Evaluation of immune persistence of vaccine / 中华预防医学杂志

The evaluation methods of immune persistence include direct evaluation, indirect evaluation, model prediction, and meta-analysis and so on. Direct evaluation is the gold standard for evaluating the immune persistence of vaccines by quantifying the protective effect of vaccines on the onset and (or) infection of preventable diseases. Indirect evaluation of immune persistence by immunological surrogate indicators is more widely used in practice. In addition, mathematical models and meta-analysis can also be used to evaluate the immune persistence of vaccines. It is of great significance to select the appropriate evaluation method to analyze the immune persistence of the vaccine according to the specific situation.

Topoisomerase inhibitor upregulates MICA/B expression in breast cancer cells through ATM/ATR and NF-κB pathway / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of chemotherapeutic agents widely used in clinical practice on major histocompatibility complex class I-related chain A and B (MICA/B) expression in breast cancer cells, and to explore the molecular mechanisms involved.@*METHODS@#We examined MICA/B mRNA and surface protein expressions in breast cancer cells treated with chemotherapeutic agents by real-time RT-PCR and flow cytometry respectively. The blocking effects of ataxia telangiectasia mutated and Rad3-related kinase (ATM/ATR) inhibitor caffeine and nuclear factor κB (NF-κB) inhibitor pynolidine dithiocarbamate (PDTC) on etoposide-upregulated MICA/B mRNA and surface protein expressions were investigated. Electrophoretic mobility shift assay (EMSA) was taken to investigate whether etoposide enhanced the binding of NF-κB to MICA/B gene promoter.@*RESULTS@#Three topoisomerase inhibitors etoposide, camptothecin and doxorubicine upregulated MICA and MICB mRNA expressions in breast cancer cell MCF-7. Comparing to no-drug-treated cells, MICA mRNA levels increased to (1.68±0.17), (2.54±0.25) and (3.42±0.15) fold, and levels of MICB mRNA increased to (1.82±0.24), (1.56±0.05) and (5.84±0.57) fold respectively in cancer cells treated by etoposide at the concentrations of 5, 20 and 100 μmol/L (P<0.05). MICA and MICB mRNA levels also increased significantly when MCF-7 cells were incubated with camptothecin or doxorubicine at the specific concentrations (P<0.05). MICB mRNA expression also increased slightly in another breast cancer cell SK-BR-3 treated by topoisomerase II inhibitors etoposide and camptothecin (P<0.05). Furthermore, etoposide and camptothecin upregulated MICA/B surface protein expression in MCF-7 cells (P<0.05), and the upregulation was found in both living and apoptotic cells. Our study showed that etoposide induced-MICA/B expression in MCF-7 was inhibited by caffeine at different concentrations. When cancer cells were treated by caffeine with 1, 5 and 10 mmol/L, MICA mRNA levels decreased from (3.75±0.25) to (0.89±0.05), (0.81±0.02) and (0.48±0.04) fold respectively (P<0.001), and MICB mRNA levels decreased from (6.85±0.35) to (1.36±0.13), (0.76±0.06) and (0.56±0.03) fold (P<0.05), while MICA/B protein levels decreased from (3.42±0.05) to (1.32±0.03), (1.21±0.06) and (1.14±0.03) fold (P<0.001), indicating that etoposide-induced MICA/B expression was inhibited by ATM/ATR inhibitor. Similarly, NF-κB inhibitor PDTC also inhibited MICA/B mRNA and protein expressions induced by etoposide significantly when MCF-7 cells were incubated with PDTC at the concentrations of 10, 50 and 100 μmol/L (P<0.05), indicating that NF-κB was also involved in this process. EMSA showed that the binding of NF-κB to MICA/B promoter enhanced in MCF-7 cells after etoposide treatment.@*CONCLUSION@#Topoisomerase inhibitor increased MICA/B mRNA and protein expressions in breast cancer cells, indicating that chemotherapeutic agents might increase the recognizing and killing ability of immunocytes to breast cancer cells. ATM/ATR and NF-κB pathways might be involved in it.

Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanism.</p><p><b>METHODS</b>Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group (saline), LPS group (LPS 5 mg/kg), RvD1 group (RvD1 5 μg/kg + LPS 5 mg/kg), and blockage group (Boc-MLP 5 μg/kg + RvD1 5 μg/kg + LPS 5 mg/kg). Boc-MLP is a RvD1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively (n = 6 in each group at each time point). Human proximal tubule epithelial cells (HK-2) were randomly divided into control group (medium only), LPS group (LPS 5 μg/ml), RvD1 group (RvD1 10 ng/ml + LPS 5 μg/ml), and blockage group (Boc-MLP 10 ng/ml + RvD1 10 ng/ml + LPS 5 μg/ml). The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively (n = 6 in each group at each time point). Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α (TNF-α) level was detected by ELISA. Kidney pathology was observed under hematoxylin and eosin (HE) staining and transmission electron microscope (TEM). We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B (NF-κB) signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining.</p><p><b>RESULTS</b>RvD1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD1 improved 48 h animal survival (80%) compared with LPS group (40%) and RvD1 blockage group (60%), while RvD1 also ameliorated kidney pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-α in both mice kidneys and HK-2 cells were all up-regulated, while RvD1 substantially inhibited the up-regulation of these genes. Western blotting showed that the phosphorylated-IκB/IκB ratio in LPS group was significantly higher than that in the control group, which was inhibited in the RvD1 group. RvD1 could inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which was prohibited in RvD1 blockage group. RvD1 group also had a lower proportion of apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group.</p><p><b>CONCLUSION</b>In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.</p>

Dendritic cells elicit cellular immune response by targeting to capture breast cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the specific anti-breast cancer immune response induced by dendritic cells (DC) loaded with trastuzumab and apoptotic Her-2+ breast cancer cells.</p><p><b>METHODS</b>DCs were generated from healthy peripheral blood mononuclear cells (PBMCs) in the presence of recombinant cytokines GM-CSF, IL-4 and TNF-alpha. Mature DCs were harvested after 7 days' co-culture of PBMCs and trastuzumab-treated apoptotic SKBr3 cells. The morphologic characteristics and ultrastructure of the DC were observed under the inverted phase-contrast microscope and transmission electron microscope (TEM), respectively. Flow cytometry (FCM) was used to check the expression of several DC specific markers: CD14, CD1a, CD64, CD80, CD83, CD86, HLA-ABC and HLA-DR. DC-cytokine induced killer (DC-CIK) cells were prepared by co-culture of DCs and peripheral blood lymphocytes in the presence of anti-CD3 antibodies and human IL-2 at an appropriate concentration. The number of antigen-specific T cells was analyzed by human interferon gamma enzyme linked immunospot (ELISPOT) assay. MTT assay was employed to assess the lysis of breast cancer cell line induced by DC-CIK cells.</p><p><b>RESULTS</b>5 minutes after the adding of DCs to SKBr3 cells pretreated with trastuzumab, the apoptotic SKBr3 cells were found to be circled by DCs. 48 hours later, many membrane-wrapped organelles of the apoptotic target cells in the cytoplasm of DCs were found by TEM. The majority of the organelles were degraded. Fewer organelles from the apoptotic cells were found in DCs without Herceptin. More than 60% in every group of DCs expressed a high-affinity receptor for IgG (FcgammaRI or CD64). CD14 expression on the mature DCs were comparatively lower, and HLA-DR and HLA-ABC expressions were higher in the trastuzumab group. The expression of CD1a, CD80, CD83 and CD86 in trastuzumab group were higher than those in immature DCs group (P < 0.05). ELISPOT assay suggests that the spot number of antigen-specific T cells were higher in trastuzumab group than that in the antigen unloaded DCs group (P < 0.05). The lysis of SKBr3 cells induced by the SKBr3 antigen loaded DC-CIK cells were 1.7 times higher than that of CIK.</p><p><b>CONCLUSION</b>The lysis of SKBr3 cells induced by DC-CIK was increased after that DCs were combined with trastuzumab to capture antigen from SKBr3 cells. These findings support further investigation into the use of combination immunotherapy of the humanized monoclonal antibody, DC vaccines and immunological effector cells.</p>

Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the influence of intranasal instilling titanium dioxide (TiO2) nanoparticles on monoaminergic neurotransmitters at different-time exposure.</p><p><b>METHODS</b>CD female mice were intranasally instilled three different-sized (25 nm, 80 nm and 155 nm) TiO, suspension every other day in a dose of 50 mg/kg body weight. The control group was instilled the same volume of Milli-Q water. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to analyze the titanium contents in murine brain after exposure to TiO2 particles 2 days, 10 days, 20 days and 30 days. The monoaminergic neurotransmitters such as norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and homovanillic (HVA), were determined by reversed-phase high performance liquid chromatography (RP-HPLC) with electrochemical detector.</p><p><b>RESULTS</b>After exposure to TiO, nanoparticles 10 days, the titanium contents in murine brain were increased, the titanium content in the 25 nm group was up to (1059.3 +/- 293.5) ng/g. In 20 days, the titanium content decreased slowly with the metabolism of titanium in vivo, but it kept at a high level, the content decreased to (654.7 +/- 269.2) ng/g in the 25 nm group. After exposure to TiO2 nanoparticles 30 days, the titanium contents had no obviously change. Because of the accumulation of TiO, in the brain, the contents of NE and 5-HT increased significantly after exposure to 80 nm and 155 nm TiO, nanoparticles 20 days, while the decreased contents of DA, DOPAC, HVA and 5-HIAA were observed.</p><p><b>CONCLUSION</b>The inhaled TiO2 nanoparticles could be translocated to and deposited in murine brain after absorbing by nasal mucosa, and further influence the releases and metabolisms of monoaminergic neurotransmitters in brain.</p>

Effects on serum glucose and lipids in chronic exposure to lanthanum chloride in rat / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effects of serum glucose and lipids by on chronically lanthanum exposure in rat.</p><p><b>METHODS</b>The Wistar rats were treated with oral exposure dose 0.1, 2 and 40 mg/kg of lanthanum chloride (LaCl(3)) respectively, after 90 days the rats were sacrificed and the blood was collected for measuring the glycosylated hemoglobin A (HbA1c), the serum was used for measuring glucose, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels.</p><p><b>RESULTS</b>There were no any differences among the control and 3 dose LaCl(3) exposed rats on the blood HbA1c and serum Glu, TG and LDL-C levels (P > 0.05). The serum TC in 0.1 and 2 mg/kg LaCl(3) dose group rats were (1.38 +/- 0.14) mmol/L and (1.37 +/- 0.26) mmol/L respectively. It was lower than that of the controls (1.57 +/- 0.14) mmol/L significantly (P < 0.05), the serum HDL-C in 0.1 mg/kg dose group rats was (0.79 +/- 0.12) mmol/L and obviously lower than that of control group rats (0.93 +/- 0.10) mmol/L (P < 0.05).</p><p><b>CONCLUSION</b>0.1 - 40 mg/kg LaCl(3) chronically exposed have not greater effect on serum glucose, TG and LDL-C levels in rats, but the lower dose LaCl(3) chronic exposure might cause serum TC and HLD-C level decreasing.</p>

Safety and immunogenicity of Bilive combined hepatitis A and B vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the safety and immunogenicity of the Bilive combined hepatitis A and B vaccine produced by Sinovac Biotech Co., Ltd.</p><p><b>METHODS</b>Samples were selected from first year students of a senior high school (adults group) and first to fifth grade 1-5 students of 3 primary schools (children group). Those who were susceptible to both hepatitis A virus (HAV) and hepatitis B virus (HBV), HAV only or HBV only were assigned to group AB, A and B respectively and were vaccinated with three doses (0, 1 and 6 month schedule) of Bilive combined hepatitis A and B vaccine, inactivated hepatitis A vaccine and recombined hepatitis B vaccine respectively. The dosage for adult group was 500 U hepatitis A antigen and/or 10 micro g hepatitis B surface antigen and the dosage for children group was half the dosage of adult group. The potential adverse effects were observed within 72 hours after vaccination. Serum samples were collected for testing anti-HAV and anti-HBs at month 2 and 7 after the initial dose.</p><p><b>RESULTS</b>The rates of local adverse effects were 0.58% and 2.56% in children AB group and adults AB group and the general adverse effects rates were 9.88% and 5.45% respectively. Both local and general adverse effect rates were not significantly different to the control group. The sero-conversion rate of anti-HAV in children and adults AB group reached 100%, one month after 3 doses. The geometric mean titer (GMTs) reached 33,910 mIU/ml and 23,435 mIU/ml respectively, significant higher than that in control group (group A). The sero-conversion rates of anti-HBs were 97.30% and 96.63%, and GMTs were 103 mIU/ml and 102 mIU/ml in children and adults AB group respectively. No significant difference on sero-conversion and GMT was observed when compared with control group.</p><p><b>CONCLUSION</b>The Bilive combined hepatitis A and B vaccine had good safety profile, and the immunogenicity both on anti-HAV and anti-HBs was similar to that of separated components.</p>