MetaboLights
A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 3 is substituted by a 2-hydroxyphenyl group.
Identification
3-(2-hydroxyphenyl)propanoic acid
2-hydroxybenzenepropanoic acid
3-(2-Hydroxyphenyl)propionic acid
3-(2-hydroxyphenyl)propionic acid
3-(o-hydroxyphenyl) propionic acid
melilotic acid
o-Hydroxyphenylpropionic acid
Species
homo sapiens
NCBI:txid9606 19573517
Europe PubMed Central results
METABOLISM OF COUMARIN BY A MICRO-ORGANISM: O-COUMARIC ACID AS AN INTERMEDIATE BETWEEN COUMARIN AND MELILOTIC ACID.
THE METABOLISM OF COUMARIN BY A MICROORGANISM. II. THE REDUCTION OF O-COUMARIC ACID TO MELILOTIC ACID.
mtDNA germ line variation mediated ROS generates retrograde signaling and induces pro-cancerous metabolic features.
Author: Singh RK, Srivastava A, Kalaiarasan P, Manvati S, Chopra R, Bamezai RN.
Abstract: mtDNA non-synonymous germ line variation (G10398A; p.A114T) has remained equivocal with least mechanistic understanding in showing an association with cancer. This has necessitated showing in-vitro how an over-expression within mitochondria of either of the variants produces higher intracellular ROS, resulting in differential anchorage dependent and independent growth. Both these features were observed to be relatively higher in ND3:114T variant. An elevated amount of intracellular carbonylated proteins and a reduced activity of a key glycolytic enzyme, Pyruvate kinase M2, along with high glucose uptake and lactate production were other pro-cancerous features observed. The retrograde signaling through surplus ROS was generated by post-ND3 over-expression regulated nuclear gene expression epigenetically, involving selectively the apoptotic-DDR-pathways. The feature of ND3 over-expression, inducing ROS mediated pro-cancerous features in the cells in in vitro, was replicated in a pilot study in a limited number of sporadic breast tumors, suggesting the importance of mitochondrial germ-line variant(s) in enabling the cells to acquire pro-cancerous features.
DOI: 10.1038/srep06571
Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints.
Author: Molkentine JM, Molkentine DP, Bridges KA, Xie T, Yang L, Sheth A, Heffernan TP, Clump DA, Faust AZ, Ferris RL, Myers JN, Frederick MJ, Mason KA, Meyn RE, Pickering CR, Skinner HD.
Abstract: <h4>Purpose</h4>Head and neck cancers (HNSCC) are routinely treated with radiotherapy; however, normal tissue toxicity remains a concern. Therefore, it is important to validate treatment modalities combining molecularly targeted agents with radiotherapy to improve the therapeutic ratio. The aim of this study was to assess the ability of the PARP inhibitor niraparib (MK-4827) alone, or in combination with cell cycle checkpoint abrogating drugs targeting Chk1 (MK-8776) or Wee1 (MK-1775), to radiosensitize HNSCCs in the context of HPV status.<h4>Materials and methods</h4>PARP1, PARP2, Chk1 or Wee1 shRNA constructs were analyzed from an in vivo shRNA screen of HNSCC xenografts comparing radiosensitization differences between HPV(+) and HPV(-) tumors. Radiosensitization by niraparib alone or in combination with MK-8776 or MK-1775 was assessed by clonogenic survival in HPV(-) and HPV(+) cells; and the role of p16 in determining response was explored. Relative expressions of DNA repair genes were compared by PCR array in HPV(+) and HPV(-) cells, and following siRNA-mediated knockdown of TRIP12 in HPV(-) cells.<h4>Results</h4>In vivo shRNA screening showed a modest preferential radiosensitization by Wee1 and PARP2 in HPV(-) and Chk1 in HPV(+) tumor models. Niraparib alone enhanced the radiosensitivity of all HNSCC cell lines tested. However, HPV(-) cells were sensitized to a greater degree, as suggested by the shRNA screen. When combined with MK-8776 or MK-1775, radiosensitization was further enhanced in an HPV dependent manner with HPV(+) cells enhanced by MK-8776 and HPV(-) cells enhanced by MK-1775. A PCR array for DNA repair genes showed PARP and HR proteins BRCA1 and RAD51 were much lower in HPV(+) cells than in HPV(-). Similarly, directly knocking down p16-dependent TRIP12 decreased expression of these same genes. Overexpressing p16 decreased TRIP12 expression and increased radiosensitivity in HPV(-) HN5. However, while PARP inhibition led to significant radiosensitization in the control, it led to no further significant radiosensitization in p16 overexpressing cells. Forced p16 expression in HPV(-) HN5 increased accumulation in G1 and subG1 and limited progression to S phase, thus reducing effectiveness of PARP inhibition.<h4>Conclusions</h4>Niraparib effectively radiosensitizes HNSCCs with a greater benefit seen in HPV(-). HPV status also plays a role in response to MK-8776 or MK-1775 when combined with niraparib due to differences in DNA repair mechanisms. This study suggests that using cell cycle abrogators in combination with PARP inhibitors may be a beneficial treatment option in HNSCC, but also emphasizes the importance of HPV status when considering effective treatment strategies.
Sleep deprivation as treatment for depression: Systematic review and meta-analysis.
Author: Ioannou M, Wartenberg C, Greenbrook JTV, Larson T, Magnusson K, Schmitz L, Sjögren P, Stadig I, Szabó Z, Steingrimsson S.
Abstract: <h4>Objective</h4>To systematically review evidence on the efficacy and safety of sleep deprivation (SD) as a treatment option for patients with unipolar or bipolar depression.<h4>Methods</h4>A systematic review according to PRISMA guidelines was conducted. The certainty of evidence was assessed using the GRADE approach. Controlled trials were included in efficacy analysis, case series for evaluating complications and qualitative studies for patients' experiences.<h4>Results</h4>Eight controlled studies (368 patients), one qualitative study and seven case series (825 patients) were included. One week after treatment start, SD combined with standard treatment did not reduce depressive symptoms compared with standard treatment (standardized mean difference, SMD = -0.29, [95% confidence interval, CI: -0.84 to 0.25], p = 0.29). When excluding a study in elderly patients in a post hoc analysis, the difference was statistically significant (SMD = -0.54 ([95% CI: -0.86 to -0.22], p < 0.001)) but it diminished two weeks after treatment start. No superiority of SD was found compared with antidepressants, but SD may be superior to exercise in certain settings. It is uncertain whether SD affects quality of sleep, quality of life, everyday functioning or length of stay. Apart from switch to mania (ranging between 2.7% and 10.7%), no other serious complications were reported.<h4>Conclusion</h4>Sleep deprivation has been studied in a wide range of settings resulting in divergent results for the short-term efficacy on depressive symptoms. Post hoc analyses indicated that there may be a significant but transient effect in certain populations. Further studies should focus on identifying subgroups of responders as well as examining feasibility in routine clinical care.
DOI: 10.1111/acps.13253