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Infection with Shiga toxin (STx)-producing bacteria can progress to a toxemic, extraintestinal injury cascade known as haemolytic uremic syndrome (HUS), the leading cause of acute renal failure in children. Mounting evidence suggests that STx activates stress response pathways in susceptible cells and has implicated the p38 mitogen-activated protein kinase (MAPK) pathway. More importantly, some of the pathology associated with HUS is believed to be a result of a STx-induced inflammatory response. From a siRNA screen of the human kinome adapted to a high-throughput format, we found that knock-down of the MAPK-activated protein kinase 2 (MK2), a downstream target of the p38 MAPK, protected against Shiga toxicity. Further characterization of the in vitro role of MK2 revealed that STx activates the p38-MK2 stress response pathway in both p38- and MK2-dependent manners in two distinct cell lines. MK2 activation was specific to damage to the ribosome by an enzymatically active toxin and did not result from translational inhibition per se. Genetic and chemical inhibition of MK2 significantly decreased the inflammatory response to STx. These findings suggest that MK2 inhibition might play a valuable role in decreasing the immuopathological component of STx-mediated disease. [ABSTRACT FROM AUTHOR]

In this article the author discusses the financial burden of epilepsy in China by considering the economy of the country. He states that developing countries bear the 90% of financial burden because of the fact that 85% of the 50 million epileptics live in these countries. The author says that opportunity cost of treating epilepsy and the oligopolistic economy of the country should be considered as part of the computation of the financial burden.

There is increasing evidence demonstrating that disorders affecting microRNAs (miRs) influence tumorigenesis and progression, which results in a poor prognosis in patients with breast cancer (BC). In the present study, the precise molecular mechanism underlying the role of miR-320 in the progression of BC was investigated. Reverse transcription-quantitative PCR was conducted to determine mRNA expression, and western blot analysis was used to test protein levels. An MTT assay was conducted to detect cell viability and Transwell assays were used to analyze cell migration and invasion abilities. Furthermore, E74-like factor 3 (ELF3) protein density was tested via immunohistochemistry. Tumor volume was detected by xenograft tumor formation assay. The current results indicated that miR-320 expression was downregulated in BC tissues and cells, and was associated with a poor prognosis of patients with BC. Overexpression of miR-320 inhibited cell proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition and the PI3K/AKT signaling pathway in BC cells. Furthermore, it was revealed that the tumor size and weight were smaller in nude mice that had been transfected to overexpress miR-320. The luciferase reporter assay demonstrated the direct binding of miR-320 to the 3' untranslated region of ELF3 mRNA, which may further downregulate ELF3. Overall, the present results provided evidence that miR-320 may be a tumor suppressor in BC, and that the miR-320/ELF3 axis regulated tumor progression via the PI3K/AKT signaling pathway, which may represent a novel treatment strategy for BC. [ABSTRACT FROM AUTHOR]

High-speed railways often run over underground metro stations. Dynamic load induced by high-speed train can influence the internal force of underground structure and hence can pose danger to the underground structure. Hence, it is necessary to estimate the safety of underground structure due to high-speed train load. In this paper, the effects of dynamic load induced by high-speed train on metro station are investigated by carrying out three-dimensional numerical analysis. Guinan high-speed railway, which is designed to run over Jinqiao metro station in Nanning, Guangxi province of China are adopted as the background of this case study. The hardening soil model with small-strain stiffness was adopted to model the behaviour of soil. Two typical speed of railway train (i.e., 160 km/h and 350 km/h) are considered in this study. Based on the numerical analysis, vertical vibration acceleration and bending moment of the structure of the metro station are presented and analysed. [ABSTRACT FROM AUTHOR]

Folliculin (FLCN) is the tumor suppressor associated with Birt-Hogg-Dubé (BHD) syndrome that predisposes patients to incident of hamartomas and cysts in multiple organs. Its inactivation causes deregulation in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. However, the underlying mechanism is poorly defined. In this study, we show that FLCN is a ciliary protein that functions through primary cilia to regulate mTORC1. In response to flow stress, FLCN associates with LKB1 and recruits the kinase to primary cilia for activation of AMPK resided at basal bodies, which causes mTORC1 down-regulation. In cells depleted of FLCN, LKB1 fails to accumulate in primary cilia and AMPK at the basal bodies remains inactive, thus nullifying the inhibitory effect of flow stress on mTORC1 activity. Our results demonstrate that FLCN is part of a flow sensory mechanism that regulates mTORC1 through primary cilia. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) form a monolayer that serves as a barrier between the blood and the underlying tissue. ECs tightly regulate their cell-cell junctions, controlling the passage of soluble materials and immune cells across the monolayer barrier. We studied the role of N-WASP, a key regulator of Arp2/3 complex and actin assembly, in EC monolayers. We report that N-WASP regulates endothelial monolayer integrity by affecting the organization of cell junctions. Depletion of N-WASP resulted in an increase in transendothelial electrical resistance, a measure of monolayer integrity. N-WASP depletion increased the width of cell-cell junctions and altered the organization of F-actin and VE-cadherin at junctions. N-WASP was not present at cell-cell junctions in monolayers under resting conditions, but it was recruited following treatment with sphingosine-1-phosphate. Taken together, our results reveal a novel role for N-WASP in remodeling EC junctions, which is critical for monolayer integrity and function. [ABSTRACT FROM AUTHOR]

Background: Let-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a. Methods: The expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells. Results: Our study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3'UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells. Conclusion: Let-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC. [ABSTRACT FROM AUTHOR]

β-amyloid precursor protein (β-AFF), also known as Ap peptide, has a key role in the pathogenesis of Alzheimer's disease, and is also likely to be involved in the development of refractory epilepsy. The mechanism behind the association between β-AFF and refractory epilepsy remains to be elucidated. The aim of the present study was to examine the levels of APP mRNA and β-AFF protein in patients with refractory epilepsy. Tissue samples were obtained from patients with chronic pharmacoresistant epilepsy who underwent surgery. Levels of APP mRNA and β-AFF protein in epileptic temporal lobe and hippocampal tissue were assessed using quantitative polymerase chain reaction, immunohistochemistry and immunofluorescence. The expression levels of protein significantly increased in the temporal cortex and the hippocampus of the patients with epilepsy. β-AFF may thus contribute to the pathogenesis of refractory epilepsy. [ABSTRACT FROM AUTHOR]

The article focuses on ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation. Topics include the necroptosis, a form of regulated necrosis, participates in tumor development and dying cell immunogenicity, and the unclear how tumor cell–intrinsic necroptotic signaling contributes to radiation-induced antitumor immunity.

The article discusses the effectiveness of mannitol and arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) relapse in the central nervous system. It states the need of major obstacle to all treatments for the therapeutic drugs penetrating the blood-brain barrier (BBB). It also emphasizes the limitation in the application of ATO and all-frans retinoic acid (ATRA) medications for APL intramarrow treatment.

Objective: In recent years, research on microRNAs (miRNAs) associated with coronary artery disease (CAD) has attracted considerable attention. However, findings of these studies on the validity of circulating miRNAs in CAD diagnosis are controversial. A meta-analysis was therefore conducted to determine the potential value of miRNAs as biomarkers in CAD diagnosis. Methods: Relevant documents on miRNAs expression levels in the diagnosis of CAD were searched and collected from Pubmed, Embase, and Web of Science. They were collected from the time of inception of the database till January 31, 2020. A meta-analysis was conducted using Stata14.0 software. Forest maps were studied and a comprehensive evaluation of the diagnostic value of the expression levels of mRNAs in CAD was conducted using statistical indicators such as the summary receiver operating characteristic curve. Results: Overall, 14 studies were included, with 38 data sets, involving 29 miRNAs with 846 cases and 898 controls. The meta-analysis revealed that the average sensitivity and specificity of miRNAs for CAD diagnosis were 0.80 (0.75–0.84) and 0.78 (0.75–0.81), respectively. The positive likelihood, negative likelihood, and diagnostic odds ratios were 3.7 (3.1–4.4), 0.26 (0.21–0.33), and 14 (10–21), respectively, and the area under the curve was 0.85 (0.82–0.88). Subgroup analysis revealed that the accuracy in the Asian population was higher than that in the non-Asian population. Multiple miRNAs may be more diagnostically accurate than single miRNAs. MiRNAs in whole blood were more accurate than those in plasma, serum, and peripheral blood mononuclear cells. The diagnostic performance of the quantitative real-time polymerase chain reaction group was better than that of the qPCR group. Conclusion: According to our study, miRNAs may be a new, non-invasive diagnostic tool for the diagnosis of CAD. As a screening tool in clinical practice, it has potential diagnostic value and is worthy of clinical promotion. Considering the number and quality of the studies included in this meta-analysis, the above conclusion requires more quality research to verify it. (Anatol J Cardiol 2020; 24: 290-9). [ABSTRACT FROM AUTHOR]

We report a case of a man with concurrent unilateral upper cervical cord infarction in Opalski's syndrome due to spontaneous vertebral artery dissection. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer of the renal parenchyma. MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length, which function as post-transcriptional regulators. Recently, the downregulation of miRNA (miR)-492 was observed to be associated with ccRCC; however, the molecular mechanism by which miR-492 inhibited ccRCC remained to be elucidated. In the present study, it was demonstrated that miR-492 was markedly downregulated in ccRCC tissues when compared with adjacent normal tissues, as determined by reverse transcription-quantitative poymerase chain reaction (PCR). This downregulation was predominantly due to the hypermethylation of the CpG island of the miR-492 promoter, which was detected by methylation specific PCR and bisulfite genomic sequencing PCR, and was shown to inhibit miR-492 transcription. Through the use of a DNA demethylation agent, 5-aza-2'-deoxycytidine or the histone deacetylase inhibitor 4-phenylbutyric acid, the expression level of miR-492 was significantly upregulated in ccRCC cells, which further inhibited cell proliferation and invasion, while promoting cell apoptosis and adhesion. In conclusion, the present study provided novel insights into the potential mechanisms involved in ccRCC and it is hypothesized that miR-492 may become a promising therapeutic agent in the treatment of ccRCC. [ABSTRACT FROM AUTHOR]

‘Targeting peptides’ have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7’s 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide’s binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer. [ABSTRACT FROM AUTHOR]

An abstract of the article "Intravenous sodium valproate for diazepam refractory convulsive status epilepticus," by Lei Chen and colleagues is presented.