Overexpression of microRNA-16 declines cellular growth, proliferation and induces apoptosis in human breast cancer cells

MicroRNAs (miRNA) are a large family of small single-stranded RNA molecules found in all multicellular organisms. Early studies have been shown that miRNA are involved in cancer development and progression, and this role can be done by working as an oncogenes and tumor suppressor genes, so manipulation of this molecules can be a promising approach in cancer therapy, and experimental results represented that the modification in breast cancer phenotype is possible by miRNA expression alteration. miR-16, which is located in 13q14 chromosome, plays critical roles as a tumor suppressor by targeting several oncogenes which regulate cell cycle and apoptosis. Hence, in the present study, we investigated whether miR-16 could decline growth and survival of MCF-7 cell line as model of human breast cancer. MCF-7 cell line was infected with lentiviruses containing miR-16 precursor sequence. The effects of ectopic expression of miR-16 on breast cancer phenotype were examined by cell cycle analysis and apoptosis assays. miR-16 cytotoxicity effect was measured by the MTT assay. We showed that the miR-16 overexpression reduces Cyclin D1 and BCL2 at messenger RNA (mRNA) and protein levels in MCF-7 cell line. In addition, this is found that enforced expression of miR-16 decreases cell growth and proliferation and induces apoptosis in MCF-7 cells. In conclusion, our results revealed that upregulation of miR-16 would be a potential approach for breast cancer therapy. © 2015, The Society for In Vitro Biology

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Robust decentralized voltage control for uncertain DC microgrids

A decentralized voltage control scheme to achieve robust stability and robust performance of islanded direct current (DC) microgrids is presented in this paper. The investigated microgrid consists of multiple distributed generation (DG) units with a general topology, each one comprising a local uncertain ZIP (constant impedance (Z), constant current (I), and constant power (P)) load. The proposed controller confers the following main advantages: 1) the design procedure is scalable, 2) it has a completely decentralized structure, 3) it prepares stability and desirable performance of the nominal closed-loop microgrid, 4) it preserves robust stability as well as robust performance of microgrid system under different sources of uncertainty, including plug-and-play (PnP) functionalities of DGs, microgrid topology changes, uncertain ZIP load, and unmodeled load dynamics, 5) every local controller is the solution of a unique convex optimization problem, resulting in the optimal performance and robustness to several different successive changes. First, a linear time-invariant (LTI) state-space model is developed for each DG subsystem with capturing disturbances, and different uncertainty sources are modeled as a new single polytope. Then, all control objectives are converted into a robust dynamic output-feedback-based controller for an LTI polytopic system with performance criterion. Finally, the obtained nonconvex problem is reduced to a linear matrix inequality (LMI) based optimization problem. Several simulation case studies are carried out in MATLAB to demonstrate the effectiveness of the proposed controller

Extending the application of a magnetic PEG three-part drug release device on a graphene substrate for the removal of Gram-positive and Gram-negative bacteria and cancerous and pathologic cells

M Ramezani Farani,1 P Khadive Parsi,1 Gh Riazi,2 M Shafiee Ardestani,3 H Saligeh Rad4,5 1School of Chemical Engineering, University College of Engineering, University of Tehran, Tehran 4563-11155, Iran; 2Institute of Biophysics and Biochemistry, University of Tehran, Tehran 1417614411, Iran; 3Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Quantitative Medical Imaging Systems Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran; 5Medical Physics and Biomedical Engineering Department, Tehran University of Medical Sciences, Tehran, Iran Objective: In this study, novel graphene oxide (GO)-based nanocomposites are presented. In fact, we have tried to replace the carboxyl groups on the surface of GO with amine groups to allow the biocompatible poly(ethylene glycol) bis(carboxymethyl) ether (average Mn 600) polymer to bond through an amide bond. Materials and methods: The synthesis was conducted accurately according to final characterization experiments (Raman, X-ray diffraction [XRD], atomic force microscopy [AFM], X-ray photoelectron spectroscopy [XPS], thermogravimetric analysis [TGA], etc). The antimicrobial property of this nanocomposite was examined in Escherichia coli (ATCC 25922) as Gram-negative and Staphylococcus aureus (ATCC 25923) as Gram-positive bacterial species. Besides, curcumin (CUR) was added to the produced nanocomposite both as a promising anticancer drug and an antioxidant, the toxicity of which was then assessed on cellular-based HepG2 and pC12. Results: An intense increase in toxicity was detected by MTT assay. Conclusion: It can mainly be concluded that the nanocomposite synthesized in this study is capable of delivering drugs with antibacterial properties. Keywords: graphene oxide, magnetic nanocomposite, drug delivery, antimicrobial, curcumi

Superplastic Behavior in High-Pressure Torsion-Processed Mo(7.5)Fe(55)Co(18)Cr(12.5)Ni(7)Medium-Entropy Alloy

In the present study, superplasticity of high-pressure torsion-processed non-equiatomic Mo(7.5)Co(18)Cr(12.5)Fe(55)Ni(7)medium-entropy alloy with nanograins was investigated. The superplastic elongation of 505 pct was achieved at a temperature of 800 degrees C and a low strain rate. The precipitation of the mu phase enriched with Mo hinders the grain boundary migration and also acts as the origin for cavity and crack formation.11Nsciescopu