Air pollution is one of the world's leading mortality risk factors contributing to seven million deaths annually. COVID-19 pandemic has claimed about one million deaths in less than a year. However, ...it is unclear whether exposure to acute and chronic air pollution influences the COVID-19 epidemiologic curve.
We searched for relevant studies listed in six electronic databases between December 2019 and September 2020. We applied no language or publication status limits. Studies presented as original articles, studies that assessed risk, incidence, prevalence, or lethality of COVID-19 in relation with exposure to either short-term or long-term exposure to ambient air pollution were included. All patients regardless of age, sex and location diagnosed as having COVID-19 of any severity were taken into consideration. We synthesised results using harvest plots based on effect direction.
Included studies were cross-sectional (n = 10), retrospective cohorts (n = 9), ecological (n = 6 of which two were time-series) and hypothesis (n = 1). Of these studies, 52 and 48% assessed the effect of short-term and long-term pollutant exposure, respectively and one evaluated both. Pollutants mostly studied were PM
(64%), NO
(50%), PM
(43%) and O
(29%) for acute effects and PM
(85%), NO
(39%) and O
(23%) then PM
(15%) for chronic effects. Most assessed COVID-19 outcomes were incidence and mortality rate. Acutely, pollutants independently associated with COVID-19 incidence and mortality were first PM
then PM
, NO
and O
(only for incident cases). Chronically, similar relationships were found for PM
and NO
. High overall risk of bias judgments (86 and 39% in short-term and long-term exposure studies, respectively) was predominantly due to a failure to adjust aggregated data for important confounders, and to a lesser extent because of a lack of comparative analysis.
The body of evidence indicates that both acute and chronic exposure to air pollution can affect COVID-19 epidemiology. The evidence is unclear for acute exposure due to a higher level of bias in existing studies as compared to moderate evidence with chronic exposure. Public health interventions that help minimize anthropogenic pollutant source and socio-economic injustice/disparities may reduce the planetary threat posed by both COVID-19 and air pollution pandemics.
Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and ...even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics. This review presents current knowledge of human-relevant PMNP exposure doses, pathways, and toxic effects. It addresses difficulties in properly assessing plastic exposure and current knowledge gaps and proposes steps that can be taken to underpin health risk perception, assessment, and mitigation through rigorous science-based evidence. Based on the existing scientific data on PMNP adverse health effects, this review brings recommendations on the development of PMNP-specific adverse outcome pathways (AOPs) following the AOP Users’ Handbook of the Organisation for Economic Cooperation and Development (OECD).
The aim of this safety study in mice was to determine
toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery ...system. The single dose did not cause any lethal effect, and its acute oral LD
was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by
imaging with the IVIS
spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.
The aim of this study is the synthesis of a novel
99m
Tc-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was ...prepared and labeled with
99m
Tc. The radiochemical yield of approximately the
99m
Tc-labeled compound amounted to 97 ± 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate.
Background and Aims: Oleic acid (OLA) and conjugated linoleic acid (CLA) occur in dairy products and meats and are also widespread at lower levels in many other foodstuffs. It is known that OLA and ...CLA are very bioactive compounds with substantially anti-carcinogenic effects. The objective of this study was to evaluate the cytotoxic potentials of OLA and CLA which were tested against cancerous and non-cancerous cell lines and to determine their genotoxicity. Methods: The cytotoxic activities of OLA and CLA against to cancer cell lines (U-87-MG, A549, MCF-7, CaCo-2, HeLa and PC-3) and a control cell line (HEK293) were assessed by MTT assay. Ames MPFTM mutagenicity assay on 4 strains (TA98, TA100, TA 1535 and TA 1537) of Salmonella typhimurium was used for genotoxicity determination. Results: CLA showed cytotoxic activity on PC-3 cells, while OLA was created on A549 and PC-3 cell lines with the IC.sub.50 of 20 nM and 15 nM, respectively. No cytotoxic activity was observed on MCF-7, HeLa, U-87-MG, and CaCo-2 cells with the administered doses of OLA and CLA. It has been proved that OLA and CLA are characterized by a high cytotoxic activity towards cancer cells, as observed in the cell line test. There was no evidence for a mutagenic effect of OLA and CLA in the Ames test, with or without metabolic activation (S9) against Salmonella typhimurium strains. Conclusion: These in vitro test results indicate that these fatty acids can be considered a beneficial dietary supplement for enhancing anti-cancer therapy. Keywords: Fatty acid, Conjugated linoleic acid, Oleic acid, Cytotoxicity, Mutagenicity
The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not ...induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) Lys-p(HEMA), loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings.
Carboplatin (cis-diamine (1,1-cyclobutandicarboxylaso)‑platinum (II)) is a second-generation antineoplastic drug, which is widely used for chemotherapy of lung, colon, breast, cervix, testicular and ...digestive system cancers. Although preferred over cisplatin due to the lower incidence of nephrotoxicity and ototoxicity, efficient carboplatin delivery remains as a major challenge. In this study, carboplatin loaded alginate- poly(amidoamine) (PAMAM) hybrid nanoparticles (CAPs) with mean sizes of 192.13 ± 4.15 nm were synthesized using a microfluidic platform, then EGF was conjugated to the surface of CAPs (EGF-CAPs) for the receptor-targeted delivery. Hence, increased FITC+ cell counts were observed in A549 spheroids after EGF-CAP treatment compared to CAP in the 3D cellular uptake study. As such, the cytotoxicity of EGF-CAP was approximately 2-fold higher with an IC50 value of 35.89 ± 10.37 μg/mL compared to the CAPs in A549 spheroids. Based on in vivo experimental animal model, anti-tumor activities of the group treated with CAP decreased by 61 %, whereas the group treated with EGF-CAP completely recovered. Additionally, EGF-CAP application was shown to induce apoptotic cell death. Our study provided a new strategy for designing a hybrid nanoparticle for EGFR targeted carboplatin delivery with improved efficacy both in vitro and in vivo applications.
•Carboplatin loaded into alginate-PAMAM hybrid nanoparticles by microfluidic platform.•EGF conjugation increased the uptake of nanoparticles in both 2D/3D in vitro assays.•EGF-CAP inhibited A549 cell viability compared to Beas-2b at 72 h with a selective manner.•The fluorescence intensity in IVIS spectrum of EGF-CAP treated tumors was much lower.•EGF-CAP induced apoptotic cell death considering the highest TUNEL immunoreactivity.•The in vivo xenograft tumor of BALB/c mice treated with EGF-CAP completely recovered.
The aim of this study is the synthesis of a novel .sup.99mTc-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was ...prepared and labeled with .sup.99mTc. The radiochemical yield of approximately the .sup.99mTc-labeled compound amounted to 97 ± 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate.
Cellular macromolecules play important roles in cellular behaviors and biological processes. In the current work, cancer (KLN205), normal (MSFs) and mouse embryonic stem cells (mESCs) are compared ...using ATR-FTIR spectroscopy. Modifications in the composition, concentration, structure and function-related changes in the cellular components were deciphered using the infrared spectra. Our results revealed that cancer and embryonic stem cells are very similar but highly different from the normal cells based on the spectral variations in the protein, lipid, carbohydrate and nucleic acid components. The longest lipid acyl chains exist in mESCs, while cancer cells harbor the lowest lipid amount, short lipid acyl chains, a high content of branched fatty acids and thin cell membranes. The highest cellular growth rate and accelerated cell divisions were observed in the cancer cells. However, the normal cells harbor low nucleic acid and glycogen amounts but have a higher lipid composition. Any defect in the signaling pathways and/or biosynthesis of these cellular parameters during the embryonic-to-somatic cell transition may lead to physiological and molecular events that promote cancer initiation, progression and drug resistance. We conclude that an improved understanding of both similarities and differences in the cellular mechanisms among the cancer, normal and mESCs is crucial to develop a potential clinical relevance, and ATR-FITR can be successfully used as a novel approach to gain new insights into the stem cell and cancer research. We suggest that targeting the cellular metabolisms (glycogen and lipid) can provide new strategies for cancer treatment.
Cilj je ovoga istraživanja bio utvrditi in vivo toksičnost i raspodjelu jednokratne i višekratnih doza polimernih nanočestica L-glutaminske kiseline-g-p(HEMA) u funkciji isporuke lijekova. ...Jednokratna oralna doza nije prouzročila smrtnost, a akutni LD50 iznosio je >2,000 mg/kg tjelesne težine. Višekratne oralne dnevne doze od 25 mg, 50 mg i 100 mg/kg tjelesne težine, davane 28 dana, nisu dovele do značajnih razlika u ukupnoj tjelesnoj i relativnoj težini organa u usporedbi s kontrolnom skupinom. Ove rezultate potvrđuju biokemijski i histološki nalazi. Izloženost nanočesticama nije uzrokovala statistički značajne razlike u broju mikronukleusa u stanicama koštane srži miševa u odnosu na kontrolu. Raspodjela nanočestica u tijelu mijenjala se s vremenom, a nanočestice bi doprle u organe, pa i u koštanu srž, unutar prvih šest sati od primitka doze, što je utvrđeno ex vivo snimkama dobivenim pomoću sustava IVIS® Spectrum. Naši rezultati upućuju na to da su polimerne nanočestice L-glutaminske kiseline-g-p(HEMA) biokompatibilne i imaju potencijala za primjenu kao sustav isporuke lijekova.
PDF
