Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

The previously known complexes {[}Ti\{(Me2CMe2C)(eta(5)-C5H4)(2)\}Cl-2] (1), {[}Ti\{Me2C(eta(5)-C5H4)(2)\}Cl-2] (2), {[}Ti \{Me2Si(eta(5)-C5H4)(2)\}Cl-2] (4), {[}Ti\{MePhSi(eta(5)-C5H4)(2)\}Cl-2] (5) and {[}Ti\{MePhSi(eta(5)-C5Me4)(2)\}Cl-2] (6) have been prepared following reported procedures. The novel complex {[}Ti\{MePhC(eta(5)-C5H4)(2)\}Cl-2] (3) has been prepared and characterized. The cytotoxic activity of 1-6 has been tested after 72 h on melanoma A375 and B16, prostate cancer DU145 and LNCaP and colon cancer HCT116, SW620 and CT26CL25 cell lines observing a high cytotoxic activity of complexes 1 and 6 compared to the reference compound ({[}Ti(eta(5)-C5H5)(2)\}Cl-2]). 1 and 6 have also been tested against primary normal mouse keratinocytes and lung fibroblasts. While viability of both type of primary cells was significantly less affected by 1 in comparison to the reference compound {[}Ti(eta(5)-C5H5)(2)Cl-2], compound 6 was completely nontoxic for nonmalignant cells, indicating a potential selectivity of this compound towards cancer cell lines. In addition CFSE staining, cell cycle analysis, AnnexinV-FITC/PI staining, detection of caspase activity and mitochondrial potential showed that 1 and 6 were acting through inhibition of proliferation and subsequent induction of mitochondrial dependent apoptosis in colon cancer cell lines, HCT116 and SW620, which express low sensitivity to cisplatin. Compound 6 was found to be the leading drug in this group since it shows the fastest and most selective anticancer profile. (C) 2013 Elsevier B.V. All rights reserved.Ministerio de Educacion y Ciencia, Spain {[}CTQ-2011-24346, CTQ-2012-30762]; Ministry of Science and Technological Development of the Republic of Serbia {[}173013]; Grant Agency of the Czech Republic {[}P207/12/2368

The politics of performance: transnationalism and its limits in former Yugoslav popular music, 1999–2004

This paper examines transnational relations between the Yugoslav successor states from the point of view of popular music, and demonstrates how transnational musical figures (such as Djordje Balaševi?, Mom?ilo Bajagi?-Bajaga and Ceca Ražnatovi?) are interpreted as symbolic reference points in national ethnopolitical discourse in the process of identity construction. Another symbolic function is served by Serbian turbofolk artists, who in Croatia serve as a cultural resource to distance oneself from a musical genre associated by many urban Croats with the ruralization (and Herzegovinization) of Croatian city space. In addition, value judgements associated with both Serbian and Croatian newly composed folk music provide an insight into the transnational negotiation of conflicting identities in the ex-Yugoslav context. Ultimately the paper shows how the ethnonational boundaries established by nationalizing ideologies created separate cultural spaces which themselves have been transnationalized after Yugoslavia's disintegration

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Modulatory in vitro effects of interleukin-1 receptor antagonist (IL-1Ra) or antisense oligonucleotide to interleukin-1 beta converting enzyme (ICE) on acute myeloid leukaemia (AML) cell growth

We investigated the effects of interleukin-1 receptor antagonist (IL-1Ra) on the spontaneous proliferation and AML colony forming unit (CFU-AML) formation of bone marrow and peripheral blood cells in 50 acute myeloid leukaemia (AML) patients. Exposure to IL-1Ra (10 mu g/ml) caused either decreased, unaltered or increased AML cell proliferation, as well as of CFU-AML colony formation, depending on the individual patient, but the inhibitory effects were dominant. To evaluate the involvement of IL-1 beta converting enzyme (ICE) in the autonomous AML cell growth, the effects of an antisense oligonucleotide on ICE were examined in 19 of these patients. In a majority of patients, antisense ICE suppressed both AML cell proliferation and CFU-AML although a stimulatory effect was sometimes evident. The proportion of AML patients with suppression obtained by antisense ICE was higher than with IL-1Ra, suggesting the involvement of additional ICE-dependent cytokine(s) in AML cell growth besides IL-1. The presence of IL-1Ra or antisense ICE also suppressed the endogenous IL-1 beta production of AML cells, at both the level of pro-IL-1 beta and mature IL-1 beta. Although inhibition by IL-1Ra or antisense ICE on growth parameters of AML cells in vitro prevailed, indicating the importance of IL-1 activity in autonomous AML cell growth, stimulatory effects on the cells of some patients suggest that AML is a heterogenous disorder regarding IL-1 beta regulation.nul

Modulatory in vitro effects of interleukin-1 receptor antagonist (IL-1Ra) or antisense oligonucleotide to interleukin-1 beta converting enzyme (ICE) on acute myeloid leukaemia (AML) cell growth

We investigated the effects of interleukin-1 receptor antagonist (IL-1Ra) on the spontaneous proliferation and AML colony forming unit (CFU-AML) formation of bone marrow and peripheral blood cells in 50 acute myeloid leukaemia (AML) patients. Exposure to IL-1Ra (10 mu g/ml) caused either decreased, unaltered or increased AML cell proliferation, as well as of CFU-AML colony formation, depending on the individual patient, but the inhibitory effects were dominant. To evaluate the involvement of IL-1 beta converting enzyme (ICE) in the autonomous AML cell growth, the effects of an antisense oligonucleotide on ICE were examined in 19 of these patients. In a majority of patients, antisense ICE suppressed both AML cell proliferation and CFU-AML although a stimulatory effect was sometimes evident. The proportion of AML patients with suppression obtained by antisense ICE was higher than with IL-1Ra, suggesting the involvement of additional ICE-dependent cytokine(s) in AML cell growth besides IL-1. The presence of IL-1Ra or antisense ICE also suppressed the endogenous IL-1 beta production of AML cells, at both the level of pro-IL-1 beta and mature IL-1 beta. Although inhibition by IL-1Ra or antisense ICE on growth parameters of AML cells in vitro prevailed, indicating the importance of IL-1 activity in autonomous AML cell growth, stimulatory effects on the cells of some patients suggest that AML is a heterogenous disorder regarding IL-1 beta regulation.nul

The analysis of impact of intensity of contact load and angular shaft speed on the heat generation within radial ball bearing

This paper considers the factors that influence the heat generation within ball bearing. Various lubrication regimes are taken into consideration and a mathematical model for determination of the coefficient of heat generation is set up. Due to the complexity of mathematical tools, and in order to perform better and easier analysis of the considered phenomenon, the application that integrates the mathematical models of load distribution and heat generation was developed. The impact of the contact load and angular shaft speed on the level of heat generated in radial ball bearing was analyzed

Expression and characterization of human interferon-beta I in the methylotrophic yeast Pichia pastoris

We describe the heterologous expression of a human interferon-beta1 in the methylotrophic yeast Pichia pastoris. Biologically active recombinant human interferon-beta1 (rHulFN-beta1) was secreted from shake-flask-grown P pastoris cells into the medium using the Saccharomyces cerevisiae alpha-mating factor prepro-leader sequence at the level of (1-3) x 10(5) i.u. (international units)/ml (6-12 mg/litre). An rHulFN-beta1 with an N-terminal sequence identical with that of native HulFN-beta1 was purified and the specific activity was determined (2-3 x 10(7) i.u./mg). It was found that the secreted recombinant protein was partially N-glycosylated

The inhibitory effect of human macrophage inflammatory protein-1 alpha (LD78) on acute myeloid leukemia cells in vitro

Macrophage inflammatory protein-la (MIP-1a) has recently been shown to inhibit proliferation of immature hemopoietic progenitors. In addition, significant inhibition of early and mature leukemic progenitors in acute myeloid leukemia (AML) has been obtained with MIP-1 alpha. We performed a study of 25 AML patients at diagnosis to evaluate the effect of a human homolog of MIP-1 alpha (LD78) on bone marrow (BM) and peripheral blood (PB) leukemic progenitors (colony-forming unit-AML [CFU-AML]) and AML cell proliferation. A methylcellulose culture system was used for CFU-AML and incorporation of H-3-TdR for AML cell proliferation, We found that LD78 inhibits CFU-AML colony formation up to 100% for the BM in 14/16 samples studied with the average maximal inhibition of 62.7 +/- 9.1% and up to 100% for the PB in 12/13 samples studied with the average maximal inhibition of 71.4 +/- 9.9%. In addition to this, LD78 inhibited AML cell proliferation up to 60% for the BM in 10/18 samples studied with the average maximal inhibition of 17.8 +/- 3.5%, and up to 87.1% for the PB cell proliferation in 10/16 samples studied with the average maximal inhibition of 27.5 +/- 6.8%, Our results have shown that LD78 is more active on AML progenitors than on AML cell proliferation, Inhibition of the AML cells, although less than that of the progenitors, indicates that more limited activity of LD78 on more mature leukemic cells is present in AML.nul

Galectin-3 deficiency confers resistance to cytokine-induced apoptosis of pancreatic islets - role of mitochondrial pathway

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Galectin-3 deficiency confers resistance to cytokine-induced apoptosis of pancreatic islets - role of mitochondrial pathway

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