Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Continuously monitoring human airway conditions is crucial for timely interventions, especially when airway stents are implanted to alleviate central airway obstruction in lung cancer and other diseases. Mucus conditions, in particular, are important biomarkers for indicating inflammation and stent patency but remain challenging to monitor. Current methods, reliant on computational tomography imaging and bronchoscope inspection, pose risks due to radiation and lack the ability to provide continuous real-time feedback outside of hospitals.
View Article and Find Full Text PDFMyopathy is a common manifestation in mitochondrial disorders, but the pathomechanisms are still insufficiently studied in children. Here, we report a severe, progressive mitochondrial myopathy in a four-year-old child, who died at eight years. He developed progressive loss of muscle strength with nocturnal hypoventilation and dilated cardiomyopathy.
View Article and Find Full Text PDFMost kidney cancers are metabolically dysfunctional, but how this dysfunction affects cancer progression in humans is unknown. We infused C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming.
View Article and Find Full Text PDFThis was a cross-sectional study on the availability of laboratory infrastructure and capacity for the diagnosis of invasive fungal diseases in 24 public hospitals in Vietnam in 2023. Among the hospitals surveyed, 66.7% (14/21) had specialized personnel assigned for mycology testing, and 95.
View Article and Find Full Text PDFBackground: This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and associated factors.
Method: A descriptive cross-sectional study was performed from August to October 2022 within five hospitals located in Hanoi, Vietnam. A total of 244 health professionals participated in the study.
Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway.
View Article and Find Full Text PDFThe idea of using quadriceps tendon autograft (QT) anterior cruciate ligament reconstruction first came into being in the 1990s; it was, however, not widely recognized and has resurfaced only in recent times. Because sufficient technological supports have not been developed to enable an optimal artificial graft, autologous grafts are still the most dependable option. The major reason for choosing QT instead of hamstring or patellar tendon to get autologous grafts is that it seems to cause the fewest donor site problems.
View Article and Find Full Text PDFDimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells.
View Article and Find Full Text PDFIn the tumor microenvironment, adipocytes function as an alternate fuel source for cancer cells. However, whether adipocytes influence macromolecular biosynthesis in cancer cells is unknown. Here we systematically characterized the bidirectional interaction between primary human adipocytes and ovarian cancer (OvCa) cells using multi-platform metabolomics, imaging mass spectrometry, isotope tracing and gene expression analysis.
View Article and Find Full Text PDFCancer cells reprogram their metabolism to support cell growth and proliferation in harsh environments. While many studies have documented the importance of mitochondrial oxidative phosphorylation (OXPHOS) in tumor growth, some cancer cells experience conditions of reduced OXPHOS in vivo and induce alternative metabolic pathways to compensate. To assess how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts and plasma from patients with inborn errors of mitochondrial metabolism, and in cancer cells subjected to inhibition of the electron transport chain (ETC).
View Article and Find Full Text PDFUnlabelled: L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive, slowly progressive neurodegenerative disease characterized by psychomotor delay and cerebellar dysfunction. The biochemical hallmark is increased concentrations of L2HG in body fluids. Brain MRI exhibits characteristic centripetal extension of the white matter involvement that differentiates it from other leukodystrophies.
View Article and Find Full Text PDFMalonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including , is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020).
View Article and Find Full Text PDFMost kidney cancers display evidence of metabolic dysfunction but how this relates to cancer progression in humans is unknown. We used a multidisciplinary approach to infuse C-labeled nutrients during surgical tumour resection in over 70 patients with kidney cancer. Labeling from [U-C]glucose varies across cancer subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours.
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