Enhanced radiosensitivity of LNCaP prostate cancer cell line by gold-photoactive nanoparticles modified with folic acid

Background: Conventional cancer treatment methods suffer from many limitations such as non-specificity in discrimination between healthy and malignant cells. The aim of this study was to investigate the role of polymeric gold-photoactive nanoparticles (PGPNPs) conjugated with folic acid (FA) as theranostic nanoparticles for active targeting, real-time fluorescence tracing and radiosensitivity inducition in LNCaP prostate cancer cells. Methods: The cellular uptake and cytotoxicity effect of gold nanoparticles (PGPNPs and PGPNPs-FA) after 2 and 24 h treatment were evaluated in in both cancer (LNCaP) and normal (HUVEC) cells using fluorescent microscopy, Induced coupled plasma optical emission spectrometry (ICP-OES) and Tetrazolium bromide dye (MTT), respectively. The therapeutic efficacy was analyzed on the LNCaP cells. For this purpose, LNCaP cells were treated by nanoparticles and ionizing radiation, and the synergistic effect of treatment methods were evaluated by colony formation assay (CFA) and Flow cytometry analysis. Results: The results of fluorescence imaging and ICP-OES data showed that the LNCaP cells absorbed PGPNP-FA nanoparticles more than PGPNP (P < 0.001). Also, the uptake of nanoparticles was significantly greater in cancer cells than in healthy ones (P < 0.01). MTT assay results indicated higher cytotoxic effect of nanoparticles conjugated with FA in folate-receptor overexpressing LNCaP cancer cells compared to HUVEC normal cells (P < 0.01). Furthermore, CFA and Flow cytometry results demonstrated that combinatorial therapy of polymeric gold nanoparticles with/without FA and ionizing radiation at various doses (2, 4 and 6 Gy) had a synergistic effect on survival fraction and induction of apoptotic and necrotizing cell death (P < 0.01). Conclusion: PGPNPs-FA nanoparticles led to higher and more specific uptake and accumulation of nanoparticles in LNCaP cells, thereby increasing the ability of gold nanoparticles as radio-sensitizer. © 2019 Elsevier B.V

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Enhanced Photogeneration of Reactive Oxygen Species and Targeted Photothermal Therapy of C6 Glioma Brain Cancer Cells by Folate-Conjugated Gold-Photoactive Polymer Nanoparticles

Tumor-selective photodynamic therapy is a successful method for ablation of malignant and cancerous cells. Herein, we introduce the design and preparation of functionalized acrylic copolymer nanoparticles with spiropyran (SP) and imidazole groups through a facile semicontinuous emulsion polymerization. Then, Au3+ ions were immobilized and reduced on their surface to obtain photoresponsive gold-decorated polymer nanoparticles (PGPNPs). The prepared PGPNPs were surface-modified with folic acid as a site-specific tumor cell targeting agent and improve intracellular uptake via endocytosis. Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy analyses, UV-vis spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy images were employed to characterize their spectral and morphological properties. Fluorescence microscopy images and inductively coupled plasma analysis demonstrated the cell line labeling capability and improved targeting efficiency of folate-conjugated PGPNPs (FA-PGPNPs) toward rat brain cancer cells (C6 glioma) with 71.8 cell uptake in comparison with 28.8 for the nonconjugated ones. Nonpolar SP groups are converted to zwitterionic merocyanine isomers under UV irradiation at 365 nm and their conjugation with Au nanoparticles exhibited enhanced photogeneration of reactive oxygen species (ROS). These were confirmed by intracellular ROS analysis and cytotoxicity evaluation on malignant C6 glioma cells. Owing to the strong surface plasmon resonance absorption of gold nanoparticles, FA-PGPNPs provided elevated local photothermal efficiency under near-IR irradiation at 808 nm. The prepared multifunctional FA-PGPNPs with a comprehensive integration of prospective materials introduced promising nanoprobes with targeting ability, enhanced tumor photodynamic therapy, cell tracking, and photothermal therapy. © 2018 American Chemical Society

Enhanced Photogeneration of Reactive Oxygen Species and Targeted Photothermal Therapy of C6 Glioma Brain Cancer Cells by Folate-Conjugated Gold-Photoactive Polymer Nanoparticles

Tumor-selective photodynamic therapy is a successful method for ablation of malignant and cancerous cells. Herein, we introduce the design and preparation of functionalized acrylic copolymer nanoparticles with spiropyran (SP) and imidazole groups through a facile semicontinuous emulsion polymerization. Then, Au3+ ions were immobilized and reduced on their surface to obtain photoresponsive gold-decorated polymer nanoparticles (PGPNPs). The prepared PGPNPs were surface-modified with folic acid as a site-specific tumor cell targeting agent and improve intracellular uptake via endocytosis. Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy analyses, UV-vis spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy images were employed to characterize their spectral and morphological properties. Fluorescence microscopy images and inductively coupled plasma analysis demonstrated the cell line labeling capability and improved targeting efficiency of folate-conjugated PGPNPs (FA-PGPNPs) toward rat brain cancer cells (C6 glioma) with 71.8 cell uptake in comparison with 28.8 for the nonconjugated ones. Nonpolar SP groups are converted to zwitterionic merocyanine isomers under UV irradiation at 365 nm and their conjugation with Au nanoparticles exhibited enhanced photogeneration of reactive oxygen species (ROS). These were confirmed by intracellular ROS analysis and cytotoxicity evaluation on malignant C6 glioma cells. Owing to the strong surface plasmon resonance absorption of gold nanoparticles, FA-PGPNPs provided elevated local photothermal efficiency under near-IR irradiation at 808 nm. The prepared multifunctional FA-PGPNPs with a comprehensive integration of prospective materials introduced promising nanoprobes with targeting ability, enhanced tumor photodynamic therapy, cell tracking, and photothermal therapy. © 2018 American Chemical Society

FRET-based acrylic nanoparticles with dual-color photoswitchable properties in DU145 human prostate cancer cell line labeling

Dual-color photoswitchable fluorescent polymer nanoparticles have emerged as an important type of cell detectors. Here, dual-color acrylic nanoparticles containing spiropyran and azo-carbazole derivatives with remarkable photostability and photoreversibility were employed. These prominent properties were attributed to the covalent bonding between the incorporated chromophores and the polymeric matrix and provided efficient fluorescence resonance energy transfer phenomenon. The obtained nanoparticles were purified after dialysis and delivered into DU145 cancer cells. Trypan blue dye exclusion assays showed that these nanoparticles were biocompatible with no toxicity to the cells. Fluorescence microscopy images demonstrated that the prostate cancer cells containing nanoparticles exhibited excellent cell uptake with green and red fluorescence emissions after primary excitation at 410 nm and subsequent irradiation at 365 nm, respectively, depicting their dual-color characteristics. © 2016 Elsevier Lt

Spiropyran-based photoswitchable acrylic nanofibers: A stimuli-responsive substrate for light controlled C6 glioma cells attachment/detachment

Reversible and remote cell manipulation with high spatiotemporal precision is now a highly attractive subject in various biological applications such as tissue engineering and cell-matrix interaction. Herein, photoresponsive poly(methyl methacrylate-co-hydroxy ethyl methacrylate-co-spiropyran ethyl acrylate) terpolymer (MHSP) was prepared using emulsion polymerization and the corresponding nanofibers (MHSP@NF) and film (MHSP@F) were prepared using electrospinning and drop-casting techniques, respectively. Structure of MHSP@NF with cylindrical cross-section and uniform diameter size of 169 nm were characterized by 1H-NMR and SEM analyses. Time-dependent UV�vis spectra of the prepared acrylic nanofibers and films demonstrated maximum forward photoisomerization after 3- and 8-min UV irradiation at 365 nm together with a 96° and 5° decrement in their surface water contact angles, respectively. High photoresponsivity of the nanofibers was attributed to their extensive surface area which exposes more spiropyran groups to UV light. MHSP@F and MHSP@NF with chemically-attached spiropyran groups demonstrated significant biocompatibility with negligible toxicity toward C6 glioma cancer cells up to 5 days. However, MH/SP@NF with doped SPOH exhibited a sudden decrease in cell viability relating to the migration and leakage of SPOH molecules. Photoreversible cell adhesion results showed a dramatic and switchable C6 cells attachment/detachment upon alternating UV and visible lights irradiations for MHSP@NF sample, while this was not observed for the similar film. These indicate potentiality of MHSP@NF as a promising substrate for dynamic switching of biomolecules and cell sheet engineering. © 2021 Elsevier B.V

Burden of transport-related injuries in the eastern mediterranean region: A systematic analysis for the global burden of disease study 2017

Background: Transport-related injuries (TIs) are a substantial public health concern for all regions of the world. The present study quantified the burden of TIs and deaths in the Eastern Mediterranean region (EMR) in 2017 by sex and age. Methods: TIs and deaths were estimated by age, sex, country, and year using Cause of Death Ensemble modelling (CODEm) and DisMod-MR 2.1. Disability-adjusted life years (DALYs), which quantify the total burden of years lost due to premature death or disability, were also estimated per 100000 population. All estimates were reported along with their corresponding 95% uncertainty intervals (UIs). Results: In 2017, there were 5.5 million (UI 4.9–6.2) transport-related incident cases in the EMR – a substantial increase from 1990 (2.8 million; UI 2.5–3.1). The age-standardized incidence rate for the EMR in 2017 was 787 (UI 705.5–876.2) per 100000, which has not changed significantly since 1990 (-0.9%; UI -4.7 to 3). These rates differed remarkably between countries, such that Oman (1303.9; UI 1167.3–1441.5) and Palestine (486.5; UI 434.5-545.9) had the highest and lowest age-standardized incidence rates per 100000, respectively. In 2017, there were 185.3 thousand (UI 170.8–200.6) transport-related fatalities in the EMR – a substantial increase since 1990 (140.4 thousand; UI 118.7–156.9). The age-standardized death rate for the EMR in 2017 was 29.5 (UI 27.1–31.9) per 100000, which was 30.5% lower than that found in 1990 (42.5; UI 36.8–47.3). In 2017, Somalia (54; UI 30–77.4) and Lebanon (7.1; UI 4.8–8.6) had the highest and lowest age-standardized death rates per 100,000, respectively. The age-standardised DALY rate for the EMR in 2017 was 1,528.8 (UI 1412.5–1651.3) per 100000, which was 34.4% lower than that found in 1990 (2,331.3; UI 1,993.1–2,589.9). In 2017, the highest DALY rate was found in Pakistan (3454121; UI 2297890- 4342908) and the lowest was found in Bahrain (8616; UI 7670-9751). Conclusion: The present study shows that while road traffic has become relatively safer (measured by deaths and DALYs per 100000 population), the number of transport-related fatalities in the EMR is growing and needs to be addressed urgently

MAPPING LOCAL PATTERNS OF CHILDHOOD OVERWEIGHT AND WASTING IN LOW- AND MIDDLE-INCOME COUNTRIES BETWEEN 2000 AND 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic