Publications by authors named "Qiang Ye"

175 Publications

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches.

Phytother Res 2021 Nov 24. Epub 2021 Nov 24.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un-cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high-quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products.
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http://dx.doi.org/10.1002/ptr.7324DOI Listing
November 2021

Naringenin: A Promising Therapeutic Agent against Organ Fibrosis.

Oxid Med Cell Longev 2021 11;2021:1210675. Epub 2021 Nov 11.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China.

Fibrosis is the final common pathology of most chronic diseases as seen in the heart, liver, lung, kidney, and skin and contributes to nearly half of death in the developed countries. Fibrosis, or scarring, is mainly characterized by the transdifferentiation of fibroblasts into myofibroblasts and the excessive accumulation of extracellular matrix (ECM) secreted by myofibroblasts. Despite immense efforts made in the field of organ fibrosis over the past decades and considerable understanding of the occurrence and development of fibrosis gained, there is still lack of an effective treatment for fibrotic diseases. Therefore, identifying a new therapeutic strategy against organ fibrosis is an unmet clinical need. Naringenin, a flavonoid that occurs naturally in citrus fruits, has been found to confer a wide range of pharmacological effects including antioxidant, anti-inflammatory, and anticancer benefits and thus potentially exerting preventive and curative effects on numerous diseases. In addition, emerging evidence has revealed that naringenin can prevent the pathogenesis of fibrosis in vivo and in vitro via the regulation of various pathways that involved signaling molecules such as transforming growth factor-1/small mother against decapentaplegic protein 3 (TGF-1/Smad3), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), sirtuin1 (SIRT1), nuclear factor-kappa B (NF-B), or reactive oxygen species (ROS). Targeting these profibrotic pathways by naringenin could potentially become a novel therapeutic approach for the management of fibrotic disorders. In this review, we present a comprehensive summary of the antifibrotic roles of naringenin in vivo and in vitro and their underlying mechanisms of action. As a food derived compound, naringenin may serve as a promising drug candidate for the treatment of fibrotic disorders.
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http://dx.doi.org/10.1155/2021/1210675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601819PMC
November 2021

The Role of RAD6B and PEDF in Retinal Degeneration.

Neuroscience 2021 Nov 11;480:19-31. Epub 2021 Nov 11.

Institute of Human Anatomy and Histoembryology, Basic Medical College, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China. Electronic address:

RAD6B is an E2 ubiquitin-conjugating enzyme, playing an important role in DNA damage repair, gene expression, senescence, apoptosis and protein degradation. However, the specific mechanism between ubiquitin and retinal degeneration requires more investigation. Pigment epithelium-derived factor (PEDF) has a potent neurotrophic effect on the retina, protecting retinal neurons and photoreceptors from cell death caused by pathological damage. In this study, we found that loss of RAD6B leads to retinal degeneration in mice, especially in old age. Affymetrix microarray analysis showed that the PEDF signal was changed in RAD6B deficient groups. The expression of γ-H2AX, β-Gal, P53, Caspase-3, P21 and P16 was increased significantly in retinas of RAD6B knockout (KO) mice. Our studies suggest that RAD6B and PEDF play an important role in the health of retina, whereas the absence of RAD6B accelerates the degeneration.
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http://dx.doi.org/10.1016/j.neuroscience.2021.11.010DOI Listing
November 2021

A phase 3 clinical trial of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old.

Vaccine 2021 Nov 24;39(47):6947-6955. Epub 2021 Oct 24.

Minhai Biotechnology Co., Ltd., Beijing, China. Electronic address:

Background: Pneumococcus lead to various kinds of invasive disease such as pneumonia, otitis media, meningitis, bacteremia and so on. It has been a great threat to children under 5. A new 13-valent pneumococcal conjugate vaccine (PCV13) with carrier tetanus toxoid and diphtheria toxoid was developed by MINHAI, aiming to prevent pneumococcus infection. In this study, we reported the safety and immunogenicity of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old.

Methods: A randomized, double-blinded, parallelized phase III clinical trial was operated in 900 participants. Haemophilus influenzae type B conjugate vaccine (Hib) served as negative control. PCV13 and Hib were intramuscular injected to participants at a ratio of 2:1. Local and systemic adverse events (AEs) and severe adverse events (SAEs) were recorded to evaluate the safety of PCV13. Blood samples were collected before and after immunization for the detecting of serotype-specific anti-polysaccharide immunoglobulin (Ig)G and opsonophagocytosis assay (OPA). The proportion of IgG concentration ≥ 0.35 μg/mL (IgG positive rate), IgG geometric mean concentration (GMC), OPA geometric mean titer (GMT), and other indicators were analyzed to evaluate the immunogenicity of PCV13.

Results: During the study period, no PCV13 associated SAE happened. Incidences of several AEs in PCV13 groups were higher than the Hib groups, but most of them were mild or moderate. For all 13 serotypes, IgG and OPA indicators of the PCV13 groups were generally superior to the Hib groups, and the differences were mostly statistically significant, which indicates that MINHAI PCV13 can effectively induce pneumococcal specific antibody.

Conclusion: The study demonstrates that MINHAI PCV13 has sufficient immunogenicity and safety in Chinese children aged from 7 months to 5 years old.

Clinical Trial Registration: NCT02494999.
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http://dx.doi.org/10.1016/j.vaccine.2021.09.047DOI Listing
November 2021

Immunogenicity of 23-Valent Pneumococcal Polysaccharide Vaccine in Patients with Chronic Obstructive Pulmonary Disease - Hebei Province, China, September-December, 2019.

China CDC Wkly 2021 Apr;3(16):331-334

National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China.

What Is Already Known On This Topic?: The global burden of chronic obstructive pulmonary disease (COPD) is serious. Pneumococcal infection is associated with acute exacerbations of COPD (AECOPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for COPD patients to decrease AECOPD due to pneumococcus, but evidence on the immunogenicity of PPSV23 in COPD patients is limited.

What Is Added By This Report?: This study showed good immunogenicity of one dose of PPSV23 in COPD patients. Antibody levels against all 23 vaccine serotypes were assessed before and four weeks after vaccination of COPD patients with one dose of PPSV23. The percent of COPD patients who had two-fold increases in pneumococcal antibody levels following vaccination ranged from 65.2% (serotype 3) to 94.4% (serotype 2). There were statistically significant differences in immunogenicity by serotype.

What Are The Implications For Public Health Practice?: This study supports current recommendations for PPSV23 vaccination of COPD patients in China to provide protection from pneumococcal diseases.
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http://dx.doi.org/10.46234/ccdcw2021.089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393071PMC
April 2021

Halogen Bonded Chiral Emitters: Generation of Chiral Fractal Architecture with Amplified Circularly Polarized Luminescence.

Angew Chem Int Ed Engl 2021 Oct 14;60(42):22711-22716. Epub 2021 Sep 14.

Beijing National Laboratory for Molecular Science, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, No.2, ZhongGuanCun BeiYiJie, Beijing, 100190, P. R. China.

Self-assembled chiroptical materials have attracted considerable attention due to their great applications in wide fields. During the chiral self-assembly, it remains unknown how achiral molecules can affect the assembly process and their final chiroptical performance. Herein, we report an achiral molecule directed chiral self-assembly via halogen bonds, exhibiting not only an unprecedented chiral fractal architecture but also significantly amplified circularly polarized luminescence (CPL). Two axially chiral emitters with halogen bond sites co-assemble with an achiral 1,4-diiodotetrafluorobenzene (F DIB) and well-ordered chiral fractal structures with asymmetry amplification are obtained. The enhancement of the dissymmetry factors of the assemblies was up to 0.051 and 0.011, which was approximately 100 folds than those of the corresponding molecules. It was found that both the design of the chiral emitter and the highly directional halogen bond played an important role in hierarchically chirality transfer from chiral emitters to the micrometer scale chiral fractal morphology and amplified dissymmetry factors. We hope that this strategy can give a further insight into the fabrication of structurally unique featured highly efficient chiroptical materials.
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http://dx.doi.org/10.1002/anie.202108661DOI Listing
October 2021

Comprehensive analysis of dysregulated genes associated with atherosclerotic plaque destabilization.

Exp Biol Med (Maywood) 2021 Dec 25;246(23):2487-2494. Epub 2021 Jul 25.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

Atherosclerotic plaque destabilization is a dominating cause of acute cardiovascular events such as myocardial infarction and stroke. This study aims to identify genetic biomarkers related to atherosclerotic plaque destabilization using bioinformatics. Three transcriptome datasets of human carotid atherosclerotic plaque samples were downloaded from ArrayExpress and Gene Expression Omnibus databases, including E-MATB-2055, E-TABM-190, and GSE120521. With Robust Rank Aggregation analysis, we documented 46 differentially expressed genes between stable and unstable/ruptured plaques. Functional enrichment analysis using DAVID tool demonstrated that these genes were mainly related to biological functions such as extracellular matrix disassembly, collagen catabolic process, response to mechanical stimulus, and PPAR signaling pathway. A protein-protein interaction network for the differentially expressed genes was constructed, and eight pivotal genes (, , , , , , , and ) were obtained from the network with a connective degree > 5. The expression patterns of these hub differentially expressed genes could be verified in atherosclerotic plaque samples with intraplaque hemorrhage. Using gene set variation analysis, the eight genes were integrated to generate an atherosclerotic plaque destabilization score, which showed a high performance in not only discriminating individuals with myocardial infarction from those with stable coronary illness, but also in predicting future acute cardiovascular events in atherosclerotic patients. In conclusion, the findings of this study will enhance our knowledge on the pathological mechanisms involved in atherosclerotic plaque destabilization, and provide potential gene biomarkers for risk stratification of patients with atherosclerotic cardiovascular disease.
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http://dx.doi.org/10.1177/15353702211033247DOI Listing
December 2021

Editing the Shape Morphing of Monocomponent Natural Polysaccharide Hydrogel Films.

Research (Wash D C) 2021 2;2021:9786128. Epub 2021 Jun 2.

Institute of Biomedical & Health Engineering, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518035, China.

Shape-morphing hydrogels can be widely used to develop artificial muscles, reconfigurable biodevices, and soft robotics. However, conventional approaches for developing shape-morphing hydrogels highly rely on composite materials or complex manufacturing techniques, which limit their practical applications. Herein, we develop an unprecedented strategy to edit the shape morphing of monocomponent natural polysaccharide hydrogel films via integrating gradient cross-linking density and geometry effect. Owing to the synergistic effect, the shape morphing of chitosan (CS) hydrogel films with gradient cross-linking density can be facilely edited by changing their geometries (length-to-width ratios or thicknesses). Therefore, helix, short-side rolling, and long-side rolling can be easily customized. Furthermore, various complex artificial 3D deformations such as artificial claw, horn, and flower can also be obtained by combining various flat CS hydrogel films with different geometries into one system, which can further demonstrate various shape transformations as triggered by pH. This work offers a simple strategy to construct a monocomponent hydrogel with geometry-directing programmable deformations, which provides universal insights into the design of shape-morphing polymers and will promote their applications in biodevices and soft robotics.
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http://dx.doi.org/10.34133/2021/9786128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214511PMC
June 2021

Research progress in the application of bile acid-drug conjugates: A "trojan horse" strategy.

Steroids 2021 09 26;173:108879. Epub 2021 Jun 26.

State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Bile acid transporters are highly expressed in intestinal cells and hepatocytes, and they determine the uptake of drugs in cells by modulating cellular entry and exit. In order to improve the oral bioavailability of drugs and investigate the potential application prospects of drugs used to target cancer, numerous studies have adopted these transporters to identify prodrug strategies. Through the connection of covalent bonds between drugs and bile acids, the resulting bile acid-drug conjugates continue to be recognized as similar to natural unmodified bile acid and is translocated by the transporter. The present mini-review provides a brief summary of recent progress of the application of bile acid-drug conjugates based primarily on ASBT, NTCP, and OATP, with the hope of contributing to subsequent research.
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http://dx.doi.org/10.1016/j.steroids.2021.108879DOI Listing
September 2021

Golgi a-mannosidase II mediates the formation of vascular smooth muscle foam cells under inflammatory stress.

Authors:
Kelan Zha Qiang Ye

Folia Histochem Cytobiol 2021 21;59(2):134-143. Epub 2021 Jun 21.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping street, Jiangyang District, 646000 Luzhou, China.

Introduction: Vascular smooth muscle cells (VSMCs)-based foam cell formation is a crucial factor in the atherosclerosis process. We aimed to explore the mechanism of Golgi a-mannosidase II (GMII) effects on the VSMCs-based foam cell formation.

Material And Methods: VSMCs were exposed to different concentrations of low-density lipoproteins (LDLs), lipopolysaccharide (LPS), and/or GMII inhibitor (swainsonine). The qRT-PCR and western blot were used for expression analysis. Oil Red O staining was used to verify changes of lipid droplets in VSMCs. The translocation of the SCAP from the endoplasmic reticulum (ER) to Golgi was detected by immunofluorescence (IF).

Results: LPS disrupted the LDLs-mediated regulation of LDL receptor (LDLr) and increased intracellular cholesterol ester, which was inversely inhibited by swainsonine. The activity of a-mannosidase II and GMII expression were decreased by LDLs but increased by the addition of LPS. Conversely, LPS-induced enhancement was reversed by swainsonine. Additionally, swainsonine reversed the LPS-induced increase of intracellular lipid droplets in the presence of LDLs. Expression analysis demonstrated that LDLr, SCAP, and SREBP2 were up-regulated by LPS, but reversed by swainsonine in LDLs-treated cells. IF staining revealed that swainsonine inhibited the translocation of SCAP to Golgi under inflammatory stress.

Conclusions: Collectively, swainsonine restrained LDLr expression to suppress the formation of VSMCs-based foam cells by reducing SREBP2 and SCAP under inflammatory stress conditions, suggesting that GMII contributes to the formation of VSMCs-based foam cells under inflammatory stress.
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http://dx.doi.org/10.5603/FHC.a2021.0015DOI Listing
September 2021

Chemometrics-Assisted Raman Spectroscopy Characterization of Tunable Polymer-Peptide Hybrids for Dental Tissue Repair.

Front Mater 2021 May 10;8. Epub 2021 May 10.

Institute for Bioengineering Research, University of Kansas, Lawrence, KS, United States.

The interfaces that biological tissues form with biomaterials are invariably defective and frequently the location where failure initiates. Characterizing the phenomena that lead to failure is confounded by several factors including heterogeneous material/tissue interfaces. To seamlessly analyze across these diverse structures presents a wealth of analytical challenges. This study aims to develop a molecular-level understanding of a peptide-functionalized adhesive/collagen hybrid biomaterial using Raman spectroscopy combined with chemometrics approach. An engineered hydroxyapatite-binding peptide (HABP) was copolymerized in dentin adhesive and dentin was demineralized to provide collagen matrices that were partially infiltrated with the peptide-functionalized adhesive. Partial infiltration led to pockets of exposed collagen-a condition that simulates defects in adhesive/dentin interfaces. The spectroscopic results indicate that co-polymerizable HABP tethered to the adhesive promoted remineralization of the defects. The spatial distribution of collagen, adhesive, and mineral as well as crystallinity of the mineral across this heterogeneous material/tissue interface was determined using micro-Raman spectroscopy combined with chemometrics approach. The success of this combined approach in the characterization of material/tissue interfaces stems from its ability to extract quality parameters that are related to the essential and relevant portions of the spectral data, after filtering out noise and non-relevant information. This ability is critical when it is not possible to separate components for analysis such as investigations focused on, chemical characterization of interfaces. Extracting essential information from complex bio/material interfaces using data driven approaches will improve our understanding of heterogeneous material/tissue interfaces. This understanding will allow us to identify key parameters within the interfacial micro-environment that should be harnessed to develop durable biomaterials.
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http://dx.doi.org/10.3389/fmats.2021.681415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186416PMC
May 2021

Solvent polarity driven helicity inversion and circularly polarized luminescence in chiral aggregation induced emission fluorophores.

Chem Sci 2020 Aug 17;11(36):9989-9993. Epub 2020 Aug 17.

Advanced Materials and Liquid Crystal Institute, Chemical Physics Interdisciplinary Program, Kent State University Kent OH 44242 USA

Development of functional materials capable of exhibiting chirality tunable circularly polarized luminescence (CPL) is currently in high demand for potential technological applications. Herein we demonstrate the formation of both left- and right-handed fluorescent helical superstructures from each enantiomer of a chiral tetraphenylethylene derivative through judicious choice of the solution processing conditions. Interestingly, both the aggregation induced emission active enantiomers exhibit handedness inversion of their supramolecular helical assemblies just by varying the solution polarity without any change in their molecular chirality. The resulting helical supramolecular aggregates from each enantiomer are capable of emitting circularly polarized light, thus enabling both right- and left-handed CPL from a single chiral material. The left- and right-handed supramolecular helical aggregates in the dried films have been characterized using spectroscopy, scanning electron microscopy, and transmission electron microscopy techniques. These new chiral aggregation induced emission compounds could find applications in devices where CPL of opposite handedness is required from the same material and would facilitate our understanding of the formation of helical assemblies with switchable supramolecular chirality.
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http://dx.doi.org/10.1039/d0sc04179cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162095PMC
August 2020

A Novel Mutation in the KCNH2 Gene Associatedwith Long QT Syndrome: A Case Report.

Authors:
Kelan Zha Qiang Ye

Ann Clin Lab Sci 2021 Mar;51(2):258-261

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, China

Objective: Long QT syndrome is a cardiovascular disease with a prolonged QT interval.

Case Report: We report a 22-year-old woman presenting with frequent syncopal episodes two months after childbirth. Electrocardiography showed a sinus rhythm, QT interval prolongation, and Torsade de Pointes. Her mother had experienced an episode of syncope, but her father had not. Genetic analyses revealed that a new mutation in the KCNH2 gene, the c.2108dupA mutation (p.H703Qfs*20, exon8, M_000238), was found in the patient and in her mother and sister.

Conclusion: The c.2108dupA mutation (p.H703Qfs*20, exon8, M_000238) is the first reported case of a KCNH2 mutation at this site.
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March 2021

Probing the mineralized tissue-adhesive interface for tensile nature and bond strength.

J Mech Behav Biomed Mater 2021 08 29;120:104563. Epub 2021 Apr 29.

Institute for Bioengineering Research (IBER), University of Kansas, 1530 W. 15th St, Lawrence, KS, 66045, USA; Department of Mechanical Engineering, University of Kansas, 1530 W. 15th St, Lawrence, KS, 66045, USA; Civil, Environmental and Architectural Engineering Department, University of Kansas, 1530 W. 15th St, Lawrence, KS, 66045, USA. Electronic address:

The mechanical performance of the dentin-adhesive interface contributes significantly to the failure of dental composite restorations. Rational material design can lead to enhanced mechanical performance, but this requires accurate characterization of the mechanical behavior at the dentin-adhesive interface. The mechanical performance of the interface is typically characterized using bond strength tests, such as the micro-tensile test. These tests are plagued by multiple limitations including large variations in the test results. The challenges associated with conventional tensile tests limit our ability to unravel the complex relationships that affect mechanical behavior at the dentin-adhesive interface. This study used the diametral compression test to overcome the challenges inherent in conventional bond strength tests. The bovine femur cortical bone tissue was considered as a surrogate material (the mineralized tissue) for human dentin. Two different adhesive formulations, which differed by means of their self-strengthening properties, were studied. The tensile behavior of the mineralized tissue, the adhesive polymer, and the bond strength of the mineralized tissue - adhesive interface was determined using the diametral compression test. The diametral compression test improved the repeatability for both the tensile and bond strength tests. The rate dependent mechanical behavior was observed for both single material and interfacial material systems. The tensile strength and bond strength of the mineralized tissue-adhesive interface was greater for the self-strengthening formulation as compared to the control.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206037PMC
August 2021

Antimicrobial Peptide-Polymer Conjugates for Dentistry.

ACS Appl Polym Mater 2020 Mar 2;2(3):1134-1144. Epub 2020 Jan 2.

University of Kansas (KU), Lawrence, Kansas.

Bacterial adhesion and growth at the composite/adhesive/tooth interface remain the primary cause of dental composite restoration failure. Early colonizers, including , play a critical role in the formation of dental caries by creating an environment that reduces the adhesive's integrity. Subsequently, other bacterial species, biofilm formation, and lactic acid from demineralize the adjoining tooth. Because of their broad spectrum of antibacterial activity and low risk for antibiotic resistance, antimicrobial peptides (AMPs) have received significant attention to prevent bacterial biofilms. Harnessing the potential of AMPs is still very limited in dentistry-a few studies have explored peptide-enabled antimicrobial adhesive copolymer systems using mainly nonspecific adsorption. In the current investigation, to avoid limitations from nonspecific adsorption and to prevent potential peptide leakage out of the resin, we conjugated an AMP with a commonly used monomer for dental adhesive formulation. To tailor the flexibility between the peptide and the resin material, we designed two different spacer domains. The spacer-integrated antimicrobial peptides were conjugated to methacrylate (MA), and the resulting MA-AMP monomers were next copolymerized into dental adhesives as AMP-polymer conjugates. The resulting bioactivity of the polymethacrylate-based AMP conjugated matrix activity was investigated. The antimicrobial peptide conjugated to the resin matrix demonstrated significant antimicrobial activity against . Secondary structure analyses of conjugated peptides were applied to understand the activity differential. When mechanical properties of the adhesive system were investigated with respect to AMP and cross-linking concentration, resulting AMP-polymer conjugates maintained higher compressive moduli compared to hydrogel analogues including polyHEMA. Overall, our result provides a robust approach to develop a fine-tuned bioenabled peptide adhesive system with improved mechanical properties and antimicrobial activity. The results of this study represent a critical step toward the development of peptide-conjugated dentin adhesives for treatment of secondary caries and the enhanced durability of dental composite restorations.
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http://dx.doi.org/10.1021/acsapm.9b00921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026165PMC
March 2020

MRI-based radiomics signature for pretreatment prediction of pathological response to neoadjuvant chemotherapy in osteosarcoma: a multicenter study.

Eur Radiol 2021 Oct 30;31(10):7913-7924. Epub 2021 Mar 30.

Department of Radiology, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics. Guangdong Province), 183 Zhongshan Da Dao Xi, Guangzhou, 510630, Guangdong, China.

Objective: To develop and validate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for preoperative prediction of pathologic response to neoadjuvant chemotherapy (NAC) in patients with osteosarcoma.

Methods: We retrospectively enrolled 102 patients with histologically confirmed osteosarcoma who received chemotherapy before treatment from 4 hospitals (68 in the primary cohort and 34 in the external validation cohort). Quantitative imaging features were extracted from contrast-enhanced fat-suppressed T1-weighted images (CE FS T1WI). Four classification methods, i.e., the least absolute shrinkage and selection operator logistic regression (LASSO-LR), support vector machine (SVM), Gaussian process (GP), and Naive Bayes (NB) algorithm, were compared for feature selection and radiomics signature construction. The predictive performance of the radiomics signatures was assessed with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA).

Results: Thirteen radiomics features selected based on the LASSO-LR classifier were adopted to construct the radiomics signature, which was significantly associated with the pathologic response. The prediction model achieved the best performance between good and poor responders with an AUC of 0.882 (95% CI, 0.837-0.918) in the primary cohort. Calibration curves showed good agreement. Similarly, findings were validated in the external validation cohort with good performance (AUC, 0.842 [95% CI, 0.793-0.883]) and good calibration. DCA analysis confirmed the clinical utility of the selected radiomics signature.

Conclusion: The constructed CE FS T1WI-radiomics signature with excellent performance could provide a potential tool to predict pathologic response to NAC in patients with osteosarcoma.

Key Points: • The radiomics signature based on multicenter contrast-enhanced MRI was useful to predict response to NAC. • The prediction model obtained with the LASSO-LR classifier achieved the best performance. • The baseline clinical characteristics were not associated with response to NAC.
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http://dx.doi.org/10.1007/s00330-021-07748-6DOI Listing
October 2021

Pretreatment Prediction of Relapse Risk in Patients with Osteosarcoma Using Radiomics Nomogram Based on CT: A Retrospective Multicenter Study.

Biomed Res Int 2021 4;2021:6674471. Epub 2021 Feb 4.

Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China.

Objective: To develop and externally validate a CT-based radiomics nomogram for pretreatment prediction of relapse in osteosarcoma patients within one year.

Materials And Methods: In this multicenter retrospective study, a total of 80 patients (training cohort: 63 patients from three hospitals; validation cohort: 17 patients from three other hospitals) with osteosarcoma, undergoing pretreatment CT between August 2010 and December 2018, were identified from multicenter databases. Radiomics features were extracted and selected from tumor regions on CT image, and then, the radiomics signature was constructed. The radiomics nomogram that incorporated the radiomics signature and clinical-based risk factors was developed to predict relapse risk with a multivariate Cox regression model using the training cohort and validated using the external validation cohort. The performance of the nomogram was assessed concerning discrimination, calibration, reclassification, and clinical usefulness.

Results: Kaplan-Meier curves based on the radiomics signature showed a significant difference between the high-risk and the low-risk groups in both training and validation cohorts ( < 0.001 and = 0.015, respectively). The radiomics nomogram achieved good discriminant results in the training cohort (-index: 0.779) and the validation cohort (-index: 0.710) as well as good calibration. Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinical-based nomogram ( < 0.001).

Conclusions: This multicenter study demonstrates that a radiomics nomogram incorporated the radiomics signature and clinical-based risk factors can increase the predictive value of the osteosarcoma relapse risk, which supports the clinical application in different institutions.
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http://dx.doi.org/10.1155/2021/6674471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878076PMC
May 2021

Meningococcal vaccines in China.

Hum Vaccin Immunother 2021 07 10;17(7):2197-2204. Epub 2021 Feb 10.

Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes of Food and Drug Control, Beijing, People's Republic of China.

Meningococcal meningitis caused by is a reportable infectious disease in China, due to the high incidence of meningitis in the era before the availability of vaccines. The disease incidence was markedly reduced after meningococcal vaccination was introduced in the 1980s. Currently, there are polysaccharide, conjugate, and combined vaccine formulations against meningococcal meningitis in the Chinese market, almost all of which are produced by domestic manufacturers. It is necessary to further enhance national meningococcal surveillance to improve the level of prevention and control of meningococcus. However, the immune efficacy and persistence of immunity of vaccines should be monitored. More importantly, additional investments should be made to develop serogroup B meningococcal vaccines.
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http://dx.doi.org/10.1080/21645515.2020.1857201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189055PMC
July 2021

Controlling Bicontinuous Structures through a Solvent Segregation-Driven Gel.

Langmuir 2021 Feb 3;37(6):2170-2178. Epub 2021 Feb 3.

Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.

The past decade has seen increased research interest in studying bicontinuous structures formed via colloidal self-assembly due to their many useful applications. A new type of colloidal gel, solvent segregation-driven gel (SeedGel), has been recently demonstrated as an effective approach to arrest bicontinuous structures with unique and intriguing properties, such as thermoreversibility, structural reproducibility, and sensitive temperature response. Here, using a model system with silica particles in the 2,6-lutidine/water binary solvent, we investigate the factors controlling the domain size of a SeedGel system by varying the particle concentration, solvent ratio, and quenching protocol. A phase diagram is identified to produce SeedGels for this model system. Our results indicate that by adjusting the sample composition, it is possible to realize bicontinuous domains with well-controlled repeating distances (periodicities). In addition, the effect of quenching rate on the domain size is systematically investigated, showing that it is a very sensitive parameter to control domain sizes. By further heating SeedGel up into the spinodal region, the structure evolution under high temperatures is also investigated and discussed. These results provide important insights into how to control bicontinuous structures in SeedGel systems.
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http://dx.doi.org/10.1021/acs.langmuir.0c03472DOI Listing
February 2021

Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer.

World J Surg Oncol 2021 Jan 26;19(1):29. Epub 2021 Jan 26.

Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Background: Aberrant DNA methylation is significantly associated with breast cancer.

Methods: In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis.

Results: In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994-1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976-1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival.

Conclusions: Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.
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http://dx.doi.org/10.1186/s12957-021-02124-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839189PMC
January 2021

Characterizations of Ischemic Stroke Complications in Cardiac Myxoma Patients at a Single Institution in Eastern China.

Neuropsychiatr Dis Treat 2021 7;17:33-40. Epub 2021 Jan 7.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People's Republic of China.

Background: Cardiac myxoma is the most common primary cardiac tumor. Even though it rarely causes a stroke, it is an important risk factor. Here, we compared our clinical experience in managing myxoma patients who developed stroke complications with those who did not present with this condition at the First Affiliated Hospital of Wenzhou Medical University.

Patients And Methods: The medical records were reviewed of 160 cardiac myxoma patients who were treated in our facility from January 2006 to December 2019. They were separated into either a stroke group or non-stroke group.

Results: Cardiac obstructive symptoms, embolic events and constitutional symptoms were observed in 92 (57.7%), 25 (15.6%) and 18 (11.2%) patients, respectively. Among 23 cardiac myxoma ischemic stroke patients, hypoesthesia (60.9%), hemiparesis (56.5%) and facial paresis (47.8%) were the three most common neurological symptoms. The middle cerebral artery (82.6%) was the most commonly affected vessel, whereas 73.9% of the ischemic patients had multiple stroke lesions. Binary logistic regression analysis showed that coronary heart disease and tumor sizes were independently associated in the stroke group (p <0.05). The 10 years cumulative survival rate was 87.9% for all patients after surgical intervention. There was no significant difference in the 10 years cumulative survival rate between the two groups (80.0% vs 88.9%, p =0.274 > 0.05).

Conclusion: The three most common neurological symptoms (hypoesthesia, hemiparesis and facial paresis), the middle cerebral artery and multiple lesions involvements were the definitive markers of patients afflicted with cardiac myxoma stroke. Small tumor sizes were independently associated with these patients. Surgical resection is a relatively safe procedure for treating both the stroke and non-stroke patients.
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http://dx.doi.org/10.2147/NDT.S280641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800702PMC
January 2021

Clinical Significance of Increasing Pressure Curve's Slope When Injecting Ultrasound Contrast Agent During Evaluation of Fallopian Tubal Patency.

J Ultrasound Med 2021 Nov 9;40(11):2329-2338. Epub 2021 Jan 9.

Department of Ultrasound, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing 210029, Jiangsu Province, China.

Objective: To explore the association between Fallopian tubal patency and the slope of the increasing pressure curve for ultrasound contrast agent.

Materials And Methods: A total of 136 patients underwent transvaginal 4-dimensional hysterosalpingo-contrast sonography (TVS 4D HyCoSy) between August 2015 and January 2016. We divided the patients into 3 groups according to different Fallopian tubal patency status: 71 patients (48.97%) in bilateral tubal patency group, 45 (31.03%) in unilateral tubal patency group, and 20 in bilateral tubal nonpatent group. The ultrasound contrast agent was injected and the pressure curve was recorded automatically in real time using a liquid-injecting machine that traces it as a pressure curve. The slopes of the different groups are compared through independent sample t test.

Results: The slopes of the 3 groups were 1.242 ± 0.572, 1.472 ± 0.638, and 2.068 ± 1.236 kPa/s. A correlation was observed between the slope of the increasing pressure curve and tubal patency (R = 0.287, P < .05). The slopes differed significantly between the bilateral tubal patency group and bilateral tubal nonpatent group (P = .001) and between the unilateral tubal patency group and bilateral tubal nonpatent group (P = .012). However, the difference between the bilateral tubal patency and unilateral tubal patency groups was not significant (P = .266).

Conclusion: The increase of the injecting pressure curve's slope for contrast agent during 4D HyCoSy is associated with the nonpatent degree of the tube. This condition can be used as an objective index of tubal patency and can be a reference in diagnosis and treatment.
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http://dx.doi.org/10.1002/jum.15616DOI Listing
November 2021

Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism.

Biomed Pharmacother 2021 Feb 17;134:111121. Epub 2020 Dec 17.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1β, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.
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http://dx.doi.org/10.1016/j.biopha.2020.111121DOI Listing
February 2021

Long Noncoding RNAs in the Progression of Atherosclerosis: An Integrated Analysis Based on Competing Endogenous RNA Theory.

DNA Cell Biol 2021 Feb 17;40(2):283-292. Epub 2020 Dec 17.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.

Long noncoding RNAs (lncRNAs) have been increasingly accepted to function importantly in human diseases by serving as competing endogenous RNAs (ceRNAs). To date, the ceRNA mechanisms of lncRNAs in the progression of atherosclerosis (AS) remain largely unclear. On the basis of ceRNA theory, we implemented a multistep computational analysis to construct an lncRNA-mRNA network for AS progression (ASpLMN). The probe reannotation method and microRNA-target interactions from databases were systematically integrated. Three lncRNAs (, , and ) with central topological features in the ASpLMN were firstly identified. By using subnetwork analysis, we then obtained two highly clustered modules and one dysregulated module from the ASpLMN network. These modules, sharing three lncRNAs (, , and ), were significantly enriched in biological pathways such as regulation of actin cytoskeleton, tryptophan metabolism, lysosome, and arginine and proline metabolism. In addition, random walking in the ASpLMN network indicated that lncRNA and may also play an essential role in the pathology of AS progression. The identified six lncRNAs from the aforementioned steps could distinguish advanced- from early-staged AS, with a strong diagnostic power for AS occurrence. In conclusion, the results of this study will improve our understanding about the ceRNA-mediated regulatory mechanisms in AS progression, and provide novel lncRNAs as biomarkers or therapeutic targets for acute cardiovascular events.
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http://dx.doi.org/10.1089/dna.2020.6106DOI Listing
February 2021

Dual Stimuli-Responsive High-Efficiency Circularly Polarized Luminescence from Light-Emitting Chiral Nematic Liquid Crystals.

ACS Appl Mater Interfaces 2020 Dec 4;12(50):56604-56614. Epub 2020 Dec 4.

Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, Key Laboratory of Advanced Functional Polymer Materials of Colleges and Universities of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, Hunan, China.

Considerable luminescence dissymmetry factor () is vital for application implementation of circularly polarized luminescence (CPL) materials. Moreover, a dual CPL switch has promising prospects in high-security encryption and sensor devices. Herein, we designed and synthesized an emissive chiral nematic liquid crystal (N*-LC) by doping a luminescent chiral additive (NO-CS-C-Chol) into a nematic liquid crystal (5CB). The helical assembly structure produced by inducing the formation of N*-LC endows the prepared emissive N*-LC with a larger value. With the increase of the doping concentration from 1 to 10 wt %, the helical pitch () of N*-LC gradually decreases from 25.48 to 3.92 μm. The corresponding value increases first, reaches the maximum value (-0.38) at 6 wt %, and then decreases slightly. Further, the prepared emissive N*-LC doped with 6 wt % NO-CS-C-Chol is injected into an indium-tin oxide (ITO)-coated LC cell, to which a direct current (DC) electric field is applied. The value can be repeatedly shuttled between the "on" and "off" state by adjusting the applied voltage. Meanwhile, owing to the inherent thermal dependence of the liquid crystal phase structure, the value can also be switched between the on and off state by regulating the temperature. Therefore, an electrically controlled and thermocontrolled dual CPL switching device is successfully constructed.
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http://dx.doi.org/10.1021/acsami.0c17241DOI Listing
December 2020

Overexpression of thioredoxin reductase 1 can reduce DNA damage, mitochondrial autophagy and endoplasmic reticulum stress in Parkinson's disease.

Exp Brain Res 2021 Feb 23;239(2):475-490. Epub 2020 Nov 23.

Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Several factors, including neuroinflammation, neuronal excitotoxicity, genetic mutations and incorrect protein folding are involved in PD pathophysiology. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. A growing body of research suggests that oxidative stress is a major factor in PD. Therefore, antioxidant therapy is an important approach for treating PD. The thioredoxin system is an important antioxidant system, and thioredoxin reductase 1 (TR1) is a major member of the thioredoxin system. The present study demonstrates that oxidative stress is increased and that the expression of TR1 is decreased in the SNc of A53T mice; TR1 has emerged as an important antioxidant agent in dopaminergic neurons. Therefore, we over-expressed TR1 in the MPP-induced cellular model and in the A53T transgenic mouse model of PD. We confirmed that the overexpression of TR1 in neuronal cells decreased DNA damage and malondialdehyde (MDA) and ROS generation, increased T-SOD and GSH production, and decreased the ER stress, and autophagy in the PD model. In summary, our findings demonstrate that the overexpression of TR1 could be effective as a novel neuroprotective strategy for PD. This research suggests a novel direction in the treatment of PD.
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http://dx.doi.org/10.1007/s00221-020-05979-5DOI Listing
February 2021

Overexpression of thioredoxin reductase 1 can reduce DNA damage, mitochondrial autophagy and endoplasmic reticulum stress in Parkinson's disease.

Exp Brain Res 2021 Feb 23;239(2):475-490. Epub 2020 Nov 23.

Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Several factors, including neuroinflammation, neuronal excitotoxicity, genetic mutations and incorrect protein folding are involved in PD pathophysiology. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. A growing body of research suggests that oxidative stress is a major factor in PD. Therefore, antioxidant therapy is an important approach for treating PD. The thioredoxin system is an important antioxidant system, and thioredoxin reductase 1 (TR1) is a major member of the thioredoxin system. The present study demonstrates that oxidative stress is increased and that the expression of TR1 is decreased in the SNc of A53T mice; TR1 has emerged as an important antioxidant agent in dopaminergic neurons. Therefore, we over-expressed TR1 in the MPP-induced cellular model and in the A53T transgenic mouse model of PD. We confirmed that the overexpression of TR1 in neuronal cells decreased DNA damage and malondialdehyde (MDA) and ROS generation, increased T-SOD and GSH production, and decreased the ER stress, and autophagy in the PD model. In summary, our findings demonstrate that the overexpression of TR1 could be effective as a novel neuroprotective strategy for PD. This research suggests a novel direction in the treatment of PD.
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http://dx.doi.org/10.1007/s00221-020-05979-5DOI Listing
February 2021

Protective effect of thioredoxin reductase 1 in Parkinson's disease.

Neurosci Lett 2021 01 7;741:135457. Epub 2020 Nov 7.

Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Many factors can explain the mechanism. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. Our study shows that oxidative stress is increased in models of PD compared with WT mice; Thioredoxin reductase 1(TR1) has emerged as an important antioxidant agent in dopaminergic neurons. In summary, our findings demonstrate that the overexpression of TR1 could be developed into a novel neuroprotective strategy for PD and that the reduction of the expression of GSK-3β and NF-κB could also be promising therapeutic strategies for PD. This research suggests a new direction in the treatment of PD.
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http://dx.doi.org/10.1016/j.neulet.2020.135457DOI Listing
January 2021

Atorvastatin Enhances Foam Cell Lipophagy and Promotes Cholesterol Efflux Through the AMP-Activated Protein Kinase/Mammalian Target of Rapamycin Pathway.

J Cardiovasc Pharmacol 2021 04;77(4):508-518

Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

Abstract: Foam cells are the main pathological components of atherosclerosis. Therapies reducing foam cell formation can effectively prevent atherosclerotic diseases and cardiovascular events. Beyond lowering plasma cholesterol levels, the pleiotropic functions of statins in atherosclerosis have not been fully elucidated. In the present study, atorvastatin reduced cholesterol content and increased cholesterol efflux from foam cells in a concentration-dependent manner. Atorvastatin (10 μM) inhibited foam cell formation within 48 hours. Furthermore, we found that atorvastatin inhibited foam cell formation by promoting lipophagy, which was manifested by increased autophagy-related gene 5 (Atg5) expression, elevated ratio of microtubule-associated protein1 light chain 3 (LC3) II to LC3I, reduced p62 expression, and increased LC3 and lipid droplets colocalization in foam cells treated with atorvastatin. The autophagy inducer, rapamycin (Rap), did not increase the lipophagy enhancement effect of atorvastatin, but the autophagy inhibitor, 3-methyladenine, suppressed the effect of atorvastatin on Atg5 expression and the LC3II/LC3I ratio, as well as the increased p62 expression, suppressed lipophagy, attenuated cholesterol efflux and increased cholesterol content in foam cells. Further analysis revealed that atorvastatin promoted lipophagy by upregulating adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation, and downregulating mammalian target of rapamycin phosphorylation, whereas the AMPK inhibiter, compound C, attenuated these effects. In conclusion, atorvastatin reduced lipid accumulation and promoted cholesterol efflux by enhancing lipophagy in foam cells and thereby inhibited foam cell formation. The enhanced lipophagy of foam cells was exerted through the AMPK/mammalian target of rapamycin signaling pathway.
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http://dx.doi.org/10.1097/FJC.0000000000000942DOI Listing
April 2021

A real-time fuzzy logic biofeedback controller for freestyle swimming body posture adjustment.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:4620-4623

Wearable body area networks (BANs) have been widely used in activity measurements for kinematic information collection. This paper presents the design and implementation of a wearable device used as a training tool in freestyle swimming. The device supplies a close-loop control mechanism via a fuzzy logic controller. Swimming posture data is collected quantitatively and audibly fed back to swimmers in real time through bone conductors. Two recreational swimmers were invited to participate in a series of experiments including 7 days of baseline capability test (no feedback), 7 days of feedback training, and 2 days of retention test. It was found that both swimmers could well adapt to the feedback instructions. A maximum of 7.62% of lap time improvement and 29.64% of trunk roll improvement were observed in FB training, and such pattern was maintained after feedback was removed. We conclude that real-time fuzzy logic feedback can be used to improve recreational swimmers performance.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176237DOI Listing
July 2020
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