Metabolic Crosstalk in Multimorbidity: Identifying Compensatory Effects Among Diabetes, Hypertension, and Dyslipidemia.

Context: Metabolomics is becoming increasingly popular for detecting markers that indicate the presence of a specific disease. However, it is usually applied to studying individual ailments, yielding results that may not be directly relevant to people with multiple health conditions. Objective: Our study proposes a different approach to explore metabolic crosstalk between various disease states. Design Setting and Patients: We conducted a study on subjects at medium to high risk of developing coronary artery disease. We measured the plasma levels of 83 metabolites using nuclear magnetic resonance and analyzed the connections between these metabolites and various risk factors such as diabetes, hypertension, and dyslipidemia. Linear regression and multivariate analysis were combined for this purpose. Results: Inspection of the metabolic maps created by our analysis helped us efficiently compare profiles. In this way, it was possible to discover opposing metabolic features among single conditions and their combination. Furthermore, we found compensating metabolic effects between diabetes, hypertension, and dyslipidemia involving mainly ketone body metabolism and fatty acid ß-oxidation. Conclusion: Our study introduces a novel approach to investigating how metabolism reacts to the simultaneous presence of multiple health conditions. This has allowed the detection of potential compensatory effects between diabetes, hypertension, and dyslipidemia, highlighting the complexity of metabolic crosstalk in patients with comorbidities. A better understanding of metabolic crosstalk like this could aid in developing focused treatments, resulting in improved therapeutic results.

Biological Evaluation of Triorganotin Derivatives as Potential Anticancer Agents.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF3) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF3. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF3, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF3 might be the prototype of a family of potential anticancer agents.

Salivary Metabolome and Soccer Match: Challenges for Understanding Exercise induced Changes.

Saliva samples of seventeen soccer players were analyzed by nuclear magnetic resonance before and after an official match. Two different ways of normalizing data are discussed, using total proteins and total metabolite concentrations. Changes in markers related to energy, hydration status, amino acids and other compounds were found. The limits and advantages of using saliva to define the systemic responses to exercise are examined, both in terms of data normalization and interpretation, and the time that the effect lasts in this biofluid, which is shorter to that commonly observed in blood. The heterogeneous nature and different timing of the exercise developed by players also plays an important role in the metabolic changes that can be measured. Our work focuses mainly on three different aspects: The effect that time sampling has on the observed effect, the type of normalization that is necessary to perform in order to cope with changes in water content, and the metabolic response that can be observed using saliva.

A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs.

A new methodology based on Nuclear Magnetic Resonance (NMR) was developed to determine plasma protein binding (PPB) of drug candidates in drug discovery programs. A strong correlation was found between the attenuation of NMR signals of diverse drugs in the presence of different plasma concentrations and their fraction bound (fb) reported in the literature. Based on these results, a protocol for a rapid calculation of fb of small molecules was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool analysis to increase throughput were also evaluated. This novel methodology proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and solubility of the compound.