Only in Titles

Search results for: AKT1

paperclip

#33946181   2021/04/30 To Up

Significance of Genetic Alterations and Telomere Length in Hepatocellular Carcinoma.

Telomerase reverse transcriptase () mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of -telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein-protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with . The PPI analysis identified eight key -interacting genes, namely , , , , , , , and . Among these, was the most strongly differentially expressed gene. promoter mutations were more frequent, expression was significantly higher, and telomere length was longer in tumors versus non-tumors. promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. promoter mutations were associated with higher levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The -telomere network may have a crucial role in the development and progression of HCC. -telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.
Jeong-Won Jang, Jin-Seoub Kim, Hye-Seon Kim, Kwon-Yong Tak, Soon-Kyu Lee, Hee-Chul Nam, Pil-Soo Sung, Chang-Min Kim, Jin-Young Park, Si-Hyun Bae, Jong-Young Choi, Seung-Kew Yoon

1599 related Products with: Significance of Genetic Alterations and Telomere Length in Hepatocellular Carcinoma.



Related Pathways

paperclip

#33945919   2021/04/20 To Up

Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling.

Allergic rhinitis (AR) is an inflammatory, immunoglobulin E (IgE)-mediated disease characterized by the typical symptoms of sneezing, rhinorrhea, nasal itching, and congestion. Higenamine (HG) is a plant-based alkaloid, possesses a wide range of activities, including vascular and tracheal relaxation, antioxidative, antiapoptotic, anti-inflammatory, and immunomodulatory activities. So far, the effect and the underlying mechanism of HG on AR have not been studied.
Xiaohan Wei, Baoping Zhang, Xiao Liang, Changshun Liu, Ting Xia, Yingjie Xie, Xue Deng, Xiaomei Tan

1337 related Products with: Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling.

14 inhibitors50 ug 1 Set100ug100ug Lyophilized100ug10mg100.00 ul250ul100 TESTS10 mg

Related Pathways

paperclip

Error loading info... Pleas try again later.
paperclip

#33940105   2021/04/30 To Up

Bisphenol B stimulates Leydig cell proliferation but inhibits maturation in late pubertal rats.

Bisphenol B (BPB) has been used as a substitute for bisphenol A (BPA) in plastic materials. Whether BPB disrupts the male reproductive system remains unknown. Here, we report the effect of BPB on Leydig cell maturation in late puberty. Male Sprague-Dawley (35 days old) rats were gavaged with BPB at 0, 10, 100, and 200 mg/kg/day for 21 days. BPB significantly reduced body and epididymis weight at 200 mg/kg. BPB markedly decreased serum testosterone levels at 100 and 200 mg/kg and serum luteinizing hormone and follicle-stimulating hormone levels at 200 mg/kg. BPB significantly increased Leydig cell number at 100 and 200 mg/kg, while down-regulating the expression of Leydig cell genes (Cyp11a1 and Hsd3b1) at ≥100 mg/kg and up-regulating the expression of Sertoli cell genes (Pdgfra, Fshr, Sox9) and cell cycle regulators (Pcna, Ccnb1, Cdk2, and Cdk4) at 10-200 mg/kg. BPB markedly increased the phosphorylation of AKT1, AKT2, and ERK1/2 at 200 mg/kg. BPB increased the proliferation of rat immature Leydig cells via promoting the S/M2 phase shift at 100 and 1000 nM after 24-h culture in vitro. In conclusion, BPB disrupts Leydig cell maturation in late puberty by increasing Leydig cell number while inhibiting its maturation.
Yang Li, Haoni Yan, Yige Yu, Cheng Zou, Lili Tian, Xiu Xin, Song Zhang, Zengqiang Li, Feifei Ma, Ren-Shan Ge

2815 related Products with: Bisphenol B stimulates Leydig cell proliferation but inhibits maturation in late pubertal rats.

100 ml.25 ml.500 ml100 ug5x5 ml500 ml96 tests5 x 1 ml100ug Lyophilized100 ml

Related Pathways

paperclip

#33936056   2021/04/15 To Up

Prioritizing Molecular Biomarkers in Asthma and Respiratory Allergy Using Systems Biology.

Highly prevalent respiratory diseases such as asthma and allergy remain a pressing health challenge. Currently, there is an unmet need for precise diagnostic tools capable of predicting the great heterogeneity of these illnesses. In a previous study of 94 asthma/respiratory allergy biomarker candidates, we defined a group of potential biomarkers to distinguish clinical phenotypes (i.e. nonallergic asthma, allergic asthma, respiratory allergy without asthma) and disease severity. Here, we analyze our experimental results using complex algorithmic approaches that establish holistic disease models (systems biology), combining these insights with information available in specialized databases developed worldwide. With this approach, we aim to prioritize the most relevant biomarkers according to their specificity and mechanistic implication with molecular motifs of the diseases. The Therapeutic Performance Mapping System (Anaxomics' TPMS technology) was used to generate one mathematical model per disease: allergic asthma (AA), non-allergic asthma (NA), and respiratory allergy (RA), defining specific molecular motifs for each. The relationship of our molecular biomarker candidates and each disease was analyzed by artificial neural networks (ANNs) scores. These analyses prioritized molecular biomarkers specific to the diseases and to particular molecular motifs. As a first step, molecular characterization of the pathophysiological processes of AA defined 16 molecular motifs: 2 specific for AA, 2 shared with RA, and 12 shared with NA. Mechanistic analysis showed 17 proteins that were strongly related to AA. Eleven proteins were associated with RA and 16 proteins with NA. Specificity analysis showed that 12 proteins were specific to AA, 7 were specific to RA, and 2 to NA. Finally, a triggering analysis revealed a relevant role for AKT1, STAT1, and MAPK13 in all three conditions and for TLR4 in asthmatic diseases (AA and NA). In conclusion, this study has enabled us to prioritize biomarkers depending on the functionality associated with each disease and with specific molecular motifs, which could improve the definition and usefulness of new molecular biomarkers.
Lucía Cremades-Jimeno, María Ángeles de Pedro, María López-Ramos, Joaquín Sastre, Pablo Mínguez, Ignacio Mahillo Fernández, Selene Baos, Blanca Cárdaba

2905 related Products with: Prioritizing Molecular Biomarkers in Asthma and Respiratory Allergy Using Systems Biology.

2x5L 1L500 grams1 Set100 250ul1 kit5 20 µl (10 mM)100 μg50μg

Related Pathways

paperclip

#33935736   2021/04/15 To Up

Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway.

Numerous studies have revealed that oxidative stress is closely associated with the occurrence and development of depression. Xiaoyao Pills (XYW) are included in the Chinese Pharmacopoeia and are frequently used for treating anxiety and depression by smoothing the liver, strengthening the spleen, and nourishing the blood. However, the antidepressant effects of XYW have not yet been thoroughly investigated. The objective of our study was to investigate the antidepressant-like effects of XYW and the underlying molecular mechanism in the olfactory bulbectomized (OB) rat model of depression using the open field test (OFT), sucrose preference test (SPT), splash test (ST), and novelty suppressed feeding test (NSFT). Results showed that XYW (0.93 and 1.86 g·kg) significantly alleviated depression-like behaviors in rats, which was indicated by increased sucrose preference in the SPT, prolonged grooming time in the ST, decreased horizontal movement in the OFT, and shorter feeding latency in the NSFT. In addition, XYW treatment dramatically reversed the reduced activity of superoxide dismutase and the decreased level of glutathione, while also lowering levels of malondialdehyde, an inflammatory mediator (nitric oxide), and pro-inflammatory cytokines (interleukin-6 and 1β) in the serum and cortex of OB rats. Mechanistically, XYW induced marked upregulation of mRNA and protein expression levels of NFE2L2, KEAP1, GPX3, HMOX1, SOD1, NQO1, OGG1, PIK3CA, p-AKT1/AKT1, NTRK2, and BDNF, and downregulation of ROS in the cortex and hippocampus via the activation of the NFE2L2/KEAP1, PIK3CA/AKT1, and NTRK2/BDNF pathways. These findings suggest that XYW exert antidepressant-like effects in OB rats with depression-like symptoms, and these effects are mediated by the alleviation of oxidative stress and the enhancement of neuroprotective effects through the activation of the PIK3CA-AKT1-NFE2L2/BDNF signaling pathways.
Yafei Ji, Jie Luo, Jiuseng Zeng, Yang Fang, Rong Liu, Fei Luan, Nan Zeng

1586 related Products with: Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway.

2 Pieces/Box2 Pieces/Box2 Pieces/BoxInhibitors2 Pieces/Box2 Pieces/Box100ug1

Related Pathways

paperclip

#33932497   2021/04/28 To Up

Regulation of PCTAIRE1 protein stability by AKT1, LKB1, and BRCA1.

PCTAIRE1, also known as CDK16, is a cyclin-dependent kinase that is regulated by cyclin Y. It is a member of the serine-threonine family of kinases and its functions have primarily been implicated in cellular processes like vesicular transport, neuronal growth and development, myogenesis, spermatogenesis and cell proliferation. However, as extensive studies on PCTAIRE1 have not yet been conducted, the signaling pathways for this kinase involved in governing many cellular processes are yet to be elucidated in detail. Here, we report the association of PCTAIRE1 with important cellular proteins involved in major cell signaling pathways, especially cell proliferation. In particular, here we show that PCTAIRE1 interacts with AKT1, a key player of the PI3K signaling pathway that is responsible for promoting cell survival and proliferation. Our studies show that PCTAIRE1 is a substrate of AKT1 that gets stabilized by it. Further, we show that PCTAIRE1 also interacts with and is degraded by LKB1, a kinase that is known to suppress cellular proliferation and also regulate cellular energy metabolism. Moreover, our results show that PCTAIRE1 is also degraded by BRCA1, a well-known tumor suppressor. Together, our studies highlight the regulation of PCTAIRE1 by key players of the major cell signaling pathways involved in regulating cell proliferation, and therefore, provide crucial links that could be explored further to elucidate the mechanistic role of PCTAIRE1 in cell proliferation and tumorigensis.
Syed Qaaifah Gillani, Misbah Un Nisa, Zarka Sarwar, Irfana Reshi, Sameer Bhat, Nusrat Nabi, Shaida Andrabi

1731 related Products with: Regulation of PCTAIRE1 protein stability by AKT1, LKB1, and BRCA1.

1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set100ul1 Set1 Set1 Set

Related Pathways

paperclip

#33932138   2021/05/01 To Up

METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukemia.

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors (HD-MSCs). However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differ from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase of AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.
Zhi-Peng Pan, Bin Wang, Di-Yu Hou, Ruo-Lan You, Xiao-Ting Wang, Wen-Hui Xie, Hui-Fang Huang

2187 related Products with: METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukemia.

500 gm.24 wells1 kit3 inhibitors1 mg10 ug5 x 10A5 cells/vial24 wells24 wells

Related Pathways

paperclip

#33932085   2021/05/01 To Up

SENP3 loss promotes M2 macrophage polarization and breast cancer progression.

Tumor-associated macrophages (TAMs) play a crucial role in promoting cancer progression. Upon cytokine stimulation, TAMs preferentially polarize to the anti-inflammatory and pro-tumor M2 subtype . The mechanism underlying such preferential polarization remains elusive. Here, we report that macrophage-specific deletion of the SUMO-specific protease SENP3 promotes macrophage polarization towards M2 in bone-marrow-derived macrophage (BMDM) induced by IL4/IL13 and in an ex vivo model (murine Py8119 cell line), as well as in a mouse orthotopic tumor model. Notably, SENP3 loss in macrophages accelerated breast cancer malignancy in ex vivo and in vivo models. Mechanistically, we identified Akt1 as the substrate of SENP3 and found that the enhanced Akt1 SUMOylation upon SENP3 loss resulted in Akt1 hyper-phosphorylation and activation, which facilitates M2 polarization. Analysis of clinical data showed that a lower level of SENP3 in TAMs has a strong negative correlation with the level of the M2 marker CD206, as well as with a worse clinical outcome. Thus, increased Akt1 SUMOylation as a result of SENP3 deficiency modulates polarization of macrophages to the M2 subtype within a breast cancer microenvironment, which in turn promotes tumor progression.
Ming Xiao, Qi Bian, Yimin Lao, Jing Yi, Xueqing Sun, Xuxu Sun, Jie Yang

2797 related Products with: SENP3 loss promotes M2 macrophage polarization and breast cancer progression.



Related Pathways

paperclip

#33931488   2021/04/30 To Up

Emerging Roles for AKT Isoform Preference in Cancer Progression Pathways.

The phosphoinositol-3 kinase (PI3K)-AKT pathway is one of the most mutated in human cancers, predominantly associated with the loss of the signaling antagonist, PTEN, and to lesser extents, with gain-of-function mutations in PIK3CA (encoding PI3K-p110α) and AKT1. In addition, most oncogenic driver pathways activate PI3K/AKT signaling. Nonetheless, drugs targeting PI3K or AKT have fared poorly against solid tumors in clinical trials as monotherapies, yet some have shown efficacy when combined with inhibitors of other oncogenic drivers, such as receptor tyrosine kinases or nuclear hormone receptors. There is growing evidence that AKT isoforms, AKT1, AKT2, and AKT3, have different, often distinct roles in either promoting or suppressing specific parameters of oncogenic progression, yet few if any isoform-preferred substrates have been characterized. This review will describe recent data showing that the differential activation of AKT isoforms is mediated by complex interplays between PTEN, PI3K isoforms and upstream tyrosine kinases, and that the efficacy of PI3K/AKT inhibitors will likely depend on the successful targeting of specific AKT isoforms and their preferred pathways.
Seamus E Degan, Irwin H Gelman

2096 related Products with: Emerging Roles for AKT Isoform Preference in Cancer Progression Pathways.



Related Pathways