Publications by authors named "Yong Lan"

46 Publications

SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging.

Mol Ther Nucleic Acids 2021 Mar 26;23:1323-1333. Epub 2021 Jan 26.

Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.

Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.
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http://dx.doi.org/10.1016/j.omtn.2021.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920857PMC
March 2021

Nanoparticle-Mediated Delivery of Emodin via Colonic Irrigation Attenuates Renal Injury in 5/6 Nephrectomized Rats.

Front Pharmacol 2020 21;11:606227. Epub 2021 Jan 21.

Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Our previous study showed that emodin enema modulates gut microbiota and delays CKD progression. However, the poor solubility, limited colonic irrigation retention time, and inadequate colon adhesion of emodin hinder its clinical application. Based on the deficiencies of emodin, we prepared monomethoxy-poly (ethylene glycol)-poly (lactic acid)-chitosan-2-mercaptobenzimidazole nanoparticles with incorporated emodin (emodin-NP) and studied their efficacy in delaying CKD progression. 5/6 nephrectomized Male Sprague Dawley rats were administered via colonic irrigation with emodin-NP every two days for eight weeks. We found that treatment with emodin-NP improved the kidney function of the rats and limited the expansion of tubulointerstitial fibrosis. Treatment with emodin-NP once every two days is comparable to emodin treatment once a day. Furthermore, emodin-NP via colonic irrigation remarkably reduced IL-1β, IL-6, and LPS levels in serum, improved intestinal barrier functions, and downregulated the key proteins (TLR4, MyD88, and NF-κB) expression in intestinal TLR4 signaling pathway. 16S rDNA analyses showed that emodin-NP can regulate microbiota disturbance in CKD. Taken together, these results suggest that emodin-NP alleviates kidney dysfunction and tubulointerstitial fibrosis by mediation through the modification of gut microbiota disorders. Emodin-NP may be a new method to treat CKD.
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http://dx.doi.org/10.3389/fphar.2020.606227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858270PMC
January 2021

Ultrasmall Superparamagnetic Iron Oxide Labeled Silk Fibroin/Hydroxyapatite Multifunctional Scaffold Loaded With Bone Marrow-Derived Mesenchymal Stem Cells for Bone Regeneration.

Front Bioeng Biotechnol 2020 30;8:697. Epub 2020 Jun 30.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Numerous tissue-engineered constructs have been investigated as bone scaffolds in regenerative medicine. However, it remains challenging to non-invasively monitor the biodegradation and remodeling of bone grafts after implantation. Herein, silk fibroin/hydroxyapatite scaffolds incorporated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were successfully synthesized, characterized, and implanted subcutaneously into the back of nude mice. The USPIO labeled scaffolds showed good three-dimensional porous structures and mechanical property, thermal stability for bone repair. After loaded with bone marrow-derived mesenchymal stem cells (BMSCs), the multifunctional scaffolds promoted cell adhesion and growth, and facilitated osteogenesis by showing increased levels of alkaline phosphatase activity and up-regulation of osteoblastic genes. Furthermore, quantitative magnetic resonance imaging (MRI) results provided valuable information on scaffolds degradation and bone formation simultaneously, which was further confirmed by computed tomography and histological examination. These findings demonstrated that the incorporation of USPIO into BMSCs-loaded multifunctional scaffold system could be feasible to noninvasively monitor bone regeneration by quantitative MRI. This tissue engineering strategy provides a promising tool for translational application of bone defect repair in clinical scenarios.
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http://dx.doi.org/10.3389/fbioe.2020.00697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338306PMC
June 2020

A CT-based deep learning model for predicting the nuclear grade of clear cell renal cell carcinoma.

Eur J Radiol 2020 Aug 20;129:109079. Epub 2020 May 20.

Department of Radiology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Guangdong Medical University, Affiliated Jiangmen Hospital of SUN YAT-SEN University, 23 Beijie Haibang Street, Jiangmen, 529030, China. Electronic address:

Purpose: To investigate the effects of different methodologies on the performance of deep learning (DL) model for differentiating high- from low-grade clear cell renal cell carcinoma (ccRCC).

Method: Patients with pathologically proven ccRCC diagnosed between October 2009 and March 2019 were assigned to training or internal test dataset, and external test dataset was acquired from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) database. The effects of different methodologies on the performance of DL-model, including image cropping (IC), setting the attention level, selecting model complexity (MC), and applying transfer learning (TL), were compared using repeated measures analysis of variance (ANOVA) and receiver operating characteristic (ROC) curve analysis. The performance of DL-model was evaluated through accuracy and ROC analyses with internal and external tests.

Results: In this retrospective study, patients (n = 390) from one hospital were randomly assigned to training (n = 370) or internal test dataset (n = 20), and the other 20 patients from TCGA-KIRC database were assigned to external test dataset. IC, the attention level, MC, and TL had major effects on the performance of the DL-model. The DL-model based on the cropping of an image less than three times the tumor diameter, without attention, a simple model and the application of TL achieved the best performance in internal (ACC = 73.7 ± 11.6%, AUC = 0.82 ± 0.11) and external (ACC = 77.9 ± 6.2%, AUC = 0.81 ± 0.04) tests.

Conclusions: CT-based DL model can be conveniently applied for grading ccRCC with simple IC in routine clinical practice.
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http://dx.doi.org/10.1016/j.ejrad.2020.109079DOI Listing
August 2020

Combination of hepatocyte fraction and diffusion-weighted imaging as a predictor in quantitative hepatic fibrosis evaluation.

Abdom Radiol (NY) 2020 11;45(11):3681-3689

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035, People's Republic of China.

Objective: To investigate the performance of the combined hepatocyte fraction (HepF) and apparent diffusion coefficient (ADC) values to stage hepatic fibrosis (HF) in patients with hepatitis B/C.

Materials And Methods: A total of 281 patients with hepatitis B/C prospectively underwent gadoxetate disodium-based T1 mapping and diffusion-weighted imaging. HepF was determined from pre and postcontrast T1 mapping with pharmacokinetics. The independent predictors of the HF stage (S0-4) were identified from HepF, ADC, conventional T1-based parameters, and age using a logistic regression analysis. The performances of independent and combined predictors in diagnosing various HF stages were compared by analyzing receiver operating characteristic curves. The intraclass correlation coefficient (ICC) was used to assess the interobserver reproducibility of each predictor.

Results: In total, 167 patients with various stages of HF were included. All measurements had excellent interobserver agreement (ICC ≥ 0.75). The hepatic relative enhancement, HepF ,and ADC values were significantly different among various HF stages (p < 0.05). The HepF and ADC were independent predictors of > S0, > S1, > S2 , and > S3 disease (p < 0.05). T1, T1, and T1 were independent predictors of S > 2 disease (p < 0.05). The performance of HepF combined with the ADC (area under the curve (AUC) = 0.84-0.95) was higher than HepF (AUC = 0.79-0.92) or ADC (AUC = 0.82-0.89) alone in diagnosing > S0, > S1, > S2 , and > S3 disease.

Conclusion: The combined predictor of HepF and ADC shows acceptable performance for staging HF.
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http://dx.doi.org/10.1007/s00261-020-02520-8DOI Listing
November 2020

Predicting the ISUP grade of clear cell renal cell carcinoma with multiparametric MR and multiphase CT radiomics.

Eur Radiol 2020 May 30;30(5):2912-2921. Epub 2020 Jan 30.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035, China.

Objective: To investigate externally validated magnetic resonance (MR)-based and computed tomography (CT)-based machine learning (ML) models for grading clear cell renal cell carcinoma (ccRCC).

Materials And Methods: Patients with pathologically proven ccRCC in 2009-2018 were retrospectively included for model development and internal validation; patients from another independent institution and The Cancer Imaging Archive dataset were included for external validation. Features were extracted from T1-weighted, T2-weighted, corticomedullary-phase (CMP), and nephrographic-phase (NP) MR as well as precontrast-phase (PCP), CMP, and NP CT. CatBoost was used for ML-model investigation. The reproducibility of texture features was assessed using intraclass correlation coefficient (ICC). Accuracy (ACC) was used for ML-model performance evaluation.

Results: Twenty external and 440 internal cases were included. Among 368 and 276 texture features from MR and CT, 322 and 250 features with good to excellent reproducibility (ICC ≥ 0.75) were included for ML-model development. The best MR- and CT-based ML models satisfactorily distinguished high- from low-grade ccRCCs in internal (MR-ACC = 73% and CT-ACC = 79%) and external (MR-ACC = 74% and CT-ACC = 69%) validation. Compared to single-sequence or single-phase images, the classifiers based on all-sequence MR (71% to 73% in internal and 64% to 74% in external validation) and all-phase CT (77% to 79% in internal and 61% to 69% in external validation) images had significant increases in ACC.

Conclusions: MR- and CT-based ML models are valuable noninvasive techniques for discriminating high- from low-grade ccRCCs, and multiparameter MR- and multiphase CT-based classifiers are potentially superior to those based on single-sequence or single-phase imaging.

Key Points: • Both the MR- and CT-based machine learning models are reliable predictors for differentiating high- from low-grade ccRCCs. • ML models based on multiparameter MR sequences and multiphase CT images potentially outperform those based on single-sequence or single-phase images in ccRCC grading.
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http://dx.doi.org/10.1007/s00330-019-06601-1DOI Listing
May 2020

In situ formed anti-inflammatory hydrogel loading plasmid DNA encoding VEGF for burn wound healing.

Acta Biomater 2019 12 4;100:191-201. Epub 2019 Oct 4.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

Excessive inflammation and reduced angiogenesis are two major obstacles in burn wound healing and skin regeneration. Here we report the fabrication and application of a sophisticated hydrogel from chemically modified hyaluronic acid (HA), dextran (Dex), and β-cyclodextrin (β-CD) integrating resveratrol (Res) and vascular endothelial growth factor (VEGF) plasmid as the anti-inflammatory and pro-angiogenic components for burn wounds. Firstly, covalent alterations were conducted to obtain methacrylic acid anhydride modified HA (HAMA), N-hydroxyethylacrylamide (HEAA) modified Dex (Dex-HEAA), and poly(ethylene glycol) methyl acrylate (526) modified β-CD (526-β-CD), respectively. Secondly, anti-inflammatory substance Res was embedded into the lipophilic central cavity of 526-β-CD to achieve a complex of 526-β-CD-Res. Then hydrogels with different HAMA, Dex-HEAA, and 526-β-CD-Res ratios were generated via UV irradiation. Lastly, plasmid DNA encoded with vascular endothelial growth factor (pDNA-VEGF) conjugating with polyethylenimine was loaded into the hydrogel scaffold. Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds. STATEMENT OF SIGNIFICANCE: Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.
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http://dx.doi.org/10.1016/j.actbio.2019.10.004DOI Listing
December 2019

A non-invasive monitoring of USPIO labeled silk fibroin/hydroxyapatite scaffold loaded DPSCs for dental pulp regeneration.

Mater Sci Eng C Mater Biol Appl 2019 Oct 9;103:109736. Epub 2019 May 9.

Guangzhou Nansha District Maternal and Child Health Care Hospital, Guangzhou 511458, China. Electronic address:

The aim of this study was to prepare a promising biomaterial for dental pulp tissue repair and regeneration. The ultrasmall superparamagnetic iron oxide (USPIO)-labeled hydroxyapatite (HA)/silk fibroin (SF) scaffold loaded dental pulp stem cells (DPSCs) was designed. The odontogenic differentiation of DPSCs was investigated, and USPIO was used as magnetic resonance imaging (MRI) contrast agent. The results indicated that scaffolds freeze-dried from SF solution with 0.025 mg/mL USPIO and 5 mg/mL HA showed stable physical properties, accurate MRI images, and low cytotoxicity in vitro. The composite scaffolds were characterized and implanted to the subcutaneous space under the nude mice with tooth fragment. After 2 W of implantation, the relaxation rate (R2) values increased because of incorporation of USPIO, then decreased with the degradation of scaffolds. The tissue regeneration and scaffolds degradation behaviors were monitored by MRI. The expression of dentin sialophosphoprotein (DSPP) and dentin matrix acidic phosphoprotein 1 (DMP1) indicated that DPSCs differentiated into odontoblast-like cells. Revascularization and mineralization evaluated by HE-stained images and alizarin red staining images showed good formation. The USPIO/HA/SF composite scaffold loaded DPSCs promoted the repair and regeneration of dental pulp tissue and provided the ability of imaging noninvasively.
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http://dx.doi.org/10.1016/j.msec.2019.05.021DOI Listing
October 2019

Integrity of zinc finger motifs in PML protein is necessary for inducing its degradation by antimony.

Metallomics 2019 08 17;11(8):1419-1429. Epub 2019 Jul 17.

Department of Pharmacology, School of Medicine, Zhejiang University, China and Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Zhejiang, 310058, China. and College of Pharmaceutical Sciences, Inner Mongolia Medical University, Hohhot, China and Department of Hematology, The First Affiliated Hospital, Zhejiang University, China.

Antimony (Sb) belongs to the same group as arsenic (As) in the periodic table, and both share similar characteristics. However, SbO (Sb) has no methylation capacity, unlike arsenic trioxide (AsO). In the present study, we determined the effect of Sb on NB4 cells and found that antimony could induce PML-RARα fusion protein degradation, reorganization of PML-NBs, and NB4 cell differentiation with low cytotoxicity. On the other hand, zinc finger motifs in PML protein are considered to be a key target binding site for arsenic-induced PML-RARα protein degradation. Interestingly, antimony and arsenic lost their ability to degrade PML-RARα fusion protein in NB4 cells following pretreatment with phenanthroline (i.e., chelator of zinc ions), indicating that the integrity of zinc finger motifs in PML-RARα fusion protein is a fundamental condition for inducing the protein's degradation by antimony and arsenic. Moreover, we found that Sb could not induce mutant PML (e.g., A126V and L218P) solubility change and degradation, similar to AsO. In contrast, we found that the organic antimony compound phenylstibine oxide (PSO) could induce mutant PML protein degradation. In conclusion, our results indicate that Sb might also be a promising agent to treat acute promyelocytic leukemia, in the same manner as AsO.
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http://dx.doi.org/10.1039/c9mt00102fDOI Listing
August 2019

Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4.

Theranostics 2019 9;9(15):4525-4541. Epub 2019 Jun 9.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.

Evidence indicates that microRNAs (miRNAs) play vital roles in regulating osteogenic differentiation and bone formation. : Here, we show that a polyethyleneimine (PEI)-functionalized graphene oxide (GO) complex efficiently loaded with the miR-214 inhibitor is assembled into silk fibroin/hydroxyapatite (SF/HAP) scaffolds that spatially control the release of the miR-214 inhibitor. : SF/HAP/GO scaffolds with nanosized GO show high mechanical strength, and their hierarchical microporous structures promote cell adhesion and growth. The SF/HAP/GO-PEI scaffolds loaded with mir-214 inhibitor (SF/HAP/GPM) were tested for their ability to enhance osteogenic differentiation by inhibiting the expression of miR-214 while inversely increasing the expression of activating transcription factor 4 (ATF4) and activating the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) . Similarly, the scaffolds activated the osteoblastic activity of endogenous osteoblast cells to repair critical-sized bone defects in rats without the need for loading osteoblast cells. : This technology is used to increase osteogenic differentiation and mineralized bone formation in bone defects, which helps to achieve cell-free scaffold-based miRNA-inhibitor therapy for bone tissue engineering.
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http://dx.doi.org/10.7150/thno.34676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599658PMC
August 2020

Enhanced cutaneous wound healing by functional injectable thermo-sensitive chitosan-based hydrogel encapsulated human umbilical cord-mesenchymal stem cells.

Int J Biol Macromol 2019 Sep 2;137:433-441. Epub 2019 Jul 2.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address:

Human umbilical cord-mesenchymal stem cells (hUCMSCs) can secrete a variety of cytokines and growth factors promoting wound repair. Hydrogel is suitable biomaterial to supply niche for cells adhesion and survival. This study constructed a functional injectable thermo-sensitive hydrogel (chitosan/glycerol phosphate sodium/cellulose nanocrystals, CS/GP/CNC) encapsulated hUCMSCs to repair full-thickness cutaneous wound. Addition of CNC to the CS/GP system not only accelerated the gel speed, but also greatly improved the mechanical properties of the gel and decreased degradation rate. The novel hydrogel was injectable and low toxicity. Histological detection showed that hydrogel-hUCMSCs combination significantly accelerated wound closure, microcirculation, tissue remodeling, re-epithelialization and hair follicle regeneration, and inhibited over-inflammation in the central and surrounding wounds. The hydrogel-hUCMSCs combination promoted collagen deposition and keratinocyte mature marker K1 expression, decreased inflammatory factors secretion namely TNF-α and IL-1β. The present data provides a potential strategy for treatment of non-healing chronic cutaneous wounds.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.06.246DOI Listing
September 2019

Controlled-release neurotensin-loaded silk fibroin dressings improve wound healing in diabetic rat model.

Bioact Mater 2019 Dec 28;4:151-159. Epub 2019 Mar 28.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.

Diabetic foot ulcers (DFU), which may lead to lower extremity amputation, is one of the severe and chronic complications of diabetic mellitus. This study aims to develop, and use dressings based on Silk fibroin (SF) as the scaffold material, gelatin microspheres (GMs) as the carrier for the neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing and NT as accelerate wound healing drug to treat DFU. We evaluated the wound healing processes and neo-tissue formation in rat diabetic model by macroscopic observation, histological observation (H&E staining and Masson's trichrome staining) and immunofluorescence analysis at 3, 7, 14, 21 and 28 post-operation days. Our results show that the NT/GMs/SF group performance the best not only in macroscopic healing and less scars in 28 post-operation days, but also in fibroblast accumulation in tissue granulation, collagen expression and deposition at the wound site. From release profiles, we can know the GMs are a good carrier for control release drugs. The SEM results shows that the NT/GMs/SF dressings have an average pore size are 40-80 μm and a porosity of ∼85%, this pore size is suit for wound healing regeneration. These results suggest that the NT/GMs/SF dressings may work as an effective support for control release NT to promote DFU wound healing.
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http://dx.doi.org/10.1016/j.bioactmat.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447858PMC
December 2019

Preparation and characterization of the collagen/cellulose nanocrystals/USPIO scaffolds loaded kartogenin for cartilage regeneration.

Mater Sci Eng C Mater Biol Appl 2019 Jun 19;99:1362-1373. Epub 2019 Feb 19.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address:

The regeneration of cartilage is a challenging problem for lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), an emerging chondroinductive non-protein small molecule, bound to the surface of the ultrasmall super-paramagnetic iron-oxide (USPIO) by innovational one-step technology, followed by being incorporated into the cross-linking collagen/cellulose nanocrystals (Col/CNC) bioactive scaffolds to stimulate an appropriate microenvironment for the growth and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), thus facilitating the formation of chondrocyte. Herein, USPIO not only served as a carrier for small molecule drugs, but also as MRI contrast agents, which can non-invasively monitor the degradation of the scaffolds and the self-repair capacity of cartilage. In vitro studies showed that the KGN could release from the composite scaffolds in a sustained and stable manner and promote the chondrogenic differentiation of BMSCs based on UV spectrophotometry test, and specific markers analysis. Of note, USPIO labeled composite scaffolds retained their stability without loss of relaxation rate the composite scaffolds can be a promising biomaterials for cartilage repair, with the function of noninvasive visualization and semiquantitative analysis of scaffolds degradation and neocartilage.
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http://dx.doi.org/10.1016/j.msec.2019.02.071DOI Listing
June 2019

Preparation and characterisation of a novel silk fibroin/hyaluronic acid/sodium alginate scaffold for skin repair.

Int J Biol Macromol 2019 Jun 22;130:58-67. Epub 2019 Feb 22.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address:

To mimic the natural structure of tissue extracellular matrix, a novel silk fibroin (SF)/hyaluronic acid (HA)/sodium alginate (SA) composite scaffold (92% in porosity) was prepared by freeze-drying. Fourier-transform infrared spectroscopy and Raman spectra indicated interactions among SF, HA, and SA molecules. Scanning electron microscopy showed that the prepared SF/HA/SA scaffold had soft, elastic characteristics, with an average pore diameter of 93 μm. Mechanical property, thermogravimetric analyses and degradation results indicated that the SF/HA/SA scaffold had good physical stability in body fluid and mechanical movement-related environments. Cell proliferation, morphological, and live-dead analyses showed that NIH-3T3 fibroblast cells were better able to attach, grow, and proliferate on the SF/HA/SA scaffold compared with SF, SF/HA, and SF/SA scaffolds. We evaluated the wound healing effects in a rat full-thickness burn model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results from SF/HA/SA scaffold showed that improved re-epithelialization, enhanced extracellular matrix remodeling. Our findings showed that the prepared SF/HA/SA scaffold can provide a potential way as a wound dressing for skin repair.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.02.120DOI Listing
June 2019

Long noncoding RNA MEG3 prevents vascular endothelial cell senescence by impairing miR-128-dependent Girdin downregulation.

Am J Physiol Cell Physiol 2019 06 21;316(6):C830-C843. Epub 2018 Dec 21.

Beijing Neurosurgical Institute, Capital Medical University , Beijing , People's Republic of China.

Long noncoding RNAs (lncRNAs) are commonly associated with various biological functions, in which the function of lncRNA maternally expressed gene 3 (MEG3) has been identified in various cancers. Strikingly, an association between MEG3 with microRNAs (miRNAs), mRNAs, and proteins has been reported. This study investigates the role of MEG3 in vascular endothelial cell (VEC) senescence. Expression of Girdin and miR-128 was monitored in the blood vessel samples of young and old mice/healthy volunteers, along with the measurement of human umbilical vein endothelial cells (HUVECs). The relationship between MEG3/Girdin and miR-128 was determined and verified. Loss- and gain-of-function approaches were applied to analyze the regulatory effects of MEG3 on platelet phagocytosis and lipoprotein oxidation of HUVEC membrane. In addition, the effect of MEG3 on HUVEC senescence was evaluated by detection of the reactive oxygen species, telomerase activity, and telomere length. To further analyze the MEG3-mediated regulatory mechanism, miR-128 upregulation and inhibition were introduced into the HUVECs. Downregulated Girdin and upregulated miR-128 were found in the blood vessels of old individuals and old mice, as well as in senescent HUVECs. MEG3 downregulation was found to be capable of inhibiting Girdin but enhancing miR-128 expression. It was also indicated to inhibit platelet phagocytosis and reduce telomerase activity and telomere length, while enhancing lipoprotein oxidation and reactive oxygen species production, which ultimately contributed in preventing and protecting HUEVCs from senescence. These findings provide evidence supporting that MEG3 leads to miR-128 downregulation and Girdin upregulation, which promotes platelet phagocytosis, thus protecting VECs from senescence.
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http://dx.doi.org/10.1152/ajpcell.00262.2018DOI Listing
June 2019

Nanoparticle-mediated delivery of Tanshinone IIA reduces adverse cardiac remodeling following myocardial infarctions in a mice model: role of NF-κB pathway.

Artif Cells Nanomed Biotechnol 2018 4;46(sup3):S707-S716. Epub 2018 Oct 4.

a Key Discipline of Integrated Chinese and Western Medicine , Second Clinical College, Guangzhou University of Chinese Medicine , Guangzhou , China.

Our previous works have shown that tanshinone IIA inhibited maladaptive extracellular matrix remodeling in cardiac fibroblasts implicating its potential role in treating of pathologic cardiac remodeling. However, the intrinsically poor solubility and bioavailability of tanshinone IIA hindered its clinical application. Here we develop monomethoxy-poly (ethylene glycol)-poly (lactic acid)-D-α-Tocopheryl polyethylene glycol 1000 succinate (mPEG-PLA-TPGS) nanoparticle incorporating tanshinone IIA (tanshinone IIA-NPs) and study its efficacy in post-infarction left ventricular (LV) remodeling. Male C57BL/6 mice underwent left coronary artery ligation followed by subsequent intravenously injected tanshinone IIA-NPs therapy for 5 consecutive days. Treatment with tanshinone IIA-NP improved cardiac function, limited infarct expansion, and prevented left ventricle dilation at 4 weeks post-MI. Furthermore, cardiomyocytes inflammation, apoptosis and myocardial fibrosis were significantly attenuated in tanshinone IIA-NP treated mice. These effects also correlated with inhibition of IκB protein phosphorylation and NF-κB activation, leading to suppression of proinflammatory cytokine expression. Together, these results demonstrate tanshinone IIA-NP attenuated adverse cardiac remodeling and dysfunction mediated through prevention of IκB phosphorylation and NF-κB activation. Tanshinone IIA-NP is a novel approach to treat myocardial IR injury in patients with MI.
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http://dx.doi.org/10.1080/21691401.2018.1508028DOI Listing
June 2019

Controlled Release of BMP-2 from a Heparin-Conjugated Strontium-Substituted Nanohydroxyapatite/Silk Fibroin Scaffold for Bone Regeneration.

ACS Biomater Sci Eng 2018 Sep 9;4(9):3291-3303. Epub 2018 Aug 9.

Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije University Amsterdam, Gustav mahlerlaan 3004, 1081 LA Amsterdam, the Netherlands.

The objective of this study was to develop heparin-conjugated strontium-substituted hydroxyapatite/silk fibroin (Sr-nHAp/SF-Hep) scaffold loaded bone morphogenetic proteins-2 (BMP-2) with sustained release to improve bone regeneration. The average pore diameters and porosity of Sr-nHAp/SF scaffolds were respectively approximately 150 μm and 90%. The mechanical properties and thermostability of the Sr-nHAp/SF scaffolds were significantly stronger than those of the SF scaffold. The weight of composite scaffolds is higher than that of the SF scaffold in simulated body fluids. The Sr-nHAp/SF scaffold exhibited excellent biological function of bone marrow mesenchymal stem cell (BMSC) proliferation and adhesion. The expression of related osteogenic genes, including osteocalcin, osteopontion, and alkaline phosphatase activity was elevated by Sr-nHAp/SF-Hep-BMP-2 scaffold, which promoted the differentiation of BMSCs into osteoblasts. results showed that Sr-nHAp/SF-Hep-BMP-2 scaffolds enhanced bone mineral density and improved new bone regeneration, which was accomplished through microcomputed tomography (micro-CT) and histological and histochemical staining analysis. These results demonstrated Sr-nHAp/SF-Hep-BMP-2 scaffolds with favorable biocompatibility and good mechanical properties have great potential to repair bone defects.
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http://dx.doi.org/10.1021/acsbiomaterials.8b00459DOI Listing
September 2018

Enhanced healing activity of burn wound infection by a dextran-HA hydrogel enriched with sanguinarine.

Biomater Sci 2018 Aug;6(9):2472-2486

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.

Burn wounds are associated with a series of risks, such as infection and pathologic scar tissue formation, which significantly delay wound healing and lead to complications. In this study, we successfully fabricated a dextran-hyaluronic acid (Dex-HA) hydrogel enriched with sanguinarine (SA) incorporated into gelatin microspheres (GMs), which had high porosity, good swelling ratio, enhanced NIH-3T3 fibroblast cell proliferation, and sustained SA release profile. The in vitro degradation results indicate that the SA/GMs/Dex-HA hydrogel can be degraded. The in vitro antibacterial tests showed that the SA/GMs/Dex-HA hydrogel can inhibit methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). We evaluated the wound-healing effects and antibacterial properties of SA/GMs/Dex-HA hydrogels in a rat full-thickness burn infection model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results of the SA/GMs/Dex-HA hydrogel showed that it improved re-epithelialization and enhanced extracellular matrix remodeling, and immunohistochemistry results showed that the expression of TGF-β1 and TNF-α was decreased, while the TGF-β3 expression was increased. Our findings suggest that the SA/GMs/Dex-HA hydrogel provides a potential way for infected burn treatment with high-quality and efficient scar inhibition.
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http://dx.doi.org/10.1039/c8bm00478aDOI Listing
August 2018

Engulfment of platelets delays endothelial cell aging via girdin and its phosphorylation.

Int J Mol Med 2018 Aug 17;42(2):988-997. Epub 2018 May 17.

Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, P.R. China.

Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood‑brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co‑cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co‑localization of PLTs, girders of actin filament (girdin) and phosphorylated (p‑)girdin. Senescence‑associated β‑galactosidase (β‑gal) staining, 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and flow cytometry were performed to examine the cell senescence, viability and apoptosis, respectively. Transwell assays were performed to examine cell invasion and migration. Western blot analysis was performed to detect the expression of girdin, AKT and p‑AKT. PLTs delayed senescence, and promoted the viability and resistance to apoptosis of the HBMECs. Cell invasion and migration were enhanced by PLTs. In addition, girdin and p‑girdin were essential to the engulfment of HBMECs to PLTs. Mechanically, the inhibition of AKT signals reversed the effect of PLTs on HBMECs by increasing the activity of β‑gal, decreasing the cell viability, and inhibiting the invasion and migration of the HBMECs. The engulfment of PLTs assisted in delaying the aging of endothelial cells via girdin and p‑girdin, in which the AKT signal was involved. The present study indicated a potential strategy for delaying endothelial cell aging in the treatment of central nervous system diseases.
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http://dx.doi.org/10.3892/ijmm.2018.3685DOI Listing
August 2018

Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing.

Artif Cells Nanomed Biotechnol 2018 13;46(sup2):493-501. Epub 2018 Apr 13.

a Post-doctoral Management Office , Southern Medical University , Guangzhou , China.

Diabetic foot ulcers (DFUs) are a threat to human health and can lead to amputation and even death. Recently neurotensin (NT), an inflammatory modulator in wound healing, was found to be beneficial for diabetic wound healing. As we demonstrated previously, polylactide-polyglycolide (PLGA) and cellulose nanocrystals (CNCs) (PLGA/CNC) nanofiber membranes show good cytocompatibility and facilitate fibroblast adhesion, spreading and proliferation. PLGA/CNC nanofiber membranes are novel materials that have not been used previously as NT carriers in diabetic wounds. This study aims to explore the therapeutic efficacy and possible mechanisms of NT-loaded PLGA/CNC nanofiber membranes in full-thickness skin wounds in spontaneously diabetic mice. The results showed that NT could be sustained released from NT-loaded PLGA/CNC composite nanofiber membranes for 2 weeks. NT-loaded PLGA/CNC composite nanofiber membranes induced more rapid healing than other control groups. After NT exposure, the histological scores of the epidermal and dermal regeneration and the ratios of the fibrotic area to the whole area were increased. NT-loaded PLGA/CNC composite nanofiber membranes also decreased the expressions of the inflammatory cytokines IL-1β and IL-6. These results suggest that NT-loaded PLGA/CNC composite nanofiber membranes for sustained delivery of NT should effectively promote tissue regeneration for the treatment of DFUs.
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http://dx.doi.org/10.1080/21691401.2018.1460372DOI Listing
June 2019

Significance of the detection of TIM-3 and FOXJ1 in prostate cancer.

J BUON 2017 Jul-Aug;22(4):1017-1021

Department of Urology, Central Hospital of Enshi Autonomous Prefecture, Enshi, China.

Purpose: This study sought to identify and evaluate the diagnostic value of T-cell immunoglobulin domain and mucin-3 (TIM-3) and forkhead box protein J1 (FOXJ1) expression in prostate cancer.

Methods: Thirty prostate cancer patients and 30 individuals with benign prostatic hyperplasia diagnosed and treated at the Central Hospital of Enshi Autonomous Prefecture between March 2016 and October 2016 were selected for this study. The expression of TIM-3 and FOXJ1 in patient prostate tissue was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TIM-3 and FOXJ1 expression diagnostic value for prostate cancer was analyzed by using the receiver operating curve (ROC).

Results: Expression of TIM-3 and FOXJ1 in prostate cancer tissues was significantly higher than those in normal prostate tissues (p<0.05), and expression of TIM-3 and FOXJ1 in prostate cancer tissues were positively correlated with Gleason score and clinical stage (p<0.05). However, the expression of the two proteins were not correlated with age, PSA level, pathological type, or the maximum tumor diameter (p>0.05). ROC analysis indicated that TIM-3 mRNA could be used to diagnose prostate cancer with an accuracy of 0.824, a sensitivity of 85.9% and a specificity of 91.2%, while the diagnostic accuracy, sensitivity, and specificity of FOXJ1 were 0.843, 86.3%, and 82.7%, respectively.

Conclusion: TIM-3 and FOXJ1 exhibited abnormally high expression levels in prostate cancer, and can therefore be important indicators for the diagnosis of this disease.
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July 2019

Need for hyperlipidemia management policy reform in China: learning from the global experience.

Curr Med Res Opin 2018 02 9;34(2):197-207. Epub 2017 Aug 9.

c Shanghai Health Development Research Center , Fudan University , Shanghai , China.

Objective: To evaluate the hyperlipidemia prevention programs and policies in different countries and highlight the need of reforming the hyperlipidemia prevention policies in China to lower the growing cardiovascular disease (CVD) risk.

Research Design And Methods: PubMed, Google Scholar and Cochrane were searched for global hyperlipidemia prevention policies. Government-funded policies pertaining to lipid management were considered for this review. Only those studies that evaluated the success of prevention policies on the basis of: (i) achievement of hyperlipidemia targets; (ii) improvement in Cardiovascular (CV) risk reduction; and (iii) outcomes with reduction in hyperlipidemia after implementation of the policy, were included.

Results: Several global policies and programs aimed to improve CV health by highlighting lipid profile management. Implementation of the global and national policies led to improvement in cholesterol related outcomes such as availability of diagnostic measures, awareness of the risk factors, decrease in cholesterol levels, achieving healthy lifestyle to prevent CVD and improvement in availability of hypolipidemic medications, etc. Statins have been covered under reimbursement policies in many countries to improve usage and thereby preventing incidence of stroke and CVD. We observed a need for introducing new programs in China as the ongoing hyperlipidemia management policies are inadequate. The World Bank Report 2016 recommended that prevention policies in China be modeled on the US Million Hearts program.

Conclusions: New hyperlipidemia prevention policies must set a time-bound target, and need to be patient and clinician centric in terms of applications, and revised periodically for long-term benefits.
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http://dx.doi.org/10.1080/03007995.2017.1354833DOI Listing
February 2018

Collagen-cellulose nanocrystal scaffolds containing curcumin-loaded microspheres on infected full-thickness burns repair.

J Tissue Eng Regen Med 2017 12 22;11(12):3544-3555. Epub 2017 Mar 22.

Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, China.

Burn infection is a serious problem that delays wound healing and leads to death. Curcumin (Cur) has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activity. However, its instability, extremely low aqueous solubility and bioavailability in physiological fluids may make it difficult to maintain local Cur concentrations above the minimum inhibitory concentration for burn infection treatment. The objective of this study was to construct complexes of Cur/gelatin microspheres (GMs) and porous collagen (Coll)-cellulose nanocrystals (CNCs) composite scaffolds for full-thickness burn infection treatment. The Cur/GMs/Coll-CNCs scaffolds had high porosity, available pore size, and a long and sustained Cur release profile. Furthermore, the composite scaffold exhibited remarkably strong antibacterial activity. Hence, we evaluated the wound-healing effects and antibacterial properties of Cur/GMs/Coll-CNCs scaffolds in a rat full-thickness burn infection model. The Cur/GMs/Coll-CNCs scaffold was able to prevent not only local inflammation but also accelerated dermis regeneration. Thus, we conclude that Cur/GMs/Coll-CNCs scaffolds can act as an effective dermal regeneration template for full-thickness burn wound infection healing in rats models. Copyright © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/term.2272DOI Listing
December 2017

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes.

Int J Mol Sci 2017 Jan 25;18(2). Epub 2017 Jan 25.

Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China.

Arsenic trioxide (As₂O₃) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As₂O₃ resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of () gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation. Here, three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners. Interestingly, PAO is found to have potential effect on induction of mutant PML-IV (A216V) protein solubility changes and degradation, but no appreciable effects were found following exposure to high concentrations of iAs, dimethylarsinous acid (DMA) and adriamycin (doxorubicin), even though they cause cell death. Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.
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http://dx.doi.org/10.3390/ijms18020247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343784PMC
January 2017

Neural substrates of the impaired effort expenditure decision making in schizophrenia.

Neuropsychology 2016 09 7;30(6):685-96. Epub 2016 Apr 7.

Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences.

Objective: Unwillingness to expend more effort to pursue high value rewards has been associated with motivational anhedonia in schizophrenia (SCZ) and abnormal dopamine activity in the nucleus accumbens (NAcc). The authors hypothesized that dysfunction of the NAcc and the associated forebrain regions are involved in the impaired effort expenditure decision-making of SCZ.

Method: A 2 (reward magnitude: low vs. high) × 3 (probability: 20% vs. 50% vs. 80%) event-related fMRI design in the effort-expenditure for reward task (EEfRT) was used to examine the neural response of 23 SCZ patients and 23 demographically matched control participants when the participants made effort expenditure decisions to pursue uncertain rewards.

Results: SCZ patients were significantly less likely to expend high level of effort in the medium (50%) and high (80%) probability conditions than healthy controls. The neural response in the NAcc, the posterior cingulate gyrus and the left medial frontal gyrus in SCZ patients were weaker than healthy controls and did not linearly increase with an increase in reward magnitude and probability. Moreover, NAcc activity was positively correlated with the willingness to expend high-level effort and concrete consummatory pleasure experience.

Conclusion: NAcc and posterior cingulate dysfunctions in SCZ patients may be involved in their impaired effort expenditure decision-making. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000284DOI Listing
September 2016

[Rapid Determination of Cu and Zn in PM2.5 with Wavelength Dispersive X-Ray Fluorescence Spectrometry].

Guang Pu Xue Yu Guang Pu Fen Xi 2016 Apr;36(4):1240-4

This paper proposes the analyzing method of adopting wavelength dispersive X-ray fluorescence spectrometry to measure the content of Cu and Zn in PM2.5. PTFE membrane is used to prepare standard samples and atmospheric particulate samples; a research into sample cup’s structure,using polypropylene film of 6.7 μm to help to improved sample cup to package atmospheric particulate samples. The improved sample cup is used to measure the content of Cu and Zn in atmospheric particulate, which can obviously reduce background, improve peak/background ratio and decrease detection limit to target element; discussion is made on the measurement condition of Cu and Zn in PM2.5: taking Kα line as analysis line of Cu and Zn, selecting PX10 as analyzer crystal, using 300 μm pitch collimator, adopting scintillation detector for the Kα of Zn, applying the integrating of flow-gas proportional counter and closed-end proportional counter to the Kα of Cu, setting 50 kV, 50 mA as operating voltage and current. The prepared Cu and Zn standard sample is used to set up working curve, the results show that their linear correlations are better, accuracy are higher, relative standard deviations of Cu and Zn are 2.43% and 2.00%(n=8), detection limit are 0.028 and 0.021 μg·cm-2respectively, and analysis of the single sample only need 60 s. To sum up, this method can quickly and accurately analyze the content of Cu and Zn in PM2.5, and provide scientific basis for study the element content characteristics and source apportionment.
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April 2016

Tobacco prevention policies in west-African countries and their effects on smoking prevalence.

BMC Public Health 2015 Dec 8;15:1216. Epub 2015 Dec 8.

Institut für Public Health, Universitätsklinikum Heidelberg, Heidelberg, Germany.

Background: The WHO Framework Convention on Tobacco Control was shown to effectively lower smoking prevalence in in high income countries, however knowledge for low and middle income settings is sparse. The objective of this study was to describe WHO MPOWER policy measures in thirteen West-African countries and to investigate their correlation with smoking prevalence.

Methods: Age-standardized smoking prevalence data and policy measures were collected from various WHO reports. For analysis MPOWER measures from 2008 and 2010, were combined with prevalence data from 2009 and 2011. Multiple linear regression models were set up.

Results: In West-Africa mean smoking prevalence was approximately 20% among males and approximately 3% among females. Policy measures were mostly at a middle or low level. Regression analysis showed that tobacco cessation programs, health warnings on cigarettes, and higher price of cigarettes were negatively correlated with smoking prevalence. Significant effects were observed for only one policy measure (tobacco cessation programs) and only within the male population where smoking prevalence is generally higher.

Conclusions: Tobacco control policies are enforced at relatively low levels in West-African countries. However, improving tobacco control policy implementation according to the WHO Framework Convention on Tobacco Control should assist in the reduction of smoking prevalence in African countries, thereby counteracting pro-smoking initiatives set forth by the tobacco industry.
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http://dx.doi.org/10.1186/s12889-015-2562-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673866PMC
December 2015

Synthesis, characterization of dextran hydrogels and their in vitro release of gentamycin sulphate.

J Appl Biomater Funct Mater 2015 Oct 16;13(3):e228-33. Epub 2015 Oct 16.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou - China.

Purpose: This study reports on the synthesis and characterization of biodegradable dextran-allyl isocyanate-ethylamine (Dex-AE)/polyethylene glycol-diacrylate (PEGDA) hydrogels for the controlled release of gentamycin sulphate (GS) and in vitro inhibition of organisms.

Methods: The Dex-AE precursor was prepared through a 2-step chemical modification and characterized by Fourier transform infrared spectroscopy (FTIR).

Results: Scanning electron microscopy (SEM) results revealed that an increase in Dex-AE content led to an initial decrease in pore size of the Dex-AE/PEGDA hydrogels, but a further increase in Dex-AE content resulted in a slightly increase of pore size. The swelling data indicated that the swelling ratio depended on the precursor feed ratio. GS was incorporated into the hydrogels through 2 different methods, i.e., immersed and crosslinked. The crosslinked GS-Dex-AE/PEGDA hydorgels exhibited stronger antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Finally, the viscoelastic properties of crosslinked GS-Dex-AE/PEGDA hydorgels were investigated.
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http://dx.doi.org/10.5301/jabfm.5000233DOI Listing
October 2015

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2016 Jan 18;64:52-9. Epub 2015 Jul 18.

Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Background: Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD.

Method: We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making.

Results: Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls.

Conclusions: These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD.
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http://dx.doi.org/10.1016/j.pnpbp.2015.07.006DOI Listing
January 2016

Poly(L-lactide)/halloysite nanotube electrospun mats as dual-drug delivery systems and their therapeutic efficacy in infected full-thickness burns.

J Biomater Appl 2015 Nov 2;30(5):512-25. Epub 2015 Jul 2.

School of Medicine, Jinan University, Guangzhou, China.

In this study, poly(L-lactide) (PLLA)/halloysite nanotube (HNT) electrospun mats were prepared as a dual-drug delivery system. HNTs were used to encapsulate polymyxin B sulphate (a hydrophilic drug). Dexamethasone (a hydrophobic drug) was directly dissolved in the PLLA solution. The drug-loaded HNTs with optimised encapsulation efficiency were then mixed with the PLLA solution for subsequent electrospinning to form composite dual-drug-loaded fibre mats. The structure, morphology, degradability and mechanical properties of the electrospun composite mats were characterised in detail. The results showed that the HNTs were uniformly distributed in the composite PLLA mats. The HNTs content in the mats could change the morphology and average diameter of the electrospun fibres. The HNTs improved both the tensile strength of the PLLA electrospun mats and their degradation ratio. The drug-release kinetics of the electrospun mats were investigated using ultraviolet-visible spectrophotometry. The HNTs/PLLA ratio could be varied to adjust the release of polymyxin B sulphate and dexamethasone. The antibacterial activity in vitro of the mats was evaluated using agar diffusion and turbidimetry tests, which indicated the antibacterial efficacy of the dual-drug delivery system against Gram-positive and -negative bacteria. Healing in vivo of infected full-thickness burns and infected wounds was investigated by macroscopic observation, histological observation and immunohistochemical staining. The results indicated that the electrospun mats were capable of co-loading and co-delivering hydrophilic and hydrophobic drugs, and could potentially be used as novel antibacterial wound dressings.
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http://dx.doi.org/10.1177/0885328215593837DOI Listing
November 2015