Publications by authors named "Zhenzhong Wang"

191 Publications

Experimental and Numerical Investigation into the Heat- and Mass-Transfer Processes of -Butane Adsorption on Activated Carbon.

ACS Omega 2021 Jul 25;6(27):17162-17172. Epub 2021 Jun 25.

Department of Environmental Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, China.

In this work, the adsorption parameters of -butane vapor on an absorbent were tested following the fixed-bed method. According to the corresponding experiments, the maximum adsorption capacity and breakthrough time of activated carbon (AC) are 0.2674 g·g and 924 min, respectively. According to the two-energy-state model formula and the classical adsorption heat formula, the values of theoretical and actual adsorption heat of AC adsorbing -butane are 5.48 and 5.56 kJ·mol, respectively. The model for adsorption of -butane by an AC fixed bed is based on the analytical solutions to the mass, momentum, and energy conservation equations. The model is built using porous media zone in ANSYS Fluent, the implementation of the model into ANSYS Fluent under user-defined functions (UDFs) is also described, the mass source term and energy source term are loaded into Fluent through UDF, and then the mass- and heat-transfer processes of AC in the absorption of -butane are simulated. Furthermore, the predictions by ANSYS Fluent are compared with in situ experimental data, and the deviation rate of breakthrough time and temperature of six monitoring points is less than 5%. The results verify the accuracy and feasibility of computational fluid dynamics (CFD). Therefore, the model can be used to predict the engineering application of the adsorption of organic gases by various porous media.
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http://dx.doi.org/10.1021/acsomega.0c06273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280664PMC
July 2021

Ultrafiltration strategy combined with nanoLC-MS/MS based proteomics for monitoring potential residual proteins in TCMIs.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 30;1178:122818. Epub 2021 May 30.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Traditional Chinese medicine injections (TCMIs) containing complex constituents frequently cause unpredictable adverse reactions. The residual heterologous proteins in TCMIs may be one kind of the sensitized constituents. However, few methods were developed to identify and monitor the residual proteins of TCMIs in industry. Here, we described a method combining the advantages of ultrafiltration and mass spectrometry-based proteomics for monitoring the potential residual proteins in Re Du Ning injection (RDNI) intermediates and preparations. We identified and quantified both de novo peptides and the proteins matched against databases of three raw plants by using PEAKS software. Interesting, we found there was a significant decrease of peptides and proteins in No. 3-5 of RDNI intermediates and some even disappeared. Besides, we found this method could greatly reduce the interference of contaminants in proteomics experiments. The rapid and accurate method proposed in this paper could be used for monitoring potential residual proteins in TCMIs to guarantee their quality and safety.
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http://dx.doi.org/10.1016/j.jchromb.2021.122818DOI Listing
May 2021

Metabolomics analysis of the therapeutic effects of Qiwei Tongbi oral liquid on rheumatoid arthritis in rats.

J Pharm Biomed Anal 2021 Aug 25;202:114166. Epub 2021 May 25.

Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing, 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, 222001, China; National Enterprise Technology Center, National Post-Doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang, 222001, China. Electronic address:

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine (TCM) formula, has a good therapeutic effect on rheumatoid arthritis (RA) and is widely used in China. To comprehensively elucidate the therapeutic mechanism of QWTB in the treatment of RA, the effects of QWTB on biomarkers and metabolic pathways in a rat model of kidney deficiency arthritis were investigated in this study. The effects of QWTB on pharmacodynamic indicators, including paw swelling, arthritis score; interleukin-1β, interleukin-6, interleukin-17 F, tumor necrosis factor-α, tartrate-resistant acid phosphatase 5b, bone alkaline phosphatase, bone-specific alkaline phosphatase, bone glaprotein, urea, and creatinine levels; and histopathology, suggested that QWTB significantly improved renal function, inhibited the inflammatory response, and reduced bone loss. In total, 39 differential metabolites were screened by comparing the endogenous components between blank and model rat plasma, among which 16 metabolites were altered by QWTB. The metabolism pathway analysis revealed that α-linolenic acid metabolism, phenylalanine metabolism, sphingolipid metabolism, histidine metabolism and glycerophospholipid metabolism were greatly disturbed. Thus, the biomarkers investigated included (1) α-linolenic acid, (2) hippuric acid, (3) phosphatidylethanolamine (15:0/22:2(13Z,16Z)), (4) phenylpyruvic acid, (5) sphinganine, and (6) urocanic acid. QWTB affected three abnormal biomarkers: (3), (4), and (6). Phenylphruvic acid, sphinganine and urocanic acid were significantly associated with pharmacodynamic indicators, as shown by Pearson correlation analysis. These results indicated that RA-related biomarkers had certain reliability and biological significance. In summary, QWTB regulated the metabolic disorders in rats with RA. Its therapeutic mechanism may involve the regulation of phenylalanine metabolism, histidine metabolism, and glycerophospholipid metabolism. The results of this study are useful for understanding the therapeutic mechanisms of TCM.
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http://dx.doi.org/10.1016/j.jpba.2021.114166DOI Listing
August 2021

Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Neurochem Res 2021 Jul 14;46(7):1881-1894. Epub 2021 May 14.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, Liaoning, People's Republic of China.

Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs. GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.
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http://dx.doi.org/10.1007/s11064-021-03315-zDOI Listing
July 2021

Ginkgolide B‑induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ1‑42.

Mol Med Rep 2021 06 21;23(6). Epub 2021 Apr 21.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, P.R. China.

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by β‑amyloid (Aβ) remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aβ‑induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aβ, GB and GB + compound C groups. Cell viability and apoptosis were analyzed using Cell Counting Kit‑8 and flow cytometry assays, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription‑quantitative PCR, respectively. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and ATP were determined using the corresponding commercial kits. The findings revealed that GB attenuated Aβ‑induced apoptosis and the 5' adenosine monophosphate‑ activated protein kinase (AMPK) inhibitor compound C reversed the protective effects of GB. In addition, GB reversed Aβ‑induced oxidative damage and energy metabolism disorders, including decreases in the levels of SOD, GSH‑Px and ATP and increased the levels of MDA and ROS in astrocytes, while compound C reversed the anti‑oxidative effect and the involvement of GB in maintaining energy metabolism in astrocytes. Finally, GB decreased the expression levels of the endoplasmic reticulum stress (ERS) proteins and the apoptotic protein CHOP and increased both mRNA and protein expression of the components of the energy metabolism‑related AMPK/peroxisome proliferator‑activated receptor γ coactivator 1α/peroxisome proliferator‑activated receptor α and anti‑oxidation‑related nuclear respiratory factor 2/heme oxygenase 1/NAD(P)H dehydrogenase (quinone 1) pathways and downregulated the expression of β‑secretase 1. However, compound C could antagonize these effects. In conclusion, the findings demonstrated that GB protected against Aβ‑induced apoptosis by inhibiting ERS, oxidative stress, energy metabolism disorders and Aβ production probably by activating AMPK signaling pathways. The findings provided an innovative insight into the treatment using GB as a therapeutic in Aβ‑related AD.
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http://dx.doi.org/10.3892/mmr.2021.12096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072312PMC
June 2021

Deciphering the Pharmacological Mechanisms of Guizhi-Fuling Capsule on Primary Dysmenorrhea Through Network Pharmacology.

Front Pharmacol 2021 3;12:613104. Epub 2021 Mar 3.

Department of Automation, Institute for TCM-X, MOE Key Laboratory of Bioinformatics/Bioinformatics Division, BNRIST, Tsinghua University, Beijing, China.

Guizhi-Fuling capsule (GZFLC), originated from a classical traditional Chinese herbal formula Guizhi-Fuling Wan, has been clinically used for primary dysmenorrhea in China. Nonetheless, the underlying pharmacological mechanisms of GZFLC remain unclear. The integration of computational and experimental methods of network pharmacology might be a promising way to decipher the mechanisms. In this study, the target profiles of 51 representative compounds of GZFLC were first predicted by a high-accuracy algorithm, drugCIPHER-CS, and the network target of GZFLC was identified. Then, potential functional modules of GZFLC on primary dysmenorrhea were investigated using functional enrichment analysis. Potential bioactive compounds were recognized by hierarchical clustering analysis of GZFLC compounds and first-line anti-dysmenorrhea drugs. Furthermore, the potential anti-dysmenorrhea mechanisms of GZFLC were verified through enzyme activity assays and immunofluorescence tests. Moreover, effects of GZFLC on primary dysmenorrhea were evaluated in oxytocin-induced dysmenorrhea murine model. In the network target analysis, GZFLC may act on five functional modules of pain, inflammation, endocrine, blood circulation and energy metabolism. Integrating computational and experimental approaches, we found that GZFLC significantly inhibited the writhing response and reduced the degree of uterine lesions in oxytocin-induced dysmenorrhea murine model. Furthermore, GZFLC may partially alleviate primary dysmenorrhea by inhibiting cyclooxygenase 2 (COX2) and downregulating MAPK signaling pathway. Consequently, GZFLC presented pain relief and sustained benefits for primary dysmenorrhea. This study could provide a scientific approach for deciphering pharmacological mechanisms of herbal formulae through network pharmacology.
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http://dx.doi.org/10.3389/fphar.2021.613104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966503PMC
March 2021

NOGEA: A Network-oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning.

Genomics Proteomics Bioinformatics 2021 Mar 17. Epub 2021 Mar 17.

College of Life Science, Northwest University, Xi'an 710069, China; College of Life Science, Northwest A & F University, Yangling 712100, China; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, China. Electronic address:

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
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http://dx.doi.org/10.1016/j.gpb.2020.06.023DOI Listing
March 2021

Nondestructive qualitative and quantitative analysis of Yaobitong capsule using near-infrared spectroscopy in tandem with chemometrics.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 1;252:119517. Epub 2021 Feb 1.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The purpose of the study is to present a nondestructive qualitative and quantitative approach of hard-shell capsule using near-infrared (NIR) spectroscopy combined with chemometrics. The Yaobitong capsule (YBTC) was used for demonstration of the proposed approach and the NIR spectra were collected using a handheld fiber probe (FP) without the damage of capsule shell. By comparing the differences and similarities of the NIR spectra of capsule shells, contents and intact capsules, a preliminary conclusion can be drawn that the NIR spectra contained the information of the contents. Characteristic variables were selected by competitive adaptive weighted resampling (CARS) method, and least squares support vector machine (LSSVM) method based on particle swarm optimization (PSO) algorithm was applied to the construction of quantitative models. The relative standard error of prediction (RSEP) values of five saponins including notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd were 3.240%, 5.468%, 5.303%, 5.043%, and 3.745%, respectively. In addition, for qualitative model, three different types of adulterated capsules were designed. The model established by data driven version of soft independent modeling of class analogy (DD-SIMCA) demonstrated a satisfactory result that all adulterated capsules were identified accurately after an appropriate number of principal components (PCs) were chosen. The results indicated that although the NIR spectra collection was affected by capsule shell, sufficient content information can be obtained for quantitative and qualitative analysis after combining with chemometrics. It further proved that acquired NIR spectra do contain the effective component information of the capsule. This study provided a reference for the rapid nondestructive quality analysis of traditional Chinese medicine (TCM) capsule without damaging capsule shell.
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http://dx.doi.org/10.1016/j.saa.2021.119517DOI Listing
May 2021

An integrated analytical approach based on enhanced fragment ions interrogation and modified Kendrick mass defect filter data mining for in-depth chemical profiling of glucosinolates by ultra-high-pressure liquid chromatography coupled with Orbitrap high resolution mass spectrometry.

J Chromatogr A 2021 Feb 13;1639:461903. Epub 2021 Jan 13.

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address:

High resolution mass spectrometry (HRMS)-based analytical technique promotes the discovery and development of new bioactive molecules from natural sources. However, challenges for MS analysis of natural products include their structural diversity, numerous trace components, as well as the interference from complex matrices that limits the rapid detection and identification of all target analytes in the extracts. Herein, we presented an integrated analytical approach to obtain chemical profile of glucosinolates (GLSs) in Eutrema yunnanense, a perennial herb, which is used as a condiment (Wasabi), by ultra-high-pressure liquid chromatography coupled with Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap/HRMS). The intelligent AcquireX deep scan greatly improved the detection efficiency and coverage of data-dependent acquisition (DDA) mode, and enhanced structurally significant product ions interrogation by generating exhaustive MS/MS spectra with more informative fragmentation. Massive HRMS data mining for searching GLSs was then achieved by a modified Kendrick mass defect filter (MKMDF), which enabled the visualization of their homologous characteristics and reduced the complicacy of data post-processing. Ultimately, a total of 175 GLSs were tentatively identified or characterized based on the MS fragmentation patterns, including 52 potentially new compounds among which 37 malonylated GLSs were first discovered. These compounds were then applied to analyse the chemical differentiation between the rhizome and leaf of E. yunnanense. This study provides a feasible approach for screening and confident structure characterization of GLSs and has practical implications for profiling other natural bioactive homologous compounds.
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http://dx.doi.org/10.1016/j.chroma.2021.461903DOI Listing
February 2021

Dissecting the novel mechanism of reduning injection in treating Coronavirus Disease 2019 (COVID-19) based on network pharmacology and experimental verification.

J Ethnopharmacol 2021 Jun 22;273:113871. Epub 2021 Jan 22.

State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu, 222001, China; The Key Laboratory for the New Technique Research of TCM Extraction and Purification, Lianyungang, Jiangsu, 222047, China. Electronic address:

Ethnopharmacological Relevance: Reduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan".

Aim Of The Study: To elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19.

Methods: This study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results.

Results: We concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 μg crude drugs/mL (2.405 μg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity.

Conclusion: RDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.
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http://dx.doi.org/10.1016/j.jep.2021.113871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825842PMC
June 2021

Systems pharmacology dissection of targeting tumor microenvironment to enhance cytotoxic T lymphocyte responses in lung cancer.

Aging (Albany NY) 2021 01 17;13(2):2912-2940. Epub 2021 Jan 17.

Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.

The clinical notably success of immunotherapy fosters an enthusiasm in developing drugs by enhancing antitumor immunity in the tumor microenvironment (TME). , is a promising herbal medicine for tumor immunotherapy due to the pharmacological actions in immunological function modulation and antitumor. Here, we developed a novel systems pharmacology strategy to explore the polypharmacology mechanism of involving in targeting TME of non-small cell lung cancer (NSCLC). This strategy integrates the active compounds screening, target predicting, network pharmacology analysis and onco-immune interacting to predict the potential active compounds that trigger the antitumor immunity. Icaritin (ICT), a major active ingredient of , was predicted to have good drug-like properties and target immune microenvironment in NSCLC via regulating multiple targets and pathways. Then, we evidenced that the ICT effectively inhibited tumor growth in LLC tumor-bearing mice and increases the infiltration of CD8+ T cells in TME. In addition, we demonstrated that ICT promotes infiltration of CD8 T cells in TME by downregulating the immunosuppressive cytokine (TNF-α, IL10, IL6) and upregulating chemotaxis (CXCL9 and CXCL10). Overall, the systems pharmacology strategy offers an important paradigm to understand the mechanism of polypharmacology of natural products targeting TME.
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http://dx.doi.org/10.18632/aging.202410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880341PMC
January 2021

A RNA-seq approach for exploring the protective effect of ginkgolide B on glutamate-induced astrocytes injury.

J Ethnopharmacol 2021 Apr 12;270:113807. Epub 2021 Jan 12.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, 116034, PR China; Institute of Chemistry and Applications of Plant Resources, Dalian Polytechnic University, Dalian, Liaoning, 16034, PR China. Electronic address:

Ethnopharmacological Relevance: There is substantial experimental evidence to support the view that Ginkgo biloba L. (Ginkgoaceae), a traditional Chinese medicine known to treating stroke, has a protective effect on the central nervous system and significantly improves the cognitive dysfunction caused by disease, including alzheimer disease (AD), vascular dementia, and diabetic encephalopathy. Although a number of studies have reported that ginkgolide B (GB), a diterpenoid lactone compound extracted from Ginkgo biloba leaves, has neuroprotective effects, very little research has been performed to explore its potential pharmacological mechanism on astrocytes under abnormal glutamate (Glu) metabolism in the pathological environment of AD.

Aim Of The Study: We investigated the protective effect and mechanism of GB on Glu-induced astrocytes injury.

Methods: Astrocytes were randomly divided into the control group, Glu group, GB group, and GB + IWP-4 group.The CCK-8 assay was used to determine relative cell viability in vitro. Furthermore, RNA sequencing (RNA-seq) was performed to assess the preventive effects of GB in the Glu-induced astrocyte model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the possible molecular mechanisms. The effects of GB on the Glu transporter and Glu-induced apoptosis of astrocytes were studied by RT-qPCR and western blot.

Results: GB attenuated Glu-induced apoptosis in a concentration-dependent manner, while the Wnt inhibitor IWP-4 reversed the protective effect of GB on astrocytes. The RNA-seq results revealed 4,032 differential gene expression profiles; 3,491 genes were up-regulated, and 543 genes were down-regulated in the GB group compared with the Glu group. Differentially expressed genes involved in a variety of signaling pathways, including the Hippo and Wnt pathways have been associated with the development and progression of AD. RT-qPCR was used to validate 14 key genes, and the results were consistent with the RNA-seq data. IWP-4 inhibited the regulation of GB, disturbed the apoptosis protective effect on astrocytes, and promoted Glu transporter gene and protein expression caused by Glu.

Conclusion: Our findings demonstrate that GB may play a protective role in Glu-induced astrocyte injury by regulating the Hippo and Wnt pathways. GB was closely associated with the Wnt pathway by promoting expression of the Glu transporter and inhibiting Glu-induced injury in astrocytes.
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http://dx.doi.org/10.1016/j.jep.2021.113807DOI Listing
April 2021

Effect of spinal manipulation on degenerative scoliosis.

J Tradit Chin Med 2020 12;40(6):1033-1040

Spine Department 2, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China.

Objective: To investigate the effect of spinal manipulation (SM) on degenerative scoliosis by evaluating patients' visual analog scale (VAS) scores, Cobb angles, sagittal vertical axis (SVA), and apical vertebral rotation (AVR) and to explore factors that influence treatment effect.

Methods: A total of 55 patients with degenerative scoliosis received 4 weeks of SM. After treatment, patients were divided into two groups: the remission group (VAS score < 40 mm) and the non-remission group (VAS score ≥ 40 mm). Pre- versus post-treatment VAS scores, Cobb angles, SVA, and AVR were compared in each group and in the total population. Baseline data (sex, age, symptom characteristics, duration of symptoms, VAS score, Cobb angle, SVA, and AVR) were compared between groups. Factors influencing the post-treatment VAS score were explored with multiple linear regression analysis.

Results: No changes were found in the Cobb angle (P = 0.722) or AVR (P = 0.424) after intervention in the overall population. However, the SVA (P < 0.001) and VAS score (P = 0.000) changed significantly after treatment. Similar changes were observed in the remission group (n = 29). Multiple linear regression revealed that the only factors influencing treatment effect were symptom characteristics, SVA, and VAS score.

Conclusion: SM relieved pain and improved sagittal imbalance in patients with degenerative scoliosis. It did not lessen the severity of coronal curvature or vertebral rotation. Factors influencing the effect of SM included symptom characteristics, VAS score, and SVA. A larger randomized trial is needed to further confirm our results.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.06.015DOI Listing
December 2020

Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway.

Biomed Pharmacother 2021 Jan 14;133:110802. Epub 2020 Nov 14.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address:

Hyperlipidaemia is one of the major risk factors for atherosclerosis, coronary heart disease, stroke and diabetes. In the present study, we synthesized a new anthraquinone compound, 1,8-dihydroxy-3-succinic acid monoethyl ester-6-methylanthraquinone, and named it Kanglexin (KLX). The aim of this study was to evaluate whether KLX has a lipid-lowering effect and to explore the potential molecular mechanism. In this study, Sprague-Dawley rats were fed a high fat diet (HFD) for 5 weeks to establish a hyperlipidaemia model; then, the rats were orally administered KLX (20, 40, and 80 mg kg·d) or atorvastatin calcium (AT, 10 mg kg·d) once a day for 2 weeks. KLX had prominent effects on reducing blood lipids, hepatic lipid accumulation, body weight and the ratio of liver weight/body weight. Furthermore, KLXdramatically reduced the total cholesterol (TC) and triglyceride (TG) levels and lipid accumulation in a HepG2 cell model of dyslipidaemia induced by 1 mmol/L oleic acid (OA). KLX may decrease lipid levels by phosphorylating adenosine monophosphate-activated protein kinase (AMPK) and the downstream sterol regulatory element binding protein 2 (SREBP-2)/proprotein convertase subtilisin/kexin type 9 (PCSK9)/low-density lipoprotein receptor (LDLR) signalling pathway in the HFD rats and OA-treated HepG2 cells. The effects of KLX on the AMPK/SREBP-2/PCSK9/LDLR signalling pathway were abolished when AMPK was inhibited by compound C (a specific AMPK inhibitor) in HepG2 cells. In summary, KLX has an efficient lipid-lowering effect mediated by activation of the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Our findings may provide new insight into and evidence for the discovery of a new lipid-lowering drug for the prevention and treatment of hyperlipidaemia, fatty liver, and cardiovascular disease in the clinic.
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http://dx.doi.org/10.1016/j.biopha.2020.110802DOI Listing
January 2021

A novel online preparative high-performance liquid chromatography system with the multiple trap columns-valve switch technique for the rapid and efficient isolation of main flavonoids from Epimedium koreanum Nakai.

J Sep Sci 2021 Jan 27;44(2):656-665. Epub 2020 Nov 27.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, P. R. China.

In this work, a new online preparative high-performance liquid chromatography was developed for the fast and efficient separation of complex chemical mixtures from natural products. This system integrates two chromatographic systems into an online automatic separation system using the technique of multiple trap columns with valve switching. The sample was first separated into 18 subfractions in the online preparative high-performance liquid chromatography, and the sample eluents were then diluted and captured online on 18 trap columns by the multiple trap columns technique, respectively. Each subfraction retained on the trap column was transferred online to the separation column for the second separation. Finally, the target compounds were purified by appropriate separation conditions and multiple heart-cutting strategies. Importantly, the system was successfully used to separate 18 high-purity flavonoids from the crude extract of Epimedium koreanum Nakai online in one step. The entire separation time was approximately 20 h, and the structures were characterized by the high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance. This online preparative high-performance liquid chromatography system represents an efficient and rapid separation system that has the potential for a wide array of applications in the separation of complex chemical components from natural products.
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http://dx.doi.org/10.1002/jssc.202000783DOI Listing
January 2021

Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer.

Phytomedicine 2020 Dec 1;79:153326. Epub 2020 Sep 1.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China. Electronic address:

Background: Lung cancer is the most common and mortal cancer worldwide. Rhodiola rosea L. (RR), a well-known traditional Chinese medicine (TCM), has been turned out to be effective in anti-lung cancer therapy, but its molecular mechanism of action has not been clearly understood.

Purpose: In this study, we aimed to elucidate the possible molecular mechanism underlying the effect of RR against non-small cell lung cancer (NSCLC) by systems pharmacology.

Methods: The effects of RR on NSCLC were examined in Lewis lung carcinoma (LLC) tumor-bearing mice models. The possible molecular mechanism was unraveled by systems pharmacology, which includes pharmacokinetics evaluation, active compounds screening, target prediction and network analysis. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay; cell apoptosis was detected by flow cytometry; protein and proinflammatory cytokines expression were evaluated by Western blot and qRT-PCR.

Results: In vivo, RR significantly inhibited the tumor growth and prolonged the survival of the tumor bearing mice. In silico, we identified 19 potential active molecules (e.g., salidroside and rhodiosin), 112 targets (e.g., COX-2 and AKT) and 27 pathways (e.g., PI3K/AKT signaling pathway and NF-κB signaling pathway) for RR. Additionally, targets analysis and networks construction further revealed that RR exerted anti-cancer effects by regulating apoptosis, angiogenesis and inflammation. In vitro, salidroside could significantly decrease expression of pro-angiogenic factors (e.g., VEGF and eNOS) and proinflammatory cytokines (e.g., COX-2, iNOS and TNF-α). Also, Bcl-2, an anti-apoptotic protein was decreased whereas Bax, a pro-apoptotic protein, was increased. Further flow cytometry analysis showed that salidroside could induce apoptosis in H1975 cells.

Conclusions: Mechanistically, the antitumor effect of RR on NSCLC was responsible for the synergy among anti-inflammatory, anti-angiogenic and pro-apoptotic.
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http://dx.doi.org/10.1016/j.phymed.2020.153326DOI Listing
December 2020

Individual-Based Transfer Learning for Dynamic Multiobjective Optimization.

IEEE Trans Cybern 2020 Sep 18;PP. Epub 2020 Sep 18.

Dynamic multiobjective optimization problems (DMOPs) are characterized by optimization functions that change over time in varying environments. The DMOP is challenging because it requires the varying Pareto-optimal sets (POSs) to be tracked quickly and accurately during the optimization process. In recent years, transfer learning has been proven to be one of the effective means to solve dynamic multiobjective optimization. However, the negative transfer will lead the search of finding the POS to a wrong direction, which greatly reduces the efficiency of solving optimization problems. Minimizing the occurrence of negative transfer is thus critical for the use of transfer learning in solving DMOPs. In this article, we propose a new individual-based transfer learning method, called an individual transfer-based dynamic multiobjective evolutionary algorithm (IT-DMOEA), for solving DMOPs. Unlike existing approaches, it uses a presearch strategy to filter out some high-quality individuals with better diversity so that it can avoid negative transfer caused by individual aggregation. On this basis, an individual-based transfer learning technique is applied to accelerate the construction of an initial population. The merit of the IT-DMOEA method is that it combines different strategies in maintaining the advantages of transfer learning methods as well as avoiding the occurrence of negative transfer; thereby greatly improving the quality of solutions and convergence speed. The experimental results show that the proposed IT-DMOEA approach can considerably improve the quality of solutions and convergence speed compared to several state-of-the-art algorithms based on different benchmark problems.
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http://dx.doi.org/10.1109/TCYB.2020.3017049DOI Listing
September 2020

Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis.

J Food Biochem 2020 11 10;44(11):e13446. Epub 2020 Sep 10.

Jiangsu Kangyuan Pharmaceutical Co., Ltd, Lianyungang, China.

The present study was aimed to investigate the mechanisms of salidroside (SAL) from Rhodiola wallichiana var. cholaensis on hypoglycemic and oxidative stress responses. The palmitate (PA)-induced GLUTag cells model and the glucosamine-induced insulin resistance model in HepG2 cells were built. SAL led to the up-regulation of the serum glucagon-like peptide 1 (GLP-1) level by facilitating the SCFAs production, the promotion of GLP-1 synthesis by improving p38 MAPK phosphorylation and regulating insulin resistance. Moreover, the production of reactive oxygen species (ROS) and the expression of MAPKs were down-regulated. Furthermore, SAL was found to be able to inhibit PA-induced apoptosis that down-regulates cleaved caspase-3 and Bax expressions, while up-regulating Bcl-2 expression and up-regulates the Bcl-2/Bax ratio in glucosamine induced insulin resistance model. Besides, SAL can also up-regulate the mTOR/p70S6k signaling pathway in the PA-induced GLUTag cells model. Our data demonstrated that SAL could reverse insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. PRACTICAL APPLICATIONS: Our data showed that SAL could increase the GLP-1 level by stimulating the SCFAs production and p38 phosphorylation and facilitate the IR and GLP-1 synthesis by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. Furthermore, the SAL has also stimulated the mTOR/p70S6k signaling pathway in PA-induced GLUTag cells model. The results provided a possibility to employ SAL for diabetes treatment.
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http://dx.doi.org/10.1111/jfbc.13446DOI Listing
November 2020

IGF-1R stimulation alters microglial polarization via TLR4/NF-κB pathway after cerebral hemorrhage in mice.

Brain Res Bull 2020 11 29;164:221-234. Epub 2020 Aug 29.

Department of Neurosurgery, Yuyao People's Hospital, Ningbo 315000, China. Electronic address:

Intracerebral hemorrhage (ICH) is a common neurological disease, causing severe disability and even deaths. Stem cell transplantation has been increasingly used in stroke therapy, and neural stem cells (NSCs) are a good source for stem cell transplantation. However, the regulatory mechanism of NSCs remains unclear. In this study, we examined the impact of insulin-like growth factor-1 (IGF-1) secreted by NSCs on microglial polarization following ICH in adult C57BL/6 mice. Mouse models of ICH were established by collagenase injection. ICH mice received NSC transplantation 1 h after model establishment. Firstly, the changes of microglial polarization in cerebral tissues of ICH mice were detected by immunofluorescence and ELISA. Secondly, the molecular mechanism underlying the microglial polarization was evaluated repeatedly with the application of IGF-1R siRNA and IGF-1R-mediated inhibition. We assessed the brain water content and behavioral deficits of ICH mice 12, 24, 48, and 72 h after surgery. The survival of neurons in the brain was examined using Nissl staining and TUNEL staining at 72 h. The TLR4/NF-κB pathway implicated in ICH-induced inflammation was profiled by Western blot analysis and immunohistochemistry. Finally, the changes in microglia after ICH in mice were re-examined under different doses of rhIGF-1. In summary, NSC transplantation changed microglial polarization in ICH mice. IGF-1R inhibition and knockdown reversed the therapeutic effect of NSCs, and rhIGF-1 had an anti-inflammatory effect. The results of this study suggest that IGF-1R stimulation is a potential target for stem cell-based treatment of cerebral hemorrhage and may attenuate inflammatory response in the brain after bleeding.
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http://dx.doi.org/10.1016/j.brainresbull.2020.08.026DOI Listing
November 2020

Systematic Evaluation of the Diagnostic and Prognostic Significance of Competitive Endogenous RNA Networks in Prostate Cancer.

Front Genet 2020 30;11:785. Epub 2020 Jul 30.

College of Life Science, Northwest A&F University, Yangling, China.

Long non-coding RNA (lncRNA)-mediated competitive endogenous RNA (ceRNA) networks act as essential mechanisms in tumor initiation and progression, but their diagnostic and prognostic significance in prostate cancer (PCa) remains poorly understood. Presently, using the RNA expression data derived from multiple independent PCa-related studies, we constructed a high confidence and PCa-specific core ceRNA network by employing three lncRNA-gene inference approaches and key node filter strategies and then established a logistic model and risk score formula to evaluate its diagnostic and prognostic values, respectively. The core ceRNA network consists of 10 nodes, all of which are significantly associated with clinical outcomes. Combination of expression of the 10 ceRNAs with a logistic model achieved AUC of ROC and PR curve up to ∼96 and 99% in excluding normal prostate samples, respectively. Additionally, a risk score formula constructed with the ceRNAs exhibited significant association with disease-free survival. More importantly, utilizing the expression of RNAs in the core ceRNA network as a molecular signature, the TCGA-PRAD cohort was divided into four novel clinically relevant subgroups with distinct expression patterns, highlighting a feasible way for improving patient stratification in the future. Overall, we constructed a PCa-specific core ceRNA network, which provides diagnostic and prognostic value.
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http://dx.doi.org/10.3389/fgene.2020.00785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406720PMC
July 2020

Continuous chromatography with multi-zone and multi-column dynamic tandem techniques for the isolation and enrichment of class compounds from natural products of Panax notoginseng.

J Chromatogr A 2020 Oct 19;1629:461499. Epub 2020 Aug 19.

School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China; Institute of Chemistry and Applications of Plant Resources, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

Efficient and economical separation and enrichment of high-content class compounds from complex natural plants are of great importance. This study describes a novel continuous chromatography system (CCS) with multi-zone and multi-column dynamic tandem techniques for the efficient and economical separation and enrichment of high-content class compounds from natural products. The CCS was split into eight zones (each zone covered 2 or 3 columns connected dynamically in a series) via a multi-channel logic control valve to continuously and automatically separate and enrich class compounds from complex natural plants. CCS separation conditions were optimized by static and dynamic adsorption and desorption experiments. With the CCS system, 120.82 kg of Panax notoginseng saponins (PNS) was isolated from 1.0 t of P. notoginseng. Importantly, the total contents of five main saponins (R, Rg, Re, Rb, and Rd) in PNS exceeded 90%, and the recovery rate exceeded 85%. In addition, this separation system enhanced the separation efficiency and decreased the mobile phase used. Thus, CCS with multi-zone and multi-column dynamic tandem techniques is an efficient and economical method for the large-scale preparation of high-content total saponins from P. notoginseng and will have wide application prospects, especially in the large-scale preparation of high-content class compounds from natural plants.
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http://dx.doi.org/10.1016/j.chroma.2020.461499DOI Listing
October 2020

An Exo-Polygalacturonase Pgc4 Regulates Aerial Hyphal Growth and Virulence in f. sp. race 4.

Int J Mol Sci 2020 Aug 16;21(16). Epub 2020 Aug 16.

Laboratory of Physiological Plant Pathology, South China Agricultural University, Guangzhou 510642, China.

f. sp. race 4 (Foc4) causes Fusarium wilt that affects banana plants, and hence, the molecular mechanisms of its virulence need to be investigated. We purified an exo-polygalacturonase (exo-PG), Pgc4, from Foc4. Pgc4 has an apparent molecular weight of 50.87 kDa based on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. We further performed its sequence analysis and biochemical characterization. The two genes encoding Pgc4 from Foc4 and Foc1 were 1434 bp in length and encoded 477 amino acids with differences, due to some nucleotide differences between the two. The m and max values of Pgc4 purified from Foc4 were determined to be 0.45 mg/mL and 105.26 Units·mg·protein ·min, respectively. The recombinant proteins, r-Foc1-Pgc4 and r-Foc4-Pgc4, were expressed and purified from and showed optimal Pgc4 activity at 55 °C and pH 4.0; both could induce tissue maceration and necrosis in the "Guangfen-1" and "Baxi" varieties of banana but to a different extent. Phenotypic assays and complementation analyses revealed that, compared to the wild-type, the generated Foc4Δ mutant strain showed a lower aerial hyphal growth, grew slower, and had a reduced virulence. Therefore, our results demonstrate the function of Pgc4 as a pathogenicity factor of Foc4.
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http://dx.doi.org/10.3390/ijms21165886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461583PMC
August 2020

Systems pharmacology reveals the multi-level synergetic mechanism of action of Ginkgo biloba L. leaves for cardiomyopathy treatment.

J Ethnopharmacol 2021 Jan 15;264:113279. Epub 2020 Aug 15.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Shihezi, Xinjiang, 832002, China; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang, Jiangsu, 222002, China; College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China. Electronic address:

Ethnopharmacological Relevance: Cardiomyopathy is a common cause of heart failure and may lead to increased risk of sudden cardiac death, lacking simple, safe and effective treatment strategies due to unclear pathogenesis. Ginkgo biloba L. leaves (GBLs), a traditional Chinese medicine (TCM), has been widely used in clinical medicine for improving blood circulation, and was demonstrated to be effective on cardiomyopathy in preclinical studies. However, because of the widely known holistic therapeutic philosophy via multi-target and multi-pathway effect for most TCMs, to explore its underlying molecular mechanisms of action (MoA) remains a great challenge.

Aim Of Study: Decipher the underlying MoA of GBLs for cardiomyopathy treatment: Study design and methods: An integrated systems pharmacology framework was employed to screen potential active compounds, identify therapeutic targets, explore the action pathways and verify mechanisms of GBLs with in vitro experiments.

Results: We firstly confirmed the therapeutic effect of GBLs on cardiomyopathy and subsequently screened 27 active compounds from GBLs according to their pharmacokinetic properties. Then Probability Ensemble Approach was applied to identify the compound combinations that exert synergetic effect from GBLs. Network analysis and functional enrichment analysis demonstrated that these compounds exhibit synergistic therapeutic effect by acting on multiple targets and thereby regulating multiple pathways mainly involved in pro-survival, anti-apoptotic and anti-inflammatory processes. Finally, using a doxorubicin-induced myocardial injury model, therapeutic effect of ginkgolide A, ginkgolide B, isorhamnetin, as well as their synergistic effect on PI3K-AKT and NF-κB signaling pathways were validated in vitro. Importantly, we demonstrated that Ginkgo diterpene lactone meglumine injection (GDJ), an approved injection derived from GBLs, could be a promising agent for cardiomyopathy treatment.

Conclusion: Collectively, the multi-level synergetic mechanism of GBLs on cardiomyopathy treatment was demonstrated with systems pharmacology approach, providing a paradigm for deciphering the complicated MoA of TCMs.
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http://dx.doi.org/10.1016/j.jep.2020.113279DOI Listing
January 2021

Novel Therapeutic Targets for Hypoxia-Related Cardiovascular Diseases: The Role of HIF-1.

Front Physiol 2020 15;11:774. Epub 2020 Jul 15.

State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, China.

Insufficient oxygen availability (hypoxia) is a precursor to numerous cardiovascular diseases, including atherosclerosis, pulmonary hypertension, and heart failure. The main site of hypoxic injury in the human body is the mitochondria, where oxygen acts as the final electron acceptor in the process of oxidative phosphorylation. Hypoxia-inducible factor (HIF) is activated in hypoxic conditions and acts as an important modulator of diverse target genes in the human body. The downstream genes of HIF include vital modulators of cardiovascular-related signaling pathways. Therefore, it is hypothesized that HIF represents a potential therapeutic target for the treatment and prevention of cardiovascular diseases. In this short review, we introduce the pathophysiology of hypoxic injury in cardiovascular disease, and we conclude from convincing evidence that HIF can modulate relevant cardioprotective signaling pathways.
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http://dx.doi.org/10.3389/fphys.2020.00774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375027PMC
July 2020

Spinosin protects N2a cells from H O -induced neurotoxicity through inactivation of p38MAPK.

J Pharm Pharmacol 2020 Nov 15;72(11):1607-1614. Epub 2020 Jul 15.

Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.

Objectives: Previous studies have suggested that spinosin (SPI) exerted neuroprotective effects through inhibition of oxidative damage, but the underlying mechanisms are still unclear. Herein, the mechanisms underlying the protective effects of SPI against oxidative stress induced by hydrogen peroxide (H O ) were examined in neuro-2a (N2a) mouse neuroblastoma cells.

Methods: N2a cells were pretreated with H O for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aβ production were determined by ELISA assay. Levels of expression of c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), p-ERK, p38 mitogen-activated protein kinase (p38MAPK), p-p38MAPK, p-Tau (Ser199), p-Tau (Ser202), p-Tau (Ser396), synaptophysin (SYP) and postsynaptic scaffold postsynaptic density-95 (PSD-95) were detected by Western blot analysis.

Key Findings: Our results showed that H O treatment enhanced intracellular ROS production in N2a cells. SPI prevented H O -induced oxidative damage via inhibiting Aβ production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H O -increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H O -induced oxidative damage in N2a cells.

Conclusions: Our findings suggest that SPI protects N2a cells from H O -induced oxidative damage through inactivation of p38MAPK.
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http://dx.doi.org/10.1111/jphp.13334DOI Listing
November 2020

Immobilization of GH78 α-L-Rhamnosidase from with High-Temperature-Resistant Magnetic Particles FeO-SiO-NH-Cellu-ZIF8 and Its Application in the Production of Prunin Form Naringin.

J Microbiol Biotechnol 2021 Mar;31(3):419-428

Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, 159 Long Pan Road, Nanjing 210037, P.R. China.

To efficiently recycle GH78 thermostable rhamnosidase (TpeRha) and easily separate it from the reaction mixture and furtherly improve the enzyme properties, the magnetic particle FeO-SiO-NH-Cellu-ZIF8 (FSNcZ8) was prepared by modifying FeO-NH with tetraethyl silicate (TEOS), microcrystalline cellulose and zinc nitrate hexahydrate. FSNcZ8 displayed better magnetic stability and higher-temperature stability than unmodified FeO-NH (FN), and it was used to adsorb and immobilize TpeRha from 13995. As for properties, FSNcZ8-TpeRha showed optimal reaction temperature and pH of 90°C and 5.0, while its highest activity approached 714 U/g. In addition, FSNcZ8-TpeRha had better higher-temperature stability than FN. After incubation at 80°C for 3 h, the residual enzyme activities of FSNcZ8-TpeRha, FN-TpeRha and free enzyme were 93.5%, 63.32%, and 62.77%, respectively. The organic solvent tolerance and the monosaccharides tolerance of FSNcZ8-TpeRha, compared with free TpeRha, were greatly improved. Using naringin (1 mmol/l) as the substrate, the optimal conversion conditions were as follows: FSNcZ8-TpeRha concentration was 6 U/ml; induction temperature was 80°C; the pH was 5.5; induction time was 30 min, and the yield of products was the same as free enzyme. After repeating the reaction 10 times, the conversion of naringin remained above 80%, showing great improvement of the catalytic efficiency and repeated utilization of the immobilized α-L-rhamnosidase.
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http://dx.doi.org/10.4014/jmb.2004.04055DOI Listing
March 2021

Guizhi Fuling Capsule Exhibits Antidysmenorrhea Activity by Inhibition of Cyclooxygenase Activity.

Evid Based Complement Alternat Med 2020 23;2020:8607931. Epub 2020 May 23.

State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu 222001, China.

Guizhi Fuling capsule (GZFLc) is a modern preparation from traditional Chinese Medicine. Guizhi Fuling was first prescribed by Zhang Zhongjing almost two thousand years ago for the treatment of primary dysmenorrhea. It has also been used to treat uterine fibroids, dysfunctional uterine bleeding, and endometriosis. Although effective against dysmenorrhea clinically, there are limited information on the mechanism of its action. The major components responsible for the activity are not well defined. The aim of this study has been to elucidate a mechanism that may facilitate the development of a bioactivity-based assay for quality control during drug formulation and manufacturing. Using an oxytocin-induced mouse dysmenorrhea model, we showed that oral administration of GZFLc at 150 and 300 mg/kg, dosages relevant to clinic usages, significantly suppressed oxytocin-induced writhing response. The antidysmenorrhea effect was also demonstrated by a rotarod assay. We showed that GZFLc treatment significantly prolonged the hanging time of mice on the rotating rod. Histological studies showed that GZFLc treatment reduced lamina propria edema, while no effect on COX2 expression was detected. GZFLc instead exhibited direct inhibitory effect against COX2, a critical enzyme that catalyzes arachidonic acid conversion to prostaglandins. By HPLC profiling, we showed that paeoniflorin, paeonol, and cinnamaldehyde are the major components from the corresponding plants. At 5 and 10 mg/kg, both paeoniflorin and paeonol were active against induced dysmenorrhea. The study not only links GZFLc antidysmenorrhea activity to COX2 inhibition but also uncovers a mechanism of action by which an assay can be developed for bioefficacy evaluation of GZFLc.
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http://dx.doi.org/10.1155/2020/8607931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262657PMC
May 2020

Systematically characterized mechanism of treatment for lumbar disc herniation based on Yaobitong capsule ingredient analysis in rat plasma and its network pharmacology strategy by UPLC-MS/MS.

J Ethnopharmacol 2020 Oct 10;260:113097. Epub 2020 Jun 10.

School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, China. Electronic address:

Ethnopharmacological Relevance: Yaobitong capsule (YBTC) was a traditional Chinese medicine (TCM) and it had clinically used to treat lumbar disc degeneration (LDH) for a long time. However, the active ingredients of YBTC absorption into the plasma and its pharmacological mechanism of treatment for LDH still remained unclear.

Aim Of The Study: In this study, our research committed to identify the absorbed active ingredients of YBTC in rat plasma, and it may be a potential mechanism of action on LDH by the biological targets regulating related pathways.

Materials And Methods: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to identify the absorption components and metabolites of YBTC in rat plasma, and the network pharmacology was further investigated to illuminate its potential mechanism of treatment for LDH by the biological targets regulating related pathways.

Results: The network analysis found that 56 components were identified as its main active ingredients including ginsenoside Rg1, ginsenoside Rb1, senkyunolide H, and tetrahydropalmatine, etc. Combining with biological process, cellular component and molecular functions of GO, and kyotoencyclopedia of genes and genomes pathway enrichment analysis to perform network topology analysis on core targets. These active ingredients regulated 29 mainly pathways by 87 direct target genes including MAPK, Ras, PI3K-Akt, and NF-kappa B signaling pathway, etc. CONCLUSION: In this study, the absorption active ingredients of YBTC in rat plasma were firstly combined with the network pharmacology investigation to elucidate its biological mechanism of treatment for LDH in vivo. It inhibited excessive inflammatory reactions, thereby reducing the sensitivity of the nerves to reduce pain and relieve LDH, and potential medicine targets could be identified to clarify the molecular mechanism of YBTCs' regulation of LDH.
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http://dx.doi.org/10.1016/j.jep.2020.113097DOI Listing
October 2020

VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway.

CNS Neurosci Ther 2020 09 27;26(9):952-961. Epub 2020 May 27.

Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Introduction: To investigate the protective effect of VX-765 on human umbilical mesenchymal stem cells (HUMSCs) in stroke and its mechanism.

Materials And Methods: Mouse models of ischemic stroke were established using the distal middle cerebral artery occlusion (dMCAO) method. The dMCAO mice were accordingly transplanted with HUMSCs, VX-765-treated HUMSCs, or VX-765 + MHY185-treated HUMSCs. The HUMSCs were inserted with green fluorescent protein (GFP) for measurement of transplantation efficiency which was determined by immunofluorescence assay. Oxygen-glucose deprivation (OGD) was applied to mimic ischemic environment in vitro experiments, and the HUMSCs herein were transfected with AMPK inhibitor Compound C or autophagy inhibitor 3-MA. MTT assay was used to test the toxicity of VX-765. TUNEL staining and ELISA were applied to measure the levels of apoptosis and inflammatory cytokines (IL-1β, IL-6, and IL-10), respectively. The expressions of autophagy-associated proteins, AMPK, and mTOR were detected by Western blotting. TTC staining was applied to reveal the infarct lesions in the brain of dMCAO mice.

Results: The pro-inflammatory cytokines, TUNEL-positive cells, and p-mTOR were decreased while the anti-inflammatory cytokine, autophagy-related proteins, and p-AMPK were increased in HUMSCs treated with VX-765 under OGD condition. Different expression patterns were found with the above factors after transfection of 3-MA or Compound C. The pro-inflammatory cytokines, TUNEL-positive cells, and infarct sections were decreased while the anti-inflammatory cytokine and autophagy-related proteins were increased in dMCAO mice transplanted with VX-765-treated HUMSCs compared to those transplanted with HUMSCs only. The autophagy was inhibited while p-mTOR was up-regulated after transfection of MHY.

Conclusion: VX-765 protects HUMSCs against stroke-induced apoptosis and inflammatory responses by activating autophagy via the AMPK/mTOR signaling pathway in vivo and in vitro.
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http://dx.doi.org/10.1111/cns.13400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415204PMC
September 2020

A Fast Dynamic Evolutionary Multiobjective Algorithm via Manifold Transfer Learning.

IEEE Trans Cybern 2021 Jul 23;51(7):3417-3428. Epub 2021 Jun 23.

Many real-world optimization problems involve multiple objectives, constraints, and parameters that may change over time. These problems are often called dynamic multiobjective optimization problems (DMOPs). The difficulty in solving DMOPs is the need to track the changing Pareto-optimal front efficiently and accurately. It is known that transfer learning (TL)-based methods have the advantage of reusing experiences obtained from past computational processes to improve the quality of current solutions. However, existing TL-based methods are generally computationally intensive and thus time consuming. This article proposes a new memory-driven manifold TL-based evolutionary algorithm for dynamic multiobjective optimization (MMTL-DMOEA). The method combines the mechanism of memory to preserve the best individuals from the past with the feature of manifold TL to predict the optimal individuals at the new instance during the evolution. The elites of these individuals obtained from both past experience and future prediction will then constitute as the initial population in the optimization process. This strategy significantly improves the quality of solutions at the initial stage and reduces the computational cost required in existing methods. Different benchmark problems are used to validate the proposed algorithm and the simulation results are compared with state-of-the-art dynamic multiobjective optimization algorithms (DMOAs). The results show that our approach is capable of improving the computational speed by two orders of magnitude while achieving a better quality of solutions than existing methods.
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http://dx.doi.org/10.1109/TCYB.2020.2989465DOI Listing
July 2021
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