Dexamethasone (Dex) is a synthetic glucocorticoid (GC) drug commonly used clinically for the treatment of several inflammatory and immune-mediated diseases. Despite its broad range of indications, the long-term use of Dex is known to be associated with specific abnormalities in several tissues and organs. In this study, the metabolomic effects on five different organs induced by the chronic administration of Dex in the Sprague–Dawley rat model were investigated using the chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS) platform, which targets the amine/phenol submetabolomes. Compared to controls, a prolonged intake of Dex resulted in significant perturbations in the levels of 492, 442, 300, 186, and 105 metabolites in the brain, skeletal muscle, liver, kidney, and heart tissues, respectively. The positively identified metabolites were mapped to diverse molecular pathways in different organs. In the brain, perturbations in protein biosynthesis, amino acid metabolism, and monoamine neurotransmitter synthesis were identified, while in the heart, pyrimidine metabolism and branched amino acid biosynthesis were the most significantly impaired pathways. In the kidney, several amino acid pathways were dysregulated, which reflected impairments in several biological functions, including gluconeogenesis and ureagenesis. Beta-alanine metabolism and uridine homeostasis were profoundly affected in liver tissues, whereas alterations of glutathione, arginine, glutamine, and nitrogen metabolism pointed to the modulation of muscle metabolism and disturbances in energy production and muscle mass in skeletal muscle. The differential expression of multiple dipeptides was most significant in the liver (down-regulated), brain (up-regulation), and kidney tissues, but not in the heart or skeletal muscle tissues. The identification of clinically relevant pathways provides holistic insights into the tissue molecular responses induced by Dex and understanding of the underlying mechanisms associated with their side effects. Our data suggest a potential role for glutathione supplementation and dipeptide modulators as novel therapeutic interventions to mitigate the side effects induced by Dex therapy.

The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in the angiogenic pathway. Inhibition of this interaction is proving of value in moderating the neovascularization accompanying age-related macular degeneration and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3) has been shown to be a natural VEGFR-2 specific antagonist—an activity that is independent of its ability to inhibit metalloproteinases. In this investigation we localize this activity to the C-terminal domain of the TIMP-3 molecule and characterize a short peptide, corresponding to part of this domain, that not only inhibits all three VEGF-family receptors, but also fibroblast growth factor and platelet-derived growth factor receptors. This multiple-receptor inhibition may explain why the peptide was also seen to be a powerful inhibitor of tumour growth and also a partial inhibitor of arthritic joint inflammation in vivo.

Objective: The aim of this study was to estimate the awareness of Saudi population in Riyadh regarding cardiovascular diseases (CVDs) and their risk factors. Methods: This was a cross-sectional study that used self-administered questionnaires conducted in universities, primary care centers, and electronic copies distributed in social media websites. Results: Overall, 47.1% of the respondents had a good awareness of CVD and associated risk factors. However, awareness of the symptoms of stroke and heart attack was low. Pulmonary embolism and deep vein thrombosis were the most commonly identified types of CVD, with 39.2% aware of these conditions. The most well-known symptom of heart attack was shortness of breath (known by 54.4% of the respondents). In relation to stroke, the most commonly recognized symptom was “sudden dizziness, trouble walking, or loss of balance” (45.4%). Respondents’ awareness of CVD risk factors was moderate. The most common factors—identified by over two-thirds of participants—were unhealthy diet, smoking, dyslipidemia, and physical inactivity. Independent predictors of good CVD awareness were age 35–44 years, living in the north of Riyadh and following a healthy diet. Conclusions: The awareness of CVD and associated risk factors is insufficient among Saudis in Riyadh City. This study emphasizes the necessity for effective education to increase the awareness about CVD in Saudi Arabia. High awareness may lead to early recognition of the risk factors and lead to early implementation of primary prevention which the cornerstone of family medicine practice.

Dexamethasone is a synthetic glucocorticoid medication vastly used to treat abnormal immune responses and inflammation. Although the medication is well-established in the medical community, the prolonged treatment with high dosages of dexamethasone may lead to severe adverse effects through mechanisms that are not yet well-known. Lipids are a large class of hydrophobic molecules involved in energy storage, signaling, modulation of gene expression, and membranes. Hence, untargeted lipidomics may help unravel the biochemical alterations following prolonged treatment with high dosages of dexamethasone. We performed comprehensive lipidomic analyses of brain, heart, kidney, liver, and muscle samples obtained from rats that were treated with intramuscular injections of dexamethasone for 14 weeks compared to healthy controls. The employed methodology and statistical analysis showed that phosphatidic acids, glycerophospholipids, plasmalogens, and fatty acids are deeply affected by prolonged use of the medication. Brain tissue was only mildly affected, but skeletal muscle showed a strong accumulation of lipids that may be correlated with alterations in the energy metabolism, myopathy, and oxidative processes. This work provides new insights into the mechanisms of action and adverse effects for one of the most commonly prescribed class of drugs in the world.

Cystic renal disease (CRD) comprises a heterogeneous group of genetic and acquired disorders. The cystic lesions are detected through imaging, either incidentally or after symptoms develop, due to an underlying disease process. In this study, we aim to study the metabolomic profiles of CRD patients for potential disease-specific biomarkers using unlabeled and labeled metabolomics using low and high-resolution mass spectrometry (MS), respectively. Dried-blood spot (DBS) and serum samples, collected from CRD patients and healthy controls, were analyzed using the unlabeled and labeled method. The metabolomics profiles for both sets of samples and groups were collected, and their data were processed using the lab’s standard protocol. The univariate analysis showed (FDR p < 0.05 and fold change 2) was significant to show a group of potential biomarkers for CRD discovery, including uridine diphosphate, cystine-5-diphosphate, and morpholine. Several pathways were involved in CRD patients based on the metabolic profile, including aminoacyl-tRNA biosynthesis, purine and pyrimidine, glutathione, TCA cycle, and some amino acid metabolism (alanine, aspartate and glutamate, arginine and tryptophan), which have the most impact. In conclusion, early CRD detection and treatment is possible using a metabolomics approach that targets alanine, aspartate, and glutamate pathway metabolites.