From arginine methylation to ADMA: A novel mechanism with therapeutic potential in chronic lung diseases

Protein arginine methylation is a novel posttranslational modification regulating a diversity of cellular processes, including protein-protein interaction, signal transduction, or histone function. It has recently been shown to be dysregulated in chronic renal, vascular, and pulmonary diseases, and metabolic products originating from protein arginine methylation have been suggested to serve as biomarkers in cardiovascular and pulmonary diseases

Functional Wnt Signaling Is Increased in Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, characterized by distorted lung architecture and loss of respiratory function. Alveolar epithelial cell injury and hyperplasia, enhanced extracellular matrix deposition, and (myo)fibroblast activation are features of IPF. Wnt/beta-catenin signaling has been shown to determine epithelial cell fate during development. As aberrant reactivation of developmental signaling pathways has been suggested to contribute to IPF pathogenesis, we hypothesized that Wnt/beta-catenin signaling is activated in epithelial cells in IPF. Thus, we quantified and localized the expression and activity of the Wnt/beta-catenin pathway in IPF. METHODOLOGY/PRINCIPAL FINDINGS: The expression of Wnt1, 3a, 7b, and 10b, the Wnt receptors Fzd1-4, Lrp5-6, as well as the intracellular signal transducers Gsk-3beta, beta-catenin, Tcf1, 3, 4, and Lef1 was analyzed in IPF and transplant donor lungs by quantitative real-time (q)RT-PCR. Wnt1, 7b and 10b, Fzd2 and 3, beta-catenin, and Lef1 expression was significantly increased in IPF. Immunohistochemical analysis localized Wnt1, Wnt3a, beta-catenin, and Gsk-3beta expression largely to alveolar and bronchial epithelium. This was confirmed by qRT-PCR of primary alveolar epithelial type II (ATII) cells, demonstrating a significant increase of Wnt signaling in ATII cells derived from IPF patients. In addition, Western blot analysis of phospho-Gsk-3beta, phospho-Lrp6, and beta-catenin, and qRT-PCR of the Wnt target genes cyclin D1, Mmp 7, or Fibronectin 1 demonstrated increased functional Wnt/beta-catenin signaling in IPF compared with controls. Functional in vitro studies further revealed that Wnt ligands induced lung epithelial cell proliferation and (myo)fibroblast activation and collagen synthesis. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that the Wnt/beta-catenin pathway is expressed and operative in adult lung epithelium. Increased Wnt/beta-catenin signaling may be involved in epithelial cell injury and hyperplasia, as well as impaired epithelial-mesenchymal cross-talk in IPF. Thus, modification of Wnt signaling may represent a therapeutic option in IPF

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

The carbon-based structures synthesized through nuclear reactions in helium at 1.1 kbar pressure under irradiation with braking γ-rays of 10 MeV threshold energy

A helium high-pressure chamber (HeHPC), made from beryllium bronze, filled with gaseous helium at an initial pressure of about 1.1 kbar was irradiated by braking γ-rays of 10 MeV threshold energy during $1.0\times10^{5}\ \text{s}$ at an electron beam current $22\text{--}24\ \mu \text{A}$ . Before opening of the chamber, the residual pressure inside was equal to 430 bar. Synthesized foils of black colour and other multiple objects were found inside the HeHPC at the inner surfaces of the reaction chamber made of high-purity copper, at the entrance window for γ-rays of beryllium bronze, and at the copper collector of nuclear and chemical reaction products. The element analysis using scanning electron microscopy (SEM) and microprobe roentgen analysis (MPRA) allowed us to establish that the foils were predominantly made of carbon and smaller quantities of other elements from carbon to iron. The developed approach agrees well with a series of studies carried out by the authors where dense hydrogen and deuterium gases are acted on by γ-rays in the presence or absence of metals in the reaction chamber

Healthcare workers highly affected during the COVID-19 epidemic wave in Poland prior to vaccination availability: seroprevalence study

The aim of the study was to assess seroprevalence of anti-SARS-CoV-2 antibodies among healthcare workers (HCW) before introduction of vaccination, in selected areas in Poland as well as to identify potential risk factors and estimate the cumulative incidence of COVID-19 infections in this population.Material and MethodsThe authors conducted a sero-epidemiological, cross-sectional study among HCW of 5 non-COVID-19 hospitals in Poland. The recruitment took place in December 1–23, 2020, all HCW at selected hospitals could volunteer into the study. All persons were screened with rapid SARS-CoV-2 IgM/IgG tests in capillary blood. In case of positive result, 5 ml of venous blood was drawn for confirmatory testing with ELISA assay. The authors estimated prevalence of laboratory confirmed anti-SARS-CoV-2 antibody presence and examined factors associated with positive result. Cumulative incidence was estimated applying 2-source capture-recapture method to serology results and self-report of past infection.ResultsOut of 1040 HCW included in the analysis, one-fourth (25.2%) received a positive result for anti-SARS-CoV-2 antibodies by ELISA test, the prevalence among women was 25.3% (95% CI: 22.5–28.4) and 24.6% (95% CI: 19–31.2) among men. The prevalence of anti-SARS-CoV-2 antibodies was the highest among respondents who declared home contact with a confirmed COVID-19 case, 43.9% (95% CI: 32.4–56.1). It was also elevated among those who indicated contact with patients with COVID-19, 32.5% (95% CI: 26.7–38.8) and business contacts, including at the workplace, 28.9% (95% CI: 22.5–36.3). The estimated cumulative incidence of COVID-19 infections in the population, using the capture-recapture method was 41.2% (95% CI: 38.1–44.2).ConclusionsHealthcare workers remained at increased risk of infection largely due to work-related contacts with infected patients, although home exposure was also common. Estimated cumulative incidence is higher than the antibody prevalence, which indicates the need to monitor HCW for possible immunity waning, also post-immunization immunity. Med Pr. 2022;73(2):109–2