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CD147 is a tumor-associated glycoprotein that regulates cell metabolism. However, CD147 methylation and its subsequent role in cancer cell metabolism remain unclear. Here, we detect CD147 di-methylation in 16 non-small-cell lung cancer (NSCLC) tissues using liquid chromatography-tandem mass spectrometry. CD147 is di-methylated to CD147-K234me2 by lysine methyltransferase 5A (KMT5A). The increase in KMT5A expression boosts the levels of CD147-K234me2, further promoting the interaction between CD147 and monocarboxylate transporter 4 (MCT4), which enhances the translocation of MCT4 from the cytoplasm to the membrane. Overexpression of CD147-K234me2 and KMT5A enhances glycolysis and lactate export in NSCLC cells. Clinical analysis shows that high CD147-K234me2 expression is significantly related to cancer progression and overall survival, and has prognostic significance in individuals with NSCLC, especially for those in the early stages. Our findings indicate that CD147-K234me2 plays a critical role in cancer metabolism, and it can be a highly promising therapeutic target for NSCLC.The metabolic role of micropeptides generated from untranslated regions remains unclear. Raf inhibitor Here we describe MP31, a micropeptide encoded by the upstream open reading frame (uORF) of phosphatase and tensin homolog (PTEN) acting as a "circuit breaker" that limits lactate-pyruvate conversion in mitochondria by competing with mitochondrial lactate dehydrogenase (mLDH) for nicotinamide adenine dinucleotide (NAD+). Knocking out the MP31 homolog in mice enhanced global lactate metabolism, manifesting as accelerated oxidative phosphorylation (OXPHOS) and increased lactate consumption and production. Conditional knockout (cKO) of MP31 homolog in mouse astrocytes initiated gliomagenesis and shortened the overall survival of the animals, establishing a tumor-suppressing role for MP31. Recombinant MP31 administered intraperitoneally penetrated the blood-brain barrier and inhibited mice GBM xenografts without neurological toxicity, suggesting the clinical implication and application of this micropeptide. Our findings reveal a novel mode of MP31-orchestrated lactate metabolism reprogramming in glioblastoma.Bacteria fromthe Vibriogenus are autochthonous to aquatic environments and ubiquitous in aquaculture production systems. Many Vibrio species are non-pathogenic and can be commonly found in healthy farmed aquatic animals. However, some Vibrio species and strains are pathogenic leading to a variety of 'vibriosis' diseases. These diseases can have a significant negative impact on animal production, including farmed crustaceans such as shrimps, lobsters, and crabs. As such, vibriosis can pose a threat to meeting growing food demand and global food security. Preventive management is essential to avoid the onset of vibriosis. This includes a robust health management plan, the use of prophylaxis and treatment measures, and enhancing animal health through nutrition. Furthermore, the use of probiotics, prebiotics, synbiotics, quorum sensing disruption, green water, biofloc, bacteriophages, and immune priming could also play a role in preventing and controlling a vibriosis outbreak. This review aims to inform and update the reader about the current state of knowledge about Vibrio and associated vibriosis in farmed crustaceans (i.e. shrimp, lobster, and crabs). Furthermore, the review will identify potential knowledge gaps in the literature, which serves as a basis for future research priorities.Uveal melanoma (UM) and conjunctival melanoma (CM) are ocular malignancies that give rise to life-threatening metastases. Although local disease can often be treated successfully, it is often associated with significant vision impairment and treatments are often not effective against metastatic disease. Novel treatment modalities that preserve vision may enable elimination of small tumors and may prevent subsequent metastatic spread. Very few mouse models of metastatic CM and UM are available for research and for development of novel therapies. One of the challenges is to follow tumor growth in-vivo and to determine the right size for treatment, mainly of the posterior, choroidal melanoma. Hence, the purpose of this study was to establish a simple, noninvasive imaging tool that will simplify visualization and tumor follow-up in mouse models of CM and UM. Tumors were induced by inoculation of murine B16LS9 cells into the sub-conjunctival or the choroidal space of a C57BL/6 mouse eye under a surgical microscopew intraocular tumor growth of both CM and UM, and to define, already at the time of cell inoculation, a grading scale to evaluate tumor size. This tool may be utilized for evaluation of new mouse models for CM and UM, as well as for testing new therapies for these diseases.This study aimed to use a reverse dosimetry PBPK modeling approach to estimate toluene atmospheric exposure from urinary measurements of S-benzylmercapturic acid (BMA) in a small group of individuals and to evaluate the uncertainty associated to urinary spot-sampling compared to 24-h collected urine samples. Each exposure assessment technique was developed namely to estimate toluene air exposure from BMA measurements in 24-h urine samples (24-h-BMA) and from distributions of daily urinary BMA spot measurements (DUBSM). Model physiological parameters were described based upon age, weight, size and sex. Monte Carlo simulations with the PBPK model allowed converting DUBSM distribution (and 24-h-BMA) into toluene air levels. For the approach relying on DUBSM distribution, the ratio between the 95% probability of predicted toluene concentration and its 50% probability in each individual varied between 1.2 and 1.4, while that based on 24-h-BMA varied between 1.0 and 1.1. This suggests more variability in estimated exposure from spot measurements. Thus, estimating toluene exposure based on DUBSM distribution generated about 20% more uncertainty. Toluene levels estimated (0.0078-0.0138 ppm) are well below Health Canada's maximum chronic air guidelines. PBPK modeling and reverse dosimetry may be combined to interpret urinary metabolites data of VOCs and assess related uncertainties.
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