Crystal structure of peroxiredoxin 3 from Vibrio vulnificus

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently, a new type of Prx, VvPrx3, was identified in the pathogenic bacterium Vibrio vulnificus as being important for survival in macrophages. It employs only one catalytic cysteine residue to decompose peroxides. Here, crystal structures of VvPrx3 representing its reduced and oxidized states have been determined, together with an H2O2-bound structure, at high resolution. The crystal structure representing the reduced Prx3 showed a typical dimeric interface, called the A-type interface. However, VvPrx3 forms an oligomeric interface mediated by a disulfide bond between two catalytic cysteine residues from two adjacent dimers, which differs from the doughnut-like oligomers that appear in most Prxs. Subsequent biochemical studies showed that this disulfide bond was induced by treatment with nitric oxide (NO) as well as with peroxides. Consistently, NO treatment induced expression of the prx3 gene in V. vulnificus, and VvPrx3 was crucial for the survival of bacteria in the presence of NO. Taken together, the function and mechanism of VvPrx3 in scavenging peroxides and NO stress via oligomerization are proposed. These findings contribute to the understanding of the diverse functions of Prxs during pathogenic processes at the molecular level

Vibrio vulnificus RtxA Is a Major Factor Driving Inflammatory T Helper Type 17 Cell Responses in vitro and in vivo

T helper type 17 (Th17) cells are a subset of pro-inflammatory T helper cells that mediate host defense and pathological inflammation. We have previously reported that host dendritic cells (DCs) infected with Vibrio vulnificus induce Th17 responses through the production of several pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. V. vulnificus produces RTX toxin (RtxA), an important virulence factor that determines successful pathophysiology. In this study, we investigated the involvement of RtxA from V. vulnificus in Th17 cell induction through the activation and maturation of DCs. The increased expression of the DC surface marker CD40 caused by V. vulnificus wild-type infection was reduced by rtxA gene mutation in V. vulnificus. The mRNA and protein levels of Th17 polarization-related cytokines also decreased in V. vulnificus rtxA mutant-infected DCs. In addition, the co-culture of Th cells and DCs infected with rtxA mutant V. vulnificus resulted in reduction in DC-mediated Th17 responses. Th17 cell responses in the small intestinal lamina propria decreased in mice inoculated with V. vulnificus rtxA mutant as compared to those inoculated with the wild-type strain. These decreases in DC maturation, Th17-polarizing cytokine secretion, and Th17 responses attributed to rtxA mutation were restored following infection with the rtxA revertant strain. Furthermore, the mutation in the hlyU gene encoding the activator of rtxA1 gene reproduced the results observed with rtxA mutation. Taken together, V. vulnificus, by means of RtxA, induces inflammatory Th17 responses, which may be associated with adaptive responses of the host against V. vulnificus infection

Clinical features and Surgical Outcome of Clear Cell Papillary Renal Cell Tumor: result from a prospective cohort

Background Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. Methods This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. Results Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5min and the estimated blood loss was 100cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. Conclusions The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. Trial registration Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371)

Electron energy increase in a laser wakefield accelerator using up-ramp plasma density profiles

The phase velocity of the wakefield of a laser wakefield accelerator can, theoretically, be manipulated by shaping the longitudinal plasma density profile, thus controlling the parameters of the generated electron beam. We present an experimental method where using a series of shaped longitudinal plasma density profiles we increased the mean electron peak energy more than 50%, from 175 +/- 1 MeV to 262 +/- 10 MeV and the maximum peak energy from 182 MeV to 363 MeV. The divergence follows closely the change of mean energy and decreases from 58.9 +/- 0.45 mrad to 12.6 +/- 1.2 mrad along the horizontal axis and from 35 +/- 0.3 mrad to 8.3 +/- 0.69 mrad along the vertical axis. Particle-in-cell simulations show that a ramp in a plasma density profile can affect the evolution of the wakefield, thus qualitatively confirming the experimental results. The presented method can increase the electron energy for a fixed laser power and at the same time offer an energy tunable source of electrons.© The Author(s) 201

Comparison of methods for proanthocyanidin extraction from pine (Pinus densiflora) needles and biological activities of the extracts

Flavonoids are known to be effective scavengers of free radicals. In particular, proanthocyanidins are flavonoids that possess cardiovascular protection, antioxidative activities, and immunomodulatory activities. Here, we evaluated proanthocyanidin contents in the total polyphenolic compounds of pine needle extracts prepared by hot water, ethanol, hexane, hot water-hexane (HWH), and hot water-ethanol (HWE). Analysis of each extract indicated that the ethanol extract contained the highest proanthocyanidin concentration. The HWH and hexane extracts also contained relatively high concentrations of proanthocyanidin. On the other hand, proanthocyanidin content analyses out of the total polyphenolic compounds indicated that the HWH extract contained the highest content. These results suggest that HWH extraction is a suitable method to obtain an extract with a high level of pure proanthocyanidins and a relatively high yield. The HWH extract possessed superior activity in diverse antioxidative analyses such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferrous ion chelating (FIC), and ferric-ion reducing power (FRAP) assays. In addition, upon assessing the effects of the pine needle extracts on macrophages (Raw 264.7 cell), the HWH extract exhibited the highest activity. In this study, we discerned an efficient extraction method to achieve relatively pure proanthocyanidins from pine needles and evaluated the biological functions of the resulting extract, which could potentially be used for its efficacious components in functional food products

Normative Values and Correlates of Mean Common Carotid Intima-Media Thickness in the Korean Rural Middle-aged Population: The Atherosclerosis RIsk of Rural Areas iN Korea General Population (ARIRANG) Study

Carotid intima-media thickness (CIMT) is considered as a surrogate marker for cardiovascular disease (CVD). We determined the normative value of CIMT and correlates of CVD risk factors and Framingham risk score (FRS) in Korean rural middle-aged population. We measured CIMT with a B-mode ultrasonography in 1,759 subjects, aged 40 to 70 yr, in a population-based cohort in Korea. A healthy reference sample (n = 433) without CVD, normal weight and normal metabolic parameters was selected to establish normative CIMT values. Correlates between CIMT and conventional CVD risk factors were assessed in the entire population. Mean values of CIMT (in mm) for healthy reference sample aged 40-49, 50-59, and 60-70 yr were 0.55, 0.59, and 0.66 for men and 0.48, 0.55, and 0.63 for women, respectively. In multivariate regression analysis, CIMT was correlated with older age, higher BMI, male gender, higher LDL-cholesterol level and history of diabetes mellitus. The mean CIMT was also correlated with FRS in both gender (r2 = 0.043, P < 0.01 for men; r2 = 0.142, P < 0.01 for women). We identified normative value of CIMT for the healthy Korean rural middle-aged population. The CIMT is associated with age, obesity, gender, LDL-cholesterol, diabetes mellitus and FRS

Alteration of CD4+CD25+Foxp3+ T cell level in Kawasaki disease

PurposeExaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD.MethodsPeripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD.ResultsThe percentage of circulating CD4+CD25highFoxp3+ T cells among CD4+ T cells was significantly higher during the subacute afebrile phase than during the acute febrile phase (1.10%±1.22% vs. 0.55%±0.53%, P=0.049). Although levels of CD4+CD25lowFoxp3+ T cells and CD4+CD25-Foxp3+ T cells were only slightly altered, the percentage of CD4+CD25+Foxp3- T cells among CD4+ T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase (2.96%±1.95% vs. 5.64%±5.69%, P=0.036). Consequently, the ratio of CD25highFoxp3+ T cells to CD25+Foxp3- T cells was higher during the subacute afebrile phase than during the acute febrile phase (0.45%±0.57% vs. 0.13%±0.13%, P=0.038).ConclusionDecreased CD4+CD25highFoxp3+ T cells and/or an imbalanced ratio of CD4+CD25highFoxp3+ T cells to CD4+CD25+Foxp3- T cells might play a role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of CD4+CD25highFoxp3+ T cells during the subacute afebrile phase could be a mechanism of IVIG

Author correction : Electron energy increase in a laser wakefield accelerator using up-ramp plasma density profiles

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47677-5, published online 02 August 201