TLR4-MyD88-NF-κB signaling imbalances Th17 and Treg cells in thymoma with myasthenia gravis.

OBJECTIVE: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells. PATIENTS AND METHODS: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3). RESULTS: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation. CONCLUSIONS: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

[Epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China].

Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.

[Research progress on the epidemiology and risk factors of dry eye in children].

The prevalence of dry eye in children is increasing with changes in the environment and the widespread use of electronic products. However, due to poor ability to express themselves and hidden symptoms of children, lack of understanding of dry eye in children, children with dry eye are likely to be misdiagnosed. Dry eye can seriously affect the quality of children's learning, life, vision and visual development. Therefore, it is urgent to raise awareness of clinical workers about dry eye in children, prevent the occurrence of related complications of dry eye, and avoid permanent visual damage to children. This review discusses and summarizes the epidemiology and common risk factors of children with dry eye, with the aim of improving doctors' understanding of dry eye in children.

[Clinical research in cell therapy of liver diseases: progress and challenges].

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.

Association between TP53 polymorphisms and chronic lymphocytic leukemia.

OBJECTIVE: The aim of this study was to explore the association between TP53 gene polymorphisms (rs8068934 A>G and rs218698 C>T) and chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: CLL patients who received treatment in our hospital were enrolled in this study as the disease group. Meanwhile, healthy subjects were taken as the control group. Peripheral blood samples were collected to detect TP53 gene polymorphisms at rs8068934 and rs218698, and the haplotype analysis was performed. The expression of TP53 was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Furthermore, the survival conditions were analyzed. RESULTS: The allele distribution at rs8068934 (p=0.046) and rs218698 (p=0.028) of TP53 gene was different between control group and disease group. A allele frequency at rs8068934 and T allele frequency at rs218698 were significantly higher in disease group (p<0.05). The genotype distribution at rs218698 of TP53 gene in disease group was also different from that in control group (p=0.038). The results demonstrated that CC genotype frequency in disease group was significantly lower than that in control group (p<0.05). Besides, the distribution of dominant model at rs8068934 (p=0.042) and recessive model at rs218698 (p=0.033) in disease group exhibited remarkable differences from control group, in which AA+AG frequency (dominant model) at rs8068934 and CC+CT frequency (recessive model) at rs218698 in disease group were significantly higher. Meanwhile, the distribution of AT (p=0.029) and GC (p=0.007) haplotypes at rs8068934 and rs218698 in disease group was evidently different from that in control group. The results indicated that disease group showed significantly higher frequency of AT haplotype and lower frequency of GC haplotype (p<0.05). Moreover, TP53 gene polymorphisms at rs8068934 were significantly associated with the levels of white blood cells (WBC) (p=0.000) and platelets (PLT) (p=0.035). Patients with GG genotype had significantly higher level of WBC, while those with AG genotype showed significantly lower level of PLT (p<0.05). TP53 gene polymorphisms at rs218698 were associated with the level of red blood cells (RBC) (p=0.000). Patients with CT genotype had a remarkably lower level of RBC (p<0.05). There were significant correlations of TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) with the expression of TP53. The expression of TP53 was lower in people with AA genotype at rs8068934 but higher in people with TT genotype at rs218698 (p<0.05). Furthermore, TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) were markedly associated with patients' survival. CONCLUSIONS: TP53 polymorphisms are significantly correlated with the occurrence and progression of CLL.

MiR-22-3p regulates the proliferation and invasion of Wilms' tumor cells by targeting AKT3.

OBJECTIVE: In this study, the regulatory mechanism of miR-22-3p/AKT3 in the development of Wilms' tumor (WT) was investigated. PATIENTS AND METHODS: Twenty-seven pairs of surgical tumor specimens and adjacent normal tissues were obtained from Jining No. 1 People's Hospital. The expression level of miR-22-3p in WT tissues and cell lines was measured by quantitative RT-PCR. MTT and transwell assays were performed to analyze cell proliferation and invasion in WT. The relationship between miR-22-3p and AKT3 was verified by a Dual-Luciferase assay. The protein expression of AKT3 was evaluated by Western blotting analysis. RESULTS: MiR-22-3p was downregulated and AKT3 was upregulated in WT. Functionally, overexpression of miR-22-3p inhibited cell proliferation and invasion in WT. Moreover, miR-22-3p directly targets AKT3. The knockdown of AKT3 suppressed cell proliferation and invasion in WT. In addition, upregulation of AKT3 restored the tumor suppressive effect of miR-22-3p in WT. CONCLUSIONS: MiR-22-3p inhibits the proliferation and invasion of WT cells by downregulating AKT3, indicating that miR-22-3p may be developed as a new biomarker for the diagnosis of WT.

Potential effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on susceptibility to gastric cancer in Chinese population: a meta-analysis.

OBJECTIVE: This meta-analysis aims to clarify the effect of IL-17 polymorphisms on the susceptibility to GCa in the Chinese population. MATERIALS AND METHODS: Relevant pieces of literature were searched in PubMed, Web of School, VIP, and CNKI using the key words as "IL-17, gastric/stomach cancer" or "IL-17 polymorphisms, gastric/stomach cancer susceptibility". The odds ratio (OR) and 95% confidence interval (CI) in the selected studies were calculated using RevMan5.3 and STATA12.0. RESULTS: A total of 12 investigations reporting mutations in IL-17A rs2275913 and IL-17F rs763780 were enrolled. There were 11 studies reporting rs2275913 G>A, involving 3299 cases of GCa patients and 3339 cases of healthy controls. The random-effects model was performed since the heterogeneity test results of the recessive genetic model (GG&GA vs. AA) and the allelic model (G vs. A) of IL-17A rs2275913 G>A were I2>66%/p=0.001. Meanwhile, the dominant genetic model (GG vs. GA&AA) and the super-dominant genetic model (GA vs. GG&AA) of IL-17A rs2275913 G>A were I2< 50%/p>0.05, and the fixed-effects model was used. The meta-analysis showed that IL-17A rs2275913 G>A was positively correlated with GCa susceptibility under four genetic models (p<0.05). Five studies reporting IL-17F rs763780 T>C were enrolled, including 2535 cases of GCa patients and 2402 cases of healthy controls. The heterogeneity test showed that, except for the super-dominant genetic model, the p-value was <0.00001 in the dominant, recessive, and allelic models, and their I2 values were 87%, 88%, and 93%, respectively. Hence, a random-effects model was selected. IL-17F rs763780 T>C was positively correlated with GCa susceptibility under the super-dominant genetic model (p=0.003), rather than the other three models (p>0.05). CONCLUSIONS: IL-17A rs2275913 G>A polymorphism contributes to susceptibility to GCa in the dominant, recessive, allelic, and super-dominant models. Meanwhile, IL-17F rs763780 T>C polymorphism is positively correlated with GCa susceptibility in the super-dominant model.

Simvastatin promotes osteogenic differentiation of mesenchymal stem cells in rat model of osteoporosis through BMP-2/Smads signaling pathway.

OBJECTIVE: By establishing osteoporosis (OP) model in rats, the specific regulatory effect of simvastatin on promoting the differentiation of mesenchymal stem cells (MSCs) into osteoblasts through the bone morphogenetic protein 2 (BMP-2)/Smads signaling pathway was investigated. MATERIALS AND METHODS: A total of 45 Sprague-Dawley rats were selected to establish the OP model by performing ovariectomy. The rats were divided into OP model group (OP group, n=15), 10-7 mmol/L simvastatin treatment group (SIM group, n=15), and normal control group (Control group, n=15). After the experimental period, the enzyme-linked immunosorbent assay (ELISA) was applied to observe the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was adopted to detect the contents of the differentiation-associated genes [runt-related transcription factor 2 (RUNX2) and Osterix (Osx)]. Later, the bone marrow MSCs (BMSCs) were selected and divided into Control group, 10-7 mol/L simvastatin group (SIM group), and osteoinduction medium group (OM group). Cell morphology in each group was observed. The Cell Counting Kit-8 (CCK-8) was performed to determine the proliferation activity of BMSCs. ELISA was performed to measure the level of alkaline phosphatase (ALP). RT-PCR was conducted to examine the levels of key differentiation-associated gene RUNX2 and those in BMP-2/Smads pathway. Moreover, the Western blotting was adopted to analyze the expressions of RUNX2 and genes in BMP-2/Smads pathway. RESULTS: The serum levels of TNF-α, IL-6, and IL-1 in OP group were remarkably higher than those in the Control group, and their levels in the SIM group were close to those in the Control group. The elevated messenger ribonucleic acid (mRNA) levels of the key differentiation-associated factors RUNX2, osteoprotegerin (OPG), osteopontin (OPN), and Osx were observed in the SIM group. In vitro cell culture revealed that the cells were in a favorable growth status in the SIM group and OM group, mostly manifesting in fusiform or spindle shape, and proliferated rapidly. In addition, the ALP level notably increased in the two groups compared with that in the Control group (p<0.05). Both SIM group and OM group had evidently higher mRNA expression levels of RUNX2, OPG, OPN, and Osx than those in the Control group (p<0.05), consistent with the expression trends of the genes in BMP-2/Smads pathway. The Western blotting indicated that the expression levels of RUNX2 and genes in BMP-2/Smads pathway in the SIM group were significantly higher than those in the Control group. CONCLUSIONS: Simvastatin can promote the differentiation of MSCs into osteoblasts in the OP rat model through the BMP-2/Smads signaling pathway.

Nonambipolar Transport due to Electrons with 3D Resistive Response in the KSTAR Tokamak.

A small nonaxisymmetric (3D) magnetic field can induce nonambipolar transport of the particle species confined in a tokamak and thus a significant change of plasma rotation. This process can be in a favor of instability control in the region where the tokamak plasma is sufficiently collisional and resistive, as observed in the applications of n=1 resonant magnetic perturbations to the KSTAR tokamak. The plasma rotation can be globally accelerated due to radially drifting electrons and constrained to the electron root, if the radial transport is enhanced by an amplified 3D response. This mechanism is verified by a kinetically self-consistent magnetohydrodynamic modeling for both response and transport, which offers the quantitative explanations on the internal n=1 structure detected by electron-cyclotron-emission imaging and the cocurrent plasma spinning observed in the experiments.

Dietary alanyl-glutamine improves growth performance of weaned piglets through maintaining intestinal morphology and digestion-absorption function.

Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.

[Clinical pathologic analysis on 3 724 cases of salivary gland tumors].

Objective: To investigate the incidence and proportion of salivary gland tumors in order to provide new thinking for clinical diagnosis and treatment. Methods: Collected 3 724 cases salivary gland tumors diagnosed by Pathology Department of Hospital of Stomatology, Jilin University from January 1961 to December 2016. The pathological diagnosis referred to the fourth edition of head and neck-salivary gland tumor histopathological classification standard of WHO. The database was established with Microsoft Excel and analyzed with SPSS 18.0. Made a retrospective analysis and comparison on the numbers of all cases in terms of types, site, gender and age and estimate the trend with the time interval of 8 years, and then make a judgement of the trend of salivary tumors. Results: The benign tumors were more common than the malignant among all periods, the proportion of all tumors was about 2.92∶1; The top three benign tumors were polymorphous adenoma [73.78% (2 046/2 773)], Warthin tumor [15.80% (438/2 773)] and base cell adenoma [8.37% (232/2 773)]. Polymorphous adenoma took up 54.94% (2 046/3 724) of all tumors. The top three malignant tumors were mucous epidermoid carcinoma [31.44% (299/951)], adenoid cystic carcinoma [26.92% (256/951)] and adenocarcinoma [11.88% (113/951)]. As for sex, male female ratio was 0.83∶1. As for site, the pathogenic site of tumors was mainly in parotid gland [63.75% (2 374/3 724)], followed by palatal gland [16.50% (615/3 724)], then submandibular gland [12.67% (472/3 724)]; As for age, the common age was between 51 and 60 years old [23.74% (884/3 724)], followed by 41 to 50 years old [21.56%(803/3 724)]. Conclusions: The incidence of benign and malignant salivary gland tumor increased in the 56 years. Females showed a higher incidence. The majority tumors occurred in parotid gland. The most common salivary gland tumor was pleomorphic adenoma and the most common malignant tumor was mucous epidermoid carcinoma. The most common age was in 51-60 years old period.

[Analysis of 20-year survival rate and prognostic indicators of systemic lupus erythematosus].

Objective: To analyze the 20-year survival rate, causes of death and predictors of systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on 217 newly SLE patients who were diagnosed and treated by Peking University People's Hospital before June 2008. The clinical features and serologic data were studied. Survival rate of SLE patients over time, living conditions, causes of death and prognostic indicators of mortality were studied. Results: The 10-, 15-and 20-year cumulative survival rate was 90.3%,88.1%and 79.6%, respectively. Infection and lupus encephalopathy were the main causes of death. Cox regression analysis revealed that lupus nephritis, neuropsychiatric systemic lupus erythematosus and age at the diagnosis were independent risk determinants for mortality. Conclusion: Prognosis of SLE remains to be improved. Early diagnosis, control of SLE organ damage and infection prevention are critical to improve survival of SLE patients.

Conceptual design of extended magnetic probe set to improve 3D field detection in NSTX-U.

Adding toroidal arrays of magnetic probes at the top and bottom of NSTX-U would improve both the detection of the multimodal plasma response to applied magnetic perturbations and the identification of the poloidal structure of unstable plasma modes, as well as contribute to the validation of MHD models, improve the understanding of the plasma response to external fields, and improve the error field correction. In this paper, the linear MHD code MARS-F/K has been used to identify poloidal locations that would improve the capability to measure stationary or near-stationary 3D fields that may result from the plasma response to external sources of non-axisymmetric fields. The study highlighted 6 poloidal positions where new arrays of both poloidal and radial magnetic field sensors would improve the poloidal resolution. The proposed set of new arrays combined with the present ones is shown to be capable of measuring the poloidal structure of perturbations with n ≤ 6 and of detecting the multimodal plasma response. Assessment of the trade-off in the poloidal length of the probes leads to an ideal length between 10 cm and 30 cm. A method to configure the probes of a toroidal array based on the singular value decomposition condition number is proposed, and an ideal solution and a low-cost one are presented.

Nanoscale diffusive memristor crossbars as physical unclonable functions.

Physical unclonable functions have emerged as promising hardware security primitives for device authentication and key generation in the era of the Internet of Things. Herein, we report novel physical unclonable functions built upon the crossbars of nanoscale diffusive memristors that translate the stochastic distribution of Ag clusters in a SiO2 matrix into a random binary bitmap that serves as a device fingerprint. The random dispersion of Ag led to an uneven number of clusters at each cross-point, which in turn resulted in a stochastic ability to switch in the Ag:SiO2 diffusive memristors in an array. The randomness of the dispersion was a barrier to fingerprint cloning and the unique fingerprints of each device were persistent after fabrication. Using an optimized fabrication procedure, we maximized the randomness and achieved an inter-class Hamming distance of 50.68%. We also discovered that the bits were not flipping after over 104 s at 400 K, suggesting superior reliability of our physical unclonable functions. In addition, our diffusive memristor-based physical unclonable functions were easy to fabricate and did not require complicated post-processing for digitization and thus, provide new opportunities in hardware security applications.

Dexamethasone alleviates allergic asthma immature rat through Toll like receptor 4.

OBJECTIVE: The allergic asthma model induced by ovalbumin (OVA) was established in the immature rat. Dexamethasone (DXM) was adopted for intervention to analyze the treatment effect and to explore the relationship with toll-like receptor 4 (TLR4). MATERIALS AND METHODS: Immature SD rat was treated by OVA to construct allergic asthma model and intervened by DXM. The rats were randomly divided into model group, experimental group, and control group. The changes in lung tissue were observed by light microscope. The EOS infiltration and reactivity of airway wall were compared. The expressions of TLR2 and TLR4 protein and mRNA in the lung tissue were tested by Western blot and RT-PCR. RESULTS: The lung tissue in the model group was infiltrated by a lot of inflammatory cells, and mucous membrane edema was observed, compared with that in the control group. There were only a few inflammatory cells in the interstitial tissue and pulmonary alveoli in the experimental group compared with that in the model group. EOS count of airway wall and airway reactivity decreased in the experimental group. The levels of TLR2 and TLR4 were significantly elevated in the third week compared with the first week (p<0.05). CONCLUSIONS: The treatment of DXM can alleviate the pathological changes of the lung tissue in SD immature rat with allergic asthma, reduce EOS infiltration in the airway wall, decrease airway reactivity, and elevate expressions of TLR2 and TLR4.

The SNP-set based association study identifies ITGA1 as a susceptibility gene of attention-deficit/hyperactivity disorder in Han Chinese.

Genome-wide association studies, which detect the association between single-nucleotide polymorphisms (SNPs) and disease susceptibility, have been extensively applied to study attention-deficit/hyperactivity disorder (ADHD), but genome-wide significant associations have not been found yet. Genetic heterogeneity and insufficient genomic coverage may account for the missing heritability. We performed a two-stage association study for ADHD in the Han Chinese population. In the discovery stage, 1033 ADHD patients and 950 healthy controls were genotyped using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Infinium HumanExome BeadChip. The genotyped SNPs were combined to generate a powerful SNP set with better genomic coverage especially for the nonsynonymous variants. In addition to the association of single SNPs, we collected adjacent SNPs as SNP sets, which were determined by either genes or successive sliding windows, to evaluate their synergetic effect. The candidate susceptibility SNPs were further replicated in an independent cohort of 1441 ADHD patients and 1447 healthy controls. No genome-wide significant SNPs or gene-based SNP sets were found to be associated with ADHD. However, two continuous sliding windows located in ITGA1 (P-value=8.33E-7 and P-value=8.43E-7) were genome-wide significant. The quantitative trait analyses also demonstrated their association with ADHD core symptoms and executive functions. The association was further validated by follow-up replications for four selected SNPs: rs1979398 (P-value=2.64E-6), rs16880453 (P-value=3.58E-4), rs1531545 (P-value=7.62E-4) and rs4074793 (P-value=2.03E-4). Our results suggest that genetic variants in ITGA1 may be involved in the etiology of ADHD and the SNP-set based analysis is a promising strategy for the detection of underlying genetic risk factors.

Anti-tumor immunity elicited by cross-linking vaccine heat shock protein 72 and alpha-fetoprotein epitope peptide.

Hepatocellular carcinoma (HCC) is one of the most common malignancies over the world. Alpha-fetoprotein (AFP) is an oncofetal protein during HCC development, which could generate weaker and less reproducible antitumor protection, and may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by using glutaraldehyde cross-linking, we constructed a potential therapeutic peptide vaccine, heat shock protein 72 (HSP72) and AFP epitope peptide (HSP72/AFP-P). ELISPOT was applied to evaluate the quantity of AFP-specific CD8+ T cell that secreted IFN-γ in immunized BALB/C mice. Granzyme B released from natural killer cells and AFP-specific antibody responses in immunized mice were detected by ELISA. The anti-tumor effects were investigated by in vitro cytotoxic T-lymphocyte assays and in vivo tumor therapeutic experiments. The results showed that reconstructed HSP72 and AFP epitope peptide vaccine synergistically exhibited significant increases in AFP-specific CD8+ T cells, natural killer cells responses and impressive antitumor effects against AFP-expressing tumors. Immunization of BALB/C mice with HSP72/AFP-P vaccine elicited stronger T-cells responses. The numbers of IFN-γ-producing CD8+ T cells from mice immunized with HSP72/AFP-P were 30 times more than those from mice immunized with AFP-P, HSP72 or PBS (P < 0.01). The concentration of granzyme B in natural killer cells from mice immunized with HSP72/AFP-P were 15 times higher than that from other groups (P < 0.01). In vitro effector cells from mice immunized with HSP72/AFP-P showed much stronger cytolytic effect on H22 target cells than those from mice vaccinated with AFP-P, HSP72 or PBS (P < 0.01). Priming mice with the reconstructed vaccine exhibited robust strong protective immunity. Mice immunized with HSP72 or AFP-P alone demonstrated higher average tumor volumes than mice immunized with HSP72/AFP-P (P < 0.05). Our study suggests that constructing a tumor vaccine by cross-linking AFP antigen epitope peptide and HSP72 is a promising approach for cancer therapy.

Three-dimensional drift kinetic response of high-ß plasmas in the DIII-D tokamak.

A quantitative interpretation of the experimentally measured high-pressure plasma response to externally applied three-dimensional (3D) magnetic field perturbations, across the no-wall Troyon ß limit, is achieved. The self-consistent inclusion of the drift kinetic effects in magnetohydrodynamic (MHD) modeling [Y. Q. Liu et al., Phys. Plasmas 15, 112503 (2008)] successfully resolves an outstanding issue of the ideal MHD model, which significantly overpredicts the plasma-induced field amplification near the no-wall limit, as compared to experiments. The model leads to quantitative agreement not only for the measured field amplitude and toroidal phase but also for the measured internal 3D displacement of the plasma. The results can be important to the prediction of the reliable plasma behavior in advanced fusion devices, such as ITER [K. Ikeda, Nucl. Fusion 47, S1 (2007)].

Knockdown of PTTG1 inhibits the growth and invasion of lung adenocarcinoma cells through regulation of TGFB1/SMAD3 signaling.

Increased expression of pituitary tumor-transforming gene 1 (PTTG1) is expressed in many tumors and regulates tumor growth and progression. However, the precise function of PTTG1 in the tumorigenesis of lung adenocarcinoma (LAC) is not defined yet. Here, we examined the expression of PTTG1 in human LAC tissues by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was carried out to investigate the effects of lentiviral vector-mediated PTTG1 shRNA (shPTTG1) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays. As a consequence, we found that the expression of PTTG1 protein was markedly upregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (54.0% vs. 28.0%, P = 0.008), and was positively associated with the lymphatic invasion of the tumor (P = 0.01). Moreover, knockdown of PTTG1 expression inhibited tumor proliferation and invasion of LAC cells, companied by the decreased expression of CyclinD1 and MMP-2 and increased expression of p-TGFß1 and p-SMAD3. Collectively, our findings indicate that high expression of PTTG1 is correlated with the tumor metastasis of LAC patients, and knockdown of PTTG1 suppresses the growth and invasion of LAC cells through upregulation of the TGFß1/SMAD3 signaling, suggesting that PTTG1 may be a potential target for developing an effective immunotherapeutic strategy for LAC.