Publications by authors named "Mengmeng Zheng"

53 Publications

Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR.

J Med Chem 2021 Jul 23. Epub 2021 Jul 23.

Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.

It is very promising to target the extracellular domain of epidermal growth factor receptor (EGFR) for developing novel and selective anticancer therapies. Herein, we report the discovery of a novel small molecule, , from a one-bead-two-compound (OBTC) cyclic γ-AApeptide library. The molecule was found to bind tightly to the extracellular domain of EGFR. Intriguingly, this molecule could also effectively antagonize EGF-stimulated EGFR phosphorylation and downstream signal transduction. Furthermore, together with its remarkable resistance to proteolytic degradation, was shown to effectively inhibit cell proliferation and migration in vitro and suppresses the growth of tumor in the A549 xenograft model in vivo, highlighting its potential therapeutic application for cancer treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00607DOI Listing
July 2021

[Preparation of luminescent silica nanoparticles with immobilized metal ion affinity for labeling phosphorylated proteins in Western Blot].

Se Pu 2021 Apr;39(4):384-390

State Key Laboratory of Bioorganic Chemistry and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.

Protein phosphorylation is an important type of post-translational protein modification. In Western Blot experiment, the assay of phosphoproteins need special phospho antibodies, which are expensive, difficult to preserve, poorly reproducible. To this end, the immobilized metal ion affinity luminescent silica nanoparticles for instead of phospho antibodies were prepared. A layer of polymer was created on the surface of the silica nanoparticles via co-polymerization to protect the nanoparticles and to functionalize them with the immobilized metal ion affinity property to specifically label the phosphorylated proteins in Western Blot assays. The affinity luminescent silica nanoparticles were prepared with the following procedure. First, the sol-gel precursor fluorescein isothiocyanate-3-aminopropyltriethoxysilane (FITC-APTES) with the fluorescent moiety was prepared by modifying APTES with FITC. The luminescent silica nanoparticles ([email protected]) were synthesized using the Stöber synthesis method in a reversed microemulsion. Briefly, 123.2 mL of cyclohexane, 25.6 mL of -hexanol, and 5.44 mL of deionized water were ultrasonically mixed, and then 28.3 g of Triton X-100 were added and the mixture was magnetically stirred for 15 min to form a clear and transparent microemulsion system. Within 10 min, 0.8 mL of FITC-APTES precursor, 1.6 mL of tetraethoxysilane (TEOS), and 0.96 mL of concentrated ammonia (25%-27%, mass fraction) were added to the microemulsion, and the mixture was stirred at 24 ℃ for 24 h. After the reaction, the microemulsion system was destroyed by adding 200 mL of ethanol. The resulting [email protected] luminescent silica nanoparticles were centrifuged, and washed three times with ethanol. After dryness, the [email protected] nanoparticles were modified with methacryloxy-propyltrimethoxysilane (MPS) to introduce the double bonds for further modification. The functional monomer nitrilotriacetic acid (NTA) and glycidyl methacrylate (GMA) were copolymerized on the surface of the nanoparticles to convert [email protected] to [email protected] The polymer coating of the silica nanoparticles was not only able to protect the silica from hydrolysis, but also to introduce the functional groups of nitrilotriacetic acid, which can chelate with metal ions. Elemental analysis demonstrated that the NTA groups had been bonded to the surface of the nanoparticles via copolymerization. The polymerization did not affect the morphology and fluorescence properties of the nanoparticles. The [email protected] nanoparticles were activated with three different metal ions Zr, Fe, and Ti, for the enrichment of phosphorylated peptides derived form -casein tryptic digestion. HPLC-MS analysis indicated that the [email protected] nanoparticles are the best for the enrichment of phosphorylated peptides. The [email protected] nanoparticles were used for labelling the phosphorylated proteins in Western Blot experiment. The electrophoretic band of -casein could be clearly labeled with the [email protected] nanoparticles, while the bovine albumin band could not be labelled. This indicates that the luminescent [email protected] can be used to label the phosphorylated proteins in Western Blot experiments.
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http://dx.doi.org/10.3724/SP.J.1123.2020.05024DOI Listing
April 2021

A microsphere nanoparticle based-serum albumin targeted adsorption coupled with surface-enhanced Raman scattering for breast cancer detection.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 1;261:120039. Epub 2021 Jun 1.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China. Electronic address:

The serum albumin level is inseparable associated with survival in patients with breast cancer, and simultaneously serve as a good indicator of prognosis of cancer. Here, we proposed a novel extraction-isolation analysis method of albumin for breast cancer detection utilizing hydroxyapatite particles (HAp) to targeted adsorb albumin from serum relying on its specific adsorption capacity. An ideal protein-release reagent was used for isolating albumin from the surface of HAp, and meanwhile ensuring that the structure and property of albumin was not suffered damage. The surface-enhanced Raman scattering (SERS) signal of extracted albumin was obtained, and partial least squares (PLS) and linear discriminant analysis (LDA) analysis approach were employed to analyze SERS spectra data, with the aim to assess the capability of HAp method for identifying breast cancer, yielding an ideal diagnostic accuracy of 98.6%, demonstrating promising potential as a non-invasive and sensitive nanotechnology for breast cancer screening.
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http://dx.doi.org/10.1016/j.saa.2021.120039DOI Listing
November 2021

Complete mitochondrial genome of (Teleostei, Cypriniformes, Balitoridae) obtained using next-generation sequencing.

Mitochondrial DNA B Resour 2021 Jan 12;6(1):69-70. Epub 2021 Jan 12.

College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.

The complete mitogenome sequence of was obtained using next generation sequencing and confirmed via overlap-PCR method. The genome was 16,565 bp in length and consisted of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 23 transfer RNA genes and 1 control region. The overall nucleotide composition of heavy strand was 30.38% A (5033), 16.62% G (2753), 25.25% T (4182) and 27.75 (4597), with a slight A-T skew (55.63%), which is most obvious in the D-loop and most transfer RNA genes. Mitochondrial genome analyses based on ML analyses yielded identical phylogenetic trees.
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http://dx.doi.org/10.1080/23802359.2020.1846471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819126PMC
January 2021

Development of Bis-cyclic Imidazolidine-4-one Derivatives as Potent Antibacterial Agents.

J Med Chem 2020 12 24;63(24):15591-15602. Epub 2020 Sep 24.

Department of Chemistry, University of South Florida, 4202 E. Fowler Ave, Tampa, Florida 33620, United States.

Antibiotic resistance has emerged as one of the biggest public health concerns all over the world. In an effort to combat bacterial infections, a series of imidazolidine-4-one derivatives with potent and broad-spectrum antibacterial activity and low rates of drug resistance were developed by mimicking the salient physiochemical features of host defense peptides. These small molecules displayed potent activity against both Gram-negative and Gram-positive bacteria including several multidrug-resistant bacteria strains. Meanwhile, time-kill kinetics and drug resistance studies suggested that the most potent compound could not only eliminate the bacteria rapidly but also exhibit a low probability of drug resistance in MRSA over many passages. Further mechanistic studies suggested that eradicated bacterial pathogens by disintegrating membranes of both Gram-negative and Gram-positive bacteria. Together with their small molecular weight and low production cost compared with HDPs, these imidazolidine-4-one compounds may be developed into a new generation of antibiotic therapeutics combating emergent drug resistance.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00171DOI Listing
December 2020

Electrochemical DNA Sensor for Sensitive BRCA1 Detection Based on DNA Tetrahedral-Structured Probe and Poly-Adenine Mediated Gold Nanoparticles.

Biosensors (Basel) 2020 Jul 20;10(7). Epub 2020 Jul 20.

Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

BRCA1 is the biomarker for the early diagnosis of breast cancer. Detection of BRCA1 has great significance for the genetic analysis, early diagnosis and clinical treatment of breast cancer. In this work, we developed a simple electrochemical DNA sensor based on a DNA tetrahedral-structured probe (TSP) and poly-adenine (polyA) mediated gold nanoparticles (AuNPs) for the sensitive detection of BRCA1. A thiol-modified TSP was used as the scaffold on the surface of the screen-printed AuNPs electrode. The capture DNA (TSP) and reporter DNA were hybridized to the target DNA (BRCA1), respectively, to form the typical sandwich system. The nanocomposites of reporter DNA (polyA at the 5' end) combined with AuNPs were employed for signal amplification which can capture multiple enzymes by the specificity between biotin and streptavidin. Measurements were completed in the electrochemical workstation by cyclic voltammetry and amperometry and we obtained the low limit of detection of 0.1 fM with the linear range from 1 fM to 1 nM. High sensitivity and good specificity of the proposed electrochemical DNA sensor showed potential applications in clinical early diagnosis for breast cancer.
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http://dx.doi.org/10.3390/bios10070078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400266PMC
July 2020

Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity.

Front Chem 2020 12;8:441. Epub 2020 Jun 12.

Department of Chemistry, University of South Florida, Tampa, FL, United States.

Over the past few decades, the emergence of antibiotic resistance developed by life-threatening bacteria has become increasingly prevalent. Thus, there is an urgent demand to develop novel antibiotics capable of mitigating this trend. Herein, we report a series of dimeric γ-AApeptide derivatives as potential antibiotic agents with limited toxicity and excellent selectivity against Gram-positive strains. Among them, compound was identified to have the best MICs without inducing drug resistance, even after exposure to MRSA for 20 passages. Time-kill kinetics and mechanistic studies suggested that could mimic host-defense peptides (HDPs) and rapidly eradicate MRSA within 2 hours through disturbing the bacteria membrane. Meanwhile, biofilm formation was successfully inhibited even at a low concentration. Taken together, these results suggested the great potential of dimeric γ-AApeptide derivatives as antibacterial agents.
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http://dx.doi.org/10.3389/fchem.2020.00441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304243PMC
June 2020

Surface-enhanced Raman scattering analysis of serum albumin via adsorption-exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening.

J Biophotonics 2020 08 2;13(8):e202000087. Epub 2020 Jun 2.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, China.

Combining serum albumin via adsorption-exfoliation on hydroxyapatite particles (HAp) with surface-enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS-SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp-adsorbed-exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.
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http://dx.doi.org/10.1002/jbio.202000087DOI Listing
August 2020

The nature of dissolved organic matter determines the biosorption capacity of Cu by algae.

Chemosphere 2020 Aug 13;252:126465. Epub 2020 Mar 13.

College of Environment, Zhejiang University of Technology, Hangzhou, 310032, China.

The role of dissolved organic matter (DOM) on the biochemical behavior and toxicity of heavy metals in water is very important but complex and unclear. The present work extracted DOM from a natural water and separated it into three fractions, namely humic acid (HA), fulvic acid (FA) and transphilic acid (TPA). Optical detection showed that HA had most aromatic ring skeletons, FA had more aromatic ring hydrophilic groups, and TPA had the largest number of hydroxyl or carboxyl groups. Their effects on the toxicity of Cu by Chlorella pyrenoidosa depended on types and concentration of DOM. In the case of algal exposure to 0.003 mM initial Cu concentration, the final algal optical density increased from 0.317 of the control group to 0.345, 0.645 and 0.435 in the presence of 20, 10 mg L HA, and 10 mg L TPA, respectively, but were suppressed to 0.246, 0.117 and 0.234 in the presence of 10, 20 mg L FA and 20 mg L TPA. Most adsorption isotherms lost the linearity in the presence of HA, FA and TPA. The adsorbed Cu increased from 0.242 to 0.477 mmol g, following the order of increased concentration of HA, FA, and TPA. The formation of ternary complex and the multi-layer adsorption were proposed to explain the significant enhancement adsorption of Cu in the presence of FA and TPA. This study showed that the type and the density of effective functional groups in DOM determined its effects on Cu toxicity and bioavailability to algae.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126465DOI Listing
August 2020

Probing Protein-Protein Interactions with Label-Free Mass Spectrometry Quantification in Combination with Affinity Purification by Spin-Tip Affinity Columns.

Anal Chem 2020 03 12;92(5):3913-3922. Epub 2020 Feb 12.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.

We describe an affinity purification-mass spectrometry (AP-MS) method for probing the interactome of a special targeting protein. The AP was implemented with monolithic micro immobilized metal ion affinity chromatography columns (m-IMAC) which were prepared by photoinitiated polymerization in the tip of a pipet (spin-tip columns). The recombinant His-tagged protein (bait protein) was reversibly immobilized on the affinity column through the chelating group nitrilotriacetic acid (NTA)-Ni. The bait protein and its interacting partners can be easily eluted from the affinity matrix. The pulled-down cellular proteins were then analyzed with label-free quantitative proteomics. We used this method for probing the interactome concerning the GOLD (Golgi dynamics) domain of the autophagy-associated adaptor protein FYCO1. Totally, 96 proteins including seven literature-reported FYCO1-associating proteins were identified. Among them CCZ1 and MON1A were further biochemically validated, and the direct interaction between the FYCO1 GOLD domain with CCZ1 was confirmed by co-immunoprecipitation experiments.
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http://dx.doi.org/10.1021/acs.analchem.9b05355DOI Listing
March 2020

Small Molecules with Membrane-Active Antibacterial Activity.

ACS Appl Mater Interfaces 2020 May 16;12(19):21292-21299. Epub 2020 Jan 16.

Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, Tampa, Florida 33620, United States.

This spotlight on application provides a brief overview of our research exploration, focusing on the research of small molecules with membrane-active antibacterial activity that mimic host-defense peptides (HDPs). The development of antimicrobial HDP agents is an emerging research area as they circumvent the potential disadvantages of HDPs. The small molecules are preferable for development due to their low production cost and potential of more practical applications. In recent years, we conducted research on the design of antibacterial agents based on small molecules including hydantoins, acylated reduced amides, biscyclic guanidines, and dimeric alkylamides of lysines. We herein sketch our journey on the exploration of the antimicrobial activity of these few classes of molecules and hopefully share our insight in the future design of small-molecular-weight antibiotic agents with membrane-active activity that mimic HDPs.
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http://dx.doi.org/10.1021/acsami.9b20161DOI Listing
May 2020

Surface-enhanced Raman spectroscopy analysis of mast cell degranulation induced by low-intensity laser.

IET Nanobiotechnol 2019 Dec;13(9):983-988

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, People's Republic of China.

Mast cell (MC) degranulation is an important step in the healing process. In this study, silver-nanoparticles-based surface-enhanced Raman spectroscopy (SERS) was used to investigate the spectral characteristics of degranulation of MCs activated by low-intensity laser. The significant spectral changes, such as Raman peak intensities, suggested the concentration variation of some degranulated substances. The Raman intensity ratio of 799-554 cm could be used as a potential internal indicator for the degranulation degree of MCs. Principal component analysis (PCA) was employed to reduce the high dimension of spectra into a few principal components (PCs) while retaining the most diagnostically significant information for sample differentiation. Using the diagnostically significant PC scores ( < 0.05), linear discriminate analysis (LDA) was applied to identify different cell degranulation groups with high sensitivity, specificity and accuracy. This exploratory work demonstrates that SERS technique combined with a PCA-LDA algorithm possesses great potential for developing a label-free, comprehensive, non-invasive and accurate method for measuring MC degranulation.
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http://dx.doi.org/10.1049/iet-nbt.2019.0145DOI Listing
December 2019

[Preparation of immobilized trypsin micro monolithic column and its application to rapid digestion of trace proteins].

Se Pu 2019 Dec;37(12):1282-1290

State key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.

A method for the preparation of a micro monolithic column with immobilized trypsin was developed for the rapid and efficient digestion of proteins. The micro monolithic column was prepared by photo-polymerization inside the tip of 20 μL pipette. The polymerization solution was composed of the functional monomers 4-pentenoic succinimide ester (PAS) and 2-hydroxyethyl methacrylate (HEMA), crosslinker pentaerythritol triacrylate (PETA) dissolved in a ternary porogenic system comprising dimethyl sulfoxide (DMSO), formyldimethylamine (DMF) and 1-dodecanol. Immobilization of trypsin was achieved by a chemical reaction between the amino group and succinimide. The effects of the active ester content in the polymerization mixture and the volumes of the monolithic bed on the column capacities of the immobilized trypsin were systematically investigated. The digestion efficiency as well as the stability and repeatability of the immobilized trypsin were systematically investigated by using standard proteins cytochrome C and bovine serum albumin. The experimental results indicated that high digestion efficiency with great reproducibility between batches and the digestion procedure could be obtained within 10 min. The trypsin immobilized columns were applied to the digestion of proteins extracted from 1×10 human acute promyelocytic leukemia (NB4) cells and human acute T-cell leukemia (Jurkat T) cells. A total of 2489 and 2572 proteins were readily identified by Nano-LC-MS/MS analysis. The quantity ratio of the identified proteins increased 2.2% and 6.1%, respectively, compared to the case of in-solution digestion, demonstrating the robustness of the trypsin immobilized micro column and its potential application to proteome studies.
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http://dx.doi.org/10.3724/SP.J.1123.2019.08039DOI Listing
December 2019

Second messenger ApA polymerizes target protein HINT1 to transduce signals in FcεRI-activated mast cells.

Nat Commun 2019 10 11;10(1):4664. Epub 2019 Oct 11.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.

Signal transduction systems enable organisms to monitor their external environments and accordingly adjust the cellular processes. In mast cells, the second messenger ApA binds to the histidine triad nucleotide-binding protein 1 (HINT1), disrupts its interaction with the microphthalmia-associated transcription factor (MITF), and eventually activates the transcription of genes downstream of MITF in response to immunostimulation. How the HINT1 protein recognizes and is regulated by ApA remain unclear. Here, using eight crystal structures, biochemical experiments, negative stain electron microscopy, and cellular experiments, we report that ApA specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. The polymerization interface overlaps with the area on HINT1 for MITF interaction, suggesting a possible competitive mechanism to release MITF for transcriptional activation. The mechanism depends precisely on the length of the phosphodiester linkage of ApA. These results highlight a direct polymerization signaling mechanism by the second messenger.
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http://dx.doi.org/10.1038/s41467-019-12710-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789022PMC
October 2019

Overexpression of may independently predict poor overall survival in patients with head and neck squamous cell carcinoma.

Onco Targets Ther 2019 5;12:7269-7279. Epub 2019 Sep 5.

Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, People's Republic of China.

Purpose: The is a novel oncogene involved in breast cancer. However, the association between and head and neck squamous cell carcinoma (HNSCC) remains unclear.

Materials And Methods: The levels of mRNA in HNSCC and normal tissues were analyzed using data from the Cancer Genome Atlas-HNSC. The expression of was also determined using quantitative real-time polymerase chain reaction in 165 paired HNSCC and adjacent normal tissues, which were used as the validation cohort.

Results: expression was significantly increased in HNSCC tissues versus normal tissues. High expression was significantly associated with human papillomavirus infection, perineural invasion, tumor invasion, lymphatic metastasis, and clinical stage. Moreover, elevated expression was correlated with unfavorable overall survival (hazard ratio [HR]: 1.711, 95% confidence interval [CI]: 1.141-2.567, =0.009) and recurrence-free survival (HR: 1.648, 95% CI: 1.060-2.563, =0.027) in HNSCC patients.

Conclusion: was significantly upregulated in HNSCC tissues, which may be attributed to both genetic and epigenetic alterations. Increased expression may be involved in the progression and metastasis of HNSCC, and serve as an independent biomarker of poor prognosis in HNSCC with respect to overall survival and recurrence-free survival.
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http://dx.doi.org/10.2147/OTT.S212200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733347PMC
September 2019

Study on the Effect of Ginsenosides Rb on Blood of Tumor Mice.

Biomed Res Int 2019 18;2019:5476076. Epub 2019 Aug 18.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Objective: The blood of cancer patients is in a state of hypercoagulability, easily leading to thrombosis. Anemia is also a complication of tumors. Anemia and thrombosis affect the treatment of tumor patients.

Methods: Ginsenosides Rb were extracted from the stems and leaves of American ginseng using water-saturated ethanol and ethyl acetate in silica gel column. Tumor mice model was established by injecting H hepatocellular carcinoma cells into the axilla of mice. Mice were randomly divided into 6 groups: normal control group, model control group, positive control group, low dose group (7 mg/kg), middle dose group (14 mg/kg), and high dose group (35 mg/kg). After 18 days, the blood was obtained by picking the eyeball of mice. The levels of red blood cells (RBC), hemoglobin (HGB), neutrophils/lymphocytes radio (NLR), platelets (PLT), platelet distribution width (PDW), fibrinogen (FIB), and D-Dimer (D-D) were measured and compared in each group of mice.

Results: The content of obtained ginsenosides Rb reached 90.05%. This extraction process was simple and reliable. Middle dose of ginsenosides Rb could significantly increase RBC and HGB levels (P<0.05). Moreover, ginsenosides Rb could significantly reduce NLR, PLT, PDW, FIB, and D-D (P<0.01).

Conclusion: ginsenosides Rb could significantly improve anaemia and hypercoagulation of blood in cancer mice. Ginsenosides Rb are a potential anticoagulant and antianemia drug in treating cancer.
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http://dx.doi.org/10.1155/2019/5476076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720054PMC
February 2020

Determining the affinity of anti-mitotic compounds binding to colchicine binding site of tubulin by affinity probe capillary electrophoresis.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Jul 14;1121:66-71. Epub 2019 May 14.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China; School of Physical Science and Technology, ShanghaiTech University, Haike Road 100, Shanghai 200120, China. Electronic address:

The colchicine binding site of tubulin is often used to screen the anti-mitotic compounds, which are widely used as anti-cancer therapies. In the present work, an affinity probe capillary electrophoresis (APCE) method was developed for determining the affinity of anti-mitotic compounds. To this end, a fluorescently labeled affinity probe, 5-carboxyfluorescein-colchicine (F-colchicine), was prepared for the affinity competition experiment. The probe can form a stable complex with tubulin with the binding stoichiometry of 0.75, and the dissociation constant K of the complex was determined as 5.7 × 10 mol/L. In the affinity competition experiment, F-colchicine was incubated with tubulin and the test compound in the solution. The F-colchicine-tubulin complexes and free F-colchicine were quickly separated by CE and the concentration of free F-colchicine was accurately determined with the laser induced fluorescence detection. The affinity constant of the tested compound can be measured with the affinity competition binding curve. The enantiomers of the anti-mitotic compound were evaluated by using the method. The binding affinity of the enantiomers displayed an enantioselective manner. Compared to other affinity binding assay methods, our method is more straightforward, more accurate, and more cost-effective.
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http://dx.doi.org/10.1016/j.jchromb.2019.05.010DOI Listing
July 2019

Alkaline Extraction, Structural Characterization, and Bioactivities of (1→6)-β-d-Glucan from .

Molecules 2019 Apr 24;24(8). Epub 2019 Apr 24.

Key Laboratory of Marine Drugs of Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

The purpose of this study is to develop a robust approach to obtain β glucans from and to characterize their structural and biological properties for sustainable utilization. The alkali extraction was optimized with an orthogonal experimental design, and a concise process for obtaining specific targeting polysaccharides from was developed in this study. After purification with a Q-Sepharose Fast Flow strong anion-exchange column, the monosaccharide composition, a methylation analysis, and NMR spectroscopy were employed for their structural characterizations. LeP-N2 was found to be composed of (1→6)-β-d-glucans with minor β-(1→3) glucosidic side chains. Atomic force microscopy (AFM) and high-performance gel permeation chromatography-refractive index-multi-angle laser light scattering (HPGPC-RI-MALLS) also revealed LeP-N2 exhibiting a compact unit in aqueous solution. This (1→6)-β-d-glucan was tested for antioxidant activities with IC at 157 μg/mL. Moreover, RAW 264.7 macrophage activation indicated that the release of nitric oxide (NO) and reactive oxygen species (ROS) was markedly increased with no cytotoxicity at a dose of 100 μg/mL. These findings suggest that the (1→6)-β-d-glucans obtained from could serve as potential agents in the fields of functional foods or medicine.
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http://dx.doi.org/10.3390/molecules24081610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515283PMC
April 2019

K27-linked ubiquitination of BRAF by ITCH engages cytokine response to maintain MEK-ERK signaling.

Nat Commun 2019 04 23;10(1):1870. Epub 2019 Apr 23.

Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

BRAF plays an indispensable role in activating the MEK/ERK pathway to drive tumorigenesis. Receptor tyrosine kinase and RAS-mediated BRAF activation have been extensively characterized, however, it remains undefined how BRAF function is fine-tuned by stimuli other than growth factors. Here, we report that in response to proinflammatory cytokines, BRAF is subjected to lysine 27-linked poly-ubiquitination in melanoma cells by the ITCH ubiquitin E3 ligase. Lysine 27-linked ubiquitination of BRAF recruits PP2A to antagonize the S365 phosphorylation and disrupts the inhibitory interaction with 14-3-3, leading to sustained BRAF activation and subsequent elevation of the MEK/ERK signaling. Physiologically, proinflammatory cytokines activate ITCH to maintain BRAF activity and to promote proliferation and invasion of melanoma cells, whereas the ubiquitination-deficient BRAF mutant displays compromised kinase activity and reduced tumorigenicity. Collectively, our study reveals a pivotal role for ITCH-mediated BRAF ubiquitination in coordinating the signals between cytokines and the MAPK pathway activation in melanoma cells.
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http://dx.doi.org/10.1038/s41467-019-09844-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478693PMC
April 2019

Orthogonal Halogen-Bonding-Driven 3D Supramolecular Assembly of Right-Handed Synthetic Helical Peptides.

Angew Chem Int Ed Engl 2019 06 30;58(23):7778-7782. Epub 2019 Apr 30.

Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, Tampa, FL, 33620, USA.

Peptide-mediated self-assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C-X⋅⋅⋅X-C/C-X⋅⋅⋅π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l-sulfono-γ-AApeptides and natural amino acids. The combination of halogen bonding, intra-/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self-assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures.
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http://dx.doi.org/10.1002/anie.201903259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534470PMC
June 2019

Cyclic Peptidomimetics as Inhibitor for miR-155 Biogenesis.

Mol Pharm 2019 02 15;16(2):914-920. Epub 2019 Jan 15.

Department of Chemistry and Chemical Biology , University of New Mexico , 300 Terrace Street NE , Albuquerque , New Mexico 87131 , United States.

miR-155 plays key promoting roles in several cancers and emerges as an important anticancer therapeutic target. However, the discovery of small molecules that target RNAs is challenging. Peptidomimetics have been shown to be a rich source for discovering novel ligands to regulate cellular proteins. However, the potential of using peptidomimetics for RNA targeting is relatively unexplored. To this end, we designed and synthesized members of a novel 320 000 compound macrocyclic peptidomimetic library. An affinity-based screening protocol led to the identification of a pre-miR-155 binder that inhibits oncogenic miR-155 maturation in vitro and in cell and induces cancer cell apoptosis. The results of this investigation demonstrate that macrocyclic peptidomimetics could serve as a new scaffold for RNA targeting.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01247DOI Listing
February 2019

Stone-free Outcomes of Flexible Ureteroscopy for Renal Calculi Utilizing Computed Tomography Imaging.

Urology 2019 Feb 2;124:52-56. Epub 2018 Nov 2.

Indiana University School of Medicine, Department of Urology, Indianapolis, IN. Electronic address:

Objective: To assess stone-free rates following ureteroscopy (URS) for renal calculi at our institution using low-dose renal only computed tomography (CT).

Methods: A retrospective review of patients undergoing flexible URS for renal stones only with subsequent CT scan within 3 months. Meticulous basketing of all stone fragments was performed whenever possible. A "true" zero-fragment stone-free rate was determined by reviewing the CT scan and radiologist's report. Patients with nephrocalcinosis (as determined by visual inspection of papilla at the time of URS) were assigned the "stone-free" category.

Results: Flexible URS was performed in 288 renal units of 214 patients with renal calculi from 2013 to 2016. Median preoperative stone size was 6.2 mm with the average kidney containing 6.4 stones. An access sheath was used in 92% of cases. A total of 73% (209/288) renal units were completely stone free by CT assessment. Patients with residual fragments were as follows: 1 mm in 2% (7/288), 2-4 mm in 16% (46/288), and >4 mm in 9% of kidneys (26/288).

Conclusion: The true stone-free rate in patients undergoing flexible URS for renal calculi utilizing active basketing of fragments as determined by strict CT assessment was 73%. In patients with residual fragments, the majority are 2-4 mm in size making URS a treatment option for renal calculi with excellent stone-free results.
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http://dx.doi.org/10.1016/j.urology.2018.09.005DOI Listing
February 2019

Visible Light-Initiated Bioorthogonal Photoclick Cycloaddition.

J Am Chem Soc 2018 11 26;140(44):14542-14546. Epub 2018 Oct 26.

State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , China.

Here we report a visible light-triggered, catalyst free bioorthogonal reaction that proceeds via a distinct pathway from reported bioorthogonal reactions. The prototype of this bioorthogonal reaction was the photocycloaddition of 9,10-phenanthrenequinone with electron-rich alkenes to form fluorogenic [4+2] cycloadducts. The bioorthogonal photoclick cycloaddition was readily initiated using a conventional visible light source such as a hand-held LED lamp. The reaction proceeded rapidly under biocompatible conditions, without observable competition from side reactions such as nucleophilic additions by water or common nucleophilic species. The bioorthogonal functionality in this reaction did not cross react with various alkynes and electron-deficient alkenes such as monomethyl fumarate. We demonstrated orthogonal labeling of two proteins using this reaction together with a strain promoting azide-alkyne click reaction or the UV-triggered reaction of tetrazole with monomethyl fumarate. The application of this reaction in the temporal and spatial labeling of live cells was also demonstrated.
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http://dx.doi.org/10.1021/jacs.8b08175DOI Listing
November 2018

Enhancement of visible-light photocatalytic activities of BiVO coupled with g-CN prepared using different precursors.

Environ Sci Pollut Res Int 2018 Nov 20;25(32):32466-32477. Epub 2018 Sep 20.

Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution Control, School of Environment and Energy, South China University of Technology, Guangzhou, 510006, People's Republic of China.

Graphitic-like carbon nitride (g-CN) photocatalyst was synthesized by a facile chemical pyrolysis method, which was built on the self-condensation of different precursors to generate g-CN, e.g., melamine, urea, and thiocarbamide. And the different precursors produced a great influence on the photocatalytic activities of g-CN. Heterojunctions of g-CN and BiVO were synthesized using a facile solvent evaporation method. The formation of BiVO/g-CN composites were confirmed by XRD, FT-IR, SEM, XPS, and UV-Vis DRS. The photocatalytic activities for RhB degradation were evaluated under visible-light irradiation. The photocatalytic activity of g-CN prepared by urea was higher than that of g-CN prepared by melamine and thiocarbamide, which was attributed to its favorable dispersibility, larger specific surface area, and higher oxidation capacity. The heterojunction composites exhibited higher photocatalytic activity than pure g-CN or BiVO. The results showed obvious removal efficiency for RhB, and the optimal sample with a BiVO content of 10% exhibited higher efficiency than pure g-CN and BiVO, and 10 wt%BiVO/CN-U showed the highest photocatalytic activity. The enhanced photocatalytic activity of BiVO/g-CN composite can be attributed to the intimate coupling between the two host substrates, resulting in an efficient charge separation.
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http://dx.doi.org/10.1007/s11356-018-3119-3DOI Listing
November 2018

Structure Properties, Acquisition Protocols, and Biological Activities of Oleuropein Aglycone.

Front Chem 2018 13;6:239. Epub 2018 Aug 13.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

Oleuropein aglycone, which is the major phenolic component of extra virgin olive oil, is gaining popularity and importance in scientific and public communities. This paper summarizes the structure properties, acquisition protocols, and biological activities of oleuropein aglycone. There are three hydrolytic methods used to obtain oleuropein aglycone from oleuropein-enzymatic hydrolysis, acid hydrolysis, and acetal hydrolysis. Enzymatic hydrolysis can be achieved with exogenous enzymes and endogenous enzymes. In addition, the diverse pharmacological effects of oleuropein aglycone are summaried. These pharmacological effects include anti-Alzheimer's disease, anti-breast cancer, anti-inflammatory, anti-hyperglycemic, anti-oxidative, and lipid-lowering properties. Therefore, we can use hydrolysis and biological activities to study oleuropein aglycone in the future.
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http://dx.doi.org/10.3389/fchem.2018.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099103PMC
August 2018

The Potential of Using Bee Pollen in Cosmetics: a Review.

J Oleo Sci 2018 Sep 14;67(9):1071-1082. Epub 2018 Aug 14.

School of Pharmacy, Shandong University of Traditional Chinese Medicine.

During ancient times in China, bee pollen was used for skin whitening and beauty. Around 70% of substances in bee pollen are biologically active, such as proteins, carbohydrates, lipids and fatty acids, phenolic compounds, vitamins and bioelements.This review describes the cosmeceutical properties of bee pollen and the mechanism of its active components action, its beneficial influence on human skin. As a natural bee product, bee pollen may effectively enhance protective mechanisms against skin aging, skin dryness, ultraviolet B radiation, oxidative damage, inflammatory and melanogenesis, which are involved in a wide range of negative effects on human skin, thus they have attracted attention for health and cosmetic applications.
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http://dx.doi.org/10.5650/jos.ess18048DOI Listing
September 2018

Anti-exercise-fatigue and promotion of sexual interest activity of total flavonoids from wasps drone-pupae in male mice.

Biomed Pharmacother 2018 Nov 8;107:254-261. Epub 2018 Aug 8.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan City, Shandong, China. Electronic address:

The aim of this research was to evaluate the anti-exercise-fatigue and promotion of sexual interest of total flavonoids from drone pupae of wasps. DPTF was prepared by ethanol extracting and its extraction conditions were optimized by response surface methodology. Then, anti-exercise-fatigue and promotion of sexual interest of DPTF were evaluated. The optimums extraction conditions by RSM were ethanol concentration 65%, extraction time 3 h and solid-to-liquid 20:1(mL/g). No mortality and general symptoms of toxicity were observed in the DPTF treated mice(1 g/kg,3 g/kg,5 g/kg body weight) the body weight and food consumption were not significantly changed compared with the normal control group. The relative weights of main organ did not markedly change. DPTF can significantly extend the duration of the swimming time to exhaustion and the times of capture the female in mice, decrease BUN, LAC and Cr levels, increase LG, GG and T activities in the DPTF treated mice. The dose of 5 g/kg body weight is the optimal dose for anti-exercise-fatigue activity and promotion of sexual interest in male mice. In conclusion, DPTF is promising traditional natural-based therapeutic remedy for relieving exercise-fatigue with high safety.
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http://dx.doi.org/10.1016/j.biopha.2018.07.172DOI Listing
November 2018

Maca Cosmetics: A Review on Constituents, Therapeutics and Advantages.

J Oleo Sci 2018 ;67(7):789-800

School of Pharmacy, Shandong University of Traditional Chinese Medicine.

Herbal cosmetics are the focus of attention nowadays, they have various therapeutics, including, anti-oxidant, anti-radiation, anti-aging, anti-inflammatory. Maca contains polysaccharides, phenolics, alkaloids, minerals and amino acids, which is said to suitable component for cosmetics due to the single action or synergy action. The review summarized the existed and potential therapeutic effects of maca ingredients in cosmetics. And compared to the marketed cosmetics, maca cosmetics have the merits of mild, low-toxicity and the clear relationship efficacy.
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http://dx.doi.org/10.5650/jos.ess18012DOI Listing
August 2018

Ginsenosides: A Potential Neuroprotective Agent.

Biomed Res Int 2018 8;2018:8174345. Epub 2018 May 8.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Ginseng is a traditional Chinese medicine with a wide range of pharmacological activities. Ginsenosides are the major constituents of ginseng. Ginsenosides have the unique biological activity and medicinal value, such as antitumor, anti-inflammatory, antioxidation, and inhibition of cell apoptosis. With the increase of stress in life, the incidence of nervous system diseases is also increasing. Neurological diseases pose a huge burden on people's life and health. In recent years, some studies have shown that ginsenosides have a certain role in the prevention and treatment of neurological diseases. However, the research is still in its infancy, and the relevant mechanisms are complex. In the paper, we review the effects and mechanisms of ginsenosides on epilepsy, depression, cerebral ischemia reperfusion injury, Alzheimer's disease, and Parkinson's disease. We hope to provide a theoretical basis for the treatment of nervous system diseases by ginsenosides.
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http://dx.doi.org/10.1155/2018/8174345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964429PMC
October 2018

A Review: The Bioactivities and Pharmacological Applications of Polygonatum sibiricum polysaccharides.

Molecules 2018 May 14;23(5). Epub 2018 May 14.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Traditional Chinese Medicine (TCM) has been widely used in China and is regarded as the most important therapeutic. (PS), a natural plant used in traditional Chinese medicine, has various functions associated with a number of its components. There are many compositions in PS including polysaccharides, steroids, anthraquinone, alkaloids, cardiac glycosides, lignin, vitamins, various acids, and so on. Of these, polysaccharides play a significant role in PS-based therapeutics. This article summarizes polysaccharides (PSP) have many pharmacological applications and biological activities, such as their antioxidant activity, anti-aging activity, an anti-fatigue effect, immunity enhancement effect, antibacterial effect, anti-inflammatory effect, hypolipidemic and antiatherosclerotic effects, anti-osteoporosis effect, liver protection, treatment of diabetes mellitus (DM), anti-cancer effect, and may help prevent Alzheimer's disease, and so on. This review summarized the extraction method, purification method, compositions, pharmacological applications, biological activities, biosynthesis, and prospects of PSP, providing a basis for further study of PS and PSP.
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http://dx.doi.org/10.3390/molecules23051170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099637PMC
May 2018
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