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1.
Cancer Med ; 8(14): 6195-6211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31305011

RESUMO

BACKGROUND: Cervical cancer is a major public health concern in China. We report the end-of-study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04-human papillomavirus (HPV)-16/18 vaccine in Chinese women aged 18-25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. METHODS: Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of AS04-HPV-16/18 vaccine or Al(OH)3 (control) at Months 0-1-6. Vaccine efficacy against HPV-16/18 infection and cervical intraepithelial neoplasia (CIN), cross-protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according-to-protocol efficacy (ATP-E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC-E; vaccine N = 2987; control N = 2985) and TVC-naïve (vaccine N = 1660; control N = 1587). RESULTS: In initially HPV-16/18 seronegative/DNA-negative women, vaccine efficacy against HPV-16/18-associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP-E, 88.7% (95% CI: 18.5, 99.7) in the TVC-E, and 100% (95% CI: 17.9, 100) in the TVC-naïve. Cross-protective efficacy against incident infection with HPV-31, HPV-33 and HPV-45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP-E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and anti-HPV-18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. CONCLUSIONS: This is the first large-scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV-16/18-associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. TRIAL REGISTRATION: NCT00779766.

2.
Zhen Ci Yan Jiu ; 44(2): 107-12, 2019 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-30945486

RESUMO

OBJECTIVE: To compare the effect of electroacupuncture (EA) of "Neiguan" (PC6) of the Pericardium Meridian, "Shenmen" (HT7) of the Heart Meridian,"Shuigou" (GV26) of the Governor Vessel and "Zhaohai" (KI6) of the Kidney Meridian on myocardial and cerebral cell apoptosis in cerebral ischemia (CI) rats, so as to explore its mechanism underlying improvement of CI based on the theory of "Heart-brain Correlation". METHODS: Forty-eight SD rats (half male and half female) were randomly divided into normal control, model, PC6, HT7, GV26 and KI6 groups (n=8 in each one). The CI model was established by occlusion of the middle cerebral artery (MCAO). EA (4 Hz/20 Hz, 1.5 mA) was applied to the right PC6, HT7, GV26 or KI6 respectively for 30 min, once every 12 h for 5 times. The cell apoptosis of the ischemic myocardial and cerebral tissues was detected by TUNEL method, and the expression of cerebral and myocardial Bax and Bcl-2 was determined by using immunohistochemistry. RESULTS: Following modeling, the cell apoptosis percentages and Bax-positive cells of both myocardial and cerebral tissues were significantly increased in the model group in comparison with the control group (P<0.01). After EA intervention, the cerebral apoptotic percentage and cerebral Bax-positive cells in the cerebral tissue of the PC6, HT7 and GV26 groups, and the myocardial apoptosis percentage in the PC6 and HT7 groups, as well as the myocardial Bax-positive cells in the PC6 group were obviously decreased (P<0.05, P<0.01), while the cerebral Bcl-2 positive cells in the PC6, HT7 and GV26 groups, and the myocardial Bcl-2 positive cells in the PC6 and HT7 groups were significantly increased relevant to the model group (P<0.01, P<0.05). No significant changes were found in the KI 6 group in the cell apoptosis index and percentages and Bax- and Bcl-2-positive cells of both myocardium and cerebral cortex tissues compared with the model group (P>0.05).. CONCLUSION: EA stimulation of PC6 and HT7 can inhibit CI injury induced cell apoptosis of cerebral and myocardial tissues in CI rats, which is possibly associated with its effects in down-regulating Bax expression and up-regulating Bcl-2 expression of both myocardial and cerebral tissues.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Apoptose , Encéfalo , Feminino , Masculino , Miocárdio , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2
3.
Zhongguo Zhen Jiu ; 39(1): 33-6, 2019 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-30672253

RESUMO

OBJECTIVE: To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period. METHODS: Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed. RESULTS: ①The pain scores of the three groups were significantly lower after treatment (all P<0.01), and scores in the observation group was better than that in the control group 1 and the control group 2 (P<0.05, P<0.01). There was no significant difference between the control group 1 and the control group 2 (P>0.05). ②After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all P<0.01), and the functional classification of shoulder joint in the observation group and the control group 2 were better than that in the control group 1 (P<0.01, P<0.05). There was no significant difference between the observation group and the control group 2 (P>0.05). ③After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both P<0.05). CONCLUSION: Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.


Assuntos
Terapia por Acupuntura , Periartrite , Ioga , Pontos de Acupuntura , Humanos , Periartrite/terapia , Postura , Resultado do Tratamento
4.
Int J Mol Med ; 43(1): 37-46, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30365093

RESUMO

The skin, as the largest organ of the human body, is an important source of stromal stem cells with multipotent differentiation potential. CD105+ mesenchymal stem cells exhibit a higher level of stemness than CD105­ cells. In the present study, human dermal­derived CD105+ fibroblast cells (CD105+ hDDFCs) were isolated from human foreskin specimens using immunomagnetic isolation methods to examine the role of bone morphogenetic protein (BMP)­7 in osteogenic differentiation. Adenovirus­mediated recombinant BMP7 expression enhanced osteogenesis­associated gene expression, calcium deposition, and alkaline phosphatase activity. Investigation of the underlying mechanisms showed that BMP7 activated small mothers against decapentaplegic (Smad) and p38/mitogen­activated protein kinase signaling in CD105+ hDDFCs. The small interfering RNA­mediated knockdown of Smad4 or inhibition of p38 attenuated the BMP7­induced enhancement of osteogenic differentiation. In an in vivo ectopic bone formation model, the adenovirus­mediated overexpression of BMP7 enhanced bone formation from CD105+ hDDFCs. Taken together, these data indicated that adenoviral BMP7 gene transfer in CD105+ hDDFCs may be developed as an effective tool for bone tissue engineering.


Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Diferenciação Celular , Derme/citologia , Endoglina/metabolismo , Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases , Osteogênese , Proteínas Smad/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Separação Celular , Forma Celular , Criança , Fibroblastos/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos C57BL , Osteogênese/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Neuromolecular Med ; 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30178266

RESUMO

Cerebral palsy (CP) is a leading cause of neurological disability among young children. Congenial and adverse perinatal clinical conditions, such as genetic factors, perinatal infection, and asphyxia, are risk factors for CP. Oligodendrocyte transcription factor (OLIG2) is a protein that is expressed in brain oligodendrocyte cells and is involved in neuron repair after brain injury. In this study, we employed a Chinese Han cohort of 763 CP infants and 738 healthy controls to study the association of OLIG2 gene polymorphisms with CP. We found marginal association of the SNP rs6517135 with CP (p = 0.044) at the genotype level, and the association was greatly strengthened when we focused on the subgroup of CP infants who suffered from hypoxic-ischemic encephalopathy (HIE) after birth, with p = 0.003 (OR = 0.558) at the allele level and p = 0.007 at the genotype level, indicating a risk-associated role of the T allele of the SNP rs6517135 under HIE conditions. The haplotype CTTG for rs6517135-rs1005573-rs6517137-rs9653711 in OLIG2 was also significantly associated with the occurrence of CP in infants with HIE (p = 0.01, OR = 0.521). Our results indicate that in the Han Chinese population, the polymorphisms of OLIG2 were associated with CP, especially in patients who had suffered HIE injury. This finding could be used to develop personalized care for infants with high susceptibility to CP.

6.
Mol Genet Genomic Med ; 6(5): 739-748, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29974678

RESUMO

BACKGROUND: Glycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively. More than 10 PIGA pathogenic or likely pathogenic variants have been reported in a wide spectrum of clinical syndromes of PIGA deficiency, including multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2). METHODS: Whole-exome sequencing (WES) was performed on two trios, that is., the proband's family and his affected maternal cousin's family, from a nonconsanguineous Chinese family pedigree with hypotonia-encephalopathy-seizures disease history and putative X-linked recessive inheritance. Sanger sequencing for PIGA variant was performed on affected members as well as unaffected members in the family pedigree to verify its familial segregation. RESULTS: A novel likely pathogenic variant in PIGA was identified through comparative WES analysis of the two affected families. The single-nucleotide substitution (NC_000023.9:g.15343279T>C) is located in intron 3 of the PIGA gene and within the splice acceptor consensus sequence (NM_002641.3:c.849-5A>G). Even though we have not performed RNA studies, in silico tools predict that this intronic variant may alter normal splicing, causing a four base pair insertion which creates a frameshift and a premature stop codon at position 297 (NP_002632.1:p.(Arg283Serfs*15)). Sanger sequencing analysis of the extended family members confirmed the presence of the variant and its X-linked inheritance. CONCLUSION: WES data analysis along with familial segregation of a rare intronic variant are suggestive of a diagnosis of X-liked PIGA deficiency with clinical features of MCAHS2.

7.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2321-2325, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29945385

RESUMO

Echinacoside (ECH) is one of the active ingredients in Cistanche Herba and the principal effective component of Memoregain© as well. Moreover, a new agent namely Naoqing Zhiming tablet, derived from ECH has been licensed for clinical trials. However, the knowledge regarding the stability of is limited, till now, initiating a significant barrier for its further development along with the clinical trials. Herein, we aim to in depth characterize the transformation pattern of ECH in methanol. When ECH was stored in methanol, two primary products (P1 and P2) could be observed in HPLC chromatogram. A home-made automated fraction collector was configured via employing two 2-phase/6-port electronic valves to prepare P1 and P2. Following ¹H-NMR and LC-MS/MS assays, P1 and P2 were unambiguously identified as acteoside and cistanoside A, respectively. Moreover, the existences of cis-ECH, cis-acteoside, and cis-cistanoside A were claimed after careful analysis of the ¹H-NMR spectra of ECH, P1 and P2. Above all, the primary transformation pathways of ECH in methanol included methylation as well as hydrolysis, and mild transformation could also be initiated by cis/trans- configuration transferring for the caffeoyl group. The findings obtained in current study are envisioned to provide useful insight for the further development of ECH and the impurity detection of Naoqing Zhiming tablet. Moreover, the automated fraction collector configured in current study is able to serve as a versatile tool for the collection of signals-of-interest within phytochemical evaluations and impurity isolation.

8.
BMC Med Genomics ; 11(1): 56, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29940959

RESUMO

BACKGROUND: Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population. METHODS: A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software. RESULTS: There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms. CONCLUSIONS: NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.

9.
Oncol Rep ; 40(1): 155-164, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29781034

RESUMO

Notch­3 is a receptor of the Notch signaling pathway and plays an important role in regulating self­renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch­3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non­small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N­[N­(3,5­difluorophenacetyl)­L­alanyl]­S­phenylglycine t­butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3). Both cell lines were subsequently treated with either DAPT or DAPT combined with GEM and then viability, apoptosis, colony formation and cell count assays were performed. DAPT treatment effectively downregulated the expression of NICD3 in both cell lines. DAPT combined with GEM also significantly reduced the percentage of viable cells in both cell lines, while increasing the percentage of apoptotic cells, compared with GEM alone. In the clonogenicity assays, the combination of DAPT and GEM led to a decrease in clone numbers and significantly greater inhibition of the H1299 and A549 cells compared to treatment with DAPT or GEM alone. Meanwhile, levels of the apoptosis­related proteins, Bcl­2 and Bax, were found to be affected by the various treatments. Thus Notch­3 appears to be a promising target for gene therapy and DAPT is able to mediate a strong antitumor effect in NSCLC cells that overexpress Notch­3. Further studies of a combined treatment regimen with DAPT and GEM are warranted and may provide greater efficacy and safety in the treatment of NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Diaminas/farmacologia , Receptor Notch3/genética , Tiazóis/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptor Notch3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
10.
Front Neurol ; 9: 182, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623066

RESUMO

Background: Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention. Objective: The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP. Methods: A total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement. Results: The differences in the rs3024490 (p = 0.033) and rs1800871 (p = 0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (pallele = 0.015, 0.009, 0.006, 0.003, and 0.006, pgenotype = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml, p = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml, p = 0.045, respectively) in CP cases. Conclusion: These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP.

11.
Fish Shellfish Immunol ; 75: 295-300, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29410138

RESUMO

The lamprey (Lampetra japonica), a representative of the jawless vertebrates, is the oldest extant species in the world. LIP-1, which has a jacalin-like domain and an aerolysin pore-forming domain, has previously been identified in Lampetra japonica. However, the structure and function of the LIP-1 protein have not been described. In this study, the LIP-1 gene was overexpressed in HeLa cells and H293T cells. The results showed that the overexpression of LIP-1 in HeLa cells significantly elevated LDH release (P < 0.05), phosphatidylserine exposure and ROS accumulation. The overexpression of LIP-1 also had remarkable effects on the organelles in HeLa cells, while it had no effect on H293T cell organelles. Array data indicated that overexpression of LIP-1 primarily upregulated P53 signaling pathways in HeLa cells. Cell cycle assay results confirmed that LIP-1 caused arrest in the G2/M phase of the cell cycle in HeLa cells. In summary, our findings provide insights into the function and characterization of LIP-1 genes in vertebrates and establish the foundation for further research into the biological function of LIP-1. Our observations suggest that this lamprey protein has the potential for use in new applications in the medical field.


Assuntos
Pontos de Checagem do Ciclo Celular/imunologia , Proteínas de Peixes/imunologia , Lampreias/imunologia , Transdução de Sinais/imunologia , Animais , Morte Celular , Proteínas de Peixes/genética , Vetores Genéticos , Células HEK293 , Células HeLa , Humanos , Lampreias/genética , Análise de Sequência de DNA
12.
Oncol Lett ; 15(1): 940-946, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29399156

RESUMO

Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.

13.
Connect Tissue Res ; 59(3): 223-232, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28696808

RESUMO

BACKGROUND: Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone morphogenetic proteins (BMPs) are a group of cytokines that promote different developmental processes, including the formation of bone. BMPs can promote hDDFC osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone formation in vivo has not been investigated in depth. MATERIALS AND METHODS: hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and osteogenic differentiation was examined by alkaline phosphatase staining and calcium accumulation. In addition, we measured the expression of osteoblast-related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined bone formation using soft X-ray, histological, and immunohistochemical analyses. RESULTS: Our findings showed that adenovirus-mediated BMP7 expression promoted osteogenic differentiation of hDDFCs and enhanced expression of osteoblast-related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced bone formation and osteoblast-related gene expression in vivo after the injection of hDDFC-hydrogel mixture. CONCLUSIONS: Taken together, our data indicate that BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.

14.
Am J Pathol ; 188(3): 757-767, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29248460

RESUMO

Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury remain largely unknown. Neonates have reduced capacity for mounting conventional αßT-cell responses. However, γδT cells are already functionally competent during early development and are important in early-life immunity. We investigated the potential contribution of γδT cells to preterm brain injury using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury-the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT cells provided protection in the mouse model. The common γδT-cell-associated cytokines interferon-γ and IL-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain, where, unlike injury in the mature brain, γδT cells function as initiators of injury independently of common γδT-cell-associated cytokines. This finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.

15.
Cell Commun Signal ; 15(1): 49, 2017 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-29179762

RESUMO

CORRECTION: Unfortunately, following publication of this article [1], it was noticed that the key in Figure 5c incorrectly showed '0 h', '5 h' and '10 h'. The corrected version, showing '0 h', '12 h' and '24 h', can be seen below and the original article has been updated to reflect this.

16.
Zhen Ci Yan Jiu ; 42(3): 229-34, 2017 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29071979

RESUMO

OBJECTIVE: To observe the changes of brain rest-state functional connectivity following electroacupuncture (EA) stimulation of right Xia-Jiquan (HT 1), Shaohai (HT 3), Lingdao (HT 4) and Shenmen (HT 7) of the Heart Meridian and non-acupoints in healthy volunteers so as to provide an imaging basis for clinical treatment of some related disorders. METHODS: A total of 20 healthy volunteers who met the inclusion criteria were randomly divided into HT-acupoint group (n=10 cases) and non-acupoint group (n=10 cases) according to the visiting sequence. EA (2 Hz, 2-5 mA) was applied to the right HT 1-HT 3, and HT 4-HT 7 (two outputs of the EA stimulator being connected to two acupuncture needle handles) and non-acupoints (4 spots on the imaginary mid-line between the HT and the Pericardium Meridian apart from the 4 acupoints HT 1-HT 3, and HT 4-HT 7) for 6 min. All the subjects underwent resting-state (rs) fMRI using an Achieva 1.5 T magnetic resonance image (MRI) scanner before and after EA stimulation. The bilateral posterior cingulate was used as the seed point and the functional connectivity data was analyzed by using DPARSF software and rs-fMRI data analysis toolkit. RESULTS: After EA stimulation of both acupoints and non-acupoints, a similar functional connectivity change was found in the bilateral postcentral gyrus, right inferior parietal lobule, and right inferior frontal gyrus. After EA of acupoints of the HT Meridian, an enhancement of brain functional connectivity was found in the left inferior temporal gyrus and right parahippocampal gyrus, and the newly activated brain regions were the left precentral gyrus, right precuneus, left angular gyrus, left inferior occipital gyrus and the left insula. After EA stimulation of non-acupoints, an increased functional connectivity was found in the left superior temporal gyrus, which was different from EA of acupoints of HT Meridian. CONCLUSIONS: EA stimulation of acupoints of the HT Meridian can enhance the rs functional connectivity in some brain regions as the postcentral gyrus, inferior temporal gyrus, etc. which is related to mediating information of somatosensory, cognitive, affective, memory, cardiovascular activities, etc. in healthy volunteer subjects. The only difference between the two EA groups is an enhanced functional connectivity found in the left superior temporal gyrus after EA of non-acupoints.


Assuntos
Pontos de Acupuntura , Encéfalo/fisiologia , Eletroacupuntura , Meridianos , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética
17.
Cell Commun Signal ; 15(1): 42, 2017 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-29037260

RESUMO

BACKGROUND: In previous research, we found that cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells, but the protein with cytocidal activity was unidentified. METHODS: A novel lamprey immune protein (LIP) as defense molecule was first purified and identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor cells were analysed and measured whether in vivo or in vitro. RESULTS: LIP induces remarkable morphological changes in tumor cells, including cell blebbing, cytoskeletal alterations, mitochondrial fragmentation and endoplasmic reticulum vacuolation, and most of the cytoplasmic and organelle proteins are released following treatment with LIP. LIP evokes an elevation of intracellular calcium and inflammatory molecule levels. Our analysis of the cytotoxic mechanism suggests that LIP can upregulate the expression of caspase 1, RIPK1, RIP3 to trigger pyroptosis and necroptosis. To examine the effect of LIP in vivo, tumor xenograft experiments were performed, and the results indicated that LIP inhibits tumor growth without damage to mice. In addition, the cytotoxic action of LIP depended on the phosphatidylserine (PS) content of the cell membrane. CONCLUSIONS: These observations suggest that LIP plays a crucial role in tumor cell survival and growth. The findings will also help to elucidate the mechanisms of host defense in lamprey.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Peixes/farmacologia , Lampreias/imunologia , Sequência de Aminoácidos , Animais , Antineoplásicos/química , Antineoplásicos/imunologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Proteínas de Peixes/química , Proteínas de Peixes/imunologia , Humanos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Fosfatidilserinas/farmacologia , Piroptose/efeitos dos fármacos
18.
Pharmacoepidemiol Drug Saf ; 26(7): 837-842, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28266092

RESUMO

PURPOSE: To evaluate the safety of HPV-16/18 AS04-adjuvanted vaccine when administered as per the PI in Korea. METHODS: A total of 3084 women aged 10-25 years were enrolled in this post-marketing surveillance from 2008 to 2014. Subjects were invited to receive three doses of the vaccine (0, 1 and 6 months), and participants who received at least one dose were included in the analysis. Adverse events (AEs), adverse drug reactions (ADRs) and serious AEs (SAEs) were recorded after each dose. All AEs, ADRs and SAEs were presented with exact 95% confidence intervals (CI) (NCT01101542). RESULTS: Injection-site pain was the most frequent AE and ADR reported by 322 subjects (10.4% [95%CI: 9.4-11.6]); the local pain was transient and lasted 4-7 days in most cases. Dysmenorrhoea and vaginitis were the most common unexpected AEs reported by 30 (1.0% [95%CI: 0.7-1.4]) and 16 subjects (0.7% [95%CI: 0.3-0.8]), respectively. Pain (toe pain, leg pain and body pain [one case each]; foot pain [two cases]) was the most common unexpected ADR reported by five subjects (0.2% [95%CI: 0.1-0.4]). Four subjects reported a single SAE (one case each of exostosis, gastroenteritis, abortion and tonsillitis); none were fatal. All SAEs were assessed as unlikely to be related to vaccination; gastroenteritis, exostosis and tonsillitis resolved during the study period. CONCLUSIONS: This is the first post-marketing surveillance study in Korea that provides 6-year safety data for HPV-16/18 AS04-adjuvanted vaccine. The vaccine showed an acceptable safety profile and favourable benefit/risk ratio when given to women aged 10-25 years in Korea. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Vigilância de Produtos Comercializados , Adolescente , Adulto , Criança , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Infecções por Papillomavirus/epidemiologia , República da Coreia/epidemiologia , Adulto Jovem
19.
J Natl Cancer Inst ; 109(7)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28132019

RESUMO

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs). Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided. Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70. Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/virologia , Costa Rica , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , Resultado do Tratamento , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Adulto Jovem
20.
Cancer Med ; 6(1): 12-25, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27998015

RESUMO

We previously reported the results of a phase II/III, double-blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7-99.9) HPV-16/18 AS04-adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6-month (M) persistent infection (PI) with a mean follow-up of <2 years, and immunogenicity until 7 months post-dose 1. Here, we report efficacy and safety results from an event-triggered analysis with ~3 years longer follow-up, and immunogenicity until M24. Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of HPV-16/18 vaccine or Al(OH)3 (control) at M0, 1, 6. VE against HPV-16/18-associated CIN2+, and cross-protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according-to-protocol efficacy cohort, in initially seronegative/DNA-negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV-16/18-associated CIN2+ was 87.3% (5.3-99.7); VE against incident infection or against 6-month persistent infection associated with HPV-31/33/45 was 50.1% (34.3-62.3) or 52.6% (24.5-70.9), respectively. At least, 99.6% of HPV-16/18-vaccines remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and -18 geometric mean titers were 1271.1 EU/mL (1135.8-1422.6) and 710.0 EU/ml (628.6-801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination-related (blinded data). VE against HPV-16/18-associated CIN2+ was demonstrated and evidence of cross-protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.


Assuntos
Anticorpos Antivirais/sangue , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Vacinas contra Papillomavirus/administração & dosagem , China , Método Duplo-Cego , Feminino , Humanos , Vacinas contra Papillomavirus/imunologia , Resultado do Tratamento , Adulto Jovem
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