SIRT7 Regulates the Vascular Smooth Muscle Cells Proliferation and Migration via Wnt/β-Catenin Signaling Pathway

A huge amount of evidence indicates that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays a crucial role in the pathogenesis of various diseases. However, little is known about the role of SIRT7 in atherosclerosis. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of human vascular smooth muscle cells (HAVSMCs) and its possible molecular mechanism. In this study, human vascular smooth muscle cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) to establish atherosclerosis (AS) cell model. Immunofluorescence staining and Western blot were used to detect the level of α-SMA expression, which was a marker protein in AS. In addition, RT-qPCR and Western blot assay were applied for exploring the mRNA and protein expression levels of SIRT7, Wnt, β-catenin, and cyclin D1 after knockdown or overexpression of SIRT7. And, furthermore, Cell Counting Kit-8 assay, flow cytometry, and wound-healing assay were used to assess HAVSMCs proliferation, cell cycle, and migration. Dickkopf-1 (DKK-1), a secretory glycoprotein that can block Wnt/β-catenin pathway, was used in SIRT7 overexpression HAVSMCs; subsequently cells proliferation and migration were assessed by Cell Counting Kit-8 assay, flow cytometry analysis, and wound-healing assay. We found that knockdown of SIRT7 significantly promoted cell proliferation and migration, decreased the percentages of cells in the G1 and G2 phases, and increased those in the S phase and downregulated the protein expression levels of Wnt, β-catenin, and cyclin D1, while overexpression of SIRT7 had reverse results. After treatment with Wnt/beta-catenin pathway inhibitor DKK-1 in SIRT7 overexpression HAVSMCs, cell proliferation and migration were increased, respectively. In conclusion, SIRT7 inhibited HAVSMCs proliferation and migration via enhancing Wnt/β-catenin activation, which provided a novel therapeutic strategy for antiatherosclerosis.

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Is Integrin Subunit Alpha 2 Expression a Prognostic Factor for Liver Carcinoma? A Validation Experiment Based on Bioinformatics Analysis

Abstract

ITGA2 (Integrin alpha-2) has been detected to be over-expressed in a number of cancers and has been suggested to be involved in cell adhesion and cell-surface mediated signaling. Our previous study using bioinformatic analyses has shown that ITGA2 might be a key gene being involved in the Cadmium-induced malignant transformation of liver cells. In the present study, we firstly aimed to learn the possible functions of ITGA2 via bioinformatics analysis, and then test its expression and clinical significance in liver carcinoma specimens through laboratory experiments. Gene ontology (GO) and pathway enrichment analysis, as well as protein-protein interaction (PPI) analysis has been conducted in Genecards. Then, a tissue microarray containing 90 cases of liver cancer and 90 paired adjacent non-cancerous samples was used for detection of ITGA2 expression by immunohistochemistry assay. Consequently, ITGA2 may be enriched in pathways regarding cell adhesion and migration. PPI analysis suggests that ITGA1, ITGB2, FLT4, LAMB1 and AGRN may have a close relationship with ITGA2. No association between ITGA2 expression and clinical parameters was observed. However, the data showed that ITGA2 might be an independent prognostic factor for liver cancer patients. In conclusion, the data suggest that ITGA2 over-expression might be a potential unfavorable prognostic factor and a potential therapeutic target for liver carcinoma.

https://ift.tt/2QE4O0A

Differences in means‐end exploration between infants at risk for autism and typically developing infants in the first 15 months of life

Abstract

Our study compared means‐end exploration in infants at risk (AR) for autism and typically developing (TD) infants using a nested box paradigm. Sixteen AR and 16 TD infants were observed at 9, 12, and 15 months with follow‐up at 18 and 24 months. We collected video data on three tasks involving retrieval of a small toy by opening (a) an opaque box, (b) a transparent box, and (c) two nested boxes. Dependent variables included hand bias, time to completion, bilateral hand use, problem‐solving strategies used, and tester assistance required. There were no group differences in terms of hand biases. Compared to TD infants, AR infants had lower bilateral hand use, poor problem solving skills, and required greater assistance. Both groups demonstrated age‐related improvements in motor and cognitive skills. Means‐end exploration provides a window into the bilateral coordination and motor planning/problem‐solving abilities of young infants at risk for autism. Lastly, object retrieval tasks could serve as important learning contexts for at‐risk infants.

https://ift.tt/2RwCiLp

Biophysical Parameters of the Sec14 Phospholipid Exchange Cycle

Sec14, the major yeast phosphatidylcholine (PC)/phosphatidylinositol (PI) transfer protein (PITP), coordinates PC and PI metabolism to facilitate an appropriate and essential lipid signaling environment for membrane trafficking from trans-Golgi membranes. The Sec14 PI/PC exchange cycle is essential for its essential biological activity, but fundamental aspects for how this PITP executes its lipid transfer cycle remain unknown. To address some of these outstanding issues, we applied time-resolved small-angle neutron scattering (SANS) for the determination of protein-mediated inter-vesicular movement of deuterated and hydrogenated phospholipids in vitro.

https://ift.tt/2RuMuUA

A Model of Piezo1-based Regulation of Red Blood Cell Volume

A red blood cell (RBC) performs its function of adequately carrying respiratory gases in blood by its volume being about 60 % of that of a sphere with the same membrane area. For this purpose, human and most other vertebrate RBCs regulate their content of potassium (K+) and sodium (Na+) ions. The focus considered here is on K+ efflux through calcium ion (Ca++) activated Gárdos channels. These channels open under conditions that allow Ca++ to enter RBCs through Piezo1 mechanosensitive cation permeable channels.

https://ift.tt/2QdBzSM

Cancer survivors’ needs during various treatment phases after multimodal treatment for colon cancer - is there a role for eHealth?

Abstract

Background

More colon cancer patients are expected to fully recover after treatment due to earlier detection of cancer and improvements in general health- and cancer care. The objective of this study was to gather participants' experiences with full recovery in the different treatment phases of multimodal treatment and to identify their needs during these phases. The second aim was to propose and evaluate possible solutions for unmet needs by the introduction of eHealth.

Methods

A qualitative study based on two focus group discussions with 22 participants was performed. The validated Supportive Care Needs Survey and the Cancer Treatment Survey were used to form the topic list. The verbatim transcripts were analyzed with Atlas.ti. 7th version comprising open, axial and selective coding. The guidelines of the consolidated criteria for reporting qualitative research (COREQ) were used.

Results

Experiences with the treatment for colon cancer were in general positive. Most important unmet needs were 'receiving information about the total duration of side effects', 'receiving information about the minimum amount of chemo needed to overall survival' and 'receiving a longer aftercare period (with additional attention for psychological guidance)'. More provision of information online, a chat function with the oncological nurse specialist via a website, and access to scientific articles regarding the optimal dose of chemotherapy were often mentioned as worthwhile additions to the current health care for colon cancer.

Conclusions

Many of the unmet needs of colon cancer survivors occur during the adjuvant treatment phase and thereafter. To further optimize recovery and cancer care, it is necessary to have more focus on these unmet needs. More attention for identifying patients' problems and side-effects during chemotherapy; and identifying patients' supportive care needs after finishing chemotherapy are necessary. For some of these needs, eHealth in the form of blended care will be a possible solution.

https://ift.tt/2Php8jy

Q-TWiST Analysis to Assess Benefit–Risk of Pembrolizumab in Patients with PD-L1–Positive Advanced or Metastatic Non-small Cell Lung Cancer

Abstract

Objectives

Pembrolizumab monotherapy showed significantly longer overall survival and fewer treatment-related adverse events compared to chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1)–positive tumors in the first-line setting in KEYNOTE (KN)-024 and in those previously treated in KN010. The objective of this analysis was to assess the benefit–risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials.

Methods

The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments. Survival time was partitioned into three health states: with toxicity before disease progression, without toxicity before disease progression, and disease progression until death. Health state utilities were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in the trials. Q-TWiST was calculated as the utility-weighted sum of the mean health state durations. Trial data analyzed included the primary analysis and subsequent data cutoffs. The base-case analysis was based on the most recent analysis of the trials.

Results

Patients randomized to pembrolizumab had 2.49 months greater Q-TWiST (P value < 0.001) compared to those randomized to platinum-based chemotherapy at a follow-up of 24 months in KN024, and 2.29 months greater Q-TWiST (P value < 0.001) compared to docetaxel over 30 months follow-up in KN010. Results across the trial analyses showed an increase in trend for the Q-TWiST improvement of pembrolizumab over time.

Conclusions

Pembrolizumab showed significant improvement in Q-TWiST compared to chemotherapy in advanced or metastatic NSCLC in both previously untreated and treated patients. The benefits of pembrolizumab continued to accrue with longer follow-ups.

https://ift.tt/2Ecc79U