Publications by authors named "Li-Jun Zhang"

244 Publications

Cardioprotection of an I channel agonist on L-thyroxine induced rat ventricular remodeling.

Am J Transl Res 2021 15;13(8):8683-8696. Epub 2021 Aug 15.

Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, The Department of Physiology, Shanxi Medical University Taiyuan, China.

Downregulation of inward rectifier potassium (I) channel is a hallmark in cardiac hypertrophy and failure. The cardioprotection of zacopride (a selective I agonist) and underlying mechanisms were investigated in L-thyroxine (T4) or Triiodothyronine (T3)-induced cardiac remodeling. In the study, adult male Sprague-Dawley (SD) rats were randomly divided into control, L-thyroxine, L-thy+zacopride, and L-thy+zacopride+chloroquine (an I antagonist) groups. Echocardiography, histopathology, TUNEL assay, western blotting and confocal imaging for intracellular Ca fluorescence were performed. In the study, zacopride and nifedipine (a LTCC blocker) were used to compare their effects on Kir2.1, SAP97, autophagy, and [Ca] in H9C2 (2-1) cardiomyocytes. Zacopride treatment attenuated L-thyroxine- or T3 induced cardiac remodeling and dysfunction which manifested as cardiac hypertrophy and collagen deposition, dilated ventricle, decreased ejection fraction (EF), increased cardiomyocytes apoptosis, hyper-activation of CaMKII and PI3K/Akt/mTOR signaling, decreased cardiac autophagy, and increased expression of integrin β3. The cardioprotection of zacopride is strongly associated with the upregulation of I, SAP97, and [Ca] homeostasis in cardiomyocytes. I antagonist chloroquine or BaCl reversed these effects. Nifedipine could attenuate intracellular Ca overload with no significant effects on I, SAP97, and autophagy. This study showed that zacopride could improve cardiac remodeling via facilitating Kir2.1 forward trafficking, and negatively regulating calcium-activated and PI3K/Akt/mTOR signalings, in an I-dependent manner.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430128PMC
August 2021

Oxidative stress in leukemia and antioxidant treatment.

Chin Med J (Engl) 2021 Jul 12;134(16):1897-1907. Epub 2021 Jul 12.

Department of Hematology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.

Abstract: Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.
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http://dx.doi.org/10.1097/CM9.0000000000001628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382483PMC
July 2021

V617F mutation to calreticulin mutation in an essential thrombocythemia patient: A case report.

Indian J Cancer 2021 Jul-Sep;58(3):431-433

Department of Hematology, The No.1 Hospital of Baoding, Baoding, Hebei Province, China.

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http://dx.doi.org/10.4103/ijc.IJC_106_20DOI Listing
August 2021

Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder.

J Clin Sleep Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan City), Huainan, 2P. R. China.

Study Objectives: The aims of this study were to explore changes in the telomere length (relative telomere repeat copy/single-copy gene, T/S ratio) and serum neurofilament light chain (sNfL) levels in female patients with chronic insomnia disorder (CID), examine their relationships with emotional abnormalities and cognitive impairment, and determine whether these 2 indicators were independently associated with sleep quality.

Methods: The CID group contained 80 patients diagnosed with CID, and 51 individuals constituted a healthy control group (HC). Participants completed sleep, emotion, and cognition assessments. Telomere length was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assay was used to determine sNfL concentrations.

Results: Relative to the HC group, the CID group had elevated Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety scale-14 (HAMA-14), and Hamilton Depression Rating scale-17 (HAMD-17) scores and reduced Montreal Cognitive Assessment scale (MoCA) scores, a decreased T/S ratio, and an increased sNfL concentration. Subgroup analysis according to various CID-associated sleep factors showed that poor sleep performance corresponded with a lower T/S ratio. Higher anxiety levels and more cognitive dysfunction correlated with shorter telomere lengths. The T/S ratio negatively correlated with age, whereas the sNfL concentration positively correlated with age in the CID group. The PSQI score negatively correlated with the T/S ratio but did not correlate with sNfL levels. Multiple linear regression analysis showed that the T/S ratio had a negative and independent effect on PSQI scores.

Conclusions: The CID group had shorter telomeres and higher sNfL concentrations, and reduced telomere length independently affected sleep quality.
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http://dx.doi.org/10.5664/jcsm.9574DOI Listing
July 2021

Genome-wide gene expression profiles of the pea aphid (Acyrthosiphon pisum) under cold temperatures provide insights into body color variation.

Arch Insect Biochem Physiol 2021 Sep 16;108(1):e21797. Epub 2021 Jul 16.

State Key Laboratory of Grassland Agro-ecosystems, Lanzhou University, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs; Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China.

Cold temperatures are one of the factors influencing color polymorphisms in Acyrthosiphon pisum, resulting in a change from a red to greenish color. Here we characterized gene expression profiles of A. pisum under different low temperatures (1°C, 4°C, 8°C, and 14°C) and durations (3, 6, 12, and 24 h). The number of differentially expressed genes (DEGs) increased as temperatures decreased and time increased, but only a small number of significant DEGs were identified. Genes involved in pigment metabolism were downregulated. An interaction network analysis for 506 common DEGs in comparisons among aphids exposed to 1°C for four durations indicated that a cytochrome P450 gene (CYP, LOC112935894) significantly downregulated may interact with a carotenoid metabolism gene (LOC100574964), similar to other genes encoding CYP, lycopene dehydrogenase and fatty acid synthase. We proposed that the body color shift in A. pisum responding to low temperatures may be regulated by CYPs.
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http://dx.doi.org/10.1002/arch.21797DOI Listing
September 2021

Enhanced anti-tumor efficacy by inhibiting HIF-1α to reprogram TAMs core-satellite upconverting nanoparticles with curcumin mediated photodynamic therapy.

Biomater Sci 2021 Sep 28;9(19):6403-6415. Epub 2021 Sep 28.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Tumor hypoxic stress after photodynamic therapy (PDT) will be inevitably exacerbated by the vascular blocking effects and oxygen consumption in the tumor microenvironment (TME) which usually leads to compromised efficacy and clinical performance. Increasing evidence links the hypoxia induced up-regulation of hypoxia inducible factor 1α (HIF-1α) with immunosuppressive TME, including the polarization of M2 phenotype tumor associated macrophages (TAMs), which promote the recurrence and metastasis. Here, we reported NIR-triggered core-satellite upconverting nanoparticles (CSNPs) with curcumin (Cur) embedded as a difunctional photosensitizer, which could realize PDT in deep tumors with long excitation wavelength (980 nm) and reverse the immunosuppressive TME induced by up-regulated HIF-1α at the same time. This Cur-loaded CSNPs (Cur-CSNPs)-mediated PDT could successfully induce the immunogenic cell death (ICD) of triple negative breast cancer (TNBC) cell lines (4T1 and MDA-MB-231) and repolarize the 4T1 cells co-cultured TAMs from pro-tumor M2 to the anti-tumor M1 phenotype. Furthermore, Cur-CSNPs-mediated PDT could suppress the 4T1 tumor growth in primary and distant sites through the synergistic immunotherapeutic effects by priming M1 type TAMs and CD4/CD8 T cells' infiltration. Our data highlight the novel application of CSNPs-embedded Cur as a difunctional photosensitizer to enhance the anti-tumor efficacy of PDT.
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http://dx.doi.org/10.1039/d1bm00675dDOI Listing
September 2021

The Cyr61 Is a Potential Target for Rotundifuran, a Natural Labdane-Type Diterpene from L., to Trigger Apoptosis of Cervical Cancer Cells.

Oxid Med Cell Longev 2021 22;2021:6677687. Epub 2021 May 22.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC less than 10 M), via induction of apoptosis , and the antitumor effect of RTF is further confirmed on the HeLa cell-inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species- (ROS-) induced mitochondrial-dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability- (DARTS-) combined mass spectrometry (DARTS-MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.
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http://dx.doi.org/10.1155/2021/6677687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218918PMC
May 2021

Application of omics- and multi-omics-based techniques for natural product target discovery.

Biomed Pharmacother 2021 Sep 25;141:111833. Epub 2021 Jun 25.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Natural products continue to be an unparalleled source of pharmacologically active lead compounds because of their unprecedented structures and unique biological activities. Natural product target discovery is a vital component of natural product-based medicine translation and development and is required to understand and potentially reduce mechanisms that may be associated with off-target side effects and toxicity. Omics-based techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, have become recognized as effective tools needed to construct innovative strategies to discover natural product targets. Although considerable progress has been made, the successful discovery of natural product targets remains a challenging time-consuming process that has come to increasingly rely on the effective integration of multi-omics-based technologies to create emerging panomics (a.k.a., integrative omics, pan-omics, multiomics)-based strategies. This review summarizes a series of successful studies regarding the application of integrative omics-based methods in natural product target discovery. The advantages and disadvantages of each technique are discussed, with a particular focus on the systematic integration of multi-omics strategies. Further, emerging micro-scale single-cell-based techniques are introduced, especially to deal with minute natural product samples.
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http://dx.doi.org/10.1016/j.biopha.2021.111833DOI Listing
September 2021

Pleural Fluid GSDMD Is a Novel Biomarker for the Early Differential Diagnosis of Pleural Effusion.

Front Microbiol 2021 7;12:620322. Epub 2021 Jun 7.

Department of Laboratory Medicine, The Second Hospital of Chongqing Medical University, Chongqing, China.

Objective: Gasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in pleural effusion (PE) remains unknown.

Methods: Sandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with a definite cause of PE, including transudative PE, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). The diagnostic accuracy of Light's criteria vs. the new marker GSDMD was performed. Clinical follow-up of 40 cases of PPE was conducted and divided into efficacy and non-efficacy groups according to the therapeutic outcome. Nucleated cells (NCs) in PE were isolated and further infected with bacteria to verify the cell source of GSDMD.

Results: The diagnostic accuracy of GSDMD for the diagnosis of PE were 96% (sensitivity) and 94% (specificity). The receiver operating characteristic (ROC) curve indicated that GSDMD can be an efficient biomarker for the differential diagnosis of transudative PE and other groups (all AUC > 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the cut-off value was 18.40 ng/mL. Moreover, the same cut-off value of PPE and MPE was 9.35 ng/mL. The combination of GSDMD, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4, which could predict the therapeutic effect at an early stage, was 0.945 ( < 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs.

Conclusion: GSDMD and its combination are candidates as a potentially novel biomarker not only to separate PEs early and effectively, but also monitor disease progression.
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http://dx.doi.org/10.3389/fmicb.2021.620322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215111PMC
June 2021

Targeting Endothelial Cell-Specific Molecule 1 Protein in Cancer: A Promising Therapeutic Approach.

Front Oncol 2021 24;11:687120. Epub 2021 May 24.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Despite the dramatic advances in cancer research in the past few years, effective therapeutic strategies are urgently needed. Endothelial cell-specific molecule 1 (ESM-1), a soluble dermatan sulfate proteoglycan, also known as endocan, serves as a diagnostic and prognostic indicator due to its aberrant expression under pathological conditions, including cancer, sepsis, kidney diseases, and cardiovascular disease. Significantly, ESM-1 can promote cancer progression and metastasis through the regulation of tumor cell proliferation, migration, invasion, and drug resistant. In addition, ESM-1 is involved in the tumor microenvironment, containing inflammation, angiogenesis, and lymph angiogenesis. This article reviews the molecular and biological characteristics of ESM-1 in cancer, the underlying mechanisms, the currently clinical and pre-clinical applications, and potential therapeutic strategies. Herein, we propose that ESM-1 is a new therapeutic target for cancer therapy.
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http://dx.doi.org/10.3389/fonc.2021.687120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181400PMC
May 2021

The complete mitochondrial genome of (Hemiptera: Pentatomidae) and phylogenetic analysis.

Mitochondrial DNA B Resour 2021 Apr 8;6(4):1326-1327. Epub 2021 Apr 8.

State Key Laboratory of Grassland Agro-Ecosystems, Lanzhou University, Lanzhou, China.

Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of (Hemiptera: Pentatomidae). This mitogenome was 15,118 bp long, comprising of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes ( and ) and a large non-coding control region. The mitogenome with an A + T content of 76.0%, presented a positive AT-skew (0.11) and a negative GC-skew (-0.13). Ten PCGs started with a typical ATN codon, two PCGs started with TTG (, ), whereas the remaining one used AAC (). All tRNAs had a typical secondary cloverleaf structure, except for which lacked the dihydrouridine arm. The Bayesian phylogenetic analysis based on mitogenomic data supported a sister relationship of and from the same tribe Nezarini and recovered a phylogeny of Pentatominae: (Menidini + (Strachiini + (Pentatomini + ((Cappaeini + Halyini) + (Eysarcorini + (Nezarini + Carpocori)))))).
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http://dx.doi.org/10.1080/23802359.2021.1909442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043517PMC
April 2021

Narciclasine inhibits LPS-induced neuroinflammation by modulating the Akt/IKK/NF-κB and JNK signaling pathways.

Phytomedicine 2021 May 9;85:153540. Epub 2021 Mar 9.

Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Gangwon-do, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea; Department of Integrative Biological Sciences and Industry, Sejong University, Seoul 05006, Republic of Korea. Electronic address:

Background: Neuroinflammation is defined as innate immune system activation in the central nervous system, and is a complex response involved in removing pathogens, toxic components, and dead cells by activating microglial cells. However, over-activated microglia have been implicated in the pathogenesis of neurodegenerative diseases, because they release large amounts of neurotoxic factors. Thus, inhibiting microglial activation may represent an attractive approach for preventing neuroinflammatory disorders. The objective of this study was to investigate the effect of narciclasine (NA) on lipopolysaccharide (LPS)-induced neuroinflammation by evaluating related markers and neurotoxic factors.

Methods: BV-2 cells were pre-incubated with NA at 0.1, 0.2, and 0.3 µM for 1h, and then co-treated with LPS for 12 h. Cellular medium and lysates were measured using a nitric oxide assay, enzyme-link immunosorbent assay (ELISA), western blotting, kinase activity assay, luciferase assay, and immunofluorescence assay. C57BL/6N mice were orally administered NA and intraperitoneally injected with LPS, and the cerebral cortex was examined using western blotting and immunofluorescence assays.

Results: NA showed novel pharmacological activity, inhibiting pro-inflammatory factors, including TNF-α, IL-6, IL-18, NO, and PGE, but increasing the anti-inflammatory cytokines IL-10 and TGF-β1 in LPS-induced microglial cells. Moreover, NA also attenuated the LPS-induced mRNA and proteins of iNOS and COX-2. The mechanistic study indicated that NA attenuates the secretion of pro-inflammatory factor by down-regulating the Akt/IKK/NF-κB and JNK signaling pathways, and directly inhibits the catalytic activity of IKKα/β. Furthermore, we found that NA also reduced the expression of the microglial markers Iba-1, COX-2, and TNF-α in the mouse brain.

Conclusion: NA inhibits the over-expression of pro-inflammatory factors but it promotes anti-inflammatory cytokines by down-regulating the Akt/IKK/NF-κB and JNK signaling pathways in experimental models. Thus, NA may be a potential candidate for relieving neuroinflammation.
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http://dx.doi.org/10.1016/j.phymed.2021.153540DOI Listing
May 2021

Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade.

Int J Mol Med 2021 05 2;47(5). Epub 2021 Mar 2.

Department of Ophthalmology, The Third People's Hospital of Dalian, Non‑Directly Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116033, P.R. China.

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G‑actin/F‑actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)‑2/MMP‑9, caspase‑3/caspase‑9/poly(ADP‑ribose) polymerase (PARP)/cytochrome , were determined by western blot analysis to assess the effects of targeting LIMK. The findings were verified by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G‑actin could be co‑transferred to the mitochondria to initiate the mitochondrial‑cytochrome  pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.
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http://dx.doi.org/10.3892/ijmm.2021.4901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952248PMC
May 2021

[Evaluation of pre-harvest sprouting resistance of wheat varieties from different ecological regions.]

Ying Yong Sheng Tai Xue Bao 2020 Dec;31(12):4161-4170

Center of Agricultural Technology Extension of Zhenping, Zhenping 474250, Henan, China.

The pre-harvest sprouting (PHS) resistance of 137 wheat varieties from different regions was evaluated and the relative germination index (RGI) was calculated. The relationships between PHS and grain quality traits, amylase activity and related gene expression level of these varieties were analyzed. The results showed that wheat varieties from the middle and lower reaches of Yangtze River Valley winter wheat region had the lowest RGI value and the highest ratio of resistant pre-harvest sprouting wheat varieties, followed by the varieties from the upper reach of Yangtze River Valley winter wheat region and from the Yellow and Huai River Valley. Red-grain wheat had lower RGI than white-grain wheat. RGI was positively correlated with seed length, seed width, and spikelet number, but not correlated with other grain traits (panicle type, ear color, ear length, and spikelet density, grain per spike and 1000-grain weight). RGI was negatively associated with the test weight, dough development time, and flour yield, but not with other quality indices (protein content, wet gluten content, water absorption, stability time, sedimentation, extension area, extensibility and max resistance). Amylase activity of different varieties increased with seed imbibition time. RGI was positively associated with α-amylase activity after germinating for 24-72 hours. The cluster analysis results of resistant varieties were consistent with the PHS resistance evaluation after 48 hours. RGI was positively associated with the related gene expression with seed imbibition time.
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http://dx.doi.org/10.13287/j.1001-9332.202012.022DOI Listing
December 2020

Mitochondrial genome of (Coleoptera: Chrysomelidae: Eumolpinae) and phylogenetic analysis.

Mitochondrial DNA B Resour 2020 Jan 16;5(1):667-668. Epub 2020 Jan 16.

Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Grassland Agro-Ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou, People's Republic of China.

Here, we determined the nearly complete mitochondrial genome (mitogenome) of (Coleoptera: Chrysomelidae: Eumolpinae), an important insect pest on in Northwestern China. This mitogenome was 14,451 bp long, encoding 13 protein-coding genes (PCGs), 21 transfer RNA genes (tRNAs), and 2 ribosomal RNA genes. The mitogenome presented an A + T content of 75.11%, with a positive AT-skew (0.064) and a negative GC-skew (-0.192). Ten PCGs started with a typical ATN codon, whereas the remaining three PCGs started with AAC () and TTG ( and ). All tRNAs had a typical secondary cloverleaf structure, except for which lacked the dihydrouridine arm. Bayesian phylogenetic analysis based on the nucleotide sequences of 13 PCGs recovered a phylogeny within Chrysomelidae: (((Chrysomelinae + Galerucinae), (((Eumolpinae, Lamprosomatinae), Cassidinae), Criocerinae)), Bruchinae).
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http://dx.doi.org/10.1080/23802359.2020.1711823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748835PMC
January 2020

CASC2 inhibits the growth, migration, and invasion of thyroid cancer cells through sponging miR-18a-5p/FIH1 axis.

Kaohsiung J Med Sci 2021 Apr 17;37(4):268-275. Epub 2020 Dec 17.

Department of Thyroid Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH-1) was potentially targeted by miR-18a-5p, which was confirmed by luciferase reporter assay. Upregulation of FIH-1 abrogated the promotive effect of miR-18a-5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR-18a-5p, thereby regulating the expression of FIH-1. These data elucidated the CASC2/miR-18a-5p ceRNA network in thyroid cancer pathogenesis.
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http://dx.doi.org/10.1002/kjm2.12331DOI Listing
April 2021

Mesoporous silica nanoparticles: facile surface functionalization and versatile biomedical applications in oncology.

Acta Biomater 2020 10 7;116:1-15. Epub 2020 Sep 7.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Mesoporous silica nanoparticles (MSNs) have received increasing interest due to their tunable particle size, large surface area, stable framework, and easy surface modification. They are increasingly being used in varying applications as delivery vehicles including bio-imaging, drug delivery, biosensors and tissue engineering etc. Precise structure control and the ability to modify surface properties of MSNs are important for their applications. This review summarises the different synthetic methods for the preparation of well-ordered MSNs with tunable pore volume as well as the approaches of drugs loading, especially highlighting the facile surface functionalization for various purposes and versatile biomedical applications in oncology. Finally, the challenges of clinical transformation of MSNs-based nanomedicines are further discussed.
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http://dx.doi.org/10.1016/j.actbio.2020.09.009DOI Listing
October 2020

Surveillance and molecular epidemiology of Neisseria gonorrhoeae isolates in Shenzhen, China, 2010-2017.

J Glob Antimicrob Resist 2020 12 2;23:269-274. Epub 2020 Sep 2.

National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing, China; Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China. Electronic address:

Objectives: The development and emergence of antimicrobial resistance in Neisseria gonorrhoeae (NG) have become a major public-health problem worldwide. This study aimed to analyse the antimicrobial susceptibility and molecular characteristics of NG isolates in Shenzhen, China.

Methods: A total of 1282 NG isolates were consecutively collected between 2010 and 2017. Patient demographic information was also collected. MICs of ceftriaxone, spectinomycin, ciprofloxacin, azithromycin and penicillin were determined by agar dilution. Isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST).

Results: Among the isolates, 97.4% were resistant to ciprofloxacin and 68.2% to penicillin. Moreover, 5.0% showed decreased susceptibility to ceftriaxone (CRO) and 17.3% were resistant to azithromycin (AZM-R); 1.3% were simultaneously CRO and AZM-R. All isolates were susceptible to spectinomycin. Increasing ceftriaxone MICs were found from 2010 to 2017. A total of 427 sequence types (STs) and 68 genogroups were identified from 724 isolates. ST5061, ST3741 and ST1766 were observed across the study years. ST14638 (n = 3) was predominant among 32 CRO isolates. Prevalent STs were ST5061 (n = 6), ST1866 (n = 5) and ST11133 (n = 5) among 96 AZM-R isolates.

Conclusions: A high prevalence of isolates resistant to ciprofloxacin and penicillin was found in this study. Azithromycin, one antimicrobial of dual antimicrobial therapy recommended by the WHO, showed a high prevalence of resistance. The other, ceftriaxone, can be used continuously in this region owing to lower resistance levels. However, the emergence of CRO and decreasing susceptibility to ceftriaxone indicate that continuous antimicrobial resistance surveillance is essential.
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http://dx.doi.org/10.1016/j.jgar.2020.08.013DOI Listing
December 2020

GPR120 Regulates Pancreatic Polypeptide Secretion From Male Mouse Islets via PLC-Mediated Calcium Mobilization.

Endocrinology 2020 10;161(10)

School of Biomedical Sciences, University of Queensland, Brisbane, Australia.

The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891-stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891-stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.
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http://dx.doi.org/10.1210/endocr/bqaa157DOI Listing
October 2020

Evaluation of the clinical diagnostic value of traditional inflammatory markers and novel biomarkers in intracellular bacterial bloodstream infections.

Cytokine 2020 12 18;136:155238. Epub 2020 Aug 18.

Department of Laboratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address:

Objectives: The clinical symptoms of the patients with intracellular bacterial bloodstream infections (Intra-bac BSIs) are atypical, and no early and accurate diagnostic biomarkers exist, which can easily lead to misdiagnosis, inappropriate and delayed treatment. Therefore, it is imperative to find novel biomarkers to help clinical diagnosis of Intra-bac BSIs. The present study was initiated to evaluate the diagnostic values of traditional inflammatory biomarkers (PCT, WBC and NEU% in identifying the patients with Intra-bac BSIs, and to further explore into the possibility of using suPAR and sCD14-ST as novel biomarkers for Intra-bac BSIs.

Methods: A multi-center retrospective study was conducted in three teaching hospitals in Chongqing. A total of 146 cases with BSIs, including 73 cases with Intra-bac BSIs and 73 cases with extracellular bacterial BSIs (Extra-bac BSIs) were enrolled in the retrospective study. We then prospectively enrolled 34 patients with Intra-bac BSIs, 34 patients with Extra-bac BSIs, 34 patients with viral infection and with normal medical examination results as a control group for further detection of sCD14-ST and suPAR by ELISA.

Results: PCT levels, WBC counts and NEU% in patients with Intra-bac BSIs were not increased or minimally increased, they were significantly lower than that with Extra-bac BSIs (P < 0.05), especially those with the Brucella bacterial BSIs, demonstrated a respective negative rate of 84% and 92% for PCT and WBC counts. In the prospective study, the levels of suPAR and sCD14-ST in both the Intra-bac BSIs and the Extra-bac BSIs groups were significantly higher than those in the viral infection group and normal control group (P < 0.05). The areas under the curve (AUC) of Intra-bac BSIs were 0.830 for suPAR, and 0.855 for sCD14-ST. The sensitivity, specificity, Youden's index for suPAR and sCD14-ST were respectively 76.5%, 88.2%, 0.647 and 94.1%, 64.7%, 0.588.

Conclusions: Our multi-center study demonstrated that while the traditional inflammatory markers such as PCT, WBC counts, NEU% could not be served as promising diagnostic markers for Intra-bac BSIs; CRP can help guide the diagnosis of Intra-bac BSIs; Both suPAR and sCD14-ST could be considered as novel diagnostic biomarkers for Intra-bac BSIs as they showed good diagnostic accuracies in Intra-bac BSIs, especially suPAR.
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http://dx.doi.org/10.1016/j.cyto.2020.155238DOI Listing
December 2020

Advances in the Study of Structural Modification and Biological Activities of Anoplin.

Front Chem 2020 7;8:519. Epub 2020 Jul 7.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Anoplin is an amphipathic, α-helical bioactive peptide from wasp venom. In recent years, pharmaceutical and organic chemists discovered that anoplin and its derivatives showed multiple pharmacological activities in antibacterial, antitumor, antifungal, and antimalarial activities. Owing to the simple and unique structure and diverse biological activities, anoplin has attracted considerable research interests. This review highlights the advances in structural modification, biological activities, and the outlook of anoplin in order to provide a basis for new drug design and delivery.
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http://dx.doi.org/10.3389/fchem.2020.00519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358703PMC
July 2020

Selenium-Containing Protein From Selenium-Enriched Attenuates High Glucose-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated DNA Damage and Regulating MAPK and PI3K/AKT Pathways.

Front Physiol 2020 9;11:791. Epub 2020 Jul 9.

Department of Cardiovascular Medicine, Taian City Central Hospital, Taian, China.

Hyperglycemia is the main feature of diabetes and may increase the risk of vascular calcification (VC), which is an independent predictor for cardiovascular and cerebrovascular diseases (CCD). Selenium (Se) may decrease the risk of CCD, and previous studies confirmed that Se-containing protein from Se-enriched platensis (Se-SP) exhibited novel antioxidant potential. However, the effect of Se-SP against VC has been not investigated. Herein, the protective effect and underlying mechanism of Se-SP against high glucose-induced calcification in mouse aortic vascular smooth muscle cells (MOVAS) were explored. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) results showed time-dependent uptake of Se-SP in MOVAS cells, which significantly inhibited high glucose-induced abnormal proliferation. Se-SP co-treatment also effectively attenuated high glucose-induced calcification of MOVAS cells, followed by decreased activity and expression of alkaline phosphatase (ALP). Further investigation revealed that Se-SP markedly prevented reactive oxygen species (ROS)-mediated DNA damage in glucose-treated MOVAS cells. ROS inhibition by glutathione (GSH) effectively inhibited high glucose-induced calcification, indicating that Se-SP could act as ROS inhibitor to inhibit high glucose-induced DNA damage and calcification. Moreover, Se-SP dramatically attenuated high glucose-induced dysfunction of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathways. Se-SP after Se addition achieved enhanced potential in inhibiting high glucose-induced calcification, which validated that Se-SP as a new Se species could be a highly effective treatment for human CCD.
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http://dx.doi.org/10.3389/fphys.2020.00791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363841PMC
July 2020

Cognitive effort-avoidance in patients with schizophrenia can reflect Amotivation: an event-related potential study.

BMC Psychiatry 2020 07 1;20(1):344. Epub 2020 Jul 1.

Department of Psychology, Wenzhou Medical University, Chashan University Town, Chashan, Wenzhou, 325035, Zhejiang Province, China.

Background: Amotivation is regarded as a core negative symptom in patients with schizophrenia. There are currently no objective methods for assessing and measuring amotivation in the scientific literature, only a trend towards assessing motivation using effort-orientated, decision-making tasks. However, it remains inconclusive as to whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation. Therefore, this study aimed to find out whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation.

Methods: In total, 28 patients with schizophrenia and 27 healthy controls were selected as participants. The demand selection task (DST) was adapted according to the feedback-based Guilty Knowledge Test (GKT) delayed response paradigm, which was combined with the mean amplitude of contingent negative variation (CNV), considered as the criterion of motivation.

Results: Our results showed that: (1) patients with schizophrenia showed a lower CNV amplitude for the target stimuli compared to the probe stimuli, whereas the control group showed the opposite trend (P < 0.05); (2) among patients with schizophrenia, the high cognitive effort-avoidance group showed a smaller CNV amplitude for the target stimuli compared to the probe stimuli, whereas the low cognitive effort avoidance group showed a higher CNV amplitude for the target stimuli compared to the probe stimuli; the opposite trend was observed in the control group (P < 0.05).

Conclusion: These findings support the claim that CNV amplitude can be used as a criterion for detecting amotivation in patients with schizophrenia. Within the context of the DST, the high and low cognitive effort-avoidance of patients with schizophrenia can reflect their state of amotivation; patients with high cognitive effort-avoidance showed severe amotivation.
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http://dx.doi.org/10.1186/s12888-020-02744-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329480PMC
July 2020

Mitochondrial genomes of three Bostrichiformia species and phylogenetic analysis of Polyphaga (Insecta, Coleoptera).

Genomics 2020 09 15;112(5):2970-2977. Epub 2020 May 15.

State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou 730020, People's Republic of China. Electronic address:

Here we determined mitogenomes of three Bostrichiformia species. These data were combined with 51 previously sequenced Polyphaga mitogenomes to explore the higher-level relationships within Polyphaga by using four different mitogenomic datasets and three tree inference approaches. Among Polyphaga mitogenomes we observed heterogeneity in nucleotide composition and evolutionary rates, which may have affected phylogenetic inferences across the different mitogenomic datasets. Elateriformia, Cucujiformia, and Scarabaeiformia were each inferred to be monophyletic by all analyses, as was Bostrichiformia by most analyses based on two datasets with low heterogeneity. The large series Staphyliniformia was never recovered as monophyletic in our analyses. The Bayesian tree using a degenerated nucleotide dataset (P123_Degen) and a site-heterogeneous mixture model in PhyloBayes was supported as the best Polyphaga phylogeny: (Scirtiformia, (Elateriformia, ((Bostrichiformia, Cucujiformia), (Scarabaeiformia + Staphyliniformia)))). For Cucujiformia, the largest series, we inferred a superfamily-level phylogeny: ((Cleroidea, Coccinelloidea), (Tenebrionoidea, (Cucujoidea + Curculionoidea + Chrysomeloidea))).
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http://dx.doi.org/10.1016/j.ygeno.2020.05.012DOI Listing
September 2020

[The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes].

Sheng Li Xue Bao 2020 Apr;72(2):175-180

Institute of Basic Medical Sciences, Department of Basic Medical Sciences, Xi'an Medical University, Xi'an 710021, China.

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
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April 2020

Brucine: A Review of Phytochemistry, Pharmacology, and Toxicology.

Front Pharmacol 2020 3;11:377. Epub 2020 Apr 3.

Institute of Interdisciplinary Integrative Biomedical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Brucine, a weak alkaline indole alkaloid, is one of the main bioactive and toxic constituents of . Modern pharmacology studies and clinical practice demonstrate that brucine possesses wide pharmacological activities, such as anti-tumor, anti-inflammatory, analgesic, and the effects on cardiovascular system and nervous system, etc. However, its central nervous system toxicity severely limits its clinical application. Herein, the physicochemical properties, pharmacological activities, and toxicity of brucine were reviewed, and the novel strategies to address the toxicity issues were discussed, aiming to bring new insights into further research and application of this active component.
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http://dx.doi.org/10.3389/fphar.2020.00377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145893PMC
April 2020

Placebo responses in ankylosing spondylitis patients worldwide: variations and possible explanations.

Expert Rev Clin Immunol 2020 05 3;16(5):447-450. Epub 2020 Apr 3.

Division of Rheumatology, Department of Medicine, The University of Hong Kong-Shenzhen Hospital , Shenzhen, China.

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http://dx.doi.org/10.1080/1744666X.2020.1748500DOI Listing
May 2020

The important effect of 5-HTTLPR polymorphism on the risk of depression in patients with coronary heart disease: a meta-analysis.

BMC Cardiovasc Disord 2020 03 18;20(1):141. Epub 2020 Mar 18.

Department of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

Background: Depression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However, the potential pathophysiological mechanisms remain unknown. It might be influenced by genetic and environmental factors. According to recent researches, there is potential association between serotonin transporter gene-linked polymorphic region (5-HTTLPR) polymorphism and risk of depression in CHD patients, but the results are still inconclusive. Therefore, we performed this meta-analysis based on unadjusted and adjusted data to ascertain a more precise conclusion.

Methods: We searched relevant articles through PubMed, Embase, Web of Science, Chinese BioMedical Literature (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases up to August 26, 2019. Study selection and data extraction were accomplished by two authors independently. The strength of the correlation was assessed via odds ratios (ORs) with their 95% confidence intervals (95%CIs).

Results: This meta-analysis enrolled six observational studies. Based on unadjusted data, there was significant relationship between 5-HTTLPR polymorphism and depression risk in CHD patients under all genetic models (S vs. L: OR = 1.31, 95%CI = 1.07-1.60; SS vs. LL: OR = 1.73, 95%CI = 1.12-2.67; LS vs. LL: OR = 1.47, 95%CI = 1.13-1.92; LS + SS vs. LL: OR = 1.62, 95%CI = 1.25-2.09; SS vs. LL + LS: OR = 1.33, 95%CI = 1.02-1.74). The results of adjusted data further strengthened this relationship (SS vs. LL: OR = 1.89, 95%CI = 1.28-2.80; LS vs. LL: OR = 1.69, 95%CI = 1.14-2.51; LS + SS vs. LL: OR = 1.80, 95%CI = 1.25-2.59). Subgroup analyses based on ethnicity and major depressive disorder revealed similar results to that of the overall analysis. No evidence of publication bias was observed.

Conclusions: Our results suggest that 5-HTTLPR polymorphism may have an important effect on the risk of depression among patients with CHD, and carriers of the S allele of 5-HTTLPR are more vulnerable to depression.
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http://dx.doi.org/10.1186/s12872-020-01424-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081537PMC
March 2020

The GPR120 Agonist TUG-891 Inhibits the Motility and Phagocytosis of Mouse Alveolar Macrophages.

Biomed Res Int 2020 20;2020:1706168. Epub 2020 Feb 20.

Institute of Basic Medical Sciences, Xi'an Medical University, Xi'an 710021, China.

Movement and phagocytosis characterize the fundamental actions of macrophages. Although it is known that the free fatty acid receptor GPR120 is expressed in macrophages and regulates cytokine expression to exert anti-inflammatory activities, the effects of GPR120 activation on the motility and phagocytosis of macrophages are not clear. In this study, mouse alveolar macrophages (AM) were stimulated with the GPR120 agonist TUG-891, and the changes in cell motility, intracellular Ca concentration ([Ca]i), and the ability of phagocytosis were measured. Mouse AM in controls exhibited active movement , and TUG-891 significantly restrained AM movement. Meanwhile, TUG-891 stimulated a quick increase in [Ca]i in AM, which was blocked separately by the Gq protein inhibitor YM-254890, the phospholipase C (PLC) inhibitor U73122, or depletion of endoplasmic reticulum (ER) Ca store by thapsigargin. The inhibition of AM movement by TUG-891 was eliminated by YM-254890, U73122, thapsigargin, and chelation of cytosolic Ca by BAPTA. Moreover, TUG-891 inhibited AM phagocytosis of fluorescent microspheres, which was also blocked by YM-254890, U73122, thapsigargin, and BAPTA. In conclusion, GPR120 activation in mouse AM increases [Ca]i but inhibits the motility and phagocytosis via Gq protein/PLC-mediated Ca release from ER Ca store.
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http://dx.doi.org/10.1155/2020/1706168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056993PMC
December 2020

Compound-based Chinese medicine formula: From discovery to compatibility mechanism.

J Ethnopharmacol 2020 May 24;254:112687. Epub 2020 Feb 24.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Naval Medical University, 325 Guohe Road, Yangpu District, Shanghai, 200433, China. Electronic address:

Ethnopharmacological Relevance: Chinese medicine formula (CMF) has a long history of clinical use in the treatment of various diseases under the guidance of traditional Chinese medicine (TCM) theory. The application of CMF can be divided into three levels, crude extracts, homologous compounds mixture, and specific compounds. However, the modern scientific connotation of the CMF theory has not been clarified.

Aim Of The Review: To critically evaluate the research strategy for the investigation of compound-based CMF (CCMF).

Materials And Methods: The related information was collected from the scientific databases, including CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and Wiley Online.

Results: The research design including discovery, screening, optimization, pharmacodynamics models, and target research techniques including the targets for compatibility compounds were evaluated. Essentially it has been evaluated that the in vitro multicellular three-dimensional culture or organoid model has been proposed for the optimization model for compatibility research of CCMF. Based on these, the traditional compatibility theory of CMF, such as Monarch-Minister-Assistant-Guide (Jun-Chen-Zuo-Shi in Chinese), can probably be elucidated by the CCMF research.

Conclusions: CCMF has the clear advantage of providing the exact composition and controllable quality of modern medicines, in addition to having the characteristics of multi-ingredients and multi-targets synergistic effects of TCM. However, CCMF is still associated with challenges which need to be addressed for its future use.
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http://dx.doi.org/10.1016/j.jep.2020.112687DOI Listing
May 2020
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