Project description:Study of Oxidative stress Markers (F2 Isoprostanes for lipid peroxidation, Carbonyl groups for protein peroxidation, 3 Nitrotyrosine for damage by nitrogens, and 8-Hydroxyguanosine for RNA peroxidation)in patients with colorectal cancer undergo surgical treatment (preoperatively during the intervention and postoperatively) and controls.
Project description:We described, for the first time, a robust protocol for direct differentiation of hPSCs into SGEP by mimicking the activity of retinoic acid and WNT signaling. These hPSC-derived SGEP expressed SOX9, KRT5 and KRT19, which were the important progenitor markers of developing salivary glands. The CD24 and α-SMA positive cells that are capable to restore the function of injured salivary glands were also present in SGEP cultures. Importantly, RNA-seq was performed to examine the similarity of SGEP to human fetal and mature salivary glands. The result revealed the SGEP resemble the transcript profile of human fetal submandibular glands. Therefore, we successfully induced hPSCs into SGEP and demonstrated that these SGEP potentially serves as models for studying mechanism underling salivary development, and as cell sources for clinical use.
Project description:ObjectivesSaliva is a biological fluid suitable for biomarker analysis, and differences in the salivary microbiota in oral health and disease have been reported. For such comparative analyses, time of sampling is critical since the bacterial composition may vary throughout the day, i.e., diurnal variation. The purpose of this study is to compare the salivary microbiome over time to determine the optimal time for sampling.DesignStimulated saliva samples were collected from 5 orally healthy individuals in 4 h intervals for 24 h, and collection was repeated 7 days later (number of samples per person, n = 12, total number of samples, n = 60). Salivary microbiota was analyzed using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using the Kruskal-Wallis test with Benjamini-Hochberg's correction for multiple comparisons, cluster analysis, principal component analysis and correspondence analysis.ResultsFrom a total of 60 saliva samples, 477 probe targets were collectively identified with a mean number of probes per sample of 207 (range: 153-307). Little or no variation in microbial profiles within subjects was observed over time.ConclusionsAlthough there was considerable variation between subjects, microbial profiles within subjects were stable throughout a 24 hour period and after 1 week. Since there is little or no evidence of diurnal variation of the salivary microbiome, time of sampling of saliva is not critical for perturbation or other microbial studies.
Project description:Oxidative stress is a common factor threating genomic stability in almost all aerobic organisms. Using a yeast screening system, we measured the frequency of mitotic recombination was greatly elevated after H2O2 treatment. H2O2 was able to break chromatid directly in G1 synchronized cells and homologous recombination was induced to repair DNA double stand breaks at S/G2 phase. By whole genome SNP microarray and sequencing, the patterns of H2O2 induced loss of heterozygosity (LOH; gene conversion and crossover), chromosomal rearrangement, and aneuploidy changes were revealed. LOH events were the most common genomic alterations induced by H2O2 and were randomly distributed throughout the genome.
Project description:Ovarian cancer is the leading cause of death in gynecological diseases, and has been considered as one of the most fatal cancers due to lack of reliable detection strategy in the early stage. Therefore the capability to detect the morbidity initiation with an sensitive and effective approach is one of the most desirable goals for curing ovarian cancer. In this study, we used microarray technology for salivary mRNA biomarkers discovery, and evaluated the performance and translational utilities of discovered markers from a clinical study using an independent sample cohort . We used microarrays to profile and compare the gene expressions between ovairan cancer patient and matched controls, and identified seven down-regulated genes after the validation study. To find salivary transcriptomic biomarkers for ovarian cancer, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled using Affymetrix HG-U133-Plus-2.0 array, and followed by t-test and fold-change analyses. The biomarker candidates selected from the microarray results were subjected to clinical validation using an independent sample cohort by RT-qPCR. The prediction power of biomarkers was analyzed by logistic regression approach
Project description:Objective: To determine the oxidative stress during cycles of chemotherapy in patients after surgery for colorectal cancer, with or without oral zinc supplementation. Subjects: Twenty four adults from both genders participated in this study. All patients underwent stage II, III or IV colorectal cancer surgical resection and were starting chemotherapy in HCFMRP- USP. Patients were randomized into two groups. The first one (QTx-Zn Group, n=10) received 70 mg/d of zinc orally and the second one received placebo (QTx-Placebo Group, n=14) for 16 weeks. The study also included 30 healthy volunteers matched for age, gender and socioeconomic status, who received 70 mg/d of zinc supplement (Control-Zn Group, n=21) or placebo (Control-Placebo Group, n=9) for 16 weeks. Methods: The questionnaires about dietary intake (semiquantitative food frequency and food record), fatigue and quality of life (FACIT-F) and questionnaires that assess the side effects of chemotherapy (CTCAE) were evaluated. Anthropometry and bioelectrical impedance measurements were made. Blood collection was performed before the 1st, 2nd, 3rd and 4th cycles of chemotherapy (median duration of 21 days among cicles). Routine laboratory tests, vitamin E and markers anti and pro-oxidants (MDA, SOD, GPx and isoprostane) ere determined. The control group underwent the same procedures, except for chemotherapy. A longitudinal linear mixed effects model was adjusted for each of the variables of interest. The models were fitted using PROC MIXED of SAS version 9 (SAS, CARY, NC, USA). To analyze the association of categorical variables in the different items of the CTCAE, the investigators used the Fisher exact test. Results: The oral zinc supplementation was sufficient to increase plasma levels of zinc and did not alter food intake, body composition and routine laboratory evaluation of patients undergoing chemotherapy for colorectal cancer. Compared with QTx-Placebo Group, QTx-Zn Group showed lower prevalence of complaint on the salivary gland (17 vs. 75%). Fatigue (43 ± 6 vs. 36 ± 13) and quality of life (126 ± 160 vs. 116 ± 27) has become worst in the period between the 1st and 4th cycles of QTx in QTx-Placebo Group. When compared with QTx-Placebo Group, QTx-Zn Group had higher values of SOD before the 1st (2297 ± 503 vs. 1604 ± 352 USOD/g Hb), 2nd (2037 ± 515 vs. 1712 ± 417 USOD/g Hb) and 4th (2202 ± 323 vs. 1821 ± 360 USOD/g Hb) cycles of QTx. GPx values decreased in QTx-Zn Group before the 3rd cycle of QTx (48.5 ± 7.0 vs. 54.3 ± 2.3 mol NADPH/min/gHb). Conclusions: These data suggest that zinc supplementation reduces complaints related to the change in salivary gland, preserving the quality of life and preventing the worsening of fatigue. The increase in SOD can be attributed to zinc supplementation per se, whereas this mineral is a cofactor that endogenous antioxidant enzyme. The highest activity of SOD increases the production of H2O2, whose detoxification involves the participation of GPx, justifying its reduction. There were no changes in plasma levels of vitamin E, MDA and isoprostane during the study period. Considering the values of MDA and isoprostane, the data indicate that regardless of zinc supplementation, the lipid peroxidation of the cell membrane was unchanged during chemotherapy.