RESUMO
This study investigated the effect of calcium (Ca) and phytase interaction on growth performance and bone quality in 1-42-day-old broiler chickens. A total of 624 female one-day-old Ross 308 broilers were allotted to 13 treatments with four replicates and 12 birds per replicate. A 2 × 6 factorial experiment was designed to test the combinations of 0.50% and 1.00% Ca with 0, 500, 1,000, 2,500, 5,000, and 10,000 FTU/kg phytase in the basal diet (0.25% non-phytate phosphorus, NPP). The control diet contained adequate Ca and phosphorus (P). Dietary Ca, phytase, and their interaction affected growth performance and bone mineralization of broilers at 1-42 days of age (p<0.05). The broilers fed with 1.00% Ca had lower body weight gain (BWG) and feed intake (FI) compared with the birds fed with 0.50% Ca (p<0.05). The BWG, FI, leg bone weight, and ash weight of the broilers fed with 0.25% NPP were lower than those of birds fed with the control diet (p<0.05). The addition of 500-10,000 FTU/kg phytase improved growth rate and leg bone quality, especially at 1.00% Ca (p<0.05). No differences were observed in growth performance and bone quality of 42-day-old broilers fed with 1.00% Ca + 2,500-10,000 FTU/kg phytase and the control diet (p>0.05). These data indicated that high doses of phytase (2,500-10,000 FTU/kg) alleviate the negative effects of Ca and P imbalance (Ca-to-NPP ratio = 4.0) on growth performance and bone mineralization of broiler chickens.(AU)
Assuntos
Animais , Feminino , Calcificação Fisiológica/efeitos dos fármacos , Galinhas/fisiologia , Fósforo/análise , Cálcio da Dieta/análise , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
BACKGROUND: The effect of postoperative chemoradiotherapy (CRT) for esophageal carcinoma (EC) was investigated. Patients who can obtain benefit from this treatment modality have not yet been well identified. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies published from January 1993 to July 2016. Research comparing surgery alone (SA) with postoperative CRT in patients with resectable EC was procured; collected articles were written in English. RESULTS: Nine studies comparing of postoperative CRT versus SA (n = 1650) in patients with resectable EC met the inclusion criteria. No survival benefit was achieved for postoperative CRT compared with SA. Subgroup analysis was conducted for patients under resection with positive lymph node carcinoma; there was a significant survival benefit at 1 year [risk ratio (RR) = 0.55 95% CI: 0.37-0.82; P = 0.003], 3 years (RR = 0.71 95% CI: 0.61-0.83; P<0.0001), as well as 5 years (RR = 0.86 95% CI: 0.78-0.94; P = 0.0007). Subgroup analysis by tumor histology of squamous cell carcinoma (SCC) was also performed, but there was no significant survival benefit when postoperative CRT was compared with SA. Fail models after surgery were performed; the RR for local control rate and distant metastasis rate were 0.64 (95% CI 0.49-0.85; P = 0.002) and 0.87 (95% CI 0.67-1.15; P = 0.34), which indicates lower local recurrence rates of post-CRT than that of SA. CONCLUSION: This meta-analysis demonstrated a survival benefit of postoperative CRT over SA in resectable EC patients with positive lymph nodes. Improvements of local control rates with postoperative CRT were also detected.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Linfonodos/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Humanos , Período Pós-Operatório , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE: Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the clinicopathologic factors that predict the outcome of routine trastuzumab therapy remain unclear. METHODS: The outcome and safety profile of trastuzumab therapy in untreated HER2 positive AGC was evaluated in this prospective observational study. Clinical and pathological data including demographics, treatment profiles, expression level of HER2 were analyzed to identify predictive factors of trastuzumab-based first-line therapy for their progression-free survival (PFS). RESULTS: Overall, 107 patients were eligible. The median number of treatment cycles was 9 (range 1-44), the median PFS and median overall survival (OS) were 7.7 months (95% CI 6.5-8.9) and 16.0 months (95% CI 13.2-18.8), respectively. The confirmed response rate was 58.9%, and the disease control rate was 82.2%. Patients with liver metastasis (HR 1.616) and poor performance status (PS, HR 2.518) were independently associated with a worse PFS, while the other clinicopathological factors including demographics, treatment profiles and some other clinical characteristics did not predict the survival. CONCLUSIONS: In routine clinical practice, the addition of trastuzumab to chemotherapy was effective and safe in real-world setting in Chinese patients with HER2 positive AGC, regardless of most of the clinicopathological factors. Further studies are needed to improve the prognosis of HER2 positive patients with liver metastasis or poor PS. Trial Registration clinicaltrials.gov Identifier: NCT03024450.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
PURPOSE: We aim to investigate the correlation of HER2 expression with liver metastasis and the impact of HER2 status and trastuzumab therapy on the prognosis of gastric cancer with liver metastasis (GCLM) patients. METHODS: This prospective observational study was carried out in Shanghai Zhongshan Hospital, Fudan University, from January 2012 to June 2015. HER2 status and baseline characteristics were collected from the patient record. GCLM patients were divided into three groups according to HER2 status and trastuzumab therapy. RESULTS: A total of 290 patients were included, and94 patients were diagnosed with liver metastasis. The HER2 positivity was 37.2 % (35/94) in GCLM patients and 21 % (61/290) in the overall GC patients. Among 94 GCLM patients, 28 HER2-positive patients received trastuzumab-based therapy (group A), 7 HER2-positive patients received chemotherapy alone (group B) and the other 59 patients were HER2 negative (group C). The median progression-free survival (PFS) for groups A, B and C was 7.83, 6.30 and 5.33 months, respectively (P = 0.007). The median overall survival (OS) for groups A, B and C was 12.00, 10.47 and 8.67 months, respectively (P = 0.056). Further Cox analysis showed that there was no significant difference in OS (P = 0.917) and PFS (P = 0.456) between group B and C. CONCLUSIONS: HER2 positivity was higher in GCLM patients. HER2 status itself was not an independent prognostic factor in GCLM patients. Trastuzumab-based therapy could significantly improve survival in HER2-positive GCLM patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Metástase Linfática , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
In this study, we investigated the role of two single nucleotide polymorphisms in the promoter region of the interleukin-8 gene (IL-8; rs4073 and rs2227306) in the susceptibility to primary gouty arthritis in a Chinese population. Three hundred and twelve patients with primary gouty arthritis and 340 healthy controls were recruited from the Yan'an University Affiliated Hospital between January 2014 and March 2015. The IL-8 rs4073 and rs2227306 polymorphisms were genotyped by polymerase chain reaction combined with restriction fragment length polymorphism. Unconditional multiple-logistic regression analysis revealed that the TT genotype of rs4073 was correlated with primary gouty arthritis risk, compared to the AA genotype [adjusted odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.08-2.54; P = 0.02]. In addition, the IL-8 rs4073 T allele was associated with a significant elevated risk of primary gouty arthritis, in comparison to the A allele (OR = 1.34, 95%CI = 1.07-1.67; P = 0.01). However, we observed no significant relationship between the IL-8 rs2227306 polymorphism and primary gouty arthritis risk. The results of this study suggest that the IL-8 rs4073 polymorphism could be a marker for primary gouty arthritis development.
Assuntos
Artrite Gotosa/genética , Povo Asiático/genética , Predisposição Genética para Doença , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The aim of this study was to investigate the expression and clinical significance of the obesity-associated gene STEAP4 in obese children. Fifty-three obese children and 33 children with a standard body weight (control) from our hospital were recruited to this study. The expression of STEAP4 mRNA and protein in the adipose tissue were detected by reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in order to analyze the relationship between STEAP4 mRNA and protein levels and blood pressure, blood lipid profile, blood glucose levels, and inflammation in obese children. Obese children showed significantly lower levels of STEAP4 mRNA and protein in the adipose tissue compared to the control subjects (P < 0.05). The obese subjects exhibited significantly higher diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, and a significantly lower high-density lipoprotein (HDL) level, compared to the control subjects (P < 0.05). Correlation analysis revealed that STEAP4 expression was negatively correlated with the DBP, SBP, TC, TG, LDL, FPG, IL-6, and TNF-α levels, and was positively correlated with the HDL level (P < 0.05). In conclusion, the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children and was closely related to the blood pressure, blood lipid, blood glucose, and inflammation in these patients; therefore, these results could provide a theoretical basis for the treatment of childhood obesity.
Assuntos
Regulação da Expressão Gênica , Proteínas de Membrana/genética , Obesidade/genética , Oxirredutases/genética , Adipócitos/metabolismo , Adipócitos/patologia , Glicemia/metabolismo , Pressão Sanguínea , Estudos de Casos e Controles , Criança , Pré-Escolar , Regulação para Baixo/genética , Feminino , Humanos , Interleucina-6/metabolismo , Lipídeos/sangue , Masculino , Proteínas de Membrana/metabolismo , Obesidade/sangue , Obesidade/fisiopatologia , Oxirredutases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The transcriptomes of salt-stressed and unstressed Betula kirghisorum plants were analyzed using high throughput sequencing technology. A total of 52,239,804 and 51,772,998 clean reads were obtained from the two libraries, respectively, and de novo assembled into 60,545 all-unigenes. A total of 39,997 unigenes were annotated using public databases. Overall, 7206 genes were differentially expressed in unigenes and were involved in 127 pathways. Thirteen transcription factor families were identified in B. kirghisorum, including GRAS proteins, which are plant-specific transcription factors. By using bioinformatic methods to predict and analyze physicochemical properties, structural data were obtained on the 19 potential GRAS proteins. The results revealed that these proteins are hydrophilic, with significant differences in their length and molecular weight. The main secondary structures were alpha helices and random coils. BkGRAS proteins possess typical GRAS domains: LHR I; VHIID motif; LHR II; PFYRE motif; and SAW motif. In the majority of BkGRAS proteins, AGG, AGA, UCU, GCU, GGG, CCA, GUU, GUG, AUU, GAU, and AAG codons were used preferentially. Aside from the BkGRAS17 gene (relative synonymous codon usage (RSCU) = 1.20), usage of the UUA codon by other BkGRAS genes was low (RSCU < 1.0). The effective number of codons showed that BkGRAS genes have low codon bias. Subcellular localization analysis that predicted these proteins are found in the nucleus, cytoplasm, or chloroplast. BkGRAS proteins were divided into six subfamilies: SCR, LISCL, SCL3, DELLA, HAM, and PAT1. These results provide important information for the further functional study of GRAS genes in B. kirghisorum.
Assuntos
Betula/genética , Biologia Computacional/métodos , Genes de Plantas , Proteínas de Plantas/genética , Transcriptoma/genética , Sequência de Aminoácidos , Composição de Bases/genética , Códon/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Anotação de Sequência Molecular , Filogenia , Proteínas de Plantas/metabolismo , Domínios Proteicos , Sinais Direcionadores de Proteínas/genética , Estrutura Secundária de Proteína , Análise de Sequência de RNA , Estresse Fisiológico/genética , Frações Subcelulares/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismoRESUMO
Hepatitis B virus (HBV) infection can cause HBV-related cirrhosis, liver failure, and hepatocellular carcinoma. At present, a hepatitis B surface antigen (HBsAg) blood test is the primary clinical and diagnostic marker for the identification of a chronic HBV infection. In the current study, we isolated a novel HBV mutant from a chronic HBV patient, capable of causing a false negative test result for most (7 of 8) commercial HBsAg ELISA kits. DNA sequencing of the HBsAg region of this HBV mutant revealed two novel mutation sites that resulted in a Thr-to-Met substitution at amino acid (aa) position 118 and a Lys to Asn substitution at aa position 122 of HBsAg. Moreover, a mutagenesis assay showed that the aa118 (Thr to Met) mutation was the leading cause of the false negative results from the HBsAg ELISA tests. The false negative result was restored, in that the mutation was correctly detected, when the Thr at aa position 118 of this mutated HBsAg was reconstituted. In conclusion, our study revealed a novel aa118 Met mutation of HBsAg HBV that will benefit the future development of HBV diagnosis.
Assuntos
Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/sangue , Mutação de Sentido Incorreto , Testes Sorológicos/normas , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Reações Falso-Negativas , Células HEK293 , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Testes Sorológicos/métodosRESUMO
The aim of this study was to investigate the abilities of cartilage-derived morphogenetic protein 1 (CDMP1) transgenic cell sheets in repairing rabbit cartilage defects. Rabbit CDMP1 transgenic bone marrow mesenchymal stem cell (BMSC) sheets (CDMP1-BMSCs) were cultured on temperature-sensitive culture dishes, and CDMP1 expression and type II collagen protein in the cell sheets were detected. Tissue-engineered cell sheets were constructed and transplanted into defect rabbit thyroid cartilage, to investigate the expression of engineered cartilage collagen protein and proteoglycan (GAG). The experiment was divided into three groups; A) BMSC sheet, B) Ad-CMV-eGFP-transfected cell sheet, and C) Ad-CMV-hCDMP1-IRES-eGFP-transfected cell sheet. The expression of CDMP1 was detected in the transgenic cell sheets. The engineered cartilage exhibited positive immunohistochemical and Alcian blue staining. The expression levels of type II collagen protein and GAG in group A were positive, whereas those in group B and group C were negative (P < 0.05). The CDMP1-BMSC sheets had a good cartilage differentiation activity, and could effectively repair rabbit laryngeal cartilage defects.
Assuntos
Cartilagem/fisiologia , Fator 5 de Diferenciação de Crescimento/genética , Transplante de Células-Tronco Mesenquimais , Regeneração , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Cartilagem/citologia , Células Cultivadas , Feminino , Fator 5 de Diferenciação de Crescimento/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Coelhos , Alicerces Teciduais/efeitos adversosRESUMO
Plasma membrane proteolipid 3 (PMP3) is a class of small hydrophobic proteins found in many organisms including higher plants. Some plant PMP3 genes have been shown to respond to abiotic stresses and to participate in the processes of plant stress tolerance. In this study, we isolated the cassava (Manihot esculenta Crantz) MePMP3-2 gene and functionally characterized its role in tolerance to abiotic stress by expressing it in rice (Oryza sativa L.). MePMP3-2 encodes a 77-amino acid protein belonging to a subgroup of plant PMP3s that have long hydrophylic C-terminal tails of unknown function. In silico analysis and co-localization studies indicated that MePMP3-2 is a plasma membrane protein with two transmembrane domains, similar to other PMP3s. In cassava leaves, MePMP3-2 expression was up-regulated by salt and drought stresses. Heterologous constitutive expression of MePMP3-2 in rice did not alter plant growth and development but increased tolerance to salt and drought stresses. In addition, under stress conditions MePMP3-2 transgenic plants accumulated less malondialdehyde, had increased levels of proline, and exhibited greater up-regulation of the stress-related genes OsProT and OsP5CS, but led to only minor changes in OsDREB2A and OsLEA3 expression. These findings indicate that MePMP3-2 may play an important role in salt and drought stress tolerance in transgenic rice.
Assuntos
Adaptação Fisiológica , Regulação da Expressão Gênica de Plantas , Manihot/fisiologia , Proteínas de Membrana/fisiologia , Oryza/fisiologia , Proteínas de Plantas/fisiologia , Plantas Geneticamente Modificadas , Sequência de Aminoácidos , Simulação por Computador , Secas , Manihot/genética , Manihot/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Oryza/genética , Oryza/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteolipídeos/fisiologia , Tolerância ao Sal , Alinhamento de Sequência , Regulação para CimaRESUMO
INTRODUCTION: The esophageal squamous cell carcinoma (ESCC) is the predominant pathological type and accounts for more than 80 % of esophageal cancer in China. The successful use of anti-epidermal growth factor receptor (EGFR) treatment in head and neck squamous cell carcinoma provides the rationale for introducing anti-EGFR targeting treatment in ESCC. One of our prospective phase II clinical trials analyzed the efficacy of nimotuzumab, an anti-EGFR agent, combined with chemotherapy (paclitaxel and cisplatin) to treat unresectable ESCC. MATERIALS AND METHODS: We analyzed the correlation of the clinical response with EGFR expression by immunohistochemical staining (IHC). RESULTS: Totally 55 tumor samples were analyzed. 18/55 (32.7 %) cases were with high EGFR expression while the other 37/55 (67.3 %) cases were with low to moderate EGFR expression. The expression of EGFR was not related to gender, age, tumor location, tumor differentiation and clinical stage of disease. The objective response rate (ORR) in high EGFR expression group was 55.6 % (10/18) while that in low to moderate EGFR expression group was 54.1 % (20/37) (P = 0.57). Both the progression-free survival (PFS) and overall survival (OS) in high EGFR expression group were much shorter than those in low to moderate EGFR expression group (PFS: 5.8 ± 0.5 vs. 11.0 ± 2.8 months, P = 0.007; OS: 9.7 ± 0.5 vs. 21.5 ± 1.5 months, P = 0.03). CONCLUSIONS: The results showed that over-expression of EGFR was related to poor survival of ESCC. The over-expression of EGFR by IHC might not be an ideal predictive biomarker of nimotuzumab treatment. Other EGFR pathway-associated molecules should be analyzed in further studies.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/biossíntese , Neoplasias Esofágicas/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagemRESUMO
Verticillium wilt is one of the main diseases in cotton (Gossypium hirsutum), severely reduces yield and fiber quality, and is difficult to be con-trolled effectively. At present, the molecular mechanism that confers resistance to this disease is unclear. Transcriptome sequencing is an important method to detect resistance genes, explore metabolic pathways, and study resistance mechanisms. In this study, the transcriptome of a disease-resistant inbred cot-ton line inoculated with Verticillium dahliae was sequenced. A total of 126,402 unigenes were obtained using de novo assembly and data analysis, 99,712 (78.88%) of which were annotated into the Nr, Nt, Swiss-Prot, KEGG, COG, and GO databases. The expression patterns of 16 candidate disease-resis-tance genes showed that some genes were upregulated soon after V. dahliae inoculation and others were upregulated later, which may indicate instanta-neous basal defense and lagged specific defense, respectively. We conducted a preliminary analysis of the transcriptome database, which will contribute to further research regarding the cloning of disease-resistance genes.
Assuntos
Gossypium/genética , Gossypium/microbiologia , Transcriptoma , Verticillium , Biologia Computacional , Resistência à Doença/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/metabolismo , Interações Hospedeiro-Patógeno/genética , Redes e Vias Metabólicas , Anotação de Sequência Molecular , Doenças das Plantas/genéticaRESUMO
This study reports the cloning of a sucrose transporter gene, PsSUT1, from the leaf of tree peony (Paeonia suffruticosa Lind. cv 'Huhong'). Expression patterns were examined in different organs and at different developmental stages. The full-length cDNA of PsSUT1 consisted of a 2001-bp sequence containing a 1557-bp open reading frame, encoding 519 amino acids with a conserved domain typical of the glycoside-pentoside-hexuronide superfamily. The amino acid sequence of PsSUT1 in tree peony shared high homology with that of other plants. At different developmental stages, PsSUT1 was expressed in roots, stems, leaves, and petals. Its expression level in stems was 10.9-fold higher than in petals at the flowering stage. Expression of PsSUT1 at the flowering stage was highest during flower development. The significant differences in PsSUT1 expression observed among developmental stages and organs were closely related to changes in sucrose content during flower opening. These results form the basis for further research on the molecular mechanisms of carbohydrate metabolism and transport during flower development in tree peony.
Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/genética , Paeonia/genética , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Membrana Transportadoras/metabolismo , Paeonia/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismoRESUMO
The aim of this in vivo study was to determine the existence of muscle-derived stem cells (MDSCs) in rat corpus cavernosum. Immunohistochemical and RT-PCR analyses were performed to determine the expression of the stem cell markers (Sca-1, Oct4, and desmin) in Sprague-Dawley (SD) rats in different age groups (10 rats in each group). Sca-1 was mainly expressed in blood vessels and cavernous sinus and demonstrated primarily cytoplasmic staining. Desmin was expressed mainly in muscle tissues and staining occurred mainly in the cytoplasm but also partially in the nucleus. An extremely small amount of double-positive stained cells (Sca-1/desmin) were detected near the cavernous sinus. Expression of the markers was significantly and negatively correlated with the age of the rats (P < 0.05). The RT-PCR results showed that the expression levels of Sca-1 and desmin significantly decreased with age (P < 0.05). Correlation analysis indicated that the expression of Sca-1 and desmin were significantly and negatively correlated with the age of rats (r = -0.929, P < 0.05). The present study provides evidence for the existence of MDSCs in rat corpus cavernosum. MDSCs may have therapeutic potential in the treatment of organic erectile dysfunction.
Assuntos
Mioblastos/citologia , Mioblastos/metabolismo , Pênis , Animais , Biomarcadores , Separação Celular , Citometria de Fluxo , Expressão Gênica , Masculino , Fenótipo , RatosRESUMO
The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of "brown adipocytes" within white fat depots. All-trans retinoic acid (t-RA) and peroxi-some proliferator-activated receptor-α (PPARα) have been implicated in "browning-like" or "browning" programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the "browning" of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of "brown-ing" using western blot. All concentrations of WY14643 failed to in-duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P < 0.05). WY14643 combined with t-RA was observed to induce UCP1 mRNA expression, protein expression, and phosphory-lation of p38 MAPK (P < 0.05). SB203580 combined with WY14643 and t-RA suppressed UCP1 mRNA expression, protein expression, and p38 MAPK phosphorylation (P < 0.05). WY14643 combined with t-RA can induce the transformation of white adipocytes to brown adipocytes through activation of the p38 MAPK signaling pathway.
Assuntos
Adipócitos Marrons/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Pirimidinas/farmacologia , RNA Mensageiro/genética , Tretinoína/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células 3T3-L1 , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação da Expressão Gênica , Imidazóis/farmacologia , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Camundongos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , PPAR alfa/agonistas , PPAR alfa/genética , PPAR alfa/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteína Desacopladora 1 , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
BACKGROUND: Liver metastasis is associated with poor prognosis in gastric cancer. Surgical resection and systemic chemotherapy have been reported to be effective in gastric cancer with liver metastasis (GCLM). However, the best strategy for GCLM has not been established. METHODS: From May 2009 to July 2014, a consecutive series of GCLM patients in Zhongshan Hospital of Fudan University were studied. Treatment strategies were evaluated with regard to different extents of metastases. RESULTS: A total of 163 patients were included. The overall survival was 10.1 months. Active treatment significantly prolongs the survival of GCLM patients. The overall survival time for patients with liver-limited metastases and extra-hepatic liver metastases was 11.6 mo and 8.7 mo, respectively (P = 0.012). The median survival time for liver-limited disease of H1, H2 and H3 was 14.2, 15.8, and 8.5 months, respectively (H3 vs H2, P = 0.001; H3 vs H1, P = 0.000; H1 vs H2, P = 0.900). Systemic chemotherapy was chosen as the main strategy for the 'extensive' patients with extra-hepatic metastases and H3 type liver-limited metastases. Patients' survival was benefited by multi-line chemotherapy. No differences were shown between systemic chemotherapy and curative resection or palliative resection in H1 and H2 liver-limited metastases (16.0 mo vs 12.0 mo, P = 0.711; 16.0 vs 18.8 months, P = 0.654). CONCLUSION: Systemic chemotherapy was the main treatment for gastric cancer patients with liver metastases. Curative resection could be considered for highly selected patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidadeRESUMO
People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.
Assuntos
Animais , Lesões Encefálicas/complicações , Córtex Cerebral/lesões , Ciclo-Oxigenase 1/fisiologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Pirazóis/uso terapêutico , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Descorticação Cerebral , Ciclo-Oxigenase 1/metabolismo , Modelos Animais de Doenças , Dinoprostona/análise , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , /sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Sinaptofisina/análise , Sinaptofisina/metabolismoRESUMO
People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.
Assuntos
Lesões Encefálicas/complicações , Córtex Cerebral/lesões , Ciclo-Oxigenase 1/fisiologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Pirazóis/uso terapêutico , Animais , Becaplermina , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Descorticação Cerebral , Ciclo-Oxigenase 1/metabolismo , Dinoprostona/análise , Dinoprostona/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , Interleucina-6/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-sis/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Sinaptofisina/análise , Sinaptofisina/metabolismoRESUMO
Broussonetia papyrifera is an important native tree species with high economic value in southwest China. Its resources are drastically reduced because of over-harvesting and habitat fragmentation. In this study, 17 natural populations of B. papyrifera were analyzed using inter-simple sequence repeat (ISSR) markers to assess the genetic diversity and population structure. In total, 100 bands were obtained from 16 ISSR primers. The B. papyrifera populations showed relatively high genetic diversity at the species level [percentage of polymorphic bands (PPB): 96%; Nei's genetic diversity (HE): 0.3074; Shannon's information index (I): 0.4617], while the genetic diversity at the population level was relatively low (PPB: 53.2%; HE: 0.1826; I: 0.2735). Relatively high level of genetic differentiation among populations (41%) was disclosed by analysis of molecular variance, which agrees with the Nei's genetic diversity statistics (40.59%) and Shannon's information measure (40.76%). Gene flow among populations (NM) was only 0.7318. A significant correlation was observed between genetic and geographic distance among the studied populations (r=0.2948). We conjectured that the genetic diversity of B. papyrifera resulted from human disturbance, habitat fragmentation, small effective population size, and geographic barrier. Given the high genetic differentiation among populations, some utilization and conservation strategies were proposed. This study provides a reference for the sustainable use of the species in southwest China.