1.Effects of scaffold materials combined with biological factors on biological characteristics of dental follicle cell proliferation and osteogenic differentiation
Zhongzheng LI ; Zhenghao CHEN ; Ziyou TANG ; Kaiyang LOU ; Rui ZHANG ; Qi LIU ; Na ZHAO ; Kun YANG
Chinese Journal of Tissue Engineering Research 2025;29(34):7405-7414
BACKGROUND:Dental follicle cells are widely used in periodontal tissue regeneration engineering because of their excellent characteristics.With the development of biological scaffold materials,their relationship with periodontal tissue regeneration technology is increasingly close.OBJECTIVE:To review the performance of ivory follicle cells under the influence of internal and external biological factors by different experiments,and analyze their effects on the biological characteristics of dental follicle cells with scaffold materials.METHODS:Using"dental follicle cell,scaffolds,material,periodontal tissue regeneration,tissue engineering,review"as English and Chinese key words,the articles published in PubMed,Sciencedirect,and CNKI from 2013 to 2023 were searched,and finally 95 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Dental follicle cells originate from dental follicle tissue,which has certain stem cell differentiation potential.Because of its excellent performance,it is actively used in periodontal tissue regeneration engineering research.(2)The proliferation and osteogenic differentiation of dental follicle cells are affected by many biological factors,and both endogenous and exogenous factors can promote the proliferation and osteogenic differentiation of dental follicle cells to a certain extent.(3)3D printing technology and nanotechnology enable researchers to manufacture more suitable scaffold materials.(4)Polymer materials show us their flexibility and plasticity in periodontal tissue regeneration.We can manufacture targeted scaffold materials according to different defect sites to achieve efficient tissue regeneration.The good biocompatibility of inorganic materials makes them widely used in periodontal tissue regeneration engineering.By adjusting the content of nanoscale inorganic materials or improving the performance of scaffolds,scaffolds with better biocompatibility can be prepared.(5)There are many new synthetic(composite)materials,which show us excellent characteristics.However,because the mechanism of biological factors in scaffold materials on dental follicle cells is complicated,and the research on dental follicle cells is mostly concentrated on in vitro culture,so how to make scaffold materials more suitable for the growth and development of dental follicle cells and apply them safely and effectively in clinical treatment is the future research direction.
2.Clinical characteristics of left-sided infective endocarditis without underlying valvular heart diseases
Na WU ; Zhenghao TANG ; Xiaohua CHEN ; Yongsheng YU ; Yi ZHANG
Chinese Journal of General Practitioners 2025;24(1):82-88
Objective:To investigate the clinical characteristics of left-sided infective endocarditis (IE) without underlying valvular heart diseases (VHD).Methods:This was a retrospective study. Clinical data of 206 patients with left-sided IE (age: (50.4±16.1) years; 144 males (69.9%)) discharged from Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2011 to May 2021 were retrospectively analyzed, including 129 cases with underlying VHD (IE+VHD group) and 77 cases without underlying VHD (IE group). The 6-month survival rate of patients after discharge was analyzed with Kaplan-Meier survival curve; and the 6-month survival rates of the patients with different sizes of endocardial vegetation and different treatment modalities in the IE group were further analyzed with log-rank method.Results:The proportions of patients with age ≥65 years old, arrhythmia and aortic valve involvement, and the in-hospital mortality in the IE group were significantly lower than those in the IE+VHD group ( P<0.05). However, the proportion of patients with fever and speech vague/limb movement disorder/headache, those with mitral valve involvement in the IE group were significantly higher than those in the IE+VHD group ( P<0.05). The median value of C-reactive protein (CRP) in the IE group was significantly higher than that in the IE+VHD group ( P<0.05). Nevertheless, the median value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the IE group was significantly lower than that in the IE+VHD group ( P<0.05). There were as no significant differences in the positive rates of bacterial/fungal blood cultures and the proportion of patients with mitral and aortic valve involvement of endocardial vegetation between the two groups (all P>0.05). Kaplan-Meier survival curve analysis showed that there was no significant difference in 6-month survival rate of patients between the IE group and IE+VHD group (88.7% vs. 93.6%, log-rank χ2=0.887, P=0.346). In the IE group, the 6-month survival rate after discharge in patients with maximum diameter of vegetation ≤10 mm was higher than that in patients with maximum diameter of vegetation >10 mm (96.3% vs. 80.7%, log-rank χ2=4.111, P=0.043). There was no significant difference in 6-month survival rate between patients treated with antibiotics combined with surgery and those treated with antibiotics alone (96.2% vs. 78.6%, log -rank χ 2=2.976, P=0.084). Conclusion:Compared to left-sided IE patients with underlying VHD, patients without underlying VHD are likely to have a younger age, more mitral valve involvement and lower in-hospital mortality; for those patients with maximum diameter of vegetation ≤10 mm there is a higher survival rate, and antibiotics combined with surgery may help to improve the survival rate.
3.Comparison of clinical features and related factors between pyogenic spondylitis and tuberculous spondylitis
Lijie GUO ; Yi ZHANG ; Baohui GUAN ; Yuanhao YANG ; Xiaohua CHEN ; Zhenghao TANG ; Yongsheng YU
Chinese Journal of General Practitioners 2025;24(5):594-602
Objective:To compare the clinical manifestations,laboratory results,and imaging features between pyogenic spondylitis(PS) and tuberculous spondylitis(TS).Methods:This was a cross-sectional study. A total of 88 patients with infectious diseases of spine(IDS) admitted to Shanghai Sixth People′s Hospital from January 2021 to December 2023 were analyzed,including 61 PS cases(PS group) and 27 TS cases(TS group). The clinical manifestations,laboratory results,and imaging features were compared between two groups. The factors associated with PS were analyzed by multivariate logistic regression. The diagnostic efficacy for pathogen identification was compared between metagenomics next-generation sequencing(mNGS) and bacterial culture methods in PS and TS patients.Results:Compared with the TS group,the PS group had a higher age-adjusted Charlson comorbidity index(aCCI)[3.0(1.5,4.0) points vs. 2.0(1.0,3.0) points, Z=-2.189, P=0.029],shorter onset time of disease[1.0(0.8,3.0) months vs. 6.0(2.0,12.0) months,Z=-4.353, P<0.001],and higher median blood leukocyte counts and serum ferritin(SF) level(7.2×10 9/L vs. 6.3×10 9/L, Z=-2.652, P=0.008; 571.3 ng/ml vs. 266.0 ng/ml, Z=-4.773, P<0.001). The proportions of lumbar spine involvement,non-collapsed involved vertebrae,and bone bridges formed were all higher in the PS group compared to the TS group[68.8%(99/144) vs. 41.4%(29/70), χ2=14.628, P<0.001; 68.9%(42/61) vs. 18.5%(5/27), χ2=19.055, P<0.001; 41.0%(25/61) vs. 7.4%(2/27), χ2=9.921, P=0.002]. The proportions of thoracic spine involvement,severe vertebral collapse,severe narrowing of the involved intervertebral space,sequestrum,and paravertebral soft tissue calcification were all higher in the TS group compared to the PS group[52.9%(37/70) vs. 18.1%(26/144), χ2=27.463, P<0.001; 55.6%(15/27) vs. 13.1%(8/61), χ2=17.462, P<0.001; 74.1%(20/27) vs. 37.7%(23/61), χ2=9.907, P=0.002; 74.1%(20/27) vs. 18.0%(11/61), χ2=25.761, P<0.001; 51.9%(14/27) vs. 6.6%(4/61), χ2=23.599, P<0.001]. Multivariate logistic regression analysis indicated that a symptom duration<5.5 months( OR=30.644,95% CI: 2.022-464.529, P<0.05) and a leukocyte count>7.35×10 9/L( OR=48.653,95% CI: 2.045-1 157.721, P<0.05) indicated a higher likelihood of PS; while the vertebral collapse indicated a higher likelihood of TS( OR=0.025,95% CI: 0.001-0.638, P<0.05). The most common pathogen in the PS group was Staphylococcus aureus(31 cases,50.8%),followed by Streptococcus species(10 cases,16.4%). The positive rates of mNGS testing in the PS and TS groups were 84.1%(37/44) and 12/13,respectively,which were higher than those of conventional bacterial culture[77.8%(42/54)] and Mycobacteriumtuberculosis culture(2/11). Conclusions:Compared with the TS patients,the PS patients have shorter onset time,higher aCCI scores,higher blood leukocyte counts and SF levels,less vertebral collapse and intervertebral space narrowing,and more bone bridge formation. The TS patients have more dead bones and calcifications. The mNGS has a higher diagnostic efficacy than bacterial cultures for PS and TS.
4.Effects of scaffold materials combined with biological factors on biological characteristics of dental follicle cell proliferation and osteogenic differentiation
Zhongzheng LI ; Zhenghao CHEN ; Ziyou TANG ; Kaiyang LOU ; Rui ZHANG ; Qi LIU ; Na ZHAO ; Kun YANG
Chinese Journal of Tissue Engineering Research 2025;29(34):7405-7414
BACKGROUND:Dental follicle cells are widely used in periodontal tissue regeneration engineering because of their excellent characteristics.With the development of biological scaffold materials,their relationship with periodontal tissue regeneration technology is increasingly close.OBJECTIVE:To review the performance of ivory follicle cells under the influence of internal and external biological factors by different experiments,and analyze their effects on the biological characteristics of dental follicle cells with scaffold materials.METHODS:Using"dental follicle cell,scaffolds,material,periodontal tissue regeneration,tissue engineering,review"as English and Chinese key words,the articles published in PubMed,Sciencedirect,and CNKI from 2013 to 2023 were searched,and finally 95 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Dental follicle cells originate from dental follicle tissue,which has certain stem cell differentiation potential.Because of its excellent performance,it is actively used in periodontal tissue regeneration engineering research.(2)The proliferation and osteogenic differentiation of dental follicle cells are affected by many biological factors,and both endogenous and exogenous factors can promote the proliferation and osteogenic differentiation of dental follicle cells to a certain extent.(3)3D printing technology and nanotechnology enable researchers to manufacture more suitable scaffold materials.(4)Polymer materials show us their flexibility and plasticity in periodontal tissue regeneration.We can manufacture targeted scaffold materials according to different defect sites to achieve efficient tissue regeneration.The good biocompatibility of inorganic materials makes them widely used in periodontal tissue regeneration engineering.By adjusting the content of nanoscale inorganic materials or improving the performance of scaffolds,scaffolds with better biocompatibility can be prepared.(5)There are many new synthetic(composite)materials,which show us excellent characteristics.However,because the mechanism of biological factors in scaffold materials on dental follicle cells is complicated,and the research on dental follicle cells is mostly concentrated on in vitro culture,so how to make scaffold materials more suitable for the growth and development of dental follicle cells and apply them safely and effectively in clinical treatment is the future research direction.
5.Clinical characteristics of left-sided infective endocarditis without underlying valvular heart diseases
Na WU ; Zhenghao TANG ; Xiaohua CHEN ; Yongsheng YU ; Yi ZHANG
Chinese Journal of General Practitioners 2025;24(1):82-88
Objective:To investigate the clinical characteristics of left-sided infective endocarditis (IE) without underlying valvular heart diseases (VHD).Methods:This was a retrospective study. Clinical data of 206 patients with left-sided IE (age: (50.4±16.1) years; 144 males (69.9%)) discharged from Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2011 to May 2021 were retrospectively analyzed, including 129 cases with underlying VHD (IE+VHD group) and 77 cases without underlying VHD (IE group). The 6-month survival rate of patients after discharge was analyzed with Kaplan-Meier survival curve; and the 6-month survival rates of the patients with different sizes of endocardial vegetation and different treatment modalities in the IE group were further analyzed with log-rank method.Results:The proportions of patients with age ≥65 years old, arrhythmia and aortic valve involvement, and the in-hospital mortality in the IE group were significantly lower than those in the IE+VHD group ( P<0.05). However, the proportion of patients with fever and speech vague/limb movement disorder/headache, those with mitral valve involvement in the IE group were significantly higher than those in the IE+VHD group ( P<0.05). The median value of C-reactive protein (CRP) in the IE group was significantly higher than that in the IE+VHD group ( P<0.05). Nevertheless, the median value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the IE group was significantly lower than that in the IE+VHD group ( P<0.05). There were as no significant differences in the positive rates of bacterial/fungal blood cultures and the proportion of patients with mitral and aortic valve involvement of endocardial vegetation between the two groups (all P>0.05). Kaplan-Meier survival curve analysis showed that there was no significant difference in 6-month survival rate of patients between the IE group and IE+VHD group (88.7% vs. 93.6%, log-rank χ2=0.887, P=0.346). In the IE group, the 6-month survival rate after discharge in patients with maximum diameter of vegetation ≤10 mm was higher than that in patients with maximum diameter of vegetation >10 mm (96.3% vs. 80.7%, log-rank χ2=4.111, P=0.043). There was no significant difference in 6-month survival rate between patients treated with antibiotics combined with surgery and those treated with antibiotics alone (96.2% vs. 78.6%, log -rank χ 2=2.976, P=0.084). Conclusion:Compared to left-sided IE patients with underlying VHD, patients without underlying VHD are likely to have a younger age, more mitral valve involvement and lower in-hospital mortality; for those patients with maximum diameter of vegetation ≤10 mm there is a higher survival rate, and antibiotics combined with surgery may help to improve the survival rate.
6.Comparison of clinical features and related factors between pyogenic spondylitis and tuberculous spondylitis
Lijie GUO ; Yi ZHANG ; Baohui GUAN ; Yuanhao YANG ; Xiaohua CHEN ; Zhenghao TANG ; Yongsheng YU
Chinese Journal of General Practitioners 2025;24(5):594-602
Objective:To compare the clinical manifestations,laboratory results,and imaging features between pyogenic spondylitis(PS) and tuberculous spondylitis(TS).Methods:This was a cross-sectional study. A total of 88 patients with infectious diseases of spine(IDS) admitted to Shanghai Sixth People′s Hospital from January 2021 to December 2023 were analyzed,including 61 PS cases(PS group) and 27 TS cases(TS group). The clinical manifestations,laboratory results,and imaging features were compared between two groups. The factors associated with PS were analyzed by multivariate logistic regression. The diagnostic efficacy for pathogen identification was compared between metagenomics next-generation sequencing(mNGS) and bacterial culture methods in PS and TS patients.Results:Compared with the TS group,the PS group had a higher age-adjusted Charlson comorbidity index(aCCI)[3.0(1.5,4.0) points vs. 2.0(1.0,3.0) points, Z=-2.189, P=0.029],shorter onset time of disease[1.0(0.8,3.0) months vs. 6.0(2.0,12.0) months,Z=-4.353, P<0.001],and higher median blood leukocyte counts and serum ferritin(SF) level(7.2×10 9/L vs. 6.3×10 9/L, Z=-2.652, P=0.008; 571.3 ng/ml vs. 266.0 ng/ml, Z=-4.773, P<0.001). The proportions of lumbar spine involvement,non-collapsed involved vertebrae,and bone bridges formed were all higher in the PS group compared to the TS group[68.8%(99/144) vs. 41.4%(29/70), χ2=14.628, P<0.001; 68.9%(42/61) vs. 18.5%(5/27), χ2=19.055, P<0.001; 41.0%(25/61) vs. 7.4%(2/27), χ2=9.921, P=0.002]. The proportions of thoracic spine involvement,severe vertebral collapse,severe narrowing of the involved intervertebral space,sequestrum,and paravertebral soft tissue calcification were all higher in the TS group compared to the PS group[52.9%(37/70) vs. 18.1%(26/144), χ2=27.463, P<0.001; 55.6%(15/27) vs. 13.1%(8/61), χ2=17.462, P<0.001; 74.1%(20/27) vs. 37.7%(23/61), χ2=9.907, P=0.002; 74.1%(20/27) vs. 18.0%(11/61), χ2=25.761, P<0.001; 51.9%(14/27) vs. 6.6%(4/61), χ2=23.599, P<0.001]. Multivariate logistic regression analysis indicated that a symptom duration<5.5 months( OR=30.644,95% CI: 2.022-464.529, P<0.05) and a leukocyte count>7.35×10 9/L( OR=48.653,95% CI: 2.045-1 157.721, P<0.05) indicated a higher likelihood of PS; while the vertebral collapse indicated a higher likelihood of TS( OR=0.025,95% CI: 0.001-0.638, P<0.05). The most common pathogen in the PS group was Staphylococcus aureus(31 cases,50.8%),followed by Streptococcus species(10 cases,16.4%). The positive rates of mNGS testing in the PS and TS groups were 84.1%(37/44) and 12/13,respectively,which were higher than those of conventional bacterial culture[77.8%(42/54)] and Mycobacteriumtuberculosis culture(2/11). Conclusions:Compared with the TS patients,the PS patients have shorter onset time,higher aCCI scores,higher blood leukocyte counts and SF levels,less vertebral collapse and intervertebral space narrowing,and more bone bridge formation. The TS patients have more dead bones and calcifications. The mNGS has a higher diagnostic efficacy than bacterial cultures for PS and TS.
7.Effects of antibiotic treatment and antibiotics combined with surgery treatment on the prognosis of patients with infective endocarditis
Na WU ; Yanting GU ; Xiaohua CHEN ; Min XI ; Hong JIANG ; Zhenghao TANG ; Guoqing ZANG ; Yongsheng YU ; Yi ZHANG
Chinese Journal of Infectious Diseases 2022;40(10):591-596
Objective:To investigate the effects of antibiotic treatment and antibiotics combined with surgery treatment on the prognosis of patients with infective endocarditis (IE).Methods:The clinical data and prognosis of all patients diagnosed as IE discharged from Shanghai Jiao Tong University Affiliated Sixth People′s Hospital from June 2011 to May 2021 were collected. There were 240 IE patients, divided into antibiotic treatment group and the antibiotics combined with surgery group according to the treatment methods. The clinical characteristics and prognosis of the IE patients were compared between the two groups, so as to investigate the timing of surgery for IE patients and to analyze the effects of the two treatment methods on the prognosis of IE patients.Statistical analysis methods including Wilcoxon rank sum test, chi-square test, Kaplan-Meier survival analysis and Cox regression analysis were used when appropriate.Results:Of the 240 patients with IE, 63 cases were only treated with antibiotics and 177 cases were treated with antibiotics combined with surgery. After propensity score matching (PSM), one-year mortality rate of the IE patients in the antibiotics combined with surgery group was 11.1%(4/36), which was significantly lower than that in the antibiotic treatment group (33.3%(12/36), χ2=5.14, P=0.023). The median values of left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD) and left ventricular fractional shortening (LVFS) in the antibiotics combined with surgery group were 59%, 47 mm and 31%, respectively, which were significantly lower than those before surgery (63%, 54 mm and 34%, respectively, Z=6.19, 9.36 and 6.11, respectively, all P<0.001). The most common surgical indication was moderate to severe heart failure, and there was no significant difference between the early operation group and the late operation group (both P>0.050). The one-year cumulative survival rate of antibiotics combined with surgery group was 94.9%, which was significantly higher than that in the antibiotic treatment group (83.2%, χ2=7.38, P=0.007). Heart failure and Pitt bacteremia scores≥4 were the independent risk factors for one-year all-cause death of the IE patients (hazard ratio ( HR)=5.668 and 19.392, respectively, both P<0.050). Hospital days and antibiotics combined with surgery were independent related factors for reducing the risks of one-year all-cause death ( HR=0.931 and 0.299, respectively, both P<0.050). Pitt bacteremia scores≥4 had the greatest impact on one-year prognosis of the IE patients. Conclusions:Surgery could significantly improve cardiac function and one-year prognosis of the IE patients. IE patients with heart failure and Pitt bacteremia score≥4 should be actively treated.
8.Effect of ubiquitination hepatitis B virus core antigen on inducing dendritic cells autophagy to enhance specific cytotoxic T lymphocyte responses
Run HUANG ; Jie CHEN ; Quanhui TAN ; Siyuan MA ; Xiaohua CHEN ; Yongsheng YU ; Guoqing ZANG ; Zhenghao TANG
Chinese Journal of Infectious Diseases 2021;39(4):228-233
Objective:To clarify the effect of ubiquitination hepatitis B virus core antigen (Ub-HBcAg) on dendritic cells (DC) autophagy, and to explore the mechanism of autophagy in enhancing DC antigen presentation and inducing hepatitis B virus-specific cytotoxic T lymphocyte (CTL) responses.Methods:Ub-HBcAg lentiviral vector (LV-Ub-HBcAg), lentiviral vector-hepatitis B virus core antigen (LV-HBcAg) and no-load plasmid LV (LV) were constructed and packaged. DC2.4 cells were divided into LV-Ub-HBcAg group, LV-HBcAg group and LV group. The blank control group (NC group) was also set. The protein expression of autophagy-related protein P62, microtubule associated protein 1 light chain 3 beta (LC3B), autophagy related 5(ATG5) and Beclin-1 were detected by Western blotting. The expressions of co-stimulatory molecules such as CD86, CD80 and major histocompatibility complex (MHC)-Ⅱ were detected by flow cytometry. Cell counting kit-8 (CCK-8) method was used to detect T lymphocytes proliferation. The non-radioactive lactic acid dehydrogenase (LDH) release method was applied to detect the killing ability of CTL. Statistical analysis was conducted by independent sample t test. Results:The relative protein expressions of LC3B-Ⅱ/LC3B-Ⅰ, Beclin-1 and ATG5 in NC group were 0.445±0.076, 0.522±0.026 and 0.761±0.038, respectively, which were all lower than those in LV-Ub-HBcAg group (0.926±0.021, 0.919±0.016 and 1.451±0.028, respectively). The relative protein expression of P62 in the NC group was higher than that in LV-Ub-HBcAg group ((1.875±0.016) vs (0.647±0.121)). The differences were all statistically significant ( t=6.102, 9.842, 17.490 and 10.590, respectively, all P<0.01). The expressions of CD86 (75.51%), CD80 (83.35%), MHC-Ⅱ (66.66%) in the LV-Ub-HBcAg group were high, and those in the NC group were 8.03%, 7.49%, 0.04%, respectively. The specific CTL killing rate ((65.310±2.091)%) of the LV-Ub-HBcAg group was significantly higher than both NC group ((14.400±0.497)%) and LV-HBcAg group ((54.870±1.443)%), and the differences were both statistically significant ( t=23.690 and 4.111, respectively, both P<0.05). Conclusion:Ub-HBcAg promotes the DC autophagy, up-regulates the expressions of costimulatory molecules on cell surface of DC to induce the maturation and activation, and then stimulates T lymphocyte to induce a stronger specific CTL response under the effort of ubiquitination.
9.The fusion protein of cytoplasmic transduction peptide (CTP)-HBcAg18-27-Tapasin enhances specific immune response to hepatitis B virus and inhibits viral replication in transgenic mice.
Yuyan TANG ; Xiaohua CHEN ; Liqin ZHOU ; Meng ZHUO ; Guoqing ZANG ; Zhenghao TANG ; Yongsheng YU
Chinese Journal of Hepatology 2014;22(1):24-29
OBJECTIVETo investigate the effect of protein transduction domain-hepatitis B virus core antigen (CTP-HBcAg18-27)-Tapasin fusion protein-induced specific cytotoxic T lymphocyte (CTL) response on hepatitis B virus (HBV) replication in HBV transgenic mice.
METHODSTwenty HBV-transgenic mice were randomly divided into two groups for a 3-week course of once weekly subcutaneous immunizations with either CTP-HBcAg18-27-Tapasin fusion protein or CTP-HBcAg18-27. Mice administered isotonic saline served as blank controls. Expressions of cytokines in splenocytes were analyzed by flow cytometry. Serum levels of hepatitis B surface antigen (HBsAg) and HBV DNA were determined by microparticle enzyme immunoassay and real-time fluorescent PCR assay, respectively. Expression of HBsAg in hepatic tissues was detected by immunohistochemistry.
RESULTSImmunization with 100 mug of CTP-HBcAg18-27-Tapasin fusion protein led to a significant increase in proportions of CTLs in spleen (2.70%+/-0.20% vs. 50 mug of CTP-HBcAg18-27-Tapasin: 1.66%+/-0.53%, 50 mug of CTP-HBcAg18-27: 1.26%+/-0.56%, and blank controls: 0.75%+/-0.71%; F = 741.45, P = 0.000) and up-regulation of inflammatory cells in hepatic tissue. In addition, both immunizations of CTP-HBcAg18-27-Tapasin led to significant decreases in serum HBsAg and HBV DNA levels compared to those in the CTP-HBcAg18-27 group.
CONCLUSIONHBV-related modification of the expression of the molecular chaperone Tapasin may affect its interaction with intracellular antigen peptides, thereby leading to increases the number of specific CTLs in the spleen, decreases in serum HBsAg and HBV DNA levels, and down-regulation of HBsAg expression in hepatic tissue. These results obtained in HBV-transgenic mice suggest that the CTP-HBcAg18-27-Tapasin fusion protein has anti-HBV activity.
Animals ; DNA, Viral ; blood ; Female ; Hepatitis B ; immunology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; physiology ; Male ; Membrane Transport Proteins ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Virus Replication
10.Effects of cytoplasmic transduction peptide-HBcAg18-27-Tapasin induced murine bone marrow derived dendritic cell maturation on T lymphocyte proliferation in vitro
Honghong LIU ; Xiaohua CHEN ; Liqin ZHOU ; Xueni LIU ; Yongsheng YU ; Guoqing ZANG ; Zhenghao TANG
Chinese Journal of Infectious Diseases 2012;30(10):593-597
Objective To observe the effects of cytoplasmic transduction peptide (CTP)-HBcAg18-27-Tapasin induced murine bone marrow-derived dendritic cell (DC) maturation on T lymphocyte proliferation in vitro,Methods Bone marrow derived DC isolated from BALB/c mice were cultured with recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleutin (IL)-4 for 5 days followed by lipopolysaccharide added to induce DC maturation.10 μg/L CTP-HBcAg18-27-Tapasin,50 μg/L CTP-HBcAg18-27-Tapasin,10 μg/L CTP-HBcAg18-27 or RPMI-1640 were added into culture medium to induce DC maturation.DC phenotypes were analyzed by flow cytometry.The level of IL-12p70 in the supernatant was detected by enzyme linked immunosorbent assay.The proliferation of.T lymphocytes was performed by using cell counting kit-8 and intracellular cytokine of proliferative T cells were analyzed by flow cytometry.The means among groups were compared using one-way ANOVA and those between two groups were compared by least significant difference test.Results DC were cultured and induced successfully.The molecules on DC surface,such as CD80,CD86 and major histocompatibility antigen-Ⅰ were upregulated by CTP-HBcAg18-27-Tapasin.IL-12p70 level induced by 50 μg/L CTP-HBcAg18-27-Tapasin was (61.12±10.25) pg/mL,which was higher than those induced by 10 μg/L CTP-HBcAg18-27-Tapasin (50.43±10.42) pg/mL,10μg/L CTP-HBcAg18-27 (40.17±8.54) pg/mL and medium control (30.51±8.03) pg/mL (F=15.85,P=0.030 and 0.037).The proliferation of T lymphocytes induced by CTP- HBcAg18-27 -Tapasin was higher than control groups.The amounts of cytotoxic T lymphocyte (CTL) induced by 50 μg/L CTP-HBcAg18-27-Tapasin [(2.05±0.41) %] and 10 μg/L CTP-HBcAg18-27-Tapasin [(1.06 ±0.10 )%] were both significantly higher than the 10 μg/L CTP-HBcAg18-27 group [(0.45±0.11)%] and medium group [(0.09±0.02)%,F=60.22,P=0.003].Conclusions CTP HBcAg18- 27 Tapasin could promote the differentiation and maturation of DC,and enhance the ability of DC stimulating T lymphocytes proliferation and increase CTL expression effectively.

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