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Toxics Oct 2021In agricultural activities, pest control is essential, and the most effective method is the use of chemical agents that also represent an important source of exposure to... (Review)
Review
In agricultural activities, pest control is essential, and the most effective method is the use of chemical agents that also represent an important source of exposure to potentially toxic compounds. Pesticides constitute a heterogeneous group of compounds designed specifically to control different pests. Besides measuring their levels or that of their metabolites in air, plasma, serum, blood, urine, etc., some studies reported increased DNA damage levels after occupational or environmental pesticides exposure, evidenced by several cytogenetic biomarkers such as chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei frequency (MN) together with other nuclear abnormalities (NA), alkaline comet assay, but also changes in oxidative stress parameters and miRNA levels. Single or combined, these techniques have also been used in genotoxic biomonitoring studies of workers occupationally exposed to pesticides in Mexico. Despite being a country with great agricultural activity and reported excessive pesticide use, genotoxic studies have been relatively few and, in some cases, contradictory. A review was made of the studies available (published until the end of 2020 on PubMed, Web of Science, Redalyc and Scielo, both in English and Spanish) in the scientific literature that evaluated occupational exposure of human samples to pesticides assessed with DNA damage and related biomarkers in Mexico.
PubMed: 34822663
DOI: 10.3390/toxics9110272 -
Particle and Fibre Toxicology Sep 2022The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union... (Review)
Review
The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.
Topics: DNA Damage; Databases, Factual; Metal Nanoparticles; Nanostructures; Reproducibility of Results
PubMed: 36104711
DOI: 10.1186/s12989-022-00499-2 -
Frontiers in Nutrition 2022Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given...
BACKGROUND
Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given the anti-inflammatory and antioxidant activities, supplementation with flavonoids that are abundant in the human diet has been suggested as a potential strategy to protect against nanomaterial-induced toxicities. However, the beneficial effects of flavonoids remain inconclusive. In the present study, we performed a meta-analysis to comprehensively explore the roles and mechanisms of flavonoids for animals intoxicated with nanomaterials.
METHODS
A systematic literature search in PubMed, EMBASE, and Cochrane Library databases was performed up to April 2022. STATA 15.0 software was used for meta-analyses.
RESULTS
A total of 26 studies were identified. The results showed that flavonoid supplementation could significantly increase the levels of antioxidative enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione-S-transferase), reduce the production of oxidative agents (malonaldehyde) and pro-inflammatory mediators (tumor necrosis factor-α, interleukin-6, IL-1β, C-reactive protein, immunoglobulin G, nitric oxide, vascular endothelial growth factor, and myeloperoxidase), and alleviate cell apoptosis (manifested by decreases in the mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2), DNA damage (reductions in tail length and tail DNA%), and nanomaterial-induced injuries of the liver (reduced alanine aminotransferase and aspartate aminotransferase activities), kidney (reduced urea, blood urea nitrogen, creatinine, and uric acid concentration), testis (increased testosterone, sperm motility, 17β-hydroxysteroid dehydrogenase type, and reduced sperm abnormalities), and brain (enhanced acetylcholinesterase activities). Most of the results were not changed by subgroup analyses.
CONCLUSION
Our findings suggest that appropriate supplementation of flavonoids may be effective to prevent the occupational detriments resulting from nanomaterial exposure.
PubMed: 35774549
DOI: 10.3389/fnut.2022.929343 -
Biochemical Society Transactions Jun 2021Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to...
Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Topics: Animals; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Hypoxia; Neoplasms; Protein Serine-Threonine Kinases; Signal Transduction; Unfolded Protein Response
PubMed: 34003246
DOI: 10.1042/BST20200861 -
Diagnostics (Basel, Switzerland) Aug 2020Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential... (Review)
Review
Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on OSMs in IBD, published between January 2000 and April 2020, was conducted. Out of 874 articles, 79 eligible studies were identified and used to prepare the interpretative synthesis. Antioxidants followed by lipid peroxidation markers were the most popular and markers of oxidative DNA damage the least popular. There was a disparity in the number of retrieved papers evaluating biomarkers in the adult and pediatric population ( = 6). Of the reviewed OSMs, a promising performance has been reported for serum total antioxidant status as a mucosal healing marker, mucosal 8-OHdG as a progression marker, and for multi-analyte panels of lipid peroxidation products assessed non-invasively in breath as diagnostic and differential markers in the pediatric population. Bilirubin, in turn, was the only validated marker. There is a desperate need for non-invasive biomarkers in IBD which, however, will not be met in the near future by oxidative stress markers as they are promising but mostly at the early research phase of discovery.
PubMed: 32824619
DOI: 10.3390/diagnostics10080601 -
Frontiers in Oncology 2023The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm...
OBJECTIVE
The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.
METHODS
After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.
RESULTS
Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I = 65%) and for those after non-PtCh (HR=0.87; I = 0%), the presence of DDRm did not show a significant association with longer OS.
CONCLUSION
1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.
PubMed: 37954082
DOI: 10.3389/fonc.2023.1267577 -
Journal of Personalized Medicine Dec 2021Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. (Review)
Review
UNLABELLED
Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated.
OBJECTIVES
The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors.
METHODS
Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle-Ottawa Scale for the randomized and non-randomized trials, respectively.
RESULTS
From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; = 0.003).
CONCLUSIONS
Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.
PubMed: 35055323
DOI: 10.3390/jpm12010008 -
BMJ Open Feb 2023To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out.
OBJECTIVE
To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out.
METHODS
We identified studies of occupational seroprevalence from a living systematic review (PROSPERO CRD42020183634). Electronic databases, grey literature and news media were searched for studies published during January-December 2020. Seroprevalence estimates and a free-text description of the occupation were extracted and classified according to the Standard Occupational Classification (SOC) 2010 system using a machine-learning algorithm. Due to heterogeneity, results were synthesised narratively.
RESULTS
We identified 196 studies including 591 940 participants from 38 countries. Most studies (n=162; 83%) were conducted locally versus regionally or nationally. Sample sizes were generally small (median=220 participants per occupation) and 135 studies (69%) were at a high risk of bias. One or more estimates were available for 21/23 major SOC occupation groups, but over half of the estimates identified (n=359/600) were for healthcare-related occupations. 'Personal Care and Service Occupations' (median 22% (IQR 9-28%); n=14) had the highest median seroprevalence.
CONCLUSIONS
Many seroprevalence studies covering a broad range of occupations were published in the first year of the pandemic. Results suggest considerable differences in seroprevalence between occupations, although few large, high-quality studies were done. Well-designed studies are required to improve our understanding of the occupational risk of SARS-CoV-2 and should be considered as an element of pandemic preparedness for future respiratory pathogens.
Topics: Humans; COVID-19; SARS-CoV-2; Seroepidemiologic Studies; Algorithms; Occupations
PubMed: 36854599
DOI: 10.1136/bmjopen-2022-063771 -
Acta Biochimica Polonica Jun 2023Vitamin D has anti-proliferative, anti-inflammatory, and apoptotic abilities. Vitamin D deficiency can induce deoxyribonucleic acid (DNA) damage. The aim of the study...
Vitamin D has anti-proliferative, anti-inflammatory, and apoptotic abilities. Vitamin D deficiency can induce deoxyribonucleic acid (DNA) damage. The aim of the study was to create a systematic review to analyze the relationship between vitamin D and DNA damage in various populations. PubMed, Scopus, EbscoHost, Google Scholar, and Epistemonikos were used to identify literature regarding the relationship between vitamin D and DNA damage. Assessment of study quality was carried out by three independent reviewers individually. A total of 25 studies were assessed as eligible and included in our study. Twelve studies were conducted in humans consisting of two studies with experimental design and ten studies with observational pattern. Meanwhile, thirteen studies were conducted in animals (in vivo). It is found that the majority of studies demonstrated that vitamin D prevents DNA damage and minimizes the impact of DNA damage that has occurred (p<0.05). However, two studies (8%) did not find such an association and one research only found a specific association in the cord blood, not in maternal blood. Vitamin D has a protective effect against DNA damage. A diet rich in vitamin D and vitamin D supplementation is recommended to prevent DNA damage.
Topics: Humans; Animals; Vitamin D; Vitamins; Vitamin D Deficiency; Inflammation; DNA; Dietary Supplements
PubMed: 37329504
DOI: 10.18388/abp.2020_6641 -
The Eurasian Journal of Medicine Oct 2020The use of some agents as radioprotectors has been evaluated for protection against normal tissue toxicity following exposure to ionizing radiation. Resveratrol, a... (Review)
Review
The use of some agents as radioprotectors has been evaluated for protection against normal tissue toxicity following exposure to ionizing radiation. Resveratrol, a natural flavonoid, with antioxidant and anti-inflammatory properties has attracted research interests for its radioprotective potential. This study systematically evaluates existing studies to examine the radioprotective effectiveness of resveratrol. A literature search of the electronic databases, including PubMed, Scopus, and Embase was conducted to retrieve articles investigating the protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. The search timeframe ranged from the inception of each database to January 2020. From an initial search of 231 articles, and after the removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 33 articles were finally included for this systematic review. Results showed promising protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. Furthermore, no adverse effect was observed after administering resveratrol. Resveratrol showed the potential to protect against ionizing radiation-induced damage to normal tissue cells via notable mechanisms, including anti-apoptotic and anti-inflammatory effects. However, further studies on the efficacy of clinical translation of resveratrol would open up more insights, while other gray areas such as the optimal radioprotective dosage of resveratrol requires further investigation. Overall, resveratrol is a potential double-edged sword in cancer therapy while protecting healthy tissues.
PubMed: 33209085
DOI: 10.5152/eurasianjmed.2020.20143