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Mycobacterium
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Flábio R. de Araújo, Nalvo F. Almeida
The total numbers of PE/PPE proteins found in MtH37Rv and MbAF2122/97 were 97 and 99, respectively. On the other hand, in MAP strains, the numbers were 42, 45, 43, 49, and 45 in MapMAP4, MapK10, Ma104, MapS397, and MapS5, respectively. Because these gene families used to be more frequent in pathogenic members of the Mycobacterium genus, this small number of PE/PPE proteins in MAP strains could suggest differences in the immunity response, compared to the MTBC species. A total of 18 families containing at least one gene of each one of the MAP strains and not containing genes of the MTBC strains have been found, showing a distinguishable group in MAP strains of this important protein class.
Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
Published in Pharmaceutical Biology, 2023
Xiaoyi Qi, Yonglan Chen, Sha Liu, Li Liu, Zehui Yu, Ling Yin, Lu Fu, Mingming Deng, Sicheng Liang, Muhan Lü
GO and KEGG pathway enrichment analyses were executed by DAVID to elucidate the underlying mechanism of SAG against melanoma. The core targets highlighted in the GO analysis results were mainly related to the nucleus, cytoplasm and plasma membrane of cytoplasm in Cellular Components (CC) (Figure 2(B)), ATP binding, protein binding and protein kinase activity in Molecular Function (MF) (Figure 2(C)), and protein phosphorylation, protein autophosphorylation and negative regulation of apoptotic processes in Biological Process (BP) (Figure 2(D)). The main pathways are as follows: pathways in cancer, ErbB signalling pathway, insulin signalling pathway, PI3K-AKT signalling pathway and focal adhesion, etc. Pathways in cancer involved 26 genes, including GSK3B, PIK3CD, PIK3CB, IGF1R, AKT2, ERBB2, MMP2, MMP9, MTOR, PTK2, MAPK10, AR, PIK3CA, FGFR1 and BCL2L1. The ErbB signalling pathway involved 12 genes, including MAPK10, GSK3B, PIK3CA, BAD, AKT2, ERBB2, PIK3CD, PIK3CB, PTK2 and MTOR. Furthermore, according to the KEGG pathway enrichment analyses, the core targets that were associated with the previous analysis were also enriched, such as cancer, ErbB and PI3K-Akt signalling pathway (Figure 2(E)). Taking these results together, a compound-target-pathway network was constructed to holistically expound the underlying mechanism of SAG against melanoma.
A patent review of cyclin-dependent kinase 7 (CDK7) inhibitors (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Markéta Kovalová, Joseph Peter Baraka, Václav Mik, Radek Jorda, Lei Luo, Hao Shao, Vladimír Kryštof
YPN-005 is highly selective for CDK7 from Yungjin Pharmaceutical with an IC50 of 31 nM and inhibited 7 other kinases over 90% at 1 µM in a 468 kinase panel screen, including CDK13, CDK19, CSNK1A1, CSNK1D, CSNK1E, MAPK15, and MAPK10 [60]. YPN-005 showed potent antiproliferative effects in SCLC cells, cisplatin- or etoposide-resistant cells, and organoids derived from SCLC patients. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the RNAP II CTD and significantly inhibited tumor growth in xenograft models established from the SCLC cell line H209 and cisplatin- or etoposide-resistant H209 cells. Another study [61] showed its antileukemic potential both in vitro and in vivo. YPN-005 induced apoptosis and suppressed the expression of c-MYC, FLT3 and STAT5. An ex vivo proliferation inhibition assay in primary leukemic cells also showed higher sensitivity in AML cells with FLT3-ITD mutation.
Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway
Published in Nutritional Neuroscience, 2022
Enrique Almanza-Aguilera, Alvaro Hernáez, Dolores Corella, Daniel Muñoz Aguayo, Emilio Ros, Olga Portolés, Julieta Valussi, Ramon Estruch, Oscar Coltell, Isaac Subirana, Jordi Salas-Salvadó, Miguel Ruiz-Canela, Rafael de la Torre, Lara Nonell, Montserrat Fitó, Olga Castañer
Eight genes were expressed in common among the neuroinflammation, TREM1, and the cholecystokinin/gastrin-mediated signaling pathways. Specifically, the expression of IL-1β, a key mediator of inflammatory processes, was found to be downregulated in the three canonical pathways. In addition, in at least two of the three canonical pathways, we observed a downregulation of the expression of cytokines (TNF-α, CCL3, IL-8, and IL10), T-cell activation receptors (CD86), pro-inflammatory enzymes (PTGS2), and regulators of cell cycle (MAPK10). Taken together, the molecular role of these genes and their expression changes after 3 months of the different dietary interventions suggest that inflammation signals are common in the three pathways, and that the three interventions could have a modulatory effect on these responses by different pathways. In agreement with this, PREDIMED sub-studies have documented that, compared to the control diet, the TMD enriched with VOO or nuts is more effective in reducing low-grade inflammation [40,41]. To the best of our knowledge, our study is the first to demonstrate at the transcriptomic level the modulation of the neuroinflammation and TREM1 signaling pathways in humans by TMD + Nuts and TMD + VOO, respectively. Furthermore, the significant downregulation of IL-1β, TNF-α, PTGS2, and IL-8 by at least two of the dietary interventions is noteworthy, since these genes are important mediators in the onset of neurodegenerative diseases [42–44].