Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor

BACKGROUND: The tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, exogenous PTEN was able to suppress their ability to grow anchorage-independently, and thus reverted one of the typical characteristics of tumor cells. As these findings indicated that PTEN might be involved in the regulation of anchorage-dependent cell growth, we analyzed this aspect of PTEN function in non-tumor cells with an anchorage-dependent phenotype. RESULTS: We found that in response to the disruption of cell-matrix interactions, expression of endogenous PTEN was transcriptionally activated, and elevated levels of PTEN protein and activity were present in the cells. These events correlated with decreased phosphorylation of focal adhesion kinase, and occurred even in the absence of p53, a tumor suppressor protein and recently established stimulator of PTEN transcription. CONCLUSIONS: In view of PTEN's potent growth-inhibitory capacity, we conclude that its induction after cell-matrix disruptions contributes to the maintenance of the anchorage-dependent phenotype of normal cells

Polyploidy levels of Chinese large-flower chrysanthemum determined by flow cytometry

Flow cytometry was used to determine the ploidy level of 405 Chinese large-flower chrysanthemum (Chrysanthemum morifolium Ramat.) cultivars. Sixty-three cultivars are triploid, 175 cultivars tetraploid, 32 cultivars pentaploid, 46 cultivars hexaploid and 1 cultivar heptaploid. Forty-eight cultivars were then randomly selected for confirmation by chromosome-counting; the results are in agreement with the classification of ploidy level by flow cytometry. Most cultivars are aneuploid. The high percentage of tetraploid and triploid, instead of hexaploid in previous studies, represents the first evidence of low ploidy in large-flower chrysanthemum, which indicated a wider range of ploidy variation in this population. The results also offer further insights to the possible evolution and the regulation of flower size of this large-flower population. Additionally, the combination of flow cytometry and chromosome-counting is proved to be efficient and necessary for large-scale ploidy screening of chrysanthemum.Keywords: Chrysanthemum, ploidy level, flow cytometr

Profiling Plasma Peptides for the Identification of Potential Ageing Biomarkers in Chinese Han Adults

Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-MS analysis. The study identified 44 peptides which varied in concentration in different age groups. In particular, apolipoprotein A-I (ApoA1) concentration gradually increased between 18 to 50 years of age, the levels of fibrinogen alpha (FGA) decreased over the same age span, while albumin (ALB) was significantly degraded in middle-aged individuals. In addition, the plasma peptide profiles of FGA and four other unidentified proteins were found to be gender-dependent. Plasma proteins such as FGA, ALB and ApoA1 are significantly correlated with age in the Chinese Han population and could be employed as indicative ageingrelated biomarkers

Serum klotho as a novel biomarker for metabolic syndrome: findings from a large national cohort

BackgroundMetabolic syndrome is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular disease and mortality. The identification of novel biomarkers associated with mortality in patients with metabolic syndrome could facilitate early risk stratification and targeted interventions.MethodsWe conducted a large prospective cohort study using data from five cycles (2009-2016) of the National Health and Nutrition Examination Survey (NHANES) database, including a total of 40,439 participants. Logistic regression analysis was used to assess the association between serum klotho protein levels and metabolic syndrome, while Cox regression analysis was employed to examine the correlation between serum klotho levels and all-cause mortality. Mortality data were updated until December 31, 2019.ResultsAfter adjusting for demographic and socioeconomic confounders, the logistic regression model demonstrated that higher serum klotho levels were significantly associated with a decreased prevalence of metabolic syndrome (OR [95% CI] Highest vs. lowest quartile: 0.84 [0.70-0.99], P=0.038). In the Cox regression model, elevated klotho levels were found to significantly reduce the risk of all-cause mortality among individuals with metabolic syndrome (HR [95% CI] Highest vs. lowest quartile: 0.68 [0.51-0.90], P=0.006).ConclusionSerum klotho levels were found to be inversely associated with the prevalence of metabolic syndrome, independent of potential confounding factors such as demographics, socioeconomic status, and lifestyle factors. Furthermore, higher klotho levels strongly indicated a lower risk of all-cause mortality in individuals with metabolic syndrome

Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD

IntroductionEarly recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival. Patients with severe GvHD, however, had much slower iNKT cell reconstitution relative to conventional T cells.MethodsTo characterize the delay of iNKT cell reconstitution and explore its possible causes, we used a haploidentical bone marrow transplantation (haplo-BMT) mouse model with GvHD. We found the delayed recovery of thymic and peripheral iNKT cell numbers with markedly decreased thymic NKT1 subset in GvHD mice. The defective generation of thymic iNKT precursors with egress capability contributed to the reduced peripheral iNKT cells in GvHD mice. We further identified intermediate NK1.1- NKT1 precursor subpopulations under steady-state conditions and found that the differentiation of these subpopulations was impaired in the thymi of GvHD mice. Detailed characterization of iNKT precursors and thymic microenvironment showed a close association of elevated TCR/co-stimulatory signaling provided by double positive thymocytes and macrophages with defective down-regulation of proliferation, metabolism, and NKT2 signature in iNKT precursor cells. Correspondingly, NKT2 but not NKT1 differentiation was favored in GvHD mice.DiscussionThese data underline the important roles of TCR and co-stimulatory signaling in the differentiation of thymic iNKT subsets under transplantation conditions