Publications by authors named "Jie Du"

557 Publications

β-Aminoisobutyric acid supplementation attenuated salt-sensitive hypertension in Dahl salt-sensitive rats through prevention of insufficient fumarase.

Amino Acids 2021 Nov 27. Epub 2021 Nov 27.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that β-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (L-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.
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http://dx.doi.org/10.1007/s00726-021-03092-7DOI Listing
November 2021

A DNA Electrochemical Sensor via Terminal Protection of Small-Molecule-Linked DNA for Highly Sensitive Protein Detection.

Biosensors (Basel) 2021 Nov 13;11(11). Epub 2021 Nov 13.

State Key Laboratory of Marine Resource Utilization in South China Sea, College of Materials Science and Engineering, Hainan University, Haikou 570228, China.

The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 μM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.
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http://dx.doi.org/10.3390/bios11110451DOI Listing
November 2021

A Novel Clinical Five-Risk Factor Panel for Individualized Recurrence Risk Assessment of Patients With Acute Anterior Uveitis.

Transl Vis Sci Technol 2021 Nov;10(13):29

School of Ophthalmology & Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, People's Republic of China.

Purpose: Detecting and managing relapses of acute anterior uveitis (AAU) is necessary for improving follow-up planning to minimize recurrences and further complications. However, reliable clinical and laboratory risk factors are lacking, as is a predictive model for use in clinical practice that is capable of identifying patients at high risk for recurrence after remission.

Methods: We analyzed 38 laboratory parameters and clinical data from a large longitudinal retrospective cohort of 233 patients with AAU. Association of laboratory parameters with recurrence-free survival (RFS) was evaluated using univariate Cox proportional hazards regression. A clinically applicable predictive model was developed using a logistic regression model.

Results: Of the 38 laboratory parameters studied, we identified 5 parameters (HDL, ankylosing spondylitis, HLA-B27, MO, and LDL) to be associated with RFS. We developed a clinical five-risk factor panel (5RF-panel), which was capable of effectively distinguishing recurrent patients from nonrelapsed patients (area under the curve [AUC] = 0.837), as well as between patients with high and low risks of AAU recurrence (hazard ratio [HR] = 45.874, 95% confidence interval [CI] = 5.232-402.2, P < 0.001). The robust performance of the 5RF-panel was further validated in the testing cohort (AUC = 0.725, and HR = 51.982, 95% CI = 4.438-608.9, P = 0.024). Furthermore, the 5RF-panel demonstrated superior performance in stratifying recurrence risk based on known risk factors.

Conclusions: We identified and validated a novel clinical 5RF-panel to predict individualized risk of AAU recurrence and improved patient classification for clinical management.

Translational Relevance: The present study identified and validated a 5RF-panel that is a promising individualized predictive tool to monitor recurrence risk and guide personalized management of patients with AAU.
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http://dx.doi.org/10.1167/tvst.10.13.29DOI Listing
November 2021

Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase.

Front Microbiol 2021 4;12:719599. Epub 2021 Nov 4.

Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as , , , , and , were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, , , , , and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to -glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography-mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients' fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in and and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.
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http://dx.doi.org/10.3389/fmicb.2021.719599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600050PMC
November 2021

Excessive DNA damage mediates ECM degradation via the RBBP8/NOTCH1 pathway in sporadic aortic dissection.

Biochim Biophys Acta Mol Basis Dis 2021 Nov 12;1868(2):166303. Epub 2021 Nov 12.

Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China. Electronic address:

Stanford type A aortic dissection (TA-AD) is a life-threatening disease. Most cases of aortic dissection (AD) are sporadic rather than inherited. Unlike that of inherited AD, the pathogenesis of sporadic AD is still unclear. In the current study, we aimed to explore the pathogenesis of sporadic AD through transcriptome sequencing data analyses. We downloaded sporadic TA-AD transcriptome profiles from Gene Expression Omnibus (GEO) and found response to DNA damage stimulus was activated in AD. Furthermore, by conducting mouse AD tissue single cell RNA sequencing and immunostaining, we found that DNA damage mainly occurred in smooth muscle cells (SMCs) and fibroblasts. Next, we examined the repair patterns in response to DNA damage and found the linker molecules RBBP8/NOTCH1 between DNA damage/repair and extracellular matrix (ECM) organization through protein-protein interaction analysis. Thus, we proposed that DNA damage could contribute to AD by regulating ECM changes. To explore the underlying mechanism, we knocked down the DNA repair-related gene RBBP8 in aortic SMCs, which could exacerbate DNA damage, and observed decreased expression level of NOTCH1. Inhibition of NOTCH1 with crenigacestat in vivo accelerated β-aminopropionitrile-induced formation of AD and increased mortality. Meanwhile, phenotype switching of SMCs was induced by Notch1 knockdown or inhibition; this switching occurred via a pathway involving downregulation of contractile marker gene expression and upregulation of MMP2 expression, which might aggravate ECM degradation. In conclusion, excessive DNA damage is a characteristic pathological change of sporadic aortic dissection, which might contribute to ECM changes and AD development via action on the NOTCH1 pathway.
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http://dx.doi.org/10.1016/j.bbadis.2021.166303DOI Listing
November 2021

A Machine Learning-Based Prediction Model for Cardiovascular Risk in Women With Preeclampsia.

Front Cardiovasc Med 2021 27;8:736491. Epub 2021 Oct 27.

Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.

Preeclampsia affects 2-8% of women and doubles the risk of cardiovascular disease in women after preeclampsia. This study aimed to develop a model based on machine learning to predict postpartum cardiovascular risk in preeclamptic women. Collecting demographic characteristics and clinical serum markers associated with preeclampsia during pregnancy of 907 preeclamptic women retrospectively, we predicted the cardiovascular risk (ischemic heart disease, ischemic cerebrovascular disease, peripheral vascular disease, chronic kidney disease, metabolic system disease or arterial hypertension). The study samples were divided into training sets and test sets randomly in the ratio of 8:2. The prediction model was developed by 5 different machine learning algorithms, including Random Forest. 10-fold cross-validation was performed on the training set, and the performance of the model was evaluated on the test set. Cardiovascular disease risk occurred in 186 (20.5%) of these women. By weighing area under the curve (AUC), the Random Forest algorithm presented the best performance (AUC = 0.711[95%CI: 0.697-0.726]) and was adopted in the feature selection and the establishment of the prediction model. The most important variables in Random Forest algorithm included the systolic blood pressure, Urea nitrogen, neutrophil count, glucose, and D-Dimer. Random Forest algorithm was well calibrated (Brier score = 0.133) in the test group, and obtained the highest net benefit in the decision curve analysis. Based on the general situation of patients and clinical variables, a new machine learning algorithm was developed and verified for the individualized prediction of cardiovascular risk in post-preeclamptic women.
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http://dx.doi.org/10.3389/fcvm.2021.736491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578855PMC
October 2021

Correction to: AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis.

Apoptosis 2021 Dec 6;26(11-12):657-659. Epub 2021 Nov 6.

Department of Pathology, Physiology and Pathophysiology, Beijing, AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China.

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http://dx.doi.org/10.1007/s10495-021-01695-9DOI Listing
December 2021

Incidence and Survival of Aortic Dissection in Urban China: Results from the National Insurance Claims for Epidemiological Research (NICER) Study.

Lancet Reg Health West Pac 2021 Dec 1;17:100280. Epub 2021 Oct 1.

Beijing Anzhen Hospital, Capital Medical University; Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education; Beijing Collaborative Innovation Centre for Cardiovascular Disorders, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.

Background: Aortic dissection (AD) represents a significant mortality; however, there is rare epidemiologic information about the demography of AD in Chinese, especially its incidence rate.

Methods: A retrospective cohort study was established using the Urban Employee Basic Medical Insurance claims data covering 346.7 million residents from 23 provinces in China, 2015-2016. AD cases were then linked to database of the Urban Employee Basic Endowment Insurance for death information. Incidence rate was age- and sex-standardized to the 2010 China census population. The associations between AD and related factors were evaluated with Poisson regression models. Moreover, mortality and sex- and age-adjusted survival rate was estimated by Cox models.

Findings: 6084 adult AD cases were included in incidence analysis. Totally 4692(77.1%) were men and 5641(92.7%) were Han Chinese. The overall age- and sex-adjusted incidence rate of AD was 2.78(95%CI:2.59-2.98) per 100,000 person-years. In terms of geographic disparities, the crude incidence rate was significantly higher in Northwest China than South China (4.96[95%CI:4.17-5.75] 2.04[95%CI:0.38-3.71] per 100,000 person-years; risk ratio: 2.67[95%CI: 2.34-3.04]). Moreover, survival analysis of 4518 AD patients with 683 recorded deaths during follow-up (median 2.2 years) showed that overall 3-year survival was 83.7%(95%CI:82.4-84.8).

Interpretation: This contemporary population-based cohort study provides a first comprehensive assessment of incidence of AD in urban Chinese adults. The distinct signatures of different incidence with respect to geographic variations may have important implications for clinical management of AD.

Funding: Chinese Ministry of Science and Technology (2020YFC2003503, 2016YFC0903000), and National Natural Science Foundation of China (91846112, 81973132, 81961128006).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495096PMC
December 2021

Reducing Hinge Flexibility of CAR-T Cells Prolongs Survival With Low Cytokines Release.

Front Immunol 2021 5;12:724211. Epub 2021 Oct 5.

Department of Hematology, Strategic Support Force Medical Center, Beijing, China.

Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in B cell malignancies. However, high tumor burden limits clinical efficacy and increases the risk of cytokine release syndrome and neurotoxicity, which is associated with over-activation of the CAR-T cells. The hinge domain plays an important role in the function of CAR-T cells. We hypothesized that deletion of glycine, an amino acid with good flexibility, may reduce the flexibility of the hinge region, thereby mitigating CAR-T cell over-activation. This study involved generating a novel CAR by deletion of two consecutive glycine residues in the CD8 hinge domain of second-generation (2nd) CAR, thereafter named 2nd-GG CAR. The 2nd-GG CAR-T cells showed similar efficacy of CAR expression but lower hinge flexibility, and its protein affinity to CD19 protein was lower than that of 2nd CAR-T cells. Compared to the 2nd CAR-T cells, 2nd-GG CAR-T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells . Furthermore, 2nd-GG CAR-T cells prolonged overall survival in an immunodeficient mouse model bearing NALM-6 when tumor burden was high. This study demonstrated that a lower-flexibility of CD8α hinge improved survival under high tumor burden and reduced proinflammatory cytokines in preclinical studies. While there is potential for improved safety and efficacy, yet this needs validation with clinical trials.
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http://dx.doi.org/10.3389/fimmu.2021.724211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524077PMC
October 2021

The function of CD146 in human annulus fibrosus cells and mechanism of the regulation by TGF-β.

J Orthop Res 2021 Oct 18. Epub 2021 Oct 18.

AO Research Institute Davos, Davos, Switzerland.

The mouse outer annulus fibrosus (AF) was previously shown to contain CD146 AF cells, while in vitro culture and exposure to transforming growth factor-beta (TGF-β) further increased the expression of CD146. However, neither the specific function of CD146 nor the underlying mechanism of TGF-β upregulation of CD146 AF cells have been elucidated yet. In the current study, CD146 expression and its role in cultured human AF cells was investigated studying the cells' capacity for matrix contraction and gene expression of functional AF markers. In addition, TGF-β pathways were blocked by several pathway inhibitors and short hairpin RNAs (shRNAs) targeting SMAD and non-SMAD pathways to investigate their involvement in TGF-β-induced CD146 upregulation. Results showed that knockdown of CD146 led to reduction in AF cell-mediated collagen gel contraction, downregulation of versican and smooth muscle protein 22α (SM22α), and upregulation of scleraxis. TGF-β-induced CD146 upregulation was significantly blocked by inhibition of TGF-β receptor ALK5, and partially inhibited by shRNA against SMAD2 and SMAD4 and by an Protein Kinase B (AKT) inhibitor. Interestingly, the inhibition of extracellular signal-regulated kinases (ERK) pathway induced CD146 upregulation. In conclusion, CD146 was shown to be crucial to maintain the cell contractility of human AF cells in vitro. Furthermore, TGF-β upregulated CD146 via ALK5 signaling cascade, partially through SMAD2, SMAD4, and AKT pathway, whereas, ERK was shown to be a potential negative modulator. Our findings suggest that CD146 can potentially be used as a functional marker in AF repair strategies.
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http://dx.doi.org/10.1002/jor.25190DOI Listing
October 2021

Prospect of compassionate use in China from remdesivir.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Aug;46(8):909-914

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008.

Compassionate use may play an important role in responding to major public health emergencies. The Jinyintan Hospital in Wuhan launched the III phase of clinical trials of antiviral drug-remdesivir on February 6, 2020. As an unapproved drug, remdesivir raised great concerns about compassionate use in China. Compassionate use is therapeutic use of unauthorized drugs outside of clinical trials. It is used for critically ill patients with life-threatening diseases and no effective treatment means in China. Patients voluntarily apply to their medical institutions. The Center for Drug Evaluation, National Medical Products Administration shall conduct scientific and reasonable review, approval, and supervision on patients' application for compassionate medication. By analyzing and comparing the current situation of compassionate use at home and abroad, it is expected to provide thinking for the development of compassionate use system in China.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200255DOI Listing
August 2021

Corrigendum to "Quantitative assessment of HR and NHEJ activities via CRISPR/Cas9-induced oligodeoxynucleotide-mediated DSB repair" [DNA Repair 70 (2018) 67-71].

DNA Repair (Amst) 2021 Nov 15;107:103226. Epub 2021 Sep 15.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, China. Electronic address:

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http://dx.doi.org/10.1016/j.dnarep.2021.103226DOI Listing
November 2021

Parameter-Free Loss for Class-Imbalanced Deep Learning in Image Classification.

IEEE Trans Neural Netw Learn Syst 2021 Sep 15;PP. Epub 2021 Sep 15.

Current state-of-the-art class-imbalanced loss functions for deep models require exhaustive tuning on hyperparameters for high model performance, resulting in low training efficiency and impracticality for nonexpert users. To tackle this issue, a parameter-free loss (PF-loss) function is proposed, which works for both binary and multiclass-imbalanced deep learning for image classification tasks. PF-loss provides three advantages: 1) training time is significantly reduced due to NO tuning on hyperparameter(s); 2) it dynamically pays more attention on minority classes (rather than outliers compared to the existing loss functions) with NO hyperparameters in the loss function; and 3) higher accuracy can be achieved since it adapts to the changes of data distribution in each mini-batch instead of the fixed hyperparameters in the existing methods during training, especially when the data are highly skewed. Experimental results on some classical image datasets with different imbalance ratios (IR, up to 200) show that PF-loss reduces the training time down to 1/148 of that spent by compared state-of-the-art losses and simultaneously achieves comparable or even higher accuracy in terms of both G-mean and area under receiver operating characteristic (ROC) curve (AUC) metrics, especially when the data are highly skewed.
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http://dx.doi.org/10.1109/TNNLS.2021.3110885DOI Listing
September 2021

Higher Serum Lysophosphatidic Acids Predict Left Ventricular Reverse Remodeling in Pediatric Dilated Cardiomyopathy.

Front Pediatr 2021 16;9:710720. Epub 2021 Aug 16.

Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.
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http://dx.doi.org/10.3389/fped.2021.710720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415784PMC
August 2021

Association of Coding Variant With Plasma-Level Soluble ST2 and Risk of Aortic Dissection.

Front Cardiovasc Med 2021 2;8:710425. Epub 2021 Aug 2.

Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, The Collaborative Innovation Center for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Aortic dissection (AD) is characterized by an acute onset, rapid progress, and high mortality. Levels of soluble ST2 (sST2) on presentation are elevated in patients with acute AD, which can be used to discriminate AD patients from patients with chest pain. sST2 concentrations were found to be highly heritable in the general population. The aim of this study was to investigate the associations of variations in ST2-related gene expression with sST2 concentrations and AD risk. This case-control study involving a total of 2,277 participants were conducted, including 435 AD patients and age- and sex-matched 435 controls in the discovery stage, and 464 patients and 943 controls in the validation stage. Eight ST2-related genes were selected by systematic review. Tag single-nucleotide polymorphisms (SNPs) were screened out from the Chinese population of the 1,000 Genomes Database. Twenty-one ST2-related SNPs were genotyped, and plasma sST2 concentrations were measured. In the discovery stage, rs13019803 located in was significantly associated with AD after Bonferroni correction ( = 0.0009) and was correlated with circulating sST2 levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) CI: 0.002 - 0.357] but not in type B. Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 (95% CI: 0.055-0.227) for per C allele]. Odds ratio of rs13019803 on the risk of AAD is 1.67 (95% CI: 1.33-2.09). The SNP rs13019803C is associated with higher sST2 levels and increased risk of AAD.
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http://dx.doi.org/10.3389/fcvm.2021.710425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365023PMC
August 2021

[Effect of arachidonic acid cytochrome P450ω hydroxylase Cyp4a14 gene knockout on skeletal muscle regeneration after injury].

Sheng Li Xue Bao 2021 Aug;73(4):577-583

Vascular Biology Department of Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Vascular Diseases, Beijing 100029, China.

The objective of this study was to explore the roles of arachidonic acid cytochrome P450ω hydroxylase CYP4A14 in skeletal muscle regeneration after injury. Wild-type (WT) control mice and Cyp4a14 knockout (A14) mice were used to establish the muscle injury and regeneration model by intramuscular injection with cardiotoxin (CTX) on the tibial anterior (TA) muscle. The TA muscles were harvested at the time points of 0, 3, 5 and 15 days after injury. The changes in skeletal muscle regeneration and fibrosis were assessed by wheat germ agglutinin (WGA) staining and Sirius Red staining. Immunohistochemical staining was used to observe the expression of proliferation-related protein Ki-67 and macrophage marker protein Mac-2. The mRNA levels of regeneration and inflammation associated genes were analyzed by real-time PCR. The results showed that the cross-section area (CSA) of regenerated myofibers in A14 mice was significantly smaller (P < 0.05), while the percentage of fibrosis area was significantly higher than those in WT mice at 15 days after injury (P < 0.05). In A14 muscles, both the ratio of Ki-67 positive proliferating cells and the mRNA levels of differentiation associated genes Myod1 and Myog were significantly lower than those in WT muscles (P < 0.05). At 3 days after injury, the mRNA expression of inflammatory cells marker genes CD45 and CD11b and Mac-2 positive macrophages in A14 muscles were significantly lower than those in WT skeletal muscle (P < 0.05). Macrophages derived pro-regeneration cytokines IL-1β, IGF-1 and SDF-1 were also significantly decreased in A14 muscles (P < 0.05). These results suggest that arachidonic acid cytochrome P450ω hydroxylase CYP4A14 plays a critical role in skeletal muscle regeneration after injury.
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August 2021

[Arachidonic acid Alox15/12-HETE signaling inhibits vascular calcification].

Sheng Li Xue Bao 2021 Aug;73(4):571-576

Vascular Biology Department of Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Vascular Diseases, Beijing 100029, China.

This study aims to explore the effects of arachidonic acid lipoxygenase metabolism in vascular calcification. We used 5/6 nephrectomy and high-phosphorus feeding to establish a model of vascular calcification in mice. Six weeks after nephrectomy surgery, vascular calcium content was measured, and Alizarin Red S and Von Kossa staining were applied to detect calcium deposition in aortic arch. Control aortas and calcified aortas were collected for mass spectrometry detection of arachidonic acid metabolites, and active molecules in lipoxygenase pathway were analyzed. Real-time quantitative PCR was used to detect changes in the expression of lipoxygenase in calcified aortas. Lipoxygenase inhibitor was used to clarify the effect of lipoxygenase metabolic pathways on vascular calcification. The results showed that 6 weeks after nephrectomy surgery, the aortic calcium content of the surgery group was significantly higher than that of the sham group (P < 0.05). Alizarin Red S staining and Von Kossa staining showed obvious calcium deposition in aortic arch from surgery group, indicating formation of vascular calcification. Nine arachidonic acid lipoxygenase metabolites were quantitated using liquid chromatography/mass spectrometry (LC-MS) analysis. The content of multiple metabolites (12-HETE, 11-HETE, 15-HETE, etc.) was significantly increased in calcified aortas, and the most abundant and up-regulated metabolite was 12-HETE. Furthermore, we examined the mRNA levels of metabolic enzymes that produce 12-HETE in calcified blood vessels and found the expression of arachidonate lipoxygenase-15 (Alox15) was increased. Blocking Alox15/12-HETE by Alox15 specific inhibitor PD146176 significantly decreased the plasma 12-HETE content, promoted calcium deposition in aortic arch and increased vascular calcium content. These results suggest that the metabolism of arachidonic acid lipoxygenase is activated in calcified aorta, and the Alox15/12-HETE signaling pathway may play a protective role in vascular calcification.
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August 2021

Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin-angiotensin system in the lung.

Sci Rep 2021 08 16;11(1):16525. Epub 2021 Aug 16.

Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL, 60637, USA.

Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-β and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin-angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-β induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-β and angiotensin II synergistically induced TGF-β, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF.
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http://dx.doi.org/10.1038/s41598-021-96152-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367953PMC
August 2021

Inhibition of Peptidyl Arginine Deiminase 4-Dependent Neutrophil Extracellular Trap Formation Reduces Angiotensin II-Induced Abdominal Aortic Aneurysm Rupture in Mice.

Front Cardiovasc Med 2021 30;8:676612. Epub 2021 Jul 30.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Neutrophil infiltration plays an important role in the initiation and development of abdominal aortic aneurysm (AAA). Recent studies suggested that neutrophils could release neutrophil extracellular traps (NETs), leading to tissue injury in cardiovascular diseases. However, the role of NETs in AAA is elusive. This study aimed to investigate the role and underlying mechanism of NETs in AAA development. An angiotensin II (Ang II) infusion-induced AAA model was established to investigate the role of NETs during AAA development. Immunofluorescence staining showed that citrullinated histone 3 (citH3), myeloperoxidase (MPO), and neutrophil elastase (NE) (NET marker) expressions were significantly increased in Ang II-infused mice. The circulating double-stranded DNA (dsDNA) level was also elevated, indicating the increased NET formation during AAA. PAD4 inhibitor YW3-56 inhibited Ang II-induced NET formation. Disruption of NET formation by YW3-56 markedly reduced Ang II-induced AAA rupture, as revealed by decreased aortic diameter, vascular smooth muscle cell (VSMC) apoptosis, and elastin degradation. Apoptosis of VSMC was evaluated by TUNEL staining and Annexin V-FITC/PI staining through flow cytometry. Western blot and inhibition experiments revealed that NETs induced VSMC apoptosis p38/JNK pathway, indicating that PAD4-dependent NET formation played an important role in AAA. This study suggests that PAD4-dependent NET formation is critical for AAA rupture, which provides a novel potential therapeutic strategy for AAA disease.
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http://dx.doi.org/10.3389/fcvm.2021.676612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360833PMC
July 2021

A Gut-Specific LITAF-Like Gene in Antheraea pernyi (Lepidoptera: Saturniidae) Involved in the Immune Response to Three Pathogens.

J Econ Entomol 2021 10;114(5):1975-1982

Henan Key Lab of Funiu Mountain Insect Biology, College of Life Science and Agricultural Engineering, Nanyang Normal University, Nanyang 473061, PR China.

Antheraea pernyi (Guérin-Méneville 1855) is an important resource for silk, food, and biohealth products; however, exogenous pathogens largely affect the commercial application potential of this species. Since the gut is a key organ for the digestion and absorption of nutrients as well as for immune defense, we used comparative transcriptome analysis to screen for a gut-specific molecular tool for further functional research in A. pernyi. In total, 3,331 differentially expressed genes (DEGs) were identified in the gut compared with all other pooled tissues of A. pernyi, including 1,463 upregulated genes in the gut. Among these, we further focused on a lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) gene because of its high gut-specific expression and the presence of a highly conserved SIMPLE-like domain, which is related to the immune response to pathogenic infections in many species. The cDNA sequence of ApLITAF was 447-bp long and contained a 243-bp open reading frame encoding an 80-amino acid protein. Immune challenge assays indicated that ApLITAF expression was significantly upregulated in the gut of A. pernyi naturally infected with nucleopolyhedrovirus (NPV) or fed leaves infected with the gram-negative bacterium Escherichia coli (Migula 1895) and the gram-positive bacterium Bacillus subtilis (Ehrenberg 1835). Cell transfection showed that ApLITAF localized to the lysosome. Collectively, these results suggested that ApLITAF played a role in the immune response of A. pernyi and could facilitate the future research and breeding application in this species.
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http://dx.doi.org/10.1093/jee/toab155DOI Listing
October 2021

Deficiency of peroxisome proliferator-activated receptor α attenuates apoptosis and promotes migration of vascular smooth muscle cells.

Biochem Biophys Rep 2021 Sep 28;27:101091. Epub 2021 Jul 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education; Beijing, China.

Peroxisome proliferator-activated receptor (PPAR) α is widely expressed in the vasculature and has pleiotropic and lipid-lowering independent effects, but its role in the growth and function of vascular smooth muscle cells (VSMCs) during vascular pathophysiology is still unclear. Herein, VSMC-specific PPARα-deficient mice ( ) were generated by Cre-LoxP site-specific recombinase technology and VSMCs were isolated from mice aorta. PPARα deficiency attenuated VSMC apoptosis induced by angiotensin (Ang) II and hydrogen peroxide, and increased the migration of Ang II-challenged cells.
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http://dx.doi.org/10.1016/j.bbrep.2021.101091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339143PMC
September 2021

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells.

Cell Commun Signal 2021 08 11;19(1):85. Epub 2021 Aug 11.

Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, No. 63 Xinjian South Road, Taiyuan, 030001, Shanxi, China.

Background: Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive.

Methods: VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein-protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3' untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay.

Results: We identify ZFP36 can bind with the AREs in the 3'UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid's mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1's nuclear translocation and ameliorate cell death in the presence of inflammation.

Conclusion: These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells. Video abstract.
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http://dx.doi.org/10.1186/s12964-021-00765-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355874PMC
August 2021

Cardiomyocyte peroxisome proliferator-activated receptor α is essential for energy metabolism and extracellular matrix homeostasis during pressure overload-induced cardiac remodeling.

Acta Pharmacol Sin 2021 Aug 10. Epub 2021 Aug 10.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (Ppara) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible Ppara mouse model. Ppara and Ppara mice were randomly subjected to sham or TAC for 2 weeks. Cardiomyocyte PPARα deficiency accelerated TAC-induced cardiac hypertrophy and fibrosis. Transcriptome analysis showed that genes related to fatty acid metabolism were dramatically downregulated, but genes critical for glycolysis were markedly upregulated in Ppara hearts. Moreover, the hypertrophy-related genes, including genes involved in extracellular matrix (ECM) remodeling, cell adhesion, and cell migration, were upregulated in hypertrophic Ppara hearts. Western blot analyses demonstrated an increased HIF1α protein level in hypertrophic Ppara hearts. PET/CT analyses showed an enhanced glucose uptake in hypertrophic Ppara hearts. Bioenergetic analyses further revealed that both basal and maximal oxygen consumption rates and ATP production were significantly increased in hypertrophic Ppara hearts; however, these increases were markedly blunted in Ppara hearts. In contrast, hypertrophic Ppara hearts exhibited enhanced extracellular acidification rate (ECAR) capacity, as reflected by increased basal ECAR and glycolysis but decreased glycolytic reserve. These results suggest that cardiomyocyte PPARα is crucial for the homeostasis of both energy metabolism and ECM during TAC-induced cardiac remodeling, thus providing new insights into potential therapeutics of cardiac remodeling-related diseases.
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http://dx.doi.org/10.1038/s41401-021-00743-zDOI Listing
August 2021

MicroRNA-27b-3p downregulates FGF1 and aggravates pathological cardiac remodelling.

Cardiovasc Res 2021 Aug 6. Epub 2021 Aug 6.

Beijing Anzhen Hospital, Capital Medical University; The Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, 100029, China.

Aims: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling.

Methods And Results: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. MiR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly downregulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart and was upregulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC or Ang II-induced models, and enhanced OXPHOS by activating PGC1α/β.

Conclusions: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.

Translational Perspective: MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. We show for the first time that miR-27b deletion attenuates cardiac hypertrophy, fibrosis, and inflammation and that rFGF1 administration inhibits cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models, and enhances OXPHOS by activating PGC1α/β. Our findings suggest that miR-27b-3p and FGF1 may be potential therapeutic targets to treat conditions characterised by pathological cardiac remodelling.
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http://dx.doi.org/10.1093/cvr/cvab248DOI Listing
August 2021

MiRNA Detection Using a Rolling Circle Amplification and RNA-Cutting Allosteric Deoxyribozyme Dual Signal Amplification Strategy.

Biosensors (Basel) 2021 Jul 4;11(7). Epub 2021 Jul 4.

State Key Laboratory of Marine Resource Utilization in South China Sea, College of Materials Science and Engineering, Hainan University, Haikou 570228, China.

A microRNA (miRNA) detection platform composed of a rolling circle amplification (RCA) system and an allosteric deoxyribozyme system is proposed, which can detect miRNA-21 rapidly and efficiently. Padlock probe hybridization with the target miRNA is achieved through complementary base pairing and the padlock probe forms a closed circular template under the action of ligase; this circular template results in RCA. In the presence of DNA polymerase, RCA proceeds and a long chain with numerous repeating units is formed. In the presence of single-stranded DNA (H1 and H2), multi-component nucleic acid enzymes (MNAzymes) are formed that have the ability to cleave substrates. Finally, substrates containing fluorescent and quenching groups and magnesium ions are added to the system to activate the MNAzyme and the substrate cleavage reaction, thus achieving fluorescence intensity amplification. The RCA-MNAzyme system has dual signal amplification and presents a sensing platform that demonstrates broad prospects in the analysis and detection of nucleic acids.
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http://dx.doi.org/10.3390/bios11070222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301874PMC
July 2021

The reciprocal relationships between social media self-control failure, mindfulness and wellbeing: A longitudinal study.

PLoS One 2021 4;16(8):e0255648. Epub 2021 Aug 4.

Department of Communication Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

This paper aims to shed light on the question whether, and how, social media self-control failure is related to mindfulness and wellbeing. Using a 3-wave longitudinal design, the present study among 594 daily social media users examined the reciprocal relationships between social media self-control failure and mindfulness, and between social media self-control failure and wellbeing (as assessed by subjective vitality and life satisfaction). Results of the random-intercept cross-lagged panel model showed that social media self-control failure has a time-invariant negative association with mindfulness and subjective vitality. No full reciprocal influence was found between social media self-control failure and mindfulness, yet part of this trajectory was observed, suggesting that social media self-control failure could impair mindfulness, which, in turn, might increase future social media self-control failure. For wellbeing, life satisfaction was found to predict subsequent drops in social media self-control failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255648PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336798PMC
August 2021

The PI3K/mTOR Inhibitor Ompalisib Suppresses Nonhomologous End Joining and Sensitizes Cancer Cells to Radio- and Chemotherapy.

Mol Cancer Res 2021 Nov 30;19(11):1889-1899. Epub 2021 Jul 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

As the predominant pathway for the repair of DNA double-strand breaks (DSB), non-homologous end joining (NHEJ) attenuates the efficacy of cancer treatment which relies on the introduction of DSBs, such as radiotherapy and genotoxic drugs. Identifying novel NHEJ inhibitors is of great importance for improving the therapeutic efficiency of radio- or chemotherapy. Here we miniaturized our recently developed NHEJ detecting system into a 96-well plate-based format and interrogated an FDA approved drug library containing 1732 compounds. A collection of novel hits were considered to be potential DSB repair inhibitors at the noncytotoxic concentration. We identified omipalisib as an efficient sensitizer for DNA damage-induced cell death Furthermore, analysis uncovered the repressive effect of omipalisib on the phosphorylation of DNA-dependent protein kinase catalytic subunit induced by ionizing radiation and doxorubicin, which led to the suppression of NHEJ pathway. IMPLICATIONS: In summary, our findings suggested the possibility for repurposing these candidates as radio- or chemosensitizers, which might extend their clinical application in cancer therapy.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0301DOI Listing
November 2021

Enhancement of edeine production in Brevibacillus brevis X23 via in situ promoter engineering.

Microb Biotechnol 2021 Jul 26. Epub 2021 Jul 26.

College of Plant Protection, Hunan Agricultural University, Changsha, 410128, China.

Edeines, a group of cationic antimicrobial peptides produced by the soil bacterium Brevibacillus, have broad biological effects, such as antimicrobial, anticancer and immunosuppressive activities. However, the yield of edeines in wild-type (WT) Brevibacillus is extremely low, and chemical synthesis of edeines is a time-consuming process. Genetic engineering has proven to be an effective approach to produce antibiotics with high yield. In this study, the edeine biosynthetic gene cluster (ede BGC), which is involved in edeine production, was identified and characterized in Brevibacillus brevis X23. To improve edeine production in B. brevis X23, the ede BGC promoter was replaced with six different promoters, P , P , P , P , P or P , through double-crossover homologous recombination. The new promoters significantly increased the expression of the ede BGC as well as edeine production by 2.9 ± 0.4 to 20.5 ± 1.2-fold and 3.6 ± 0.1to 8.7 ± 0.7-fold respectively. The highest yield of edeines (83.6 mg l ) was obtained in B. brevis X23 with the P promoter. This study provides a practical approach for producing high yields of edeines in B. brevis.
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http://dx.doi.org/10.1111/1751-7915.13825DOI Listing
July 2021

The Impact of Urban Development Intensity on Ecological Carrying Capacity: A Case Study of Ecologically Fragile Areas.

Int J Environ Res Public Health 2021 07 2;18(13). Epub 2021 Jul 2.

School of Microelectronics and Communication Engineering, Chongqing University, Chongqing 400045, China.

In ecologically fragile areas, an uncontrolled increase in urban development intensity (UDI) will erode the ecological carrying capacity (ECC). This study aimed to explore the relationship between UDI and ECC and quantify the impacts of UDI on ECC. The Three Gorges Reservoir Area (Chongqing section) was chosen for the case study. Firstly, the UDI and ECC were comprehensively evaluated. Then, the coupling coordination relationship between the two was analyzed by a coupling coordination degree model. Finally, the influences of UDI on the coordinated development of the two were analyzed by a geographically weighted regression model. The results show that the distributions of UDI and ECC are opposite; UDI and ECC are mutually restricted to some extent. UDI and ECC are moderately coupled and poorly coordinated, and a higher UDI is mostly correlated to a higher coordination degree of UDI and ECC. In areas with higher UDI, an appropriate control on population and economy may benefit the coordinated development. Meanwhile, in areas with lower UDI, the promotion of population aggregation and economic investment would enhance the coordinated development between UDI and ECC. This study could optimize the dimensional control of UDI, which contributes to the long-term sustainability of ecologically fragile areas.
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http://dx.doi.org/10.3390/ijerph18137094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295838PMC
July 2021

Cardiac Glycoside Ouabain Exerts Anticancer Activity Downregulation of STAT3.

Front Oncol 2021 30;11:684316. Epub 2021 Jun 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Cardiac glycosides are plant-derived steroid-like compounds which have been used for the treatment of cardiovascular diseases. Ouabain, a cardiotonic steroid and specific Na/K-ATPase inhibitor, has been rediscovered for its potential use in the treatment of cancer. However, the cellular targets and anticancer mechanism of ouabain in various cancers remain largely unexplored. In this study, we confirmed the cytotoxic effects of ouabain on several cancer cell lines. Further examination revealed the increase of apoptosis, intracellular ROS generation and DNA double-strand breaks induced by ouabain treatment. Besides, ouabain effectively suppressed STAT3 expression as well as phosphorylation in addition to block STAT3-mediated transcription and downstream target proteins. Interestingly, these inhibitory activities seemed to be independent of the Na/K-ATPase. Furthermore, we found that ouabain inhibited protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E binding protein 1 (4EBP1). Taken together, our study provided a novel molecular insight of anticancer activities of ouabain in human cancer cells, which could raise the hope of using cardiac glycosides for cancer therapeutics more rational.
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http://dx.doi.org/10.3389/fonc.2021.684316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279743PMC
June 2021
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