Publications by authors named "Dan-Dan Zhu"

29 Publications

  • Page 1 of 1

Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury.

World J Gastroenterol 2021 Jun;27(22):2944-2962

Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide. In addition to respiratory symptoms, COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of antioxidant proteins, participating in COVID-19-mediated inflammation and liver injury. Here, we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury. Additionally, we describe some mechanisms and treatment strategies.
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http://dx.doi.org/10.3748/wjg.v27.i22.2944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192291PMC
June 2021

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.

Chin Med J (Engl) 2021 Apr 28;134(11):1289-1298. Epub 2021 Apr 28.

NHC Key Laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention), Nanjing, Jiangsu 210009, China.

Background: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.

Methods: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.

Results: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.

Conclusions: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.

Trial Registration: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
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http://dx.doi.org/10.1097/CM9.0000000000001573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183795PMC
April 2021

Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression.

Front Oncol 2021 25;11:569295. Epub 2021 Feb 25.

Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.

Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study's findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.
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http://dx.doi.org/10.3389/fonc.2021.569295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970754PMC
February 2021

SRC-1 Knockout Exerts No Effect on Amyloid β Deposition in APP/PS1 Mice.

Front Aging Neurosci 2020 17;12:145. Epub 2020 Jun 17.

Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Steroid receptor coactivator 1 (SRC-1) is the key coactivator because of its transcriptional activity. Previous studies have shown that SRC-1 is abundant in the hippocampus and has been implicated in cognition. SRC-1 is also related to some major risk factors for Alzheimer's disease (AD), such as a decline in estrogen and aging, however, whether SRC-1 is involved in the pathogenesis of AD remains unclear. In this study, we established SRC-1 knockout in AD mice by cross breeding SRC-1 mutant mice with APP/PS1 transgenic mice, and investigated the expression of some synaptic proteins, the amyloid β (Aβ) deposition, and activation of astrocytes and microglia in the hippocampus of APP/PS1×SRC-1 mice. The results showed that SRC-1 knockout neither affects the Aβ plaque and activation of glia, nor changes the expression of synaptic proteins in AD model mice. The above results suggest that the complete deletion of SRC-1 in the embryo exerts no effect on the pathogenesis of APP/PS1 mice. Nevertheless, this study could not eliminate the possible role of SRC-1 in the development of AD due to the lack of observation of other events in AD such as tau hyperphosphorylation and the limitation of the animal model employed.
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http://dx.doi.org/10.3389/fnagi.2020.00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311769PMC
June 2020

Multiscale simulations of drug distributions in polymer dissolvable microneedles.

Colloids Surf B Biointerfaces 2020 May 4;189:110844. Epub 2020 Feb 4.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China. Electronic address:

Drug distribution in polymer dissolvable microneedles (MNs) is essential for enhancing the efficiency of drug delivery. In the present work, multiscale simulation was applied to study the interactions between polymer and drug molecules, which may influence the drug distribution in the MNs. In this study, Hyaluronic acid (HA) and Polyvinyl alcohol (PVA) were used to fabricate the MNs and sulfonhodamine B (SRB) was selected as the model drug. Firstly, from the quantum chemical calculations, the global electronegativity of HA (3.786 eV) is stronger than that of PVA (2.435 eV), which means that HA owns stronger electronegativity. The Flory-Huggins parameter of HA-SRB is -1.16 which is lower than that of PVA-SRB (53.51), indicating that HA has better compatibility with SRB molecules than PVA. From molecular dynamic simulations, the binding energy of HA-SRB is 93.52 kcal/mol which is much higher than that of PVA-SRB (-2.40 kcal/mol), meaning that HA is easier than PVA to combined with SRB. The mesoscale-based dissipative particle dynamics (DPD) simulations were applied to visualize the diffusion behavior of SRB and the swelling properties of the polymers. All the results indicated that SRB has a lower diffusion coefficient in PVA solution than that in HA solution, which may prevent the diffusion of drug from MN tips to the bases, facilitating the fabrication of MNs with drug concentrated MN tips. Finally, the SRB loaded PVA and HA MNs were prepared and the experimental results are consisted with the simulation results.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110844DOI Listing
May 2020

Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Branch Retinal Vein Occlusion.

Authors:
Dan-Dan Zhu Xun Liu

J Ophthalmol 2019 31;2019:6043612. Epub 2019 Oct 31.

Department of Ophthalmology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

. To evaluate the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio(PLR) value in the development of branch retinal vein occlusion (BRVO)patients.

Methods: 81 patients with BRVO and 81 age and sex-matched subjects were recruited as the control group. The BRVO diagnosis was confirmed under comprehensive ophthalmologic examinations. NLR and PLR parameters obtained from peripheral blood were recorded.

Results: Both the mean NLR and PLR was significantly higher in the BRVO group compared with the control group ( < 0.001). In ROC analysis, the AUC for NLR was 0.82, and NLR of >2.48 predicted BRVO with a sensitivity of 58% and specificity of 98%. The AUC for PLR was 0.78, and PLR of >110.2 predicted BRVO with a sensitivity of 72% and specificity of 72%.

Conclusion: The current study demonstrated that BRVO patients had increased NLR and PLR levels compared with control subjects. The NLR and PLR may be used as independent predictors for identifying risk for the development of BRVO.
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http://dx.doi.org/10.1155/2019/6043612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925675PMC
October 2019

Scorpion Venom Heat-Resistant Peptide is Neuroprotective against Cerebral Ischemia-Reperfusion Injury in Association with the NMDA-MAPK Pathway.

Neurosci Bull 2020 Mar 9;36(3):243-253. Epub 2019 Sep 9.

Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Our previous studies have shown that SVHRP is neuroprotective in models of Alzheimer's disease and Parkinson's disease. The present study aimed to explore the potential neuroprotective effects of SVHRP on cerebral ischemia/reperfusion (I/R) injury, using a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R). Our results showed that SVHRP treatment decreased the neurological deficit scores, edema formation, infarct volume and neuronal loss in the MCAO/R mice, and protected primary neurons against OGD/R insult. SVHRP pretreatment suppressed the alterations in protein levels of N-methyl-D-aspartate receptors (NMDARs) and phosphorylated p38 MAPK as well as some proinflammatory factors in both the animal and cellular models. These results suggest that SVHRP has neuroprotective effects against cerebral I/R injury, which might be associated with inhibition of the NMDA-MAPK-mediated excitotoxicity.
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http://dx.doi.org/10.1007/s12264-019-00425-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056763PMC
March 2020

The maximum possible amount of drug in rapidly separating microneedles.

Drug Deliv Transl Res 2019 12;9(6):1133-1142

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.

There is an increasing concern on the drug loading capacity of microneedles (MNs) to meet higher drug dosage requirement. The present study describes the fabrication of modified rapidly separating polyvinyl alcohol (PVA)-based MNs (RS-P-MNs) with high drug loading using a mechanical agitation process. The drugs encapsulated within the PVA polymer gel by mechanical agitation served as an encapsulating agent for drugs that provide a high drug loading capacity and also release of drugs in a controlled manner. The various parameters such as microscopic analysis, atomic force microscopy (AFM), drug loading, drug delivery efficiency, mechanical test, skin penetration ability, and in vitro and in vivo analyses indicate the great potential of the RS-P-MNs. The maximum drug loading capacity of RS-P-MNs was measured to be approximately 900 ng per microneedle, which was almost a hundred times than the traditional drug encapsulating mode. The in vitro and in vivo results suggested that the controlled release of drugs is due to the encapsulating mode (mechanical agitation) of drugs. The prepared RS-P-MNs with high drug loading in this study provided a gentle and controlled release of drugs instead of the robust release of drugs from traditional MNs. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-019-00658-7DOI Listing
December 2019

Kinetic stability studies of HBV vaccine in a microneedle patch.

Int J Pharm 2019 Aug 2;567:118489. Epub 2019 Jul 2.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China; Key Laboratory of Biomedical Materials of Natural Macromolecules, Beijing University of Chemical Technology, Ministry of Education, Beijing 100029, PR China. Electronic address:

This study systematically demonstrated the antigenicity kinetics of HBV vaccine microneedles (MNs) during the fabrication, application and storage. To improve the stability of HBsAg in a microneedle patch, several selected saccharides were added to the MN formulations as stabilizers. According to the experimental data, no significant decrease of the bio-activity of HBsAg antigen was found during the microneedle fabrication process. And then immune effects of HBsAg added with different sugars were tested. Chitosan and trehalose loaded HBsAg MNs enhanced the antibody levels to approximately 1.5-fold and 2-fold of the plain HBsAg MNs respectively while sucrose and glucose were not obviously beneficial. During the short-term storage under 60 °C, the antigenicity of HBsAg MNs encapsulated with glucose and chitosan declined sharply in 24 h and hardly left after 7 days. As for the groups of HBsAg MNs added with sucrose and trehalose, approximately 90% of HBsAg initial antigenicity maintained, which could be attributed to the protective function of non-reductive disaccharides. As for the long-term storage experiments, the pharmacological activity of HBsAg antigen protected by sucrose and trehalose slightly reduced in 3 months except for the samples under 60 °C. In extreme condition, trehalose performed even better protection function than sucrose, of which the antigenicity of HBsAg in MNs left approximately 81% and 63% of its initial, respectively. These results confirmed that trehalose loaded HBsAg MNs enabled stable encapsulation and storage of HBsAg antigen and realized reasonable enhancement of immune effect in a relatively painless, safe, and convenient manner.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118489DOI Listing
August 2019

Ginsenoside Rg1 Accelerates Paracrine Activity and Adipogenic Differentiation of Human Breast Adipose-Derived Stem Cells in a Dose-Dependent Manner In Vitro.

Cell Transplant 2019 03 24;28(3):286-295. Epub 2019 Jan 24.

4 Department of Plastic and Aesthetic Surgery, The Fifth Affiliated Hospital of Guangxi Medical University & The First People's Hospital of Nanning, Nanning, China.

Augmenting the biological function of adipose-derived stromal cells (ASCs) is a promising approach to promoting tissue remodeling in regenerative medicine. Here, we examined the effect of ginsenoside Rg1 on the paracrine activity and adipogenic differentiation capacity of human breast ASCs (hbASCs) in vitro. hbASCs were isolated and characterized in terms of stromal cell surface markers and multipotency. Third-passage hbASCs were cultured in basic media only or basic media containing different concentrations of G-Rg1 (0.1-100 μM). Cell proliferation was assessed by CCK-8 assay. Paracrine activity was assessed using ELISA. Gene expression was measured by qRT-PCR. Adipogenic differentiation capacity was evaluated by Oil red O staining. We found that hbASCs differentiated into adipocytes, osteoblasts, and chondrocytes in appropriate induction culture medium. hbASCs showed expression of CD29, CD44, CD49d, CD73, CD90, CD105, and CD133 but not CD31 and CD45 surface markers. G-Rg1 increased hbASC proliferation and adipogenic differentiation capacity at lower concentrations (0.1-1 μM) and had the opposite effects at higher concentrations (10-100 μM), while enhanced paracrine activity was observed in all experimental groups compared with control group, and the activation effect of lower concentration G-Rg1 was greater than at higher concentration. These results indicate that G-Rg1 can enhance the proliferation, paracrine activity, and adipogenic differentiation capacity of hbASCs within a certain concentration range. Therefore, the use of G-Rg1 may be beneficial to ASC-assisted fat graft regeneration and soft tissue engineering.
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http://dx.doi.org/10.1177/0963689719825615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425106PMC
March 2019

The role of uric acid in the pathogenesis of diabetic retinopathy based on Notch pathway.

Biochem Biophys Res Commun 2018 09 22;503(2):921-929. Epub 2018 Jun 22.

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China. Electronic address:

Objective: Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown.

Methods: We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively.

Results: In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly decreased.

Conclusion: Our study reported that high uric acid can promote the inflammation of the retina and increase the activity of Notch signaling pathway on the basis of high glucose. Hyperuricemia promotes the development of diabetic retinopathy by increasing the activity of Notch signaling pathway. Notch signaling pathway is a potential therapeutic target for diabetic retinopathy.
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http://dx.doi.org/10.1016/j.bbrc.2018.06.097DOI Listing
September 2018

Precise Intradermal Injection of Nanofat-Derived Stromal Cells Combined with Platelet-Rich Fibrin Improves the Efficacy of Facial Skin Rejuvenation.

Cell Physiol Biochem 2018 11;47(1):316-329. Epub 2018 May 11.

Department of Plastic and Aesthetic Surgery, The Fifth Affiliated Hospital of Guangxi Medical University & The First People's Hospital of Nanning, Nanning, China.

Background/aims: The rejuvenation properties of nanofat grafting have been described in recent years. However, it is not clear whether the clinical efficacy of the procedure is attributable to stem cells or linked to other components of adipose tissue. In this study we isolated nanofat-derived stem cells (NFSCs) to observe their biological characteristics and evaluate the efficacy of precise intradermal injection of nanofat combined with platelet-rich fibrin (PRF) in patients undergoing facial rejuvenation treatment.

Methods: Third-passage NFSCs were isolated and cultured using a mechanical emulsification method and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic nature and chondrogenic differentiation capacity of NFSCs were determined using Oil Red O staining, alizarin red staining, and Alcian blue staining, respectively. Paracrine function of NFSCs was evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 3, 7, 14, and 28 days after establishing the culture. Then, the effects of PRF on NFSC proliferation were assessed in vitro. Finally, we compared the outcome in 103 patients with facial skin aging who underwent both nanofat and intradermal PRF injection (treatment group) and 128 patients who underwent hyaluronic acid (HA) injection treatment (control group). Outcomes in the two groups were compared by assessing pictures taken at the same angle before and after treatment, postoperative recovery, incidence of local absorption and cysts, and skin quality before treatment, and at 1, 12, 24 months after treatment using the VISIA Skin Image Analyzer and a SOFT5.5 skin test instrument.

Results: NFSCs expressed CD29, CD44, CD49d, CD73, CD90, and CD105, but did not express CD34, CD45, and CD106. NFSCs also differentiated into adipocytes, osteoblasts, and chondrocytes under appropriate induction conditions. NFSCs released large amounts of growth factors such as VEGF, bFGF, EGF, and others, and growth factor levels increased in a time-dependent manner. At the same time, PRF enhanced proliferation of NFSCs in vitro in a dose-dependent manner, and the growth curves under different concentrations of PRF all showed plateaus 6d after seeding. Facial skin texture was improved to a greater extent after combined injection of nanofat and PRF than after control injection of HA. The nanofat-PRF group had a higher satisfaction rate. Neither treatment caused any complications such as infection, anaphylaxis, or paresthesia during long-term follow-up.

Conclusion: NFSCs demonstrate excellent multipotential differentiation and paracrine function, and PRF promotes proliferation of NFSCs during the early stage after seeding. Both nanofat-PRF and HA injection improve facial skin status without serious complications, but the former was associated with greater patient satisfaction, implying that nanofat-PRF injection is a safe, highly effective, and long-lasting method for skin rejuvenation.
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http://dx.doi.org/10.1159/000489809DOI Listing
August 2018

Controlled Delivery of Insulin Using Rapidly Separating Microneedles Fabricated from Genipin-Crosslinked Gelatin.

Macromol Rapid Commun 2018 Oct 2;39(20):e1800075. Epub 2018 May 2.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.

Rapidly separating genepin-crosslinked gelatin (RS-GC) microneedles (MNs) mounted on the polyvinyl alcohol (PVA)-coated polylactic acid (PLA) MNs (RS-PGC-MNs) are fabricated, in which GC-MNs deliver insulin within the skin and the PLA supporting array is easily separated by the dissolution of the PVA layer. The release of insulin is controlled by utilizing the virtue of genipin as a crosslinking agent for producing biocompatible GC-MNs. The degree of crosslinking enhances the mechanical strength as well as humidity resistance. The in vitro and in vivo insulin release tests show significant changes in the release rates in the RS-PGC-MNs with different crosslinking degree. The hypoglycemic effect in diabetic mice demonstrate that the higher crosslinking GC-MNs result in characteristic controlled insulin release compared with other treatments and prolonged effectiveness of the RS-PGC-MNs. The proposed RS-PGC-MNs is a promising device for effective use as a noninvasive and painless controlled insulin delivery system.
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http://dx.doi.org/10.1002/marc.201800075DOI Listing
October 2018

Insulin delivery systems combined with microneedle technology.

Adv Drug Deliv Rev 2018 03 29;127:119-137. Epub 2018 Mar 29.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and poke" and "poke and release" approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation.
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http://dx.doi.org/10.1016/j.addr.2018.03.011DOI Listing
March 2018

Microneedles with Controlled Bubble Sizes and Drug Distributions for Efficient Transdermal Drug Delivery.

Sci Rep 2016 12 8;6:38755. Epub 2016 Dec 8.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P.R. China.

Drug loaded dissolving microneedles (DMNs) fabricated with water soluble polymers have received increasing attentions as a safe and efficient transdermal drug delivery system. Usually, to reach a high drug delivery efficiency, an ideal drug distribution is gathering more drugs in the tip or the top part of DMNs. In this work, we introduce an easy and new method to introduce a bubble with controlled size into the body of DMNs. The introduction of bubbles can prevent the drug diffusion into the whole body of the MNs. The heights of the bubbles are well controlled from 75 μm to 400 μm just by changing the mass concentrations of polymer casting solution from 30 wt% to 10 wt%. The drug-loaded bubble MNs show reliable mechanical properties and successful insertion into the skins. For the MNs prepared from 15 wt% PVA solution, bubble MNs achieve over 80% of drug delivery efficiency in 20 seconds, which is only 10% for the traditional solid MNs. Additionally, the bubble microstructures in the MNs are also demonstrated to be consistent and identical regardless the extension of MN arrays. These scalable bubble MNs may be a promising carrier for the transdermal delivery of various pharmaceuticals.
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http://dx.doi.org/10.1038/srep38755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144082PMC
December 2016

Rapidly separating microneedles for transdermal drug delivery.

Acta Biomater 2016 09 3;41:312-9. Epub 2016 Jun 3.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Unlabelled: The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery.

Statement Of Significance: Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery.
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http://dx.doi.org/10.1016/j.actbio.2016.06.005DOI Listing
September 2016

van der Waals epitaxy and photoresponse of two-dimensional CdSe plates.

Nanoscale 2016 Jun;8(22):11375-9

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Here we demonstrate the first growth of two-dimensional (2D) single-crystalline CdSe plates on mica substrates via van der Waals epitaxy. The as-synthesized 2D plates exhibit hexagonal, truncated triangular and triangular shapes with the lateral size around several microns. Photodetectors based on 2D CdSe plates present a fast response time of 24 ms, revealing that 2D CdSe is a promising building block for ultrathin optoelectronic devices.
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http://dx.doi.org/10.1039/c6nr02779bDOI Listing
June 2016

A fabrication method of microneedle molds with controlled microstructures.

Mater Sci Eng C Mater Biol Appl 2016 Aug 13;65:135-42. Epub 2016 Apr 13.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Microneedle (MN) offers an attractive, painless and minimally invasive approach for transdermal drug delivery. Polymer microneedles are normally fabricated by using the micromolding method employing a MN mold, which is suitable for mass production due to high production efficiency and repeat-using of the mold. Most of the MN molds are prepared by pouring sylgard polymer over a MN master to make an inverse one after curing, which is limited in optimizing or controlling the MN structures and failing to keep the sharpness of MNs. In this work we describe a fabrication method of MN mold with controlled microstructures, which is meaningful for the fabrication of polymer MNs with different geometries. Laser micro-machining method was employed to drill on the surface of PDMS sheets to obtain MN molds. In the fabrication process, the microstructures of MN molds are precisely controlled by changing laser parameters and imported patterns. The MNs prepared from these molds are sharp enough to penetrate the skin. This scalable MN mold fabrication method is helpful for future applications of MNs.
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http://dx.doi.org/10.1016/j.msec.2016.03.097DOI Listing
August 2016

Physical vapor deposition synthesis of two-dimensional orthorhombic SnS flakes with strong angle/temperature-dependent Raman responses.

Nanoscale 2016 Jan;8(4):2063-70

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Anisotropic layered semiconductors have attracted significant interest due to the huge possibility of bringing new functionalities to thermoelectric, electronic and optoelectronic devices. Currently, most reports on anisotropy have concentrated on black phosphorus and ReS2, less effort has been contributed to other layered materials. In this work, two-dimensional (2D) orthorhombic SnS flakes on a large scale have been successfully synthesized via a simple physical vapor deposition method. Angle-dependent Raman spectroscopy indicated that the orthorhombic SnS flakes possess a strong anisotropic Raman response. Under a parallel-polarization configuration, the peak intensity of Ag (190.7 cm(-1)) Raman mode reaches the maximum when incident light polarization is parallel to the armchair direction of the 2D SnS flakes, which strongly suggests that the Ag (190.7 cm(-1)) mode can be used to determine the crystallographic orientation of the 2D SnS. In addition, temperature-dependent Raman characterization confirmed that the 2D SnS flakes have a higher sensitivity to temperature than graphene, MoS2 and black phosphorus. These results are useful for the future studies of the optical and thermal properties of 2D orthorhombic SnS.
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http://dx.doi.org/10.1039/c5nr07675gDOI Listing
January 2016

Mesoscopic simulation studies on the formation mechanism of drug loaded polymeric micelles.

Colloids Surf B Biointerfaces 2015 Dec 30;136:536-44. Epub 2015 Sep 30.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

In this work, the formation of polymeric micelles as drug delivery vehicles in an aqueous environment is investigated by dissipative particle dynamics (DPD) simulations. Doxorubicin (DOX) is selected as the model drug, whereas docosahexaenoic acid (DHA) conjugated His10Lys10 (DHA-His10Lys10) as the drug carrier. It is shown from DPD simulation that drug molecules and DHA-His10Lys10 molecules could aggregate and form micelles under a defined composition recipe; drug molecules are homogeneously distributed inside the carrier matrix, on whose surface the stabilizer lysine segments are absorbed. Under different compositions of drug and water, aggregate morphologies of polymeric micelles are observed as spherical, columnar, and lamellar structures. We finally proposed the formation mechanism of drug loaded polymeric micelles and apply it in practice by analyzing the simulated phenomena. All the results can effectively guide the experimental preparation of drug delivery system with desired properties or explore a novel polymeric micelle with high performance.
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http://dx.doi.org/10.1016/j.colsurfb.2015.09.049DOI Listing
December 2015

Significance of NF-κB activation in immortalization of nasopharyngeal epithelial cells.

Int J Cancer 2016 Mar 13;138(5):1175-85. Epub 2015 Oct 13.

School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.

NF-κB is a key regulator of inflammatory response and is frequently activated in human cancer including the undifferentiated nasopharyngeal carcinoma (NPC), which is common in Southern China including Hong Kong. Activation of NF-κB is common in NPC and may contribute to NPC development. The role of NF-κB activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF-κB activation in immortalization of NPE cells is of particular interest as the site of NPC is often heavily infiltrated with inflammatory cellular components. We found that constitutive activation of NF-κB signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-κB activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-κB activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-κB downregulated expression of c-Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-κB activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-κB activation in immortalized NPE cells. Elucidation of events underlying immortalization of NPE cells may provide insights into early events in pathogenesis of NPC. The identification of NF-κB activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC.
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http://dx.doi.org/10.1002/ijc.29850DOI Listing
March 2016

Identification and Characterization of the Major Chemical Constituents in Fructus Akebiae by High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time-of-Flight Mass Spectrometry.

J Chromatogr Sci 2016 Feb 26;54(2):148-57. Epub 2015 Aug 26.

Department of Pharmaceutical and Life Sciences, Jiujiang University, Jiujiang 332005, People's Republic of China

Fructus Akebiae (FA), the dry fruit of Akebia quinata (THUNB.) DECNE., possesses potent antidepressant properties. Owing to the structural complexity, high polarity and thermal lability in plants, it is difficult and time-consuming to analyze the major chemical constituents by traditional strategies that involve extraction, isolation, purification and identification by chemical manipulations and spectroscopic methods. In this study, a high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS-MS) method was established for quickly identifying the chemical constituents in the extract of Fructus Akebiae. The main saponin components in the extract of Fructus Akebiae were detected with the HPLC-ESI-Q-TOF-MS-MS in negative-ion mode. These components were further analyzed by MS(2) spectra, and compared with the corresponding reference substances and literature data. Nineteen saponins in the extract of Fructus Akebiae were well separated in one run. The new method is accurate and rapid. It can be used to identify the main chemical constituents in the extract of Fructus Akebiae and can be suitable for the quality control of Fructus Akebiae.
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http://dx.doi.org/10.1093/chromsci/bmv119DOI Listing
February 2016

The complete mitochondrial genome sequence and mutations of the lung cancer model inbred rat strain (Muridae; Rattus).

Mitochondrial DNA A DNA Mapp Seq Anal 2016 12;27(2):1260-1. Epub 2014 Nov 12.

a Department of Oncology Ward Two , Daqing Oil Field General Hospital , Daqing , People's Republic of China and.

We reported the complete mitochondrial genome sequencing of an important Lung cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,312 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region. The mutation sites were analyzed by comparing with the reference BN strain.
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http://dx.doi.org/10.3109/19401736.2014.945546DOI Listing
September 2016

CVD synthesis of large-area, highly crystalline MoSe2 atomic layers on diverse substrates and application to photodetectors.

Nanoscale 2014 Aug;6(15):8949-55

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P.R. China.

Synthesis of large-area, atomically thin transition metal dichalcogenides (TMDs) on diverse substrates is of central importance for the large-scale fabrication of flexible devices and heterojunction-based devices. In this work, we successfully synthesized a large area of highly-crystalline MoSe2 atomic layers on SiO2/Si, mica and Si substrates using a simple chemical vapour deposition (CVD) method at atmospheric pressure. Atomic force microscopy (AFM) and Raman spectroscopy reveal that the as-grown ultrathin MoSe2 layers change from a single layer to a few layers. Photoluminescence (PL) spectroscopy demonstrates that while the multi-layer MoSe2 shows weak emission peaks, the monolayer has a much stronger emission peak at ∼ 1.56 eV, indicating the transition from an indirect to a direct bandgap. Transmission electron microscopy (TEM) analysis confirms the single-crystallinity of MoSe2 layers with a hexagonal structure. In addition, the photoresponse performance of photodetectors based on MoSe2 monolayer was studied for the first time. The devices exhibit a rapid response of ∼ 60 ms and a good photoresponsivity of ∼ 13 mA/W (using a 532 nm laser at an intensity of 1 mW mm(-2) and a bias of 10 V), suggesting that MoSe2 monolayer is a promising material for photodetection applications.
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http://dx.doi.org/10.1039/c4nr02311kDOI Listing
August 2014

Rockall score in predicting outcomes of elderly patients with acute upper gastrointestinal bleeding.

World J Gastroenterol 2013 Jun;19(22):3466-72

Department of Emergency, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.

Aim: To validate the clinical Rockall score in predicting outcomes (rebleeding, surgery and mortality) in elderly patients with acute upper gastrointestinal bleeding (AUGIB).

Methods: A retrospective analysis was undertaken in 341 patients admitted to the emergency room and Intensive Care Unit of Xuanwu Hospital of Capital Medical University with non-variceal upper gastrointestinal bleeding. The Rockall scores were calculated, and the association between clinical Rockall scores and patient outcomes (rebleeding, surgery and mortality) was assessed. Based on the Rockall scores, patients were divided into three risk categories: low risk ≤ 3, moderate risk 3-4, high risk ≥ 4, and the percentages of rebleeding/death/surgery in each risk category were compared. The area under the receiver operating characteristic (ROC) curve was calculated to assess the validity of the Rockall system in predicting rebleeding, surgery and mortality of patients with AUGIB.

Results: A positive linear correlation between clinical Rockall scores and patient outcomes in terms of rebleeding, surgery and mortality was observed (r = 0.962, 0.955 and 0.946, respectively, P = 0.001). High clinical Rockall scores > 3 were associated with adverse outcomes (rebleeding, surgery and death). There was a significant correlation between high Rockall scores and the occurrence of rebleeding, surgery and mortality in the entire patient population (χ² = 49.29, 23.10 and 27.64, respectively, P = 0.001). For rebleeding, the area under the ROC curve was 0.788 (95%CI: 0.726-0.849, P = 0.001); For surgery, the area under the ROC curve was 0.752 (95%CI: 0.679-0.825, P = 0.001) and for mortality, the area under the ROC curve was 0.787 (95%CI: 0.716-0.859, P = 0.001).

Conclusion: The Rockall score is clinically useful, rapid and accurate in predicting rebleeding, surgery and mortality outcomes in elderly patients with AUGIB.
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http://dx.doi.org/10.3748/wjg.v19.i22.3466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683686PMC
June 2013

Protective effect of DNA vaccine with the gene encoding 55kDa antigen fragment against Pneumocystis carinii in mice.

Asian Pac J Trop Med 2011 May 22;4(5):353-6. Epub 2011 Jun 22.

Department of Parasitology and Microbiology, School of Medicine, Nantong University, Nantong, Jiangsu Province, 226001, China.

Objective: To evaluate the protective effect of DNA vaccine with the gene encoding 55kDa antigen fragment of Pneumocystis carinii (P. carinii) against P. carinii in mice.

Methods: The fragment of the antigen within p55(p55-582) was cloned. Then recombinant plasmid was constructed based on the eukaryotic expression vector pcDNA3.1(+). BALB/c mice were used as experimental models to examine the immunogenicity of pcDNA3.1(+)-p55-582. ELISA and RT-PCR were used to evaluate the role of this kind of DNA vaccine.

Results: The results of western blot indicated that the recombinant DNA[pcDNA3.1(+)-p55-582] could be expressed correctly and had antigenicity in transfected COS-7 cells. ELISA and RT-PCR showed that pcDNA3.1(+)-p55-582 elicited antibody production, stimulated lymphocyte proliferation and provided partial protection by reducing the P. carinii burden.

Conclusions: The data demonstrate that pcDNA3.1(+)-p55-582 might be potent vaccination that can afford the partial protection for the immunized animals.
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http://dx.doi.org/10.1016/S1995-7645(11)60102-8DOI Listing
May 2011

[Immunogenicity of p55 gene fragment from Pneumocystis carinii].

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2009 Dec;27(6):494-7

Department of Parasitology, School of Medicine, Nantong University, Nantong 226001, China.

Objective: To evaluate immunogenicity of the recombinant protein GST-p55/570 of Pneumocystis carinii.

Methods: The fusion protein GST-p55/570 was expressed from the prokaryotic expression plasmid pGEX-570, and purified by using glutathione-agarose. The expressed product was analyzed by SDS-PAGE. Thirty-three mice were randomly divided into three groups, immunized with GST-p55/570, GST and PBS, respectively. Each group was immunized for four times at 2 week intervals. At the 7th day after final immunization, spleen was removed to obtain single cell suspension. Proliferation ability of lymphocytes was determined by MTT. Serum samples were collected at pre-immunization and two weeks after each immunization. Antibody level in sera of mice was determined by ELISA. The immune response to the recombinant GST-p55/570 recognized by sera of immunized mice was examined by Western blotting.

Results: The expressed fusion protein GST-p55/570 showed a Mr 47,000. Compared with GST group (1.134 5 +/- 0.073 5) or PBS group (1.124 8 +/- 0.041 6), a higher stimulation index (2.063 0 +/- 0.1602) was revealed in GST-p55/570-immunized mice (P < 0.01). At the 14th to 49th day after immunization, the antibody titer against GST-p55/570 in the immunized group was significantly higher than that of GST or PBS groups (P < 0.01). Western blotting indicated that the fusion protein (GST-p55/ 570) had specific immune response to positive serum.

Conclusion: The fusion protein GST-p55/570 elicits significant humoral and cellular immune responses.
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December 2009

[Effects of acute and chronic murine cytomegalovirus infections on the ratio of regulatory T cells and expression of Th1/Th2 transcription factors T-bet/GATA-3].

Zhonghua Yi Xue Za Zhi 2008 Nov;88(42):2999-3002

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Objective: To explore the effects of acute and chronic murine cytomegalovirus (MCMV) infections on the regulatory T cells (Treg) ratio and protein expression of the Th1/Th2 transcription factors T-bet/GATA-3.

Methods: 120 BALB/c mice were randomly divided into 2 equal groups: MCMV-infected group undergoing infra-peritoneal injection of homogenate of salivary gland containing MCMV, and mock infection group undergoing infra-peritoneal injection of normal homogenate of salivary gland 1, 3, 7, 14, 28, 45, 60, 75, 90, and 120 days after infection 6 mice from each group were killed to examine the viral load of the heart, lung, liver, and kidney by plaque assay to access the status of MCMV infection. Suspension of splenocytes was prepared. The proportion of CD4+CD25+Foxp3+Treg in the splenocytes was measured by flow cytometry. Western blotting was used to detect the protein expression of T-bet/GATA-3.

Results: The cutoff point between acute and chronic points was the 28th day. The CD4+CD25+Foxp3+Treg proportion in splenocytes significantly decreased during the acute infection stage and to the lowest level of (1.46+/-0.27)% at day 28, significantly lower than that of the mock infection group [(2.78+/-0.29)%, P<0.05]; then obviously increased in the chronic infection stage, increased to (4.51+/-0.24)% at day 60, significantly higher than that of the mock infection group [(2.69+/-0.12)%, P<0.05], and continued to increase still. The protein level (K value) of T-bet of the MCMV infection group peaked to the level of (0.618+/-0.053) on day 3, obviously higher than that of the mock infected group [(0.205+/-0.026)], then decreased to the level similar to that of the mock infection group on day 28, and was obviously lower than that of the mock infection group on day 75. Whereas the protein level of GATA-3 of the MCMV group increased to (0.836+/-0.061) on day 3, markedly higher than that of the mock infection group (0.398+/-0.022), peaked on day 7, then gradually decreased, and remained at the levels similar to those of the mock infection group from day 75 to day 120.

Conclusion: In the acute infection stage, MCMV up-regulates the T-bet and GATA-3 protein expression. But during the chronic infection stage, MCMV induces a marked proliferation and activation of Treg cells which further inhibit the Th1 and Th2 reactions, especially Th1 response. Treg proliferation may be an important mechanism of chronic and persistent CMV infection in the host.
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November 2008

[Preparation and permeation studies of soybean lecithin-based vesicles].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2006 Aug;28(4):492-6

Institute of Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Objective: To investigate various methods for constructing soybean lecithin (SL)-based vesicles and evaluate the permeation-enhancing effect of SL-based vesicles on the penetration of insulin through buccal mucosa.

Methods: The ultrasonic method, high speed shear method and high pressure homogenization method were respectively used to prepare the SL-based vesicles, and the particle size of the vesicles was measured with photon correlation spectrometry (PCS). The penetration rate of insulin through porcine buccal mucosa was investigated with the Valia-Chien diffusion cells.

Results: The average particle sizes of 3 formulations of SL-based vesicles were 97.39, 85.60, and 100.60 nm when prepared by ultrasonic method, and were 58.7, 88.7, and 91.9 nm when prepared by high pressure homogenization method. Both vesicles presented good stability. However, the SL-based vesicles prepared by high speed shear method had larger average diameters and were found to be unstable. Transmission electron microscopy showed that SL-based vesicles had a spherical shape and the result accorded with PCS. The permeation flux of insulin of formulation 1 and control solution were 0.0024 and 0.0008 IU x ml(-1) x min(-1), respectively. The accumulative amount of formulation 1 at 180 min was (0.436 +/- 0.010 ) IU x ml(-1), which was 1.46 times higher than the control solution.

Conclusions: The SL-based vesicles obtained using high pressure homogenization method are characterized by small particle size, narrow distribution, good stability, and powerful permeation-enhancing effect, which enables them to be good carriers for the buccal delivery of insulin.
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August 2006
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