RESUMO
Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are members of the transforming growth factor-ß (TGF-ß) family, and their roles in oocyte maturation and cumulus expansion are well known in the mouse and human, but not in the pig. We investigated GDF9 and BMP15 expressions in porcine oocytes during in vitro maturation. A significant increase in the mRNA levels of GDF9 and BMP15 was observed at germinal vesicle breakdown, with expression levels peaking at metaphase I (MI), but decreasing at metaphase II (MII). GDF9 and BMP15 protein localized to the oocyte cytoplasm. While treatment with GDF9 and BMP15 increased the expression of genes involved in both oocyte maturation (c-mos, cyclinb1 and cdc2) and cumulus expansion (has2, ptgs2, ptx3 and tnfaip6), SB431542 (a TGFß-GDF9 inhibitor) decreased meiotic maturation at MII. Following parthenogenetic activation, the percentage of blastocysts in SB431542 treatment was lower than in the control (41.3% and 74.4%, respectively). Treatment with GDF9 and BMP15 also increased the mRNA levels of maternal genes such as c-mos [a regulatory subunit of mitogen-activated protein kinase (MAPK)], and cyclinb1 and cdc2 [regulatory subunits of maturation/M-phase-promoting factor (MPF)]; however, SB431542 significantly decreased their mRNA levels. These data were supported by poly (A)-test PCR and protein activity analyses. Our results show that GDF9 and BMP15 participate in cumulus expansion and that they stimulate MPF and MAPK activities in porcine oocytes during in vitro maturation.
Assuntos
Proteína Morfogenética Óssea 15/metabolismo , Fator 9 de Diferenciação de Crescimento/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/efeitos dos fármacos , Suínos/fisiologia , Animais , Proteína Morfogenética Óssea 15/genética , Células do Cúmulo/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Fator 9 de Diferenciação de Crescimento/genética , Técnicas de Maturação in Vitro de Oócitos/métodos , Sistema de Sinalização das MAP Quinases/fisiologia , Mesotelina , Oócitos/citologia , Oócitos/fisiologiaRESUMO
OBJECTIVE: The aim of this study was to analyze the effects of nursing intervention based on a positive motivational model on cardiac function, self-management, and life quality in elderly patients with coronary heart disease (CHD). PATIENTS AND METHODS: A total of 112 elderly CHD patients were picked as the subjects of this research from August 2021 to August 2022. All patients were randomized to the observation group and regular group by a two-color sampling method, with 56 cases in each group. Subjects in the regular group and observation group received traditional interventions and additional positive motivational model nursing interventions, respectively. The cardiac function [left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD)], sports endurance, self-management ability, psychological status [depression self-assessment scale (SDS), anxiety self-assessment scale (SAS)], and life quality before and after the intervention were compared between two groups. The readiness for discharge scores and satisfaction with nursing care were compared between the two groups after the intervention. RESULTS: After the intervention, the LVEF levels of the patients in both groups were elevated, and the LVESD and LVEDD levels were sharply decreased (p < 0.05). The improvement in cardiac function indexes was more evident in the observation group than in the regular group (p < 0.001). The readiness for discharge score of patients was markedly higher in the observation group than in the regular group (p < 0.01). After the intervention, the self-management score and sports endurance score of patients in both groups were evidently elevated (p < 0.05), which were much higher in the observation group than in the control (p < 0.001). The nursing satisfaction of patients in the observation group was 92.86%, much higher than 73.21% in the regular group (p < 0.05). The observation group had much lower SDS and SAS scores than the regular group after the intervention (p < 0.001). After the intervention, the observation group had a much higher life quality score than the regular group (p < 0.001). CONCLUSIONS: The nursing intervention model based on the positive motivation model could significantly improve the cardiac function, discharge readiness, sports endurance, and self-management behavior of elderly patients with CHD, thereby improving their quality of life and achieving higher patient satisfaction.
Assuntos
Doença das Coronárias , Autogestão , Idoso , Humanos , Motivação , Qualidade de Vida , Volume Sistólico , Função Ventricular Esquerda , Doença das Coronárias/terapiaRESUMO
Recent attention in pig breeding programs has focused on the improvement of pork quality in response to increasing consumer demands. Compared to the fatty-type Northeastern Indigenous (Chinese) breed of pigs, the lean-type Large White has lower intramuscular fat and inferior eating quality from the perspective of the Chinese consumer. In order to investigate the molecular basis of differences in pork quality in Chinese indigenous and Western breeds, longissimus dorsi samples were collected from three adult Northeastern Indigenous and three adult Large White pigs. The RNAs were extracted and hybridized to the porcine Affymetrix GeneChip. Microarray analysis demonstrated differential expression of 1134 genes of which 401 have a known function. One hundred and thirty-six genes were up-regulated and 998 down-regulated in Northeastern Indigenous breed compared to Large White pigs. We screened 10 genes as candidate genes associated with pork quality. We investigated a single nucleotide polymorphism in the 5' regulatory region of the gene FABP4 in 65 Songliao black swine, using PCR-single-strand conformational polymorphism. We found this polymorphism to be highly significantly associated with marbling and intra-muscular fat content (P ≤ 0.01). Genotype BB had higher marbling than AB and AA, but there was no significant difference between AB and AA. Genotype BB and AB had higher intra-muscular fat content than AA, but there was no significant difference between BB and AB. These results help to elucidate the genetic mechanisms behind differences in pork quality and provide a theoretical basis for selection and genetic improvement of meat quality traits in pigs.
Assuntos
Produtos da Carne/análise , Suínos/genética , Animais , Distribuição da Gordura Corporal , Proteínas de Ligação a Ácido Graxo/genética , Preferências Alimentares , Frequência do Gene , Análise em Microsséries , Músculo Esquelético , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
It is now becoming possible to control and tailor micro/nanoscale chemical structures with different geometrical patterns on various substrates to achieve so-called superhydrophobic surfaces, which show promising industrial applications. In spite of significant advances in preparation of such surfaces, to date the effects of surface patterns or geometries on superhydrophobicity have not been understood completely, in particular, in the theoretical aspect. It has therefore been a challenge to design optimal geometry for ideal superhydrophobic behavior. In this study, a trapezoid microtextured superhydrophobic surface has been thermodynamically analyzed using a 2-D model. Furthermore, based on the calculations of free energy (FE) and free energy barrier (FEB), the effects of all the geometrical parameters for the trapezoid microtexture on contact angle (CA) and contact angle hysteresis (CAH) have been investigated systematically. It is demonstrated that besides height, base angle plays a significant important role in equilibrium contact angle (ECA) and CAH; in particular, a critical base angle for the present geometrical system is necessary for the transition from noncomposite to composite states. Moreover, the trapezoid base width affects strongly various CAs; a small base width is necessary for the large ECA and the small CAH. However, the effects of trapezoid base spacing are considerably complex. For the above transition, a small base spacing is necessary, but decreasing base spacing can decrease the ECA only for the composite state and can increase CAH only for the noncomposite state. Based on the above findings, some fundamental principles for the design of optimal geometry of ideal superhydrophobic surfaces are therefore suggested, which are also consistent with the experimental observations and previous theoretical investigations.
Assuntos
Desenho de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície , TermodinâmicaRESUMO
To obtain insights into the cytoplasmic maturation status of cat oocytes recovered from cat ovaries following hormone treatment, we first examined microtubule and microfilament assembly in cat oocytes recovered from hormone-treated ovaries at various stages of maturation. Additionally, we determined the alteration of spindle and microfilament assembly, as well as mitogen-activated protein kinase (MAPK) activity, in cat oocytes at 0, 6, 12 and 18 h of further maturation in vitro. We then looked at pronuclear formation and cleavage of these oocytes following parthenogenetic activation. Similar to other species, microtubules are present in germinal vesicle (GV) stage cat oocytes, and following GV breakdown, microtubules encompassed condensed chromatin particles to form the meiotic metaphase spindle. Microfilaments were located in the cortex and around the GV. A microfilament-rich area, in which the chromatin is located, was observed in the oocytes during meiotic maturation. Maturation rates in aged oocytes (cultured for 18 h) were increased when compared with that in relatively fresh oocytes (<12 h culture), and the number of oocytes with abnormal spindle shapes was also increased in aged oocytes. Furthermore, in aged oocytes, the incidence of the metaphase plate observed outside the thick microfilament domain was higher compared with that of young oocytes, and this seemed to result in an increase in the number of oocytes with two pronuclei and one polar body following activation. Western blot analysis revealed a decrease in MAPK activity in aged cat oocytes. Taken collectively, these results suggest that the optimum time for improved cytoplasmic maturation is <12 h in cat oocytes recovered from hormone-treated ovaries.
Assuntos
Citoesqueleto de Actina/fisiologia , Envelhecimento/fisiologia , Gatos/fisiologia , Microtúbulos/fisiologia , Oócitos/citologia , Oócitos/fisiologia , Animais , Técnicas de Cultura de Células/veterinária , Cromatina/fisiologia , Feminino , Fertilização in vitro , Meiose/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismoRESUMO
The tumor suppressor p53 transcriptionally regulates a large number of target genes that may affect cell growth and cell death pathways. To better understand the role of p53 loss in tumorigenesis, we have developed a mouse mammary cancer model, the Wnt-1 TG/p53 model. Wnt-1 transgenic females that are p53-/- develop mammary adenocarcinomas that arise sooner, grow faster, appear more anaplastic, and have higher levels of chromosomal instability than their Wnt-1 transgenic p53+/+ counterparts. In this study, we used several assays to determine whether the presence or absence of p53 affects gene expression patterns in the mammary adenocarcinomas. Most of the differentially expressed genes are increased in p53+/+ tumors and many of these represent known target genes of p53 (p21WAF/C1P1, cyclin G1, alpha smooth muscle actin, and cytokeratin 19). Some of these genes (cytokeratin 19, alpha smooth muscle actin, and kappa casein) represent mammary gland differentiation markers which may contribute to the inhibited tumor progression and are consistent with the more differentiated histopathology observed in the p53+/+ tumors. Several differentially expressed genes are growth regulatory in function (p21, c-kit, and cyclin B1) and their altered expression levels correlate well with the differing growth properties of the p53+/+ and p53-/- tumors. Thus, while tumors can arise and progress in the presence of functioning wild type p53, p53 may directly or indirectly regulate expression of an array of genes that facilitate differentiation and inhibit proliferation, contributing to a more differentiated, slow growing, and genomically stable phenotype.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Peixe-Zebra , Actinas/genética , Adenocarcinoma/patologia , Animais , Western Blotting , Caseínas/genética , Divisão Celular , Ciclina B/genética , Ciclina B1 , Ciclina G , Ciclina G1 , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/genética , Feminino , Deleção de Genes , Imuno-Histoquímica , Incidência , Queratinas/genética , Neoplasias Mamárias Animais/patologia , Camundongos , Proteínas de Neoplasias/genética , Ensaios de Proteção de Nucleases , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/fisiologia , RNA Neoplásico/análise , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Wnt , Proteína Wnt1RESUMO
The metabolites of 2-nitrofluorene (NF), 5-, 7- and 9-OH-2-nitrofluorene (OH-NF) were compared for their genotoxicity. Seventy-two hours after intraperitoneal administration of these substances individually to rats (100 mg/kg body wt.), DNA adducts in liver tissue were analyzed with 32P-TLC and 32P-HPLC. An in vivo liver model was used to test the initiating capacity of the said substances for the formation of preneoplastic lesions. 5-OH-NF showed low capacity to induce DNA adduct formation and low potential as initiator to induce preneoplastic lesions-foci/nodules in the liver of rats. Both 7- and 9-OH-NF induced DNA adducts and preneoplastic liver lesions but with smaller quantities compared to NF. It seems that 7- and 9-OH-NF can not be considered as detoxification products of NF. In general, the initiating capacity of these substances for the formation of preneoplastic lesions has a good correlation with their potency to form DNA adducts.
Assuntos
Poluentes Atmosféricos/toxicidade , Fluorenos/toxicidade , Animais , Testes de Carcinogenicidade , Adutos de DNA , Fluorenos/metabolismo , Fígado/patologia , Testes de Mutagenicidade , Lesões Pré-Cancerosas , RatosRESUMO
2-Nitrofluorene (NF) is an environmental pollutant. Our previous studies have shown that NF is a carcinogen, primarily targeting the liver, kidney and forestomach in rats. NF-induced DNA adducts were also shown higher levels in the tumor-targeting tissues compared to non-tumor targeting organs. The present study was aimed to observe the kinetics of DNA adduct formation and persistence during the process of NF-induced tumor formation. NF was supplemented in diet at three dose levels and was fed to rats continuously for up to 11 months. DNA adduct formation in the liver, kidney, spleen and stomach of rats after different period (10 days and 11 months) of NF administration was analyzed with 32P-HPLC techniques. DNA adduct persistence in the liver was also assessed after the withdrawal of NF administration. Four major NF-DNA adducts (adducts A, B, C and D) were found in the liver and kidney. DNA adduct D showed high level in the forestomach mucosa after 10 days of NF feeding while adducts A and C were undetectable. DNA adduct C and D co-migrated with C3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG-N2-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), respectively, by 32P-HPLC co-chromatography. DNA adducts A and B constituted the major part (>80%) of NF-DNA adducts after a long period (11 months) of NF feeding. The four NF-DNA adducts showed different recovery from different enrichment procedures, i.e., nuclease P1 or butanol treatment. Three out of the four NF-DNA adducts were still detectable in the rat liver after 11 months on the basal diet. In conclusion, four major DNA adducts are induced by NF oral administration. Among those, one is identified as dG-N2-AAF and another one as dG-C8-AF. The four NF-DNA adducts showed different kinetics of formation and persistence, which may play different roles in NF-induced tumor formation.
Assuntos
Poluentes Atmosféricos/toxicidade , Adutos de DNA/metabolismo , Fluorenos/toxicidade , Mutagênicos/toxicidade , Animais , Carcinógenos/toxicidade , Mucosa Gástrica/metabolismo , Rim/metabolismo , Cinética , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Baço/metabolismo , Fatores de TempoRESUMO
Lactulose is a drug mainly used as a laxative and for the treatment of porto-systemic encephalopathy. Following oral administration, intact lactulose reaches the colon, where it is split by bacteria, leading to a reduction in faecal pH and creating intestinal conditions beneficial to Lactobacillus acidophilus and inhibitory to coliform bacteria, bacteroides, Salmonella and Shigella. It was shown that lactulose therapy clears faecal salmonella and shigella species and reduces the prevalence of urinary-tract infection and respiratory tract infections. Oral administration of lactulose abolishes and prevents systemic endotoxemia of gut origin. Therefore lactulose may be used for treatment of inflammatory bowel disease as bacteria and bacterial endotoxin have an important role in the pathogenesis of this disease.
Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Lactulose/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Endotoxinas/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/etiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Lactulose/farmacologia , Infecções Respiratórias/prevenção & controle , Infecções Urinárias/prevenção & controleRESUMO
It has been recognized well that it is necessary to achieve superhydrophobic surfaces on intrinsically hydrophobic materials. However, recently experiments have demonstrated that it is possible to fabricate superhydrophobic surfaces on intrinsically hydrophilic materials by creating adequate roughness. In this study, such a possibility for superhydrophobicity on a hydrophilic surface with an intrinsic contact angle (CA) of 80 degrees, with a comparison to a hydrophobic surface with an intrinsic CA of 120 degrees, is thermodynamically analyzed using a pillared microtexture. Based on the calculations of free energy (FE) and free energy barrier (FEB), it is found that for such hydrophilic materials, generally, the FE for noncomposite or Wenzel's state is lower than that composite or Cassie's state for various geometrical wetting systems. Furthermore, even if pillar height or roughness is adequately large, it is hard to realize superhydrophobic behavior because of the surface wicking resulted from its special FE state. In addition, due to the negative FEB of the noncomposite state, there is no transition between noncomposite and composite states no matter how surface geometry varies. The above results also indicates that once noncomposite state is formed, it can hardly be become composite state, or in other words, even if superhydrophobic behavior is possible, it could be temporary and unstable. The present theoretical investigation therefore keeps a reservation on the practicability of superhydrophobic surfaces built on hydrophilic materials.
RESUMO
The urinary mutagenicity (unconjugated forms) after administration of 2,7-dinitrofluorene (2,7-dNF) orally or i.p. was lower compared to 2-nitrofluorene (NF) administration. When partial hepatectomy (PH) was performed before i.p. administration, both substances had higher excretion of mutagens in which 2,7-dNF increased dramatically and showed a higher level of mutagenicity compared to NF. NF and 2,7-dNF formed DNA adducts in liver tissue. By different routes of administration (oral or i.p.) of the same substance at the same dose (200 mg/kg body wt), the patterns of DNA adducts were different. It seemed to be that PH, which was performed 18 h before i.p. administration, had no significant effects on the amount of DNA adducts. Generally, the total amount of DNA adducts after oral administration was higher compared to i.p. administration. Dramatic increases of the nitroreduced DNA adducts were noticed after oral compared to i.p. administration. When given i.p., both substances showed initiating capacity in foci formation both at 50 mg/kg body wt and 200 mg/kg body wt. When NF and 2,7-dNF were administered orally by single gavage, 2,7-dNF was more potent as an initiator in foci formation compared to NF and the initiating capacity of the two substances was higher compared to i.p. administration. The great difference between these two nitro-PAHs seen in the bacterial tests for mutagenicity was not seen in the in vivo genotoxic experiments. The results indicate that both NF and 2,7-dNF formed DNA adducts and preneoplastic lesions after both i.p. and oral administration. After oral administration, both substances were more potent in causing DNA adduct and foci formation compared to i.p. administration. 2,7-dNF was more potent as an initiator than NF especially after oral administration. The urinary excretion of unconjugated mutagens did not indicate the genotoxic effects of the parent substance.
Assuntos
Dano ao DNA , Fluorenos/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Mutagênicos/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Animais , Neoplasias Hepáticas/genética , Masculino , Lesões Pré-Cancerosas/genética , Ratos , Ratos WistarRESUMO
2-Nitrofluorene (NF) is a model compound for nitroarenes which has been identified in diesel exhaust and in urban air. The current study was carried out to observe the carcinogenicity of different doses of NF to rats and DNA adduct formation in different organs at an early stage of NF administration. One group of rats was fed basal diet as a control, whereas the other three groups of rats were fed basal diet supplemented with different amounts of NF (0.24, 0.95 and 2.37 mmol NF/kg diet, referred to as low, medium and high dose, respectively). The rats were exposed to NF continuously for 11 months, after which all groups of rats were fed basal diet without NF for another 13 months. In the high dose group hepatocellular carcinomas were found in all rats (20/20), forestomach squamous carcinomas in 11 and cortical kidney carcinomas in 10 rats. Fifteen out of 19 rats fed the medium dose of NF had hepatocellular carcinomas, 16 had forestomach squamous carcinomas and 15 had cortical kidney carcinomas. The major tumors of the rats fed the low dose of NF were forestomach squamous carcinomas (10/18). DNA adducts formed in tumor target organs after 1, 2, 6 and 10 days NF administration were dose- and time-dependent. Ten days after the start of NF administration DNA adduct levels were found to be 54, 11 and 6 DNA adducts/10(8) normal nucleotides in forestomach, liver and kidney respectively. In the non-tumor target organs levels in the range 1.7-4.8 DNA adducts/10(8) normal nucleotides were found. DNA adduct formation in this study showed a good correlation with the localization of tumors, although there is a need for additional factors for tumor formation. The results indicate that DNA adduct formation is an important factor for tumor formation and suggest that DNA adducts could be used as biomarkers for genotoxic risk.
Assuntos
Carcinógenos/toxicidade , Adutos de DNA/biossíntese , DNA/efeitos dos fármacos , Fluorenos/toxicidade , Neoplasias Experimentais/induzido quimicamente , Animais , Peso Corporal/efeitos dos fármacos , DNA/metabolismo , Relação Dose-Resposta a Droga , Masculino , Neoplasias Experimentais/metabolismo , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The p21(WAF1/cIP1) cyclin-dependent kinase (cdk) inhibitor is a regulator of the G(1)-S cell cycle checkpoint. Despite the importance of p21 in cell cycle inhibition, its role as a tumor suppressor is uncertain. p21 mutations are infrequent in human tumors, and p21 null mice exhibit no increased tumor incidence. To ascertain whether p21 could influence tumor formation or progression in the context of other oncogenic stimuli, we crossed p21-deficient mice with mammary tumor susceptible Wnt-1 transgenic mice. The p21+/+, p21+/-, and p21-/- Wnt-1 transgenic female offspring were monitored for mammary tumor incidence and growth rates. p21 status had no effect on the age at which mammary tumors formed. However, p21+/- mammary tumors grew significantly faster than p21+/+ and p21-/- mammary tumors. The increased growth rates were confirmed by mitotic index counts and by BrdUrd labelling assays, indicating that a significantly higher percentage of p21+/- tumor cells were in S phase and mitosis than their p21+/+ and p21-/- counterparts. Moreover, cyclin D1-associated phosphorylation of retinoblastoma protein was significantly increased in p21+/- tumor lysates compared with p21+/+ and p21-/- lysates. These results are consistent with data indicating that reduced levels of p21 can facilitate cyclin/cdk complex formation while enhancing cdk activity. Thus, a reduction of p21 dosage may promote tumor progression in the presence of other oncogenic initiators. The dependence of p21 on prior oncogenic stimuli for its tumor-promoting activities suggests that it may behave as a tumor modifier gene rather than as a tumor suppressor gene.
Assuntos
Ciclina D1/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Heterozigoto , Neoplasias Mamárias Experimentais/genética , Fatores Etários , Alelos , Animais , Apoptose , Bromodesoxiuridina/metabolismo , Divisão Celular , Cruzamentos Genéticos , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/farmacologia , Relação Dose-Resposta a Droga , Feminino , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosfotransferases/metabolismo , Testes de Precipitina , Fatores de Tempo , Células Tumorais CultivadasRESUMO
Blood superoxide dismutase (SOD) activity and blood copper, zinc-superoxide dismutase (Cu.Zn-SOD) content were measured by luminol chemiluminescence assay and by single radial immunodiffusion assay, respectively, in 50 patients with paraplegia due to traumatic injury to the spinal cord by the Tangshan Earthquake on July 28, 1976, compared with 20 age-matched healthy subjects. We found that blood SOD activity and blood Cu.Zn-SOD content in the paraplegic patients were significantly lower than those in healthy subjects (p < 0.01). In healthy subjects, blood Cu.Zn-SOD fully expressed the enzymatic activity, whereas only 77% of blood Cu.Zn-SOD in the paraplegic patients expressed the enzymatic activity, indicating that in the patients, part of blood Cu.Zn-SOD protein is in a state without function. Also the serum lipid peroxide level in the paraplegic patients was higher than that in healthy subjects (p < 0.05). These findings suggest decreased endogenous blood protection against oxygen derived free radicals in these paraplegic patients.
Assuntos
Peroxidação de Lipídeos/fisiologia , Paraplegia/enzimologia , Traumatismos da Medula Espinal/enzimologia , Superóxido Dismutase/sangue , Adulto , Idoso , Feminino , Radicais Livres , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes. By gene disruption, we show that CHK1 deficiency results in a severe proliferation defect and death in embryonic stem (ES) cells, and peri-implantation embryonic lethality in mice. Through analysis of a conditional CHK1-deficient cell line, we demonstrate that ES cells lacking Chk1 have a defective G(2)/M DNA damage checkpoint in response to gamma-irradiation (IR). CHK1 heterozygosity modestly enhances the tumorigenesis phenotype of WNT-1 transgenic mice. We show that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU). Overexpression of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced by UV treatment. Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1.