Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

Jejuketomycins A and B,polyketide glycosides with cancer cell migration inhibitory activity from Streptomyces sp. KCB15JA151

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data. Compounds 1 and 2 possess an unusual 6/6/8 tricyclic ring system. Biological evaluation with the wound healing assay and time-lapse cell tracking analysis revealed that compounds 1 and 2 have significant inhibitory activities against cancer cell migration with low cytotoxicity.

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151.     

The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175

Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB⁺Iba1⁺ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB⁺CD11c⁺ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.     

Impact of the COVID-19 Pandemic on Patient Delay and Clinical Outcomes for Patients With Acute Myocardial Infarction

BackgroundIt has been known that the fear of contagion during the coronavirus disease 2019 (COVID-19) creates time delays with subsequent impact on mortality in patients with acute myocardial infarction (AMI). However, difference of time delay and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI between the COVID-19 pandemic and pre-pandemic era has not been fully investigated yet in Korea. The aim of this study was to investigate the impact of COVID-19 pandemic on time delays and clinical outcome in patients with STEMI or non-STEMI compared to the same period years prior.MethodsA total of 598 patients with STEMI (n = 195) or non-STEMI (n = 403) who underwent coronary angiography during the COVID-19 pandemic (February 1 to April 30, 2020) and pre-pandemic era (February 1 to April 30, 2017, 2018, and 2019) were analyzed in this study. Main outcomes were the incidence of time delay, cardiac arrest, and in-hospital death.ResultsThere was 13.5% reduction in the number of patients hospitalized with AMI during the pandemic compared to pre-pandemic era. In patients with STEMI, door to balloon time tended to be longer during the pandemic compared to pre-pandemic era (55.7 ± 12.6 minutes vs. 60.8 ± 13.0 minutes, P = 0.08). There were no significant differences in cardiac arrest (15.6% vs. 10.4%, P = 0.397) and in-hospital mortality (15.6% vs. 10.4%, P = 0.397) between pre-pandemic and the pandemic era. In patients with non-STEMI, symptom to door time was significantly longer (310.0 ± 346.2 minutes vs. 511.5 ± 635.7 minutes, P = 0.038) and the incidence of cardiac arrest (0.9% vs. 3.5%, P = 0.017) and in-hospital mortality (0.3% vs. 2.3%, P = 0.045) was significantly greater during the pandemic compared to pre-pandemic era. Among medications, angiotensin converting enzyme inhibitors/angiotensin type 2 receptor blockers (ACE-I/ARBs) were underused in STEMI (64.6% vs. 45.8%, P = 0.021) and non-STEMI (67.8% vs. 57.0%, P = 0.061) during the pandemic.ConclusionDuring the COVID-19 pandemic, there has been a considerable reduction in hospital admissions for AMI, time delay, and underuse of ACE-I/ARBs for the management of AMI, and this might be closely associated with the excess death in Korea.     

Comparative toxicity of silicon dioxide,silver and iron oxide nanoparticles after repeated oral administration to rats

Although silicon dioxide (SiO₂), silver (Ag) and iron oxide (Fe₂O₃) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well‐dispersed nanoparticles were orally administered to Sprague–Dawley rats daily over a 13‐week period. Based on the results of an acute toxicity and a 14‐day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg^–1 were selected as the highest dose of the SiO₂, Ag and Fe₂O₃ nanoparticles, respectively, for the 13‐week repeated oral toxicity study. The SiO₂ and Fe₂O₃ nanoparticles did not induce dose‐related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg^–1, respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO₂ and Fe₂O₃ nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle‐treated group significantly increased with a positive and/or dose‐related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form. Copyright © 2015 John Wiley & Sons, Ltd.