Ukrain Affects Pancreas Cancer Cell Phenotype in vitro by Targeting MMP-9 and Intra-/Extracellular SPARC Expression

Background/Aims: We investigated whether the anticancer drug Ukrain (UK) is able to modulate the expression of some of the key markers of tumor progression in pancreatic cell carcinoma, in order to assess its potential therapeutic effect. Methods: Three cell lines (HPAF-II, PL45,HPAC) were treated with UK (5,10 and 20 μM) for 48 h, or left untreated. Secreted protein acidic and rich in cysteine (SPARC) mRNA levels were assessed by real-time PCR. Matrix metalloproteinases (MMP)-2 and -9 activity was analyzed by SDS zymography; SPARC protein levels in cell lysates and supernatants were determined by Western blot. Cell cycle was determined by flow cytometric analysis, and invasion by matrigel invasion assay. Results: UK down-regulated MMP-2 and MMP-9, suggesting that UK may decrease pancreatic cancer cell invasion, as confirmed by the matrigel invasion assay. SPARC protein down-regulation in supernatants points to an inhibition by UK of extracellular matrix remodeling in the tumor microenvironment. At the same time, SPARC mRNA and cellular protein level up-regulation suggests that UKcan affect cell proliferation by cell cycle inhibition, showing a cell cycle G2/M arrest in UK-treated cells. Conclusion: Our results suggest that UK modulates two major aspects involved in tumorigenesis of pancreatic cancer cells, such as extracellular matrix remodeling and cell proliferation.     

Use of confirmatory factor analysis for the identification of new components of the metabolic syndrome: the role of plasminogen activator inhibitor-1 and Haemoglobin A1c

BACKGROUND AND AIM: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers. METHODS AND RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome. CONCLUSIONS: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.     

Glycaemic,blood pressure and cholesterol control in 25 629 diabetics

Objective

To examine and compare the extent to which people with type 2 diabetes (T2DM) are achieving haemoglobin A_1c (HbA_1c), blood pressure (BP) and LDL cholesterol (LDL-C) treatment targets.

Methods

A review of databases (MEDLINE Ovid, Pubmed and Sabinet) was performed and limited to the following terms: type 2 diabetes mellitus AND guideline AND goal achievement for the years 2009 to 2014 (five years).

Results

A total of 14 studies (25 629 patients) were selected across 19 different countries. An HbA_1c level of 7.0% (or less) was achieved by 44.5% of subjects (range 19.2–70.5%), while 35.2% (range 7.4–66.3%) achieved BP of 130/80 mmHg (or less), and 51.4% (range 20.0–82.9%) had an LDL-C level of either 2.5 or 2.6 mmol/l (100 mg/dl or less).

Conclusion

Despite guideline recommendations that lowering of HbA_1c, BP and lipids to target levels in T2DM will lead to a reduction in morbidity and mortality rates, we found that control of these risk factors remains suboptimal, even across different settings.     

Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells

Recently, human multi-CSF was obtained by molecular cloning. In the present study, the effects of multi-CSF in vitro were investigated by comparative culture of whole bone marrow or progenitor cells obtained by sorting the cell fraction that binds the monoclonal antibody (MoAb) B13C5 (CD 34). Multi-CSF stimulated erythroid (BFU-E), multipotential (CFU-GEMM) and eosinophil (CFU-Eo) colonies in cultures of the progenitor cell enriched fraction, whereas (besides BFU-E, CFU-GEMM, and CFU-Eo) granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and macrophage (CFU-M) colony-forming cells also were stimulated by multi- CSF when unfractionated bone marrow was cultured. Reconstitution of the progenitor cell fraction (B13C5 positive) with the B13C5-negative population restored the broad spectrum of progenitor cell stimulation. This suggested that accessory cells are required for expression of the full spectrum of progenitor cell stimulation by multi-CSF. Subsequently, specific marrow cell populations, including T lymphocytes, granulocytic cells, and monocytes, were prepared by using selected MoAbs in complement-mediated lysis or cell sorting, added to cultures of hematopoietic progenitors and tested for accessory cell function. The results demonstrate that small numbers of monocytes permit the stimulation of CFU-G, CFU-GM, and CFU-M by multi-CSF. These monocyte-dependent stimulating effects on CFU-G, CFU-GM, and CFU-M could also be achieved by adding recombinant GM-CSF as a substitute for monocytes to the cultures. Therefore, multi-CSF most likely has direct stimulative effects on BFU-E, CFU-GEMM, and CFU-Eo and indirect effects on CFU-G, CFU-GM, and CFU-M in the presence of monocytes.     

Nutritional status of Palestinian preschoolers in the Gaza Strip: a cross-sectional study

Background  

The authors examined factors associated with nutritional resilience/vulnerability among preschoolers in the Gaza Strip in 2007, where political violence and deprivation are widespread.     

Accuracy of anthropometric measurements in estimating fat mass in individuals with 21-hydroxylase deficiency

ObjectiveThe use of anthropometric measurements to estimate the percentage of body fat (%BF) is easy and inexpensive. However, the accuracy of these methods in patients with 21-hydroxylase deficiency (21OHD) has not been explored. The objective of this study was to evaluate the accuracy of skinfold-based models, body mass index (BMI), and waist circumference (WC) in estimations of %BF using dual-energy X-ray absorptiometry (DXA) as the reference method in individuals with 21OHD.MethodsFifty-four 21OHD patients (32 women and 22 men), aged 7 to 20 y, were recruited for the study. DXA was used to determine %BF; four predictive skinfold equations, BMI, and WC were assessed for accuracy in determining %BF.ResultsAll predictive skinfold equations were highly associated (R, range: 0.82-0.89) with DXA %BF values. In women, BMI and WC showed moderate correlations (R = 0.69 for both BMI and WC) with DXA values. In contrast, among men there was a low explanatory power for BMI (13%) and WC (4%) and high errors (BMI, 6.9%; WC, 7.4%). All predictive equations significantly underestimated %BF (range of differences, ?4.1 to ?8.9) compared with DXA (women, 31.3 ± 6.1; men, 24.4 ± 7.3), and large limits of agreement were observed (range, ?15.3 to 1.7 and ?15.5 to 4.2 for women and men, respectively).ConclusionIn children and adolescents with 21OHD, %BF as estimated by skinfold measurements was associated more strongly with DXA-assessed %BF than both BMI and WC. However, still, the skinfold-based assessment underestimated DXA %BF and showed moderate agreement.