The essential amino acid, methionine, is important for cancer cell growth and metabolism. A growing body of evidence indicates that methionine restriction inhibits cancer cell growth and may enhance the efficacy of chemotherapeutic agents. This review summarizes the efficacy and mechanism of action of methionine restriction on hallmarks of cancer in vitro and in vivo. The review highlights the role of glutathione formation, polyamine synthesis, and methyl group donation as mediators of the effects of methionine restriction on cancer biology. The translational potential of the use of methionine restriction as a personalized nutritional approach for the treatment of patients with cancer is also discussed.

Although a few studies show that the use of electronic nicotine delivery systems (ENDS) may ameliorate objective and subjective outcomes in COPD smokers who switched to electronic cigarettes, it is unclear whether e-cigarette exposure alters lung pathological features and inflammatory response in COPD. Here, we employed βENaC-overexpressing mice bearing COPD-like pulmonary abnormality, and exposed them to ENDS. We found that ENDS exposure aggravated airspace enlargement and mucus production in βENaC-overexpressing mice, which was associated with increased MMP12 and Muc5ac, respectively. ENDS exposure to mice significantly increased the numbers of macrophages, particularly in M2 macrophages in bronchoalveolar lavage (BAL) fluid, despite ENDS did not induce M2 macrophage polarization in a cultured murine macrophage cell line (RAW264.7). There were no changes in neutrophils in BAL fluid by ENDS exposure. Multiple cytokine productions were increased including M-CSF, IL-1rα, IL-10, and TGF-β1, in BAL fluid from mice when exposed to ENDS. The Sirius Red staining and hydroxyproline assay showed ENDS-exposed mice displayed enhanced fibrotic phenotypes compared to control mice. In conclusion, ENDS exposure enhances airspace enlargement, mucus secretion, and fibrogenesis in COPD mice. This is associated with increased MMP12, inflammatory responses, and M2 macrophage phenotype. This study provides pre-clinical data implicating that electronic cigarette exposure is not safe in COPD patients who want to replace traditional cigarettes with ENDS.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment. The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status. Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD. Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD. Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism. Methods: In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group). After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species. Later, the comparisons of individual lipids were performed between controls and patients with COPD. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers. Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated. Results: Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD. Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change. In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers. Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity. Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years. Conclusion: Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD. Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.

Dysmorphic pulmonary vascular growth and abnormal endothelial cell (EC) proliferation are paradoxically observed in premature infants with bronchopulmonary dysplasia (BPD), despite vascular pruning. The pentose phosphate pathway (PPP), a metabolic pathway parallel to glycolysis, generates NADPH as a reducing equivalent and ribose 5-phosphate for nucleotide synthesis. It is unknown whether hyperoxia, a known mediator of BPD in rodent models, alters glycolysis and the PPP in lung ECs. We hypothesized that hyperoxia increases glycolysis and the PPP, resulting in abnormal EC proliferation and dysmorphic angiogenesis in neonatal mice. To test this hypothesis, lung ECs and newborn mice were exposed to hyperoxia and allowed to recover in air. Hyperoxia increased glycolysis and the PPP. Increased PPP, but not glycolysis, caused hyperoxia-induced abnormal EC proliferation. Blocking the PPP reduced hyperoxia-induced glucose–derived deoxynucleotide synthesis in cultured ECs. In neonatal mice, hyperoxia-induced abnormal EC proliferation, dysmorphic angiogenesis, and alveolar simplification were augmented by nanoparticle-mediated endothelial overexpression of phosphogluconate dehydrogenase, the second enzyme in the PPP. These effects were attenuated by inhibitors of the PPP. Neonatal hyperoxia augments the PPP, causing abnormal lung EC proliferation, dysmorphic vascular development, and alveolar simplification. These observations provide mechanisms and potential metabolic targets to prevent BPD-associated vascular dysgenesis.

Coronavirus disease 2019 (COVID-19) has so far infected hundreds of million individuals, with several million deaths worldwide. The lack of understanding of the disease pathophysiology and the host’s immune response has resulted in this rapid spread of the disease on a global scale. In this respect, we employed UPLC-MS to compare the metabolites in the serum from COVID-19-positive patients and COVID-19-recovered subjects to determine the metabolic changes responsible for an infection. Our investigations revealed significant increase in the levels of serum phospholipids including sphingomyelins, phosphatidylcholines and arachidonic acid in the serum of COVID-19-positive patients as compared to COVID-19-recovered individuals. We further show increased levels of tryptophan and its metabolites in the serum of COVID-19-positive patients thus emphasizing the role of tryptophan metabolism in the disease pathogenesis of COVID-19. Future studies are required to determine the changes in the lipid and tryptophan metabolism at various stages of COVID-19 disease development, progression and recovery to better understand the host–pathogen interaction and the long-term effects of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in humans.

Metabolites are essential intermediate products in metabolism, and metabolism dysregulation indicates different types of diseases. Previous studies have shown that cigarette smoke dysregulated metabolites; however, limited information is available with electronic cigarette (e-cig) vaping. We hypothesized that e-cig vaping and cigarette smoking alters systemic metabolites, and we propose to understand the specific metabolic signature between e-cig users and cigarette smokers. Plasma from non-smoker controls, cigarette smokers, and e-cig users was collected, and metabolites were identified by UPLC-MS (ultra-performance liquid chromatography mass spectrometer). Nicotine degradation was activated by e-cig vaping and cigarette smoking with increased concentrations of cotinine, cotinine N-oxide, (S)-nicotine, and (R)-6-hydroxynicotine. Additionally, we found significantly decreased concentrations in metabolites associated with tricarboxylic acid (TCA) cycle pathways in e-cig users versus cigarette smokers, such as d-glucose, (2R,3S)-2,3-dimethylmalate, (R)-2-hydroxyglutarate, O-phosphoethanolamine, malathion, d-threo-isocitrate, malic acid, and 4-acetamidobutanoic acid. Cigarette smoking significant upregulated sphingolipid metabolites, such as d-sphingosine, ceramide, N-(octadecanoyl)-sphing-4-enine, N-(9Z-octadecenoyl)-sphing-4-enine, and N-[(13Z)-docosenoyl]-sphingosine, versus e-cig vaping. Overall, e-cig vaping dysregulated TCA cycle-related metabolites while cigarette smoking altered sphingolipid metabolites. Both e-cig and cigarette smoke increased nicotinic metabolites. Therefore, specific metabolic signatures altered by e-cig vaping and cigarette smoking could serve as potential systemic biomarkers for early pathogenesis of cardiopulmonary diseases.