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1.
Phys Rev Lett ; 125(17): 170503, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33156665

RESUMO

We report the analog simulation of an ergodic-localized junction by using an array of 12 coupled superconducting qubits. To perform the simulation, we fabricated a superconducting quantum processor that is divided into two domains: one is a driven domain representing an ergodic system, while the second is localized under the effect of disorder. Because of the overlap between localized and delocalized states, for a small disorder there is a proximity effect and localization is destroyed. To experimentally investigate this, we prepare a microwave excitation in the driven domain and explore how deep it can penetrate the disordered region by probing its dynamics. Furthermore, we perform an ensemble average over 50 realizations of disorder, which clearly shows the proximity effect. Our work opens a new avenue to build quantum simulators of driven-disordered systems with applications in condensed matter physics and material science.

3.
J Cell Mol Med ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215816

RESUMO

Pathological myocardial fibrosis and hypertrophy occur due to chronic cardiac stress. The microRNA-27a (miR-27a) regulates collagen production across diverse cell types and organs to inhibit fibrosis and could constitute an important therapeutic avenue. However, its impact on hypertrophy and cardiac remodelling is less well-known. We employed a transverse aortic constriction (TAC) murine model of left ventricular pressure overload to investigate the in vivo effects of genetic miR-27a knockout, antisense inhibition of miR-27a-5p and fibroblast-specific miR-27a knockdown or overexpression. In silico Venn analysis and reporter assays were used to identify miR-27a-5p's targeting of Early Growth Response Protein 3 (Egr3). We evaluated the effects of miR-27a-5p and Egr3 upon transforming growth factor-beta (Tgf-ß) signalling and secretome of cardiac fibroblasts in vitro. miR-27a-5p attenuated TAC-induced cardiac fibrosis and myofibroblast activation in vivo, without a discernible effect on cardiac myocytes. Molecularly, miR-27a-5p inhibited transforming growth factor-beta (Tgf-ß) signalling and pro-fibrotic protein secretion in cardiac fibroblasts in vitro through suppressing the pro-fibrotic transcription factor Early Growth Response Protein 3 (Egr3). This body of work suggests that cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Egr3 expression.

4.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142808

RESUMO

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 µg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

5.
BMC Med Res Methodol ; 20(1): 258, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059588

RESUMO

BACKGROUND: Unstructured data from clinical epidemiological studies can be valuable and easy to obtain. However, it requires further extraction and processing for data analysis. Doing this manually is labor-intensive, slow and subject to error. In this study, we propose an automation framework for extracting and processing unstructured data. METHODS: The proposed automation framework consisted of two natural language processing (NLP) based tools for unstructured text data for medications and reasons for medication use. We first checked spelling using a spell-check program trained on publicly available knowledge sources and then applied NLP techniques. We mapped medication names into generic names using vocabulary from publicly available knowledge sources. We used WHO's Anatomical Therapeutic Chemical (ATC) classification system to map generic medication names to medication classes. We processed the reasons for medication with the Lancaster stemmer method and then grouped and mapped to disease classes based on organ systems. Finally, we demonstrated this automation framework on two data sources for Mylagic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): tertiary-based (n = 378) and population-based (n = 664) samples. RESULTS: A total of 8681 raw medication records were used for this demonstration. The 1266 distinct medication names (omitting supplements) were condensed to 89 ATC classification system categories. The 1432 distinct raw reasons for medication use were condensed to 65 categories via NLP. Compared to completion of the entire process manually, our automation process reduced the number of the terms requiring manual labor for mapping by 84.4% for medications and 59.4% for reasons for medication use. Additionally, this process improved the precision of the mapped results. CONCLUSIONS: Our automation framework demonstrates the usefulness of NLP strategies even when there is no established mapping database. For a less established database (e.g., reasons for medication use), the method is easily modifiable as new knowledge sources for mapping are introduced. The capability to condense large features into interpretable ones will be valuable for subsequent analytical studies involving techniques such as machine learning and data mining.

6.
Signal Transduct Target Ther ; 5(1): 231, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028807

RESUMO

Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions and redox balance. NADPH homeostasis is regulated by varied signaling pathways and several metabolic enzymes that undergo adaptive alteration in cancer cells. The metabolic reprogramming of NADPH renders cancer cells both highly dependent on this metabolic network for antioxidant capacity and more susceptible to oxidative stress. Modulating the unique NADPH homeostasis of cancer cells might be an effective strategy to eliminate these cells. In this review, we summarize the current existing literatures on NADPH homeostasis, including its biological functions, regulatory mechanisms and the corresponding therapeutic interventions in human cancers, providing insights into therapeutic implications of targeting NADPH metabolism and the associated mechanism for cancer therapy.

7.
BMC Anesthesiol ; 20(1): 260, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036554

RESUMO

BACKGROUND: The optimal position for continuous adductor canal block (ACB) for analgesia after total knee anthroplasty (TKA) remians controversial, mainly due to high variability in the localization of the the adductor canal (AC). Latest neuroanatomy studies show that the nerve to vastus medialis plays an important role in innervating the anteromedial aspect of the knee and dives outside of the exact AC at the proximal end of the AC. Therefore, we hypothesized that continuous ACB at the proximal end of the exact AC could provide a better analgesic effect after TKA compared with that at the middle of the AC (which appeared to only block the saphenous nerve). METHODS: Sixty-two adult patients who were scheduled for a unilateral TKA were randomized to receive continuous ACB at the proximal end or middle of the AC. All patients received patient-controlled intravenous analgesia with sufentanil postoperatively. The primary outcome measure was cumulative sufentanil consumption within 24 h after the surgery, which was analyzed using Mann-Whitney U tests. P-values < 0.05 (two-sided) were considered statistically significant. The secondary outcomes included postoperative sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. RESULTS: Sixty patients eventually completed the study (30/group). The 24-h sufentanil consumption was 0.22 µg/kg (interquartile range [IQR]: 0.15-0.40 µg/kg) and 0.39 µg/kg (IQR: 0.23-0.52 µg/kg) in the proximal end and middle groups (P = 0.026), respectively. There were no significant inter-group differences in sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. CONCLUSIONS: Continuous ACB at the proximal end of the AC has a better opioid-sparing effect without a significant influence on quadriceps motor strength compared to that at the middle of the AC after TKA. These findings indicates that a true ACB may not produce the effective analgesia, instead, the proximal end AC might be a more suitable block to alleviate pain after TKA. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT03942133 ; registration date: May 06, 2019; enrollment date: May 11, 2019).

8.
Cancer Commun (Lond) ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119215

RESUMO

Altered metabolism is a hallmark of cancer, and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors. It is well recognized that long noncoding RNAs (lncRNAs) regulate energy metabolism in cancer. However, lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at present. In this review, we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes, transcription factors, and other proteins involved in metabolic pathways. In addition, we discuss the mechanisms through which these interactions contribute to tumor initiation and progression, and the key roles and clinical significance of functional lncRNAs. We believe that an in-depth understanding of lncRNA-mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.

9.
Rheumatol Ther ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106937

RESUMO

INTRODUCTION: Risk prediction is challenging in patients with idiopathic inflammatory myopathies (IIM) and acute exacerbation of interstitial lung disease (AE-ILD) because of heterogeneity and patient-specific variables. Our objective was to assess whether mortality is accurately predicted in patients with IIM and AE-ILD by using the gender age physiology ILD (GAP-ILD) model, a clinical prediction model that was previously validated in patients with idiopathic pulmonary fibrosis. METHODS: A retrospective cohort study was conducted in the First Affiliated Hospital, Zhejiang University, wherein 60 consecutive patients with IIM and AE-ILD admitted between February 2011 and April 2019. The GAP-ILD was assessed retrospectively on the basis of gender, age and pulmonary function test. RESULTS: Patients with AE-ILD (n = 60) were identified and collected, 26 deaths occurred during follow-up, and the non-survivors group presented a higher level of GAP-ILD index (P = 0.005), bacterial infection (P = 0.013), and myositis disease activity assessment (MYOACT) (P = 0.031). The subsequent multivariate logistic regression analysis of overall mortality in AE-ILD revealed that bacterial infection (OR 5.275, P = 0.037) and GAP-ILD index (OR 2.292, P = 0.011) conferred significant risk of mortality. The GAP-ILD index was able to separate patients with AE-ILD into two groups with a statistically significant difference in survival rate (log rank P = 0.002). Satisfactory mortality estimation was maintained in the corresponding GAP-ILD index across the AE-ILD group. CONCLUSION: The GAP-ILD model preforms well in risk prediction of mortality among patients with IIM and AE-ILD. Pulmonary bacterial infection can also be taken as an initial predictor of poor prognosis in patients with IIM and AE-ILD that must be taken seriously.

10.
Inflammation ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009637

RESUMO

Acute kidney injury (AKI) is the most common complication of sepsis with a high mortality rate. In this study, we focus on the renal injury caused by the immune response of renal tubular epithelial cells and inflammation-induced renal tubular epithelial cell apoptosis. We studied the role of GRP120 in the inflammation and apoptosis of human renal cell line HK-2 and mouse primary renal tubular epithelial cells. GPR120 agonist GW9508 activated the GPR120 pathway. Inflammatory factors were detected using quantitative real-time PCR and enzyme-linked immunosorbent assay. Cell apoptosis experiments included the annexin V and PI double-staining method combined with flow cytometry, TUNEL method, and Western blot. The level of cytokines including TNF-α, IL-6, IL-1ß, and iNOS was significantly decreased (P < 0.05) in HK-2 and TECs after the activation of the GPR120 pathway. Besides, the cell apoptosis of both cells increased. Overexpressed GPR120 and shGPR120 were established. Treatment with lipopolysaccharide (LPS) increased the level of cytokines including TNF-α, IL-6, IL-1ß, and iNOS in HK-2 cell and TECs. Compared with control-LPS and negative control (NC)-LPS, the overexpression of GPR120 and shGPR120 could decrease and increase the level of secreted cytokines significantly (P < 0.05), respectively, after LPS-induced apoptosis. After H2O2- and LPS-induced apoptosis, respectively, compared with the control and NC groups, overexpressed GPR120 and shGPR120 could reduce and increase the expression of caspase-3, respectively. GPR120 could suppress the cellular immune response and apoptosis in renal tubular epithelial cells, thereby possibly protecting the kidney and relieving sepsis-induced AKI.

12.
J Surg Oncol ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895951

RESUMO

OBJECTIVE: The aim of this study was to present a novel bile-duct obstructed area imaging (BOAI) and to investigate the feasibility and accuracy of this method in guiding hepatectomy for intrahepatic cholangiocarcinoma (ICC) with intrahepatic biliary obstruction. METHODS: From May 2017 to October 2019, eligible patients who underwent hepatectomy guided by BOAI were enrolled. Perioperative outcomes and operative data were analyzed. To assess the feasibility of BOAI and Glissonean pedicle approach, demarcations based on them were compared. To verify the accuracy of BOAI staining of the target territory, simple linear regression analysis, and intraclass correlation coefficient were used to examine the relationship between predicted resected liver volume (PRLV) and actual resected liver volume (ARLV). RESULTS: BOAI staining achieved valid demarcation in 15 (93.8%) of 16 patients, whereas the ischemic line achieved valid demarcation in only nine patients (57.3%; p = .017). ARLV and PRLV had a strong positive correlation (PRLV = 60.06 + 0.925 × ARLV; R = .945; p = .000). Meanwhile, ARLV (intraclass correlation coefficient = .971) achieved an excellent agreement with PRLV (p < .001). CONCLUSIONS: The novel BOAI staining method can provide valid, feasible, and accurate demarcation line and may be an effective method in the surgical treatment of intrahepatic biliary obstruction.

13.
Biomed Res Int ; 2020: 9809347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908931

RESUMO

We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms' tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student's t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p < 0.05 and r > 0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p = 0.0285, ROC = 100%, SMD = 2.74). Student's t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p < 0.05, SMD = 2.89, sROC = 0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.

14.
J Ovarian Res ; 13(1): 114, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962729

RESUMO

BACKGROUND: The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown. METHODS: Whole-exome sequencing (WES) was performed on DNA samples obtained from patients with POI, and Sanger sequencing was used to validate the detected potentially pathogenic variants. An in silico analysis was carried out to predict the pathogenicity of the variants. RESULTS: We recruited 24 patients with POI and identified variants in POI-related genes in 14 patients, including bi-allelic mutations in DNAH6, HFM1, EIF2B2, BNC, and LRPPRC and heterozygous variants in BNC1, EIF2B4, FOXL2, MCM9, FANCA, ATM, EIF2B3, and GHR. No variants in the above genes were detected in the WES data obtained from 29 women in a control group without POI. Determining a clear genetic etiology could significantly increase patient compliance with appropriate intervention strategies. CONCLUSIONS: Our study confirmed that POI is a genetically heterogeneous condition and that whole-exome sequencing is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggests the potential of WES for the detection of POI and thus early interventions for patients with POI.

15.
Signal Transduct Target Ther ; 5(1): 183, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900990

RESUMO

The acidic tumor microenvironment provides an energy source driving malignant tumor progression. Adaptation of cells to an acidic environment leads to the emergence of cancer stem cells. The expression of the vitamin D receptor (VDR) is closely related to the initiation and development of colorectal carcinoma (CRC), but its regulatory mechanism in CRC stem cells is still unclear. Our study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta (PPARD) expression. Overexpression of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in acidosis. The nuclear export signal in VDR was sensitive to acidosis, and VDR was exported from the nucleus. Chromatin immunoprecipitation (ChIP) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses showed that VDR transcriptionally repressed SRY-box 2 (SOX2) by binding to the vitamin D response elements in the promoter of SOX2, impairing tumor growth and drug resistance. We demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in vivo. These findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling, resulting in a lack of efficacy of vitamin D in antineoplastic process.

16.
Anal Methods ; 12(19): 2434-2442, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32930232

RESUMO

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have recently exhibited fascinating pretreatment performance as solid-phase microextraction coatings. In this report, a ß-ketoenamine-linked covalent organic framework (TpPa-1) was successfully constructed through a Schiff-base-type reaction between 1,3,5-triformylphloroglucinol (Tp) and para-phenylenediamine (Pa-1). A TpPa-1 coating was then fabricated on a stainless-steel fiber for capturing trace synthetic musks. This TpPa-1 coating exhibited strong interaction with synthetic musks because of its hydrophobicity and π-π affinity. This TpPa-1-based solid-phase microextraction methodology, coupled with gas chromatography-tandem mass spectrometry, provided high enrichment factors (1214-12 487), wide linearity (0.5-1000 ng L-1), low limits of detection (0.04-0.31 ng L-1), and acceptable reproducibility (relative standard deviation, <10%) for nine synthetic musks. Recoveries at three spiked levels in three types of water samples were between 76.2% and 118.7%. These results indicated the promising applicability of the TpPa-1 as a solid-phase microextraction fiber coating for reliably detecting trace concentrations of synthetic musks in the environment.

17.
Ecotoxicol Environ Saf ; 206: 111182, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32911370

RESUMO

As a lipophilic fungicide, pyraclostrobin is highly toxic to aquatic organisms, especially to fish. In recent years, research has mainly focused on the pyraclostrobin residue in fish tissues under chronic toxicity, but less is known about its distribution in fish tissues under acute toxicity conditions. In this study, the distribution of pyraclostrobin in fish tissues (blood, liver, muscle and gill) was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The purification effects of different purification materials [1) mixtures of PSA, C18 and MgSO4; 2) QuEChERS-PC; and 3) Oasis HLB SPE] were compared for the detection of pyraclostrobin in fish tissues. Finally, the quick and easy clean-up tool of the Oasis HLB SPE procedure was selected. Under optimum conditions, the linearities had a good relationship (determination coefficient R2 > 0.999). The mean recoveries of the analyte for all tested concentrations ranged from 86.94% to 108.81% with RSDs of 0.7%-4.9%. The pyraclostrobin residue amount was much different in fish tissues. Furthermore, the pyraclostrobin residue in different fish tissues increased initially and then decreased gradually. The concentrations in each tissue were initially ranked before 120 min in the following order: gill > liver > blood > muscle. These phenomena may be attributed to the stress response of fish under acute poisoning. This is the first study to document the distribution of pyraclostrobin in fish tissues under acute toxicity conditions, and it provides reference for the management of agrochemicals in terms of aquatic ecological risks.

18.
Chem Commun (Camb) ; 56(86): 13101-13104, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-32974625

RESUMO

A novel manganese catalyst bearing an l-proline-derived N4 ligand has been developed for enabling acid-free asymmetric epoxidation of olefins with tert-butyl hydroperoxide as the oxidant. A variety of olefins that are well-matched in size with the ligand pocket can be transformed to epoxides with excellent enantioselectivities. The smaller ligand pocket is also beneficial to the enantioselective epoxidation of simple olefins. Cryospray ionization mass spectrometry experiments reveal that a MnIV[double bond, length as m-dash]O species serves as an active epoxidizing species.

19.
Org Lett ; 22(19): 7704-7708, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32910665

RESUMO

An efficient Mizoroki-Heck/amination cascade reaction of o-dihaloarenes with allylamines has been developed using nickel and IPr carbene ligand as catalyst. This protocol enables the synthesis of a broad range of substituted indoles by a cascade process, from readily available starting materials. Mechanistic studies suggest that the Mizoroki-Heck reaction occurred first under IPr-nickel catalysis.

20.
Biochem Pharmacol ; : 114192, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32783891

RESUMO

Exposure to toxic metal contaminants, such as cadmium compounds (Cd2+), has been shown to induce adverse effects on various organs and tissues. In particular, blood vessels are severely impacted by Cd2+ exposure, which may lead to cardiovascular diseases (CVDs). According to previous studies, CVDs are associated with increased cyclooxygenase 2 (COX-2) levels. However, the mechanisms by which CdCl2-induced COX-2 overexpression leads to cardiovascular dysfunction remain unclear. Herein, we show that the relative gene expressions of VEGF and PTGS2 (COX-2 encoding gene) are positively correlated in CVDs patients. Moreover, we demonstrate that the in vitro administration of CdCl2 induces cytotoxicity and endoplasmic reticulum (ER) stress in primary human umbilical vein endothelial cells (HUVECs). The induction of ER stress and the overexpression of COX-2 in CdCl2-treated cells alters the protein level of vascular endothelial growth factor (VEGF), resulting in abnormal angiogenesis and increased cytotoxicity. At the pre-transcription level, the inhibition of ER stress by siGRP78 (a key mediator of ER stress) can restore normal angiogenesis in the CdCl2-exposed cells. Meanwhile, at the transcription level, the adverse effects of CdCl2 exposure may be reversed via genetic modification with siRNA (siPTGS2) or by using phytochemical inhibitors (parthenolide, PN) of COX-2. Finally, at the post-transcription level, COX-2 expression may be restricted by the binding of microRNA-101 (miR-101) to the 3'-UTR of PTGS2 mRNA. The use of mimic miR-101 (mi101) to induce the expression of miR-101 eventually leads to reduced COX-2 protein levels, relieved ER stress, and less abnormal angiogenesis and cytotoxicity of CdCl2-exposed primary HUVECs. Overall, our results suggest that CdCl2-induced abnormal angiogenesis is mediated by miR-101/COX-2/VEGF-axis-dependent ER stress, and that cardiovascular dysfunction may be controlled by manipulating COX-2 at the pre-transcription, transcription, and post-transcription levels.

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