Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Low-cost, high-yield production of graphene nanosheets (GNs) is essential for practical applications. We have achieved high yield of edge-selectively carboxylated graphite (ECG) by a simple ball ...milling of pristine graphite in the presence of dry ice. The resultant ECG is highly dispersable in various solvents to self-exfoliate into single-and few-layer (<5 layers) GNs. These stable ECG (or GN) dispersions have been used for solution processing, coupled with thermal decarboxylation, to produce large-area GN films for many potential applications ranging from electronic materials to chemical catalysts. The electrical conductivity of a thermally decarboxylated ECG film was found to be as high as 1214 S/cm, which is superior to its GO counterparts. Ball milling can thus provide simple, but efficient and versatile, and eco-friendly (CO₂-capturing) approaches to low-cost mass production of high-quality GNs for applications where GOs have been exploited and beyond.
In 21 consecutive patients with confirmed Covid-19, the median times from symptom onset to negative viral culture and negative real-time RT-PCR were 7 days and 34 days, respectively. The longest ...interval from symptom onset and from resolution of fever to positive culture was 12 days and 3 days, respectively.
The increasing influx into Australia of (im)migrants whose first language is not English has made Australia linguistically more diverse than ever. Despite this, Australia remains a strongly ...Anglocentric nation, and migrants, in response, tend to abandon their heritage languages (HL) and shift to English relatively quickly. Korean migrants in Australia buck this trend, as they show a relatively high level of language maintenance. The Australian Korean community, nevertheless, experiences a language shift to English among different generations, and a sharp decline in the rate of high school students enrolled in Korean community language schools. The present study expands existing accounts of HL maintenance in Australia. Specifically, drawing on interviews with six Korean-speaking children, it compares the views about the HL of primary and secondary school students. In line with language ideologies (Kroskrity 2004. "Language Ideologies." In A Companion to Linguistic Anthropology, edited by A. Duranti, 496-517. Malden, MA: Blackwell.; Woolard 1998. "Language Ideology as a Field of Inquiry." In Language Ideologies: Practice and Theory, edited by B. B. Schieffelin, K. A. Woolard, and P. V. Kroskrity, 20-86. New York: Oxford University Press.), data analysis and interpretation employ positioning theory (Davies and Harré 1990. "Positioning: The Discursive Production of Selves." Journal for the Theory of Social Behaviour 20 (1): 43-63.). A key finding is that their ideologies around the HL vary by school age. The comparison also suggests that their language ideologies are associated with the domains where they practise their HL, and the ways they position themselves. The study contributes to a dynamic understanding of multilingualism and HL education in a multicultural society.
Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA‐binding C‐domain in RPA1, which mediates DNA metabolic ...processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen‐activated protein kinase (MAPK)/p53 in non‐small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA‐damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage‐induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti‐tumor efficacy. Thus, hNoxin is a DNA damage‐induced anti‐apoptotic protein and potential therapeutic target in cancer.
What's new?
Noxin was previously identified in mice as a stress‐induced gene that may be an important component of the defense machinery of stressed cells. Here, the authors identified human Noxin as a novel cancer‐specific gene whose expression is cell cycle‐regulated and induced by ultraviolet radiation. Knockdown of hNoxin induced apoptosis of A549 cancer cells via p38 MAPK/p53 signaling. Overexpression of hNoxin suppressed DNA damage‐induced apoptosis. These data suggest that hNoxin has anti‐apoptotic activity that protects cancer cells against DNA damage. Knockdown of hNoxin reduced tumor growth in a mouse xenograft model, suggesting that hNoxin is a potential therapeutic target in cancer.
Background The role of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) is still unclear in patients with acute myocardial infarction acute myocardial infarction. This ...study aimed to evaluate the long-term impact of IVUS-guided PCI in patients with acute myocardial infarction. Methods and Results Among a total of 13 104 patients with acute myocardial infarction, enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health, we selected patients who underwent PCI with second-generation drug-eluting stent implantation. The primary outcome was the risk of target lesion failure at 3 years. Among the study population, 1887 patients (21.0%) underwent IVUS-guidance, and 7120 patients (79.0%) underwent angiography-guidance for second-generation drug-eluting stent implantation. IVUS-guided PCI was associated with a significantly lower risk of target lesion failure at 3 years (4.8% versus 8.0%; hazard ratio HR, 0.59; 95% CI, 0.47 to 0.73;
<0.001) compared with angiography-guided PCI. The difference was driven mainly by a lower risk of cardiac death and target vessel myocardial infarction. The results were consistent after confounder adjustment by multiple sensitivity analyses. Moreover, quartile analysis of volume of IVUS use showed that higher IVUS use was associated with a decreased risk of 3-year target lesion failure (adjusted HR, 0.58; 95% CI, 0.45 to 0.75;
<0.001 for quartile 1 versus 4;
<0.001 for trend comparison across all quartiles). Conclusions In patients with acute myocardial infarction who underwent PCI with second-generation drug-eluting stent implantation, the use of IVUS guidance was associated with a significant reduction in 3-year target lesion failure, mainly driven by hard end points, such as cardiac death and target vessel myocardial infarction.
Background Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on ...left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. Methods A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis). Results The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group. Conclusions Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption. Keywords: Heart failure, Diabetes mellitus, Sodium-glucose cotransporter 2 inhibitor, Left ventricular diastolic function
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
Previous studies analyzing intrapartum fever by dichotomization of fever just above 38.0°C or not may lead to overlook clinical significance of borderline fever. We aimed to investigate the ...maternal baseline and intrapartum characteristics, neonatal outcomes, and inflammatory placental pathology in relation to the degree of intrapartum fever by three group analysis.
Methods
We performed a retrospective analysis of consecutive singleton deliveries between 370/7 to 410/7 weeks divided into three groups based on the peak body temperature during labor: No fever (< 37.5°C), borderline fever (≥ 37.5°C and < 38.0°C), and overt fever (≥ 38.0°C). Maternal and intrapartum characteristics, neonatal outcomes, and inflammatory placental pathology were compared by trend analysis, intergroup difference analysis, and multivariable analysis.
Results
The degree of intrapartum fever was significantly associated with younger maternal age, nulliparity, longer duration of rupture of membrane, and epidural analgesia (p < 0.001). And the incidence of neonatal proven sepsis and mortality were not significantly different among the groups. The degree of intrapartum fever was associated with the stage of acute chorioamnionitis and funisitis (p < 0.001). Multivariate analysis revealed that the association with epidural analgesia was stronger in borderline fever than overt fever (adjusted odds ratio 95% confidence interval, borderline fever = 18.487 11.447–29.857; overt fever = 11.068 4.874–25.133) after controlling for maternal age, parity, induction or augmentation, duration of ROM, birth weight, and meconium staining.
Conclusion
Our data support that both epidural analgesia and inflammation of the placenta may contribute to the development of intrapartum fever at term.
Preeclampsia is one of the most serious complications of pregnancy, affecting 5-10% of parturients worldwide. Recent studies have suggested that autophagy is involved in trophoblast invasion and may ...be associated with defective placentation underlying preeclampsia. We thus aimed to understand the mechanistic link between autophagy and trophoblast invasion. Using the two most commonly used trophoblast cell lines, JEG-3 and HTR-8/SVneo, we inhibited autophagy by ATG5 and beclin-1 shRNA. Conversion of LC3-II was evaluated in ATG5 and beclin-1 knock-down cells in the presence of the lysosomal protease inhibitors E-64d and pepstatin A, to detect the efficiency of autophagy inhibition. Upon autophagy inhibition, we measured cell invasion, activity of NF-κB and related signaling pathways, MMP-2, MMP-9, sFlt-1, and TNF-α levels. Autophagy inhibition increased the invasiveness of these trophoblastic cell lines and increased Akt and NF-κB activity as well as p65 expression. Of note, an NF-κB inhibitor significantly attenuated the trophoblast invasion induced by autophagy inhibition. Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-α. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-κB pathway and MMP-2, MMP-9, sFlt-1 and TNF-α levels are affected.
Background Although intravascular ultrasound (IVUS) has been widely used for complex lesions during coronary intervention, IVUS for stenting at bifurcation lesions has not been sufficiently assessed. ...The aim of this study was to investigate the impact of IVUS guidance on long-term clinical outcomes during drug-eluting stent (DES) implantation for bifurcation lesions. Methods The Korean multicenter bifurcation registry listed 1,668 patients with non-left main de novo bifurcation lesions who underwent DES implantation between January 2004 and June 2006. Using propensity score matching with clinical and angiographic characteristics, 487 patients with IVUS guidance and 487 patients with angiography guidance were selected. The long-term clinical outcomes were compared between the 2 groups. Results Baseline clinical and angiographic characteristics were well matched and showed no significant differences between the 2 groups. Two-stent technique and final kissing ballooning angioplasty were more frequently performed in the IVUS-guided group. Maximal stent diameters at both the main vessel and the side branch were larger in the IVUS-guided group. Periprocedural creatine kinase–MB elevation (>3 times of upper normal limits) was frequently observed in the angiography-guided group. The incidence of death or myocardial infarction was significantly lower in the IVUS-guided group compared to the angiography-guided group (3.8% vs 7.8%, log rank test P = .03, hazard ratio 0.44, 95% CI 0.12-0.96, Cox model P = .04). Conclusions Intravascular ultrasound guidance during DES implantation at bifurcation lesions may be helpful to improve long-term clinical outcomes by reducing the occurrence of death or myocardial infarction.
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