RESUMO
PURPOSE: Metabolomics is an emerging field in cancer research. Plasma free amino acid profiles (PFAAs) have shown different features in various cancers, but the characteristic in advanced sarcoma remains unclear. We aimed to uncover the specific PFAAs in advanced sarcoma and to find the relationship between the altering of PFAAs and response to chemotherapy. PATIENTS AND METHODS: We analyzed the differences in PFAAs between 23 sarcoma patients and 30 healthy subjects basing on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we compared the dynamics of PFAAs after chemotherapy between improvement group and deterioration group. RESULTS: We identified seven biological differential amino acids and four pathways which were perturbed in the sarcoma patients compared with healthy subjects. After one cycle chemotherapy, the levels of γ-aminobutyric acid (GABA) and carnosine (Car) decreased significantly in the improvement group but not in deterioration group. The levels of α-aminobutyric acid (Abu) increased significantly in the deterioration group but not in the improvement group. CONCLUSION: Our study suggests the potential specific PFAAs in sarcoma patients. The unusual amino acids and metabolic pathways may provide ideas for clinical drugs targeting therapy. Three amino acids including Car, GABA and Abu may be metabolic biomarkers playing a role in dynamic monitoring of the therapeutic effect.
Assuntos
Aminobutiratos/sangue , Biomarcadores Tumorais/sangue , Carnosina/sangue , Sarcoma/tratamento farmacológico , Ácido gama-Aminobutírico/sangue , Adulto , Idoso , Aminoácidos/sangue , Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Sarcoma/sangue , Sarcoma/patologia , Espectrometria de Massas em Tandem , Resultado do Tratamento , Adulto JovemRESUMO
Bone desensitization after mechanical loading is essential for bone to adapt to its mechanical environment. However, the desensitization mechanism is unknown. Previous studies suggest that G protein-coupled receptors (GPCRs), including P2Y and parathyroid hormone receptors, play important roles in osteoblast mechanobiology. Thus, for the present research, we examined the role of G protein-coupled receptor kinase 2 (GRK2) in osteoblast desensitization after exposure to mechanical stimulation. We first showed the existence of osteoblast desensitization after mechanical stimulation based on cytosol Ca2+ and phosphorylated ERK1/2 activities, detected using a fluorescent Ca2+-sensitive dye and western blotting, respectively. We then demonstrated that GRK2 overexpression in MC3T3-E1 cells inhibits flow-induced ERK1/2 phosphorylation, while siRNA knockdown of GRK2 enhances ERK1/2 phosphorylation. Additionally, we found that GRK2 overexpression in MC3T3-E1 cells inhibits cyclooxygenase-2 mRNA expression in the short term and alkaline phosphatase activity in the long term. More importantly, we discovered that GRK2 translocated to the cell membrane shortly after flow stimulation - a step necessary for GPCR desensitization. Previously, we have demonstrated that P2Y2 purinergic receptors, one type of GPCRs, are involved in various flow-induced osteoblastic responses. In this research, we also showed that GRK2 overexpression does not affect ATP release. Accordingly, GRK2 is able to inhibit flow-induced osteoblast responses possibly through desensitizing P2Y2 receptors.
Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Fenômenos Mecânicos , Osteoblastos/fisiologia , Animais , Biomarcadores , Linhagem Celular , Humanos , Camundongos , Fosforilação , Receptores Purinérgicos P2Y2/metabolismo , Transdução de SinaisRESUMO
Sacral nerve stimulation (SNS) is an alternative surgical approach to alleviate fecal incontinence and constipation. This study aimed to explore the effects and underlying mechanisms of SNS with acupuncture on gut transit time and colon c-kit protein expression in rats with slow transit constipation (STC). Fifty Sprague-Dawley rats were randomly divided into five groups: blank control, SNS, Mosapride, sham SNS, and STC model control group. The STC model was established by subcutaneous injection of morphine. Each group was treated over a 15-day period. Gut transit time was measured 1 day before the treatment started and after 5, 10, and 15 days of treatment. After the 15-day treatment, animals were sacrificed and colonic tissues were collected for analysis of c-kit protein expression, using western blot analysis. We found significant differences in gut transit time in the SNS group compared with the Mosapride group after 5 (P = 0.001) and 10 (P = 0.004) days of treatment. After 15 days of treatment, there were no differences in gut transit time among the SNS, Mosapride, and blank control groups. However, significant differences were observed when comparing the SNS and Mosapride groups with the STC model and sham SNS groups. A decreased c-kit protein expression was observed in the STC model control, sham SNS, and Mosapride groups, compared with the SNS group (P = 0.001). Our data indicate that SNS can decrease gut transit time and increase the expression of c-kit protein in rats with STC to improve colon transit function.
Assuntos
Terapia por Acupuntura , Colo/metabolismo , Colo/fisiopatologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sacro/inervação , Animais , Estimulação Elétrica , Feminino , Masculino , Ratos Sprague-Dawley , Fatores de TempoRESUMO
We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.
Assuntos
Fatores Imunológicos/uso terapêutico , Pancreatite Necrosante Aguda/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Citocinas/sangue , Endotoxinas/sangue , Feminino , Humanos , Lactulose/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Equilíbrio Th1-Th2RESUMO
Numerous studies have evaluated the association between the angiotensin II type-1 receptor (AGTR1) gene A1166C polymorphism and breast cancer risk. However, the specific association is controversial. The aim of the present study was to derive a more precise estimation of the relationship. A comprehensive research was conducted of the PubMed and the Google Scholar databases through February 2015. Data were assessed using STATA version 12.0. Pooled odds ratios with 95%CIs were derived from the fixed-effect or random-effect models. A total of 911 patients with breast cancer and 1284 controls from 5 case-control studies were included in this meta-analysis. The meta-analysis results showed no significant association between the AGTR1 gene A1166C polymorphism and breast cancer risk. Similarly, in the subgroup analysis regarding ethnicity, no associations were observed. Heterogeneity and publication bias were not observed in this meta-analysis. The A1166C polymorphism in the AGTR1 gene may not be a risk factor for breast cancer. Further, large, and well-designed studies are needed to confirm this conclusion.
Assuntos
Neoplasias da Mama/genética , Polimorfismo Genético/genética , Receptor Tipo 1 de Angiotensina/genética , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Genéticos , Razão de Chances , Fatores de RiscoRESUMO
This study evaluates the relationship between the genotype and milk protein components in goats. Milk samples were collected from cloned goats and normal white goats during different postpartum (or abortion) phases. Two cloned goats, originated from the same somatic line of goat mammary gland epithelial cells, and three sexually reproduced normal white goats with no genetic relationships were used as the control. The goats were phylogenetically analyzed by polymerase chain reaction-restriction fragment length polymorphism. The milk protein components were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicated that despite the genetic fingerprints being identical, the milk protein composition differed between the two cloned goats. The casein content of cloned goat C-50 was significantly higher than that of cloned goat C-4. Conversely, although the genetic fingerprints of the normal white goats N-1, N-2, and N-3 were not identical, the milk protein profiles did not differ significantly in their milk samples (obtained on postpartum day 15, 20, 25, 30, and 150). These results indicated an association between milk protein phenotypes and genetic polymorphisms, epigenetic regulation, and/or non-chromosomal factors. This study extends the knowledge of goat milk protein polymorphisms, and provides new strategies for the breeding of high milk-yielding goats.
Assuntos
Estudos de Associação Genética , Cabras/genética , Cabras/metabolismo , Leite , Polimorfismo Genético , Característica Quantitativa Herdável , Animais , Clonagem de Organismos , Feminino , Genótipo , Masculino , Leite/química , Leite/metabolismo , Proteínas do Leite/genética , Fenótipo , ReproduçãoRESUMO
The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals, and it has evolved several unusual biological and behavioral traits. During puberty, pregnancy, lactation, and involution, the mammary gland undergoes profound morphological and functional changes. A large number of microRNAs (miRNAs) have been identified to be involved in mammary gland development and lactation. In this study, we identified 202 conserved mature miRNAs, corresponding to 147 pre-miRNAs, in giant panda peripheral blood using a small RNA-sequencing approach. In addition, 27 miRNA families and 29 miRNA clusters were identified. We analyzed the arm selection preference of pre-miRNAs and found that: 1) most giant panda pre-miRNAs generated one-strand miRNAs, and the 5p-arm only miRNAs have a higher expression level than 3p-arm only miRNAs; 2) there were more 5p-arm dominant miRNAs than 3p-arm dominant miRNAs; and 3) 5p-arm dominant miRNAs have a larger fold change within miRNA pairs than 3p-arm dominant miRNAs. Expression of 12 lactation-related miRNAs was detected across late pregnancy and early lactation stages by qPCR, and seven miRNAs were identified as clustered in one significant model. Most of these clustered miRNAs exhibited inhibitory roles in proliferation and differentiation of mammary epithelial cells. Functional analysis highlighted important roles of the seven as signed miRNAs in mammary development and metabolic changes, including blood vessel morphogenesis, macromolecule biosynthesis, cell cycle regulation, and protein transport.
Assuntos
Lactação/genética , Glândulas Mamárias Animais/fisiologia , MicroRNAs/sangue , Prenhez/genética , Ursidae/genética , Animais , Feminino , Perfilação da Expressão Gênica/veterinária , Glândulas Mamárias Animais/metabolismo , MicroRNAs/genética , Gravidez , Prenhez/sangue , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA/métodos , Maturidade Sexual/genética , Ursidae/sangueRESUMO
Synechococcus sp PCC 7336 represents a newly sequenced strain, and its genome is obviously different from that of other Synechococcus strains. In this analysis, local alignment and annotation databases were constructed and combined with various bioinformatic tools to carry out gene annotation and functional analysis of this strain. From this analysis, we identified 5096 protein-coding genes and 47 RNA genes. Of these, 116 genes that were classified into 9 categories were associated with photosynthesis, and type V polymerase proteins that were identified are unique for this strain. An additional 107 genes were closely related to signal transduction pathways, which primarily comprised parts of two-component regulatory systems. Gene ontogeny analysis showed that 2377 genes were annotated with a total number of 9791 functional categories, and specifically that 41 genes distributed in 4 protein complexes were involved in oxidative phosphorylation. Clusters of orthologous groups classification showed that there were 1463 homologous proteins associated with 17 specific metabolic pathways, and that most of the proteins participated in primary metabolic processes such as binding and catalysis. The phylogenetic tree based on 16S rRNA sequences indicated that Synechococcus PCC 7336 is highly likely to represent a new branch.
Assuntos
Synechococcus/genética , Ontologia Genética , Anotação de Sequência Molecular , Filogenia , Synechococcus/classificaçãoRESUMO
Gastric cancer (GC) is a prevalent disease with a high mortality rate, especially in developing countries. Accumulating evidence suggests that single nucleotide polymorphisms in microRNA (miRNA) genes might influence the susceptibility to GC; such sequence variation might contribute to the development of disease by altering crucial cellular pathways. In this study, we assessed the correlation between the miR-146a G>C, miR-196a-2 C>T, miR-499 T>C, miRNA-27a A>G, and miRNA-149 T>C polymorphisms and the susceptibility to GC. A comprehensive literature search for relevant studies published prior to August 2014 was conducted using PubMed/Medline, Embase, Web of Science, the Cochrane Library, and CNKI databases along with Google Scholar. Meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs) as effect measures, incorporating 19 studies encompassing 8285 patients and 10,716 controls. Allelic, dominant, recessive, homozygous, and heterozygous genetic models were examined. Pooled results showed that none of the five polymorphisms studied were statistically related to GC. Stratified analyses by ethnicity and source of controls were conducted for miR- 146a G>C and miR-196a-2 C>T. Subgroup analysis suggested that the miR-146a G allele might increase the risk of GC in hospital-based case-control (HCC) but not in population-based case-control studies (HCC: recessive model: OR = 1.23, 95%CI = 1.10-1.37, P < 0.001; heterozygous model: OR = 1.19, 95%CI = 1.06-1.34, P = 0.004). Overall, this meta-analysis failed to detect an association between five common miR-146a gene polymorphisms and GC susceptibility. However, this does not necessarily completely rule out a correlation between miRNA polymorphisms and GC susceptibility.
Assuntos
MicroRNAs/genética , Neoplasias Gástricas/genética , Alelos , Povo Asiático , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Fatores de Risco , Neoplasias Gástricas/patologiaRESUMO
Meat quality traits are very important in the poultry industry. To identify single nucleotide polymorphisms (SNPs) and candidate genes affecting meat quality traits, a genome-wide association study was performed using the Illumina chicken 60K SNP beadchip in Jinghai yellow chicken. Four meat quality traits were measured. Two SNPs reached 5% Bonferroni genome-wide significance (P < 1.8E-6) and 7 SNPs reached "suggestive" genome-wide significance (P < 3.59E-6) with meat quality. These SNPs were located nearby or in 7 candidate genes, including CBLN2, HPGDS, SETD2, and ANKRD46, among others. A total of 5650 haplotpyes were established and only 1 was found to be associated with fat content in leg muscle. These results indicate that the 9 SNPs and 7 genes are important candidate markers and may influence meat quality traits in chicken.