Publications by authors named "Rongrong Wu"

94 Publications

Improved Mechanistic Model of the Atmospheric Redox Chemistry of Mercury.

Environ Sci Technol 2021 11 17;55(21):14445-14456. Epub 2021 Aug 17.

Department of Physics and Astronomy, Mississippi State University, Starkville, Mississippi 39759, United States.

We present a new chemical mechanism for Hg/Hg/Hg atmospheric cycling, including recent laboratory and computational data, and implement it in the GEOS-Chem global atmospheric chemistry model for comparison to observations. Our mechanism includes the oxidation of Hg by Br and OH, subsequent oxidation of Hg by ozone and radicals, respeciation of Hg in aerosols and cloud droplets, and speciated Hg photolysis in the gas and aqueous phases. The tropospheric Hg lifetime against deposition in the model is 5.5 months, consistent with observational constraints. The model reproduces the observed global surface Hg concentrations and Hg wet deposition fluxes. Br and OH make comparable contributions to global net oxidation of Hg to Hg. Ozone is the principal Hg oxidant, enabling the efficient oxidation of Hg to Hg by OH. BrHgOH and Hg(OH), the initial Hg products of Hg oxidation, respeciate in aerosols and clouds to organic and inorganic complexes, and volatilize to photostable forms. Reduction of Hg to Hg takes place largely through photolysis of aqueous Hg-organic complexes. 71% of model Hg deposition is to the oceans. Major uncertainties for atmospheric Hg chemistry modeling include Br concentrations, stability and reactions of Hg, and speciation and photoreduction of Hg in aerosols and clouds.
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http://dx.doi.org/10.1021/acs.est.1c03160DOI Listing
November 2021

Interfacial Interactions within Amyloid Protein Corona Based on 2D MoS Nanosheets.

Chembiochem 2021 Oct 28. Epub 2021 Oct 28.

Institute for Advanced Materials, Jiangsu University, Xuefu Road 301, Zhenjiang, 212000, P. R. China.

The interfacial interaction within the amyloid protein corona based on MoS nanomaterial is crucial, both for understanding the biological effects of MoS nanomaterial and the evolution of amyloid diseases. The specific nano-bio interface phenomenon of human islet amyloid peptide (hIAPP) and MoS nanosheet was investigated by using theoretical and experimental methods. The MoS nanosheet enables the attraction of hIAPP monomer, dimer, and oligomer on its surface through van der Waals forces. Especially, the means of interaction between two hIAPP peptides might be changed by MoS nanosheet. In addition, it is interesting to find that the hIAPP oligomer can stably interact with the MoS nanosheet in one unique "standing" binding mode with an entire exposed β-sheet surface. All the interaction modes on the surface of MoS nanosheet can be the essence of amyloid protein corona that may provide the venue to facilitate the fibrillation of hIAPP proteins. Further, it was verified experimentally that MoS nanosheets could accelerate the fibrillation of hIAPP at a certain concentration mainly based on the newly formed nano-bio interface. In general, our results provide insight into the molecular interaction mechanism of the nano-bio interface within the amyloid protein corona, and shed light on the pathway of amyloid protein aggregation that is related to the evolution of amyloid diseases.
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http://dx.doi.org/10.1002/cbic.202100581DOI Listing
October 2021

Apoptosis-like bacterial death modulated by photoactive hyperthermia nanomaterials and enhanced wound disinfection application.

Nanoscale 2021 Sep 17;13(35):14785-14794. Epub 2021 Sep 17.

Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.

Photothermal therapy (PTT) is considered as an efficient therapeutic strategy for wound disinfection. However, there is a dilemma that on the one hand, the high PTT temperature for killing bacteria (>58 °C) could cause serious injury to normal tissue, however, low-temperature results in unsatisfactory treatment efficiency. To settle the issue, we have proposed a novel approach to gently kill bacteria in an apoptosis-like mode PTT, in which the bacteria can maintain intact membranes but cannot proliferate. This is different from the typical necrosis-like mode of bacterial cell death requiring higher temperatures. We found that PTT prefers to trigger the gradual efflux of Ca/Mg ions from the bacterial intracellular content rather than directly destroy the outer membranes, but can cause the dynamic variation of the membrane surface micromorphology. Hence, the microbial viability of can be dynamically changed from the live state to an apoptosis-like state (45-55 °C), then to apoptosis/necrosis ( 58 °C), and finally to necrosis (>61 °C). Based on this strategy, we can kill bacteria through an apoptosis-like mode. Better healing efficacy of mice wounds was achieved at a PTT temperature of 50 °C as compared to that at 58 °C, which sheds light on the wound disinfection and healing applications in clinics with a mild PTT strategy.
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http://dx.doi.org/10.1039/d1nr02881bDOI Listing
September 2021

The effect of cold exposure on serum cholesterol is dependent upon ApoE.

J Therm Biol 2021 Jul 24;99:102972. Epub 2021 Apr 24.

National Drug Clinical Trial Institution, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. Electronic address:

Background: Several lines of evidence indicate that cold stimulation may not only activate brown adipose tissue (BAT) and the white adipose tissue (WAT), but also regulate the lipid metabolism and influence the development of atherosclerosis. However, the study of cold exposure affecting cholesterol metabolism have opposite results in different experiments, and Apolipoprotein E (ApoE) may play an important role. There is still a lack of complete research to illustrate this problem.

Methods: In this study, we first analyzed and discussed the activation of interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) under cold exposure (4 °C) in male wild-type C57BL/6 J (WT) and ApoE-deficient mice (ApoE) fed high-fat diet (HFD) for 4 weeks. Subsequently, we investigated the effect of cold exposure on blood lipid profiles in both models. We further explored whether cold exposure can reduce serum cholesterol.

Results: In both WT and ApoE mice, cold exposure activates iBAT and iWAT, as well as hardly affects eWAT. In WT mice,4 weeks cold exposure (4 °C) reduces serum triglyceride by 28%, cholesterol by 30% and LDL-cholesterol by 63%. In ApoE mice, cold stimulation decreases serum triglyceride by 59%, but increases cholesterol by 20% and LDL-cholesterol by 25%.

Conclusions: Based on these findings, we conclude that cold exposure decreases serum cholesterol is dependent upon the existence of ApoE.
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http://dx.doi.org/10.1016/j.jtherbio.2021.102972DOI Listing
July 2021

A versatile pH-responsive peptide based dynamic biointerface for tracking bacteria killing and infection resistance.

Biomater Sci 2021 Sep 5;9(17):5785-5790. Epub 2021 Aug 5.

Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, Jiangsu, China.

Herein we reported a versatile dynamic biointerface based on pH-responsive peptide self-assembly and disassembly to capture the bacteria to avoid bacteria further infected tissue around that can release peptides from the surface in a slightly acidic environment to kill the bacteria with the specificity. The exposed biointerface still presented infection resistance.
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http://dx.doi.org/10.1039/d1bm00950hDOI Listing
September 2021

A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.

Adv Sci (Weinh) 2021 09 28;8(18):e2004629. Epub 2021 Jul 28.

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, P. R. China.

Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under-explored. Human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow-derived MSCs (hBM-MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES-MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES-MSCs versus hBM-MSCs, and named as SCDAL (stem cell-derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES-MSCs in the infarcted hearts, while overexpression of SCDAL in either hES-MSCs or hBM-MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non-canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL-GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA-dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL-GDF6 pathway has potential as a therapy for ischemic heart diseases.
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http://dx.doi.org/10.1002/advs.202004629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456203PMC
September 2021

Activatable Ratiometric NIR-II Fluorescence Nanoprobe for Quantitative Detection of HS in Colon Cancer.

Anal Chem 2021 07 30;93(27):9356-9363. Epub 2021 Jun 30.

MOE key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China.

As key characteristic molecules, several HS-activated probes have been explored for colon cancer studies. However, a few ratiometric fluorescence (FL) probes with NIR-II emissions have been reported for the quantitative detection of HS in colon cancer . Here, we developed an HS-activatable ratiometric nanoprobe with two NIR-II emission signals for the detection of HS and intelligently lighting up colon cancer. The nanoprobe comprised a down conversion nanoparticle (DCNP), which emitted NIR-II FL at 1550 nm on irradiation with a 980 nm laser (F). Further, human serum albumin (HSA) was combined with Ag on the surface of DCNP to form a [email protected] nanoprobe. In the presence of HS, AgS quantum dots (QDs) were formed in coated HSA, which emitted FL at approximately 1050 nm on irradiation with an 808 nm laser (F) through an HS-induced chemical reaction between HS and Ag; however, the FL signal of DCNP was stable at 1550 nm (F), generating a HS concentration-dependent ratiometric F/F signal. The NIR-II ratiometric nanoprobe was successfully used for the accurate quantitative detection of HS and the detection of the precise location of colon cancer through an endogenous HS-induced reduction reaction to form AgS QDs. Thus, these findings provide a new strategy for the specific detection of targeted molecules and diagnosis of disease based on the -activatable NIR-II ratiometric FL nanoprobe.
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http://dx.doi.org/10.1021/acs.analchem.1c00427DOI Listing
July 2021

HFBD: a biomarker knowledge database for heart failure heterogeneity and personalized applications.

Bioinformatics 2021 Jun 23. Epub 2021 Jun 23.

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610212, Sichuan, China.

Motivation: Heart failure (HF) is a cardiovascular disease with a high incidence around the world. Accumulating studies have focused on the identification of biomarkers for HF precision medicine. To understand the HF heterogeneity and provide biomarker information for the personalized diagnosis and treatment of HF, a knowledge database collecting the distributed and multiple-level biomarker information is necessary.

Results: In this study, the HF biomarker knowledge database (HFBD) was established by manually collecting the data and knowledge from literature in PubMed. HFBD contains 2618 records and 868 HF biomarkers (731 single and 137 combined) extracted from 1237 original articles. The biomarkers were classified into proteins, RNAs, DNAs, and the others at molecular, image, cellular and physiological levels. The biomarkers were annotated with biological, clinical and article information as well as the experimental methods used for the biomarker discovery. With its user-friendly interface, this knowledge database provides a unique resource for the systematic understanding of HF heterogeneity and personalized diagnosis and treatment of HF in the era of precision medicine.

Availability: The platform is openly available at http://sysbio.org.cn/HFBD/.
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http://dx.doi.org/10.1093/bioinformatics/btab470DOI Listing
June 2021

Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A.

ChemistryOpen 2021 06;10(6):630-638

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC values of 2.30 and 2.45 μM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A , but also higher binding selectivity to A receptors than to A and A receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A receptors.
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http://dx.doi.org/10.1002/open.202100022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186885PMC
June 2021

MAP kinase Hog1 mediates a cytochrome P450 oxidoreductase to promote the Sporisorium scitamineum cell survival under oxidative stress.

Environ Microbiol 2021 06 19;23(6):3306-3317. Epub 2021 May 19.

College of Plant Protection, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

The MAP kinase high osmolarity glycerol 1 (Hog1) plays a central role in responding to external oxidative stress in budding yeast Saccchromyces cerevisiae. However, the downstream responsive elements regulated by Hog1 remain poorly understood. In this study, we report that a Sporisorium scitamineum orthologue of Hog1, named as SsHog1, induced transcriptional expression of a putative cytochrome P450 oxidoreductase encoding gene SsCPR1, to antagonize oxidative stress. We found that upon exposure to hydrogen peroxide (H O ), SsHog1 underwent strikingly phosphorylation, which was proved to be critical for transcriptional induction of SsCPR1. Loss of SsCPR1 led to hypersensitive to oxidative stress similar as the sshog1Δ mutant did, but was resistant to osmotic stress, which is different from the sshog1Δ mutant. On the other hand, overexpression of SsCPR1 in the sshog1Δ mutant could partially restore its ability of oxidative stress tolerance, which indicated that the Hog1 MAP kinase regulates the oxidative stress response specifically through cytochrome P450 (SsCpr1) pathway. Overall, our findings highlight a novel MAPK signalling pathway mediated by Hog1 in regulation of the oxidative stress response via the cytochrome P450 system, which plays an important role in host-fungus interaction.
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http://dx.doi.org/10.1111/1462-2920.15565DOI Listing
June 2021

Gas-Particle Partitioning and SOA Yields of Organonitrate Products from NO-Initiated Oxidation of Isoprene under Varied Chemical Regimes.

ACS Earth Space Chem 2021 Apr 11;5(4):785-800. Epub 2021 Mar 11.

Chemistry Department and Environmental Studies Program, Reed College, Portland, Oregon 97202, United States.

Alkyl nitrate (AN) and secondary organic aerosol (SOA) from the reaction of nitrate radicals (NO) with isoprene were observed in the Simulation of Atmospheric PHotochemistry In a large Reaction (SAPHIR) chamber during the NOIsop campaign in August 2018. Based on 15 day-long experiments under various reaction conditions, we conclude that the reaction has a nominally unity molar AN yield (observed range 90 ± 40%) and an SOA mass yield of OA + organic nitrate aerosol of 13-15% (with ∼50 μg m inorganic seed aerosol and 2-5 μg m total organic aerosol). Isoprene (5-25 ppb) and oxidant (typically ∼100 ppb O and 5-25 ppb NO) concentrations and aerosol composition (inorganic and organic coating) were varied while remaining close to ambient conditions, producing similar AN and SOA yields under all regimes. We observe the formation of dinitrates upon oxidation of the second double bond only once the isoprene precursor is fully consumed. We determine the bulk partitioning coefficient for ANs ( ∼ 10 m μg), indicating an average volatility corresponding to a C hydroxy hydroperoxy nitrate.
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http://dx.doi.org/10.1021/acsearthspacechem.0c00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054245PMC
April 2021

A case of hereditary metachronous bilateral triple-negative breast cancer that was highly sensitive to carboplatin.

J Surg Case Rep 2021 Apr 14;2021(4):rjab018. Epub 2021 Apr 14.

Department of Breast Oncology and Surgery, Tokyo Medical University, Tokyo, Japan.

A 52-year-old woman with a strong family history of breast cancer was diagnosed as having triple-negative breast cancer (TNBC) in her right breast. Neoadjuvant chemotherapy (NAC; four cycles of epirubicin/cyclophosphamide/5-fluorouracil) was performed, followed by breast-conserving surgery and axillary lymph node dissection. Histopathological analysis of the surgical specimens demonstrated a few focal tumor cells remaining in the stroma, but not a pathological complete response (pCR). Weekly paclitaxel was subsequently added to the treatment regimen. A total of 17 months after the adjuvant treatments, TNBC recurred in her left breast with massive lymph node metastasis. Because of the early recurrence after standard treatment, NAC was administered together with carboplatin and paclitaxel. Histopathological analysis of the partially resected breast and axillary lymph nodes demonstrated a pCR. No recurrent disease was found 2 years after the second TNBC treatment. This case underlines the importance of platinum-based chemotherapy and prophylactic mastectomy for patients with BRCA dysfunction.
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http://dx.doi.org/10.1093/jscr/rjab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046408PMC
April 2021

Human gut bacterial β-glucuronidase inhibition: An emerging approach to manage medication therapy.

Biochem Pharmacol 2021 08 16;190:114566. Epub 2021 Apr 16.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. Electronic address:

Bacterial β-glucuronidase enzymes (BGUSs) are at the interface of host-microbial metabolic symbiosis, playing an important role in health and disease as well as medication outcomes (efficacy or toxicity) by deconjugating a large number of endogenous and exogenous glucuronides. In recent years, BGUSs inhibition has emerged as a new approach to manage diseases and medication therapy and attracted an increasing research interest. However, a growing body of evidence underlines great genetic diversity, functional promiscuity and varied inhibition propensity of BGUSs, which have posed big challenges to identifying BGUSs involved in a specific pathophysiological or pharmacological process and developing effective inhibition. In this article, we offered a general introduction of the function, in particular the physiological, pathological and pharmacological roles, of BGUSs and their taxonomic distribution in human gut microbiota, highlighting the structural features (active sites and adjacent loop structures) that affecting the protein-substrate (inhibitor) interactions. Recent advances in BGUSs-mediated deconjugation of drugs and carcinogens and the discovery and applications of BGUS inhibitors in management of medication therapy, typically, irinotecan-induced diarrhea and non-steroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy, were also reviewed. At the end, we discussed the perspectives and the challenges of tailoring BGUS inhibition towards precision medicine.
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http://dx.doi.org/10.1016/j.bcp.2021.114566DOI Listing
August 2021

Research for improvement on the extract efficiency of lignans in traditional Chinese medicines by hybrid ionic liquids: As a case of Suhuang antitussive capsule.

Ultrason Sonochem 2021 May 25;73:105539. Epub 2021 Mar 25.

State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:

Recently, efficient extraction of natural products from traditional Chinese medicines (TCMs) by green solvents is deemed an essential area of green technology and attracts extensive attentions. In this work, a green protocol for simultaneous ultrasonic-extraction of the native compounds with different polarities of TCMs by using a hybrid ionic liquids (HILs)-water system was reported for the first time. As a case study, three superior ILs (1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), and 1-allyl-3-methylimidazolium chloride ([AMIM]Cl)) were chosen as the compositions of the HILs system, and the TCMs Suhuang antitussive capsule (SH) containing different-polarity lignans was selected. Primarily, an ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method in the multiple reaction monitoring (MRM) mode was established for qualitative and quantitative analysis of 18 lignans. After majorization by uniform design experiment, the HILs prepared with [AMIM]Cl, [EMIM][BF4], and [EMIM][OAc] at a volume ratio of 1:5:5 could simultaneously extract multi-polarity lignans compared to single IL. Subsequently, the conditions of ultrasonic extraction employing with HILs and traditional organic solvent were optimized by the response surface methodology, respectively. The results indicated that the extract efficiency of the HILs system for target compounds was significantly improved compared with the traditional organic solvent-extraction, i.e. the content of total lignans in ethanol system was up to 47 mg/g, while that in the HILs system was up to 69 mg/g, with an increasing of 47%. Additionally, H-NMR and C-NMR spectra were used to characterize the hydrogen-bond interactions in the HILs-lignan mixtures. Extraction with the HILs in TCMs is a new application schema of ILs, which not only avoids the use of volatile toxic organic solvents, but also shows the potential to be comprehensively applied for the extraction of bioactive compounds from TCMs.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053792PMC
May 2021

Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates.

Sci Transl Med 2021 03;13(584)

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China.

Stem cell-derived small extracellular vesicles (sEVs) promote angiogenesis after myocardial infarction (MI). However, the components of sEVs that contribute to these effects and the safety and efficiency of engineered sEV treatment for MI remain unresolved. Here, we observed improved cardiac function, enhanced vascular density, and smaller infarct size in mice treated with the sEVs from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) (HP-sEVs) than in mice treated with normoxia-preconditioned (N) MSCs (N-sEVs). MicroRNA profiling revealed a higher abundance of miR-486-5p in HP-sEVs than in N-sEVs, and miR-486-5p inactivation abolished the benefit of HP-sEV treatment, whereas miR-486-5p up-regulation enhanced the benefit of N-sEV treatment. Matrix metalloproteinase 19 (MMP19) abundance was lower in HP-sEV-treated than N-sEV-treated mouse hearts but was enriched in cardiac fibroblasts (CFs), and was identified as one of the target genes of miR-486-5p. Conditioned medium from CFs that overexpressed miR-486-5p or silenced MMP19 increased the angiogenic activity of endothelial cells; however, medium from CFs that simultaneously overexpressed and miR-486-5p abolished this effect. silencing in CFs reduced the cleavage of extracellular vascular endothelial growth factor (VEGF). Furthermore, miR-486-5p-overexpressing N-sEV treatment promoted angiogenesis and cardiac recovery without increasing arrhythmia complications in a nonhuman primate (NHP) MI model. Collectively, this study highlights the key role of sEV miR-486-5p in promoting cardiac angiogenesis via fibroblastic MMP19-VEGFA cleavage signaling. Delivery of miR-486-5p-engineered sEVs safely enhanced angiogenesis and cardiac function in an NHP MI model and may promote cardiac repair.
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http://dx.doi.org/10.1126/scitranslmed.abb0202DOI Listing
March 2021

Crystalline silica particles induce DNA damage in respiratory epithelium by ATX secretion and Rac1 activation.

Biochem Biophys Res Commun 2021 04 23;548:91-97. Epub 2021 Feb 23.

Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177, Stockholm, Sweden. Electronic address:

Autotaxin (ATX) and its product lysophosphatidic acid (LPA) have been implicated in lung fibrosis and cancer. We have studied their roles in DNA damage induced by carcinogenic crystalline silica particles (CSi). In an earlier study on bronchial epithelia, we concluded that ATX, via paracrine signaling, amplifies DNA damage. This effect was seen at 6-16 h. A succeeding study showed that CSi induced NLRP3 phosphorylation, mitochondrial depolarization, double strand breaks (DSBs), and NHEJ repair enzymes within minutes. In the current study we hypothesized a role for the ATX-LPA axis also in this rapid DNA damage. Using 16HBE human bronchial epithelial cells, we show ATX secretion at 3 min, and that ATX inhibitors (HA130 and PF8380) prevented both CSi-induced mitochondrial depolarization and DNA damage (detected by γH2AX and Comet assay analysis). Experiments with added LPA gave similar rapid effects as CSi. Furthermore, Rac1 was activated at 3 min, and a Rac1 inhibitor (NSC23766) prevented mitochondrial depolarization and genotoxicity. In mice the bronchial epithelia exhibited histological signs of ATX activation and signs of DSBs (53BP1 positive nuclei) minutes after a single inhalation of CSi. Our data indicate that CSi rapidly activate the ATX-LPA axis and within minutes this leads to DNA damage in bronchial epithelial cells. Thus, ATX mediates very rapid DNA damaging effects of inhaled particles.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.020DOI Listing
April 2021

Knockdown of estrogen-related receptor α inhibits valve interstitial cell calcification in vitro by regulating heme oxygenase 1.

FASEB J 2021 02 13;35(2):e21183. Epub 2020 Nov 13.

Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in adults. The cellular mechanisms of CAVD are still unknown, but accumulating evidence has revealed that osteogenic differentiation of human valve interstitial cells (hVICs) plays an important role in CAVD. Thus, we aimed to investigate the function of estrogen-related receptor α (ERRα) in the osteogenic differentiation of hVICs. We found that the level of ERRα was significantly increased in CAVD samples compared to normal controls. In addition, ERRα was significantly upregulated during hVIC osteogenic differentiation in vitro. Gain- and loss-of-function experiments were performed to identify the function of ERRα in hVIC calcification in vitro. Inhibition of endogenous ERRα attenuated hVIC calcification, whereas overexpression of ERRα in hVICs promoted this process. RNA sequencing results suggested that heme oxygenase-1 (Hmox1) was a downstream target of ERRα, which was further confirmed by western blotting. Additionally, we also found that downregulation of Hmox1 by shHmox1 efficiently reversed the inhibition of calcification induced by ERRα shRNA in hVICs. ChIP-qPCR and luciferase assays indicated that Hmox1 was negatively regulated by ERRα. We found that overexpression of Hmox1 or its substrates significantly inhibited hVIC calcification in vitro. In conclusion, we found that knockdown of ERRα can inhibit hVIC calcification through upregulating Hmox1 and that ERRα and Hmox1 are potential targets for the treatment of CAVD.
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http://dx.doi.org/10.1096/fj.202001588RRDOI Listing
February 2021

Visualizing and Isolating Iron-Reducing Microorganisms at the Single-Cell Level.

Appl Environ Microbiol 2021 01 15;87(3). Epub 2021 Jan 15.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Iron-reducing microorganisms (FeRM) play key roles in many natural and engineering processes. Visualizing and isolating FeRM from multispecies samples are essential to understand the location and geochemical role of FeRM. Here, we visualized FeRM by a "turn-on" Fe-specific fluorescent chemodosimeter (FSFC) with high sensitivity, selectivity, and stability. This FSFC could selectively identify and locate active FeRM from either pure culture, coculture of different bacteria, or sediment-containing samples. Fluorescent intensity of the FSFC could be used as an indicator of Fe concentration in bacterial cultures. By combining the use of the FSFC with that of a single-cell sorter, we obtained three FSFC-labeled cells from an enriched consortium, and all of them were subsequently shown to be capable of iron reduction; two unlabeled cells were shown to have no iron-reducing capability, further confirming the feasibility of the FSFC. Visualization and isolation of FeRM from samples containing multiple species are commonly needed by researchers from different disciplines, such as environmental microbiology, environmental sciences, and geochemistry. However, no available method has been reported. In this study, we provide a method to visualize FeRM and evaluate their activity even at the single-cell level. When this approach is combined with use of a single-cell sorter, FeRM can also be isolated from samples containing multiple species. This method can be used as a powerful tool to uncover the or role of FeRM and their interactions with ambient microbes or chemicals.
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http://dx.doi.org/10.1128/AEM.02192-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848898PMC
January 2021

Structural conversion of human islet amyloid polypeptide aggregates under an electric field.

Chem Commun (Camb) 2020 Sep;56(77):11497-11500

Institute for Advanced Materials, Jiangsu University, China.

Electric fields (EFs) in biological systems are well known, and their presence implies the activity of protein ion channels and pumps in various cells. The aggregation of islet amyloid polypeptides (IAPP) was recently found in human brain tissue, and this was related to the electrical activity of neurons and caused neuronal loss. However, the association between amyloid formation and the electric field is still unknown. Herein a direct method to stimulate the formation of the hIAPP peptide under an EF is reported.
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http://dx.doi.org/10.1039/d0cc04466kDOI Listing
September 2020

Crystalline silica particles cause rapid NLRP3-dependent mitochondrial depolarization and DNA damage in airway epithelial cells.

Part Fibre Toxicol 2020 08 10;17(1):39. Epub 2020 Aug 10.

Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177, Stockholm, Sweden.

Background: Respirable crystalline silica causes lung carcinomas and many thousand future cancer cases are expected in e.g. Europe. Critical questions are how silica causes genotoxicity in the respiratory epithelium and if new cases can be avoided by lowered permissible exposure levels. In this study we investigate early DNA damaging effects of low doses of silica particles in respiratory epithelial cells in vitro and in vivo in an effort to understand low-dose carcinogenic effects of silica particles.

Results: We find DNA damage accumulation already after 5-10 min exposure to low doses (5 μg/cm) of silica particles (Min-U-Sil 5) in vitro. DNA damage was documented as increased levels of γH2AX, pCHK2, by Comet assay, AIM2 induction, and by increased DNA repair (non-homologous end joining) signaling. The DNA damage response (DDR) was not related to increased ROS levels, but to a NLRP3-dependent mitochondrial depolarization. Particles in contact with the plasma membrane elicited a Ser198 phosphorylation of NLRP3, co-localization of NLRP3 to mitochondria and depolarization. FCCP, a mitochondrial uncoupler, as well as overexpressed NLRP3 mimicked the silica-induced depolarization and the DNA damage response. A single inhalation of 25 μg silica particles gave a similar rapid DDR in mouse lung. Biomarkers (CC10 and GPRC5A) indicated an involvement of respiratory epithelial cells.

Conclusions: Our findings demonstrate a novel mode of action (MOA) for silica-induced DNA damage and mutagenic double strand breaks in airway epithelial cells. This MOA seems independent of particle uptake and of an involvement of macrophages. Our study might help defining models for estimating exposure levels without DNA damaging effects.
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http://dx.doi.org/10.1186/s12989-020-00370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418441PMC
August 2020

Neurally adjusted ventilatory assist after surgical treatment of intracerebral hemorrhage: a randomized crossover study.

J Int Med Res 2020 Jul;48(7):300060520939837

Department of Neurosurgery, Research Center for Functional Maintenance and Reconstruction of Viscera, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, China.

Objective: We assessed the neuromechanical efficiency (NME), neuroventilatory efficiency (NVE), and diaphragmatic function effects between pressure support ventilation (PSV) and neutrally adjusted ventilatory assist (NAVA).

Methods: Fifteen patients who had undergone surgical treatment of intracerebral hemorrhage were enrolled in this randomized crossover study. The patients were assigned to PSV for the first 24 hours and then to NAVA for the following 24 hours or vice versa. The monitored ventilatory parameters under the two ventilation models were compared. NME, NVE, and diaphragmatic function were compared between the two ventilation models.

Results: One patient's illness worsened during the study. The study was stopped for this patient, and intact data were obtained from the other 14 patients and analyzed. The monitored tidal volume was significantly higher with PSV than NAVA (487 [443-615] vs. 440 [400-480] mL, respectively). NME, NVE, diaphragmatic function, and the partial pressures of arterial carbon dioxide and oxygen were not significantly different between the two ventilation models.

Conclusion: The tidal volume was lower with NAVA than PSV; however, the patients' selected respiratory pattern during NAVA did not change the NME, NVE, or diaphragmatic function.Clinical trial registration no. ChiCTR1900022861.
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http://dx.doi.org/10.1177/0300060520939837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388128PMC
July 2020

Establishment of two induced pluripotent stem cell line from healthy elderly (IPTi005-A and IPTi007-A).

Stem Cell Res 2020 05 21;45:101808. Epub 2020 Apr 21.

Beijing Institute of Pharmacology and Toxicology; Beijing, China; State Key Laboratory of Toxicology and Medical Countermeasures; Beijing, China.

Two healthy elderly donated their peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell lines (IPTi005-A and IPTi007-A) were reprogrammed by episomal vector system with Yamanaka factors OCT4, SOX2, C-MYC and KLF4. Both the two iPSC lines can differentiate into three germ layers determined by embryoid bodies (EBs) differentiation. Flow cytometry analysis showed that more than 90% cells expressed NANOG, OCT4 and SSEA4. Besides, the iPSC lines of IPTi005-A and IPTi007-A were confirmed to exhibit a normal karyotype. In the studies of age-related disease, the iPSC lines can be used as controls.
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http://dx.doi.org/10.1016/j.scr.2020.101808DOI Listing
May 2020

MicroRNA Alterations for Diagnosis, Prognosis, and Treatment of Osteoporosis: A Comprehensive Review and Computational Functional Survey.

Front Genet 2020 3;11:181. Epub 2020 Mar 3.

Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, China.

Osteoporosis (OP) is a systemic bone disease with a series of clinical symptoms. The use of screening biomarkers in OP management is therefore of clinical significance, especially in the era of precision medicine and intelligent healthcare. MicroRNAs (miRNAs) are small, non-coding RNAs with the potential to regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs may serve as biomarkers for OP prediction and prevention. However, few studies have emphasized the role of miRNAs in systems-level pathogenesis during OP development. In this article, literature-reported OP miRNAs were manually collected and analyzed based on a systems biology paradigm. Functional enrichment studies were performed to decode the underlying mechanisms of miRNAs in OP etiology and therapeutics in three-dimensional space, i.e., integrated miRNA-gene-pathway analysis. In particular, interactions between miRNAs and three well-known OP pathways, i.e., estrogen-endocrine, WNT/β-catenin signaling, and RANKL/RANK/OPG, were systematically investigated, and the effects of non-genetic factors on personalized OP prevention and therapy were discussed. This article is a comprehensive review of OP miRNAs, and bridges the gap between an understanding of OP pathogenesis and clinical translation.
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http://dx.doi.org/10.3389/fgene.2020.00181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063117PMC
March 2020

A randomized controlled pilot study of the effectiveness of magnolia tea on alleviating depression in postnatal women.

Food Sci Nutr 2020 Mar 10;8(3):1554-1561. Epub 2020 Feb 10.

Department of Laboratory Jiaxing University Affiliated Women and Children Hospital Jiaxing China.

The magnolia tea has been used in traditional oriental medicine for multiple purposes including sleep aid. Postpartum depression is a mental illness that adversely affects the health and well-being of many families with newborns. Given the known effectiveness and relative safety, herein we aimed to investigate whether magnolia tea has a palliative effect on postpartum depression. The qualified participants were randomly assigned to the intervention group or the control group. The participants in the intervention group drunk magnolia tea, while the control group received regular postpartum care only. The outcome variables including Postpartum Sleep Quality Scale (PSQS), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Fatigue Scale (PFS) were assessed and compared. In comparison with the control group, the intervention group demonstrated significant difference for physical-symptom-related sleep inefficiency (PSQS Factor 2) at 3 weeks post-test ( = -2.10,  = .03). The comparison results also revealed significant differences for PFS at both 3 weeks post-test ( = -2.02,  = .04) and 6 weeks post-test ( = -1.99,  = .04). Further, magnolia tea intervention significantly alleviated the symptoms of depression, reflected by the EPDS scores at 3 weeks post-test ( = -2.38,  = .02) and 6 weeks post-test ( = -2.13,  = .02). Our trial results suggested that drinking single-ingredient magnolia tea for a 3-week duration has positive effects on postpartum women. Magnolia tea is recommended as a supplementary approach to ameliorate sleep quality of postpartum women, while alleviating their symptoms of depression.
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http://dx.doi.org/10.1002/fsn3.1442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063344PMC
March 2020

Early Detection of Sudden Cardiac Death by Using Ensemble Empirical Mode Decomposition-Based Entropy and Classical Linear Features From Heart Rate Variability Signals.

Front Physiol 2020 25;11:118. Epub 2020 Feb 25.

Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, China.

Sudden cardiac death (SCD), which can deprive a person of life within minutes, is a destructive heart abnormality. Thus, providing early warning information for patients at risk of SCD, especially those outside hospitals, is essential. In this study, we investigated the performances of ensemble empirical mode decomposition (EEMD)-based entropy features on SCD identification. EEMD-based entropy features were obtained by using the following technology: (1) EEMD was performed on HRV beats to decompose them into intrinsic mode functions (IMFs), (2) five entropy parameters, namely Rényi entropy (RenEn), fuzzy entropy (FuEn), dispersion Entropy (DisEn), improved multiscale permutation entropy (IMPE), and Renyi distribution entropy(RdisEn), were computed from the first four IMFs obtained, which were named EEMD-based entropy features. Additionally, an automated scheme combining EEMD-based entropy and classical linear (time and frequency domains) features was proposed with the intention of detecting SCD early by analyzing 14 min (at seven successive intervals of 2 min) heart rate variability (HRV) in signals from a normal population and subjects at risk of SCD. Firstly, EEMD-based entropy and classical linear measurements were extracted from HRV beats, and then the integrated measurements were ranked by various methodologies, i.e., -test, entropy, receiver-operating characteristics (ROC), Wilcoxon, and Bhattacharyya. Finally, these ranked features were fed into a k-Nearest Neighbor algorithm for classification. Compared with several state-of-the-art methods, the proposed scheme firstly predicted subjects at risk of SCD up to 14 min earlier with an accuracy of 96.1%, a sensitivity of 97.5%, and a specificity of 94.4% 14 min before SCD onset. The simulation results exhibited that EEMD-based entropy estimators showed significant difference between SCD patients and normal individuals and outperformed the classical linear estimators in SCD detection, the EEMD-based FuEn and IMPE indexes were particularly useful assessments for identification of patients at risk of SCD and can be used as novel indices to reveal the disorders of rhythm variations of the autonomic nervous system when affected by SCD.
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http://dx.doi.org/10.3389/fphys.2020.00118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052183PMC
February 2020

Phenotype-genotype network construction and characterization: a case study of cardiovascular diseases and associated non-coding RNAs.

Database (Oxford) 2020 01;2020

Institutes for Systems Genetics, West China Hospital, Sichuan University, No. 17 Gaopeng Avenue, Ji Tai'an Center, Chengdu, Sichuan 610041, China.

The phenotype-genotype relationship is a key for personalized and precision medicine for complex diseases. To unravel the complexity of the clinical phenotype-genotype network, we used cardiovascular diseases (CVDs) and associated non-coding RNAs (ncRNAs) (i.e. miRNAs, long ncRNAs, etc.) as the case for the study of CVDs at a systems or network level. We first integrated a database of CVDs and ncRNAs (CVDncR, http://sysbio.org.cn/cvdncr/) to construct CVD-ncRNA networks and annotate their clinical associations. To characterize the networks, we then separated the miRNAs into two groups, i.e. universal miRNAs associated with at least two types of CVDs and specific miRNAs related only to one type of CVD. Our analyses indicated two interesting patterns in these CVD-ncRNA networks. First, scale-free features were present within both CVD-miRNA and CVD-lncRNA networks; second, universal miRNAs were more likely to be CVDs biomarkers. These results were confirmed by computational functional analyses. The findings offer theoretical guidance for decoding CVD-ncRNA associations and will facilitate the screening of CVD ncRNA biomarkers. Database URL: http://sysbio.org.cn/cvdncr/.
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http://dx.doi.org/10.1093/database/baz147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964217PMC
January 2020

Asymptomatic Mediastinal Extra-adrenal Paraganglioma as a Cause of Sudden Death: A Case Report.

Open Life Sci 2019 Jan 31;14:564-567. Epub 2019 Dec 31.

Department of Critical Care Medicine, Research Center for functional maintenance and reconstruction of viscera, Wannan Medical College First Affiliated Hospital, Yijishan Hospital, Wuhu, China, 241000.

A 23-year-old female patient was referred for treatment of a posterior mediastinal tumour. There was no history of hypertension or headache and no other complaints. The patient's blood pressure increased to 210/125 mmHg after surgically manipulating the tumour, subsequently reversing to severe hypotension (25/15 mmHg) immediately after the tumour was removed. The life-threatening and irreversible blood pressure drop was difficult to treat with fluid and vasopressors, and the patient ultimately died of cardio-respiratory failure. Asymptomatic paraganglioma can be non-functional but can also be fatal. For any lump in the thoracic cavity, paraganglioma should be ruled out.
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http://dx.doi.org/10.1515/biol-2019-0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874807PMC
January 2019

Plasma homocysteine, folate and vitamin B12 levels in Parkinson's disease in China: A meta-analysis.

Clin Neurol Neurosurg 2020 01 4;188:105587. Epub 2019 Nov 4.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China. Electronic address:

Epidemiological studies evaluating the associations of plasma homocysteine (Hcy), folate and vitamin B12 levels with Parkinson's disease (PD) in China have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. PubMed, Cochrane Library, Elsevier Science Direct, Springer, CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) databases were searched for eligible studies from January 2000 to November 2018. The pooled standardized mean difference (SMD), Fisher's Z and corresponding 95% confidence interval (95% CI) were calculated with fix-effects or random-effects model. In total, 26 case-control studies and 1 cross-sectional study were included in this meta-analysis. The results showed that: (1) PD patients had a higher Hcy level than the control individuals (P <0.05). After stratification subgroup, significant differences of plasma Hcy level between PD patients and controls were found in subgroup with sample size< 100, sample size ≥100, as well as in the subgroup analysis by levodopa therapy. (2) Both plasma folate and vitamin B12 levels were lower in the PD patients compared with the control group (P <0.05). (3) Plasma Hcy level was negatively correlated with plasma levels of folate and vitamin Bl2 in PD patients (P <0.05). (4) The relevant influential factors of plasma Hcy level in PD patients were clinical types, Hoehn & Yahr stage, cognitive impairment, or levodopa therapy (P <0.05). In conclusion, PD patients had a higher Hcy level in China. Multiple factors were associated with Hcy levels of Chinese PD patients.
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http://dx.doi.org/10.1016/j.clineuro.2019.105587DOI Listing
January 2020

Generation of induced pluripotent stem cell line (IPTi001-A) from a 62-year old sporadic Alzheimer's disease patient with APOE3 (ε3/ε3) genotype.

Stem Cell Res 2019 12 15;41:101589. Epub 2019 Oct 15.

Beijing Institute of Pharmacology and Toxicology, Beijing, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China. Electronic address:

A 62-year old sporadic Alzheimer's disease (sAD) male patient with APOE3 (ε3/ε3) genotype donated his peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell (iPSC) line was established by episomal vector system with the four factors OCT4, SOX2, C-MYC and KLF4. EB differentiation in vitro showed that iPSC line had a potential to differentiate into three germ layers. More than 90% cells expressed NANOG, OCT4 and SSEA4 detected by flow cytometry. In addition, the iPSC line was karyotypically normal. The iPSC line may provide new valuable tools for studying pathogenesis of sAD and screening candidate drugs for the disease.
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http://dx.doi.org/10.1016/j.scr.2019.101589DOI Listing
December 2019

MIRKB: a myocardial infarction risk knowledge base.

Database (Oxford) 2019 01;2019

Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu 610041, China.

Myocardial infarction (MI) is a common cardiovascular disease and a leading cause of death worldwide. The etiology of MI is complicated and not completely understood. Many risk factors are reported important for the development of MI, including lifestyle factors, environmental factors, psychosocial factors, genetic factors, etc. Identifying individuals with an increased risk of MI is urgent and a major challenge for improving prevention. The MI risk knowledge base (MIRKB) is developed for facilitating MI research and prevention. The goal of MIRKB is to collect risk factors and models related to MI to increase the efficiency of systems biological level understanding of the disease. MIRKB contains 8436 entries collected from 4366 articles in PubMed before 5 July 2019 with 7902 entries for 1847 single factors, 195 entries for 157 combined factors and 339 entries for 174 risk models. The single factors are classified into the following five categories based on their characteristics: molecular factor (2356 entries, 649 factors), imaging (821 entries, 252 factors), physiological factor (1566 entries, 219 factors), clinical factor (2523 entries, 561 factors), environmental factor (46 entries, 26 factors), lifestyle factor (306 entries, 65 factors) and psychosocial factor (284 entries, 75 factors). MIRKB will be helpful to the future systems level unraveling of the complex mechanism of MI genesis and progression.
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http://dx.doi.org/10.1093/database/baz125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830040PMC
January 2019
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