Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics

This study examined the clinical and biological importance of thioredoxin-1, a redox-active defensive protein that controls multiple biological functions, in pregnant women. We measured serum concentrations of thioredoxin-1, total hydroperoxides, and redox potential in 60 pregnant women at the early third trimester: gestational age of 27-29 weeks. The thioredoxin-1 concentration (mean +/- SD) was 90 +/- 42 ng/ml. Total hydroperoxides was 471 +/- 105 U.CARR (1 U.CARR = 0.08 mg/dl H2O2). Redox potential was 2142 +/- 273 mu mol/l. The total hydroperoxides: redox potential ratio (oxidative stress index) was 0.23 +/- 0.08. Thioredoxin-1, total hydroperoxides, and oxidative stress index were higher and redox potential was lower than in blood of healthy adults. Total hydroperoxides and redox potential were mutually correlated significantly and negatively. Thioredoxin-1 correlated significantly and negatively and redox potential correlated significantly and positively with body weight and body mass index. Thioredoxin-1 and redox potential correlated significantly and positively with uric acid and albumin, respectively. Thioredoxin-1 and oxidative stress index correlated significantly and negatively and redox potential significantly and positively with neonatal birth weight. These results suggest that high concentrations of thioredoxin-1 are linked to high oxidative stress status in pregnant women and that neonatal birth weight is affected by the maternal oxidative condition during later pregnancy

Cell-Surface Phenol Soluble Modulins Regulate Staphylococcus aureus Colony Spreading.

Staphylococcus aureus produces phenol-soluble modulins (PSMs), which are amphipathic small peptides with lytic activity against mammalian cells. We previously reported that PSMα1-4 stimulate S. aureus colony spreading, the phenomenon of S. aureus colony expansion on the surface of soft agar plates, whereas δ-toxin (Hld, PSMγ) inhibits colony-spreading activity. In this study, we revealed the underlying mechanism of the opposing effects of PSMα1-4 and δ-toxin in S. aureus colony spreading. PSMα1-4 and δ-toxin are abundant on the S. aureus cell surface, and account for 18% and 8.5% of the total amount of PSMα1-4 and δ-toxin, respectively, in S. aureus overnight cultures. Knockout of PSMα1-4 did not affect the amount of cell surface δ-toxin. In contrast, knockout of δ-toxin increased the amount of cell surface PSMα1-4, and decreased the amount of culture supernatant PSMα1-4. The δ-toxin inhibited PSMα3 and PSMα2 binding to the S. aureus cell surface in vitro. A double knockout strain of PSMα1-4 and δ-toxin exhibited decreased colony spreading compared with the parent strain. Expression of cell surface PSMα1-4, but not culture supernatant PSMα1-4, restored the colony-spreading activity of the PSMα1-4/δ-toxin double knockout strain. Expression of δ-toxin on the cell surface or in the culture supernatant did not restore the colony-spreading activity of the PSMα1-4/δ-toxin double knockout strain. These findings suggest that cell surface PSMα1-4 promote S. aureus colony spreading, whereas δ-toxin suppresses colony-spreading activity by inhibiting PSMα1-4 binding to the S. aureus cell surface

Association of combustible cigarettes and heated tobacco products use with SARS-CoV-2 infection and severe COVID-19 in Japan: a JASTIS 2022 cross-sectional study

Abstract Insufficient evidence has been accumulated regarding associations of heated tobacco products (HTPs) use with coronavirus infection and severity of coronavirus disease 2019 (COVID-19), an ongoing pandemic. We conducted a cross-sectional study using data from an internet questionnaire administered in February 2022 to 30,130 individuals from the general Japanese population (age range, 16–81 years). Single users of HTPs and dual users of combustible cigarettes and HTPs comprised 5.2% and 7.3% of respondents, and 6.7% and 38.0% of those infected (n = 1117). Approximately 70% of infected dual users experienced severe disease. Single users of HTPs and dual users were more likely to be infected with coronavirus than never-users (adjusted odds ratio [aOR] = 1.65/4.66; 95% confidence interval [CI] 1.26–2.15/3.89–5.58). Regarding severity, former and current tobacco users (former/combustible cigarettes/HTPs: aOR = 1.88/3.17/1.90; 95%CI 1.11–3.19/1.77–5.67/1.01–3.59) were more likely to be administered oxygen than never-users, and dual users required oxygen administration the most (aOR = 4.15, 95%CI 2.70–6.36). Use of HTPs may increase risks of coronavirus infection and severe COVID-19. Our results provide an opportunity to consider the safety of tobacco products use, including HTPs, during the COVID-19 pandemic

Summary of the cell surface PSMα1–4 and the colony spreading in <i>S</i>. <i>aureus</i> gene knockout strains.

<p>PSMα1–4 and δ-toxin are presented as orange and blue dots, respectively. Knockout of δ-toxin increases the amount of cell surface PSMα1–4. In contrast, knockout of PSMα1–4 does not affect the amount of cell surface δ-toxin. The amount of cell surface PSMα1–4 and the colony-spreading activity in the wild-type strain, the δ-toxin knockout strain, the PSMα1–4 knockout strain, and the PSMα1-4/δ-toxin knockout strain is summarized in the lower part of this figure. The amount of cell surface PSMα1–4 is a determinant of colony-spreading activity.</p

Effect of PSMα1–4 knockout on δ-toxin distribution.

<p><i>S</i>. <i>aureus</i> Newman strain (parent) and PSMα1–4 knockout strain (Δ<i>psmα</i>) were cultured for 19 h. The amount of δ-toxin on the cell surface or in the culture supernatant was measured. Vertical axis represents the amount of δ-toxin per 1 ml bacterial culture. Data are means±standard errors from four independent experiments. Asterisk indicates Student’s t-test p value less than 0.05 between parent and Δ<i>psmα</i>.</p

Competitive binding assay of PSMs against <i>S</i>. <i>aureus</i> cell surface.

<p><b>A.</b> Inhibitory activity of δ-toxin against PSMα2 binding to the <i>S</i>. <i>aureus</i> cell surface of the PSMα1-4/δ-toxin knockout strain was measured. Binding assay of PSMα2 (10 nmol) to the cell surface of the PSMα1-4/δ-toxin knockout strain was performed in the absence or presence of δ-toxin (0, 10, 20, and 30 nmol) and the amount of PSMα2 bound to the cell surface was measured (left graph). In the competition assay, the binding of δ-toxin to the <i>S</i>. <i>aureus</i> cell surface was also measured (center graph) and the binding of total PSM (PSMα2 and δ-toxin) is presented (right graph). In all graphs, horizontal axis represents the amount of PSM added to <i>S</i>. <i>aureus</i> cells and vertical axis represents the amount of PSM bound to <i>S</i>. <i>aureus</i> cells (3 x 10⁸ CFU). B. Inhibitory activity of PSMα2 against δ-toxin binding to the <i>S</i>. <i>aureus</i> cell surface was measured. Binding assay of δ-toxin (10 nmol) to the cell surface of the PSMα1-4/δ-toxin knockout strain was performed in the absence or presence of PSMα2 (0, 10, 20, and 30 nmol) and the amount of δ-toxin bound to the cell surface was measured (left graph). In the competition assay, binding of PSMα2 to the <i>S</i>. <i>aureus</i> cell surface was also measured (center graph) and the binding of total PSM (δ-toxin and PSMα2) is presented (right graph). C. Inhibitory activity of δ-toxin against PSMα3 binding to the <i>S</i>. <i>aureus</i> cell surface was measured. Binding assay of PSMα3 (10 nmol) to the cell surface of the PSMα1-4/δ-toxin knockout strain was performed in the absence or presence of δ-toxin (0, 10, 20, and 30 nmol) and the amount of PSMα3 bound to the cell surface was measured (left graph). In the competition assay, binding of δ-toxin to the <i>S</i>. <i>aureus</i> cell surface was also measured (center graph) and the binding of total PSM (PSMα3 and δ-toxin) is presented (right graph). D. Inhibitory activity of PSMα3 against δ-toxin binding to <i>S</i>. <i>aureus</i> cell surface was measured. Binding assay of δ-toxin (10 nmol) to the cell surface of the PSMα1-4/δ-toxin knockout strain was performed in the absence or presence of PSMα3 (0, 10, 20, and 30 nmol) and the amount of δ-toxin bound to the cell surface was measured (left graph). In the competition assay, binding of PSMα3 to the <i>S</i>. <i>aureus</i> cell surface was also measured (center graph) and the binding of total PSM (δ-toxin and PSMα3) is presented (right graph).</p

Amount of PSMα1–4 and δ-toxin on the <i>S</i>. <i>aureus</i> cell surface and in the culture supernatant.

<p>A. <i>S</i>. <i>aureus</i> Newman strain was cultured for 19 h. Cells were washed with 6 M guanidine HCl and PSMs on the cell surface were obtained. PSMs on the cell surface (from 1.33 ml bacterial culture) and in the culture supernatant (from 0.267 ml bacterial culture) were analyzed by HPLC. Dotted line indicates the respective PSMs. B. The amount of PSMs on the cell surface or in the culture supernatant was measured. Vertical axis represents the amount of each PSM per 1 ml bacterial culture. Data are means±standard errors from three independent experiments.</p

Correlation analysis between the amount of cell surface PSMs and the colony-spreading activity in <i>S</i>. <i>aureus</i> clinical isolates.

<p>HA-MRSA isolates (n = 40), CA-MRSA isolates (n = 14), and Newman strain were cultured for 19 h. The total amount of PSMα1, PSMα2, and PSMα3 (PSMα1–3) (<i>A</i>) or the amount of δ-toxin (<i>B</i>) in each strain was measured by HPLCs and the mean value from three independent experiments was plotted on the horizontal axis as the relative value against that of Newman strain. The colony-spreading activity of each strain, which was reported in our previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164523#pone.0164523.ref018" target="_blank">18</a>], was plotted on the vertical axis. A linear approximation and correlation coefficient are presented in the graph.</p