Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data ...manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145–5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145–5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145–5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future.
Proposed signaling mechanism of dioscin on restoring MTX-induced liver and kidney damages via regulating miR-145-5p-mediated oxidative stress. Dioscin up-regulated Sirt5 level by down-regulating miR-145–5p level to adjust the expression levels of Nrf2, HO-1, GCLC, NQO1, Gst, SOD1 and Keap1. Dioscin protected hepatorenal damages caused by MTX via regulating miR-145-5p-mediated oxidative stress. Display omitted
•Dioscin significantly relieved MTX-induced hepatorenal damages in vitro and in vivo.•MTX caused oxidative damages to the liver and kidney in vitro and in vivo.•miR-145–5p directly targeted Sirt5 to adjust oxidative stress.•Dioscin reduced the expression levels of miR-145–5p and suppressed w miR-145-5p-medicated oxidative stress.
Summary
Background
Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD).
Objectives
To determine the risk of CKD in patients ...with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis.
Methods
We identified 4344 patients with psoriasis for the study cohort and randomly selected 13 032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD.
Results
After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow‐up period hazard ratio (HR) 1·28; 95% confidence interval (CI) 1·14–1·44. The increased incidence of GN in patients with psoriasis (HR 1·50, 95% CI 1·24–1·81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1·62 vs. 1·26). Among drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1·69, 95% CI 1·14–2·49).
Conclusions
Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.
What's already known about this topic?
There is an increased risk of multiple comorbidities in patients with psoriasis.
What does this study add?
Both mild and severe psoriasis presented an increased risk of chronic kidney disease (CKD) and glomerulonephritis, independent of traditional risk factors for CKD.
The development of CKD in patients with psoriasis was multifaceted. High severity, psoriatic arthritis involvement and concomitant nonsteroidal anti‐inflammatory drug use further increased the risk of CKD in patients with psoriasis.
Compared with other nanofiber fabrication processes, electrospinning is versatile and superior in production and construction of ordered or more complex nanofibrous assemblies. Besides traditional ...two-dimensional (2D) nanofibrous structures, electrospinning is powerful in fabrication of three-dimensional (3D) fibrous macrostructures, especially for tissue engineering applications. This article summarizes and reviews recent advances in various promising and cutting-edge electrospinning techniques, including multilayering electrospinning, post-processing after electrospinning, liquid-assisted collection, template-assisted collection, porogen-added electrospinning, and self-assembly. And their formation mechanisms, features, and the challenges of electrospinning have also been discussed. Furthermore, these 3D nanofibrous macrostructures have been demonstrated to have potential applications in tissue engineering, energy harvesting and storage, and filtration.
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•HI/R injury significantly decreased the expression level of miR-142-3p.•miR-142-3p alleviated apoptosis and inflammation to relieve HI/R injury.•miR-142-3p directly targeted ...MARCKS.•MARCKS siRNA markedly inhibited HI/R injury.
MiR-142-3p as one key molecule in oncogenesis and inflammation plays crucial roles in hepatic fibrosis, hepatocellular carcinoma and other liver disease. However, there have no literatures to report its effects on hepatic ischemia-reperfusion (HI/R) injury. In the present work, hypoxia reoxygenation (H/R) models on AML12 and HepG2 cells, and ischemia/reperfusion model in mice were established. The methods of real-time PCR, dual luciferase reporter, mimic, inhibitor, agomir, antagomir and siRNA transfection assays were used. The expression levels of miR-142-3p were decreased in model groups in vitro and in vivo compared with control group or Sham group, which directly targeted MARCKS to regulate its expression. Then, MARCKS activated p38/JNK signal, up-regulated NF-κB expression to accelerate inflammation, and inhibited PI3K/AKT signal to promote apoptosis. Moreover, miR-142-3p mimic in vitro and agomir in vivo lowered the expression levels of MARCKS, thereby alleviating apoptosis and inflammation to relieve HI/R injury. Furthermore, miR-142- 3p inhibitor in vitro and antagomir in vivo up-regulated the expression levels of MARCKS to aggravate HI/R damage via promoting inflammation and apoptosis. Consistently, MARCKS siRNA markedly inhibited HI/R injury by restraining apoptosis and inflamm- ation in mice. MiR-142-3p played a considerable part in adjusting HI/R injury by targeting MARCKS, and miR-142-3p/MARCKS should be a new therapeutic target for HI/R injury.
Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. ...Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.
Summary
Although millions of people receive antithrombotic agents (ATAs) or anticoagulating agents (ACAs) for vascular prophylaxis daily, the negative impact of these agents on sexual function has ...not been systematically studied. Therefore, a literature search was conducted to determine the effects of the marketed ATAs and ACAs on sexual function. In regard to men, the results show that thienopyridine derivatives increase the risk of erectile dysfunction (ED) and decrease libido and sexual function. The relationship between aspirin use and ED is inconsistent, ranging from a moderate risk to beneficial effects. Nonetheless, aspirin appears to result in a lower risk for ED than does clopidogrel, and seems to benefit patients with lithium‐induced ED. Coumarin can cause vasculogenic priapism. In regard to women, only a single report of genital haemorrhage was found. Available data exclusively focus on male subjects. Taken together, ATAs and ACAs can disturb sexual function in different aspects in men. Newer thienopyridine derivatives, such as prasugrel or ticagrelor, may be used as a substitute for clopidogrel when sexual dysfunction occurs. Priapism and genital haemorrhage were found to be uncommon but serious complications of ACA treatment. Additional studies examining the effects of ATAs and ACAs on sexual function are needed, especially in woman and elderly.
Data on the efficacy and safety of sorafenib in combination with transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) are lacking.
In this multicenter ...retrospective study, 222 consecutive HCC patients receiving combination therapy were enrolled between June 2008 and July 2011.
Chronic hepatitis B was the predominant cause of HCC (86%). Eighty percent patients were at Barcelona Clinic Liver Cancer (BCLC) stage C, and 86% patients were in Child-Pugh (CP) A class. The overall median survival was 12 months (95% CI 10.1–13.9). The overall incidence of adverse events (AEs) was 87%. In 177 BCLC-C patients, performance status, the number of HCC nodules, Child-Pugh score and macrovascular invasion were significantly associated with overall survival (OS) and were included in the final risk scores (R), where R = 5 × (vascular invasion: 0 if no, 1 yes) + 6 × (CP: 0 if A, 1 if B) + 7 × (no. of lesions: 0 if 1–2, 1 ≥3) + 8 × ( Eastern Cooperative Oncology Group, ECOG: 0 if 0, 1 ≥1).
Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.
Al-Zn-Cu-Mg alloys (e.g., AA7075) have been widely used to form structural components in aerospace and other industries. For Al-Zn-Cu-Mg alloys, although dynamic recovery was dominant in hot ...deformation, dynamic recrystallization also occurred frequently, such as continuous dynamic recrystallization (CDRX), for which various mechanisms were found, e.g. subgrain boundary migration, subgrain coalescence, and subgrain rotation. However for the as-extruded AA7075 alloy subjected to hot compression, the mechanisms of CDRX process and model for it are lacking. In this paper by conducting thermal simulation compression tests combined with electron back scattered diffraction (EBSD) experiments, a continuous dynamic recrystallization (CDRX) process during the hot deformation of the as-extruded Al-Zn-Cu-Mg alloy (AA7075) is revealed based on the analysis on deformation behavior and characteristics of the recrystallized microstructures. It was found that subgrains, which were formed through dynamic recovery (DRV), rotated by absorbing dislocations into its boundaries, and resulted in the formation of the recrystallized grains. Then based on the explored CDRX mechanism, the dislocation density, subgrain boundary area, recrystallized grain boundary area, high angle grain boundary area and subgrain boundary misorientation were determined as internal-state-variables, and a continuous dynamic recrystallization model for AA7075 alloy was developed. In the established model, the process of subgrain rotation was described by introducing subgrain boundary stored energy, which related to dislocation density, subgrain size and misorientation. Finally, the continuous dynamic recrystallization model was combined with a constitutive model for the unified prediction of the flow stress and the microstructure evolution during the hot deformation of AA7075. Predictions of the model are in good agreement with the experimental ones.
•CDRX occurred during hot compression of as-extruded Al-Zn-Cu-Mg alloy (AA7075).•Subgrain formed in DRV and rotated by absorbing dislocations to result in HABs and CDRX.•CDRX was modeled based on ISV and combined with constitutive model for unified prediction.•Subgrain rotation was modeled by introducing subgrain stored energy.
The phylum Cnidaria represents a close outgroup to Bilateria and includes familiar animals including sea anemones, corals, hydroids, and jellyfish. Here we report genome sequencing and assembly for ...true jellyfish Sanderia malayensis and Rhopilema esculentum. The homeobox gene clusters are characterised by interdigitation of Hox, NK, and Hox-like genes revealing an alternate pathway of ANTP class gene dispersal and an intact three gene ParaHox cluster. The mitochondrial genomes are linear but, unlike in Hydra, we do not detect nuclear copies, suggesting that linear plastid genomes are not necessarily prone to integration. Genes for sesquiterpenoid hormone production, typical for arthropods, are also now found in cnidarians. Somatic and germline cells both express piwi-interacting RNAs in jellyfish revealing a conserved cnidarian feature, and evidence for tissue-specific microRNA arm switching as found in Bilateria is detected. Jellyfish genomes reveal a mosaic of conserved and divergent genomic characters evolved from a shared ancestral genetic architecture.
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