Burnetteadamsen3015
IS, pCS, and IAA in nondialyzed patients with CKD. The interactions among uremic toxins and anti-inflammatory and proinflammatory pathways deserve more studies.
MLF1IP has been correlated with the progression and prognosis of a few tumors. However, the role of MLF1IP in colorectal cancer remains unclear. Here, we examined the expression and function of MLF1IP in colorectal cancer and investigated possible molecular mechanisms.
MLF1IP expressions in colorectal cancer tissues and cell lines were detected by quantitative real-time PCR, western blotting, and immunohistochemistry. In vitro and in vivo assays were performed to explore the function and underlying molecular mechanisms of MLF1IP in colorectal cancer.
The expression levels of MLF1IP were significantly up-regulated in colorectal cancer tissues and CRC cell lines (P<0.05). High expression of MLF1IP was significantly associated with TNM stage, T classification, lymph node involvement, distant metastasis, and poor patient survival (all P<0.05). Overexpressing MLF1IP promoted while silencing MLF1IP inhibited, the proliferation and clonogenicity of colorectal cancer cells and tumorigenicity in NOD/SCID mice (P<0.05). In addition, we demonstrated that the pro-proliferative effect of MLF1IP on colorectal cancer cells was associated with mediating the G1-to-S phase transition. MLF1IP knockdown enhanced BRCA1 activity concomitantly with p-AKT downregulation and p27 upregulation, while overexpression of MLF1IP has the opposite effect. Moreover, upregulation of BRCA1 can partially abolish the proliferative activity of MLF1IP.
These findings suggest that MLF1IP may promote proliferation and tumorigenicity of colorectal cancer cells via BRCA1/AKT/p27 signaling axis, and thereby provides potential targets for colorectal cancer therapy.
These findings suggest that MLF1IP may promote proliferation and tumorigenicity of colorectal cancer cells via BRCA1/AKT/p27 signaling axis, and thereby provides potential targets for colorectal cancer therapy.The Signal Transducer and Activator of Transcription 3 (STAT3) protein is encoded on chromosome 17q21. The SH2 and the DNA binding domains are critical structural components of the protein, together with tyrosine and serine residues that initiate phosphorylation. STAT3 interacts with DNA directly and functions in cells as both a signal transducer and a transcription factor. Its cytoplasmic activation results in dimerisation and nuclear translocation, where it is involved in the transcription of a large number of target genes. STAT3 is hyperactive in cancer cells as a result of upstream STAT3 mutations or enhanced cytokine production in the tumour environment. The STAT3 signalling pathway promotes many hallmarks of carcinogenesis and metastasis, including enhanced cell proliferation and survival, as well as migration and invasion into the extracellular matrix. Recent investigations into novel STAT3-based therapies describe a range of innovative approaches, such as the use of novel oligonucleotide drugs. These limit STAT3 binding to its target genes by attaching to SH2 and DNA-binding domains. JNK-IN-8 in vivo Yet, despite these significant steps in understanding the underpinning mechanisms, there are currently no therapeutic agents that addresses STAT3 signalling in a clinically relevant manner.We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined by RT-qPCR and Western blot analysis. The interaction among C-MYC, miR-9-5p, and TBPL1 was detected by ChIP assay and dual luciferase reporter gene assay. After alteration of C-MYC, miR-9-5p, and TBPL1, their roles in pulmonary fibrosis and collagen fiber deposition in mice as well as proliferation and differentiation of pulmonary fibroblasts were assessed. Upregulated C-MYC expression was seen in the lung tissues of IPF mice and its silencing retarded IPF in mice. C-MYC could activate miR-9-5p that negatively regulated TBPL1 expression. Up-regulated C-MYC promoted proliferation and differentiation of pulmonary fibroblasts by inhibiting TBPL1 via activation of miR-9-5p, thus triggering IPF. Moreover, in the lung tissues-derived cells of IPF mice, C-MYC inhibitor, 10,058-F4, was observed to inhibit miR-9-5p expression, thereby repressing pulmonary fibrosis by up-regulating TBPL1. Our data provided evidence pinpointed the aggravative role of C-MYC in IPF by activating miR-9-5p to regulate TBPL1 expression.
The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms.
Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy.
Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expressions of TGF-β1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H
O
-treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H
O
.
Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-β/Smad signaling pathway.
Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-β/Smad signaling pathway.Growing concern regarding non-biodegradable plastics and the impact of these materials on the environment has promoted interest in biodegradable plastics. The intensification of separate biowastes collection in most European countries has also contributed to the development of biodegradable plastics, and the subject of their end-of-life is becoming a key issue. To date, there has been relatively little research to evaluate the biodegradability of biodegradable plastics by anaerobic digestion (AD) compared to industrial and home composting. However, anaerobic digestion is a particularly promising strategy for treating biodegradable organic wastes in the context of circular waste management. This critical review aims to provide an in-depth update of anaerobic digestion of biodegradable plastics by providing a summary of the literature regarding process performance, parameters affecting biodegradability, the microorganisms involved, and some of the strategies (e.g., pretreatment, additives, and inoculum acclimation) used to enhance the degradation rate of biodegradable plastics. In addition, a critical section is dedicated to suggestions and recommendations for the development of biodegradable plastics sector and their treatment in anaerobic digestion.
To identify early doxorubicin-induced cardiotoxicity by applying 7.0T cardiac magnetic resonance (CMR) combined with creatine kinase isoenzymes (CKMB) from rat models, using pathological results as a reference standard.
The 48 male rats included in the study were divided into a doxorubicin (DOX) group (n=32) and a control group (n=16). Each group was further divided into four subgroups according to the interval weeks between the first administration and CMR examination. DOX group and the controls were injected with DOX (2.5mg/kg) or physiological saline (2.5mg/kg) through vena caudalis weekly. The rats in first subgroup received 4 weekly injections and were sacrificed after CMR examination at week 4. Rats in the second, third and fourth DOX or control subgroups underwent 6 weekly injections and were sacrificed after CMR examination at weeks 6, 8 and 10, respectively. The conventional cardiac function parameters, myocardial strain, standardized myocardial T2 value, late gadolinium enhancement, CKMB and patnduced cardiotoxicity at early stage, with the LV mass index, global circumference strain, normalized myocardial T2 relaxation time as the early markers. CKMB can indicate the optimal timing for CMR examination of chemotherapy recipients to improve medical efficiency. Myocardial fibrosis persists in the advanced stage of doxorubicin-induced cardiotoxicity which comprises the main cause of LV dysfunction.
This work aims at developing a novel calibration-free fast parallel MRI (pMRI) reconstruction method incorporate with discrete-time optimal control framework. The reconstruction model is designed to learn a regularization that combines channels and extracts features by leveraging the information sharing among channels of multi-coil images. We propose to recover both magnitude and phase information by taking advantage of structured convolutional networks in image and Fourier spaces.
We develop a novel variational model with a learnable objective function that integrates an adaptive multi-coil image combination operator and effective image regularization in the image and Fourier spaces. We cast the reconstruction network as a structured discrete-time optimal control system, resulting in an optimal control formulation of parameter training where the parameters of the objective function play the role of control variables. We demonstrate that the Lagrangian method for solving the control problem is equivalent to back-propagation, ensuring the local convergence of the training algorithm.
We conduct a large number of numerical experiments of the proposed method with comparisons to several state-of-the-art pMRI reconstruction networks on real pMRI datasets. The numerical results demonstrate the promising performance of the proposed method evidently.
The proposed method provides a general deep network design and training framework for efficient joint-channel pMRI reconstruction.
By learning multi-coil image combination operator and performing regularizations in both image domain and k-space domain, the proposed method achieves a highly efficient image reconstruction network for pMRI.
By learning multi-coil image combination operator and performing regularizations in both image domain and k-space domain, the proposed method achieves a highly efficient image reconstruction network for pMRI.High spatial resolution is desirable in magnetic resonance imaging (MRI) as it can provide detailed anatomical information, facilitating radiologists with accurate quantitative analysis. Super-resolution (SR) algorithms are effective approaches to enhance MR images' spatial resolution. In the past few years, convolutional neural network (CNN)-based SR methods have significantly improved and outperformed conventional ones. However, existing CNN-based SR methods usually do not explicitly consider the frequency property of images, leading to the limited representation of high-frequency components reflecting image details. To alleviate this problem, a dense channel splitting network (DCSN) algorithm is proposed to process the frequency bands for better feature detection. Specifically, a channel splitting module, a cascaded multi-branch dilation module, and a dense-in and recursive-out mechanism are designed to separate frequency bands of MR images and forward the high-frequency information to deeper layers for reconstruction.
