Publications by authors named "Xueyuan Yang"

30 Publications

  • Page 1 of 1

Intracisternal administration of tanshinone IIA-loaded nanoparticles leads to reduced tissue injury and functional deficits in a porcine model of ischemic stroke.

IBRO Neurosci Rep 2021 Jun 5;10:18-30. Epub 2021 Jan 5.

Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, United States.

Background: The absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model.

Results: Tan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (-37.30 ± 3.67 vs. -46.33 ± 0.73%) and white matter integrity (-19.66 ± 5.58 vs. -30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs.

Conclusion: The findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ibneur.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019951PMC
June 2021

UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes.

EBioMedicine 2020 Jul 20;57:102835. Epub 2020 Jun 20.

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu 210042, China. Electronic address:

Background: Little is known about whether UVB can directly influence epigenetic regulatory pathways to induce cutaneous squamous cell carcinoma (CSCC). This study aimed to identify epigenetic-regulated signalling pathways through global methylation and gene expression profiling and to elucidate their function in CSCC development.

Methods: Global DNA methylation profiling by reduced representation bisulfite sequencing (RRBS) and genome-wide gene expression analysis by RNA sequencing (RNA-seq) in eight pairs of matched CSCC and adjacent normal skin tissues were used to investigate the potential candidate gene(s). Clinical samples, animal models, cell lines, and UVB irradiation were applied to validate the mechanism and function of the genes of interest.

Findings: We identified the downregulation of the TGF-β/BMP-SMAD-ID4 signalling pathway in CSCC and increased methylation of inhibitor of DNA binding/differentiation 4 (ID4). In normal human and mouse skin tissues and cutaneous cell lines, UVB exposure induced ID4 DNA methylation, upregulated DNMT1 and downregulated ten-eleven translocation (TETs). Similarly, we detected the upregulation of DNMT1 and downregulation of TETs accompanying ID4 DNA methylation in CSCC tissues. Silencing of DNMT1 and overexpression of TET1 and TET2 in A431 and Colo16 cells led to increased ID4 expression. Finally, we showed that overexpression of ID4 reduced cell proliferation, migration, and invasion, and increased apoptosis in CSCC cell lines and reduced tumourigenesis in mouse models.

Interpretation: The results indicate that ID4 is downregulated by UVB irradiation via DNA methylation. ID4 acts as a tumour suppressor gene in CSCC development.

Funding: CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-3-021, 2017-I2M-1-017), the Natural Science Foundation of Jiangsu Province (BK20191136), and the Fundamental Research Funds for the Central Universities (3332019104).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317242PMC
July 2020

Diterpenoids as potential anti-inflammatory agents from Ajuga pantantha.

Bioorg Chem 2020 08 22;101:103966. Epub 2020 May 22.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

A phytochemical survey to obtain bioactive natural products from Ajuga pantantha afforded five new neo-clerodane diterpenoids (1-5). The structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. Compounds 2 and 5 were found to have the property of inhibiting NO production (IC values < 40 μM). Molecular docking and Western blotting were used to study the mechanism of anti-inflammatory action. Furthermore, compound 5 with the highest activity was tested for its in vivo anti-inflammatory effects using a zebrafish model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103966DOI Listing
August 2020

Anti-inflammatory -Clerodane Diterpenoids from .

J Nat Prod 2020 04 27;83(4):894-904. Epub 2020 Mar 27.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.

Eight new -clerodane diterpenoids (-) were acquired from the aerial parts of . Spectroscopic data analysis permitted the definition of their structures, and experimental and calculated electronic circular dichroism data were used to define their absolute configurations. Compounds and - were found to have NO inhibitory effects with IC values of 20.2, 45.5, 34.0, 27.0, 45.0, and 25.8 μM, respectively. The more potent compounds , , and were analyzed to establish their anti-inflammatory mechanism, including regulation of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins as well as their binding interactions with the two proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.9b00629DOI Listing
April 2020

Caseahomopene A, a ring-expanded homotriterpenoid from Casearia kurzii showing anti-inflammatory activities in vitro and in vivo.

Bioorg Chem 2020 05 13;98:103758. Epub 2020 Mar 13.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

Caseahomopene A (1), a rare natural product with a ring-expanded homotriterpenoid skeleton, was isolated from the leaves of Casearia kurzii. The structure including the absolute configuration was determined by spectroscopic data and X-ray crystallography analysis. Compound 1 showed anti-inflammatory effects in vitro and in vivo using LPS-stimulated cell and zebrafish model. As a potential anti-inflammatory agent, the anti-inflammatory mechanism of 1 was also investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103758DOI Listing
May 2020

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities.

Bioorg Chem 2020 05 9;98:103741. Epub 2020 Mar 9.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC value of 9.7 μM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103741DOI Listing
May 2020

Nanoparticles Encapsulating Nitrosylated Maytansine To Enhance Radiation Therapy.

ACS Nano 2020 02 21;14(2):1468-1481. Epub 2020 Jan 21.

Department of Chemistry , University of Georgia , Athens , Georgia 30602 , United States.

Radiotherapy remains a major treatment modality for cancer types such as non-small cell lung carcinoma (or NSCLC). To enhance treatment efficacy at a given radiation dose, radiosensitizers are often used during radiotherapy. Herein, we report a nanoparticle agent that can selectively sensitize cancer cells to radiotherapy. Specifically, we nitrosylated maytansinoid DM1 and then loaded the resulting prodrug, DM1-NO, onto poly(lactide--glycolic)--poly(ethylene glycol) (PLGA--PEG) nanoparticles. The toxicity of DM1 is suppressed by nanoparticle encapsulation and nitrosylation, allowing the drug to be delivered to tumors through the enhanced permeability and retention effect. Under irradiation to tumors, the oxidative stress is elevated, leading to the cleavage of the S-N bond and the release of DM1 and nitric oxide (NO). DM1 inhibits microtubule polymerization and enriches cells at the G2/M phase, which is more radiosensitive. NO under irradiation forms highly toxic radicals such as peroxynitrites, which also contribute to tumor suppression. The two components work synergistically to enhance radiotherapy outcomes, which was confirmed by clonogenic assays and with H1299 tumor-bearing mice. Our studies suggest the great promise of DM1-NO PLGA nanoparticles in enhancing radiotherapy against NSCLC and potentially other tumor types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b05976DOI Listing
February 2020

Correction: Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy.

Nanoscale 2019 12 4;11(48):23504-23505. Epub 2019 Dec 4.

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Department of Orthopaedics Trauma and Hand Surgery, Guangxi Medical University, Nanning, 530021, China.

Correction for 'Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy' by Gang Zhong et al., Nanoscale, 2019, 11, 11605-11616.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr90272dDOI Listing
December 2019

NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum.

Bioorg Chem 2019 11 4;92:103237. Epub 2019 Sep 4.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, People's Republic of China. Electronic address:

Two new ent-atisane-type diterpenoids (1 and 2), three new lathyrane-type diterpenoids (3-5), and seven known analogues (6-12) were isolated from Euphorbia antiquorum. The structures of these diterpenoids were established by analysis of their NMR, MS, and electronic circular dichroism data. The anti-inflammatory activities were evaluated biologically and compounds 1, 4, 7, 8, and 10 displayed strong NO inhibitory effects with IC values less than 40 μM. The potential anti-inflammatory mechanism was also investigated using molecular docking and Western blotting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.103237DOI Listing
November 2019

Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii.

Bioorg Chem 2019 08 23;89:102995. Epub 2019 May 23.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

A search for bioactive natural products as anticancer lead compounds has led to the isolation of five new clerodane diterpenoids (1-5) from the twigs of Casearia kurzii. Their structures were elucidated by extensive analysis of their NMR, IR, and HRESIMS data, and the absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analysis. The isolates were biologically evaluated and showed cytotoxic activities toward human lung cancer cells (A549), human cervical cancer cells (HeLa), and human hepatocellular carcinoma cells (HepG2). The most active compound (5) with an IC value of 5.3 μM against HeLa cells, was found to induce apoptosis and arrest the HeLa cell cycle at G0/G1 stage to exert cytotoxic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.102995DOI Listing
August 2019

Clerodane diterpenoids from Casearia kurzii and their cytotoxic activities.

J Nat Med 2019 Sep 10;73(4):826-833. Epub 2019 Jun 10.

State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University, Tianjin, 300350, People's Republic of China.

A search for bioactive natural products as anticancer lead compounds resulted in the isolation of one previously undescribed and three known clerodane diterpenoids (1-4) from Casearia kurzii. The structures of these compounds were established by analysis of their NMR, MS, and electronic circular dichroism data. The cytotoxic activities of four compounds against three human cancer cell lines were evaluated. Compound 2 was found to be the most active with an IC value of 4.1 μM against HeLa cells, and was selected to investigate the possible cytotoxic mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11418-019-01324-5DOI Listing
September 2019

Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy.

Nanoscale 2019 Jun;11(24):11605-11616

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Department of Orthopaedics Trauma and Hand Surgery, Guangxi Medical University, Nanning, 530021, China.

Anti-oxidative agents hold great potential in osteoarthritis (OA) therapy. However, most radical scavengers have poor biocompatibility and potential cytotoxicity, which limit their applications. Herein we explore dopamine melanin (DM) nanoparticles as a novel scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS). DM nanoparticles show low cytotoxicity and a strong ability to sequester a broad range of ROS and RNS, including superoxides, hydroxyl radicals, and peroxynitrite. This translates to excellent anti-inflammatory and chondro-protective effects by inhibiting intracellular ROS and RNS and promoting antioxidant enzyme activities. With an average diameter of 112.5 nm, DM nanoparticles can be intra-articularly (i.a.) injected into an affected joint and retained at the injection site. When tested in vivo in rodent OA models, DM nanoparticles showed diminished inflammatory cytokine release and reduced proteoglycan loss, which in turn slowed down cartilage degradation. Mechanistic studies suggest that DM nanoparticles also enhance autophagy that benefits OA control. In summary, our study suggests DM nanoparticles as a safe and promising therapeutic for OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr03060cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776464PMC
June 2019

Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

Bioorg Chem 2019 06 22;87:585-593. Epub 2019 Mar 22.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300050, People's Republic of China. Electronic address:

A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The NO inhibitory effects were examined by inhibiting NO release in lipopolysaccharide-stimulated murine microglial BV-2 cells. Molecular docking studies showed the strong interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein, revealing the potential mechanism of NO inhibition of bioactive compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.03.051DOI Listing
June 2019

Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities.

Bioorg Chem 2019 06 15;87:447-456. Epub 2019 Mar 15.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A-F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.03.022DOI Listing
June 2019

NO inhibitory phytochemicals as potential anti-inflammatory agents from the twigs of Trigonostemon heterophyllus.

Bioorg Chem 2019 06 15;87:417-424. Epub 2019 Mar 15.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address:

Studies on the relationship of nitric oxide (NO) and inflammation have revealed that compounds with NO inhibitory effects are potentially useful for inflammation and related inflammatory disorders. A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of two new cleistanthane diterpenoids (1 and 2) and 11 known terpenoids (3-13) from Trigonostemon heterophyllus. The structures of these terpenoids were established by analysis of their NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 possess rare 3,4-seco-cleistanthane diterpenoid skeletons. All of the isolates were evaluated biologically for their NO inhibitory effects in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells and compounds 1, 6, and 8-10 showed strong NO inhibitory effects with IC values less than 40 μM. Using Western blotting experiments and molecular docking, the possible mechanism of NO inhibition was investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.03.029DOI Listing
June 2019

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii.

Bioorg Chem 2019 04 2;85:558-567. Epub 2019 Feb 2.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A-F (1-6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1-6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC value of 5.3 μM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.01.048DOI Listing
April 2019

Bioactive Diterpenoids from the Stems of Euphorbia royleana.

J Nat Prod 2019 02 7;82(2):183-193. Epub 2019 Feb 7.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research , Nankai University , Tianjin 300350 , People's Republic of China.

Two ingenane- (1 and 2), two ent-atisane- (3 and 4), two ent-kaurane- (5 and 6), two ent-abietane- (7 and 8), and one ent-isopimarane-type (9) diterpenoid and 12 known analogues have been isolated from the methanolic extract of the stems of Euphorbia royleana. Their structures, including absolute configurations, were determined by extensive spectroscopic methods and ECD data analysis. The nitric oxide inhibitory activities of those diterpenoids were examined biologically in lipopolysaccharide-stimulated BV-2 cells, with compounds 1, 2, 5-7, 10, and 12 having IC values lower than 40 μM. Molecular docking was used to investigated the possible mechanism of compounds 1, 2, 5-7, 10, and 12.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.8b00493DOI Listing
February 2019

Nitric oxide inhibitory limonoids as potential anti-neuroinflammatory agents from Swietenia mahagoni.

Bioorg Chem 2019 03 19;84:177-185. Epub 2018 Nov 19.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

Recent studies have revealed that there is a close relationship between neuroinflammation and Alzheimer's disease (AD) and compounds with anti-neuroinflammatory effects are potentially useful for the treatment of AD. A phytochemical investigation to obtain new neuroinflammatory inhibitors resulted in the isolation of four new and three known limonoids from Swietenia mahagoni. The structures of these limonoids were established by NMR, MS, and electronic circular dichroism (ECD) data analysis. Compounds 1-3 feature complicated polycyclic caged structures of limonoid orthoester and represent new examples of phragmalin-type limonoids. All of the isolates showed anti-neuroinflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells with compounds 1 and 3-6 having IC values of 26.8, 26.1, 26.0, 37.1, and 16.5 μM, respectively. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2018.11.012DOI Listing
March 2019

Seco-labdane diterpenoids from the leaves of Callicarpa nudiflora showing nitric oxide inhibitory activity.

Phytochemistry 2018 May 15;149:31-41. Epub 2018 Feb 15.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

Nine previously undescribed seco-labdane diterpenoids, nudiflopenes A-I, were isolated from the leaves of Callicarpa nudiflora. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by the modified Mosher's method and experimental and calculated electronic circular dichroism spectra. Nudiflopenes A-I belong to the class of seco-labdane diterpenoids. All of the isolates showed inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2018.02.001DOI Listing
May 2018

NO inhibitors function as potential anti-neuroinflammatory agents for AD from the flowers of Inula japonica.

Bioorg Chem 2018 04 4;77:168-175. Epub 2018 Jan 4.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address:

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. Inula japonica is a member of the Asteraceae plant family and its flowers have been used as a healthy tea and a traditional Chinese medicine. Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of two new sesquiterpenes and ten known terpenes from the flowers of I. japonica. Their structures were established on the basis of extensive analysis of NMR and MS spectroscopic data, as well as calculated and experimental electronic circular dichroism (ECD) spectra. Among these isolates, compound 1 is a new sesquiterpene with a rare tricyclic fused skeleton, and 2 processes a 1,10-seco-eudesmane skeleton. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein. The present study disclosed that the flowers of I. japonica as a healthy tea are potentially useful for AD and related neuroinflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2018.01.009DOI Listing
April 2018

Daphnane diterpenoids with nitric oxide inhibitory activities and interactions with iNOS from the leaves of Trigonostemon thyrsoideus.

Phytochemistry 2018 Mar 28;147:57-67. Epub 2017 Dec 28.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

A phytochemical investigation to search for new nitric oxide (NO) inhibitors resulted in the isolation of seven previously undescribed daphnane diterpenoids, thyrsoidpenes A-G, from the leaves of Trigonostemon thyrsoideus. Their structures including absolute configurations were elucidated on the basis of extensive NMR spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Thyrsoidpenes B-G feature rare polycyclic caged structures of daphnane diterpenoid orthoester. The NO inhibitory effects were examined and all of the compounds showed inhibitory activities toward LPS-induced NO production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2017.12.010DOI Listing
March 2018

Nitric oxide inhibitors with a spiro diterpenoid skeleton from Scutellaria formosana: Structures, NO inhibitory effects, and interactions with iNOS.

Bioorg Chem 2018 02 21;76:53-60. Epub 2017 Oct 21.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin-300350, People's Republic of China. Electronic address:

A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of five new spiro diterpenoids (1 -5) from the aerial parts of Scutellaria formosana. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The nitric oxide (NO) inhibitory effects were evaluated and all of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2017.10.008DOI Listing
February 2018

Nitric oxide inhibitory daphnane diterpenoids as potential anti-neuroinflammatory agents for AD from the twigs of Trigonostemon thyrsoideus.

Bioorg Chem 2017 12 7;75:149-156. Epub 2017 Sep 7.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address:

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1-4) and eight known (5-12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1-4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2017.09.007DOI Listing
December 2017

Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum: Structures, PTP1B inhibitory activities, and interactions with PTP1B.

Bioorg Chem 2017 12 6;75:139-148. Epub 2017 Sep 6.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address:

Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2017.09.001DOI Listing
December 2017

Clerodane diterpenoids from Scutellaria formosana with inhibitory effects on NO production and interactions with iNOS protein.

Phytochemistry 2017 Dec;144:141-150

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address:

A phytochemical study on Scutellaria formosana afforded five previously undescribed spiro-diterpenoids, scutellapenes A-E. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Scutellapenes B-E possess a spiro-diterpenoid skeleton. All of the compounds showed inhibitory effects on LPS-induced nitric oxide (NO) production in murine microglial BV-2 cells. The further molecular docking studies revealed that these bioactive compounds had strong interactions with the iNOS protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2017.09.005DOI Listing
December 2017

Phytochemicals with NO inhibitory effects and interactions with iNOS protein from Trigonostemon howii.

Bioorg Chem 2017 12 24;75:71-77. Epub 2017 Aug 24.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address:

A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1-3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2017.08.008DOI Listing
December 2017

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis.

Oncotarget 2017 Feb;8(7):12323-12332

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age≤18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.12468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355347PMC
February 2017

Corrosion-wear of β-Ti alloy TMZF (Ti-12Mo-6Zr-2Fe) in simulated body fluid.

Acta Biomater 2016 09 7;42:429-439. Epub 2016 Jul 7.

Department of Materials Science and Engineering, Monash University, Clayton, VIC 3800, Australia. Electronic address:

Unlabelled: Titanium alloys are popular metallic implant materials for use in total hip replacements. Although, α+β titanium alloys such as Ti-6Al-4V have been the most commonly used alloys, the high Young's modulus (∼110GPa) leads to an undesirable stress shielding effect. An alternative is to use β titanium alloys that exhibit a significantly lower Young's modulus (∼70GPa). Femoral stems made of a β titanium alloy known as TMZF (Ti-12Mo-6Zr-2Fe (wt.%)) have been used as part of modular hip replacements since the early 2000's but these were recalled in 2011 by the US Food & Drug Administration (FDA) due to unacceptable levels of 'wear debris'. The wear was caused by small relative movement of the stem and neck at the junction where they fit together in the modular hip replacement design. In this study, the corrosion and wear properties of the TMZF alloy were investigated in simulated body fluid to identify the reason for the wear debris generation. Ti64 was used as a control for comparison. It is shown that the interaction between the surfaces of Ti64 and TMZF with simulated body fluid is very similar, both from the point of view of the products formed and the kinetics of the reaction. The dry wear behaviour of TMZF is also close to that of Ti64 and consistent with expectations based on Archard's law for abrasive wear. However, wear of Ti64 and TMZF in simulated body fluid show contrasting behaviours. A type of time-dependent wear test is used to examine the synergy between corrosion and wear of TMZF and Ti64. It is shown that the wear of TMZF accelerated rapidly in SBF whereas that of Ti64 is reduced. The critical role of the strain hardening capacity of the two materials and its role in helping the surface resist abrasion by hydroxyapatite particles formed as a result of the reaction with the SBF is discussed and recommendations are made for modifications that could be made to the TMZF alloy to improve the corrosion-wear response.

Statement Of Significance: TMZF is a low modulus β-Ti alloy that has been used as the femoral stem in the Stryker modular design total hip replacement. It went into service in the early 2000's but was recalled by the FDA in 2011 due to unacceptable levels of wear debris released in the body which led to adverse physiological reactions. A large number of these implants remain in patients today. In this contribution, we investigate the corrosion (interaction of the alloy with simulated body fluid (SBF)), dry wear and then corrosion-wear in SBF to identify the origin of the unacceptable levels of wear that led to the FDA recall of this material. We use Ti-6Al-4V as a control and demonstrate that the reaction between Ti64 and TMZF with SBF is very similar in terms of both products formed and kinetics. We also show that the dry wear behaviour of TMZF is very similar to that of Ti64 and exactly as should be expected for the hardness of this material. However, the wear behaviours of TMZF and Ti64 are completed different in SBF and wear of TMZF is significantly accelerated in SBF. A type of time-dependent wear test is used to demonstrate the synergy between corrosion and wear and the key role of the strain hardening capacity (or lack thereof in the case of β-Ti) is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2016.07.008DOI Listing
September 2016

[An outbreak of foot pain syndrome among students from a senior high school in Foshan, Guangdong province, 2014].

Zhonghua Liu Xing Bing Xue Za Zhi 2015 Jun;36(6):629-33

Chinese Field Epidemiology Training Program, Chinese Center for Disease Control and Prevention.

Objective: To identify the cause of an outbreak of foot pain syndrome among students from a senior high school in Foshan.

Methods: We defined a suspect case as onset of foot pain/numbness with unknown reason among students and teachers in a school of Foshan city, from February 10 to March 16, 2014. A suspect case was noticed as having both food pain and numbness. All the cases were searched through reviewing medical records in the nearby hospitals and school's clinic, also the records of absenteeism in school. Clinical information was collected from all the students, using a standardized questionnaire. Daily temperature was collected from all the students, between January 1 and March 31, 2014. A 1 : 2 individual matched case-control study was conducted to identify related risk factors on this epidemic. We interviewed all the cases and controls on their diet, physical activities and measures used for warming.

Results: A total of 407 case-students were identified, with an attack rate (AR) as 26.5%. The AR was 37.3% in girls, compared to 12.9% in boys. The difference was statistically significant (χ² = 115.1, P < 0.01). Boarding students had a higher AR (31.8%) than the commuting students (16.2%). The difference was statistically significant (χ² = 43.2, P < 0.01). In girls, boarding students had higher AR (46.1%) than those commuting students (18.5%). The difference was statistically significant (χ² = 61.4, P < 0.01). No statistically significant difference was found between boarding or commuting students in boys. Outdoor temperature was coming down from 23 °C on February 6 to 6 °C on February 13, but gradually rose to 23 °C on February 28. There was a positive relationship (r = 0.65, P = 0.002) noticed between daily maximum temperature and the number of cases during February 13-28. Results from this case-control study showed that factors as lacking physical activities (OR = 2.8, 95% CI: 1.5-5.6), feeling cold in bed (OR = 3.0, 95% CI: 1.3-7.0) and having experienced similar symptoms (OR = 3.4, 95% CI: 1.1-11.0) could increase the risk of this disease.

Conclusion: This outbreak was possibly caused by the abrupt fluctuation of temperature within a short period.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2015

mRNA profiles of cytokine receptors in unstimulated peripheral blood mononuclear cells from patients with chronic idiopathic urticaria.

J Biomed Res 2011 Mar;25(2):141-7

Department of Dermatology, Haidian Hospital, Beijing 10080, China ; Section of Clinical Immunology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, Jiangsu, China.

This present study was aimed to investigate the roles of the receptors of Th1/Th2 cytokines and chemokines in the pathogenesis of chronic idiopathic urticaria (CIU). Thirty patients with CIU, 30 patients with dermographism and 30 healthy controls were randomly enrolled. Reverse transcription-PCR (RT-PCR) was used to analyze the mRNA of cytokine receptors in peripheral blood mononuclear cells (PBMCs). The mRNA levels of tumor necrosis factor receptor (TNFR), interferon-γ receptor (IFN-γR), and interleukin-10 receptor (IL-10R) were statistically increased in the CIU group (P < 0.05), while IL-2R, IL-4R, IL-6R, and IL-13R showed no significant differences between the CIU and other groups. The mRNA levels of CCR3 and CCR6 were statistically increased in the CIU group (P < 0.05). The toll-like receptor 2 (TLR2) mRNA level was significantly lower in the CIU group than the healthy control group (P < 0.05). These findings indicate that the regulation of mRNA of TNFR, IFN-γR, IL-10R, CCR3, CCR6 and TLR2 may be involved in the pathogenesis of CIU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1674-8301(11)60018-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596706PMC
March 2011