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We investigated factors associated with postoperative lipiduria and hypoxemia in patients undergoing surgery for orthopedic fractures. We enrolled patients who presented to our emergency department due to traumatic fractures between 2016 and 2017. We collected urine samples within 24 h after the patients had undergone surgery to determine the presence of lipiduria. Hypoxemia was defined as an SpO2

Metabolic reprogramming is linked to tumorigenesis, disease progression, clinical outcome and resistance to chemotherapy. However, the significance of glycolytic metabolism in non-Hodgkin lymphoma (NHL) remains unclear. Here we report that both NHL patient-samples and cell lines exhibited significant up-regulation of glycolytic metabolism. The glycolytic inhibitor 2-deoxy- d-glucose (2-DG) inhibited glucose consumption, lactic acid generation and cell proliferation and induced cell cycle arrest in NHL cell lines under both normoxia and hypoxia, and hypoxia could even enhance the inhibitory effects of 2-DG. Furthermore, 2-DG combined with methylprednisolone synergistically inhibited cell proliferation, induced cell apoptosis and cell cycle arrest, and thus increased the sensitivity of NHL cells to methylprednisolone via down-regulation of HIF-1α and c-MYC. In conclusion, these results present a novel insight into critical roles of glycolytic pathway activation in NHL progression and glucocorticoid resistance. Inhibition of the glycolytic pathway may provide a new therapeutic strategy for the treatment of NHL. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase IX (CAIX) is a membrane-bound, tumorrelated enzyme whose expression is often considered a marker for hypoxia, an indicator of poor prognosis in the majority of cancer patients, and is associated with acidification ofthe tumor microenvironment. Here, we describe for the first time the catalytic properties of native CAIX in MDA-MB-231 breast cancer cells that exhibit hypoxia-inducible CAIX expression. Using "*O exchange measured by membrane inlet mass spectrometry, we determined catalytic activity in membrane ghosts and intact cells. Exofacial carbonic anhydrase activity increases with exposure to hypoxia, an activity which is suppressed by impermeant sulfonamide CA inhibitors. Inhibition by sulfonamide inhibitors is not sensitive to reoxygenation. CAIX activity in intact cells increases in response to reduced pH. Data from membrane ghosts show that the increase in activity at reduced pH is largely due to an increase in the dehydration reaction. In addition, the kinetic constants of CAIX in membrane ghosts are very similar to our previous measurements for purified, recombinant, truncated forms. Hence, the activity of CAIX is not affected by the proteoglycan extension or membrane environment. These activities were measured at a total concentration for all CO2 species at 25 mM and close to chemical equilibrium, conditions which approximate the physiological extracellular environment. Our data suggest that CAIX is particularly well suited to maintain the extracellular pH at a value that favors the survival fitness of tumor cells. [ABSTRACT FROM AUTHOR]

Canstatin, a newly identified antiangiogenesis protein, has a potent inhibitory effect on the proliferation and growth of endothelial cells. To enhance the expression and antiangiogenic effects of canstatin in solid tumors, we constructed a eukaryotic expression vector that encodes human canstatin cDNA downstream from nine copies of the hypoxia-response element. [ABSTRACT FROM AUTHOR]

Ascites syndrome (AS) is a common nutritional metabolic disease in broilers that results in major loss to the breeding industry. The occurrence of AS is closely related to the abnormal proliferation of pulmonary artery smooth muscles cells (PASMCs) caused by hypoxia. The transient receptor potential cation channel subfamily C member 6 (TRPC6) is a Ca2+ channel situated on cell membranes, and belongs to the proliferation of PASMCs caused by hypoxia in mammals. However, its role in hypoxic PASMCs in broilers remains unclear. Here, we investigated the effects of TRPC6 on the proliferation and apoptosis of primary chicken PASMCs under hypoxic conditions using an in vitro model. Primary chicken PASMCs were cultured under normoxic or hypoxic conditions (3% O2). The hypoxic cells were treated with 10 μM of SKF 96365 or 50 μM of fluofenamic acid (FFA) to inhibit or activate TRPC6, respectively. Cell viability was detected by CCK-8, intracellular Ca2+ levels, cell cycle and cell apoptosis were assayed by a flow cytometric assay, the mRNA levels of TRPC6 were measured by digital-droplet PCR (ddPCR), the protein levels of TRPC6 were tested by immunoblotting, and the mRNA levels of caspase3 were detected by RT-PCR. Our results revealed that exposing PASMCs to hypoxic conditions for 48h increased cell viability and intracellular Ca2+ levels. Additionally, hypoxic conditions increased the expression of TRPC6 and promoted cell cycle progression, but decreased cell apoptosis and caspase 3 mRNA levels. When the hypoxic PASMCs were treated with SKF 96365, inhibition of TRPC6 and cell proliferation and promotion of apoptosis were observed only in the first 24h of treatment. Treatment with FFA for 24h had the opposite effects. These results suggested that TRPC6-mediated Ca2+ entry contributed to hypoxia-induced PASMCs proliferation and apoptosis resistance, which identified TRPC6 as a possible key target in vascular remodeling in chicken. [ABSTRACT FROM AUTHOR]

Background: Mitophagy and microRNA both regulate the occurrence of neurodegenerative diseases and cancers. Results: MicroRNA-137, a hypoxia responsive microRNA, inhibits mitophagy via targeting two mitophagy receptors. Conclusion: A novel link between miR-137 and mitophagy has been revealed. Significance: Understanding mitophagy regulation and microRNA functions may provide new concepts to fight human diseases. Mitophagy receptors mediate the selective recognition and targeting of damaged mitochondria by autophagosomes. The mechanism for the regulation of these receptors remains unknown. Here, we demonstrated that a novel hypoxia-responsive microRNA, microRNA-137 (miR-137), markedly inhibits mitochondrial degradation by autophagy without affecting global autophagy. miR- 137 targets the expression of two mitophagy receptors NIX and FUNDC1. Impaired mitophagy in response to hypoxia caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression vectors lacking the miR-137 recognition sites at their 3' UTR. Conversely, miR-137 also suppresses the mitophagy induced by fundc1 (CDS'3'UTR) but not fundc1 (CDS) overexpression. Finally, we found that miR-137 inhibits mitophagy by reducing the expression of the mitophagy receptor thereby leads to inadequate interaction between mitophagy receptor and LC3. Our results demonstrated the regulatory role of miRNA to mitophagy receptors and revealed a novel link between miR-137 and mitophagy. [ABSTRACT FROM AUTHOR]