RESUMO
Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 â, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1â¶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1â¶1â¶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.
Assuntos
Vacinas Meningocócicas , Neisseria meningitidis , Humanos , Lactente , Pré-Escolar , Vacinas Conjugadas , Vacinação , Polissacarídeos , Anticorpos AntibacterianosRESUMO
Taiwan had been using many important public health management strategies to beat Coronavirus disease 2019 (COVID-19) without a lockdown. Mask wearing by the general public was thought to be the major factor for the success of Taiwan to stop the spread of COVID-19. We share our experience in Taiwan as an example for other countries to safely reopen from a lockdown.
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Objective: The aim of this study was to evaluate the safety and immunogenicity of the first domestic ACYW135 meningococcal conjugate vaccine and a control vaccine named AC group meningococcal conjugate vaccine for 3 months (90-119 days) infants. Methods: From February 2017 to June 2018, a randomized, blinded, and similar vaccine-controlled clinical trial design was adopted at the Henan Vaccine Clinical Research Base. The subjects were 3 months old healthy infants, a total of 720, based on a 1â¶1 ratio. The random allocation table for entry was randomly assigned to the experimental group and the control group. According to the 3, 4, and 5 month-old vaccination procedures, the subjects were vaccinated with test vaccine (ACYW135 group meningococcal conjugate vaccine) and control vaccine (group A group C meningococcal polysaccharide conjugate vaccine), of which 720 were given the first dose, 696 were given the second dose (test group: 346; control group: 350), and 692 were given the third dose (test group: 344; Control group: 348). Results: The overall adverse reaction rate of the test vaccine was 21.90% (230 cases), which was lower than the 32.04% (339 cases) of the control vaccine (P<0.001). The incidence of systemic adverse reactions was 19.52% (205 cases), which was lower than that of the control vaccine (27.69%) (293 cases) (P<0.001). The local adverse reaction rate was 3.04% (32 cases), which was lower than the control group (7.84%) (83 cases) (P<0.001). The graded adverse reaction test vaccine was 0.57% (6 cases), which was lower than the control group of 2.36% (25 cases) (P<0.001). The positive conversion rate of anti-bacterial serum antibodies showed that there was no significant difference between the test vaccine group A (91.42%), C (88.76%) and the control vaccine (92.92%) (87.02%) (P>0.05). Group Y and W135 was 88.17% (298 cases), 99.41% (336 cases), respectively. The GMT results showed that the test vaccine group A was 56.24, the control vaccine was 57.43 (P>0.05); the group C test vaccine (43.53) was higher than the control group (27.28) (P<0.001). The group Y and W135 are 89.22 and 140.66, respectively. Among them, the proportion of the group C GMT antibody ≥ 1â¶128 for test vaccine (31.07%, 105 cases) was higher than the control vaccine (16.22%, 55 cases) (P<0.001). Conclusion: ACYW135 group meningococcal conjugate vaccine has more safety and immunogenicity after application to 3 month old infants.
Assuntos
Vacinas Meningocócicas/efeitos adversos , Anticorpos Antibacterianos , Humanos , Lactente , Vacinas Meningocócicas/imunologia , Vacinas ConjugadasRESUMO
OBJECTIVE: Various microRNAs (miRNAs) have been reported to be involved in the pathogenesis and development of human cancers, including papillary thyroid carcinoma (PTC). However, the role of miR-224-5p in PTC progression remains unclear. Therefore, the purpose of this study is to illuminate the function of miR-224-5p in PTC. PATIENTS AND METHODS: Expression of miR-224-5p and EGR2 was examined in PTC by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Transwell assay was used to detect cell migration and invasion. Western blot analysis was used to detect epithelial-mesenchymal transition (EMT). The relationship between miR-224-5p and EGR2 was confirmed by Dual-Luciferase assay. RESULTS: Upregulation of miR-224-5p and downregulation of EGR2 expression were detected in PTC tissues and cells. Upregulation of miR-224-5p was found to be associated with TNM stage and lymph node metastasis. Meanwhile, it also predicted poor prognosis in PTC patients. Functionally, upregulation of miR-224-5p promoted cell metastasis and EMT in PTC. In addition, miR-224-5p was detected to directly target EGR2. EGR2 expression was negatively correlated with EGR2 expression in PTC. Of note, overexpression of EGR2 attenuated the carcinogenic effects of miR-224-5p in PTC. CONCLUSIONS: MiR-224-5p promotes cell migration, invasion, and EMT in PTC by targeting EGR2.
Assuntos
Carcinoma Papilar/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Carcinoma Papilar/diagnóstico , Células Cultivadas , Proteína 2 de Resposta de Crescimento Precoce/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
In this study, the nasopharyngeal carcinoma cell line was cultured in a superparamagnetic iron oxide nanoparticle aqueous solution with a concentration of 1⯵g/mL by using magnetic labeling technology. The cells took up superparamagnetic nanoparticles through the endocytosis process, which caused the cells to become magnetic and manipulable by a magnetic field gradient. Each cell contained 5.266â¯×â¯106 superparamagnetic nanoparticles, as determined using the magnetophoresis method. A specific domain configuration and its related distribution of magnetic poles in a patterned thin film were obtained after applying a magnetic field in a specific direction. Here, patterned magnetic thin films were designed to form square grid and square ring structures. When the magnetic field of 3000â¯G was applied along the diagonal of the square (45° direction) and then released, magnetic cells were trapped at the intersection of the square grid and the 45° diagonal corner of the square ring structure. From micromagnetic simulation results, it was determined that head-to-head and tail-to-tail domain walls with a high magnetic pole density formed at the corners of the square ring structure in the 45° diagonal direction, and the attractive force between a head-to-head/tail-to-tail domain wall and a cell at a height of 1⯵m above the corner was approximately 2.055â¯×â¯10-10â¯N. In the square grid case, the attractive force between the domain wall at the intersection and a cell at a height of 1⯵m above the intersection was approximately 2.245â¯×â¯10-10â¯N. The results of this study demonstrated that cells can simultaneously be arranged at designated locations physically by using patterned magnetic thin films in a noninvasive manner without chemical modification of the substrate.
Assuntos
Imãs/química , Nanopartículas/química , Compostos Férricos/química , Magnetismo/métodosRESUMO
OBJECTIVE: Satb1 regulates chromatin structure and gene expression, and is aberrantly expressed in many tumors. However, there is still no report about Satb1 functions in peripheral nerve injury until now. In this study, we explored the regulatory effect of Satb1 on Schwann cells. MATERIALS AND METHODS: MTT assay, transwell assay, and flow cytometry assay were respectively used to determine Schwann cell viability, migration, and apoptosis. The mRNA and phosphorylation levels of Satb1 and SHIP1 were assessed by RT-PCR and Western blotting analysis, respectively. The correlation between Satb1 and SHIP1 was examined by ChIP assay. The expressions of PI3K/AKT pathway related factors were detected by Western blotting. RESULTS: In the present study, we found that knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis. Conversely, over-expression of Satb1 promoted cell viability, migration, and inhibited apoptosis. Satb1 inhibited SHIP1 expression by recruiting HDAC1. Furthermore, results showed that Satb1 activated the PI3K/AKT signaling pathway by inhibiting the expression of SHIP1. SHIP1 showed significant reversal effects on the regulatory roles of Satb1 in Schwann cells. Over-expression of Satb1 and SHIP1 inhibited cell viability, migration, and promoted apoptosis. CONCLUSIONS: Our study demonstrated that the Satb1 knock-out could inhibit the activation of PI3K/AKT pathway by up-regulating SHIP1, thus inhibiting cell viability and migration, and promoting Schwann cell apoptosis.
Assuntos
Proteínas de Homeodomínio/metabolismo , Células de Schwann/fisiologia , Transdução de Sinais/genética , Animais , Animais Recém-Nascidos , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Proteínas de Homeodomínio/genética , Humanos , Regeneração Nervosa/genética , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-DawleyRESUMO
The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22-4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20-3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30-7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35-7·85, P = 0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22.
Assuntos
Genótipo , Interleucinas/genética , Nefropatias/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Interleucinas/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Adulto Jovem , Interleucina 22RESUMO
BACKGROUND: Geniposide (GEN) is the major ingredient of Gardenia jasminoides Ellis, which has anti-inflammatory and anti-apoptotic activities and is widely used to treat ischemia disease. Inflammation and apoptosis play an important role in hepatic ischemia/reperfusion (I/R) injury. The current study was conducted to explore the effects of geniposide on hepatic I/R injury and its potential molecular mechanism in mice. METHODS: Fifty Sprague-Dawley rats were randomly divided into 5 groups: the sham group (sham), the hepatic I/R injury group (IRI) and the GEN groups (low, middle, and high). In the GEN and IRI groups, hepatic IRI by was induced by means of clamping the left and median liver lobes for 30 minutes with noninvasive endoclips. The GEN groups were pretreated with GEN (5, 10, 20 mg/kg) at 30 minutes before ischemia by use of intraperitoneal injection. Rats in the IRI group and sham group were administrated with same dosage of saline at the same time. After reperfusion for 6 hours, the hepatic pathology and the expression of alanine aminotransferase (ALT), AST aspartate aminotransferase, LDH lactic acid dehydrogenase, PI3K, AKT, p-AKT, m-TOR, Bax, BCL-2, interleukin (IL)-6, MCP-1, and tumor necrosis factor (TNF)-α were examined. RESULTS: Compared with the sham group, the IRI group had higher expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and lower expression of BCL-2, PI3K, p-AKT, and mammalian target of rapamycin (mTOR), with more inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. Compared with the IRI group, the GEN group had lower expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and higher expression of BCL-2, PI3K, p-AKT, and mTOR, with less inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. There were no differences in the expression of AKT among several groups. CONCLUSIONS: GEN can protect rats against hepatic I/R injury and partly relies on suppressing inflammation and apoptosis by inducing the activation of the PI3K/Akt/mTOR signaling pathway.
Assuntos
Iridoides/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/análise , Proliferação de Células , Neoplasias Pulmonares/patologia , Linfócitos T/patologia , Células A549 , Animais , Anticorpos Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Células Cultivadas , Citometria de Fluxo , Humanos , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Neoplasias Esplênicas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To understand the epidemiological characteristics of pertussis in adults and related factors in Tianjin. METHODS: Descriptive epidemiological analysis was conducted by using the epidemiological data of pertussis in adults in Tianjin during 2005-2014. The transmission routes of family cluster cases were analyzed. ELISA was conducted to detect pertussis immunity levels in adults aged 18-83 years. RESULTS: The pertussis cases in adults accounted for 28.57%(252/882)of the total cases in Tianjin , the annual incidence of pertussis in adults was 0.16/100 000. The highest incidence was 0.46/100 000 in 2013. The age specific proportion of the cases was highest in age group 21-30 years(36.12%, 91/252). Three household transmission routes of pertussis were identified, the major one was adult-to-infant(77.78%,98/126). The parents were the infection sources of 81.64% of infant cases(80/98). Of the 904 study subjects, the average positive rate of antibody against pertussis was 55.20%(95%CI: 51.96%-58.44%). There were significant differences in antibody positive rate among different age groups(P= 0.015), and which had the linear correlation with the reported annual incidence(r=0.98, P=0.003)and showed upward trend(χ(2)=11.79, P=0.001). CONCLUSION: The study indicated that adults have become the population at high risk for pertussis and the major infection sources for infants in Tianjin. The positive rate of antibody against pertussis was low in adults. It is suggested to conduct pertussis vaccination in adults.
Assuntos
Vacina contra Coqueluche/imunologia , Vacinação , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Adulto , Anticorpos , Bordetella pertussis , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Incidência , Lactente , Toxina Pertussis/imunologia , Coqueluche/diagnóstico , Coqueluche/microbiologiaRESUMO
OBJECTIVE: To explore whether T lymphocytes subgroup, B lymphocytes, platelet antigen CD41a, CD61 or platelet antibodies are involved in the platelet transfusion refractoriness. METHODS: Forty-seven patients diagnosed as platelet transfusion refractoriness and 32 patients that achieved effective platelet therapy were ennolled in this study. Flow cytometry was performed to detect the proportion of cytotoxic T cell (CD3(+)CD4(-)CD8(+)), helper T cell (CD3(+)CD4(+)CD8(-)) and B lymphocytes (CD19 (+) ), and the expression of platelet glycoproteins, including CD41a and CD61, while platelet antibodies were also measured by solid-phase agglutination. RESULTS: The significant lower level of helper T cell (36.60% vs 48.53%), higher level of cytotoxic T cell (53.26% vs 44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in platelet refractoriness group when compared with effective platelet therapy group (P<0.05). However, the significant difference was not observed in B lymphocytes between the two group (3.02% vs 2.85%, P>0.05). Platelet glycoproteins CD41a and CD61 and antibodies were both expressed at high levels in platelet refractoriness group (88.10% vs 51.69%, 88.36% vs 51.83%, 85.37% vs 14.82%, respectively, P<0.05). CONCLUSIONS: Activation of cytotoxic T cells, suppression of helper T cells, higher expression level of platelet glycoproteins CD41a and CD61 as well as the development of anti-platelet antibodies are involved in the immunologic mechanism of platelet refractoriness.
Assuntos
Autoanticorpos/sangue , Plaquetas/imunologia , Subpopulações de Linfócitos/citologia , Transfusão de Plaquetas , Linfócitos B/citologia , Citometria de Fluxo , Humanos , Linfócitos T Citotóxicos/citologia , Linfócitos T Auxiliares-Indutores/citologia , Falha de TratamentoRESUMO
BACKGROUND: TGF-ß is a key modulator in the regulation of cell proliferation and migration, and is also involved in the process of cancer development and progression. Previous studies have indicated that TGF-ß responsiveness is determined by TGF-ß receptor partitioning between lipid raft/caveolae-mediated and clathrin-mediated endocytosis. Lipid raft/caveolae-mediated endocytosis facilitates TGF-ß degradation and thus suppressing TGF-ß responsiveness. By contrast, clathrin-mediated endocytosis results in Smad2/3-dependent endosomal signaling, thereby promoting TGF-ß responsiveness. Because betulinic acid shares a similar chemical structure with cholesterol and has been reported to insert into the plasma membrane, we speculate that betulinic acid changes the fluidity of the plasma membrane and modulates the signaling pathway associated with membrane microdomains. We propose that betulinic acid modulates TGF-ß responsiveness by changing the partitioning of TGF-ß receptor between lipid-raft/caveolae and non-caveolae microdomain on plasma membrane. METHODS: We employed sucrose-density gradient ultracentrifugation and confocal microscopy to determine membrane localization of TGF-ß receptors and used a luciferase assay to examine the effects of betulinic acid in TGF-ß-stimulated promoter activation. In addition, we perform western blotting to test TGF-ß-induced Smad2 phosphorylation and fibronectin production. RESULTS AND CONCLUSIONS: Betulinic acid induces translocation of TGF-ß receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-ß receptors. The betulinic acid-induced TGF-ß receptors translocation is rapid and correlate with the TGF-ß-induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells.
Assuntos
Células Epiteliais/metabolismo , Pulmão/metabolismo , Microdomínios da Membrana/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Triterpenos/farmacologia , Animais , Linhagem Celular , Células Epiteliais/citologia , Pulmão/citologia , Vison , Triterpenos Pentacíclicos , Ácido BetulínicoRESUMO
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
Assuntos
Humanos , Animais , Camundongos , Adenocarcinoma/patologia , Antígeno B7-H1/análise , Proliferação de Células , Neoplasias Pulmonares/patologia , Linfócitos T/patologia , Células A549 , Anticorpos Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Células Cultivadas , Citometria de Fluxo , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Neoplasias Esplênicas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
UNLABELLED: Reorganization of the actin cytoskeleton is essential for cell motility and chemotaxis. Actin-binding proteins (ABPs) and membrane lipids, especially phosphoinositides PI(4,5)P2 and PI(3,4,5)P3 are involved in the regulation of this reorganization. At least 15 ABPs have been reported to interact with, or regulated by phosphoinositides (PIPs) whose synthesis is regulated by extracellular signals. Recent studies have uncovered several parallel intracellular signalling pathways that crosstalk in chemotaxing cells. Here, we review the roles of ABPs and phosphoinositides in chemotaxis and cell migration. LINKED ARTICLES: This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.
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Citoesqueleto de Actina/metabolismo , Quimiotaxia/fisiologia , Proteínas dos Microfilamentos/metabolismo , Fosfatidilinositóis/metabolismo , Movimento Celular/fisiologia , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Pulmonary fibrosis (PF) is a progressing lung injury initiated by pulmonary inflammation (PI). Bleomycin (BLM) is the most common pathogenesis of PF through early PI and extensive extracellular matrix deposition. This study is aimed to determine whether NO-releasing KMUP-1 inhibits PI and PF, and if so, the benefits of KMUP-1S resulted from simvastatin (SIM)-bonding to KMUP-1. EXPERIMENT APPROACH: C57BL/6 male mice were intra-tracheally administered BLM (4 U/kg) at day 0. KMUP-1 (1-5 mg/kg), KMUP-1S (2.5 mg/kg), SIM (5 mg/kg), Plus (KMUP-1 2.5 mg/kg + SIM 2.5 mg/kg), and clarithromycin (CAM, 10 mg/kg) were orally and daily administered for 7 and 28 days, respectively, to mice, sacrificed at day-7 and day-28 to isolate the lung tissues, for examining the inflammatory and fibrotic signaling and measuring the cell population and MMP-2/MMP-9 activity in broncholaveolar lavage fluid (BAL). KEY RESULTS: KMUP-1 and KUP-1S significantly decreased neutrophil counts in BAL fluid. Fibroblastic foci were histologically assessed by H&E and Masson's trichrome stain and treated with KMUP-1 and references. Lung tissues were determined the contents of collagen and the expressions of TGF-ß, α-SMA, HMGB1, CTGF, eNOS, p-eNOS, RhoA, Smad3, p-Smad3, MMP-2 and MMP-9 by Western blotting analyses, respectively. These changes areregulated by NO/cGMP and inhibited by various treatments. KMUP-1 and KMUP-1S predominantly prevented HMGB1/MMP-2 expression at day-7 and reduced TGF-ß/phosphorylated Smad3 and CTGF at day-28. CONCLUSIONS AND IMPLICATIONS: KMUP-1 and KMUP-S restore eNOS, inhibit iNOS/ROCKII/MMP-2/MMP-9, attenuate histologic collagen disposition and reduce BALF inflammatory cells, potentially useful for the treatment of BLM-lung PF.
Assuntos
Piperidinas/farmacologia , Pneumonia/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Sinvastatina/farmacologia , Xantinas/farmacologia , Animais , Bleomicina/toxicidade , Western Blotting , Líquido da Lavagem Broncoalveolar , Claritromicina/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/administração & dosagem , Piperidinas/química , Pneumonia/patologia , Fibrose Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacos , Sinvastatina/administração & dosagem , Sinvastatina/química , Fatores de Tempo , Xantinas/administração & dosagem , Xantinas/químicaRESUMO
Minimally invasive total knee replacement (MIS-TKR) has been reported to have better early recovery than conventional TKR. Quadriceps-sparing (QS) TKR is the least invasive MIS procedure, but it is technically demanding with higher reported rates of complications and outliers. This study was designed to compare the early clinical and radiological outcomes of TKR performed by an experienced surgeon using the QS approach with or without navigational assistance (NA), or using a mini-medial parapatellar (MP) approach. In all, 100 patients completed a minimum two-year follow-up: 30 in the NA-QS group, 35 in the QS group, and 35 in the MP group. There were no significant differences in clinical outcome in terms of ability to perform a straight-leg raise at 24 hours (p = 0.700), knee score (p = 0.952), functional score (p = 0.229) and range of movement (p = 0.732) among the groups. The number of outliers for all three radiological parameters of mechanical axis, frontal femoral component alignment and frontal tibial component alignment was significantly lower in the NA-QS group than in the QS group (p = 0.008), but no outlier was found in the MP group. In conclusion, even after the surgeon completed a substantial number of cases before the commencement of this study, the supplementary intra-operative use of computer-assisted navigation with QS-TKR still gave inferior radiological results and longer operating time, with a similar outcome at two years when compared with a MP approach.
Assuntos
Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Idoso , Artroplastia do Joelho/efeitos adversos , Feminino , Seguimentos , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Prospectivos , Radiografia , Resultado do TratamentoRESUMO
Collagen VI, one of the extracellular matrix proteins, has been implicated in regulating cell proliferation and reducing apoptosis in several different systems. However, the role of collagen VI in the central nervous system remains unclear. In this manuscript, we demonstrated that upon ultraviolet (UV) irradiation, mouse primary hippocampal neurons specifically up-regulate the expression of Col6a1, Col6a2, and Col6a3 mRNA and secreted collagen VI protein. Augmentation of collagen VI mRNA and protein after UV irradiation may have a neuroprotective role as suggested by the fact that extracellular supplying soluble collagen VI protein, but not other collagen proteins, reduced UV induced DNA damage, mitochondria dysfunction, and neurite shrinkage. We also tried to determine the signaling molecules that mediate the protective effect of collagen VI via Western blot and inhibitor analysis. After collagen VI treatment, UV irradiated neurons increased phosphorylation of Akt and decreased phosphorylation of JNK. Inhibiting Akt/phosphatidylinositol 3-kinases (PI3K) pathway diminished the protective effect of collagen VI. Our study suggested a potential protective mechanism by which neurons up-regulate collagen VI production under stress conditions to activate Akt/PI3K anti-apoptotic signaling pathway.
Assuntos
Apoptose/efeitos dos fármacos , Colágeno Tipo VI/farmacologia , Neurônios , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Relação Dose-Resposta a Droga , Embrião de Mamíferos , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Hipocampo/citologia , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/efeitos dos fármacos , Neuritos/efeitos da radiação , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/efeitos da radiação , Gravidez , Transdução de Sinais/efeitos dos fármacos , Estatísticas não Paramétricas , Sais de Tetrazólio , Tiazóis , Fatores de TempoRESUMO
A comparative study of a frequency-doubling 532 nm laser based on gray-tracking-resistant KTP (GTR-KTP) and conventional KTP is presented. The intracavity GTR-KTP was proved to have better temperature characteristics than that of conventional KTP. Within the normalized output power variation range of 0.8-1.0, GTR-KTP has a temperature tolerance of 35 degrees C, broader than the 21 degrees C obtained with conventional KTP. Under the laser diode (LD) pump power of 180 W, the maximum average output power at 532 nm was 40.6 W for GTR-KTP at a repetition frequency of 10 kHz. In the case of conventional KTP, the maximum available LD pump power was limited to 150 W, with the corresponding maximum green average output power of 27.2 W.