Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 24 min ago

metabolomics; +22 new citations

Sun, 10/01/2021 - 16:13
22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +22 new citations

Sun, 10/01/2021 - 13:11
22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +24 new citations

Sat, 09/01/2021 - 13:06
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/09PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +29 new citations

Fri, 08/01/2021 - 15:57
29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +29 new citations

Fri, 08/01/2021 - 12:55
29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +26 new citations

Thu, 07/01/2021 - 18:52
26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +35 new citations

Wed, 06/01/2021 - 15:46
35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +35 new citations

Wed, 06/01/2021 - 12:44
35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +36 new citations

Tue, 05/01/2021 - 15:38
36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +36 new citations

Tue, 05/01/2021 - 12:34
36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Development and validation of an analysis method for pesticide residues by gas chromatography-tandem mass spectrometry in Daikenchuto.

Mon, 04/01/2021 - 12:19
Related Articles Development and validation of an analysis method for pesticide residues by gas chromatography-tandem mass spectrometry in Daikenchuto. J Nat Med. 2021 Jan 03;: Authors: Saegusa H, Nomura H, Takao M, Hamaguchi T, Yoshida M, Kodama Y Abstract Daikenchuto (DKT) is one of the most widely used "Kampo" in Japan as a representative of herbal medicine. Because DKT is made from a natural product like food, it requires the management of pesticides; therefore, an analysis of residual pesticides in Kampo is required. The World Health Organization (WHO) indicates that pesticide residue analysis by the U.S. Pharmacopeia (USP) is required. USP defines 107 compounds containing organochlorine pesticides and organophosphorus pesticides and their metabolites, which have a high residual risk. Accordingly, to guarantee the safety of herbal medicines according to global standards is a very important issue. In this study, we developed an analytical method for 91 compounds, which are listed in USP, using DKT as the subject. The method could extract pesticides from DKT with acetone, elute pesticides with acetonitrile using a SepPak C18 column (5 g) and with ethyl acetate using a DSC-NH2 column (2 g), and perform simultaneous analyses by gas chromatography-tandem mass spectrometry (GC-MS/MS). This method, which could quantify 88 compounds, was validated according to USP. A pesticide residue analysis method that meets USP requirements enables the analysis of pesticide residues with a high residue risk and contributes to improving the safety of "Kampo" and other herbal medicines. PMID: 33389591 [PubMed - as supplied by publisher]

Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis.

Mon, 04/01/2021 - 12:19
Related Articles Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis. Neurochem Res. 2021 Jan 03;: Authors: Liu X, Ruan Z, Shao XC, Feng HX, Wu L, Wang W, Wang HM, Mu HY, Zhang RJ, Zhao WM, Zhang HY, Zhang NX Abstract 28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats. PMID: 33389470 [PubMed - as supplied by publisher]

A novel method to detect intracellular metabolite alterations in MCF-7 cells by doxorubicin induced cell death.

Mon, 04/01/2021 - 12:19
Related Articles A novel method to detect intracellular metabolite alterations in MCF-7 cells by doxorubicin induced cell death. Metabolomics. 2021 Jan 03;17(1):3 Authors: Kumar A, Patel S, Bhatkar D, Sarode SC, Sharma NK Abstract BACKGROUND: Metabolic reprogramming within cancer cells has been recognized as a potential barrier to chemotherapy. Additionally, metabolic tumor heterogeneity is the one of factors behind discernible hallmarks such as drug resistance, relapse of the tumor and the formation of secondary tumors. METHODS: In this paper, cell-based assays including PI/annexin V staining and immunoblot assay were performed to show the apoptotic cell death in MCF-7 cells treated with DOX. Further, MCF-7 cells were lysed in a hypotonic buffer and the whole cell lysate was purified by a novel and specifically designed metabolite (~ 100 to 1000 Da) fractionation system called vertical tube gel electrophoresis (VTGE). Further, purified intracellular metabolites were subjected to identification by LC-HRMS technique. RESULTS: Cleaved PARP 1 in MCF-7 cells treated with DOX was observed in the present study. Concomitantly, data showed the absence of active caspase 3 in MCF-7 cells. Novel findings are to identify key intracellular metabolites assisted by VTGE system that include lipid (CDP-DG, phytosphingosine, dodecanamide), non-lipid (N-acetyl-D-glucosamine, N1-acetylspermidine and gamma-L-glutamyl-L-cysteine) and tripeptide metabolites in MCF-7 cells treated by DOX. Interestingly, we reported the first evidence of doxorubicinone, an aglycone form of DOX in MCF-7 cells that are potentially linked to the mechanism of cell death in MCF-7 cells. CONCLUSION: This paper reported novel methods and processes that involve VTGE system based purification of hypotonically lysed novel intracellular metabolites of MCF-7 cells treated by DOX. Here, these identified intracellular metabolites corroborate to caspase 3 independent and mitochondria induced apoptotic cell death in MCF-7 cells. Finally, these findings validate a proof of concept on the applications of novel VTGE assisted purification and analysis of intracellular metabolites from various cell culture models. PMID: 33389242 [PubMed - as supplied by publisher]

Osmolality-based normalization enhances statistical discrimination of untargeted metabolomic urine analysis: results from a comparative study.

Mon, 04/01/2021 - 12:19
Related Articles Osmolality-based normalization enhances statistical discrimination of untargeted metabolomic urine analysis: results from a comparative study. Metabolomics. 2021 Jan 02;17(1):2 Authors: Mervant L, Tremblay-Franco M, Jamin EL, Kesse-Guyot E, Galan P, Martin JF, Guéraud F, Debrauwer L Abstract INTRODUCTION: Because of its ease of collection, urine is one of the most commonly used matrices for metabolomics studies. However, unlike other biofluids, urine exhibits tremendous variability that can introduce confounding inconsistency during result interpretation. Despite many existing techniques to normalize urine samples, there is still no consensus on either which method is most appropriate or how to evaluate these methods. OBJECTIVES: To investigate the impact of several methods and combinations of methods conventionally used in urine metabolomics on the statistical discrimination of two groups in a simple metabolomics study. METHODS: We applied 14 different strategies of normalization to forty urine samples analysed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). To evaluate the impact of these different strategies, we relied on the ability of each method to reduce confounding variability while retaining variability of interest, as well as the predictability of statistical models. RESULTS: Among all tested normalization methods, osmolality-based normalization gave the best results. Moreover, we demonstrated that normalization using a specific dilution prior to the analysis outperformed post-acquisition normalization. We also demonstrated that the combination of various normalization methods does not necessarily improve statistical discrimination. CONCLUSIONS: This study re-emphasized the importance of normalizing urine samples for metabolomics studies. In addition, it appeared that the choice of method had a significant impact on result quality. Consequently, we suggest osmolality-based normalization as the best method for normalizing urine samples. TRIAL REGISTRATION NUMBER: NCT03335644. PMID: 33389209 [PubMed - as supplied by publisher]

Serum metabolic profiling analysis of gout patients based on UPLC-Q-TOF/MS.

Mon, 04/01/2021 - 12:19
Related Articles Serum metabolic profiling analysis of gout patients based on UPLC-Q-TOF/MS. Clin Chim Acta. 2020 Dec 31;: Authors: Zhong Z, Huang Y, Huang Q, Zheng S, Huang Z, Deng W, Li T Abstract BACKGROUND: Gout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the serum metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). METHODS: Serum metabolites were extracted from 31 gout patients and 31 healthy controls. Metabolite extracts were analyzed in negative mode by UPLC-Q-TOF/MS for global metabolomics. Principal components analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and hierarchical clustering analysis were performed to detect different compounds between the 2 groups. Receiver operating characteristic (ROC) curve analysis and pathway analysis of the different metabolites were conducted. RESULTS: A total of 9192 compounds were detected, of which 138 significantly different compounds were selected, according to the criteria of (Variable importance in projection (VIP)>3). Hierarchical clustering analysis showed that the relative levels of the differential compounds were different between the 2 groups. Ninety-one reliable metabolites matching the human metabolome database (HMDB) were confirmed. ROC curve results revealed that 4-hydroxytriazolam, urate and bilirubin exerted higher AUC values. Pathway analysis indicated that the significantly different metabolites were mainly involved in primary bile acid biosynthesis, purine metabolism and glycerophospholipid metabolism. CONCLUSIONS: The serum metabolic profiling of gout patients was significantly different from healthy subjects based on UPLC-Q-TOF/MS. Bilirubin was the potential biomarker. Primary bile acid biosynthesis may be a novel metabolic pathway of gout. PMID: 33388309 [PubMed - as supplied by publisher]

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata.

Mon, 04/01/2021 - 12:19
Related Articles Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata. J Biomed Sci. 2021 Jan 02;28(1):1 Authors: Chew SY, Brown AJP, Lau BYC, Cheah YK, Ho KL, Sandai D, Yahaya H, Than LTL Abstract BACKGROUND: Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection. METHODS: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches. RESULTS: Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages. CONCLUSION: Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host. PMID: 33388061 [PubMed - as supplied by publisher]

Analysis of the metabolic switch induced by the spirulina peptide SP6 in high fat diet ApoE-/- mice model: A direct infusion FT-ICR-MS based approach.

Sun, 03/01/2021 - 12:12
Related Articles Analysis of the metabolic switch induced by the spirulina peptide SP6 in high fat diet ApoE-/- mice model: A direct infusion FT-ICR-MS based approach. J Pharm Biomed Anal. 2020 Dec 24;195:113865 Authors: Sommella E, Carrizzo A, Merciai F, Di Sarno V, Carbone D, De Lucia M, Musella S, Vecchione C, Campiglia P Abstract Atherosclerosis, dyslipidemia and hypertension are comorbid diseases often found in combination. Among different pharmacological approaches the employment of natural multifunctional peptides is an attractive option as side therapy. Mass spectrometry-based metabolomics provide valuable information on metabolic changes and can be useful to elucidate peptide pharmacodynamics. In this this work we performed a preliminary investigation on the potential effect of a recently characterized Spirulina platensis peptide named SP6 (GIVAGDVTPI) on the modulation of metabolism in a high fat diet ApoE-/- mice atherosclerotic model. A direct infusion Fourier transform ion cyclotron resonance mass spectrometry (DI-FT-ICR-MS) approach was used to elucidate polar and non-polar metabolites extracted by mice plasma following four weeks SP6 treatment. The method delivered fast analysis time, repeatability, high mass accuracy and resolution for unambiguous molecular formula assignment. Multivariate statistical analysis (PLS-DA) highlighted a clear class separation, revealing the alteration of numerous metabolites levels belonging to different classes. In particular sphingolipids, glycerophospholipids, TCA cycle intermediates, and amino acids, which are key players in the atherosclerotic process and progression, were upregulated in saline alone HFD ApoE-/- group, while were sensibly decreased after treatment with SP6 peptide. These results could open the way to further, large-scale, investigation of SP6 peptide effects in the regulation of atherosclerotic disease development and progression, and show the potential of DI-FT-ICR as fast analytical tool to take snaphshots of metabolic changes before moving to targeted MS-based approaches. PMID: 33387838 [PubMed - as supplied by publisher]

Impacts of manganese bio-based nanocomposites on phytochemical classification, growth and physiological responses of Hypericum perforatum L. shoot cultures.

Sun, 03/01/2021 - 12:12
Related Articles Impacts of manganese bio-based nanocomposites on phytochemical classification, growth and physiological responses of Hypericum perforatum L. shoot cultures. Ecotoxicol Environ Saf. 2020 Dec 30;209:111841 Authors: Jafarirad S, Kosari-Nasab M, Mohammadpour Tavana R, Mahjouri S, Ebadollahi R Abstract We report a new green route for preparing MnO2/perlite nanocomposites (NCs) by leaf extract of Hypericum perforatum. Characterization of the physicochemical properties of the MnO2/perlite-NCs was performed using XRD, FESEM, EDX, FT-IR, and DLS techniques. Furthermore, their effects on the phytochemical classification and growth parameters of H. perforatum shoot cultures were assessed. According to the FESEM image, the synthesized spherical MnO2 nanoparticles on the sheet-like structure of nano-perlite were formed, ranging about 20-50 nm. In addition, based on the EDX spectra, the elemental analysis showed the presence of Carbon, Oxygen, Silicon, Aluminum, and Manganese elements in the as-synthesized MnO2/perlite-NCs. Biological studies confirmed that nano-perlite and MnO2/perlite-NCs were non-toxic to H. perforatum shoot cultures and showed positive effects on plant growth in specific concentrations. Overall, phytochemical classification demonstrated that the terpenoids decreased in the evaluated treatments, while hypericin and pseudohypericin were increased in some treatments (25, 50 and 150 mg/L of nano-perlite) relative to control. Metabolomics results suggested that both nano-perlite and MnO2/perlite-NCs can be used as elicitors and new nanofertilizers for generating some secondary metabolites. PMID: 33387772 [PubMed - as supplied by publisher]

Mitochondrial dysfunction as a mechanistic biomarker in patients with Non-Alcoholic fatty liver disease (NAFLD).

Sun, 03/01/2021 - 12:12
Related Articles Mitochondrial dysfunction as a mechanistic biomarker in patients with Non-Alcoholic fatty liver disease (NAFLD). Mitochondrion. 2020 Dec 30;: Authors: Ajaz S, McPhail MJ, Gnudi L, Trovato FM, Mujib S, Napoli S, Carey I, Agarwal K Abstract BACKGROUND: Dysfunctional metabolism lies at the centre of the pathogenesis for Non-Alcoholic Fatty Liver Disease (NAFLD) and involves mitochondrial dysfunction, lipid dysmetabolism and oxidative stress. This study, for the first time, explores real-time energy changes in peripheral blood and corresponding metabolite changes, to investigate whether mitochondria-related immunometabolic biomarkers can predict progression in NAFLD. METHODS: Thirty subjects divided into 3 groups were assessed: NAFLD with biopsy-proven mild fibrosis (n=10), severe fibrosis (n=10) and healthy controls (HC, n=10). Mitochondrial functional analysis was performed in a Seahorse XFp analyzer in live peripheral blood mononuclear cells (PBMCs). Global metabolomics quantified a broad range of human plasma metabolites. Mitochondrial carbamoyl phosphate synthase 1(CPS-1), Ornithine transcarbamoylase (OTC), Fibroblast growth factor-21 (FGF-21) and a range of cytokines in plasma were measured by ELISA. RESULTS: NAFLD patients with severe fibrosis demonstrated reduced maximal respiration (106 ± 25 versus 242 ± 62, p < 0.05) and reserve capacity (56 ± 16 versus 184 ± 42, p = 0.006) compared to mild/moderate fibrosis. Comparing mild/moderate vs severe liver fibrosis in patients with NAFLD, 14 out of 493 quantified metabolites were significantly changed (p < 0.05). Most of the amino acids modulated were the urea cycle (UC) components which included citrulline/ornithine ratio, arginine and glutamate. Plasma levels of CPS-1 and FGF-21 were significantly higher mild versus severe fibrosis in NAFLD patients. This novel panel generated an area under the ROC of 0.95, sensitivity of 100% and specificity 80% and p = 0.0007 (F1-F2 versus F3-F4). CONCLUSION: Progression in NAFLD is associated with mitochondrial dysfunction and changes in metabolites associated with the urea cycle. We demonstrate a unique panel of mitochondrial-based, signatures which differentiate between stages of NAFLD. Lay summary Mitochondrial dysfunction in peripheral cells along with alterations in metabolites of urea cycle act as a sensor of hepatocyte mitochondrial damage. These changes can be measured in blood and together represent a unique panel of biomarkers for progression of fibrosis in NAFLD. PMID: 33387664 [PubMed - as supplied by publisher]

Metabolic Reprogramming: A Driver of Cigarette Smoke-Induced Inflammatory Lung Diseases.

Sun, 03/01/2021 - 12:12
Related Articles Metabolic Reprogramming: A Driver of Cigarette Smoke-Induced Inflammatory Lung Diseases. Free Radic Biol Med. 2020 Dec 30;: Authors: Li L, Yang DC, Chen CH Abstract Cigarette smoking is a well-known risk factor for pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma and pulmonary fibrosis. Despite major progress in dissecting the mechanisms associated with disease development and progression, findings only represent one aspect of multifaceted disease. A crucial consequence of this approach is that many therapeutic treatments often fail to improve or reverse the disease state as other conditions and variables are insufficiently considered. To expand our understanding of pulmonary diseases, omics approaches, particularly metabolomics, has been emerging in the field. This strategy has been applied to identify putative biomarkers and novel mechanistic insights. In this review, we discuss metabolic profiles of patients with COPD, asthma, and idiopathic pulmonary fibrosis (IPF) with a focus on the direct effects of cigarette smoking in altering metabolic regulation. We next present cell- and animal-based experiments and point out the therapeutic potential of targeting metabolic reprogramming in inflammatory lung diseases. In addition, the obstacles in translating these findings into clinical practice, including potential adverse effects and limited pharmacological efficacy, are also addressed. PMID: 33387604 [PubMed - as supplied by publisher]

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