Glycyrrhizic acid (GA), a triterpene isolated from the roots and rhizomes of licorice, named Glycyrrhiza glabra, is the principal bioactive ingredient of anti-viral, anti-inflammatory and ...hepatoprotective effects. GA has been used in the clinical treatment of hepatitis, bronchitis, gastric ulcer, AIDS (acquired immunodeficiency syndrome), certain cancers and skin diseases. It has a direct effect on anti-HBV (hepatitis B virus) via affecting the HBsAg (hepatitis B surface antigen) to extracellular secretion, improving liver dysfunction in patients with chronic hepatitis B, and ultimately improving the immune status of HBV. GA can significantly inhibit the proliferation of HIV, showing an immune activation. The clinical application of GA on the prevention and treatments of various diseases may derive from its numerous pharmacological properties. This review provides the summary of the antiviral effects of GA on research progress and mechanism in recent years.
Inspired by metabolic processes in biological systems, animal blood as a biowaste rich in biological enzymes with molecular Fe-N centers was successfully explored to produce an efficient ...electrocatalyst with single atomic Fe-N-C active sites for oxygen reduction reaction.
The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor ...(EGFR) and overall survival (OS) in NSCLC patients with brain metastases.
Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017.
4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method.
This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous studies implied that dietary isoflavone intake may reduce the risk of developing breast cancer, but some have shown ambiguous results. This study aimed to systematically evaluate and ...summarize available evidence on the effect dietary isoflavone intake has on the risk of developing breast cancer.
PubMed, Embase, and the Cochrane Library were searched for prospective cohort studies published through April 2017 that evaluated the effect of dietary isoflavone intake on the development of breast cancer.
Sixteen prospective cohort studies, involving 11,169 breast cancer cases and 648,913 participants, were identified and included in our data analysis. The pooled relative risk (RR) of breast cancer was 0.99 for high versus low intake of isoflavones (95% confidence interval CI, 0.91–1.09; P = 0.876) and 0.99 for moderate versus low intake of isoflavones (95%CI, 0.92–1.05; P = 0.653), with insignificant heterogeneity (P = 0.187 for high versus low, and P = 0.192 for moderate versus low). While a moderate consumption of soy-based foods did not significantly affect breast cancer risk, a high intake of soy-based foods associated with a lower risk of developing breast cancer. Considering specific foods, an increased the risk of developing breast cancer was seen with a moderate intake of formononetin, but no significant associations were found between breast cancer risk and other isoflavone-rich diets.
The present meta-analysis indicates that women with a high dietary intake of soy foods may experience a statistically significant reduction in breast cancer risk. However, moderate formononetin consumption may increase the risk of developing breast cancer.
Histone deacetylase (HDAC) inhibitors are promising anti-fibrosis drugs; however, nonselective inhibition of class I and class II HDACs does not allow a detailed elucidation of the individual HDAC ...functions in renal fibrosis. In this study, we investigated the effect of MS-275, a selective class I HDAC inhibitor, on the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO) and activation of cultured renal interstitial fibroblasts.
The UUO model was established by ligation of the left ureter and the contralateral kidney was used as a control. At seven days after UUO injury, kidney developed fibrosis as indicated by deposition of collagen fibrils and increased expression of collagen I, fibronectin and alpha-smooth muscle actin (alpha-SMA). Administration of MS-275 inhibited all these fibrotic responses and suppressed UUO-induced production of transforming growth factor-beta1 (TGF-beta), increased expression of TGF-beta receptor I, and phosphorylation of Smad-3. MS-275 was also effective in suppressing phosphorylation and expression of epidermal growth factor receptor (EGFR) and its downstream signaling molecule, signal transducer and activator of transcription-3. Moreover, class I HDAC inhibition reduced the number of renal tubular cells arrested in the G2/M phase of the cell cycle, a cellular event associated with TGF-beta1overproduction. In cultured renal interstitial fibroblasts, MS-275 treatment inhibited TGF-beta induced phosphorylation of Smad-3, differentiation of renal fibroblasts to myofibroblasts and proliferation of myofibroblasts.
These results demonstrate that class I HDACs are critically involved in renal fibrogenesis and renal fibroblast activation through modulating TGF-beta and EGFR signaling and suggest that blockade of class I HDAC may be a useful treatment for renal fibrosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anchoring transition metal (TM) atoms on suitable substrates to form single‐atom catalysts (SACs) is a novel approach to constructing electrocatalysts. Graphdiyne with sp−sp2 hybridized carbon atoms ...and uniformly distributed pores have been considered as a potential carbon material for supporting metal atoms in a variety of catalytic processes. Herein, density functional theory (DFT) calculations were performed to study the single TM atom anchoring on graphdiyne (TM1−GDY, TM=Sc, Ti, V, Cr, Mn, Co and Cu) as the catalysts for CO2 reduction. After anchoring metal atoms on GDY, the catalytic activity of TM1−GDY (TM=Mn, Co and Cu) for CO2 reduction reaction (CO2RR) are significantly improved comparing with the pristine GDY. Among the studied TM1−GDY, Cu1−GDY shows excellent electrocatalytic activity for CO2 reduction for which the product is HCOOH and the limiting potential (UL) is −0.16 V. Mn1−GDY and Co1−GDY exhibit superior catalytic selectivity for CO2 reduction to CH4 with UL of −0.62 and −0.34 V, respectively. The hydrogen evolution reaction (HER) by TM1−GDY (TM=Mn, Co and Cu) occurs on carbon atoms, while the active sites of CO2RR are the transition metal atoms . The present work is expected to provide a solid theoretical basis for CO2 conversion into valuable hydrocarbons.
BackgroundPast studies have found a strong relationship between alcohol drinking and human health.MethodsIn this study, we first tested the association of rs671 with alcohol use in 2349 participants ...in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis.ResultsWe found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship.ConclusionsCompared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.
Summary Background Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose ...dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. Methods We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn , number ChiCTR-TRC-10000802. Findings Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 9% of 350 patients) than in the placebo group (79 23% of 350 patients; odds ratio OR 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 18% of 350 patients) than with dexmedetomidine (34 10% of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 14% of 350 patients) than in patients given dexmedetomidine (23 7% of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. Interpretation For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Funding Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its ...effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml). Cell cytotoxicity, apoptosis, mitochondrial respiration, and mitochondrial permeability transition pore (mPTP) were determined. Western blotting was employed to determine active-caspase 3, annexin V, and HDAC4 expression. As compared to wild type H9c2 group, HDAC4 overexpression remarkably led to a great increase in cell death as evident by the increased lactate dehydrogenase (LDH) leakage, ratio of caspase-3-positive cells as well as the upregulated levels of active-caspase 3 and annexin V shown by western blot analysis. In addition, HDAC4 overexpression also induced much severe mitochondrial dysfunction, as indicated by apoptotic mitochondria and increased mPTP. However, irisin treatment significantly attenuated all of these effects. Though irisin treatment did not influence the expression of HDAC4 at the transcriptional level, western blot analysis showed that HDAC4 protein levels decreased in a time-dependent way after administration of irisin, which is associated with the degradation of HDAC4 mediated by small ubiquitin-like modification (SUMO). Our results are the first to demonstrate that the protective effects of irisin in cardiomyoblasts exposed to hypoxia/reoxygenation might be associated with HDAC4 degradation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Golden 2-Like (G2-like) transcription factors play an important role in plant development. However, the roles of these G2-like regulatory genes in response to abiotic stresses in tomato are not well ...understood.
In this study, we identified 66 putative G2-like genes in tomato (Solanum lycopersicum) and classified them into 5 groups (I to V) according to gene structure, motif composition and phylogenetic analysis. The G2-like genes were unevenly distributed across all 12 chromosomes. There were nine pairs of duplicated gene segments and four tandem duplicated SlGlk genes. Analysis of the cis-regulatory elements (CREs) showed that the promoter regions of SlGlks contain many kinds of stress- and hormone-related CREs. Based on RNA-seq, SlGlks were expressed in response to three abiotic stresses. Thirty-six differentially expressed SlGlks were identified; these genes have multiple functions according to Gene Ontology (GO) analysis and are enriched mainly in the zeatin biosynthesis pathway. Further studies exhibited that silencing SlGlk16 in tomato would reduce drought stress tolerance by earlier wilted, lower superoxide dismutase (SOD), peroxidase (POD) activities, less Pro contents and more MDA contents.
Overall, the results of this study provide comprehensive information on G2-like transcription factors and G2-like genes that may be expressed in response to abiotic stresses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK