Publications by authors named "Qing Gao"

304 Publications

Tachy-brady syndrome induced by a transversus thoracis muscle plane block.

J Clin Anesth 2021 May 5;73:110327. Epub 2021 May 5.

Department of Cardiac Surgery, Peking University People's Hospital, Beijing 100044, China.

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http://dx.doi.org/10.1016/j.jclinane.2021.110327DOI Listing
May 2021

A newly identified polyunsaturated macamide alleviates dextran sulfate sodium-induced colitis in mice.

Fitoterapia 2021 May 1;152:104916. Epub 2021 May 1.

Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address:

Macamides are a class of bioactive amide alkaloids found only in maca (Lepidium meyenii). Recent studies have shown that macamide-rich extracts possess various biological activities, such as antioxidative, immune-enhancing, and reproductive health-improving activities. In the present study, N-benzyl docosahexaenamide (NB-DHA), a newly identified macamide with the highest degree of unsaturation among all identified macamides, was identified from the maca extract. Microalgae oil, a docosahexaenoic acid-rich substance, was used as the starting material for the synthesis of NB-DHA. The effects of NB-DHA in colitis-induced mice were evaluated. NB-DHA significantly alleviated weight loss, shortening of colon length, and occult blood occurrence in mice with dextran sulfate sodium-induced colitis. Histological analysis revealed that following the administration of NB-DHA in mice with colitis, the infiltration of inflammatory cells and levels of proinflammatory factors, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and myeloperoxidase, decreased, whereas the level of the anti-inflammatory factor IL-10 increased. Furthermore, the decreased expression of intestinal tight junction proteins caused by colitis was upregulated by the administration of NB-DHA. These results indicate that NB-DHA could be developed as a therapeutic agent for ulcerative colitis.
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http://dx.doi.org/10.1016/j.fitote.2021.104916DOI Listing
May 2021

Kinetic Resolution of Tertiary Allylic Alcohols: Highly Enantioselective Access to Cyclic Ethers Bearing an α-Tetrasubstituted Stereocenter.

Org Lett 2021 Apr 30. Epub 2021 Apr 30.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

A chiral phosphoric acid-catalyzed kinetic resolution of tertiary allylic alcohols was developed to provide structurally valuable enantioenriched 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, and oxepane. A variety of tertiary allylic alcohols were resolved with selectivity factors of ≤120. A tertiary allylic carbocationic intermediate mediates the enantioselective intramolecular substitution to achieve high regio- and enantioselectivity. A gram-scale reaction with low catalyst loading and subsequent transformations of the recovered alcohols and products demonstrated the utility of this method.
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http://dx.doi.org/10.1021/acs.orglett.1c01110DOI Listing
April 2021

Recovering dense 3D point clouds from single endoscopic image.

Comput Methods Programs Biomed 2021 Apr 3;205:106077. Epub 2021 Apr 3.

Xian Polytechnic University, Xian, Shaanxi 710048, China. Electronic address:

Background And Objective: Recovering high-quality 3D point clouds from monocular endoscopic images is a challenging task. This paper proposes a novel deep learning-based computational framework for 3D point cloud reconstruction from single monocular endoscopic images.

Methods: An unsupervised mono-depth learning network is used to generate depth information from monocular images. Given a single mono endoscopic image, the network is capable of depicting a depth map. The depth map is then used to recover a dense 3D point cloud. A generative Endo-AE network based on an auto-encoder is trained to repair defects of the dense point cloud by generating the best representation from the incomplete data. The performance of the proposed framework is evaluated against state-of-the-art learning-based methods. The results are also compared with non-learning based stereo 3D reconstruction algorithms.

Results: Our proposed methods outperform both the state-of-the-art learning-based and non-learning based methods for 3D point cloud reconstruction. The Endo-AE model for point cloud completion can generate high-quality, dense 3D endoscopic point clouds from incomplete point clouds with holes. Our framework is able to recover complete 3D point clouds with the missing rate of information up to 60%. Five large medical in-vivo databases of 3D point clouds of real endoscopic scenes have been generated and two synthetic 3D medical datasets are created. We have made these datasets publicly available for researchers free of charge.

Conclusions: The proposed computational framework can produce high-quality and dense 3D point clouds from single mono-endoscopy images for augmented reality, virtual reality and other computer-mediated medical applications.
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http://dx.doi.org/10.1016/j.cmpb.2021.106077DOI Listing
April 2021

LncRNA MEG3 involved in NiO NPs-induced pulmonary fibrosis via regulating TGF-β1-mediated PI3K/AKT pathway.

Toxicol Sci 2021 Apr 24. Epub 2021 Apr 24.

Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.

Long noncoding RNA maternally expressed gene 3 (MEG3) involves in fibrotic diseases, but its role in nickel oxide nanoparticles (NiO NPs)-induced pulmonary fibrosis remains unclear. The present study aimed to explore the relationships among MEG3, transforming growth factor-β1 (TGF-β1) and phosphoinositide 3-kinase (PI3K)/AKT pathway in NiO NPs-induced pulmonary fibrosis. Wistar rats were intratracheally instilled with NiO NPs twice a week for 9 weeks, and human lung adenocarcinoma epithelial cells (A549 cells) were exposed to NiO NPs for 24 hours. The pathological alterations and increased hydroxyproline indicated that NiO NPs caused pulmonary fibrosis in rats. The up-regulated type I collagen (Col-I) suggested that NiO NPs induced collagen deposition in A549 cells. Meanwhile, NiO NPs could significantly down-regulate MEG3, up-regulate TGF-β1 and activate PI3K/AKT signaling pathway both in vivo and in vitro. However, we found that the PI3K/AKT pathway activated by NiO NPs could be suppressed by 10 μM TGF-β1 inhibitor (SB431542) in A549 cells. The protein markers (Col-I, Fibronectin and alpha-smooth muscle actin) of collagen deposition up-regulated by NiO NPs were reduced by 10 μM PI3K inhibitor (LY294002). Furthermore, we further found that overexpressed MEG3 inhibited the expression of TGF-β1, resulting in the inactivation of PI3K/AKT pathway and the reduction of collagen formation. In summary, our results validated that MEG3 could arrest NiO NPs-induced pulmonary fibrosis via inhibiting TGF-β1-mediated PI3K/AKT pathway.
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http://dx.doi.org/10.1093/toxsci/kfab047DOI Listing
April 2021

Aortic Intimo-intimal Intussusception: A Pooled Analysis of Published Reports.

Ann Vasc Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R.China. Electronic address:

Aim: Aortic intimo-intimal intussusception (AoII) is a rare manifestation of aortic dissection with high mortality. This study aimed to obtain a comprehensive understanding of AoII.

Methods: Three databases (Pubmed, Scopus, Embase) were searched with predefined search terms ["intimal intussusception", "aortic intussusception", "(circumferential) AND (intimal dissection)" and "(circumferential) AND (aortic dissection)"]. Demographics, clinical manifestations, imaging methods, therapies, and follow-up data were recorded and analyzed.

Results: The literature search finally identified 81 papers comprising 87 patients (Mean age: 53.7±14.9 years old; male: n=63). According to morphologic criteria (orientation of AoII intimal flap), patients were divided into three groups: antegrade(n=37), retrograde (n=49) and bidirectional (n=1) orientation. The most frequent symptoms in antegrade group were chest pain (62.2%), syncope (27%), and unconsciousness (21.6%), while in retrograde group, they were chest pain (71.4%), dyspnea (20.4%), and back pain (16.3%). Regarding applied imaging modalities, 67.5% of patients in antegrade group were diagnosed with≥2 methods, comparing with 87.7% in retrograde group. A total of 21 patients (24.1%) with AoII finally died, among which 13.8% (12/87) died before surgery.

Conclusion: AoII is a rare form of aortic dissection with high mortality. Antegrade orientation of the intima flap was more accompanied with neurological disorders and asymmetric blood pressure, while retrograde orientation mostly manifested with aortic regurgitation. Application of multiple imaging examinations may detect this rare entity in time.
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http://dx.doi.org/10.1016/j.avsg.2021.02.041DOI Listing
April 2021

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis.

Front Cell Infect Microbiol 2021 18;11:618265. Epub 2021 Mar 18.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: Aging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.

Objective: To explore the underlying mechanism of how aging aggravates AS advancement.

Methods: A young (five-week-old, YM) and aged group (32-week-old, OM) male apoE mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.

Results: ApoE mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as , , , and were significantly increased in the aged apoE mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.

Conclusions: Aging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.
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http://dx.doi.org/10.3389/fcimb.2021.618265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012722PMC
March 2021

Cell nucleus as endogenous biological micropump.

Biosens Bioelectron 2021 Jun 17;182:113166. Epub 2021 Mar 17.

Institute of Nanophotonics, Jinan University, Guangzhou, 511443, China.

Micropumps can generate directional microflows in blood vessels or bio-capillaries for targeted transport of nanoparticles and cells in vivo, which is highly significant for biomedical applications from active drug delivery to precision clinical therapy. Meanwhile, they have been extensively used in the biosensing fields with their unique features of autonomous motion, easy surface functionalization, dynamic capture and effective isolation of analytes in complex biological media. However, synthetic devices for actuating microflows, including pumps and motors, generally exhibit poor or limited biocompatibility with living organisms as a result of the invasive implantation of exogenous materials into blood vessels. Here we demonstrate a method of constructing endogenous micropumps by extracting nuclei from red blood cells, thus making them intrinsically and completely biocompatible. The nuclei are extracted and then driven by a scanning optical tweezing system. By a precise actuation of the microflows, nanoparticles and cells are navigated to target destinations, and the transport velocity and direction is controlled by the multifunctional dynamics of the micropumps. With the targeted transport of functionalized micro/nanoparticles followed by a dynamic mixing in microliter blood samples, the micropumps provide considerable promises to enhance the target binding efficiency and improve the sensitivity and speed of biological assays in vivo. Furthermore, multiplexing by simultaneously driving an array of multiple nuclei is demonstrated, thus confirming that the micropumps could provide a bio-friendly high-throughput in vivo platform for the treatment of blood diseases, microenvironment monitoring, and biomedical analysis.
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http://dx.doi.org/10.1016/j.bios.2021.113166DOI Listing
June 2021

Investigations on the influence of energy source on time-dependent hormesis: A case study of sulfadoxine to Aliivibrio fischeri in different cultivation systems.

Sci Total Environ 2021 Jun 15;775:145877. Epub 2021 Feb 15.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Key Lab of Chemical Assessment and Sustainability, Shanghai, China; Post-doctoral Research Station, College of Civil Engineering, Tongji University, Shanghai 200092, China. Electronic address:

Hormesis is a biphasic dose-response relationship featured by low-dose stimulation and high-dose inhibition. Although the hormetic phenomenon has been extensively studied over the past decades, there is little information regarding the influence of energy source on the occurrence of hormesis, especially the time-dependent one. In this study, to explore the role of cultivation system's energy source in time-dependent hormesis, the toxic dose-responses of Aliivibrio fischeri (A. fischeri) bioluminescence to Sulfadoxine (SDX) during 24 h were determined in four cultivation systems with different energy source conditions. The results indicated that the time-dependent hormetic effects were induced by SDX in all cultivation systems: SDX triggered hormetic phenomenon on the bioluminescence at each growth stage over 24 h in the cultivation systems with sufficient and insufficient energy source; due to the diauxic growth of A. fischeri under multiple energy source conditions, the hormetic effects of SDX gradually disappeared after the preferred energy source was used up. It was speculated that the inhibitory action of SDX was derived from its interaction with DHPS to impede the synthesis of proteins, and SDX bound with AC to upregulate the quorum sensing (QS) system to exhibit the stimulatory action. Comparing the time-dependent hormesis in each cultivation system, it was obtained that the energy source could impact the hourly maximum stimulatory rate, the EC of SDX, and the time point that hormesis occurred, which might result from the influence of energy source on the stimulatory and inhibitory actions of SDX through regulating the metabolic system (individual level) and QS system (group level) of bacteria. This study clarifies the importance of energy source for hormesis occurrence, which may further promote the development of hormesis.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145877DOI Listing
June 2021

Single-Cell Virtual Cytometer allows user-friendly and versatile analysis and visualization of multimodal single cell RNAseq datasets.

NAR Genom Bioinform 2020 Jun 20;2(2):lqaa025. Epub 2020 Apr 20.

Centre de Recherches en Cancérologie de Toulouse, INSERM UMR1037, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Toulouse, France, Institut Universitaire du Cancer-Oncopole de Toulouse, Toulouse, France, laboratoire d'Excellence Toulouse Cancer, TOUCAN.

The development of single-cell transcriptomic technologies yields large datasets comprising multimodal informations, such as transcriptomes and immunophenotypes. Despite the current explosion of methods for pre-processing and integrating multimodal single-cell data, there is currently no user-friendly software to display easily and simultaneously both immunophenotype and transcriptome-based UMAP/t-SNE plots from the pre-processed data. Here, we introduce Single-Cell Virtual Cytometer, an open-source software for flow cytometry-like visualization and exploration of pre-processed multi-omics single cell datasets. Using an original CITE-seq dataset of PBMC from an healthy donor, we illustrate its use for the integrated analysis of transcriptomes and epitopes of functional maturation in human peripheral T lymphocytes. So this free and open-source algorithm constitutes a unique resource for biologists seeking for a user-friendly analytic tool for multimodal single cell datasets.
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http://dx.doi.org/10.1093/nargab/lqaa025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671361PMC
June 2020

Nonoxidative Strategy for Monitoring Peroxynitrite Fluctuations in Immune Responses of Tumorigenesis.

Anal Chem 2021 02 11;93(7):3426-3435. Epub 2021 Feb 11.

Key Laboratory of Life-Organic Analysis of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, P. R. China.

Phagocyte respiratory burst in immune responses generates enormous amounts of reactive oxygen species (ROS) to fulfill primary defense against neoplasia. However, the beneficial functions associated with ROS, especially the potent oxidant/nucleophile peroxynitrite, in an immunological process are still ambiguous. Herein, we report the construction and biological assessment of cyanine-based fluorescent biosensors, which are based on a nonoxidative strategy for peroxynitrite detection. The established nonoxidative strategy is composed of nucleophilic substitution and nanoaggregate formation initiated by peroxynitrite. The proposed nonoxidative strategy in this study could maintain cellular oxidative stress in the critical process of detection and preserve homeostasis of cell metabolism. The remarkable detection sensitivity, reaction selectivity, and spectral photostability of our biosensors enabled us to visualize endogenous peroxynitrite levels in immune-stimulated phagocytes. With the aid of basal peroxynitrite imaging in an acute peritonitis model, the visualization of peroxynitrite level variations in immune responses of tumorigenesis was accomplished assisted by our biosensors. It is envisioned that our strategy provides a promising tool for early tumor diagnosis and evaluation of tumor suppression in the process of immune responses without disturbing the functions of ROS signaling transduction.
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http://dx.doi.org/10.1021/acs.analchem.0c04512DOI Listing
February 2021

LncRNA MEG3 mediates nickel oxide nanoparticles-induced pulmonary fibrosis via suppressing TGF-β1 expression and epithelial-mesenchymal transition process.

Environ Toxicol 2021 Jun 6;36(6):1099-1110. Epub 2021 Feb 6.

Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.

Nickel oxide nanoparticles (NiO NPs) causes pulmonary fibrosis via activating transforming growth factor-β1 (TGF-β1) in rats, but its upstream regulatory mechanisms are unknown. This study aimed to explore the role of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in NiO NPs-induced collagen deposition. Male Wistar rats were intratracheally instilled with NiO NPs (0.015, 0.06, and 0.24 mg/kg b.w.) twice a week for 9 weeks. Human lung adenocarcinoma epithelial cells (A549 cells) were cultured with NiO NPs (25, 50, and 100 μg/ml) to establish collagen deposition model. We discovered that NiO NPs-induced rat pulmonary fibrosis was accompanied by the epithelial-mesenchymal transition (EMT) occurrence and MEG3 down-regulation in rat lung tissues. In cell collagen deposition model, NiO NPs also evoked EMT and decreased MEG3 expression in a dose-dependent manner in A549 cells. By overexpressing MEG3 in A549 cells, we found that MEG3 inhibited the level of TGF-β1, EMT process and collagen formation. Moreover, our data showed that SB431542 (TGF-β1 inhibitor) had an inhibitory effect on NiO NPs-induced EMT and collagen formation. Our results indicated that MEG3 inhibited NiO NPs-induced collagen deposition by regulating TGF-β1-mediated EMT process, which may provide some clues for insighting into the mechanisms of NiO NPs-induced pulmonary fibrosis.
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http://dx.doi.org/10.1002/tox.23109DOI Listing
June 2021

3D "honeycomb" cell/carbon nanofiber/gelatin methacryloyl (GelMA) modified screen-printed electrode for electrochemical assessment of the combined toxicity of deoxynivalenol family mycotoxins.

Bioelectrochemistry 2021 Jun 18;139:107743. Epub 2021 Jan 18.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China. Electronic address:

A "honeycomb" electrochemical biosensor based on 3D printing was developed to noninvasively monitor the viability of 3D cells and evaluate the individual or combined toxicity of deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), and 15-acetyldeoxynivalenol (15-ADON). Carbon nanofiber (CN)/gelatin methacryloyl (GelMA) conductive composite hydrogel with strong processability was printed on 8-channel screen-printed carbon electrodes (SPCEs) to maintain cell viability and form tight cell-to-cell contacts. A "3D honeycomb" printing infill pattern was selected in the construction of the biosensors to improve conductivity. Based on 3D printing technology, the electrochemical biosensor can prevent manual error and provide for high-throughput detection. Electrochemical impedance spectroscopy (EIS) was used to evaluate mycotoxin toxicity. The EIS response decreased with the concentration of DON, 3-ADON and 15-ADON in the range of 0.1-10, 0.05-100, and 0.1-10 μg/mL, respectively, with a limit of detection of 0.07, 0.10 and 0.06 μg/mL, respectively. Mycotoxin interactions were analyzed using the isobologram-combination index (CI) method. The electrochemical cytotoxicity evaluation result was confirmed by biological assays. Therefore, a novel method for evaluating the combined toxicity of mycotoxins is proposed, which exhibits potential for application to food safety and evaluation.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107743DOI Listing
June 2021

Encapsulation of caffeine into starch matrices: Bitterness evaluation and suppression mechanism.

Int J Biol Macromol 2021 Mar 11;173:118-127. Epub 2021 Jan 11.

School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China; Sino-Singapore International Joint Research Institute, Guangzhou 511363, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou 510640, China. Electronic address:

In this study, caffeine (CA) was encapsulated into food-grade starch matrices, including swelled starch (SS), porous starch (PS), and V-type starch (VS). The bitterness of the microcapsules and suppression mechanisms were investigated using an electronic tongue, molecular dynamics (MD) simulation and the in vitro release kinetics of CA. All the CA-loaded microcapsules showed a lower bitterness intensity than the control. The MD results proved that the weak interactions between starch and CA resulted in a moderate CA release rate for SS-CA microcapsules. The PS-CA microcapsule presented the longest CA release, up to 40 min, whereas the VS-CA microcapsule completely released CA in 9 min. The CA release rate was found to be related to the microcapsule structure and rehydration properties. A low CA bitterness intensity could be attributed to a delay in the CA release rate and resistance to erosion of the microcapsules. The results of this work are valuable for improving starch-based microcapsules (oral-targeted drug-delivery systems) by suppressing the bitterness of alkaloid compounds.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.043DOI Listing
March 2021

Pediatric Tuina (massage) for primary monosymptomatic nocturnal enuresis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Dec;99(51):e23738

The Affiliated Hospital of Shandong University of TCM, Shandong Province, China.

Background: Primary monosymptomatic nocturnal enuresis is one of the common diseases of preschool and school-age children and it will cause adverse effects on the healthy growth. Pediatric Tuina (massage) has been widely used in the treatment of monosymptomatic nocturnal enuresis in China. The study is conducted to summarize the current evidence on the effects and safety of Pediatric Tuina (massage) therapy for the treatment of primary monosymptomatic nocturnal enuresis in children.

Methods: The following electronic databases will be searched from establishment to December, 2019: Cochrane Library, MEDLINE, EMBASE, Web of Science, World Health Organization International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan-fang database, Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Databases (CBM), and other databases, without any language restrictions. Randomized controlled trials about this theme will be retrieved. Independent reviewers will operate literature retrieval, duplication removing, screening, quality evaluation, data analyses by EndNote (X9), and Review Manager (5.3). Meta-analysis, subgroup analysis, and/or descriptive analysis will be performed based on the included data form.

Results: High-quality synthesis and/or descriptive analysis of current evidence will be provided from improvement of nocturia frequency, improvement of sleep wakefulness disorder, and total efficiency.

Conclusion: This review will provide evidence of whether Pediatric Tuina (massage) is an effective and safe intervention for primary monosymptomatic nocturnal enuresis in children.

Trail Registration Number: This protocol of systematic review has been registered on PROSPERO website (No. CRD42020165107).
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http://dx.doi.org/10.1097/MD.0000000000023738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748190PMC
December 2020

The chloroplast genome of (Apiaceae), an endemic medicinal plant to China.

Mitochondrial DNA B Resour 2020 Nov 20;5(3):3782-3783. Epub 2020 Nov 20.

College of Architecture and Environment, Sichuan University, Chengdu, P. R. China.

is a traditional Chinese medicinal herb endemic to Southeast and South China, but now is becoming very rare because of rapid habit loss. The complete chloroplast genome of was sequenced herein and suggested that the complete chloroplast genome was 155,919 bp in length, comprising the large single-copy (LSC) region of 85,393 bp, the small single-copy (SSC) region of 19,760 bp, and a pair of inverted regions (IRs) of 25,383 bp. Totally 127 genes were distributed in the whole genome, including 4 rRNAs, 37 tRNAs, and 81 protein coding genes. The G + C content of this chloroplast genome was 38%. Phylogenetic inference revealed that was accompanied with and sister to , indicating a close relationship between and .
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http://dx.doi.org/10.1080/23802359.2020.1778560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682742PMC
November 2020

Enhancer II-targeted dsRNA decreases GDNF expression via histone H3K9 trimethylation to inhibit glioblastoma progression.

Brain Res Bull 2021 Feb 3;167:22-32. Epub 2020 Dec 3.

Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China. Electronic address:

Background: Glial cell line-derived neurotrophic factor (GDNF) is expressed in both astrocytes and glioblastoma (GBM) cells. GDNF expression is significantly increased in GBM, and inhibiting its expression can retard GBM progression. However, there is no known method for specific inhibition of GDNF in GBM cells.

Methods: Promoter-targeted dsRNA-induced transcriptional gene silencing or activation was recently achieved in human cells. This approach has the potential to specifically regulate gene transcription via epigenetic modifications. In this study, we designed six candidate dsRNAs targeting the enhancer or silencer in GDNF gene promoter II to check their effects on GDNF transcription and GBM progression.

Results: Among these dsRNAs, enhancer II-targeted dsRNA significantly inhibited U251 GBM progression by downregulating GDNF (P < 0.05), while silencer II-targeted dsRNA exerted an opposite effect. Moreover, enhancer II-targeted dsRNA did not significantly change GDNF expression in human astrocytes (HA) and the proliferation and migration of HA cells (P > 0.05). Bisulfate PCR and chromatin immunoprecipitation analyses revealed that both DNA methylation and trimethylation of histone 3 at lysine 9 (H3K9me3) at silencer II-targeted region significantly increased, and H3K9me3 at enhancer II-targeted region significantly decreased, in U251 cells compared with HA cells in non-intervention condition (P < 0.05). Both enhancer II- and silencer II-targeted dsRNA significantly increased H3K9me3 methylation rather than DNA at the targeted site in U251 cells (P < 0.05). The expression and activity of histone methyltransferase SETDB1 increased dramatically in U251 cells compared with HA cells, and it was recruited to enhancer II targeting region after enhancer II-targeted dsRNA treatment in U251 cells (P < 0.05).

Conclusions: Our results demonstrate that a promoter-targeted dsRNA can silence or promote gene transcription depending on its targeted site in different cis-acting elements in the gene promoter. Targeted inhibition of GDNF by enhancer II-targeted dsRNA may be explored as a novel treatment for GBM.
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http://dx.doi.org/10.1016/j.brainresbull.2020.11.022DOI Listing
February 2021

Adrenomedullin 2 attenuates LPS-induced inflammation in microglia cells by receptor-mediated cAMP-PKA pathway.

Neuropeptides 2021 Feb 24;85:102109. Epub 2020 Nov 24.

Department of Physiology, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Inflammation plays a critical role in the development of neurodegenerative diseases. Adrenomedullin 2 (AM2), a member of the calcitonin gene-related peptide family, has been known to have anti-inflammatory effects. Here, we evaluated the anti-inflammatory effects of AM2 in LPS-activated microglia and BV2 cells. The endogenous mRNA and protein expressions of AM2, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMPs) including RAMP1, RAMP2 and RAMP3 and the production of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by RT-PCR and Western blot. Our results revealed that LPS (1 μg/mL) significantly stimulated CLR, RAMP1, RAMP2 and RAMP3 protein expressions in BV2 microglia cells, but AM2 had a significant decrease. However, the mRNA levels of AM2, CLR, and RAMP1/2/3 were all markedly increased. LPS also induced obvious increases in mRNA and protein levels of the inflammatory mediators (TNF-α, IL-1β, COX2 and iNOS). More importantly, AM2 (10 nM) administration effectively inhibited the mRNA and protein expressions of these mediators induced by LPS and increased the cAMP content in LPS-stimulated BV2 cells. Furthermore, the antagonism with AM2 receptor antagonist IMD17-47, adrenomedullin (AM) receptor antagonist by AM22-52 or the inhibition of protein kinase A (PKA) activation by P1195 effectively prevented the inhibitory role of AM2 in LPS-induced production of the above inflammatory mediators. In conclusion, AM2 inhibits LPS-induced inflammation in BV2 microglia cells that may be mainly through AM receptor-mediated cAMP-PKA pathway. Our results indicate AM2 plays an important protective role in microglia inflammation, suggesting therapeutic potential for AM2 in neuroinflammation diseases caused by activated microglia.
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http://dx.doi.org/10.1016/j.npep.2020.102109DOI Listing
February 2021

Lightweight 3D bioprinting with point by point photocuring.

Bioact Mater 2021 May 10;6(5):1402-1412. Epub 2020 Nov 10.

State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China.

As photocrosslinkable materials, methacryloyl-modified hydrogels are widely used as bioinks in tissue engineering. Existing printing methods to use these hydrogels, including changing the viscosity of the material or mixing them with other printing components, have been explored, but their application has been limited due to low printing quality or high cost. In addition, the complex operation of bulky equipment restricts the application of these existing printing methods. This study presents a lightweight stereolithography-based three-dimensional (3D) bioprinting system with a smart mechanical and structural design. The developed bioprinter dimensions were 300 mm × 300 mm × 200 mm and it can be placed on a benchtop. The equipment has a mini bioink chamber to store a small amount of bioink for each printing. We systematically investigated the point-by-point curing process in the 3D bioprinting method, which can print mixed cells accurately and have good biocompatibility. Here, we provide a compact, low-cost stereolithography bioprinting system with excellent biocompatibility for 3D bioprinting with methacryloyl-modified hydrogels. It can be potentially used for drug screening, studying pathological mechanisms, and constructing biological disease models.
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http://dx.doi.org/10.1016/j.bioactmat.2020.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658498PMC
May 2021

Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity.

Drug Des Devel Ther 2020 22;14:4423-4438. Epub 2020 Oct 22.

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People's Republic of China.

Introduction: Berberrubine (BRB), an isoquinoline alkaloid, is a major constituent of medicinal plants Franch or Schneid. BRB exhibits various pharmacological activities, whereas exposure to BRB may cause toxicity in experimental animals.

Methods: In this study, we thoroughly investigated the liver injury induced by BRB in mice and rats. To explore the underlying mechanism, a study of the metabolic activation of BRB was conducted. Furthermore, covalent modifications of cysteine residues of proteins were observed in liver homogenate samples of animals after exposure to BRB, by application of an exhaustive proteolytic digestion method.

Results: It was demonstrated that BRB-induced hepatotoxicities in a time- and dose-dependent manner, based on the biochemical parameters ALT and AST. H&E stained histopathological examination showed the occurrence of obvious edema in liver of mice after intraperitoneal (i.p.) administration of BRB at a single dose of 100 mg/kg. Slight hepatotoxicity was also observed in rats given the same doses of BRB after six weeks of gavage. As a result, four GSH adducts derived from reactive metabolites of BRB were detected in microsomal incubations with BRB fortified with GSH as a trapping agent. Moreover, four cys-based adducts derived from reaction of electrophilic metabolites of BBR with proteins were found in livers.

Conclusion: These results suggested that the formation of protein adducts originating from metabolic activation of BRB could be a crucial factor of the mechanism of BRB-induced toxicities.
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http://dx.doi.org/10.2147/DDDT.S274627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588839PMC
October 2020

Quantitative analysis of analytical elements in Al-In-Sn-O thin film based on comprehensive calibration curves using picosecond laser-induced breakdown spectroscopy.

Appl Opt 2020 Oct;59(29):9152-9158

Al-In-Sn-O (AITO) thin film refers to a novel wide-bandgap transparent conductive material, which is formed by doping the aluminum element into In-Sn-O material. It is of promising application in deep ultraviolet optoelectronic devices. /++ and /++ are capable of impacting the optical and electrical properties of AITO thin film. Three groups of AITO thin film samples with different sputtering powers, sputtering pressures, and sputtering times were prepared with magnetron sputtering. The concentration ratio of /++ and /++ in AITO samples was quantitatively analyzed with laser-induced breakdown spectroscopy (LIBS) technology. A single calibration curve was drawn based on the sputtering parameters of each group, and the comprehensive calibration curves of two concentration ratios under any sputtering parameters were plotted. The accuracy of the comprehensive calibration curve was determined with samples prepared under random sputtering parameters, and the energy dispersive x-ray spectroscopy analysis results were compared with the LIBS technical analysis results. The relative error was less than 5%, so the LIBS technical analysis was demonstrated to be accurate. By building the comprehensive calibration curve, a novel method to conduct rapid online analysis of AITO thin films and timely determination of photoelectrical properties is presented, and the new application of LIBS technology is developed in thin film semiconductor materials.
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http://dx.doi.org/10.1364/AO.402542DOI Listing
October 2020

Altered Brain Functional Connectivity Density in Fast-Ball Sports Athletes With Early Stage of Motor Training.

Front Psychol 2020 25;11:530122. Epub 2020 Sep 25.

School of Mathematical Sciences, University of Electronic Science and Technology of China, Chengdu, China.

The human brain shows neuroplastic adaptations caused by motor skill training. Of note, there is little known about the plastic architecture of the whole-brain network in resting state. The purpose of the present study was to detect how motor training affected the density distribution of whole-brain resting-state functional connectivity (FC). Resting-state functional magnetic resonance imaging data was assessed based on a comparison of fast-ball student athletes (SA) and non-athlete healthy controls (NC). The voxel-wise data-driven graph theory approach, global functional connectivity density (gFCD) mapping, was applied. Results showed that the SA group exhibited significantly decreased gFCD in brain regions centered at the left triangular part of the inferior frontal gyrus (IFG), extending to the opercular part of the left IFG and middle frontal gyrus compared to the NC group. In addition, findings suggested the idea of an increased neural efficiency of athletes' brain regions associated with attentional-motor modulation and executive control. Furthermore, behavioral results showed that in the SA group, faster executive control reaction time relates to smaller gFCD values in the left IFG. These findings suggested that the motor training would decrease the numbers of FC in IFG to accelerate the executive control with high attentional demands and enable SA to rapidly focus the attention to detect the intriguing target.
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http://dx.doi.org/10.3389/fpsyg.2020.530122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546905PMC
September 2020

The predictive value of intraoperative transit-time flow measurement parameters for early graft failure in different target territories.

J Cardiol 2021 Feb 2;77(2):201-205. Epub 2020 Oct 2.

Cardiac Surgery Department, Peking University People's Hospital, Beijing, China. Electronic address:

Background: Early graft failure can affect the short- and long-term outcomes of patients undergoing coronary bypass grafting surgery (CABG). The aim of our study was to explore the predictive value of transit-time flow measurement (TTFM) parameters for early graft failure (before discharge) after CABG in different coronary territories and calculate the TTFM cut-off values.

Methods: We analyzed a total of 761 grafts (360 patients) that were evaluated by intraoperative TTFM and computed tomography angiography prior to discharge. Logistic model was established to detect the parameters of TTFM to predict early graft failure and receiver operating characteristic curve analysis was used to calculate the cut-off values.

Results: The overall early graft failure was 3.5%. The results demonstrated that compared with off-pump CABG, mean graft flow volume was higher (28.0 vs 21.0 mL/min, p = 0.000), but pulse index (PI) (2.3 vs 2.5, p = 0.049) and diastolic flow fraction (DF) (68.0% vs 71.0%, p = 0.001) were lower in on-pump CABGs. DF (73.0% vs 65.5%, p = 0.000) of arterial grafts was higher than that of venous grafts. DF (72.0% vs 62.0%, p = 0.000) in left was higher than that in the right coronary artery territories. The results of multivariate logistic analysis showed that not only in the overall (OR 1.18, 95% CI 1.07-1.30, p = 0.001), but also the left (OR 1.21, 95% CI 1.03-1.41, p = 0.017) and right (OR 1.15, 95% CI 1.03-1.29, p = 0.017) coronary artery target territories, PI was a risk factor for early graft failure and the cut-off value was 3.4, 3.4, and 3.6, respectively. For grafts in left target territories, the results showed that DF (OR 0.94, 95% CI 0.91-0.97, p = 0.000) just in the univariate analysis was a risk factor that affected graft failure.

Conclusions: The overall early graft failure was about 3.5%. High PI value is a risk factor for early graft failure in not only overall grafts but in grafts of different target territories. DF might be more useful for the quality evaluation of grafts in left than in right target territories.
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http://dx.doi.org/10.1016/j.jjcc.2020.09.003DOI Listing
February 2021

3D printed high-resolution scaffold with hydrogel microfibers for providing excellent biocompatibility.

J Biomater Appl 2021 Jan 30;35(6):633-642. Epub 2020 Sep 30.

Institute of Optical and Electromechanical Technology and Applications, School of Mechatronics & Vehicle Engineering, East China Jiaotong University, Nanchang, China.

Melt electrowriting (MEW) can print high-resolution scaffolds with the ultrafine fibers from 800 nm to 20 µm. However, the cell seeding efficiency relatively low due to the large pore size of the MEW scaffold. Here, we reported a method to solve this dilemma by electrospinning a gelatin methacrylate (GelMA) hydrogel fibers membrane (HFM) on the MEW scaffold. This composite scaffold can own the controlled structures and porosity and excellent cell seeding performance. We systematically investigate the fabrication, morphology, and biocompatibility of composite scaffolds. The implanting of human umbilical vein endothelial cells(HUVES) showed excellent adhesion and biocompatibility on the composite scaffold. Moreover, the cells migrated gradually into the MEW scaffold along the GelMA HFM to form the cell sheet. We hold the opinion that the composite scaffolds have potential applications in the field of tissue engineering repair.
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http://dx.doi.org/10.1177/0885328220962606DOI Listing
January 2021

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

Obesity (Silver Spring) 2021 Jan 28;29(1):86-97. Epub 2020 Sep 28.

Department of Physiology, Nanjing Medical University, Nanjing, China.

Objective: Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study.

Methods: Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks.

Results: When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)-treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL-1β, cyclooxygenase-2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF-κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP-dependent protein kinase (PKA) activation inhibitor.

Conclusions: ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.
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http://dx.doi.org/10.1002/oby.23012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821304PMC
January 2021

Correlation of serum N-Acetylneuraminic acid with the risk and prognosis of acute coronary syndrome: a prospective cohort study.

BMC Cardiovasc Disord 2020 09 10;20(1):404. Epub 2020 Sep 10.

Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, 287 Zhihuai Road, Bengbu, 233000, Anhui, China.

Background: N-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study.

Methods: Patients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up.

Results: A total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002-1.005, p < 0.001).

Conclusions: Serum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.
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http://dx.doi.org/10.1186/s12872-020-01690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488474PMC
September 2020

Apigetrin ameliorates streptozotocin-induced pancreatic β-cell damages via attenuating endoplasmic reticulum stress.

In Vitro Cell Dev Biol Anim 2020 Sep 8;56(8):622-634. Epub 2020 Sep 8.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.

The pathogenesis of diabetes is associated with dysfunction of pancreatic β-cells. To ameliorate the β-cell dysfunction, it has propelled great interest to search pharmacological agents from natural plants. This study explored the protective effect of apigetrin, a flavonoid present in natural plants, against streptozotocin (STZ)-induced cell damages in RINm5F cells and the potential mechanisms. Apigetrin was found to inhibit the elevation of intracellular reactive oxygen species levels, restore the impairment of antioxidant enzymes, and recover the disruption of redox homeostasis in the STZ-treated pancreatic β-cells. Moreover, treatment of apigetrin significantly suppressed the STZ-induced apoptosis in the analysis of apoptotic sub-G population and the protein expressions of cleaved poly(ADP-ribose) polymerase and caspase-3. Furthermore, apigetrin attenuated STZ-induced endoplasmic reticulum (ER) stress, indicated by the reduction of ER stress biomarkers, including overloading of mitochondrial calcium, increase in glucose-regulated protein 78, phosphorylation of protein kinase RNA-like ER kinase and its downstream eukaryotic initiation factor 2α, cleavage of activating transcription factor 6 and caspase-12, up-regulation of CCAAT/enhancer binding protein homologous protein, and induction of spliced X-box binding protein 1. Additionally, pretreatment with 4-phenylbutyric acid, a classic ER stress inhibitor, augmented these beneficial effects of apigetrin. In conclusion, these results demonstrated that apigetrin could improve the STZ-induced pancreatic β-cell damages via mitigation of oxidative stress and ER stress and supported the application of apigetrin to developing the novel therapeutics of diabetes.
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http://dx.doi.org/10.1007/s11626-020-00478-xDOI Listing
September 2020

7,8-Dihydroxyflavone Alleviates Anxiety-Like Behavior Induced by Chronic Alcohol Exposure in Mice Involving Tropomyosin-Related Kinase B in the Amygdala.

Mol Neurobiol 2021 Jan 7;58(1):92-105. Epub 2020 Sep 7.

Department of Physiology & Neurobiology, Mudanjiang Medical University, Mudanjiang, 157011, China.

Alcohol use-associated disorders are highly comorbid with anxiety disorders; however, their mechanism remains unknown. The amygdala plays a central role in anxiety. We recently found that 7,8-dihydroxyflavone (7,8-DHF) significantly reduces withdrawal symptoms in a rat model of chronic intermittent alcohol (ethanol) exposure. This study aimed to determine the role of 7,8-DHF in regulating anxiety induced by chronic alcohol exposure and its associated underlying mechanism. Male C57BL/6J mice were exposed to chronic intermittent alcohol for 3 weeks followed by alcohol withdrawal for 12 h with or without 7,8-DHF administered intraperitoneally. All mice were tested using an open field test and elevated plus maze to assess anxiety-like behaviors. Synaptic activity and intrinsic excitability in basal and lateral amygdala (BLA) neurons were assessed using electrophysiological recordings. 7,8-DHF alleviated alcohol-induced anxiety-like behavior and attenuated alcohol-induced enhancement of activities in BLA pyramidal neurons. Furthermore, 7,8-DHF prevented alcohol withdrawal-evoked augmentation of glutamatergic transmission in the amygdala and had no effect on GABAergic transmission in the amygdala, as demonstrated by unaltered frequency and amplitude of spontaneous inhibitory postsynaptic currents. Microinjection of K252a, a tropomyosin-related kinase B (TrkB) antagonist, into the BLA blocked the effects of 7,8-DHF on anxiety-like behavior and neuronal activity in the BLA. Our findings suggest that 7,8-DHF alleviates alcohol-induced anxiety-like behavior induced by chronic alcohol exposure through regulation of glutamate transmission involving TrKB in the BLA.
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http://dx.doi.org/10.1007/s12035-020-02111-0DOI Listing
January 2021

Roles of Gut Microbiota in Pathogenesis of Alzheimer's Disease and Therapeutic Effects of Chinese Medicine.

Chin J Integr Med 2020 Sep 1. Epub 2020 Sep 1.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive impairment. The pathogenesis of AD is complex, and its susceptibility and development process are affected by age, genetic and epigenetic factors. Recent studies confirmed that gut microbiota (GM) might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflflammatory and immune processes. CM formula, herbs, and monomer enjoy unique advantages to treat and prevent AD. Hence, the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD. Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed. The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.
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http://dx.doi.org/10.1007/s11655-020-3274-5DOI Listing
September 2020

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia.

Bioact Mater 2021 Jan 7;6(1):1-11. Epub 2020 Aug 7.

Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine. Chinese Academy of Medical Sciences and Peking Union Medical College. Graduate School of Peking Union Medical College, Beijing, 100730, PR China.

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn and EGCG, thus enabling the direct application to limb ischemia.
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http://dx.doi.org/10.1016/j.bioactmat.2020.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415630PMC
January 2021