ObjectiveThe adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.DesignData were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death).ResultsIn the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19.ConclusionPatients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit–risk assessments in the management of acid-related diseases amid the COVID-19 pandemic.

Microglia are major immune cells in the central nervous system. A characterization of microglia proteome would facilitate on the study of microglial functions in association with various neurodegenerative diseases. To build a reference proteome, we established a BV-2 microglial proteome to a depth of 5494 unique protein groups using a novel strategy that combined FASP, StageTip-based high pH fractionation, and high-resolution MS quickly and cost efficiently. By bioinformatics analysis, the BV-2 proteome is a valuable resource for studies of microglial function, such as in the immune response, inflammatory response, and phagocytosis. All MS data have been deposited in the ProteomeXchange with identifier PXD000168.

We expressed a protein in Saccharomyces cerevisiae in order to evaluate the humoral immune responses to the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax. This protein (Pv200 18 ) had a molecular mass of 18 kDa and was reactive with the sera of individuals with patent vivax malaria on immunoblotting analysis. The levels of immunoglobulin M (IgM) and IgG antibodies against Pv200 18 were measured in 421 patients with vivax malaria (patient group), 528 healthy individuals from areas of nonendemicity (control group 1), and 470 healthy individuals from areas of endemicity (control group 2), using the indirect enzyme-linked immunosorbent assay (ELISA) method. To study the longevity of the antibodies, 20 subjects from the patient group were also tested for the antibody levels once a month for 1 year. When the cutoff values for seropositivity were determined as the mean ؉ 3 ؋ standard deviation of the antibody levels in control group 1, both IgG and IgM antibody levels were negative in 98.5% (465 of 472) of control group 2. The IgG and IgM antibodies were positive in 88.1% (371 of 421) and 94.5% (398 of 421) of the patient group, respectively. The IgM antibody became negative 2 to 4 months after the onset of symptoms, whereas the IgG antibody usually remained positive for more than 5 months. In conclusion, indirect ELISA using Pv200 18 expressed in S. cerevisiae may be a useful diagnostic method for vivax malaria.

Type 2 diabetes results from aberrant regulation of the phosphorylation cascade in beta-cells. Phosphorylation in pancreatic beta-cells has not been examined extensively, except with regard to subcellular phosphoproteomes using mitochondria. Thus, robust, comprehensive analytical strategies are needed to characterize the many phosphorylated proteins that exist, because of their low abundance, the low stoichiometry of phosphorylation, and the dynamic regulation of phosphoproteins. In this study, we attempted to generate data on a large-scale phosphoproteome from the INS-1 rat pancreatic beta-cell line using linear ion trap MS/MS. To profile the phosphoproteome in-depth, we used comprehensive phosphoproteomic strategies, including detergent-based protein extraction (SDS and SDC), differential sample preparation (in-gel, in-solution digestion, and FASP), TiO2 enrichment, and MS replicate analyses (MS2-only and multiple-stage activation). All spectra were processed and validated by stringent multiple filtering using target and decoy databases. We identified 2467 distinct phosphorylation sites on 1419 phosphoproteins using 4 mg of INS-1 cell lysate in 24 LC-MS/MS runs, of which 683 (27.7%) were considered novel phosphorylation sites that have not been characterized in human, mouse, or rat homologues. Our informatics data constitute a rich bioinformatics resource for investigating the function of reversible phosphorylation in pancreatic beta-cells. In particular, novel phosphorylation sites on proteins that mediate the pathology of type 2 diabetes, such as Pdx-1, Nkx.2, and Srebf1, will be valuable targets in ongoing phosphoproteomics studies.