Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs

Trends in corrected lung cancer mortality rates in Brazil and regions

ABSTRACT OBJECTIVE: To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. METHODS: The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. RESULTS: Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. CONCLUSIONS: Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Emotional ratings and skin conductance response to visual, auditory and haptic stimuli

The human emotional reactions to stimuli delivered by different sensory modalities is a topic of interest for many disciplines, from Human-Computer-Interaction to cognitive sciences. Different databases of stimuli eliciting emotional reaction are available, tested on a high number of participants. Interestingly, stimuli within one database are always of the same type. In other words, to date, no data was obtained and compared from distinct types of emotion-eliciting stimuli from the same participant. This makes it difficult to use different databases within the same experiment, limiting the complexity of experiments investigating emotional reactions. Moreover, whereas the stimuli and the participants’ rating to the stimuli are available, physiological reactions of participants to the emotional stimuli are often recorded but not shared. Here, we test stimuli delivered either through a visual, auditory, or haptic modality in a within participant experimental design. We provide the results of our study in the form of a MATLAB structure including basic demographics on the participants, the participant’s self-assessment of his/her emotional state, and his/her physiological reactions (i.e., skin conductance)

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Zgamma Production in pbarp Collisions at sqrt(s)=1.8 TeV and Limits on Anomalous ZZgamma and Zgammagamma Couplings

We present a study of Z +gamma + X production in p-bar p collisions at sqrt{S}=1.8 TeV from 97 (87) pb^{-1} of data collected in the eegamma (mumugamma) decay channel with the D0 detector at Fermilab. The event yield and kinematic characteristics are consistent with the Standard Model predictions. We obtain limits on anomalous ZZgamma and Zgammagamma couplings for form factor scales Lambda = 500 GeV and Lambda = 750 GeV. Combining this analysis with our previous results yields 95% CL limits |h{Z}_{30}| < 0.36, |h{Z}_{40}| < 0.05, |h{gamma}_{30}| < 0.37, and |h{gamma}_{40}| < 0.05 for a form factor scale Lambda=750 GeV.Comment: 17 Pages including 2 Figures. Submitted to PR

A Measurement of the W Boson Mass

We report a measurement of the W boson mass based on an integrated luminosity of 82 pb$^{-1}$ from \ppbar collisions at $\sqrt{s}=1.8$ TeV recorded in 1994--1995 by the \Dzero detector at the Fermilab Tevatron. We identify W bosons by their decays to $e\nu$ and extract the mass by fitting the transverse mass spectrum from 28,323 W boson candidates. A sample of 3,563 dielectron events, mostly due to Z to ee decays, constrains models of W boson production and the detector. We measure \mw=80.44\pm0.10(stat)\pm0.07(syst)~GeV. By combining this measurement with our result from the 1992--1993 data set, we obtain \mw=80.43\pm0.11 GeV.Comment: 11 pages, 5 figure

Ultrasound Evidence of Early Fetal Growth Restriction after Maternal Malaria Infection

BACKGROUND: Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation. METHODOLOGY/PRINCIPAL FINDINGS: In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001-10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; -0.57 (1.13) versus -0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis. CONCLUSIONS/SIGNIFICANCE: Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom