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1.
Avian Pathol ; 49(1): 29-35, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31429308

RESUMO

To determine whether geese are susceptible to infection by avian leukosis virus (ALV), 702 serum samples from domestic and foreign goose breeds were screened for p27 antigen as well as being inoculated into DF-1 cell cultures to isolate ALV. Although 5.7% of samples were positive for p27 antigen, reactivity appeared to be non-specific because no ALV was detected in the corresponding DF-1 cultures. To further determine whether geese are susceptible to ALV-J isolated from chickens, ALV-J strain JS09GY7 was artificially inoculated into 10-day-old goose embryos, with one-day-old hatched goslings then screened for p27 antigen and the presence of ALV. In all cases, the results of both tests were negative. Liver tissues from the 1-day-old goslings were screened using a polymerase chain reaction-based assay, which failed to amplify ALV-J gene fragments from any of the samples. Further, no histopathological damage was observed in the liver tissues. ALV-J was further inoculated intraperitoneally into one-day-old goslings, with cloacal swabs samples and plasma samples then collected every 5 days for 30 days. All samples were again negative for the presence of p27 antigen and ALV, and liver tissues from the challenged geese showed no histopathological damage and were negative for the presence of ALV-J gene fragments. Furthermore, p27 antigen detection, PCR-based screening, and indirect immunofluorescence assays were all negative following the infection of goose embryo fibroblasts with ALV-J. Together, these results confirm that virulent chicken-derived ALV-J strains cannot infect geese, and that p27 antigen detection in goose serum is susceptible to non-specific interference.


Assuntos
Vírus da Leucose Aviária/patogenicidade , Leucose Aviária/virologia , Galinhas , Gansos , Animais , Leucose Aviária/imunologia , Vírus da Leucose Aviária/genética , Vírus da Leucose Aviária/imunologia , Vírus da Leucose Aviária/isolamento & purificação , Galinhas/virologia , Cloaca/virologia , DNA Viral/química , DNA Viral/isolamento & purificação , Fibroblastos/virologia , Imunofluorescência/veterinária , Gansos/embriologia , Gansos/virologia , Fígado/patologia , Fígado/virologia , Antígeno Nuclear de Célula em Proliferação/sangue , Antígeno Nuclear de Célula em Proliferação/isolamento & purificação , Virulência
2.
Comp Immunol Microbiol Infect Dis ; 67: 101348, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31527012

RESUMO

Feline leukemia virus (FeLV) is an oncogenic retrovirus of cats. While higher viral RNA and proviral DNA loads have been correlated with progressive infections and disease, a similar correlation has been suggested for p27 antigen concentrations. This analytical study compared the results of a quantitative ELISA for p27 antigen with quantitative real-time PCR results for FeLV proviral DNA in patient samples. A significant positive correlation between copies of proviral DNA and the concentration of p27 antigen was identified (r = 0.761, P < 0.0001). Samples with high proviral DNA loads, at least 1 × 106 copies/mL of whole blood, typically had p27 antigen concentrations greater than 30 ng/mL in plasma. Samples with proviral DNA loads below this level all had concentrations of p27 antigen in plasma that were less than 10 ng/mL. Given this correlation, it is hypothesized that the concentration of p27 antigen at a given point in time may help to indicate the likelihood of a progressive or regressive infection similar to what has been demonstrated for proviral DNA loads.


Assuntos
DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Vírus da Leucemia Felina/genética , Vírus da Leucemia Felina/imunologia , Antígeno Nuclear de Célula em Proliferação/sangue , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Gatos , DNA Viral/genética , Antígeno Nuclear de Célula em Proliferação/imunologia , Provírus/genética , Infecções por Retroviridae/diagnóstico , Infecções por Retroviridae/veterinária , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/virologia , Carga Viral/métodos
3.
Neurosci Lett ; 672: 53-58, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29474873

RESUMO

Age-related changes are increased in patients with Alzheimer's disease (AD), including oxidative stress and DNA damage. We propose that genotoxic stress and DNA repair responses influence neurodegeneration in the pathogenesis of AD. Here, we focus on nucleotide excision repair (NER). Real-time qPCR and mass spectrometry were employed to determine the expression levels of selected NER components. The mRNA levels of the genes encoding the NER proteins RAD23B, RPA1, ERCC1, PCNA and LIG3 as well as the NER-interacting base excision repair protein MPG in blood and brain tissue from four brain regions in patients with AD or mild cognitive impairment and healthy controls (HC), were assessed. NER mRNA levels were significantly higher in brain tissue than in blood. Further, LIG3 mRNA levels in the frontal cortex was higher in AD versus HC, while mRNA levels of MPG and LIG3 in entorhinal cortex and RPA1 in the cerebellum were lower in AD versus HC. In blood, RPA1 and ERCC1 mRNA levels were lower in AD patients than in HC. Alterations in gene expression of NER components between brain regions were associated with AD, connecting DNA repair to AD pathogenesis and suggesting a distinct role for NER in the brain.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , DNA Ligase Dependente de ATP/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína de Replicação A/metabolismo , Doença de Alzheimer/sangue , DNA Ligase Dependente de ATP/sangue , Enzimas Reparadoras do DNA/sangue , Proteínas de Ligação a DNA/sangue , Endonucleases/sangue , Feminino , Humanos , Masculino , Estresse Oxidativo/fisiologia , Proteínas de Ligação a Poli-ADP-Ribose/sangue , Antígeno Nuclear de Célula em Proliferação/sangue , Proteína de Replicação A/sangue
4.
Integr Cancer Ther ; 17(1): 115-123, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28102098

RESUMO

BACKGROUND: Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. RESULTS: After 12 weeks, patients on JP had significantly higher serum α-carotene ( P = .009), ß-carotene ( P < .0001), and lutein ( P = .003) but did not differ significantly in p27 ( P = .23) or Ki-67 ( P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. CONCLUSIONS: Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.


Assuntos
Sucos de Frutas e Vegetais , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/terapia , Micronutrientes/sangue , Extratos Vegetais/administração & dosagem , Antioxidantes/administração & dosagem , Biomarcadores Tumorais/sangue , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Antígeno Ki-67/sangue , Micronutrientes/administração & dosagem , Fitoterapia , Pós , Antígeno Nuclear de Célula em Proliferação/sangue
5.
Zhongguo Zhong Yao Za Zhi ; 42(16): 3191-3197, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29171240

RESUMO

To explore the effect of leech on proliferation and apoptosis of vascular smooth muscle cells(VSMCs) in early atherosclerosis rats via p38MAPK signaling pathway and investigate its possible mechanism. Biochemical analyzer was used to examine the regulation of leech on levels of triglycerides(TG), total cholesterol(TC), low-density lipoprotein(LDL-C), and high-density lipoprotein(HDL-C) in blood lipid of rats. The expression of transforming growth factor-beta 1(TGF-ß1) in serum was detected by ELISA. Immunological histological chemistry (IHC) was taken to measure the expression levels of proliferating cell nucleus antigen(PCNA) and cell apoptosis proteinase-3(Caspase-3), while the protein expression levels of MKK3, p38 and C-myc were detected by Western blot. In addition, hematoxylin and eosin(HE) staining was used to observe the morphological change of thoracic aortas. The results showed that leech decreased the levels of TC, LDL-C obviously and increased HDL-C, suppressed the expression levels of TGF-ß1 and PCNA, up-regulated Caspase-3, down-regulated the expression levels of MKK3, p38, and C-myc protein. HE staining indicated that it could inhibit intimal thickening and reduce plaque formation. The above results indicated that leech may affect the protein expression of the p38MAPK signaling pathway to inhibit proliferation and promote the apoptosis of VSMCs via reducing blood lipid levels and suppressing TGF-ß1, aiming at inhibiting intimal thickening and reducing plaque formation, tand then slowing down the process of early atherosclerosis.


Assuntos
Aterosclerose/terapia , Sanguessugas , Sistema de Sinalização das MAP Quinases , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Apoptose , Caspase 3/sangue , Proliferação de Células , Lipídeos/sangue , MAP Quinase Quinase 3/metabolismo , Antígeno Nuclear de Célula em Proliferação/sangue , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Fator de Crescimento Transformador beta1/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Acta Histochem ; 119(4): 372-381, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28385400

RESUMO

Current study was done to assess possible anti-proliferative effect of nanomicelle curcumin (NMCM) against germ cells in testicular tissue. For this purpose, 24 mature male Wistar rats were divided into control and test groups. The animals in test groups received 7.5mg/kg, 15mg/kg and 30mg/kg of NMC (NO=6 rats in each group). Following 48days, the expression of Bcl-2, Bax, caspase-3, P53 and proliferating cell nuclear antigen (PCNA) were evaluated by using reverse transcription-PCR and immunohistochemistry. Histological changes, tubular differentiation index (TDI), tissue cellularity and serum level of testosterone were analyzed. Finally, the DNA laddering test was used to assess the DNA fragmentation as hallmark for apoptosis. The NMCM significantly (P<0.05) diminished the Bcl-2, p53 and PCNA and enhanced the Bax and caspase-3 mRNA levels. The NMCM significantly (P<0.05) elevated the percentage of Bax and caspase-3-positive tubules and remarkably reduced the percentage of tubules with positive reaction for Bcl-2, p53 and PCNA. The NCMN-received animals exhibited remarkable (P<0.05) reduction in cell population, TDI ratio and serum level of testosterone. Severe DNA fragmentation was observed in 30mg/kg NMCM-received group. In conclusion, the NMCM by reducing the testicular endocrine status, down-regulating Bcl-2 expression and by enhancing the Bax and caspase-3 expression initiates the intrinsic apoptosis pathway. On the other hand, inhibited expression of p53 and PCNA (at dose level of 30mg/kg) suppresses the p53 and PCNA-related hemostasis/preservative reactions. All these alterations adversely affect the spermatogenesis.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/toxicidade , Fragmentação do DNA/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Imuno-Histoquímica , Masculino , Micelas , Antígeno Nuclear de Célula em Proliferação/sangue , Ratos , Ratos Wistar , Testículo/ultraestrutura
7.
Zhonghua Gan Zang Bing Za Zhi ; 24(10): 761-766, 2016 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-27938562

RESUMO

Objective: To investigate the protective effect of augmenter of liver regeneration (ALR) against acute liver injury and related mechanisms. Methods: HL-7702 cells were divided into normal control group, carbon tetrachloride (CCl4)-induced acute liver injury group, ALR+CCl4 intervention group, 3-methyladenine (3-MA)+CCl4 intervention group, and ALR+3-MA+CCl4 intervention group. The ALR+CCl4 and ALR+3-MA+CCl4 intervention groups were transfected with ALR plasmids at 8 hours before CCl4 treatment. All groups except the normal control group were treated with CCl4, and 30 minutes later, the 3-MA+CCl4 and ALR+3-MA+CCl4 intervention groups were treated with 3-MA. The cells were collected at 24 hours after CCl4 treatment. The HL-7702 cells and supernatant were collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (IU/L). Western blot was used to measure the levels of ALR, cyclin D, cyclin E, proliferating cell nuclear antigen (PCNA), autophagy-related gene 7 (Atg7), and autophagy genes LC3, p62, and Beclin-1. Quantitative real-time PCR was used to measure the mRNA expression of ALR. A one-way analysis of variance was used for comparison of means between any two groups. Results: The ALR+CCl4 intervention group had significant increases in the protein and mRNA expression of ALR compared with the acute liver injury group (both P < 0.05). The CCl4-induced acute liver injury group had significant increases in the protein and mRNA expression of ALR compared with the normal control group (both P < 0.05). Compared with the CCl4-induced acute liver injury group, the ALR+CCl4 intervention group had significant reductions in ALT (0.73±0.17 IU/L vs 1.43±0.38 IU/L, P < 0.05) and AST (19.85±1.83 IU/L vs 56.73±6.25 IU/L, P < 0.05) in supernatant, significantly increased expression of cyclin D, cyclin E, PCNA, LC3, Atg7, and Beclin-1 in hepatocytes, and significantly reduced expression of p62, which suggested that ALR protected the liver against acute liver injury, promoted the regeneration of hepatocytes, and enhanced the autophagy of hepatocytes. The ALR+3-MA+CCl4 intervention group had a significant reduction in the expression of regeneration-associated proteins compared with the ALR+CCl4 intervention group, while there was no significant difference between the ALR+3-MA+CCl4 intervention group and 3-MA+CCl4 intervention group, which suggested that after the inhibition of autophagy, there were significant reductions in the regeneration of hepatocytes and liver regeneration promoted by ALR. Conclusion: ALR can promote the regeneration of hepatocytes in liver parenchyma, which is achieved by the regulation of autophagy.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/patologia , Regeneração Hepática , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Adenina/análogos & derivados , Alanina Transaminase , Aspartato Aminotransferases , Autofagia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatócitos , Humanos , Fígado , Falência Hepática Aguda/metabolismo , Antígeno Nuclear de Célula em Proliferação/sangue , Reação em Cadeia da Polimerase em Tempo Real
8.
J Med Food ; 19(8): 746-54, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27441629

RESUMO

Even though rice hull has various physiological functions with high antioxidant potential, the molecular mechanism(s) underlying the effects of rice hull on benign prostatic hyperplasia (BPH) have not been evaluated. The aim of this study was to determine the protective effect of rice hull water extract (RHE) against BPH, which is a common disorder in elderly men and involves inflammation that induces an imbalance between cell proliferation and cell death. In this study, RHE-treated mice exhibited lower prostate weights and ratios of prostate weight to body weight compared to those for the BPH-induced group. In addition, RHE-treated mice had lower serum levels of dihydrotestosterone, mRNA expression of 5α-reductase2, and protein expressions of proliferating cell nuclear antigen (PCNA). Furthermore, RHE treatment significantly decreased cell proliferation by regulating the expression levels of inflammatory-related proteins (iNOS and COX-2) and apoptosis-associated proteins (Fas, FADD, procaspase-8, -3, and Bcl-2 family proteins). These results suggest that RHE could protect against the development of BPH through its anti-inflammatory and apoptotic properties and has good potential as a treatment for BPH.


Assuntos
Proliferação de Células/efeitos dos fármacos , Inflamação/sangue , Oryza , Fitoterapia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/patologia , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Di-Hidrotestosterona/sangue , Hiperplasia , Inflamação/tratamento farmacológico , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/sangue , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Ratos Sprague-Dawley , Sementes
9.
Exp Biol Med (Maywood) ; 240(12): 1656-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26085572

RESUMO

Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH.


Assuntos
Apoptose/efeitos dos fármacos , Venenos de Abelha/uso terapêutico , Inflamação/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Animais , Western Blotting , Di-Hidrotestosterona/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/sangue , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Testosterona/farmacologia
10.
Rev Med Chir Soc Med Nat Iasi ; 118(2): 399-406, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25076707

RESUMO

OBJECTIVES: To evaluate the rate of morbidity and mortality associated with colorectal polyps after the next 8-years period of endoscopic polypectomy, in a high risk managed care population. MATERIAL AND METHOD: Cohorts of 77 subjects with benign neoplasms were identified with a colonoscopy in 1999. Three groups of subjects: benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms were evaluated. Five years recurrence rates (1999-2004) of benign or new malignant colorectal neoplasms were identified: for the benign determined for the baseline benign neoplasms with polypectomy and no neoplasm groups neoplasm without polypectomy, only rates for malignancy were observed. Malignancy was evaluated with immunohistochemical p53 (tumor protein 53) and PCNA (Proliferating Cell Nuclear Antigen) staining pattern. Over the next 8 years 2004-2012 were evaluated the mortality and the recurrence rate of the benign polyps. RESULTS: 77 subjects were enrolled in our study; 71.4% were diagnosed with benign and 2.5% with malignant neoplasms. The 5-years cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 20) and benign neoplasm groups (n = 55) were (n = 1) 5% and ( n = 10) 18.1%, respectively (p < 0.005). A lower 5-years malignancy rate was observed in benign neoplasms group with polypectomy (12%) compared to the benign neoplasm group without polypectomy (33.3%) (p < 0.05). The 8-years mortality rate was compared into benign recurrent polyps group and into malign group: the lower 8-years mortality rate was observed into benign polyp no neoplasm group (0%) and into benign recurrent polyps group (40%); the highest rate was observed into neoplasm group (100%). CONCLUSIONS: The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk-history of benign colorectal neoplasm-highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.


Assuntos
Biomarcadores Tumorais/sangue , Pólipos do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Antígeno Nuclear de Célula em Proliferação/sangue , Proteína Supressora de Tumor p53/sangue , Estudos de Coortes , Colectomia , Pólipos do Colo/sangue , Pólipos do Colo/mortalidade , Pólipos do Colo/cirurgia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Romênia/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento
11.
Asian Pac J Cancer Prev ; 15(10): 4129-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24935358

RESUMO

BACKGROUND: The objective was to study the effect of Scutellaria baicalensis Georgi ethanol extracts (SBGE) on immune and anti-oxidant function in U14 tumor-bearing mice. MATERIALS AND METHODS: U14 tumor-bearing mice were randomly divided into eight groups: a control group, a cyclophosphamide (CTX) group, three dose groups of SBGEI (high, medium, low), and three dose groups of SBGEII (high, medium, low). After two weeks, the thymus and spleen weight indices of mice bearing U14 cervical cancer were calculated. Enzyme linked immunosorbent assays (ELISA) was used to determine the levels of serum IL-2, TNF-α, IL-8, and PCNA. MDA activity and SOD activity in plasma were measured with detection kits. RESULTS: In the SBGE groups, thymus weight and spleen weight indices of U14 tumor-bearing mice were significantly higher than in the control group or CTX group (p<0.05). Compared to control group, the levels of serum IL-2 and TNF-α in U14 tumor-bearing mice increased significantly, whereas the contents of serum IL-8 and PCNA decreased (p<0.05). The activity of SOD increased with the growing dose of SBGE, while the activity of MDA decreased significantly in the higher- dose groups of SBGE. CONCLUSIONS: These findings suggested that SBGE, especially at high dose, 1000 mg/kg, showed significant immune and anti-oxidant effects in U14 tumor-bearing mice, which might be the mechanisms of SBGE inhibition of tumor growth.


Assuntos
Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Scutellaria baicalensis/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Interleucina-2/sangue , Interleucina-8/sangue , Medicina Tradicional Chinesa , Camundongos , Fitoterapia , Antígeno Nuclear de Célula em Proliferação/sangue , Baço/fisiologia , Superóxido Dismutase/sangue , Timo/fisiologia , Fator de Necrose Tumoral alfa/sangue , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia
12.
J Toxicol Sci ; 39(2): 339-51, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24646716

RESUMO

Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 µg/100 µl, 200 µg/100 µl or 300 µg/100 µl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl4. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy.


Assuntos
Proteínas ADAM/imunologia , Proteínas ADAM/fisiologia , Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Antígenos CD/fisiologia , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Proteínas de Membrana/imunologia , Proteínas de Membrana/fisiologia , Alanina Transaminase/sangue , Animais , Anticorpos Monoclonais/administração & dosagem , Biomarcadores/sangue , Tetracloreto de Carbono/administração & dosagem , Proliferação de Células , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP1A2/sangue , Hepatócitos/citologia , Humanos , Injeções Intraperitoneais , Fígado/irrigação sanguínea , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/genética , Antígeno Nuclear de Célula em Proliferação/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
13.
Toxicol Lett ; 220(3): 205-18, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23665045

RESUMO

Hepatocellular carcinoma (HCC) is a global health problem and is fourth leading cause of cancer related deaths. Now-a-days new strategies have been accounted for the chemoprevention of liver cancer due to ineffective traditional treatments against HCC. In the present study, we have shown that diosmin attenuates 2-AAF induced hepatic toxicity and early tumor promotion markers (ODC, PCNA and Ki67), its chemopreventive efficacy against DEN initiated and 2-AAF promoted hyper-proliferation and hepatocarcinogenesis in Wistar rats. Hepatocarcinogenesis has been characterized by the presence of apparent hepatic nodules, hepatic proliferation, elevation in the levels of proliferation markers (PCNA and Ki67), and inflammatory markers (COX-2 and iNOS) in DEN and 2-AAF administered rats. Protective efficacy of diosmin has been investigated in terms of its potential in reducing the percentage of visible hepatic nodules and the restoration of early tumor markers (PCNA, Ki67 and ODC), oxidative stress biomarkers, serum cytotoxicity markers (AST, ALT and LDH), cell necrosis markers (NF-kappa B and TNF-α) and inflammatory markers (COX-2 and iNos). Our study demonstrates that the inhibition of cell proliferation and down regulation of inflammatory markers may be, at least in part, the underlying mechanisms related to the liver tumor inhibition by diosmin. The present study allows us to conclude that diosmin being a dietary supplement, could be used as chemopreventive agent to prevent hepatocarcinogenesis.


Assuntos
Diosmina/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , 2-Acetilaminofluoreno/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/metabolismo , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Antígeno Ki-67/sangue , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , NF-kappa B/sangue , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Ornitina Descarboxilase/sangue , Ornitina Descarboxilase/metabolismo , Antígeno Nuclear de Célula em Proliferação/sangue , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
14.
Proc Natl Acad Sci U S A ; 110(7): 2617-22, 2013 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-23359692

RESUMO

Gastrin releasing-peptide (GRP) is a potent growth factor in many malignancies. Benign prostatic hyperplasia (BPH) is a progressive age-related proliferation of glandular and stromal tissues; various growth factors and inflammatory processes are involved in its pathogenesis. We have demonstrated that potent antagonists of GRP inhibit growth of experimental human tumors including prostate cancer, but their effect on models of BPH has not been studied. Here, we evaluated the effects of GRP antagonist RC-3940-II on viability and cell volume of BPH-1 human prostate epithelial cells and WPMY-1 prostate stromal cells in vitro, and in testosterone-induced BPH in Wistar rats in vivo. RC-3940-II inhibited the proliferation of BPH-1 and WPMY-1 cells in a dose-dependent manner and reduced prostatic cell volume in vitro. Shrinkage of prostates was observed after 6 wk of treatment with RC-3940-II: a 15.9% decline with 25 µg/d; and a 18.4% reduction with 50 µg/d (P < 0.05 for all). Significant reduction in levels of proliferating cell nuclear antigen, NF-κß/p50, cyclooxygenase-2, and androgen receptor was also seen. Analysis of transcript levels of genes related to growth, inflammatory processes, and signal transduction showed significant changes in the expression of more than 90 genes (P < 0.05). In conclusion, GRP antagonists reduce volume of human prostatic cells and lower prostate weight in experimental BPH through direct inhibitory effects on prostatic GRP receptors. GRP antagonists should be considered for further development as therapy for BPH.


Assuntos
Bombesina/análogos & derivados , Tamanho Celular/efeitos dos fármacos , Peptídeo Liberador de Gastrina/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Próstata/citologia , Hiperplasia Prostática/tratamento farmacológico , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Bombesina/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/sangue , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Humanos , Masculino , NF-kappa B/sangue , Antígeno Nuclear de Célula em Proliferação/sangue , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptores Androgênicos/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testosterona/toxicidade , Sais de Tetrazólio , Tiazóis
15.
Toxicol Lett ; 216(2-3): 146-58, 2013 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-23194824

RESUMO

Flavonoid family is a rich source of polyphenolic compounds and hence possess strong antioxidant and anti inflammatory properties. The aim of this study was to determine the efficacy of chrysin; a bio-active flavonoid as an anticancer agent. Renal cancer was initiated by single intraperitoneal (i.p.) injection of N-nitrosodiethylamine (DEN 200 mg/kg BW body weight) and promoted by twice weekly administration of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg BW for 16 wk. In the present study, we report the chemopreventive effects of chrysin against (Fe-NTA) induced renal oxidative stress, inflammation, hyperproliferative response, and two-stage renal carcinogenesis. To ascertain the molecular mechanism implicated in the antitumor promoting activity of chrysin, its effect was investigated on markers of tumor promotion and inflammation: ornithine decarboxylase (ODC) activity, proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression, and on levels of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E(2) (PGE(2)). Pretreatment of animals with chrysin at both doses (20 and 40 mg/kg body weight) markedly inhibited all. Further, Fe-NTA enhances renal lipid peroxidation, with concomitant reduction in reduced glutathione content (GSH), antioxidant enzymes, and phase II metabolizing enzymes. It induces serum toxicity markers, viz., blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH). Prophylactic treatment of animals with chrysin before the administration of Fe-NTA was effective in modulating oxidative and renal injury markers and resulted in the diminution of Fe-NTA mediated injury. These results suggest chrysin as an effective chemopreventive agent having the capability to obstruct DEN initiated and Fe-NTA promoted renal cancer in the rat model.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Flavonoides/farmacologia , Neoplasias Renais/tratamento farmacológico , NF-kappa B/sangue , Estresse Oxidativo/efeitos dos fármacos , Animais , Carcinógenos , Carcinoma de Células Renais/induzido quimicamente , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/sangue , Citocinas/sangue , Dietilnitrosamina , Compostos Férricos , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Óxido Nítrico Sintase Tipo II/sangue , Ácido Nitrilotriacético/análogos & derivados , Ornitina Descarboxilase/sangue , Projetos Piloto , Antígeno Nuclear de Célula em Proliferação/sangue , Distribuição Aleatória , Ratos , Ratos Wistar
16.
Autoimmunity ; 45(7): 540-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22849293

RESUMO

The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.


Assuntos
Antioxidantes/metabolismo , Catequina/análogos & derivados , Reparo do DNA , Glândulas Exócrinas/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Animais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Catequina/metabolismo , Modelos Animais de Doenças , Feminino , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos NOD , Peroxirredoxina VI/metabolismo , Antígeno Nuclear de Célula em Proliferação/sangue , Antígeno Nuclear de Célula em Proliferação/imunologia , Síndrome de Sjogren/patologia , Fatores de Tempo
17.
BMC Vet Res ; 8: 125, 2012 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-22839692

RESUMO

BACKGROUND: Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. RESULTS: In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. CONCLUSION: In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.


Assuntos
Envelhecimento/imunologia , Vírus da Leucemia Felina/imunologia , Leucemia Felina/prevenção & controle , Vacinas Virais/imunologia , Animais , Antígenos Virais , Gatos , Antígeno Nuclear de Célula em Proliferação/sangue , Vacinas de Produtos Inativados/imunologia
18.
J Feline Med Surg ; 14(6): 392-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22403413

RESUMO

Most studies that investigate the prevalence of infections with feline leukemia virus (FeLV) are based on the detection of p27 antigen in blood, but they do not detect proviral DNA to identify the prevalence of regressive FeLV infections. The aim of the present study was to assess the prevalence and status of FeLV infection in cats in Southern Germany. P27 antigen enzyme-linked immunosorbent assay (ELISA), anti-p45 antibody ELISA, DNA polymerase chain reaction (PCR) of blood and RNA PCR of saliva were performed. Nine out of 495 cats were progressively (persistently) infected (1.8%) and six were regressively (latently) infected (1.2%). Cats with regressive infections are defined as cats that have been able to overcome antigenemia but provirus can be detected by PCR. Twenty-two unvaccinated cats likely had abortive infections (regressor cats), testing FeLV antigen- and provirus-negative but anti-p45 antibody-positive. Most of the FeLV-vaccinated cats did not have anti-FeLV antibodies. Both progressive, as well as regressive infections seem to be rare in Germany today.


Assuntos
Doenças do Gato/virologia , Vírus da Leucemia Felina/isolamento & purificação , Infecções por Retroviridae/veterinária , Infecções Tumorais por Vírus/veterinária , Animais , Anticorpos Antivirais/sangue , Doenças do Gato/epidemiologia , Gatos , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Alemanha/epidemiologia , Vírus da Leucemia Felina/imunologia , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Prevalência , Antígeno Nuclear de Célula em Proliferação/sangue , Infecções por Retroviridae/epidemiologia , Infecções por Retroviridae/virologia , Saliva/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia
19.
Cancer Immunol Immunother ; 61(10): 1639-51, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22350072

RESUMO

Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.


Assuntos
Antígenos de Neoplasias/imunologia , Células da Medula Óssea/imunologia , Chaperonina 60/imunologia , Proteínas Mitocondriais/imunologia , Mieloma Múltiplo/imunologia , Transplante de Células-Tronco , Antígenos de Neoplasias/sangue , Chaperonina 60/sangue , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Proteínas Mitocondriais/sangue , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/imunologia , Fosfopiruvato Hidratase/sangue , Fosfopiruvato Hidratase/imunologia , Antígeno Nuclear de Célula em Proliferação/sangue , Antígeno Nuclear de Célula em Proliferação/imunologia , Regulação para Cima , Vimentina/sangue , Vimentina/imunologia , alfa-Glucosidases/sangue , alfa-Glucosidases/imunologia
20.
Hepatogastroenterology ; 59(118): 1933-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22246190

RESUMO

BACKGROUND/AIMS: To search for a new regenerative marker to estimate the prognosis of acute-on-chronic liver failure (ACLF). METHODOLOGY: The CCl4 induced liver regeneration models were prepared and observed the change of ALR, hepatocyte growth factor (HGF), proliferation cell nuclear antigen (PCNA) and pathology. Meanwhile the sera of patients with HBV related liver disease were collected to examine the changes of ALR level and the prognosis of patients with ACLF was followed up. RESULTS: After CCl4 injection, serum ALR level rose firstly and then declined in the ensuing 12 hours to near-basal level (F=30.495, p<0.01). ALR level in the liver tissue showed an inverse pattern. The changes of PCNA, HGF and pathology showed a consistent trend with serum ALR level. Serum ALR level was higher in ACLF (n=20) and hepatocellular carcinoma (n=20) than in normal control (n=10) (2.68±1.95 vs. 0.74±0.31, p<0.01; 1.77±1.32 vs. 0.74±0.31, p=0.035). Serum ALR level of patients with ACLF was more significant in survival group (n=10) than in dead group (n=10) in early stage of disease (7.83±1.77 vs. 2.14±1.58, t=7.576, p<0.01). CONCLUSIONS: ALR level in serum may indicate hepatocyte proliferation or liver regeneration. High ALR level in serum in early stage of ACLF may mean a good prognosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Terminal/sangue , Hepatite B/complicações , Falência Hepática Aguda/sangue , Regeneração Hepática , Fígado/metabolismo , Proteínas/metabolismo , Análise de Variância , Animais , Biomarcadores/sangue , Tetracloreto de Carbono , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , China , Modelos Animais de Doenças , Doença Hepática Terminal/patologia , Doença Hepática Terminal/virologia , Fator de Crescimento de Hepatócito/sangue , Humanos , Fígado/patologia , Fígado/virologia , Falência Hepática Aguda/patologia , Falência Hepática Aguda/virologia , Masculino , Prognóstico , Antígeno Nuclear de Célula em Proliferação/sangue , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Regulação para Cima
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