Publications by authors named "Yongjian Yang"

90 Publications

Effects of dexmedetomide, propofol and remifentanil on perioperative inflammatory response and lung function during lung cancer surgery.

Am J Transl Res 2021 15;13(4):2537-2545. Epub 2021 Apr 15.

Department of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University Jinan 250014, Shandong Province, China.

Objective: To investigate the effects of combined anesthesia with dexmedetomide, propofol and remifentanil on perioperative inflammatory response and pulmonary function in patients with lung cancer.

Methods: 90 patients with lung cancer admitted to our hospital from April 2017 to April 2019 were selected. According to different anesthesia schemes, patients undergoing combined anesthesia with propofol and remifentanil were included in group A (GA), and patients receiving combined anesthesia with dexmedetomidine, propofol and remifentanil were included in group B (GB). The blood gas, pulmonary function index, inflammatory factor level in serum, anesthetic effect and complications were compared between the two groups.

Results: HR indexes at T1 and T2 in GB were significantly lower than those in GA (P<0.001). There was no significant fluctuation in PaCO2 and PaO2 indexes in the two groups at different time points (P>0.05). At T0, T1 and T2, RV/TLC levels in serum increased significantly in the two groups. (MVV-VE)/FEV1 and MVV/FEV levels were significantly decreased (all P<0.05). The fluctuation levels of RV/TLC, (MVV-VE)/FEV1 and MVV/FEV levels in serum of GB were significantly lower than those of GA at T1 and T2 (P<0.05). At T0, T1 and T2, the levels of inflammatory factors in serum were significantly decreased in the two groups (P<0.05), but the levels of inflammatory factors in serum of GB were significantly lower than those of GA at T1 and T2 (P<0.05). The VAS scores of GB were significantly lower than those of GA at 1 hour and 4 hours after operation (P<0.05). Ramsay scores of GB were significantly higher than those of GA at 1 hour and 4 hours after operation (P<0.05). The restlessness score and choking cough score in GB were lower than those in GA (P<0.05). Perioperative complications in GB were better than those in GA (P<0.05).

Conclusion: On the basis of propofol and remifentanil anesthesia, the combination of dexmedetomidine for anesthesia induction can achieve satisfactory anesthesia effect. On the basis of propofol and remifentanil anesthesia combined with dexmedetomidine for anesthesia induction, it can significantly inhibit the inflammatory response of lung cancer patients during perioperative period and it can more effectively stabilize the blood gas microcirculation and lung function of patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129352PMC
April 2021

Increased AT receptor expression mediates vasoconstriction leading to hypertension in Snx1 mice.

Hypertens Res 2021 May 10. Epub 2021 May 10.

Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.

Angiotensin II type 1 receptor (ATR) is a vital therapeutic target for hypertension. Sorting nexin 1 (SNX1) participates in the sorting and trafficking of the renal dopamine D receptor, while angiotensin and dopamine are counterregulatory factors in the regulation of blood pressure. The effect of SNX1 on ATR is not known. We hypothesized that SNX1, through arterial ATR sorting and trafficking, is involved in blood pressure regulation. CRISPR/Cas9 system-generated SNX1 mice showed dramatic elevations in blood pressure compared to their wild-type littermates. The angiotensin II-mediated contractile reactivity of the mesenteric arteries and ATR expression in the aortas were also increased. Moreover, immunofluorescence and immunoprecipitation analyses revealed that SNX1 and ATR were colocalized and interacted in the aortas of wild-type mice. In vitro studies revealed that ATR protein levels and downstream calcium signaling were upregulated in A10 cells treated with SNX1 siRNA. This may have resulted from decreased ATR protein degradation since the ATR mRNA levels showed no changes. ATR protein was less degraded when SNX1 was downregulated, as reflected by a cycloheximide chase assay. Furthermore, proteasomal rather than lysosomal inhibition increased ATR protein content, and this effect was accompanied by decayed binding of ubiquitin and ATR after SNX1 knockdown. Confocal microscopy revealed that ATR colocalized with PSMD6, a proteasomal marker, and the colocalization was reduced after SNX1 knockdown. These findings suggest that SNX1 sorts ATR for proteasomal degradation and that SNX1 impairment increases arterial ATR expression, leading to increased vasoconstriction and blood pressure.
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http://dx.doi.org/10.1038/s41440-021-00661-xDOI Listing
May 2021

Chrysin Ameliorates Sepsis-Induced Cardiac Dysfunction Through Upregulating Nfr2/Heme Oxygenase 1 Pathway.

J Cardiovasc Pharmacol 2021 04;77(4):491-500

College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, PR China.

Abstract: The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.
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http://dx.doi.org/10.1097/FJC.0000000000000989DOI Listing
April 2021

Atomistic Mechanisms of Thermal Transformation in a Zr-Metal Organic Framework, MIL-140C.

J Phys Chem Lett 2021 Jan 15;12(1):177-184. Epub 2020 Dec 15.

Department of Mechanical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

To understand the mechanisms responsible for thermal decomposition of a Zr-MOF (MIL-140C), we perform atomistic-scale molecular dynamics (MD) simulations and discuss the simulation data in comparison with the TEM images obtained for the decomposed Zr-MOF. First, we introduce the ReaxFF parameters suitable for the Zr/C/H/O chemistry and then apply them to investigate the thermal stability and morphological changes in the MIL-140C during heating. Based on the performed simulations we propose an atomic mechanism for the collapse of the MIL-140C and the molecular pathways for carbon monoxide formation, the main product of the MIL-140C thermal degradation. We also determine that the oxidation state of the ZrO clusters, evolved due to the thermal degradation, approximates the tetragonal phase of ZrO. Both simulations and experiments show a distribution of very small ZrO clusters embedded in the disrupted organic sheet that could contribute to the unusual high catalytic activity of the decomposed MIL-140C.
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http://dx.doi.org/10.1021/acs.jpclett.0c02930DOI Listing
January 2021

Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway.

Aging (Albany NY) 2020 11 26;13(1):493-515. Epub 2020 Nov 26.

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu 610083, China.

Mitochondrial calcium uptake 1 (MICU1) is a pivotal molecule in maintaining mitochondrial homeostasis under stress conditions. However, it is unclear whether MICU1 attenuates mitochondrial stress in angiotensin II (Ang-II)-induced cardiac hypertrophy or if it has a role in the function of melatonin. Here, small-interfering RNAs against MICU1 or adenovirus-based plasmids encoding MICU1 were delivered into left ventricles of mice or incubated with neonatal murine ventricular myocytes (NMVMs) for 48 h. MICU1 expression was depressed in hypertrophic myocardia and MICU1 knockdown aggravated Ang-II-induced cardiac hypertrophy and . In contrast, MICU1 upregulation decreased cardiomyocyte susceptibility to hypertrophic stress. Ang-II administration, particularly in NMVMs with MICU1 knockdown, led to significantly increased reactive oxygen species (ROS) overload, altered mitochondrial morphology, and suppressed mitochondrial function, all of which were reversed by MICU1 supplementation. Moreover, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α)/MICU1 expression in hypertrophic myocardia increased with melatonin. Melatonin ameliorated excessive ROS generation, promoted mitochondrial function, and attenuated cardiac hypertrophy in control but not MICU1 knockdown NMVMs or mice. Collectively, our results demonstrate that MICU1 attenuates Ang-II-induced cardiac hypertrophy by inhibiting mitochondria-derived oxidative stress. MICU1 activation may be the mechanism underlying melatonin-induced protection against myocardial hypertrophy.
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http://dx.doi.org/10.18632/aging.202159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834983PMC
November 2020

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases.

Front Aging Neurosci 2020 6;12:584743. Epub 2020 Oct 6.

Department of Cardiovasology, General Hospital of Western Theater Command, Chengdu, China.

Neurogranin (Ng) is a small protein usually expressed in granule-like structures in pyramidal cells of the hippocampus and cortex. However, its clinical value is not fully clear so far. Currently, Ng is proved to be involved in synaptic plasticity, synaptic regeneration, and long-term potentiation mediated by the calcium- and calmodulin-signaling pathways. Due to both the synaptic integrity and function as the growing concerns in the pathogenesis of a wide variety of neurological and mental diseases, a series of researches published focused on the associations between Ng and these kinds of diseases in the past decade. Therefore, in this review, we highlight several diseases, which include, but are not limited to, Alzheimer's disease, Parkinson disease, Creutzfeldt-Jakob disease, neuro-HIV, neurosyphilis, schizophrenia, depression, traumatic brain injury, and acute ischemic stroke, and summarize the associations between cerebrospinal fluid or blood-derived Ng with these diseases. We propose that Ng is a potential and promising biomarker to improve the diagnosis, prognosis, and severity evaluation of these diseases in the future.
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http://dx.doi.org/10.3389/fnagi.2020.584743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573493PMC
October 2020

Postnatal renin-angiotensin system inhibition prevents renal damage from prenatal inflammation in rats.

J Tradit Chin Med 2020 08;40(4):646-653

Institute of Materia Medica, College of Pharmacy and Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Objective: To assess the protective role of benazepril, an angiotensin-converting enzyme inhibitor, in renal damage caused by prenatal inflammation.

Methods: Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague- Dawley rats on gestation days 8, 10, and 12. After birth, offspring received either tap water or benazepril in water between 7 and 68 weeks. Blood pressure, blood urea nitrogen, creatinine, and 24-h urine volume were measured as indices of renal function. Hematoxylin, eosin, periodic acid-Schiff, and Sirius Red staining were used to evaluate renal damage.

Results: Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels. Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation.

Conclusion: Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation, our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.04.012DOI Listing
August 2020

Tom70 protects against diabetic cardiomyopathy through its antioxidant and antiapoptotic properties.

Hypertens Res 2020 10 28;43(10):1047-1056. Epub 2020 Jul 28.

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, PR China.

Mitochondrial dysfunction plays a critical role in the pathogenesis of diabetic cardiomyopathy. Translocase of mitochondrial outer membrane 70 (Tom70) primarily facilitates the import of mitochondrial preproteins that may be involved in the regulation of oxidative stress and mitochondrial function. This study aimed to investigate the role of Tom70 in the development of myocardial injury in leptin receptor-deficient (db/db) diabetic mice. Tom70 siRNA or an overexpressing lentivirus was intramuscularly injected into mouse hearts or used to treat cultured neonatal cardiomyocytes. We found that Tom70 was downregulated in the diabetic hearts compared with the level in the wild-type hearts and that knocking down Tom70 exacerbated cardiac hypertrophy, fibrosis, and ventricular dysfunction in the db/db mice. Similarly, the in vitro data demonstrated that silencing Tom70 enhanced high-glucose and high-fat (HGHF) medium treatment-induced mitochondrial superoxide production, decreased ATP production and the mitochondrial membrane potential, and enhanced cell apoptosis in neonatal cardiomyocytes. Importantly, overexpression of Tom70 alleviated HGHF medium-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Furthermore, in vivo data confirmed that reconstitution of Tom70 ameliorated cardiac hypertrophy, interstitial fibrosis, and ventricular dysfunction in the db/db mice. In addition, Tom70 overexpression mitigated mitochondrial fragmentation and dysfunction in the hearts of the db/db mice. Taken together, these findings suggest that downregulation of Tom70 contributes to the development of diabetic cardiomyopathy and that reconstitution of Tom70 may be a new therapeutic strategy for the prevention and treatment of diabetic cardiomyopathy.
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http://dx.doi.org/10.1038/s41440-020-0518-xDOI Listing
October 2020

NF2 deficiency accelerates neointima hyperplasia following vascular injury via promoting YAP-TEAD1 interaction in vascular smooth muscle cells.

Aging (Albany NY) 2020 05 18;12(10):9726-9744. Epub 2020 May 18.

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu 610083, China.

Neurofibromin 2 (NF2), a potent tumor suppressor, is reported to inhibit proliferation in several cell types. The role of NF2 in neointima hyperplasia after vascular injury is unknown. We explored the role of NF2 in proliferation, migration of vascular smooth muscle cell (VSMC) and neointima hyperplasia after vascular injury. NF2 phosphorylation was elevated in VSMC subjected to platelet-derived growth factor (PDGF)-BB and in artery subjected to vascular injury. Mice deficient for in VSMC showed enhanced neointima hyperplasia after injury, increased proliferation and migration of VSMC after PDGF-BB treatment. Mechanistically, we observed increased nuclear p-NF2, declined p-Yes-Associated Protein (YAP), nuclear translocation of YAP after PDGF-BB treatment or injury. NF2 knockdown or YAP overexpression showed similar phenotype in VSMC proliferation, migration and neointima hyperplasia. YAP inhibition abolished the above effects mediated by NF2 knockdown. Finally, NF2 knockdown further promoted YAP-TEA Domain Transcription Factor 1 (TEAD1) interaction after PDGF-BB treatment. Inhibition of TEAD1 blocked PDGF-BB-induced VSMC proliferation and migration, which were not reversed by either NF2 knockdown or YAP overexpression. In conclusion, NF2 knockdown promotes VSMC proliferation, migration and neointima hyperplasia after vascular injury via inducing YAP-TEAD1 interaction.
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http://dx.doi.org/10.18632/aging.103240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288949PMC
May 2020

Comparative transcriptomics characterized the distinct biosynthetic abilities of terpenoid and paeoniflorin biosynthesis in herbaceous peony strains.

PeerJ 2020 20;8:e8895. Epub 2020 Apr 20.

National Key Facility for Crop Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

The herbaceous peony ( Pall.) is a perennial flowering plant of the Paeoniaceae species that is widely cultivated for medical and ornamental uses. The monoterpene glucoside paeoniflorin and its derivatives are the active compounds of the roots. However, the gene regulation pathways associated with monoterpene and paeoniflorin biosynthesis in are still unclear. Here, we selected three genotypes of with distinct morphologic features and chemical compositions that were a result of long-term reproductive isolation. We performed an RNA-sequencing experiment to profile the transcriptome changes of the shoots and roots. Using de novo assembly analysis, we identified 36,264 unigenes, including 521 genes responsible for encoding transcription factors. We also identified 28,925 unigenes that were differentially expressed in different organs and/or genotypes. Pathway enrichment analysis showed that the unigenes were significantly overrepresented in several secondary metabolite biosynthesis pathways. We identified and profiled 33 genes responsible for encoding the enzymescontrolling the major catalytic reactions in the terpenoid backbone and in monoterpenoid biosynthesis. Our study identified the candidate genes in the terpenoid biosynthesis pathways, providing useful information for metabolic engineering of intended for pharmaceutical uses and facilitating the development of strategies to improve marker-assist in the future.
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http://dx.doi.org/10.7717/peerj.8895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179566PMC
April 2020

TRPA1 regulates macrophages phenotype plasticity and atherosclerosis progression.

Atherosclerosis 2020 05 13;301:44-53. Epub 2020 Apr 13.

Department of Cardiology, The General Hospital of Western Theater Command, PR China. Electronic address:

Background And Aims: TRPA1 is a calcium permeable non-selective cation channel, its expression is up-regulated in atherosclerosis plaque, yet its function in macrophages activation is unknown. We sought to establish the role of TRPA1 in inflammatory macrophages activation.

Methods: TRPA1ApoE mice and C57BL/6 J control were treated with a high-fat diet (HFD) and the TRPA1 agonist cinnamaldehyde (CIN). Third-order branches of superior aorta of patients and mice were collected. Oil Red O staining and hematoxylin and eosin staining were performed to measure atherosclerotic lesions. The RNA-seq was performed to identify TRPA1 function in atherosclerosis. The expression of bone marrow-derived macrophages (BMDMs) markers was tested by Western blot. In addition, the levels of inflammatory factors were checked by ELISA. Chromatin immunoprecipitation (ChIP)-PCR and luciferase reporter gene assays were used to explore if TRPA1 could regulate histone modifications.

Results: TRPA1ApoE mice showed a significant increase in atherosclerosis plaques compared to ApoE mice after HFD treatment. Conversely, activation of TRPA1 by CIN sharply reduced atherosclerosis progression. Atherosclerosis was associated with a significant change in macrophage polarization toward the M1 proinflammatory phenotype. We found that inhibition of TRPA1 remarkably stimulated M1 marker genes expression, while repressed M2 marker genes expression. The interaction between TRPA1 and Ezh2, a subunit of polycomb repressive complex 2, suppressed the proteasome-dependent degradation of Ezh2. Thus, TRPA1 epigenetically regulated H3K27 trimethylation level in macrophages.

Conclusions: Our results demonstrate that TRPA1, up-regulated in atherosclerosis plaque, could regulate the macrophages toward an inflammatory phenotype, thereby modulating atherosclerosis progression. Activation of TRPA1 might serve as an atherosclerosis therapeutic target.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.04.004DOI Listing
May 2020

Storage Management Strategy in Mobile Phones for Photo Crowdsensing.

Sensors (Basel) 2020 Apr 13;20(8). Epub 2020 Apr 13.

Department of Computer Science and Technology, Tsinghua University, Beijing 100084, China.

In mobile crowdsensing, some users jointly finish a sensing task through the sensors equipped in their intelligent terminals. In particular, the photo crowdsensing based on Mobile Edge Computing (MEC) collects pictures for some specific targets or events and uploads them to nearby edge servers, which leads to richer data content and more efficient data storage compared with the common mobile crowdsensing; hence, it has attracted an important amount of attention recently. However, the mobile users prefer uploading the photos through Wifi APs (PoIs) rather than cellular networks. Therefore, photos stored in mobile phones are exchanged among users, in order to quickly upload them to the PoIs, which are actually the edge services. In this paper, we propose a utility-based Storage Management strategy in mobile phones for Photo Crowdsensing (SMPC), which makes a sending/deleting decision on a user's device for either maximizing photo delivery ratio (SMPC-R) or minimizing average delay (SMPC-D). The decision is made according to the photo's utility, which is calculated by measuring the impact of reproducing or deleting a photo on the above performance goals. We have done simulations based on the random-waypoint model and three real traces: , , and . The results show that, compared with other storage management strategies, SMPC-R gets the highest delivery ratio and SMPC-D achieves the lowest average delay.
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http://dx.doi.org/10.3390/s20082199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218852PMC
April 2020

Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2.

Am J Hypertens 2020 07;33(7):610-619

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, PR China.

Background: Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear.

Methods: Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group.

Results: CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice.

Conclusions: A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.
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http://dx.doi.org/10.1093/ajh/hpaa024DOI Listing
July 2020

Relating structural disorder and melting in complex mixed ligand zeolitic imidazolate framework glasses.

Dalton Trans 2020 Jan;49(3):850-857

Department of Materials Science and Metallurgy, University of Cambridge, UK.

We report the formation of zeolitic imidazolate framework glasses incorporating three organic linkers, from their corresponding novel crystalline structures [Zn(Im2-x-ybImxmbImy)]. Structure-property relationships between chemical compositions and thermal properties are analysed, in addition to the effect on the nanoscale porosity of the glasses formed. A probabilistic model is used to explain melting and the glass transition temperatures of the obtained glasses and link to the nanoscale structural disorder of their crystalline starting structures.
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http://dx.doi.org/10.1039/c9dt03559aDOI Listing
January 2020

Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism Bidirectionally.

Oxid Med Cell Longev 2019 17;2019:8690746. Epub 2019 Oct 17.

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu 610083, China.

Background: Hyper-free fatty acidemia (HFFA) impairs cardiac capillaries, as well as type 2 diabetes mellitus (T2DM). Perilipin 5 (Plin5) maintains metabolic balance of free fatty acids (FFAs) in high oxidative tissues via the states of nonphosphorylation and phosphorylation. However, when facing to T2DM-HFFA, Plin5's role in cardiac microvascular endothelial cells (CMECs) is not defined.

Methods: In mice of WT or Plin5, T2DM models were rendered by high-fat diet combined with intraperitoneal injection of streptozocin. CMECs isolated from left ventricles were incubated with high glucose (HG) and high FFAs (HFFAs). Plin5 phosphorylation was stimulated by isoproterenol. Plin5 expression was knocked down by small interfering RNA (siRNA). We determined cardiac function by small animal ultrasound, apoptotic rate by flow cytometry, microvessel quantity by immunohistochemistry, microvascular integrity by scanning electron microscopy, intracellular FFAs by spectrophotometry, lipid droplets (LDs) by Nile red staining, mRNAs by quantitative real-time polymerase chain reaction, proteins by western blots, nitric oxide (NO) and reactive oxygen species (ROS) by fluorescent dye staining and enzyme-linked immunosorbent assay kits.

Results: In CMECs, HFFAs aggravated cell injury induced by HG and activated Plin5 expression. In mice with T2DM-HFFA, Plin5 deficiency reduced number of cardiac capillaries, worsened structural incompleteness, and enhanced diastolic dysfunction. Moreover, in CMECs treated with HG-HFFAs, both ablation and phosphorylation of Plin5 reduced LDs content, increased intracellular FFAs, stimulated mitochondrial -oxidation, added ROS generation, and reduced the expression and activity of endothelial nitric oxide synthase (eNOS), eventually leading to increased apoptotic rate and decreased NO content, all of which were reversed by N-acetyl-L-cysteine.

Conclusion: Plin5 preserves lipid balance and cell survival in diabetic CMECs by regulating FFAs metabolism bidirectionally via the states of nonphosphorylation and phosphorylation.
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http://dx.doi.org/10.1155/2019/8690746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854993PMC
April 2020

Dietary Menthol Attenuates Inflammation and Cardiac Remodeling After Myocardial Infarction via the Transient Receptor Potential Melastatin 8.

Am J Hypertens 2020 03;33(3):223-233

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, PR China.

Background: Transient receptor potential melastatin subtype 8 (TRPM8) is a cold-sensing cation channel, mainly localized in the sensory neurons, which can be activated by menthol, a compound with a naturally cold sensation in mint. However, the effect of TRPM8 activation in inflammation and cardiac remodeling after myocardial infarction (MI) is not well defined.

Methods: TRPM8 knockout (KO) mice (TRPM8-/-) and their wild-type littermates, aged 8 weeks, were randomly divided into sham and MI groups and were fed with chow or chow plus menthol.

Results: Dietary menthol significantly attenuated MI injury, evidenced by decreased survival rates and plasma cardiac troponion I levels, reduced infarct size and cardiomyocytes, declined collagen deposition, and rescued cardiac function and hemodynamics. However, these effects of menthol disappeared when mice were lacking TRPM8. Furthermore, feeding of menthol ameliorated elevated expression of inflammatory cytokines and chemokines, and aggravated inflammation infiltration in the MI mice but not in TRPM8-/- mice. In addition, menthol treatment increased the release of calcitonin gene-related peptide (CGRP), which were absent in TRPM8-/- mice.

Conclusions: In conclusion, our results suggest that dietary menthol can protect against inflammation and cardiac remodeling after MI through activation of TRPM8.
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http://dx.doi.org/10.1093/ajh/hpz162DOI Listing
March 2020

Topical anesthetic analgesic therapy using the combination of ropivacaine and dexmedetomidine: hyaluronic acid modified long-acting nanostructured lipid carriers containing a skin penetration enhancer.

Drug Des Devel Ther 2019 18;13:3307-3319. Epub 2019 Sep 18.

Department of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University, Ji'nan, Shandong Province 250013, People's Republic of China.

Purpose: Hyaluronic acid-poly(ethylene glycol)-distearoyl phosphoethanolamine (HA-PEG-DSPE) modified and tocopheryl polyethylene glycol 1000 succinate (TPGS) contained nanostructured lipid carriers (NLCs) were prepared loading ropivacaine and dexmedetomidine to improve the topical anesthetic analgesic anesthesia efficiency.

Methods: NLCs were prepared by the solvent diffusion method. The average particle size, zeta potential, release behavior, and cytotoxicity of the NLCs were tested. Ex vivo skin permeation was studied using a Franz diffusion cell mounted with depilated rat skin. Local anesthesia antinociceptive efficiency was evaluated by rat tail flick latency study in vivo.

Results: NLCs have sizes of about 100 nm, with negative zeta potentials. All the NLCs formulations were found to be significantly less cytotoxic than free drugs at equivalent concentrations. The cumulative amount of drugs penetrated through rat skin from NLCs was 2.0-4.7 folds higher than that of the drugs solution. The in vivo anesthesia antinociception study displayed that NLCs showed stronger and longer anesthesia antinociceptive effect when compared with single drugs loaded NLCs and drugs solution even at a lower dosage of drugs.

Conclusion: The results demonstrated that the HA modified, TPGS contained, dual drugs loaded NLCs could perform a synergistic effect and may reduce the amount of drugs, which can lower the toxicity of the system and at the meanwhile, increase the anesthesia antinociceptive efficiency.
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http://dx.doi.org/10.2147/DDDT.S211443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755955PMC
February 2020

TRPA1 Promotes Cardiac Myofibroblast Transdifferentiation after Myocardial Infarction Injury via the Calcineurin-NFAT-DYRK1A Signaling Pathway.

Oxid Med Cell Longev 2019 14;2019:6408352. Epub 2019 May 14.

Department of Cardiology, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, China.

Cardiac fibroblasts (CFs) are a critical cell population responsible for myocardial extracellular matrix homeostasis. After stimulation by myocardial infarction (MI), CFs transdifferentiate into cardiac myofibroblasts (CMFs) and play a fundamental role in the fibrotic healing response. Transient receptor potential ankyrin 1 (TRPA1) channels are cationic ion channels with a high fractional Ca current, and they are known to influence cardiac function after MI injury; however, the molecular mechanisms regulating CMF transdifferentiation remain poorly understood. TRPA1 knockout mice, their wild-type littermates, and mice pretreated with the TRPA1 agonist cinnamaldehyde (CA) were subjected to MI injury and monitored for survival, cardiac function, and fibrotic remodeling. TRPA1 can drive myofibroblast transdifferentiation initiated 1 week after MI injury. In addition, we explored the underlying mechanisms via experiments through gene transfection alone or in combination with inhibitor treatment. TRPA1 overexpression fully activated CMF transformation, while CFs lacking TRPA1 were refractory to transforming growth factor - (TGF--) induced transdifferentiation. TGF- enhanced TRPA1 expression, which promoted the Ca-responsive activation of calcineurin (CaN). Moreover, dual-specificity tyrosine-regulated kinase-1a (DYRK1A) regulated CaN-mediated NFAT nuclear translocation and TRPA1-dependent transdifferentiation. These findings suggest a potential therapeutic role for TRPA1 in the regulation of CMF transdifferentiation in response to MI injury and indicate a comprehensive pathway driving CMF formation in conjunction with TGF-, Ca influx, CaN, NFATc3, and DYRK1A.
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http://dx.doi.org/10.1155/2019/6408352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537015PMC
December 2019

Wild-type p53-induced phosphatase 1 promotes vascular smooth muscle cell proliferation and neointima hyperplasia after vascular injury via p-adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin complex 1 pathway.

J Hypertens 2019 11;37(11):2256-2268

Objectives: Vascular smooth muscle cell (VSMC) proliferation is a crucial cause of vascular neointima hyperplasia and restenosis, thus limiting the long-term efficacy of percutaneous vascular intervention. We explored the role of wild-type p53-induced phosphatase 1 (Wip1), a potent regulator of tumorigenesis and atherosclerosis, in VSMC proliferation and neointima hyperplasia.

Methods And Results: Animal model of vascular restenosis was established in wild type C57BL/6J and VSMC-specific Tuberous Sclerosis 1 (TSC1)-knockdown mice by wire injury. We observed increased protein levels of Wip1, phospho (p)-S6 Ribosomal Protein (S6), p-4EBP1 but decreased p-adenosine 5'-monophosphate-activated protein kinase (AMPK)α both in carotid artery at day 28 after injury and in VSMCs after 48 h of platelet derived growth factor-BB (PDGF-BB) treatment. By using hematoxylin-eosin staining, Ki-67 immunohistochemical staining, cell counting kit-8 assay and Ki-67 immunofluorescence staining, we found Wip1 antagonist GSK2830371 (GSK) or mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin both obviously reversed the neointima formation and VSMC proliferation induced by wire injury and PDGF-BB, respectively. GSK also reversed the increase in mRNA level of Collagen I after wire injury. However, GSK had no obvious effects on VSMC migration induced by PDGF-BB. Simultaneously, TSC1 knockdown as well as AMPK inhibition by Compound C abolished the vascular protective and anti-proliferative effects of Wip1 inhibition. Additionally, suppression of AMPK also reversed the declined mTORC1 activity by GSK.

Conclusion: Wip1 promotes VSMC proliferation and neointima hyperplasia after wire injury via affecting AMPK/mTORC1 pathway.
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http://dx.doi.org/10.1097/HJH.0000000000002159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784764PMC
November 2019

Inter-urban mobility via cellular position tracking in the southeast Songliao Basin, Northeast China.

Sci Data 2019 May 23;6(1):71. Epub 2019 May 23.

College of Computer Science and Technology, Jilin University, 130012, Changchun, China.

Position tracking using cellular phones can provide fine-grained traveling data between and within cities on hourly and daily scales, giving us a feasible way to explore human mobility. However, such fine-grained data are traditionally owned by private companies and is extremely rare to be publicly available even for one city. Here, we present, to the best of our knowledge, the largest inter-city movement dataset using cellular phone logs. Specifically, our data set captures 3-million cellular devices and includes 70 million movements. These movements are measured at hourly intervals and span a week-long duration. Our measurements are from the southeast Sangliao Basin, Northeast China, which span three cities and one country with a collective population of 8 million people. The dynamic, weighted and directed mobility network of inter-urban divisions is released in simple formats, as well as divisions' GPS coordinates to motivate studies of human interactions within and between cities.
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http://dx.doi.org/10.1038/s41597-019-0070-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533259PMC
May 2019

Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system.

Clin Sci (Lond) 2019 05 9;133(9):1097-1113. Epub 2019 May 9.

Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, P.R. China

Environmental temperature plays a role in the variation of blood pressure. Maternal cold stress could affect the physiological phenotype of the offspring, including blood pressure elevation. In the present study, we found that adult offspring of dams exposed to cold have increased systolic and diastolic blood pressure, and decreased urine volume and sodium excretion, accompanied by increased heart rate and heart rate variability, secondary to increased activity of the sympathetic nervous system. Renal denervation or adrenergic receptor blockade decreased blood pressure and increased sodium excretion. The increase in peripheral sympathetic nerve activity can be ascribed to the central nervous system because administration of clonidine, a centrally acting α adrenergic receptor agonist, lowered blood pressure to a greater degree in the prenatal cold-exposed than control offspring. Moreover, these prenatal cold-exposed offspring had hypothalamic paraventricular nucleus (PVN) disorder because magnetic resonance spectroscopy showed decreased N-acetylaspartate and increased choline and creatine ratios in the PVN. Additional studies found that prenatal cold exposure impaired the balance between inhibitory and excitatory neurons. This led to PVN overactivation that was related to enhanced PVN-angiotensin II type 1 (AT) receptor expression and function. Microinjection of the AT receptor antagonist losartan in the PVN lowered blood pressure to a greater extent in prenatal cold-exposed that control offspring. The present study provides evidence for overactive peripheral and central sympathetic nervous systems in the pathogenesis of prenatal cold-induced hypertension. Central AT receptor blockade in the PVN may be a key step for treatment of this type hypertension.
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http://dx.doi.org/10.1042/CS20190254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833955PMC
May 2019

The temporal geographically-explicit network of public transport in Changchun City, Northeast China.

Sci Data 2019 02 26;6:190026. Epub 2019 Feb 26.

College of Computer Science and Technology, Jilin University, Changchun, 130012, China.

The vehicle trajectory data is a feasible way for us to understand and reveal urban traffic conditions and human mobility. Therefore, it is extremely valuable to have a fine-grained picture of large-scale vehicle trajectory data, particularly in two different modes, taxis and buses, over the same period at an urban scale. This paper integrates the trajectory data of approximately 7,000 taxis and 1,500 buses in Changchun City, China and accesses the temporal geographically-explicit network of public transport via sequential snapshots of vehicle trajectory data every 30 seconds of the first week in March 2018. In order to reveal urban traffic conditions and human mobility, we construct two-layer urban traffic network (UTN) between these two different transport modes, take crossings as nodes and roads as edges weighted by the volume or average speed of vehicles in each hour. We released this temporal geographically-explicit network of public transport and the dynamics, weighted and directed UTN in simple formats for easy access.
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http://dx.doi.org/10.1038/sdata.2019.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390825PMC
February 2019

NeuO: Exploiting the sentimental bias between ratings and reviews with neural networks.

Neural Netw 2019 Mar 8;111:77-88. Epub 2019 Jan 8.

Rutgers, The State University of New Jersey, NJ, USA.

Traditional recommender systems rely on user profiling based on either user ratings or reviews through bi-sentimental analysis. However, in real-world scenarios, there are two common phenomena: (1) users only provide ratings for items but without detailed review comments. As a result, the historical transaction data available for recommender systems are usually unbalanced and sparse; (2) in many cases, users' opinions can be better grasped in their reviews than ratings. For the reason that there is always a bias between ratings and reviews, it is really important that users' ratings and reviews should be mutually reinforced to grasp the users' true opinions. To this end, in this paper, we develop an opinion mining model based on convolutional neural networks for enhancing recommendation. Specifically, we exploit two-step training neural networks, which utilize both reviews and ratings to grasp users' true opinions in unbalanced data. Moreover, we propose a Sentiment Classification scoring (SC) method, which employs dual attention vectors to predict the users' sentiment scores of their reviews rather than using bi-sentiment analysis. Next, a combination function is designed to use the results of SC and user-item rating matrix to catch the opinion bias. It can filter the reviews and users, and build an enhanced user-item matrix. Finally, a Multilayer perceptron based Matrix Factorization (MMF) method is proposed to make recommendations with the enhanced user-item matrix. Extensive experiments on several real-world datasets (Yelp, Amazon, Taobao and Jingdong) demonstrate that (1) our approach can achieve a superior performance over state-of-the-art baselines; (2) our approach is able to tackle unbalanced data and achieve stable performances.
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http://dx.doi.org/10.1016/j.neunet.2018.12.011DOI Listing
March 2019

Prediction of the Glass Transition Temperatures of Zeolitic Imidazolate Glasses through Topological Constraint Theory.

J Phys Chem Lett 2018 Dec 3;9(24):6985-6990. Epub 2018 Dec 3.

Department of Materials Science and Engineering , The Pennsylvania State University , University Park , Pennsylvania 16802 , United States.

A topological constraint model is developed to predict the compositional scaling of glass transition temperature ( T) in a metal-organic framework glass, aZIF-62 [Zn(ImbIm )]. A hierarchy of bond constraints is established using a combination of experimental results and molecular dynamic simulations with ReaxFF. The model can explain the topological origin of T as a function of the benzimidazolate concentration with an error of 3.5 K. The model is further extended to account for the effect of 5-methylbenzimidazolate, enabling calculation of a ternary diagram of T with a mixture of three organic ligands in an as-yet unsynthesized, hypothetical framework. We show that topological constraint theory is an effective tool for understanding the properties of metal-organic framework glasses.
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http://dx.doi.org/10.1021/acs.jpclett.8b03348DOI Listing
December 2018

The temporal network of mobile phone users in Changchun Municipality, Northeast China.

Sci Data 2018 10 30;5:180228. Epub 2018 Oct 30.

College of Computer Science and Technology, Jilin University, 130012, Changchun, China.

Mobile data are a feasible way for us to understand and reveal the feature of human mobility. However, it is extremely hard to have a fine-grained picture of large-scale mobility data, in particular at an urban scale. Here, we present a large-scale dataset of 2-million mobile phone users with time-varying locations, denoted as the temporal network of individuals, conducted by an open-data program in Changchun Municipality. To reveal human mobility across locations, we further construct the aggregated mobility network for each day by taking cellular base stations as nodes coupled by edges weighted by the total number of users' movements between pairs of nodes. The resulting temporal network of mobile phone users and the dynamic, weighted and directed mobility network are released in simple formats for easy access to motivating research using this new and extensive data of human mobility.
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http://dx.doi.org/10.1038/sdata.2018.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207067PMC
October 2018

Predictors and Management of Antiplatelet-Related Bleeding Complications for Acute Coronary Syndrome in Chinese Elderly Patients.

Cell Physiol Biochem 2018 24;50(3):1164-1177. Epub 2018 Oct 24.

Department of Cardiology, Chengdu Military General Hospital, Chengdu, China.

Background/aims: Bleeding complications after percutaneous coronary intervention (PCI) are strongly associated with adverse patient outcomes. However, there are no specific guidelines for the predictors and management of antiplatelet-related bleeding complications in Chinese elderly patients with acute coronary syndrome (ACS).

Methods: A retrospective analysis of 237 consecutive patients (aged ≥ 75 years) with ACS who had undergone successful PCI from January 2010 to December 2016 was performed to identify predictors and management of antiplatelet-related bleeding complications. Multivariate logistic regression analysis was conducted to investigate independent predictors of antiplatelet-related bleeding complications. We defined antiplatelet-related bleeding complications as first hospitalization received long-term oral antiplatelet therapy and required hospitalization, including gastrointestinal and intracranial bleedings.

Results: After multivariable adjustment, independent risk predictors of antiplatelet-related bleeding complications included female gender (odds ratio [OR]: 2.96; 95% confidence interval [CI]: 1.98 to 4.15; P = 0.011), body mass index (OR: 1.54; 95% CI: 1.06 to 1.94; P = 0.034), previous history of bleeding (OR: 4.03; 95% CI: 1.84 to 6.12; P = 0.004), fasting blood glucose (OR: 2.79; 95% CI: 1.23 to 4.46; P = 0.025), and chronic total occlusion lesion (OR: 4.69; 95% CI: 2.19 to 7.93; P = 0.007). Of 46 patients with antiplatelet-related bleeding complications, 54.3% were treated short-term dual antiplatelet therapy (DAPT) cessation (0-7 days) and 45.7% underwent long-term DAPT cessation (> 7 days). Among these, 14 patients presented major adverse cardiac and cerebrovascular events (MACCE), whereas no re-bleeding happened over all available follow-up. The incidence of MACCE was not significantly different between the two groups one year after PCI (36.0% for short-term DAPT cessation versus 23.8% for long-term DAPT cessation, P = 0.522).

Conclusion: For elderly patients with ACS, multiple factors were likely to contribute to antiplatelet-related bleeding complications, especially previous history of bleeding and chronic total occlusion lesion. Better individualized, tailored and risk-adjusted antiplatelet therapy after PCI is urgently needed in this high-risk population.
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http://dx.doi.org/10.1159/000494543DOI Listing
November 2018

Enabling Computational Design of ZIFs Using ReaxFF.

J Phys Chem B 2018 Oct 9;122(41):9616-9624. Epub 2018 Oct 9.

Department of Materials Science and Metallurgy , University of Cambridge , 27 Charles Babbage Road , Cambridge CB3 0FS , U.K.

Classical force fields have been broadly used in studies of metal-organic framework crystals. However, processes involving bond breaking or forming are prohibited due to the nonreactive nature of the potentials. With emerging trends in the study of zeolitic imidazolate frameworks (ZIFs) that include glass formation, defect engineering, and chemical stability, enhanced computational methods are needed for efficient computational screening of ZIF materials. Here, we present simulations of three ZIF compounds using a ReaxFF reactive force field. By simulating the melt-quench process of ZIF-4, ReaxFF can reproduce the atomic structure, density, thermal properties, and pore morphology of the glass formed ( aZIF-4), showing remarkable agreement with experimental and first-principles molecular dynamics results. The predictive capability of ReaxFF is further exemplified in the melting of ZIF-62, where the balancing of electronic and steric effects of benzimidazolate yields a lower T. On the basis of the electron-withdrawing effect of the -NO group, ReaxFF simulations predict that ZIF-77 has an even lower T in terms of Zn-N interaction, but its low chemical stability makes it unsuitable as a glass former. Because of its low computational cost and transferability, ReaxFF will enable the computational design of ZIF materials by accounting for properties associated with disorder/defects.
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http://dx.doi.org/10.1021/acs.jpcb.8b08094DOI Listing
October 2018

Identification of a Panel of MiRNAs as Positive Regulators of Insulin Release in Pancreatic Β-Cells.

Cell Physiol Biochem 2018 13;48(1):185-193. Epub 2018 Jul 13.

Background/aims: MicroRNAs (miRNAs) are a novel class of small RNAs that participate in a variety of biological processes. Although miRNAs have been linked to insulin synthesis and glucose homeostasis, their role in the targeting of mitochondrial uncoupling protein 2 (UCP2), a negative modulator of insulin secretion, remains unclear.

Methods: miRNA levels were determined by real-time quantitative PCR analysis using TaqMan probes, and insulin secretion from isolated islets was quantified by ELISA. Effects of miRNAs on UCP2 expression were checked with a luciferase assay and western blotting analysis.

Results: An overall change in a set of miRNAs was discovered, with miR-15a, miR-424, miR-497, and miR-185 coinciding with insulin levels in islets maintained under high-glucose conditions. Moreover, experiments in MIN6 cells illustrated that miR-15a, miR-424, miR-497, and miR-185 positively regulated insulin biosynthesis by co-inhibiting UCP2 expression. Furthermore, the four miRNAs were found to post-transcriptionally repress UCP2 expression by directly targeting the 3'UTR of UCP2 mRNA.

Conclusions: Thus, our results shed further light on the regulatory network in β-cells consisting of miRNAs, UCP2, and insulin and provide novel therapeutic targets for diabetes.
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http://dx.doi.org/10.1159/000491717DOI Listing
September 2018

Overexpression of SARAF Ameliorates Pressure Overload-Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in Mice.

Cell Physiol Biochem 2018 22;47(2):817-826. Epub 2018 May 22.

Department of Cardiology, Chengdu Military General Hospital, Chengdu, China.

Background/aims: Activation of stromal interaction molecule 1 (STIM1) and Orai1 participates in the development of cardiac hypertrophy. Store-operated Ca2+ entry-associated regulatory factor (SARAF) is an intrinsic inhibitor of STIM1-Orai1 interaction. Thus, we hypothesized that SARAF could prevent cardiac hypertrophy.

Methods: Male C57BL/6 mice, aged 8 weeks, were randomly divided into sham and abdominal aortic constriction surgery groups and were infected with lentiviruses expressing SARAF and GFP (Lenti-SARAF) or GFP alone (Lenti-GFP) via intramyocardial injection. At 4 weeks after aortic constriction, left ventricular structure and function were assessed by echocardiography and hemodynamic assays. The gene and protein expressions of SARAF, STIM1, and Orai1 were measured by quantitative PCR and Western blot, respectively.

Results: Gene and protein expressions of SARAF were significantly decreased, while STIM1 and Orai1 were increased in the heart tissue compared with sham group. Overexpression of SARAF in the heart prevented the upregulation of STIM1 and Orai1, and importantly, attenuated aortic constriction-induced decrease in maximal rate of left ventricular pressure decay and increases in thickness of interventricular septum and left ventricular posterior wall, heart weight/body weight ratio, and size of cardiomyocytes. Blood pressure detected through the carotid artery and left ventricular systolic function were not affected by SARAF overexpression. In addition, overexpression of SARAF also attenuated angiotensin II-induced upregulation of STIM1 and Orai1 and hypertrophy of cultured cardiomyocytes.

Conclusion: Overexpression of SARAF in the heart prevents cardiac hypertrophy, probably through suppressing the upregulation of STIM1/Orai1.
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http://dx.doi.org/10.1159/000490036DOI Listing
July 2018

Potential Protective Mechanism in the Cardiac Microvascular Injury.

Hypertension 2018 07 7;72(1):116-127. Epub 2018 May 7.

From the Graduate School, Third Military Medical University, Chongqing, China (X.L., J.H., J.D., H.P., Y.Y.)

Cardiac microvascular injury often occurs in patients with type 2 diabetes mellitus (T2DM) who develop hyperglycemia and hyperlipidemia. However, besides reported contradictory roles in cardiac diseases, the function of TRPV1 (transient receptor potential vanilloid 1) in cardiac microvessels is not well defined. This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding. CMECs were cultured separately in mediums of normal glucose, high glucose (HG), high fatty acid (HF), and HG plus HF (HG-HF). HG-HF inhibited TRPV1 expression in CMECs, reducing cellular Ca content ([Ca]). T2DM impaired cardiac function, disturbed glucose uptake, and damaged microvascular barrier, which were further aggravated by TRPV1 Exposure to HG-HF, particularly in TRPV1 CMECs, led to a higher level of apoptosis and a lower level of nitric oxide production in viable CMECs. HG-HF markedly enhanced generation of reactive oxygen species and nitrotyrosine, especially in the absence of TRPV1. HO administration reduced TRPV1 expression in CMECs. HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca], whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1 Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM. Collectively, T2DM leads to cardiac microvascular injury by exacerbating the vicious circle of TRPV1 blockage and reactive oxygen species overload. Long-term capsaicin can protect cardiac microvessels against T2DM via suppressing oxidative/nitrative stress mediated by TRPV1/Ca/PGC-1α/OPA1 pathway in CMECs.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11035DOI Listing
July 2018
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