Publications by authors named "Fang Wang"

4,666 Publications

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Hydralazine as a Versatile and Universal Matrix for High-Molecular Coverage and Dual-Polarity Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Anal Chem 2021 Jun 21. Epub 2021 Jun 21.

State Key Laboratory of Natural Medicines and School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Few matrices have the potential to be universally applicable for imaging vast endogenous compounds ranging from micro to macromolecules. In this article, we present hydralazine (HZN) as a versatile and universal matrix for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) of a wide range of endogenous compounds between 50.0 and 20,000.0 Da. HZN was prepared from its hydrochloride by alkalizing HZN·HCl with ammonia to enhance the optical absorptivity at the preferred MALDI UV laser wavelength. To further improve its performance for MALDI MS, HZN was doped with NHOH or TFA, resulting in matrix superior performance for imaging biologically relevant compounds in the negative and positive-ion modes, respectively. The analyte-matrix interaction was also enhanced by the optimized matrix solvent and the deposition amount. Compared with conventional matrices such as 2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, and 9-aminoacridine (9-AA), the HZN matrix provided higher sensitivity, broader molecular coverage, and improved signal intensities. Its broad acquisition range makes it versatile for imaging small molecular metabolites and lipids, as well as proteins. In addition, HZN was applied successfully for the visualization of tissue-specific distributions and changes of small molecules, lipids, and proteins in the kidney and liver sections of obese and diabetic mice. The use of the HZN matrix shows great potential application in the field of pathological research.
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http://dx.doi.org/10.1021/acs.analchem.1c00498DOI Listing
June 2021

Zijuan tea- based kombucha: Physicochemical, sensorial, and antioxidant profile.

Food Chem 2021 Jun 9;363:130322. Epub 2021 Jun 9.

Tea Research Institute Chinese Academy of Agricultural Sciences, National Engineering Research Center for Tea Processing, Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, 9 South Meiling Road, Hangzhou 310008, China. Electronic address:

Zijuan tea is a representative anthocyanin-rich tea cultivar in China. In this study, Zijuan tea was used to produce a novel kombucha beverage (ZTK). The physicochemical, sensory properties, and antioxidant activity of ZTK were compared with that of black tea kombucha (BTK) and green tea kombucha (GTK). Results indicated that after fermentation, the color of ZTK changed from yellowish-brown to salmon-pink, because its anthocyanins (4.5 mg/L) appeared red in acidic conditions. Meanwhile no significant changes of color were observed in BTK and GTK. The dynamic changes of pH, biomass, and concentrations of sugars, amino acids, and main organic acids were similar in three kombucha beverages, except catechins showing different trends. Moreover, ZTK showed the highest overall acceptability score, antioxidant activity, and concentration of volatiles among the three kombucha beverages. Therefore, Zijuan tea is suitable for the preparation of kombucha beverage with attractive color and health benefits.
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http://dx.doi.org/10.1016/j.foodchem.2021.130322DOI Listing
June 2021

Facile and effective repair of Pt/Nafion IPMC actuator by dip-coating of [email protected]

Nanotechnology 2021 Jun 18. Epub 2021 Jun 18.

Zhengzhou University of Light Industry, State Laboratory of Surface & Interface, State Laboratory of Surface & Interface, Zhengzhou University of Light Industry, zhengzhou, 450001, CHINA.

Ionic polymer metal composite (IPMC) always takes big risks of electrode cracking and peeling, which lead to energy wasting, waterloss, and uneven electric field distribution, thus hamper its commercial applications. To address this issue, we propose a facile and effective technique to repair the electrode fatigue by coating polyvinylpyrrolidone (PVP) encapsulated Ag nanoparticles ([email protected]) on the long-term used IPMC surface. To improve the electrochemical stability, the silver nanoparticles (Ag NPs) with a diameter of ~34 nm are encapsulated by a 1.3 nm thick PVP film, thus forming a shell-core structure to resist corrosion from the electrolyte solution. Physiochemical investigations reveal that, [email protected] closely attach to the interior and exterior surfaces of the original Pt nanograin electrode, thus refreshing its electronic conductivity; the repaired IPMC actuator exhibits better electromechanical properties compared to its precursor actuator: 7.62 folds in displacement output, 9.38 folds in force output, and 9.73 folds in stable working time.
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http://dx.doi.org/10.1088/1361-6528/ac0caeDOI Listing
June 2021

SrPb(BeBO)(BO): An Excellent Ultraviolet Nonlinear-Optical Beryllium Borate by the Pb-Modified Construction of a Conjugated System and Lone-Pair Effect.

Inorg Chem 2021 Jun 18. Epub 2021 Jun 18.

Key Laboratory of Magnetic Molecules and Magnetic Information Material of Ministry of Education, School of Chemistry and Material Science, Shanxi Normal University, Linfen 041004, China.

The design of material by chemical and/or crystalline modification of a classic structure model benefits not only the optimized physical properties but also the controllability and efficiency. Herein, a new nonlinear-optical (NLO) beryllium borate crystal, SrPb(BeBO)(BO) (SPBBO), is successfully designed and synthesized by chemical and crystalline modification of the perovskite-like KBOCl NLO crystal. SPBBO displays a 3D BeBO open-framework structure composed of interconnecting BeBO groups with filled cationic Sr/Pb and anionic BO groups, which exhibits the striking enhancement of the second-harmonic-generation (SHG) response (8 × KDP) and birefringence (0.10) compared to the parent model. Replacement of K by Sr and Pb with a lone pair and replacement of Cl by conjugated BO result in the synergistic conjugation of Pb with host BeBO and filled BO groups, contributing to the striking enhancement of the SHG and birefringence. Single-crystal measurements show that SPBBO has a short UV absorption edge of 280 nm with a wide energy band gap of 4.35 eV and an outstanding laser-induced resistant behavior with a remarkably high laser-induced damage threshold of 2100 MW cm. The excellent properties indicate that the SPBBO crystal is a very promising UV NLO functional material.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01181DOI Listing
June 2021

Morphologic, Immunohistochemical, and Genetic Differences Between High-grade and Low-grade Fetal Adenocarcinomas of the Lung.

Am J Surg Pathol 2021 Jun 17. Epub 2021 Jun 17.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Departments of Molecular Diagnostics Pathology, Sun Yat-Sen University Cancer Center Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Fetal adenocarcinoma of the lung (FLAC) is a rare lung tumor classified into low-grade fetal adenocarcinoma of the lung (LG-FLAC) and high-grade fetal adenocarcinoma of the lung (HG-FLAC). It remains debatable whether HG-FLAC is a subset of FLAC or a distinct subtype of the conventional lung adenocarcinoma (CLA). In this study, samples of 4 LG-FLAC and 2 HG-FLAC cases were examined, and the clinicopathologic, immunohistochemical (IHC), and mutational differences between the 2 subtypes were analyzed using literature review. Morphologically, LG-FLACs had a pure pattern with complex glandular architecture composed of cells with subnuclear and supranuclear vacuoles, mimicking a developing fetal lung. In contrast, HG-FLACs contained both fetal lung-like (FLL) and CLA components. With regard to IHC markers, β-catenin exhibited a nuclear/cytoplasmic staining pattern in LG-FLACs but a membranous staining pattern in HG-FLACs. Furthermore, p53 was expressed diffusely and strongly in HG-FLACs, whereas in LG-FLACs, p53 staining was completely absent. Using next-generation sequencing targeting a 1021-gene panel, mutations of CTNNB1 and DICER1 were detected in all 4 LG-FLAC samples, and a novel mutation, MYCN P44L, was discovered in 2 LG-FLAC samples. DNA samples of the FLL and CLA components of HG-FLACs were separately extracted and sequenced. The FLL component harbored no CTNNB1, DICER1, or MYCN mutations; moreover, the FLL genetic profile largely overlapped with that of the CLA component. The morphologic, IHC, and genetic features of HG-FLAC indicate that it is a variant of CLA rather than a subset of FLAC. Thus, HG-FLAC should be treated differently from LG-FLAC.
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http://dx.doi.org/10.1097/PAS.0000000000001744DOI Listing
June 2021

Targeting the αv integrin-TGF-β axis improves natural killer cell function against glioblastoma stem cells.

J Clin Invest 2021 Jun 17. Epub 2021 Jun 17.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, United States of America.

Glioblastoma, the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single cell RNA sequencing of primary tumor samples revealed that glioblastoma-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from glioblastoma patients or healthy donors. We attributed this immune evasion tactic to direct cell-cell contact between GSCs and NK cells via integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling, or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings revealed an important mechanism of NK cell immune evasion by GSCs and implicated the integrin-TGF-β axis as a potentially useful therapeutic target in glioblastoma.
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http://dx.doi.org/10.1172/JCI142116DOI Listing
June 2021

ROS-Responsive Boronate-Stabilized Polyphenol-Poloxamer 188 Assembled Dexamethasone Nanodrug for Macrophage Repolarization in Osteoarthritis Treatment.

Adv Healthc Mater 2021 Jun 16:e2100883. Epub 2021 Jun 16.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.

Osteoarthritis (OA) is a disabling joint disease associated with chronic inflammation. The polarization of macrophages plays the key role in inflammatory microenvironment of joint which is a therapeutic target for OA treatment. Herein, a boronate-stabilized polyphenol-poloxamer assembled dexamethasone nanodrug with reactive oxygen species (ROS)-responsive drug release behavior and ROS scavenging ability is prepared. Thanks to that, the nanodrug can efficiently inhibit the ROS and nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages and modulate macrophages M2 polarization at a much lower concentration than free drug dexamethasone. Furthermore, the monosodium iodoacetate-induced OA mice treated with this nanodrug is very similar with the normal mice with the evaluation of body weight and scores including clinical arthritis scores, claw circumference, and kinematics score. The inflammation associated angiogenesis is also reduced which revealed by Ga-labeled arginine-glycine-aspartic acid peptide micro-positron emission tomography imaging. Cartilage degradation and bone erosion in the joints are also inhibited by the nanodrug, along with the inhibition of proinflammatory cytokines. In addition, the biosafety of this nanodrug is also verified. This nanodrug with excellent immunomodulation properties can be used not only for OA therapy but also for other inflammatory diseases associated with excess oxidative stress and macrophage polarization.
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http://dx.doi.org/10.1002/adhm.202100883DOI Listing
June 2021

Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay.

Front Pharmacol 2021 31;12:659716. Epub 2021 May 31.

Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Inflammatory bowel disease, irritable bowel syndrome and severe central nervous system injury can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases. Hence, repairing the intestinal barrier represents a potential therapeutic target for many diseases. Enteral afferent nerves, efferent nerves and the intrinsic enteric nervous system (ENS) play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors. In addition, intestinal microorganisms and their metabolites play a regulatory role in the intestinal mucosal barrier. This paper primarily discusses the interactions between norepinephrine and β-adrenergic receptors, cholinergic anti-inflammatory pathways, nociceptive receptors, complex ENS networks, gut microbes and various immune cells with their secreted cytokines to summarize the key roles in regulating intestinal inflammation and improving mucosal barrier function.
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http://dx.doi.org/10.3389/fphar.2021.659716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201607PMC
May 2021

The first principle calculation of improving p-type characteristics of BAlN.

Sci Rep 2021 Jun 16;11(1):12720. Epub 2021 Jun 16.

National Center for International Joint Research of Electronic Materials and Systems, Zhengzhou University, Zhengzhou, Henan, China.

AlN is one of the third-generation semiconductor materials with wide application prospects due to its 6.2 eV band gap. In the application of semiconductor deep ultraviolet lasers, progress is slow due to the difficulty in obtaining p-type AlN with good performance. In this paper, the commonly used way of Mg directly as AlN dopant is abandoned, the inhibition effect of the B component on self-compensation of AlN crystal was studied. The improvement of self-compensation performance of AlN crystal by B component is studied by first principles calculation. The results show that the addition of B component can increase the hole concentration of AlN, which is conducive to the formation of p-type AlN.
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http://dx.doi.org/10.1038/s41598-021-92260-6DOI Listing
June 2021

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center.

Blood Cancer J 2021 Jun 16;11(6):112. Epub 2021 Jun 16.

Division of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, 065201, Langfang, China.

Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.
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http://dx.doi.org/10.1038/s41408-021-00504-5DOI Listing
June 2021

CD36 as a target for metabolic modulation therapy in cardiac disease.

Expert Opin Ther Targets 2021 Jun 21:1-8. Epub 2021 Jun 21.

Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands.

: Disturbances in myocardial lipid metabolism are increasingly being recognized as drivers of the development and progression of heart disease. Therefore, there is a need for treatments that can directly target lipid metabolic defects in heart failure. The membrane-associated glycoprotein CD36 plays a pivotal role in governing myocardial lipid metabolism by mediating lipid signaling and facilitating the cellular uptake of long-chain fatty acids. Emerging evidence suggests that CD36 is a prominent target in the treatment of heart failure.: This article provides an overview of the key role of CD36 for proper contractile functioning of a healthy heart, its implications in the development of cardiac disease (ischemia/reperfusion, cardiac hypertrophy, and diabetic cardiomyopathy), and its application as a target to normalize cardiac metabolism as part of so-called metabolic modulation therapy.: CD36 appears a promising and effective therapeutic target in the treatment of heart failure. Natural compounds and chemical agents known to alter the amount or subcellular distribution of CD36 or inhibit its functioning, should be evaluated for their potency to correct cardiac metabolism and cure heart disease.
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http://dx.doi.org/10.1080/14728222.2021.1941865DOI Listing
June 2021

Gasdermin D in peripheral nerves: the pyroptotic microenvironment inhibits nerve regeneration.

Cell Death Discov 2021 Jun 14;7(1):144. Epub 2021 Jun 14.

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Wallerian degeneration (WD) involves the recruitment of macrophages for debris clearance and nerve regeneration, and the cause of the foamy macrophages that are frequently observed in peripheral transection injuries is unknown. Recent studies indicated that these foamy cells are generated by gasdermin D (GSDMD) via membrane perforation. However, whether these foamy cells are pyroptotic macrophages and whether their cell death elicits immunogenicity in peripheral nerve regeneration (PNR) remain unknown. Therefore, we used GSDMD-deficient mice and mice with deficiencies in other canonical inflammasomes to establish a C57BL/6 J mouse model of sciatic nerve transection and microanastomosis (SNTM) and evaluate the role of GSDMD-executed pyroptosis in PNR. In our study, the GSDMD mice with SNTM showed a significantly diminished number of foamy cells, better axon regeneration, and a favorable functional recovery, whereas irregular axons or gaps in the fibers were found in the wild-type (WT) mice with SNTM. Furthermore, GSDMD activation in the SNTM model was dependent on the NLRP3 inflammasome and caspase-1 activation, and GSDMD-executed pyroptosis resulted in a proinflammatory environment that polarized monocytes/macrophages toward the M1 (detrimental) but not the M2 (beneficial) phenotype. In contrast, depletion of GSDMD reversed the proinflammatory microenvironment and facilitated M2 polarization. Our results suggested that inhibition of GSDMD may be a potential treatment option to promote PNR.
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http://dx.doi.org/10.1038/s41420-021-00529-6DOI Listing
June 2021

Meta-Analysis of the Effect of Kangfuxin Liquid on Diabetic Patients with Skin Ulcers.

Evid Based Complement Alternat Med 2021 3;2021:1334255. Epub 2021 Jun 3.

Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.

In this study, we used meta-analysis to comprehensively evaluate the clinical efficacy of Kangfuxin Liquid in the treatment of diabetic patients with skin ulcers. Literature search was performed through PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang Data. The retrieval was not limited by language, and the search period was from 2010 to October 12, 2020. Diabetic patients with skin ulcers were treated with Kangfuxin Liquid combined with basic treatment as the treatment group and only basic treatment as the control group. Stata16.0 software was used for system evaluation. A total of 11 studies and 874 patients were included. Meta-analysis showed that 11 studies compared the treatment efficacy between the two groups, and the results showed that the treatment efficacy in the treatment group was significantly higher than that in the control group [OR = 5.38, 95% CI (3.52, 8.24), < 0.001]. Among them, 9 studies compared the healing time of wounds. The healing time of the treatment group was significantly longer than that of the control group [SMD = -2.13, 95% CI (-2.85, -1.41), < 0.001]. Five studies compared the length of stay, and the length of stay in the treatment group was shorter than that in the control group [SMD = -3.68, 95% CI (-5.38, -1.97), < 0.001]. Compared with basic treatment, Kangfuxin Liquid combined with basic treatment has an ideal effect in the treatment of diabetic skin ulcers, which can improve the overall treatment efficiency and shorten the wound rehabilitation time and the length of stay.
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http://dx.doi.org/10.1155/2021/1334255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192188PMC
June 2021

Dexmedetomidine protects against degeneration of dopaminergic neurons and improves motor activity in Parkinson's disease mice model.

Saudi J Biol Sci 2021 Jun 20;28(6):3198-3203. Epub 2021 Apr 20.

Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054 Shaanxi, China.

Parkinson's disease (PD) is the result of dopaminergic (DA) neuronal death in the substantianigra pars compacta (SNc). Current treatments for PD such as L-dopa are limited in effectiveness and fail to address the cause. Targeted anti-inflammatory therapies, particularly directed at nuclear factor kappa B (NF-κB) activity in alleviating degeneration of DA-neurons is of evolving interest. In the present study, we hypothesised that dexmedetomidine (DEX), an alpha-2 receptor adrenergic agonist, suppress the inflammatory responses associated with PD and restores dopaminergic levels by alleviating substantia nigral degeneration. Male mice (C57Bl/10, 8-11 months old and of 34-40 g of weight) were divided into: the control, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and MPTP + dexmedetomidine (MPTP + DEX) (n = 26 each group). Dex restored dopamine levels in SNpc of MPTP-induced PD mice model. Results of immunohisto staining revealed that Dex treatment post-MPTP induction restored TH-positive cells, with only 12.37% increase (p < 0.01 vs MPTP) on the third day and a steep 55% increase (p < 0.001 vs MPTP) following the seventh day of Dex treatment. Moreover, the expressions of proinflammatory markers regulated by NF-κB were diminished in Dex + MPTP group. In addition, cylinder test revealed that Dex treatment improved asymmetric limb usage pattern in MPTP induced mice over the course of 7 days. Hence, in this study, we provided insight on the effect of Dex in the inhibition of NF-κB1 regulated proinflammatory mediators to improve dopamine levels and reduce SNpc dopaminergic neuronal degeneration.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176059PMC
June 2021

Ensemble machine learning approach for screening of coronary heart disease based on echocardiography and risk factors.

BMC Med Inform Decis Mak 2021 Jun 11;21(1):187. Epub 2021 Jun 11.

Department of Cardiology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing, China.

Background: Extensive clinical evidence suggests that a preventive screening of coronary heart disease (CHD) at an earlier stage can greatly reduce the mortality rate. We use 64 two-dimensional speckle tracking echocardiography (2D-STE) features and seven clinical features to predict whether one has CHD.

Methods: We develop a machine learning approach that integrates a number of popular classification methods together by model stacking, and generalize the traditional stacking method to a two-step stacking method to improve the diagnostic performance.

Results: By borrowing strengths from multiple classification models through the proposed method, we improve the CHD classification accuracy from around 70-87.7% on the testing set. The sensitivity of the proposed method is 0.903 and the specificity is 0.843, with an AUC of 0.904, which is significantly higher than those of the individual classification models.

Conclusion: Our work lays a foundation for the deployment of speckle tracking echocardiography-based screening tools for coronary heart disease.
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http://dx.doi.org/10.1186/s12911-021-01535-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196502PMC
June 2021

Viperin_sv1 promotes RIG-I expression and suppresses SVCV replication through its radical SAM domain.

Dev Comp Immunol 2021 Jun 8;123:104166. Epub 2021 Jun 8.

College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention, Wuhan, 430070, Hubei, China. Electronic address:

SVCV infection is known to activate the host's innate immune responses, including the production of interferon (IFN) and interferon-stimulated genes (ISGs). Viperin_sv1 is a novel splice variant of viperin, which is induced during SVCV infection and proves to positively regulate the IFN activation and production. However, the underlying mechanism remains unsolved. In this study, the P protein of SVCV was identified to be the key to induce the mRNA modification and production of viperin_sv1 during the virus infection. Besides, Viperin_sv1 was able to trigger the RLR signaling cascades to activate type-1 interferon response. Additional analysis revealed that viperin_sv1 promoted the stability and function of RIG-I, which result in the production of IFN and ISGs. Moreover, the central SAM domain of viperin_sv1 was demonstrated to be essential for regulating RIG-I protein expression and inducing IFN production. Furthermore, this study also showed that SVCV replication could be inhibited by the viperin_sv1 SAM domain. In conclusion, our study demonstrates that viperin_sv1 reduces the replication of SVCV by promoting the RIG-I protein expression. Our findings identified the antiviral function played by the SAM domain of viperin_sv1 and suggested an antiviral mechanism that is conserved among different species.
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http://dx.doi.org/10.1016/j.dci.2021.104166DOI Listing
June 2021

Triple-Layered Metal-Organic Framework Hybrid for Tandem Response-Driven Enhanced Chemotherapy.

Chem Asian J 2021 Jun 11. Epub 2021 Jun 11.

Nanjing University, School of Chemistry and Chemical Engineering, Xianlilin Ave 163, 210023, Nanjing, CHINA.

The precise release of drug is essential to improve cancer therapeutic efficacy. In this work, a tandem responsive strategy was developed based on a triple-layered metal-organic framework (MOF) hybrid. The MOF nanoprobe was stepwise fabricated with a telomerase-responsive inner, a pH-sensitive MOF filling and H2O2-responsive coordination complex shell of Fe3+ and eigallocatechin gallate (EGCG). Under tumor microenvironment, the shell was dissociated by endogenous H2O2 and simultaneously produced highly reactive hydroxyl radicals by Fenton reaction. Meanwhile, the released EGCG could down-regulate the expression of P-glycoprotein responsible for drug resistance. After the dissociation of the framework by protons, telomerase could trigger the release of the drug from the DNA duplex on the exposed inner. By integrating confined drug release, inhibited efflux pump and chemodynamic therapy, the all-in-one chemotherapy strategy was identified with enhanced therapeutic efficacy in drug resistant cancer cells.
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http://dx.doi.org/10.1002/asia.202100505DOI Listing
June 2021

The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis.

Oncogene 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.
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http://dx.doi.org/10.1038/s41388-021-01854-xDOI Listing
June 2021

Clinical and Prognostic Significance of CD117 in Non-Small Cell Lung Cancer: A Systemic Meta-Analysis.

Pathobiology 2021 Jun 9:1-10. Epub 2021 Jun 9.

Department of Oncology, People's Hospital of Xinjiang Uygur, Urumqi, China.

The aim of this study was to assess the relationship of cluster of differentiation 117 (CD117) expression with the clinicopathological characteristics and the prognosis in patients with non-small cell lung cancer (NSCLC). No meta-analysis concerning the correlation of CD117 expression with clinical and prognostic values of the patients with NSCLC is reported. A systematic literature search was conducted to achieve eligible studies. The combined odds ratios (ORs) or hazard ratios (HRs: multivariate Cox analysis) with their 95% confidence intervals (CIs) were calculated in this analysis. Final 17 eligible studies with 4,893 NSCLC patients using immunohistochemical detection were included in this meta-analysis. CD117 expression was not correlated with gender (male vs. female), clinical stage (stages 3-4 vs. stages 1-2), tumor grade (grade 3 vs. grades 1-2), T-stage (T-stages 3-4 vs. T-stages 0-2), distal metastasis, and disease-free survival (DFS) of NSCLC (all p values >0.05). CD117 expression was associated with lymph node metastasis (positive vs. negative: OR = 0.74, 95% CI = 0.56-0.97, p = 0.03), histological type (adenocarcinoma (AC) versus squamous cell carcinoma (SCC): OR = 1.74, 95% CI = 1.26-2.39, p = 0.001), and a worse overall survival (OS) (HR = 1.89, 95% CI = 1.22-2.92, p = 0.004). The expression of CD117 was significantly higher in AC than in SCC. CD117 may be an independent prognostic indicator for worse OS in NSCLC.
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http://dx.doi.org/10.1159/000514386DOI Listing
June 2021

Measurement of postpartum blood loss using a new two-set liquid collection bag for vaginal delivery: A prospective, randomized, case control study.

Medicine (Baltimore) 2021 May;100(19):e25906

Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.

Background: Postpartum hemorrhage (PPH) is a major obstetric complication, and the real-time measurement of blood loss is important in the management and treatment of PPH. We designed a new two-set liquid collection bag (TSLCB) for measuring postpartum blood loss in vaginal delivery. The aim of this study was to evaluate the effectiveness of the TSLCB in separating the blood from the amniotic fluid during vaginal delivery and in determining the accuracy of the measured postpartum blood loss.

Methods: A prospective, randomized, case control study was conducted in the Women's Hospital, Zhejiang University School of Medicine, from March 2018 to April 2018. Sixty single pregnant women with spontaneous labor at 37-41 weeks without maternal complications were randomly divided into the experimental and control groups. The TSLCB was used to evaluate separately the amount of blood and amniotic fluid. For the control group, visual estimation and traditional plastic blood-collecting consumables were used to estimate the amount of postpartum blood loss. The measured blood loss between the two groups was compared, and the association of the measured blood loss with various clinical lab indices and vital signs was investigated.

Results: The TSLCB (the experimental group) improved the detection of the measured blood loss compared with visual estimation and the traditional method (the control group) (P < .05). In the experimental group, correlation analysis showed that the measured blood loss at delivery and within 24 h of delivery was significantly associated with the decreased hemoglobin level, red blood cell count, and hematocrit level of patients (r = -0.574, -0.455, -0.437; r = 0.-595, -0.368, -0.374; P < .05). In the control group, only the measured blood loss within 24 h of delivery was associated with the decreased hemoglobin level (r = -0.395, P < .05). No blood transfusion and plasma expanders were required in the treatment of PPH for both groups.

Conclusions: The TSLCB can be used to accurately measure the postpartum blood loss in vaginal delivery by medical personnel.
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http://dx.doi.org/10.1097/MD.0000000000025906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133090PMC
May 2021

Supramolecular Nanosubstrate-Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion.

Small 2021 Jun 8:e2100546. Epub 2021 Jun 8.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, California NanoSystems Institute (CNSI), Crump Institute for Molecular Imaging (CIMI), University of California, Los Angeles, Los Angeles, CA, 90095, USA.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) is an efficient and precise gene-editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate-mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular-uptake of the RNP-laden nanoparticles are examined. Dose- and time-dependent CRISPR/Cas9-mediated gene disruption is further examined in a green fluorescent protein (GFP)-expressing U87 cell line (GFP-U87). The utility of an optimized SMNP formulation in co-delivering Cas9 protein and two sgRNAs that target deletion of exons 45-55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.
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http://dx.doi.org/10.1002/smll.202100546DOI Listing
June 2021

αB-crystallin/HSPB2 is critical for hyperactive mTOR-induced cardiomyopathy.

J Cell Physiol 2021 Jun 8. Epub 2021 Jun 8.

State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Even though aberrant mechanistic target of rapamycin (mTOR) signaling is known to cause cardiomyopathy, its underlying mechanism remains poorly understood. Because augmentation of αB-crystallin and hspB2 was presented in the cortical tubers and lymphangioleiomyomatosis of tuberous sclerosis complex patients, we deciphered the role of αB-crystallin and its adjacent duplicate gene, hspB2, in hyperactive mTOR-induced cardiomyopathy. Cardiac Tsc1 deletion (T1-hKO) caused mouse mTOR activation and cardiomyopathy. Overexpression of αB-crystallin and hspB2 was presented in the hearts of these mice. Knockout of αB-crystallin/hspB2 reversed deficient Tsc1-mediated fetal gene expression, mTOR activation, mitochondrial damage, cardiomyocyte vacuolar degeneration, cardiomyocyte size, and fibrosis of T1-hKO mice. These cardiac-Tsc1; αB-crystallin; hspB2 triple knockout (tKO) mice had improved cardiac function, smaller heart weight to body weight ratio, and reduced lethality compared with T1-hKO mice. Even though activated mTOR suppressed autophagy in T1-hKO mice, ablation of αB-crystallin and hspB2 failed to restore autophagy in tKO mice. mTOR inhibitors suppressed αB-crystallin expression in T1-hKO mice and rat cardiomyocyte line H9C2. Starvation of H9C2 cells activated autophagy and suppressed αB-crystallin expression. Since inhibition of autophagy restored αB-crystallin expression in starved H9C2 cells, autophagy is a negative regulator of αB-crystallin expression. mTOR thus stimulates αB-crystallin expression through suppression of autophagy. In conclusion, αB-crystallin and hspB2 play a pivotal role in Tsc1 knockout-related cardiomyopathy and are therapeutic targets of hyperactive mTOR-associated cardiomyopathy.
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http://dx.doi.org/10.1002/jcp.30465DOI Listing
June 2021

sp. nov., isolated from rhizosphere soil of .

Int J Syst Evol Microbiol 2021 Jun;71(6)

Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, PR China.

A novel Gram-stain positive, facultatively anaerobic, motile, irregularly rod-shaped bacterium, designated GY 10621, was isolated from rhizosphere soil of in Beihai City, Guangxi Province, PR China, and characterized using a polyphasic taxonomic approach. GY 10621 was positive for catalase and oxidase. Growth occurred at 4-42 °C (optimum 30-37 °C), at pH 5.0-9.0 (optimum pH 7.0) and in the presence of 0-5% NaCl (w/v) (optimum 1-3%). The main menaquinones were MK-9 (H) (92.2 %) and MK-10 (7.8 %). The major cellular fatty acids were anteiso-C and C. The peptidoglycan was the type A4α (l-Lys-Ser-d-Glu). The polar lipids included four phosphoglycolipids, four glycolipids, an unidentified lipid and six unidentified phospholipids. The DNA G+C content of the type strain was 71.7 mol%. On the basis of the results of 16S rRNA gene analysis, the type strain of a species with a validly published name with the highest similarity to GY 10621 was KCTC 13155 (97.16 %), followed by NBRC 16159 (96.39 %). The calculated results indicated that compared with GY 10621, the average nucleotide identity (ANI) values of three strains closely related to GY 10621 (the two aforementioned type strains and '' Marseille-P3815) were 74.18-94.97 %, and the digital DNA-DNA hybridization (dDDH) values were 20.3-60.6 %. The results of 16S rRNA-based and genome-based phylogenetic tree analysis indicated that GY 10621 should be assigned to the genus . On the basis of evidence from polyphasic studies, GY 10621 should be designated as representing a novel species of the genus , for which the name sp. nov. is proposed. The type strain is GY 10621 (=CGMCC 1.17411=KCTC 49515).
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http://dx.doi.org/10.1099/ijsem.0.004829DOI Listing
June 2021

Targeting of VPS18 by the lysosomotropic agent RDN reverses TFE3-mediated drug resistance.

Signal Transduct Target Ther 2021 Jun 7;6(1):224. Epub 2021 Jun 7.

Department of Natural Product Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

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http://dx.doi.org/10.1038/s41392-021-00547-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184988PMC
June 2021

Hemoglobin subunit beta interacts with the capsid, RdRp and VPg proteins, and antagonizes the replication of rabbit hemorrhagic disease virus.

Vet Microbiol 2021 Jun 2;259:109143. Epub 2021 Jun 2.

Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China. Electronic address:

Rabbit hemorrhagic disease virus (RHDV) causes a highly contagious disease in rabbits that is associated with high mortality. Because of the lack of a suitable cell culture system for RHDV, its pathogenic mechanism and replication remain unclear. This study found that the expression level of host protein rabbit hemoglobin subunit beta (HBB) was significantly downregulated in RHDV-infected cells. To investigate the role of HBB in RHDV replication, small interfering RNAs for HBB and HBB eukaryotic expression plasmids were used to change the expression level of HBB in RK-13 cells and the results showed that the RHDV replication level was negatively correlated with the expression level of HBB. It was also verified that HBB inhibited RHDV replication using constructed HBB stable overexpression cell lines and HBB knockout cell lines. The interaction of HBB with viral capsid protein VP60, replicase RdRp, and VPg protein was confirmed, as was the activation of the expression of interferon γ by HBB. The results of this study indicated that HBB may be an important host protein in host resistance to RHDV infection.
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http://dx.doi.org/10.1016/j.vetmic.2021.109143DOI Listing
June 2021

Rituximab Therapy for Primary Membranous Nephropathy in a Chinese Cohort.

Front Med (Lausanne) 2021 20;8:663680. Epub 2021 May 20.

Renal Division, Peking University First Hospital, Beijing, China.

Rituximab has become one of the first-line therapies for the treatment of moderate and high-risk primary membranous nephropathy (pMN). We retrospectively reviewed 95 patients with pMN who received rituximab therapy and focused on the therapeutic effects and safety of this therapy in a Chinese cohort. Ninety-five consecutive patients with pMN diagnosed by kidney biopsy received rituximab and were followed up for >6 months. Four weekly doses of rituximab (375 mg/m) was adopted as the initial administration. Repeated single infusions were administrated to maintain B cell depletion levels of <5 cells/mL. A total of 91 patients completed rituximab therapy with the total dose of 2.4 (2.0, 3.0) g; 64/78 (82.1%) patients achieved anti-PLA2R antibody depletion in 6.0 (1.0, 12.0) months; 53/91 (58.2%) patients achieved clinical remission in 12.0 (6.0, 24.0) months, including complete remission in 18.7% of patients and partial remission in 39.6% of patients. Multivariate logistic regression analysis showed that severe proteinuria (OR = 1.22, = 0.006) and the persistent positivity of anti-PLA2R antibodies (OR = 9.00, = 0.002) were independent risk factors for no-remission. The remission rate of rituximab as an initial therapy was higher than rituximab as an alternative therapy (73.1 vs. 52.3%, = 0.038). Lastly, 45 adverse events occurred in 37 patients, but only one patient withdrew from treatment due to severe pulmonary infection. Rituximab is a safe and effective treatment option for Chinese patients with pMN, especially as an initial therapy.
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http://dx.doi.org/10.3389/fmed.2021.663680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172988PMC
May 2021

Energy metabolism disorders and potential therapeutic drugs in heart failure.

Acta Pharm Sin B 2021 May 14;11(5):1098-1116. Epub 2020 Oct 14.

State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function energy metabolism to provide new research ideas for the development and application of drugs for treating HF.
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http://dx.doi.org/10.1016/j.apsb.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144890PMC
May 2021

Associations of BNIP3 and DAPK1 gene polymorphisms with disease susceptibility, clinicopathologic features, anxiety, and depression in gastric cancer patients.

Int J Clin Exp Pathol 2021 15;14(5):633-645. Epub 2021 May 15.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University Hefei, Anhui, China.

The purpose of this study is to explore the associations of BNIP3 and DAPK1 polymorphisms with disease susceptibility, clinicopathologic characteristics, depression, and anxiety in gastric cancer (GC) patients. In this study, 150 GC patients and 100 healthy controls were recruited. 1000 Genomes database and Haploview 4.0 software were used to select tag SNPs. Improved multiplex ligase detection reaction was used for genotyping. Data were analyzed using Chi-square test (χ test) and univariate and multivariate logistic regression. The results demonstrated that the rs10781582 of BNIP3 in the dominant model was associated with a reduced risk of GC in the younger group ( = 0.015), and the minor allele G of rs1329600 at DAPK1 was associated with reduced risk of GC ( = 0.018). In the stratified analysis, the rs3793742 and rs10781582 of BNIP3 in the dominant model were associated with gender and age of GC patients, respectively (rs3793742: = 0.033; rs10781582: = 0.030). The rs10781582 of BNIP3 in the dominant model was correlated with depression in GC patients ( = 0.003). However, no association was found between BNIP3 and DAPK1 polymorphisms and differentiation degree, TNM stage, lymph node metastases, visceral metastasis, and anxiety. In summary, polymorphisms of BNIP3 and DAPK1 were associated with a protective effect against GC. So far, this is the first study to explore the association between BNIP3 and DAPK1 gene polymorphism and GC risk, which may provide new insight about biologic mechanisms of GC pathogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167493PMC
May 2021

Research Progress in Prognostic Factors and Biomarkers of Ovarian Cancer.

J Cancer 2021 13;12(13):3976-3996. Epub 2021 May 13.

Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 210029.

Ovarian cancer is a serious threat to women's health; its early diagnosis rate is low and prone to metastasis and recurrence. The current conventional treatment for ovarian cancer is a combination of platinum and paclitaxel chemotherapy based on surgery. The recurrence and progression of ovarian cancer with poor prognosis is a major challenge in treatment. With rapid advances in technology, understanding of the molecular pathways involved in ovarian cancer recurrence and progression has increased, biomarker-guided treatment options can greatly improve the prognosis of patients. This review systematically discusses and summarizes existing and new information on prognostic factors and biomarkers of ovarian cancer, which is expected to improve the clinical management of patients and lead to effective personalized treatment.
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http://dx.doi.org/10.7150/jca.47695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176232PMC
May 2021

Curcumin-mediated photodynamic therapy inhibits the phenotypic transformation, migration, and foaming of oxidized low-density lipoprotein-treated vascular smooth muscle cells by promoting autophagy.

J Cardiovasc Pharmacol 2021 Jun 2. Epub 2021 Jun 2.

Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, Sichuan, China.

Abstract: Vascular smooth muscle cells (VSMCs) are becoming a hot spot and target of atherosclerosis research. This study aimed to observe the specific effects of curcumin (CUR)-mediated photodynamic therapy (CUR-PDT) on oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and confirm whether these effects are mediated by autophagy. In this study, the MOVAS and A7r5 cell lines were used for parallel experiments. VSMC viability was evaluated by CCK-8 assay. VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro. The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting. The migration ability of the cells was detected by using transwell assay. The presence of intracellular lipid droplets was detected by Oil Red O staining. The results showed that VSMCs transformed from the contraction phenotype to the synthetic phenotype when stimulated by ox-LDL, during which autophagy was inhibited. However, CUR-PDT treatment significantly promoted the level of autophagy and inhibited the process of phenotypic transformation induced by ox-LDL. Additionally, ox-LDL significantly promoted VSMC migration and increased the number of lipid droplets number, whereas CUR-PDT treatment significantly reduced the ox-LDL-induced increase in the migration ability of, and lipid droplet numbers in, VSMCs. When the VSMCs were pretreated with the autophagy inhibitor 3-methyladenine (3-MA) for 24 h, the effects of CUR-PDT were reversed. Therefore, our study indicated that CUR-PDT can inhibit the phenotypic transformation, migration, and foaming of ox-LDL-treated VSMCs by inducing autophagy.
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http://dx.doi.org/10.1097/FJC.0000000000001069DOI Listing
June 2021