed reduction of GBM cell viability, migration, and invasion. Using an intracranial xenograft GBM mouse model, we showed that with treatment of waixenicin A, there was increased cleaved caspase 3 activity, alongside reduction in Ki-67, cofilin, and Akt activity in vivo. Together, these data demonstrate higher GBM cell apoptosis, and lower proliferation, migration, invasion and survivability following treatment with waixenicin A.
Raymond Wong, Haifan Gong, Rahmah Alanazi, Andrew Bondoc, Amanda Luck, Nesrin Sabha, F David Horgen, Andrea Fleig, James T Rutka, Zhong-Ping Feng, Hong-Shuo Sun

1397 related Products with: Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions.

48 assays 0.1ml (1mg/ml)96 assays96 assays 48 assays

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#33080274   2020/10/17 To Up

Characterization and expression analysis of tandemly-replicated asc genes in the Japanese medaka, Oryzias latipes.

ASC is a component of the inflammasome playing crucial roles in the inflammatory response. In mammals, ASC induces pyroptosis and inflammatory cytokine production. In this study, three asc genes (asc1, asc2, and asc3) from the Japanese medaka (Oryzias latipes) were identified and characterized. These asc genes were tandem replicates on chromosome 16, and their exon-intron structures differed between them. All three ASCs conserved the pyrin and caspase-recruitment domains, which are important for inflammasome formation. In phylogenetic analysis, all ASCs clustered with those of other teleosts. The asc1 expression levels were significantly higher in several organs than those of asc2 and asc3, suggesting that asc1 may act as a dominant asc in the Japanese medaka. Expression of the three asc genes showed different patterns during Aeromonas hydrophila and Edwardsiella piscicida infections. Furthermore, their expression was adequately down-regulated in the medaka fin-derived cells stimulated with ATP for 12 h, while asc2 expression was statistically up-regulated after nigericin stimulation for 24 h. Moreover, the expression of asc2 and asc3 was significantly higher in the skin of ASC-1-knockout medaka than in that of the wild type medaka during A. hydrophila infection.
Natsuki Morimoto, Yo Okamura, Tomoya Kono, Masahiro Sakai, Jun-Ichi Hikima

2373 related Products with: Characterization and expression analysis of tandemly-replicated asc genes in the Japanese medaka, Oryzias latipes.

1300 units100 μg

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#33080132   2020/10/20 To Up

Protective Action of Monomeric and Fibrillar α-Synuclein on Neuronal Cells Exposed to the Dopaminergic Toxins Salsolinol and DOPAL.

The aggregation of α-synuclein (aSyn) is believed to be mechanistically linked to the degeneration of dopamine (DA)-producing neurons in Parkinson's disease (PD). In this respect, one crucial question that yet remains unsolved is whether aSyn aggregation is associated with either a gain- or loss-of-function of the protein in neuronal cells. Herein, we investigated the effect of monomeric versus fibrillar aSyn on mesencephalic dopaminergic neurons in primary cultures challenged with the neurotoxic catechols: salsolinol (SALSO; 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) and 3,4-dihydroxyphenylacetaldehyde (DOPAL). aSyn monomer protected cells against either SALSO- or DOPAL-induced toxicity via inhibition of caspase-3-mediated apoptosis. While fibrillar aSyn failed in attenuating SALSO neurotoxicity, it increased the viability of DOPAL-treated cells, which was apparently not associated with the inhibition of caspase-3 cleavage. The fact that DOPAL-derived aSyn adducts exhibit lower toxicity compared with DOPAL itself raises the question of whether the generation of these adducts could be part of or a collateral effect of aSyn-mediated protection in neurons exposed to DOPAL. Overall, our work provides important evidence on the impact of the fibrillation of aSyn on its protective role in neuronal cells exposed to the toxic catechols SALSO and DOPAL.
Phelippe Carmo-Gonçalves, Luciana Romão, Cristian Follmer

2305 related Products with: Protective Action of Monomeric and Fibrillar α-Synuclein on Neuronal Cells Exposed to the Dopaminergic Toxins Salsolinol and DOPAL.

100 mg100ug1000 tests100ug500 MG2.5 mg25 mg100ug10 mg50 mg50 ug 25 mg

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#33079922   2020/10/20 To Up

Verteporfin Promotes the Apoptosis and Inhibits the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Downregulating SULT2B1 Expression.

BACKGROUND Cervical cancer threatens women's health worldwide. Verteporfin (VP), a small-molecule YAP1 inhibitor, inhibits cancer cell growth. This study investigated whether VP could inhibit the proliferation and promote the apoptosis of cervical cancer cells by decreasing SULT2B1 expression. MATERIAL AND METHODS Normal and cancerous cervical cell proliferation after VP treatment was detected by CCK-8 assay. HeLa cell migration, invasion, and apoptosis after VP treatment and transfection were analyzed by wound healing assay, transwell assay, and TUNEL assay, respectively. The expression of related proteins was determined by western blot analysis. Western blot and RT-qPCR analysis detected mRNA and protein expression of SULT2B1. RESULTS Different VP concentrations (0.5, 1, 2, and 5 μM) inhibited the viability of HeLa cells and had no obvious effect on H8 cells. Therefore, 5 μM VP was selected for subsequent experiments. VP inhibited the proliferation, migration, and invasion of HeLa cells and promoted their apoptosis. Bcl-2 expression decreased, and expression of Bax, caspase-3, and caspase-9 in VP-treated HeLa cells increased. SULT2B1 expression increased in cervical cancer cells compared with normal cervical cells. Furthermore, SULT2B1 expression increased in HeLa cells and VP suppressed SULT2B1 expression. SULT2B1 overexpression reduced the inhibiting effect of VP on the proliferation, migration, and apoptosis of HeLa cells, and reduced VP effect on apoptosis of HeLa cells. SULT2B1 overexpression upregulated the Bcl-2 expression and downregulated the expression of Bax, caspase-3, and caspase-9 in VP-treated HeLa cells. CONCLUSIONS VP inhibited the proliferation, migration, and invasion and promoted apoptosis of cervical cancer cells by decreasing SULT2B1 expression.
Lijun Yin, Guilin Chen

1933 related Products with: Verteporfin Promotes the Apoptosis and Inhibits the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Downregulating SULT2B1 Expression.

11 mg100ug1 ml200 units1,000 tests200 1

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#33079735   2020/10/16 To Up

Glibenclamide treatment prevents depressive-like behavior and memory impairment induced by chronic unpredictable stress in female mice.

Glibenclamide is a second-generation sulfonylurea used in the treatment of Type 2 Diabetes Mellitus. The primary target of glibenclamide is ATP-sensitive potassium channels inhibition; however, other possible targets include the control of inflammation and blood-brain barrier permeability, which makes this compound potentially interesting for the management of brain-related disorders. Here, we showed that systemic treatment with glibenclamide (5 mg/kg, p.o., for 21 days) could prevent the behavioral despair and the cognitive dysfunction induced by chronic unpredictable stress (CUS) in mice. In nonhypoglycemic doses, glibenclamide attenuated the stress-induced weight loss, decreased adrenal weight, and prevented the increase in glucocorticoid receptors in the prefrontal cortex, suggesting an impact in hypothalamic-pituitary-adrenal (HPA) axis function. Additionally, we did not observe changes in Iba-1, NLRP3 and caspase-1 levels in the prefrontal cortex or hippocampus after CUS or glibenclamide treatment. Thus, this study suggests that chronic treatment with glibenclamide prevents the emotional and cognitive effects of chronic stress in female mice. On the other hand, the control of neuroinflammation and NLRP3 inflammasome pathway is not the major mechanism mediating these effects. The behavioral effects might be mediated, in part, by the normalization of glucocorticoid receptors and HPA axis.
Axel Fogaça Rosado, Priscila Batista Rosa, Nicolle Platt, Bruna Caroline Pierone, Vivian Binder Neis, Ana Lúcia Severo Rodrigues, Manuella Pinto Kaster, Fernanda Neutzling Kaufmann

1773 related Products with: Glibenclamide treatment prevents depressive-like behavior and memory impairment induced by chronic unpredictable stress in female mice.

50 UG1 mg100ug100 ul1 mg 100ul100ug50 ul5ug2ug50 ul400 ug

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#33079558   2020/10/20 To Up

Enhanced Caspase-Mediated Abrogation of Autophagy by Temozolomide-Loaded and Panitumumab-Conjugated Poly(lactic--glycolic acid) Nanoparticles in Epidermal Growth Factor Receptor Overexpressing Glioblastoma Cells.

The mechanism of cell death has attracted a great deal of research interest in the design of antitumor therapy in recent days. Several attempts have been carried out in this direction and in our study also, we studied this phenomenon with the design of panitumumab (PmAb)-conjugated and temozolomide (TMZ)-loaded poly(lactic--glycolic acid) nanoparticles (PLGA-NPs), termed PmAb-TMZ-PLGA-NPs. First, PmAb was functionalized on the surface of TMZ-PLGA-NPs using ethyl(dimethylaminopropyl)carbodiimide (EDC)--hydroxysuccinimide (NHS) chemistry. Targeted PLGA-NPs significantly enhanced the cellular uptake of nanoparticles in the U-87 MG cell line as a result of the high epidermal growth factor receptor (EGFR) expression, compared to the LN229 cell line. Our study demonstrated that following the treatment of PmAb-TMZ-PLGA-NPs, a more pronounced anticancer effect was noticed in comparison with free TMZ and TMZ-PLGA-NPs. Further, a more pronounced cytotoxic effect of PmAb-TMZ-PLGA-NPs was observed in the high EGFR-overexpressed glioblastoma multiforme (GBM) model (U-87 MG) cell line compared to the low EGFR GBM model (LN229). Our study demonstrated that the treatment of PmAb-TMZ-PLGA-NPs in GBM tried to adopt the autophagic pathway of the cell survival mechanism with the elevated level of autophagic marker (Beclin-1 and LC3B) at 24 h time point, thereby suppressing the expression of caspase-9 and PARP. However, at the 48 h time point, the elevated expression of caspase-9 and PARP with the downregulation of Beclin-1 and LC3B, following the treatment of PmAb-TMZ-PLGA-NPs in the GBM model, suggested that apoptotic cell death was superior over autophagic cell survival. It was also noteworthy the activation of caspase-9 was correlated with the continuous overproduction of reactive oxygen species up to a 48 h time point after the treatment of PmAb-TMZ-PLGA-NPs. This result sheds light on the biological effect of targeted chemotherapy and illustrates that PmAb-TMZ-PLGA-NPs could be applied for EGFR-overexpressed different cancer models.
Asmita Banstola, Ramesh Duwa, Fakhrosaddat Emami, Jee-Heon Jeong, Simmyung Yook

2022 related Products with: Enhanced Caspase-Mediated Abrogation of Autophagy by Temozolomide-Loaded and Panitumumab-Conjugated Poly(lactic--glycolic acid) Nanoparticles in Epidermal Growth Factor Receptor Overexpressing Glioblastoma Cells.

5 x 50 ug2 Pieces/Box50 ug100ug100ug100ug Lyophilized1 kit(96 Wells)100.00 ug100ug50 ug100ug100ug Lyophilized

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#33079459   2020/10/20 To Up

Ferulic acid (FA) protects human retinal pigment epithelial cells from H O -induced oxidative injuries.

The aim of present study is to investigate whether Ferulic acid (FA), a natural polyphenol antioxidant, was able to protect ARPE-19 cells from hydrogen peroxide (H O )-induced damage, and elucidate the underlying mechanisms. Our results revealed that FA pre-treatment for 24 hours can reverse cell loss of H O -induced ARPE-19 cells via the promotion of cell proliferation and prevention of apoptosis, as evidenced by 5-ethynyl-2'-deoxyuridine (EdU) incorporation and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay, respectively. Moreover, the addition of FA (5 mM) can decrease Bax and cleaved caspase-3 protein expression, but increase Bcl-2 protein expression in ARPE-19 cells. Furthermore, H O -induced oxidative stress in ARPE-19 cells was significantly alleviated by FA, illustrated by reduced levels of ROS and MDA. In addition, the attenuated antioxidant enzymes activities of (SOD, CAT and GPX) and GSH level were reversed almost to the normal base level by the pre-addition of FA for 24 hours. In all assays, FA itself did not exert any effect on the change of the above parameters. These novel findings indicated that FA effectively protected human ARPE-19 cells from H O -induced oxidative damage through its pro-proliferation, anti-apoptosis and antioxidant activity, suggesting that FA has a therapeutic potential in the prevention and treatment of AMD.
Kunpeng Xie, Bo Jin, Haiyan Zhu, Pengyi Zhou, Liping Du, Xuemin Jin

1837 related Products with: Ferulic acid (FA) protects human retinal pigment epithelial cells from H O -induced oxidative injuries.

1 mg.1.00 flask1.00 flask1.00 flask1 mg25 TESTS1.00 flask25 100ul500 µg

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