Ingestion of Porphyromonas gingivalis, a periodontal pathogen, disrupts the intestinal barrier in mice. However, the involvement of outer membrane vesicles (OMVs) secreted from P. gingivalis in the ...destruction of the intestinal barrier remains unclear. In this study, we tested the hypothesis that OMVs carrying gingipains, the major cysteine proteases produced by P. gingivalis, affects the intestinal barrier function. OMVs increased the permeability of the Caco-2 cell monolayer, a human intestinal epithelial cell line, accompanied by degradation of the tight junction protein occludin. In contrast, OMVs prepared from mutant strains devoid of gingipains failed to induce intestinal barrier dysfunction or occludin degradation in Caco-2 cells. A close histological examination revealed the intracellular localization of gingipain-carrying OMVs. Gingipain activity was detected in the cytosolic fraction of Caco-2 cells after incubation with OMVs. These results suggest that gingipains were internalized into intestinal cells through OMVs and transported into the cytosol, where they then directly degraded occludin from the cytosolic side. Thus, P. gingivalis OMVs might destroy the intestinal barrier and induce systemic inflammation via OMV itself or intestinal substances leaked into blood vessels, causing various diseases.
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•OMVs from Porphyromonas gingivalis increased permeability of Caco-2 monolayer.•Gingipains on OMVs is responsible for destruction of Caco-2 cell barrier.•Gingipains on OMVs degraded tight junction protein, occludin.•Porphyromonas gingivalis OMVs deliver gingipains into cytosol in Caco-2 cells.
Numerous studies have suggested that the titers of antibodies against SARS-CoV-2 are associated with the COVID-19 severity, however, the types of antibodies associated with the disease maximum ...severity and the timing at which the associations are best observed, especially within one week after symptom onset, remain controversial. We attempted to elucidate the antibody responses against SARS-CoV-2 that are associated with the maximum severity of COVID-19 in the early phase of the disease, and to investigate whether antibody testing might contribute to prediction of the disease maximum severity in COVID-19 patients. We classified the patients into four groups according to the disease maximum severity (severity group 1 (did not require oxygen supplementation), severity group 2a (required oxygen supplementation at low flow rates), severity group 2b (required oxygen supplementation at relatively high flow rates), and severity group 3 (required mechanical ventilatory support)), and serially measured the titers of IgM, IgG, and IgA against the nucleocapsid protein, spike protein, and receptor-binding domain of SARS-CoV-2 until day 12 after symptom onset. The titers of all the measured antibody responses were higher in severity group 2b and 3, especially severity group 2b, as early as at one week after symptom onset. Addition of data obtained from antibody testing improved the ability of analysis models constructed using a machine learning technique to distinguish severity group 2b and 3 from severity group 1 and 2a. These models constructed with non-vaccinated COVID-19 patients could not be applied to the cases of breakthrough infections. These results suggest that antibody testing might help physicians identify non-vaccinated COVID-19 patients who are likely to require admission to an intensive care unit.
Several types of laboratory tests for COVID-19 have been established to date; however, the clinical significance of the serum SARS-CoV-2 nucleocapsid (N) antigen levels remains to be fully ...elucidated. In the present study, we attempted to elucidate the usefulness and clinical significance of the serum N antigen levels.
We measured the serum N antigen levels in 391 serum samples collected from symptomatic patients with a confirmed diagnosis of COVID-19 and 96 serum samples collected from patients with non-COVID-19, using a fully automated chemiluminescence immunoassay analyzer.
Receiver operating characteristic analysis identified the optimal cutoff value of the serum N antigen level (cutoff index, based on Youden's index) as 0.255, which yielded a sensitivity and specificity for the diagnosis of COVID-19 of 91.0 and 81.3%, respectively. The serum N antigen levels were significantly higher in the patient groups with moderate and severe COVID-19 than with mild disease. Moreover, a significant negative correlation was observed between the serum N antigen levels and the SARS-CoV-2 IgG antibody titers, especially in patients with severe COVID-19.
Serum N antigen testing might be useful both for the diagnosis of COVID-19 and for obtaining a better understanding of the clinical features of the disease.
Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In ...particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio HR, 1.15 95% CI, 1.03–1.27, P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 95% CI, 1.19–2.25, P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 95% CI, 1.02–2.86, P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.
Abstract
A prototype Dual Gain Multilayer Thick Gas Electron Multiplier (DG-M-THGEM) with an active area of 10 cm × 10 cm was manufactured aiming at the production of a large-volume active-target ...time projection chamber which can work under the condition of high-intensity heavy-ion beam injections. The DG-M-THGEM has an alternating structure of electrodes and insulators. Effective gas gains of two regions, which are called beam and recoil regions, are separately controlled. Performance of the prototype DG-M-THGEM in hydrogen gas at a pressure of 40 kPa was evaluated. Irradiating a 132Xe beam, an effective gas gain lower than 100 with a charge resolution of 3% was achieved in the beam region while an effective gas gain of 2000 was maintained in the recoil region. Position distributions of measured charges along the beam axis were investigated in order to evaluate gain uniformity in the high-intensity beam injection. The gain shift was estimated by simulations considering space charges in the drift region. The gain shift was suppressed within 3% even at the beam intensity of 2.5 × 106 particles per second.
Aims
The impacts of high density lipoprotein cholesterol (HDL‐C) as an anti‐inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At ...present, the clinical significance of the HDL‐C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown.
Methods and results
We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow‐up duration was 420 ± 346 days. All‐cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all‐cause death (odds ratio = 1.84, 95% CI: 1.06–3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36–6.01, P = 0.003). HDL‐C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta‐coefficient = −0.085, P = 0.034 and standardized beta‐coefficient = 0.081, P = 0.044, respectively).
Conclusions
HDL‐C/CRP ratio was a useful marker for predicting all‐cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.
We performed the immunophenotyping of 101 patients with B‐cell non‐Hodgkin's lymphoma (B‐NHL) using two‐colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of ...T‐cell‐associated antigen (T‐Ag; CD2, CD5, CD7) in 25 patients (24·8%). Among these three T‐Ags, CD5 was the most frequently expressed, in 21 patients (20·8%), followed by CD7, expressed in five patients (5·0%), and CD2, which was expressed in two patients (2·0%). Two kinds of T‐Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T‐Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T‐Ag‐positive B‐NHL (T‐Ag(+) B‐NHL) who were analysed. When comparing the clinical features between T‐Ag(+) B‐NHL and T‐Ag‐negative B‐NHL (T‐Ag(–) B‐NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0·0119 and P = 0·0302 respectively).
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