A metabolomics study: Could plasma metabolites be a guide for the prevention of tamsulosin side effects?

BACKGROUND: The understanding of precision medicine, which aims for high efficacy and low toxicity in treatments, has gained more importance with omics technologies. In this study, it was aimed to reach new suggestions for low-toxicity treatment by clarifying the relationship between tamsulosin side effects and metabolome profiles. MATERIALS AND METHODS: Plasma samples of control and tamsulosin-treated rats were analyzed by LC-Q-TOF/MS/MS. MS/MS data was processed in XCMS software for the identification of metabolite and metabolic pathway analysis. Data were classified with MATLAB 2019b for multivariate data analysis. 34m/z values were found to be significantly different between the drug and control groups (P≤0.01 and fold analysis≥1.5) and identified by comparing METLIN and HMDB databases. RESULTS: According to multivariate data analysis, α-Linolenic Acid, Thiamine, Retinoic acid, 1.25-Dihydroxyvitamin D3-26.23-Lactone, L-Glutamine, L-Serine, Retinaldehyde, Sphingosine 1-phosphate, L-Lysine, 23S.25-Dihydroxyvitamin D3, Sphinganine, L-Cysteine, Uridine 5'-diphosphate, Calcidiol, L-Tryptophan, L-Alanine levels changed significantly compared to the control group. Differences in the metabolisms of Retinol, Sphingolipid, Alanine-Aspartate-Glutamate, Glutathione, Fatty Acid, Tryptophan, and biosynthesis of Aminoacyl-tRNA, and Unsaturated Fatty Acid have been successfully demonstrated by metabolic pathway analysis. According to our study, vitamin A and D supplements can be recommended to prevent side effects such as asthenia, rhinitis, nasal congestion, dizziness and IFIS in the treatment of tamsulosin. Alteration of aminoacyl-tRNA biosynthesis and sphingolipid metabolism pathways during tamsulosin treatment is effective in the occurrence of nasal congestion. CONCLUSIONS: Our study provides important information for tamsulosin therapy with high efficacy and low side effects in precision medicine.

Novel chemometrics­assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.

OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics­assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples. METHODS: Samples were deparaffinized and 20­micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model. RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones. CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).

miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo.

miR-200a has been implicated in the pathogenesis of meningiomas, one of the most common central nervous system tumors in humans. To identify how miR-200a contributes to meningioma pathogenesis at the molecular level, we used a comparative protein profiling approach using Gel-nanoLC-MS/MS and identified approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma cells. Following the bioinformatic analysis to identify potential genes targeted by miR-200a, we focused on the non-muscle heavy chain IIb (NMHCIIb), and showed that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in cell division and cell migration, we aimed to identify whether miR-200a regulated these processes through NMHCIIb. We found that NMHCIIb overexpression partially rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression resulted in a similar migration phenotype in these cells and inhibited meningioma tumor growth in mice. Taken together, these results suggest that NMHCIIb might serve as a novel therapeutic target in meningiomas.

Spectrofluorimetric Determination of α-Tocopherol in Capsules and Human Plasma.

A simple, sensitive and rapid spectrofluorimetric method for determination of α-tocopherol in pharmaceutical capsule and human plasma was developed and validated. The native fluorescence of α-tocopherol was measured at 334 nm with excitation at 291 nm, after extraction of α-tocopherol from human plasma hexane:dichloromethane mixture. The calibration curves were linear (R≥0.9993) in the concentration range of 0.25-2.5 µg/ml of α-tocopherol in both standard solutions and plasma samples. The developed method was directly and easily applied for determination of α-tocopherol in the plasma of healthy volunteers and different type of bladder cancer and stomach cancer patients and also pharmaceutical capsule.