Pulmonary arterial hypertension (PAH) is a multi-factorial disease characterized by the hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Excessive reactive oxygen species (ROS) formation resulted in alterations of the structure and function of pulmonary arterial walls, leading to right ventricular failure and death. Diabetes mellitus has not yet been implicated in pulmonary hypertension. However, recently, variable studies have shown that diabetes is correlated with pulmonary hypertension pathobiology, which could participate in the modification of pulmonary artery muscles. The metabolomic changes in PASMCs were studied in response to 25 mM of D-glucose (high glucose, or HG) in order to establish a diabetic-like condition in an in vitro setting, and compared to five mM of D-glucose (normal glucose, or LG). The effect of co-culturing these cells with an ideal blood serum concentration of cholecalciferol-D3 and tocopherol was also examined. The current study aimed to examine the role of hyperglycemia in pulmonary arterial hypertension by the quantification and detection of the metabolomic alteration of smooth muscle cells in high-glucose conditions. Untargeted metabolomics was carried out using hydrophilic interaction liquid chromatography and high-resolution mass spectrometry. Cell proliferation was assessed by cell viability and the [³H] thymidine incorporation assay, and the redox state within the cells was examined by measuring reactive oxygen species (ROS) generation. The results demonstrated that PASMCs in high glucose (HG) grew, proliferated faster, and generated higher levels of superoxide anion (O₂·⁻) and hydrogen peroxide (H₂O₂). The metabolomics of cells cultured in HG showed that the carbohydrate pathway, especially that of the upper glycolytic pathway metabolites, was influenced by the activation of the oxidation pathway: the pentose phosphate pathway (PPP). The amount of amino acids such as aspartate and glutathione reduced via HG, while glutathione disulfide, N6-Acetyl-L-lysine, glutamate, and 5-aminopentanoate increased. Lipids either as fatty acids or glycerophospholipids were downregulated in most of the metabolites, with the exception of docosatetraenoic acid and PG (16:0/16:1(9Z)). Purine and pyrimidine were influenced by hyperglycaemia following PPP oxidation. The results in addition showed that cells exposed to 25 mM of glucose were oxidatively stressed comparing to those cultured in five mM of glucose. Cholecalciferol (D3, or vitamin D) and tocopherol (vitamin E) were shown to restore the redox status of many metabolic pathways.

Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD.

This study aimed to determine the pattern of alcohol consumption and its poisoning among the Saudi population in the city of Hail, KSA. Data from a retrospective cohort were collected qualitatively at King Khalid Hospital (KKH) and Hail General Hospital (HGH), covering 550 participants from 2015 to 2022. Two groups were formed comprising patients admitted to the emergency room (ER) and community members; their ages ranged from 19 to 75 years. Group 1 contained 400 participants, of which 250 were patients (244 males, six females) who came to the (ER) with a suspected alcohol overdose or poisoning, and 150 were patients (128 males and 22 females) who were discharged from the (ER) with minimal complaints because of their drinking. Group 2 comprised 150 participants (128 males, 22 females) who were community members, who were surveyed using a questionnaire or interview. In Group 1, 30% of patients reported an altered state of consciousness as a major complaint, 28.8% of patients exhibited abnormal liver function tests (LFTs), 27% had abnormal renal function tests (RFT) with decreased glomerular filtration rates (GFR) and elevated levels of urea and creatinine or low levels of electrolytes or calcium, and 35.6% patients showed elevated levels of pancreatic enzymes. One death was reported due to high alcohol consumption. In Group 2, the community participants reported that they started drinking alcohol due to the influence of other people (29%), stress (11%), depression (10.8%), curiosity (4.4%), and boredom (4%). In addition, 77% of participants were frequent alcohol drinkers and 20% consumed it daily. Further, 68.7% claimed to drink alcohol for more than one hour at a time, while 83.3% experienced blackouts and 70% had problems related to their liver. Moreover, 72.7% of the participants ended up in the hospital and 34.6% suffered from multiple chronic diseases. It is concluded that social influences and stress contributed to the initiation of alcohol use. Despite data gaps, the findings of this study provide a practical understanding of alcohol consumption among the Saudi population and guidance for policymakers.