Chitkara University

Hypoxia-induced brain damage can cause consciousness, memory failure and death. HK2 and TPI1 were investigated to see how they change hypoxia sensitivity in neurons and non-neurons. Hypoxia sensitivity is determined by the differential overexpression of both important glycolytic enzymes in neuronal and non-neuronal cells. C6 glioma cells expressed greater HK2 and TPI1 protein than neuro 2A cells, which were more sensitive to hypoxia-induced cell death by MTT and lactate dehydrogenase leakage assay. After 48 h of hypoxia, C6 glioma cells displayed substantial protein upregulation of HK2 and TPI1 glycolytic proteins but not mRNA. Hypoxia did not raise HK2 and TPI1 mRNA transcription, pointing at post-transcriptional protein regulation. Using di-cistronic and promoter-less di-cistronic assays, we discovered significant IRES regions in HK2 and TPI1 mRNA's 5'UTR, more active in C6 glioma cells with polypyrimidine tract binding (PTB) protein. We concluded that non-neuronal cells varied in HK2 and TPI1 overexpression, altering their vulnerability to hypoxia-induced cell death. Adjusting HK2, TP1 and PTB levels may prevent hypoxia-induced brain cell death. These results offer new information on glycolytic enzyme modulation under hypoxia, crucial for comprehending cell survival in hypoxic situations. This could affect situations like neurodegenerative illnesses or ischaemic injuries, where hypoxia-induced cell death is crucial.

Several Candida species such as C. albicans and C. auris have emerged as formidable multidrug-resistant pathogens, posing significant challenges to global healthcare.C. albicans can rapidly adapt its metabolism under nutrient-limited conditions, such as low-carbon environments, leading to virulence and drug resistance.Therefore, identifying novel compounds that can disrupt this metabolic adaptability is crucial for developing effective therapeutic strategies against this elusive pathogen.In this study, we first employed an in-silico dynamics approach to investigate the inhibitory effects of guaiazulene and aureusidin on C. albicans metabolic adaptability and virulence.By employing mol. docking and mol. dynamics simulations, we demonstrated that these compounds strongly interacted with crucial enzymes involved in the glyoxylate cycle, impairing their catalytic functions.Guaiazulene exhibited the highest binding affinity for malate synthase and isocitrate lyase, with a docking score of -8.5 and -9.3 kcal/mol, resp.The ADME properties of these mols. were also examined to evaluate the pharmacol. parameters.Furthermore, we investigated the impact of guaiazulene and aureusidin on C. albicans growth and biofilm formation.Our findings indicated that the targeting the glyoxylate cycle represents a promising strategy to counteract the metabolic adaptability of C. albicans and enhance the efficacy of antifungal agents.

Neurodegenerative diseases (NDDs) are characterised by the progressive loss of neurons in the central nervous system (CNS), resulting in memory impairment, cognition abnormalities, and motor dysfunctions. The common pathological features include altered energy metabolism, neuroinflammation, loss of neurons, aberrant protein aggregation, and synaptic dysfunction. Lipids, fundamental components of cell membranes play a critical role in energy storage and cell signaling. The brain, comprising approximately 60% lipid content by dry weight, underscores the significance of lipid dynamics in maintaining CNS integrity. Variations in lipid distribution across brain regions further highlight their specialised functions. Dysregulation of lipid metabolism, encompassing synthesis, transport, and utilization, has been implicated in the pathogenesis of neurodegenerative diseases. Lipid droplets (LDs), key intermediates of lipid metabolism, accumulate in neurons, microglia, and astrocytes, particularly in aging brains. The deposition of these LDs disrupts cellular homeostasis and links the dynamics of LDs to pathology of disease. Therefore, this review explores the pivotal role of lipid metabolism and LDs in NDDs, providing insights into their contributions to neuronal dysfunction and potential therapeutic implications.