Modulation of Apoptosis in Colon Cancer Cells by Bioactive Compounds

A big challenge for a successful colon cancer treatment is the lack of eradication of the entire tumour cell population and consequent development of chemoresistance. Control of cell number from tissues and elimination of cells predisposed to malignant transformation, having an aberrant cell cycle or presenting DNA mutations, might be performed by a cellular ‘suicide’ mechanism — the programmed cell death, or apoptosis. Coordinated activation and execution of multiple subprograms are needed, added by a good knowledge of the basic components of the death machinery, besides their interaction to regulate apoptosis in a coordinated manner. Triggering apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. Many anti‐cancer drugs act during physiological pathways of apoptosis, leading to tumour cell destruction. New therapeutic approaches in cancer induce tumour cells to undergo apoptosis and break the cancer cell resistance to apoptosis commands. Administrations of natural compounds that prevent induction, inhibit or delay the progression of cancer, or induce inhibition or reversal of carcinogenesis at a premalignant stage represent chemoprevention strategies. Several natural compounds have been shown to be promising based on their anti‐cancer effects and low toxicity; alternative approaches might be taken into account to obtain a stronger anti‐tumour response when lower concentrations of anti‐cancer drugs are used, and to diminish the undesirable side‐effects

The O(N) linear sigma model at finite temperature beyond the Hartree approximation

We study the O(N) linear sigma model with spontaneous symmetry breaking, using a Hartree-like ansatz with a classical field and variational masses. We go beyond the Hartree approximation by including the two-loop contribution, the sunset diagram, using the 2PPI expansion. We have computed numerically the effective potential at finite temperature. We find a phase transition of second order, while it is first order in the Hartree approximation. We also discuss some implications of the fact that in this order, the decay of the sigma into two pions affects the thermal diagrams.Comment: 22 pages, 14 figures. v2: minor corrections, some more references. v3: added new set of data, new appendix. Submitted to Phys.Rev.

Nonequilibrium evolution in scalar O(N) models with spontaneous symmetry breaking

We consider the out-of-equilibrium evolution of a classical condensate field and its quantum fluctuations for a scalar O(N) model with spontaneously broken symmetry. In contrast to previous studies we do not consider the large N limit, but the case of finite N, including N=1, i.e., plain $\lambda \phi^ 4$ theory. The instabilities encountered in the one-loop approximation are prevented, as in the large-N limit, by back reaction of the fluctuations on themselves, or, equivalently, by including a resummation of bubble diagrams. For this resummation and its renormalization we use formulations developed recently based on the effective action formalism of Cornwall, Jackiw and Tomboulis. The formulation of renormalized equations for finite N derived here represents a useful tool for simulations with realistic models. Here we concentrate on the phase structure of such models. We observe the transition between the spontaneously broken and the symmetric phase at low and high energy densities, respectively. This shows that the typical structures expected in thermal equilibrium are encountered in nonequilibrium dynamics even at early times, i.e., before an efficient rescattering can lead to thermalization.Comment: 31 pages, 19 Figures, LaTeX; extended discussion on the basis of: fluctuations, eff. potential, correlations, analytic calculation of parametric resonance for "pion"_and_ "sigma" field

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Platelet indices in Philadelphia-negative chronic myeloproliferative neoplasms / Indicii plachetari de volum în neoplasmele mieloproliferative cronice Philadelphia-negative

Introducere: Neoplasmele mieloproliferative cronice cromozom Philadelphia negative (Ph-MPN) -policitemia vera (PV), trombocitemia esenţială (TE) şi mielofibroza primară (MP) - sunt caracterizate de o rată mare de complicaţii trombotice, parţial date de activarea trombocitară. Trombocitele mari sunt mai active, cu o funcţie procoagulantă crescută şi au rol patogenic demonstrat în tromboza arterială şi venoasă. În studiul nostru am încercat să stabilim dacă indicii trombocitari (MPV, PDW, P-LCR), furnizaţi de analizoarele de hematologie în hemoleucograma completă, sunt modificaţi la pacienţii diagnosticaţi cu Ph-MPN comparativ cu subiecţii sănătoşi. Material şi metodă: Hemoleucograma, ce a inclus şi indicii trombocitari, a fost determinată la 102 pacienţi Ph- MPN şi la 102 subiecţi sănătoşi cu ajutorul analizorului de hematologie Sysmex XS 1000i (metoda impedanţei), iar testele biochimice (glucoza şi parametrii metabolismului lipidic), pe analizorul Architect c8000. Prezenţa mutaţiei JAK2 V617F, la pacienţii cu Ph-MPN, a fost evidenţiată prin tehnica ARMS-PCR. Rezultate: Indicii de volum plachetari (IVP) măsuraţi prin metoda impedanţei, nu au fost semnificativ modificaţi la pacienţii cu Ph-MPN comparativ cu cei ai subiecţilor sănătoşi. Totuşi, am observat o moderată corelaţie între valoarea acestor indici şi prezenţa mutaţiei JAK2V617F, fără însă a se atinge o diferenţă semnificativă din punct de vedere statistic. IVP au fost crescuţi la micul subgrup de pacienţi trataţi cu anagrelide şi scăzuţi la cei trataţi cu simvastatin, comparativ cu pacienţii care nu au primit aceste terapii. Concluzii: Folosind metoda impedanţei în determinarea indicilor trombocitari, în studiul nostru nu am demonstrat o diferenţă semnificativă între valorile indicilor trombocitari la pacienţii cu Ph- MPN comparativ cu subiecţii sănătoşi. Sunt necesare studii ulterioare pentru a demonstra o posibilă corelaţie între indicii trombocitari şi mutaţia JAK2V617F, respectiv cu tratamentul cu anagrelide şi statine

The Influence of Periodontal Disease on Oral Health Quality of Life in Patients with Cardiovascular Disease: A Cross-Sectional Observational Single-Center Study

Background and Objectives: Cardiovascular disease is a leading cause of global death with a rising prevalence and a heavy economic burden. Periodontal disease has been associated with cardiovascular diseases—including incident coronary heart disease, peripheral artery disease and ischemic stroke. The study evaluates the quality of life of patients with cardiovascular and periodontal disease from the point of view of oral health by using the short version of the Oral Health Impact Profile (OHIP-14) questionnaire. Materials and Methods: This study included a total of 221 patients (61.86 ± 15.03 years old) selected from the Emergency Hospital of Sibiu, Romania. The participants self-completed the OHIP-14 questionnaire and they benefited from an oral health examination conducted to assess the presence and the severity of periodontal disease. Results: Out of the 147 patients with cardiovascular disease, 77.5% had periodontal disease (32.6% stage I, 29.2% stage II, and 15.6% stage III and IV). The presence of periodontal disease was associated with a lower oral-health-related quality of life (p p Conclusions: By increasing the patients’ awareness to oral healthcare measures, better outcomes and improved oral-health-related quality of life could be observed

Anticancer Activity of Some Ruthenium(III) Complexes with Quinolone Antibiotics: In Vitro Cytotoxicity, Cell Cycle Modulation, and Apoptosis-Inducing Properties in LoVo Colon Cancer Cell Line

Cisplatin is one of the most effective anticancer agents used to treat colon cancer, which is the third malignancy between the most common human cancers in the world, but the resistance developed represents an obstacle against the full success of chemotherapy. An emerging interest appeared in finding other metallic compounds, such as ruthenium(III) complexes, for chemotherapeutic application in cancer. Our study focused on the anticancer activity of several ruthenium (Ru) complexes with quinolone antibiotics in colon tumor cell cultures. Real-time cell analysis and drug-mediated cytotoxicity tests monitored the inhibitory effects in the drug-treated LoVo colon cancer cells. Flow cytometry assays were performed to evaluate cell cycle phases distribution and apoptotic events. The obtained results showed dose-dependent increased levels of cell lysis and induction of apoptosis in LoVo cancer cells treated with the Ru(III) complexes. In addition, data showed a major decrease in cell proliferation, since the percentages of cells distributed in the S cell cycle phase diminished, and a G0/G1 cell arrest was observed. Therefore, our results strongly suggest that the newly synthesized Ru(III) complexes might play an important role in future chemotherapeutic approaches, since their activity is based on diminishing cell proliferation, induction of apoptosis, and modulation of cell cycle phases

Synthesis and Anticancer Evaluation of New 1,3,4-Oxadiazole Derivatives

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of new 2,5-diaryl/heteroaryl-1,3,4-oxadiazoles were designed and synthesized. The structures of the new compounds were established using elemental analyses, IR and NMR spectral data. The compounds were evaluated for their anticancer potential on two standardized human cell lines, HT-29 (colon adenocarcinoma) and MDA-MB-231 (breast adenocarcinoma). Cytotoxicity was measured by MTS assay, while cell cycle arrest and apoptosis assays were conducted using a flow cytometer, the results showing that the cell line MDA-MB-231 is more sensitive to the compounds’ action. The results of the predictive studies using the PASS application and the structural similarity analysis indicated STAT3 and miR-21 as the most probable pharmacological targets for the new compounds. The promising effect of compound 3e, 2-[2-(phenylsulfanylmethyl)phenyl]-5-(4-pyridyl)-1,3,4-oxadiazole, especially on the MDA-MB-231 cell line motivates future studies to improve the anticancer profile and to reduce the toxicological risks. It is worth noting that 3e produced a low toxic effect in the D. magna 24 h assay and the predictive studies on rat acute toxicity suggest a low degree of toxic risks

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: Implications for transcatheter mitral valve implantation

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR). METHODS: We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes. RESULTS: Maximum (MA area 10.7\u2009\ub1\u20092.5 cm2 vs 11.6\u2009\ub1\u20092.7 cm2, p\u2009>\u20090.05) and the best fit plane MA area (9.9\u2009\ub1\u20092.3 cm2 vs 10.7\u2009\ub1\u20092.5 cm2, p\u2009>\u20090.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8\u2009\ub1\u20092.3 cm2 vs 10.8\u2009\ub1\u20092.7 cm2, p\u2009\u20090.05). CONCLUSIONS: Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis's selection