Thoracic aorta pseudoaneurysm with hemopericardium: unusual presentation of warfarin overdose

There have been few case reports which discuss a relationship between warfarin overdose and aortic pseudoaneurysm leakage. We report the case of a female receiving warfarin who presented with dsypnea. Her international normalized ratio was > 10. Chest radiograph revealed cardiomegaly, and chest computed tomography (CT) showed a bulging pouch-like lesion below the aortic arch greater than 6x6 cm in size and a fluid collection suggesting blood in the pericardium. Thoracic endovascular aneurysm repair (TEVAR) was successfully performed by a cardiovascular surgeon. Aortic pseudoaneurysm formation and leakage may be considered as a rare complication in patients receiving warfarin therapy. Further study regarding warfarin use and the incidence of pseudoaneurysm leakage is needed

Pulmonary Hilar Tumor: An Unusual Presentation of Sclerosing Hemangioma

Pulmonary sclerosing hemangioma is an uncommon benign tumor of the lung; however, on rare occasions it can arise from the pulmonary hilar region. Herein, we report a 53-year-old female patient who presented with a round opacity in the right upper lung field on a radiograph. Chest computed tomography scanning revealed a 3.1 cm mass in the right pulmonary hilum. Thoracoscopic tumor excision was subsequently performed. On pathohistologic study, the tumor was well defined and composed of round stromal cells and surface cells arranged in a papillary, sclerotic, solid, and hemorrhagic pattern. In immunochemical study, the round cells were positive for thyroid transcription factor-1 (TTF-1) and epithelial membrane antigen (EMA) and negative for cytokeratin. The surface cells were positive for TTF-1, EMA, and cytokeratin. Therefore, a final diagnosis of sclerosing hemangioma was confirmed. In conclusion, pulmonary sclerosing hemangioma is uncommon and rare in the pulmonary hilar region. CT scanning is useful to determine its benignity, although imaging features are not specific for a definite differential diagnosis from other pulmonary tumors. Therefore, tissue diagnosis is usually necessary, and pulmonary sclerosing hemangioma should be listed in the differential diagnoses of pulmonary hilar tumors

Targeting Chondroitin Sulfate Reduces Invasiveness of Glioma Cells by Suppressing CD44 and Integrin β1 Expression

Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cancer progression and approaches for interrupting its functions in cancer cells remain largely unexplored. Here, we have found that CS was significantly enriched surrounding the vasculature in a subset of glioma tissues, which was akin to the perivascular niche for cancer-initiating cells. Silencing or overexpression of the major CS synthase, chondroitin sulfate synthase 1 (CHSY1), significantly regulated the glioma cell invasive phenotypes and modulated integrin expression. Furthermore, we identified CD44 as a crucial chondroitin sulfate proteoglycan (CSPG) that was modified by CHSY1 on glioma cells, and the suppression of CS formation on CD44 by silencing the CHSY1-inhibited interaction between CD44 and integrin β1 on the adhesion complex. Moreover, we tested the CS-specific binding peptide, resulting in the suppression of glioma cell mobility in a fashion similar to that observed upon the silencing of CHSY1. In addition, the peptide demonstrated significant affinity to CD44, promoted CD44 degradation, and suppressed integrin β1 expression in glioma cells. Overall, this study proposes a potential regulatory loop between CS, CD44, and integrin β1 in glioma cells, and highlights the importance of CS in CD44 stability. Furthermore, the targeting of CS by specific binding peptides has potential as a novel therapeutic strategy for glioma

An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2

Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcγ receptors (FcγR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE). Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs) against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP) mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R) DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT)-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines

Chronic obstructive pulmonary disease trajectory: severe exacerbations and dynamic change in health-related quality of life

Background The life trajectory of chronic obstructive pulmonary disease (COPD) remains unknown.Patients and methods We collected data from two populations. In the first cohort, we recruited 375 patients with COPD from our hospital, and 1440 repeated assessments of quality of life (QoL) using the European Quality of Life-5 Dimensions questionnaire from 2006 to 2020. We analysed their dynamic changes using the kernel-smoothing method. The second cohort comprised 27 437 patients from the National Health Insurance (NHI) dataset with their first severe acute exacerbations (AEs) requiring hospitalisation from 2008 to 2017 were analysed for their long-term course of AEs. We employed a Cox hazard model to analyse the predictors for mortality or AEs.Results Cohorts from our hospital and NHI were male predominant (93.6 and 83.5%, respectively). After the first severe AE, the course generally comprised three phases. The first was a 1-year period of elevated QoL, followed by a 2-year prolonged stable phase with a slowly declining QoL. After the second AE, the final phase was characterised by a rapid decline in QoL. For NHI cohort, 2712 died during the 11-year follow-up, the frequency of the first AE was approximately 5 per 10 000 per day. The median time from the first to the second AE was 3 years, which decreased to less than 6 and 3 months from 4th to 5th and 8th to 9th AE, respectively. The frequency of AE was increased 10-fold and 15-fold and risk of subsequent AE was increased 12-fold and 20-fold after the 6th and the 10th AE, relative to the first. Male gender, heart failure comorbidities were associated with the risk of subsequent AE and death.Conclusions The life trajectory of COPD includes the accelerated frailty phase, as well as elevated health and prolonged stable phase after the first AE

Screening of a phage-displayed peptide library with DB21-6 and DB39-2 mAbs.

<p>(A) After 3 rounds of biopanning, phage titers were increased by 12,871-fold (DB21-6) and 5,000-fold (DB39-2), respectively. (B) The immunopositive phage clones selected by DB21-6 and DB39-2 were identified by ELISA. NMIgG was used as a negative control.</p

ADE of DENV mediated by cross-reactive mAbs.

<p>(A) Infection of K562 cells with DENV1 (MOI = 1), DENV2 (MOI = 1), DENV3 (MOI = 5), or DENV4 (MOI = 1) in the presence of serially-diluted mAbs was examined at 72 hours post-infection by staining with 4G2 and RPE-conjugated goat anti-mouse IgG, followed by flow cytometry. The percentages of infected K562 cells are shown. Data shown are the mean ± standard error of the mean (SEM) from three independent experiments. (B) The indicated mAbs were serially diluted and incubated with DENV2 (MOI = 1 or 10) at 4°C for 1 hour. The mixtures were then added to THP-1 cells, and the infected cells were examined by flow cytometry at 72 hours post-infection. The infected cells were stained with hDB32-6 and RPE-conjugated goat anti-human IgG. The percentage of infected THP-1 cells is shown. NMIgG was used as a control. Data shown are the mean ± SEM from three independent experiments.</p

<i>In vitro</i> and <i>in vivo</i> neutralization assays of DENV2 with immunized sera.

<p>(A) Mice were immunized with vector, WT, or N8R plasmids at three-week intervals. After the 3^rd immunization, serum samples were collected and pooled for each immunized group. The immunized sera were evaluated by ELISA using plates containing C6/36 cells infected with DENV2 16681. The OD was measured at 490 nm. Data shown are from one representative experiment of two independent experiments. The <i>P</i> values (**<i>P</i><0.01, NS not significant) were analyzed using two-way ANOVA with Bonferroni <i>post-hoc</i> test. (B) After the 3^rd immunization, the pooled sera were serially diluted and incubated with DENV2 (MOI = 1) for 1 hour at 4°C. The mixtures were then used to infect BHK-21 cells. After 3 days, the cells were stained with 4G2, and analyzed by flow cytometry. Inhibition percentages are shown for the mean of an experiment conducted in triplicate. Data shown are from one representative experiment of two independent experiments. (C) Table showing titers conferring 50% inhibition against DENV2 infection. (D and E) After the 3^rd immunization, the pooled sera were serially diluted and incubated with 25-fold LD₅₀ of DENV2 for 0.5 hour at 4°C. Next, the mixtures were injected into ICR suckling mice by the intracerebral route (i.c.). The survival rates were recorded for 28 days. The number of animals tested for each immunized sera ranged from 4 to 16 per group. Kaplan-Meier survival curves and <i>P</i> values are shown (***<i>P</i><0.001, **<i>P</i><0.01, compared to vector-immunized sera). Data shown are from one representative experiment of two independent experiments.</p