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Zhongguo Ying Yong Sheng Li Xue Za Zhi... Dec 2023Silver nanoparticles (AgNPs) have garnered significant attention in recent years due to their unique properties and diverse applications across various industries. This... (Review)
Review
Silver nanoparticles (AgNPs) have garnered significant attention in recent years due to their unique properties and diverse applications across various industries. This review provides an overview of the synthesis methods, characterization techniques, applications, regulatory guidelines, and challenges associated with AgNPs. Green synthesis routes, utilizing natural extracts or biomolecules, have emerged as environmentally sustainable alternatives for producing AgNPs with reduced environmental impact. Characterization techniques such as spectroscopy, microscopy, and chromatography are employed to analyze the physicochemical properties of AgNPs and ensure their quality and stability. AgNPs find applications in biomedical, environmental, and consumer product sectors, including wound dressings, water purification filters, cosmetics, and medical devices, owing to their antimicrobial, catalytic, and optical properties. Regulatory guidelines play a crucial role in ensuring the safe and responsible use of AgNPs, addressing concerns related to biocompatibility, toxicity, and environmental impact. However, challenges remain in standardization, scalability, and long-term safety assessment of AgNP-based products. Future research efforts should focus on optimizing synthesis methods, enhancing characterization techniques, and addressing regulatory gaps to unlock the full potential of AgNPs while ensuring their safety and sustainability. Overall, AgNPs offer promising opportunities for addressing global challenges and driving technological innovation across diverse sectors.
Topics: Metal Nanoparticles; Silver; Green Chemistry Technology
PubMed: 38763765
DOI: 10.62958/j.cjap.2023.007 -
Food Research International (Ottawa,... Jul 2024The presence of contaminants in cacao-derived products, especially in chocolates, has raised concerns regarding food safety and human health. The study assessed the...
The presence of contaminants in cacao-derived products, especially in chocolates, has raised concerns regarding food safety and human health. The study assessed the concentration variation of 16 elements in 155 chocolate samples from the US market by cacao content and country of geographic origin. The study further examined the potential health risks posed by toxic metals and determined the contribution of essential elements to the Daily Recommended Intake (DRI), estimated based on an ounce (∼28.4 g) of daily chocolate consumption. Dark chocolates with ≥50 % cacao exhibited consecutively increasing mean levels from 1.2 to 391 µg/kg for U, Tl, Th, As, Pb, Se, Cd, and Co. Similarly, Ni, Sr, Cu, Mn, Zn, Fe, Ca, and Mg had mean concentrations from 4.0 to 1890 mg/kg. Dark chocolates sourced from Central and South America exhibited the highest mean levels of Cd, and South America samples also contained elevated Pb, whereas those from West Africa and Asia had low Cd and Pb, respectively. Cacao contents showed increasingly strong association with Cd, Co, Mn, Sr, Ni, Cu, Zn, and Mg (r = 0.60-0.84), and moderately with Se, Fe, As, and Tl (r = 0.35-0.49), indicating these elements are primarily derived from cacao beans. Weak association of cacao contents with Pb, Th, and U levels (r < 0.25), indicates post-harvest contaminations. Hazard Quotient (HQ) > 1 was found only for Cd in 4 dark chocolates, and Hazard Index (HI) > 1 for cumulative risk of Cd, Pb, Ni, As, and U was found in 33 dark chocolates, indicating potential non-carcinogenic risks for 15 kg children but none for 70 kg adults. Dark chocolate also substantially contributed to 47-95 % of the DRI of Cu for children and 50 % for adults. Dark chocolates also provided notable Fe, Mn, Mg, and Zn contributions to the DRI. These essential elements are recognized to reduce the bioavailability of toxic metals such as Cd, Pb, or Ni, thereby potentially lowering associated health risks. This study informs consumers, food industries, and regulatory agencies to target cacao origins or chocolate brands with lower toxic metal contents for food safety and minimizing adverse health effects.
Topics: Metals, Heavy; Risk Assessment; Chocolate; Humans; Cacao; Food Contamination; United States; Trace Elements; Recommended Dietary Allowances
PubMed: 38763644
DOI: 10.1016/j.foodres.2024.114360 -
European Journal of Pharmaceutical... May 2024Lung cancer is one of the most common cancers and a leading cause of death, with poor prognosis and high unmet clinical need. Chemotherapy is a common part of the...
Lung cancer is one of the most common cancers and a leading cause of death, with poor prognosis and high unmet clinical need. Chemotherapy is a common part of the treatment, either alone or in combination with other treatment modalities, but with limited efficacy and severe side effects. Encapsulation of drugs into nanoparticles can enable a more targeted delivery with reduced off-target toxicity. Delivery to the lungs is however often insufficient due to various biological barriers in the body and in the tumor microenvironment. Here we demonstrate that by incorporating drug-loaded nanoparticles into air-filled microbubbles, a more effective targeting to the lungs can be achieved. Fluorescence imaging and mass spectrometry revealed that the microbubbles could significantly improve accumulation of drug in the lungs of mice, compared to injecting either the free drug by itself or only the drug-loaded nanoparticles. Therapeutic efficacy was verified in a preclinical mouse model with non-small cell lung cancer, monitoring tumor growth by luminescence. In addition to increased accumulation of drug, the microbubbles were found to reduce tumor growth in the animals compared to treatment with drug alone.
PubMed: 38763448
DOI: 10.1016/j.ejps.2024.106804 -
Chemosphere May 2024Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research...
Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research into safer applications. Our investigation, drawing from 7,182 arsenic-containing molecules in the Cambridge Structural Database (CSD), outlines their diverse bonding patterns. Notably, 51% of these molecules exhibit cyclic connections, while 49% display acyclic ones. Arsenic forms eight distinct bonding types with other elements, with significant interactions observed, particularly with phenyl rings. Top interactions involve carbon, nitrogen, oxygen, fluorine, sulfur, and arsenic itself. We meticulously evaluated average bond lengths under three conditions: without an R-factor cut-off, with R-factor ≤ 0.075, and with R-factor ≤ 0.05, supporting the credibility of our results. Comparative analysis with existing literature data enriches our understanding of arsenic's bonding behaviour. Our findings illuminate the structural attributes, molecular coordination, geometry, and bond lengths of arsenic with diverse atoms, enriching our comprehension of arsenic chemistry. These revelations not only offer a pathway for crafting innovative and safer arsenic-based compounds but also foster the evolution of arsenic detoxification mechanisms, tackling pivotal health and environmental challenges linked to arsenic exposure across different contexts.
PubMed: 38763400
DOI: 10.1016/j.chemosphere.2024.142349 -
Environmental Research May 2024Polycyclic aromatic hydrocarbons (PAH) are persistent environmental pollutants, which occasionally appear as contaminants in consumer products. Upon dermal contact,...
Polycyclic aromatic hydrocarbons (PAH) are persistent environmental pollutants, which occasionally appear as contaminants in consumer products. Upon dermal contact, transfer of PAH into the stratum corneum (s.c.) and migration through the skin may occur, resulting in this class of highly toxic compounds to become bioavailable. In this study, dermal penetration through human and porcine skin of 24 PAH, comprising broad mass (152-302 g/mol) and octanol-water partition coefficient (logP: 3.9-7.3) ranges, was evaluated via Franz diffusion cell in vitro assays. More lipophilic and potentially more toxic PAH had decreased permeation rates through the rather lipophilic s.c. into the more hydrophilic viable (epi-)dermis. Furthermore, human skin was less permeable than pigskin, a commonly used surrogate frequently applied in skin penetration studies. In particular, the s.c. of human skin retains a greater share of PAH, an effect that is more pronounced for smaller PAH. Moreover, we compared the skin permeation kinetics of different PAH in pigskin. While small PAH (< 230 g/mol, logP < 6) permeate the skin quickly and are detected in the receptor fluid after 2 h, large PAH (> 252 g/mol, logP ≥ 6) do not fully permeate the skin up to 48 h. This indicates that highly lipophilic PAH do not become bioavailable as readily as their smaller congeners when transferred to the skin surface. Our data suggest that pigskin could be used as a surrogate for worst case scenario estimates of dermal PAH permeation through human skin.
PubMed: 38763278
DOI: 10.1016/j.envres.2024.119118 -
Lancet (London, England) May 2024Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for...
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.
BACKGROUND
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
METHODS
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
INTERPRETATION
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
FUNDING
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
PubMed: 38763154
DOI: 10.1016/S0140-6736(24)00548-8 -
Lancet (London, England) May 2024Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate...
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.
BACKGROUND
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
METHODS
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
INTERPRETATION
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
FUNDING
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
PubMed: 38763153
DOI: 10.1016/S0140-6736(24)00549-X -
Arquivos de Neuro-psiquiatria May 2024New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly... (Review)
Review
New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly influenced by a variety of stimuli, including pesticides exposure. These effects are particularly important because neurogenesis dysregulation could be associated with the decline of neuronal and cognitive functions and the possible development of neuropsychiatric disorders.
Topics: Pesticides; Humans; Hippocampus; Neurogenesis; Neurons; Animals
PubMed: 38763143
DOI: 10.1055/s-0044-1786853 -
Ecotoxicology and Environmental Safety May 2024Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs...
Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-β-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.
PubMed: 38763051
DOI: 10.1016/j.ecoenv.2024.116461 -
Bioorganic Chemistry May 2024A new class of compounds, namely highly substituted diaminocyclopentane-l-lysine adducts, have been discovered as potent inhibitors of O-GlcNAcase, an enzyme crucial for...
A new class of compounds, namely highly substituted diaminocyclopentane-l-lysine adducts, have been discovered as potent inhibitors of O-GlcNAcase, an enzyme crucial for protein de-O-glycosylation. These inhibitors exhibit exceptional selectivity and reversibility and are the first example of human O-GlcNAcase inhibitors that are structurally related to the transition state of the rate-limiting step with the "aglycon" still in bond-length proximity. The ease of their preparation, remarkable biological activities, stability, and non-toxicity make them promising candidates for the development of anti-tau-phosphorylation agents holding significant potential for the treatment of Alzheimer's disease.
PubMed: 38763001
DOI: 10.1016/j.bioorg.2024.107452