Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey.

BACKGROUND: The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein. RESULTS: Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice. CONCLUSIONS: This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.

Flavonoid biosynthesis controls fiber color in naturally colored cotton.

The existence of only natural brown and green cotton fibers (BCF and GCF, respectively), as well as poor fiber quality, limits the use of naturally colored cotton (Gossypium hirsutum L.). A better understanding of fiber pigment regulation is needed to surmount these obstacles. In this work, transcriptome analysis and quantitative reverse transcription PCR revealed that 13 and 9 phenylpropanoid (metabolic) pathway genes were enriched during pigment synthesis, while the differential expression of phenylpropanoid (metabolic) and flavonoid metabolic pathway genes occurred among BCF, GCF, and white cotton fibers (WCF). Silencing the chalcone flavanone isomerase gene in a BCF line resulted in three fiber phenotypes among offspring of the RNAi lines: BCF, almost WCF, and GCF. The lines with almost WCF suppressed chalcone flavanone isomerase, while the lines with GCF highly expressed the glucosyl transferase (3GT) gene. Overexpression of the Gh3GT or Arabidopsis thaliana 3GT gene in BCF lines resulted in GCF. Additionally, the phenylpropanoid and flavonoid metabolites of BCF and GCF were significantly higher than those of WCF as assessed by a metabolomics analysis. Thus, the flavonoid biosynthetic pathway controls both brown and green pigmentation processes. Like natural colored fibers, the transgenic colored fibers were weaker and shorter than WCF. This study shows the potential of flavonoid pathway modifications to alter cotton fibers' color and quality.

Promoter Hypermethylation of FANCF and Susceptibility and Prognosis of Epithelial Ovarian Cancer.

OBJECTIVE: To assess the 5' CpG island methylation of Fanconi anemia, complementation group F (FANCF) gene in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues and to investigate the relationship between FANCF methylation and clinicopathologic features and prognosis of EOC. METHODS: The experiment was performed with 112 EOC tissue samples (case group) and 60 normal ovarian tissues (control group). With methylation-specific polymerase chain reaction (MSP), FANCF methylation status of cases and controls was assessed. And the association between FANCF methylation and the clinicopathological features of EOC was investigated with univariate survival analysis and Cox regression model analysis. RESULTS: The methylation-positive rate of the case group was significantly higher than that of the control group (P = 0.015). The FANCF promoter methylation rates showed significant differences in the comparisons stratified by age, International Federation of Gynecology and Obstetrics (FIGO) staging, histopathological classification, and lymph node metastasis (all P < .05). Univariate survival analysis showed there were significant differences in mean survival time between the groups based on FIGO staging, histopathological classification, lymph node metastasis, and FANCF methylation (all P < .05). Cox regression model analysis suggested that FIGO staging and FANCF methylation were independent risk factors for EOC prognosis. CONCLUSION: CpG island methylation of FANCF gene promoter region is strongly associated with the susceptibility and clinicopathologic features of EOC. The FIGO staging and FANCF methylation are independent risk factors for EOC prognosis.

A clinical Comparison of Lobaplatin or Cisplatin with Mitomycine and Vincristine in Treating Patients with Cervical Squamous Carcinoma.

BACKGROUND: The research was to compare the efficacy and side effects of cisplatin or lobaplatin in combination with mitomycine (MMC) and vincristine in treating patients with cervical squamous carcinoma. MATERIALS AND METHODS: Cervical squamous carcinoma patients who were pathologically diagnosed with stage Ib-IIb from April 2012 to May 2013 in the general hospital of Chinese People's Libration Amy were enrolled. All patients were confirmed without prior treatment and were randomly divided into two groups, Group A and B. Efficacy and side effects were evaluated after one cycle of chemotherapy. RESULTS: Group A (n=42) were treated with Loubo® (Lobaplatin) 50mg/m2, MMC 16mg/m2 and Vincristine 2mg/m2 every 21 days. Group B (n=44) were treated with Cisplatin 100mg/m2, MMC 16mg/m2 and Vincristine 2mg/m2 every 21 days. All 86 patients completed one cycle of chemotherapy with cisplatin or lobaplatin in combination with MMC and vincristine. No difference was observed regardiing short-term effect between two groups. Main side effects were bone marrow suppression and gastrointestinal reactions including decrease of white blood cells, platelet and nausea/vomiting. Grade III-VI liver and kidney impairment was not reported in two groups. In group A the incidence of uterine artery spasm in the process of drug delivery was significantly lower than the group B. CONCLUSIONS: Cisplatin or lobaplatin with MMC and Vincristine in the interventional treatment of cervical squamous carcinoma were effective, especially after uterine artery perfusion chemotherapy at tumor reduction and tumor downstaging period. The adverse reactions of concurrent chemotherapy are tolerable, and low physical and mental pressure even more less stimulation of vascular in treatment with lobaplatin. However, the long-term effects of this treatment need further observation.

[Expressions of heat shock protein in cervical cancer and precancerosis].

AIM: To investigate the expressions of main subtypes of heat shock protein (HSP) in cervical cancer and precancerosis tissues. METHODS: According to the pathological diagnosis, 478 cases of cervical biopsy specimen were divided into invasive carcinoma of cervix group (63 cases), cervical intraepithelial neoplasia group (CIN, 106 cases), chronic cervicitis group (293 cases) and normal uterine cervix (16 cases).The expression levels of HSP70, HSP90a and HSP90beta3 mRNA were detected by quantitative RT-PCR with specific complex cRNA as internal control. RESULTS: (1) The expressions of HSP70, HSP90a and HSP90beta mRNA were significantly down-trended stepwise in invasive carcinoma of cervix, CIN, chronic cervicitis and normal cervix tissue (P < 0.01, respectively). (2) In the invasive carcinoma of cervix group, the expression level of HSP90beta mRNA was higher in advanced stage (FIGO II b) compared with incipient(FIGO-II a) carcinoma of the cervix (P < 0.05). (3) The expressions of HSP70 and HSP90 mRNA were each higher in poorly differentiated tumor than in well-differentiated tumor (P < 0.05, respectively). (4) The expression levels of all three HSP mRNA had no significant differences, it was observed with different histological types of cervical cancer (P > 0.05). CONCLUSION: Heat shock protein may play some important roles in malignant transformation of cervix cell and aggravation of cervix cancer. HSP70 and HSP90alpha may promote cancer cell transition and proliferation, and HSP90beta may participate in cell differentiation.

Changes in epidemiology and clinical characteristics of cervical cancer over the past 50 years.

OBJECTIVE: To evaluate the changes in the epidemiology and clinical characteristics of cervical cancer over the past 50 years, and explore appropriate treatment corresponding to these changes. METHODS: The clinical and pathological data of 1557 patients with invasive cervical cancer treated between January, 1955 and December, 2004 were retrospectively analyzed. RESULTS AND CONCLUSIONS: The average age of cervical cancer onset gradually decreased over the past 50 years, from 56.27+/-8.45 in 1955-1964 to 43.81+/-8.9 years in 1995-2004, whereas the ratio of young (< or =35 years old) patients rose from 3.42% to 24.91%. The ratio of early clinical stage (stages I-II) and non-squamous cancer also steadily increased (P<0.05, respectively). The tumor stage, pathological type and rate of lymph node metastasis were all significantly different among different age groups (P<0.05). In particular, the young (< or =35 years old) group had evidently higher ratios of non-squamous and advanced stage (III-IV) cancers with a higher rate of lymphatic metastasis in comparison with other age groups (P<0.01, respectively). Because of the changes in epidemiology and clinical characteristics of cervical cancer, it is necessary to modify the conventional treatment regimens and explore reasonable therapy corresponding to these changes. Preservation of reproductive endocrine function ought to be fully considered in cervical cancer treatment in women at childbearing age. Neoadjuvant intraarterial chemotherapy is an useful method for cervical cancer treatment at present.