scholarly journals Pharmacometabolomics by NMR in Oncology: A Systematic Review

2021 ◽  
Vol 14 (10) ◽  
pp. 1015
Author(s):  
Nuria Gómez-Cebrián ◽  
Pedro Vázquez Ferreiro ◽  
Francisco Javier Carrera Hueso ◽  
José Luis Poveda Andrés ◽  
Leonor Puchades-Carrasco ◽  
...  
Keyword(s):  
Drug Efficacy ◽  
Metabolic Changes ◽  
Therapeutic Interventions ◽  
Significant Advance ◽  
Metabolic Profiles ◽  
Efficacy And Safety ◽  
Drug Treatments ◽  
Experimental Approaches ◽  
Analytical Platforms

Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug treatments. Overall, these studies inform us about how individuals will respond to a drug treatment based on their metabolic profiles obtained before, during, or after the therapeutic intervention. In the era of precision medicine, metabolic profiles hold great potential to guide patient selection and stratification in clinical trials, with a focus on improving drug efficacy and safety. Metabolomics is closely related to the phenotype as alterations in metabolism reflect changes in the preceding cascade of genomics, transcriptomics, and proteomics changes, thus providing a significant advance over other omics approaches. Nuclear Magnetic Resonance (NMR) is one of the most widely used analytical platforms in metabolomics studies. In fact, since the introduction of PMx studies in 2006, the number of NMR-based PMx studies has been continuously growing and has provided novel insights into the specific metabolic changes associated with different mechanisms of action and/or toxic effects. This review presents an up-to-date summary of NMR-based PMx studies performed over the last 10 years. Our main objective is to discuss the experimental approaches used for the characterization of the metabolic changes associated with specific therapeutic interventions, the most relevant results obtained so far, and some of the remaining challenges in this area.

Nanomedicine in the treatment of diabetic nephropathy

2021 ◽  
Author(s):  
Nimeet Desai ◽  
HariPriya Koppisetti ◽  
Shreya Pande ◽  
Havish Shukla ◽  
Bhagwat Sirsat ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Targeted Drug Delivery ◽  
Molecular Level ◽  
Drug Efficacy ◽  
Therapeutic Interventions ◽  
Efficacy And Safety ◽  
Lipid Control ◽  
Stage Renal Disease ◽  
End Stage ◽  
Day By Day

Globally, diabetic nephropathy (DN) is the foremost cause of end-stage renal disease. With the incidence of diabetes increasing day by day, DN's occurrence is expected to surge to pandemic proportions. Current available therapeutic interventions associated with DN emphasize blood pressure, glycemia and lipid control while ignoring DN's progression mechanism at a molecular level. This review sheds light on the molecular insights involved in DN to help understand the initiation and progression pattern. Further, we summarize novel strategies with reported applications in developing a nanomedicine-based platform for DN-targeted drug delivery to improve drug efficacy and safety.

scholarly journals Physicochemical Characterization Cascade of Nanoadjuvant–Antigen Systems for Improving Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 544
Author(s):  
Giuditta Guerrini ◽  
Antonio Vivi ◽  
Sabrina Gioria ◽  
Jessica Ponti ◽  
Davide Magrì ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Structure ◽  
Physicochemical Properties ◽  
Physicochemical Characterization ◽  
Protein Antigen ◽  
Efficacy And Safety

Adjuvants have been used for decades to enhance the immune response to vaccines, in particular for the subunit-based adjuvants. Physicochemical properties of the adjuvant-protein antigen complexes, such as size, morphology, protein structure and binding, influence the overall efficacy and safety of the vaccine. Here we show how to perform an accurate physicochemical characterization of the nanoaluminum–ovalbumin complex. Using a combination of existing techniques, we developed a multi-staged characterization strategy based on measurements of increased complexity. This characterization cascade has the advantage of being very flexible and easily adaptable to any adjuvant-protein antigen combinations. It will contribute to control the quality of antigen–adjuvant complexes and immunological outcomes, ultimately leading to improved vaccines.

scholarly journals First Insight into Nutraceutical Properties of Local Salento Cichorium intybus Varieties: NMR-Based Metabolomic Approach

2021 ◽  
Vol 18 (8) ◽  
pp. 4057
Author(s):  
Chiara Roberta Girelli ◽  
Francesca Serio ◽  
Rita Accogli ◽  
Federica Angilè ◽  
Antonella De Donno ◽  
...  
Keyword(s):  
1H Nmr ◽  
Cichorium Intybus ◽  
Resonance Spectroscopy ◽  
Metabolic Profiles ◽  
Whole Plant ◽  
Different Content ◽  
Insight Into ◽  
Nutraceutical Properties ◽  
Metabolomic Approach

Background: Plants of genus Cichorium are known for their therapeutic and nutraceutical properties determined by a wealth of phytochemical substances contained in the whole plant. The aim of this paper was to characterize the metabolic profiles of local Salento chicory (Cichorium intybus L.) varieties (“Bianca”, “Galatina”, “Leccese”, and “Otranto”) in order to describe their metabolites composition together with possible bioactivity and health beneficial properties. Methods: The investigation was performed by 1H-NMR spectroscopy and Multivariate Analysis (MVA), by which the metabolic profiles of the samples were easily obtained and compared. Results: The supervised Partial Least Squares Discriminant Analysis (PLS-DA) analysis showed as “Bianca” and “Galatina” samples grouped together separated by “Leccese” and “Otranto” varieties. A different content of free amino acids and organic acids was observed among the varieties. In particular a high content of cichoric and monocaffeoyl tartaric acid was observed for the “Leccese” variety. The presence of secondary metabolites adds significant interest in the investigation of Cichorium inthybus, as this vegetable may benefit human health when incorporated into the diet. Conclusions: The 1H-NMR (Nuclear Magnetic Resonance Spectroscopy) based characterization of Salento chicory varieties allowed us to determine the potential usefulness and nutraceutical properties of the product, also providing a method to guarantee its authenticity on a molecular scale.

scholarly journals Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 504
Author(s):  
Seunggwi Park ◽  
Hashizume Rintaro ◽  
Seul Kee Kim ◽  
Ilwoo Park
Keyword(s):  
Metabolic Imaging ◽  
Metabolic Profiles ◽  
Rodent Models ◽  
In Vivo Metabolism ◽  
Hyperpolarized 13C ◽  
Noninvasive Assessment ◽  
Diffuse Midline Glioma ◽  
Mr Spectroscopic Imaging

The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.

Top-down analytical platforms for the characterization of the human salivary proteome

Bioanalysis ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 563-581 ◽  
Author(s):  
Tiziana Cabras ◽  
Federica Iavarone ◽  
Barbara Manconi ◽  
Alessandra Olianas ◽  
Maria Teresa Sanna ◽  
...  
Keyword(s):  
Top Down ◽  
Analytical Platforms

scholarly journals Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers

2021 ◽  
Author(s):  
Carolina Perales‐Chorda ◽  
David Obeso ◽  
Laura Twomey ◽  
Ayelén Rojas‐Benedicto ◽  
Leonor Puchades‐Carrasco ◽  
...  
Keyword(s):  
Metabolic Changes

The Position of ADME Predictions in Multi-Objective QSAR

2021 ◽  
Vol 6 (1) ◽  
pp. 1-8
Author(s):  
Anna Tsantili-Kakoulidou
Keyword(s):  
Drug Efficacy ◽  
Clinical Development ◽  
Efficacy And Safety ◽  
Huge Amount ◽  
Multi Objective ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Qsar Models ◽  
Adme Properties ◽  
Single Objective

ADME properties and toxicity predictions play an essential role in prioritization and optimization of drug molecules. According to recent statistics, drug efficacy and safety are principal reasons for drug failure. In this perspective, the position of ADME predictions in the evolution of traditional QSAR from the single objective of biological activity to a multi-task concept is discussed. The essential features of ADME and toxicity QSAR models are highlighted. Since such models are applied to prioritize existing or virtual project compounds with already established or predicted target affinity, a mechanistic interpretation, although desirable, is not a primary goal. However, a broad applicability domain is crucial. A future challenge with multi-objective QSAR is to adapt to the realm of big data by integrating techniques for the exploitation of the continuously increasing number of ADME data and the huge amount of clinical development endpoints for the sake of efficacy and safety of new drug candidates.

scholarly journals Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation

2017 ◽  
Vol 91 (13) ◽  
Author(s):  
Normand Blais ◽  
Martin Gagné ◽  
Yoshitomo Hamuro ◽  
Patrick Rheault ◽  
Martine Boyer ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Human Respiratory Syncytial Virus ◽  
Vaccine Antigen ◽  
Significant Advance ◽  
F Protein ◽  
Syncytial Virus

ABSTRACT The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

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