RESUMEN
Background: As increasing experimental evidence suggests that iron metabolism play crucial roles in cancer and non-cancer conditions, there is a lack of data on serum soluble transferrin receptor (sTfR), a promising marker representing unmet cellular iron demands, between cancer risk from epidemiological studies. Here, we aimed to evaluate the predictive value of sTfR and cancer prevalence. Materials and methods: We analyzed on 5,480 adult participants from 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to investigate the correlations between sTfR and other characteristics. To identify the associations between sTfR and the prevalence of cancers, stratified multivariable logistic regression models, subgroup and sensitivity analyses were also performed. Results: In tertile analyses, participants in the highest level of sTfR were significantly associated with increased prevalence of total cancers [odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.15-2.02] as compared with those at the lowest tertile. Each unit increment in ln-transformed sTfR concentration was shown to be associated with 39% increased risks of total cancers. Similar associations were found in males rather than females. Further subgroup and sensitivity analyses indicated that, in continuous and tertile analyses, sTfR was more closely associated with male- and female-specific cancers of prostate and testis (2.35: 1.03-5.40; 2.03: 1.00-4.09; respectively), and breast, cervix, ovary and uterus (1.92: 1.11-3.35; 1.66: 1.02-2.69; respectively). Conclusions: Our findings suggested that elevated level of sTfR was associated with the prevalence of cancers, especially in sex-specific cancers. In order to better determine them, further research in humans will be required.
RESUMEN
Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.
