ARTICLE | doi:10.20944/preprints201609.0107.v1
Online: 27 September 2016 (11:34:40 CEST)
Reducing the levels of toxic chemicals that cause adverse health and environmental impacts is a challenge for the international community. There is a need of a global strategy. Indeed, too often the problems associated to the exposure of chemical substances is recognized a posteriori, in the presence of consequences already observed. The prediction of the likely effects of chemical exposure on human health is based on classical tests with animals, which are time and money consuming, may deviate from an accurate prediction towards humans, and arises ethical concerns. Regulations are now considering the adoption of in silico (or computational) methods, which can be used for prioritizing substances according to the probability to be toxic for the biosphere. Several initiatives have prioritized chemicals, typically based according to some criteria, such as chemicals which may be endocrine disruptors, or persistent, bioaccumulative, or toxic (PBT). However, these initiatives focused on a certain range of adverse properties, and covered a certain number of substances only. We applied a set of largely validated and widely used predictive methods to large collections of chemicals: (i) to about 340,000 with a defined function, and (ii) to about 6 millions, which have been synthetized. The aim of this study is to quantify the putative impact of existing and future chemicals on towards human health, ecological and environment properties. The impact on the environment is the cause of major concern. This is the case of pesticides and hazardous, which is quite expected; however, also pharmacologically active candidate compounds of natural origin may have a high level of ecotoxicity. Pesticides and hazardous are also the categories of higher concern for humans, followed by pharmaceuticals. The pesticides and the hazardous are the categories of higher concern also on the environmental point of view. The results of our analysis could be the basis for the identification of new safety rules.
REVIEW | doi:10.20944/preprints202305.0816.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Sulphite; food additive; food toxicology.
Online: 11 May 2023 (08:05:15 CEST)
Sulphites are the most widely used food additives for their versatile applications in processing; perhaps we are negligence of its shortcomings. On account of various research studies, sulphites induce serious allergic reactions and other health alignments, but still regulatory agents permit its usage. Is it a wiser choice? The purpose of this paper is to clear up ambiguity and provide a clear view on why sulphites are employed in the food industry, why its usage is restricted, and why sulphite is a toxicant
ARTICLE | doi:10.20944/preprints202305.0255.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: forensic toxicology; khat; cathinone; cathine; postmortem
Online: 4 May 2023 (10:22:24 CEST)
Interpreting khat-related fatalities is challenging due to a lack of data on cathinone and cathine reference concentrations in postmortem tissues. This study investigated the autopsy findings and toxicological results of Khat-related fatalities in Saudi Arabia's Jazan region from January 1, 2018 to December 31, 2021. All confirmed cathine and cathinone results in postmortem blood, urine, brain, liver, kidney, and stomach samples were recorded and analyzed. Autopsy findings and the manner and cause of death of the deceased were assessed. Saudi Arabia's Forensic Medicine Center investigated 651 fatality cases over four years. Thirty postmortem samples were positive for khat's active constituents, cathinone and cathine. The percentage of khat-related fatalities was 3% in 2018 and 2019, and increased from 4% in 2020 to 9% in 2021, when compared to all fatal cases. They were all male ranging in age from 23 to 45. Firearm injuries (10 cases), hanging (7 cases), road traffic accident (2 cases), head injury (2 cases), stab wounds (2 cases), poisoning (2 cases), unknown (2 cases), ischemic heart disease (1 case), brain tumor (1 case), and choking (1 case) were responsible for deaths. 57% of postmortem samples tested positive for khat only, while 43% tested positive for khat with other drugs. Amphetamine is the drug most frequently involved. Cathinone and cathine average concentrations were 85 and 486 ng/mL in blood, 69 and 682 ng/mL in brain, 64 and 635 ng/mL in liver, and 43 and 758 ng/mL in kidney. The 10th–90th percentiles of blood concentrations of cathinone and cathine were 18 – 218 ng/mL and 222 – 843 ng/mL, respectively. These findings show that 90% of khat-related fatalities had cathinone concentrations greater than 18 ng/mL and cathine concentrations greater than 222 ng/mL. According to the cause of death, homicidal was most common in fatalities involving khat alone (77%). More research is required, especially toxicological and autopsy findings, to determine the involvement of khat in crimes and fatalities. This study may help forensic scientists and toxicologists investigate khat-related fatalities.
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: toxicology; microbiota; symbiosis; contaminants; resilience; environment
Online: 8 August 2020 (05:01:26 CEST)
Over the last 15 years, the advent of high-throughput ‘omics’ techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment. This microbiome revolution has radically changed our views of biology, evolution and individuality. Sitting at the interface between a host and its environment, the microbiome is a relevant yet understudied compartment for ecotoxicology research. Various recent works confirm that the microbiome reacts to and interacts with contaminants, with consequences for hosts and ecosystems. In this paper, we thus advocate for the development of a “microbiome-aware ecotoxicology” of organisms. We emphasize its relevance and discuss important conceptual and technical pitfalls associated with study design and interpretation. We identify topics such as functionality, quantification, temporality, resilience, interactions and prediction as major challenges and promising venues for microbiome research applied to ecotoxicology.
REVIEW | doi:10.20944/preprints201910.0034.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: microcystin; cyanobacteria; cyanotoxin; structural elucidation; toxicology
Online: 3 October 2019 (03:43:55 CEST)
Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical structure of the first MC was elucidated in the early 1980s and since then the number of reported structural analogues has grown steadily and continues to do so, thanks largely to advances in analytical methodology. The structures of some of these analogues have been definitively elucidated after chemical isolation using a combination of techniques including nuclear magnetic resonance, amino acid analysis and tandem mass spectrometry (MS/MS). Others have only been tentatively identified using liquid chromatography-MS/MS without chemical isolation. An understanding of the structural diversity of MCs, the genetic and environmental controls for this diversity and the impact of structure on toxicity are all essential to the ongoing study of MCs across several scientific disciplines. However, because of the diversity of MCs and the range of approaches that have been taken for characterizing them, comprehensive information on the state of knowledge in each of these areas can be challenging to gather. We have conducted an in-depth review of the literature surrounding the identification and toxicity of known MCs and present here a concise review of these topics. At present, at least 269 MCs have been reported. Among these, about 20% (54 of 269) appear to be the result of chemical or biochemical transformations of MCs that can occur in the environment or during sample handling and extraction of cyanobacterial, including oxidation products, methyl esters, or post-biosynthetic metabolites. The toxicity of many MCs has also been studied using a range of different approaches and a great deal of variability can be observed between reported toxicities, even for the same congener. This review will help clarify the current state of knowledge on the structural diversity of MCs as a class and the impacts of structure on toxicity, as well as to identify gaps in knowledge that should be addressed in future research.
REVIEW | doi:10.20944/preprints202008.0167.v1
Subject: Biology And Life Sciences, Toxicology Keywords: Organophosphate Pesticides, Pesticide Toxicology, Human Health, Environment
Online: 6 August 2020 (12:22:38 CEST)
Organophosphate pesticides (also known OPPs) have for many years been the choice candidate globally for pest control. OPPs have for over 80 years, been used in gardens, fields and greenhouses as crop protection agents, and even in homes as insecticides and mosquito abatement. Thus, year after year and with the repeated application of organophosphate agents, many problems have appeared as a result of excessive use of pesticides. The adverse effects of pesticides are well documented in human health, environment, pesticide residue in crops, soil and water contaminated by these pesticides. Therefore, it is necessary to shed more light on the risks associated with the irresponsible usage of organophosphate pesticides.
ARTICLE | doi:10.20944/preprints202006.0261.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: adverse outcome pathway; toxicity pathway; computational toxicology
Online: 21 June 2020 (11:10:34 CEST)
Background: Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. Objectives: To identify molecular mechanisms sensitive to chemical exposures in an unbiased manner. Methods: We used data on 641,516 unique chemical-gene interactions from the Comparative Toxicogenomic Database. Only data from high-throughput gene expression experiments with human, rat or mouse cells/tissues were extracted. The total number of chemical-gene interactions was calculated for every gene, and used as a measure of gene sensitivity to chemical exposures. These values were further used in enrichment analyses to identify molecular mechanisms sensitive to chemical exposures. Results: Remarkably, use of different input subsets with non-overlapping lists of chemical compounds identified largely the same genes and molecular pathways as most sensitive to chemical exposures, indicative of an unbiased nature of our analysis. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, our analysis identified a range of highly sensitive molecular pathways, which are not widely recognized by modern toxicology as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade and cytokine mediated signaling. Discussion: Molecular mechanisms identified as the most sensitive to chemical exposures are relevant for significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health system will likely benefit from future research focus on these sensitive molecular mechanisms. Additionally, approach used in this study may guide identification of priority adverse outcome pathways (AOP) for in-vitro and in-silico toxicity testing methods.
ARTICLE | doi:10.20944/preprints202303.0231.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Aluminum phosphide; Clinical Toxicology; Dihydroxyacetone; Pharmacotherapy; Phosphine; Suicide; Toxicity
Online: 13 March 2023 (10:37:23 CET)
Background: Aluminum phosphide (AlP), also known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture and acid. Phosphine is a robust mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning rather than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n =18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5% DHA solution w/v, i.v.) in addition to routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and time of hospitalization were evaluated in both DHA-treated (n = 58) and AlP-poisoned patients without DHA administration (n = 18). Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO2, and HCO3 levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.Interpretation: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning.Trial registration: IR.SUMS.REC.1394.102
ARTICLE | doi:10.20944/preprints201701.0100.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: toxin release; blue-green algae; tetracycline antibiotics; environmental toxicology
Online: 23 January 2017 (09:42:15 CET)
The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC10 and EC25 values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.
ARTICLE | doi:10.20944/preprints202205.0193.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Tolerana®; Pregnancy; Fetal-Maternal Recognition; Reproduction; Reproductive Safety Toxicology
Online: 13 May 2022 (15:14:42 CEST)
As recommended in the ICH Guidelines (S5-R2 and S6-R1), and based on bioethical concerns, we chose bovine embryos (BE) to check the in vitro embryo development considering the use of different amounts of rHGAL-1 as supplementations of in vitro embryo culture (IVP) mediums. Based on procedures for commercial BE in vitro production, using oocytes aspirated from slaughterhouse ovaries, the rHGAL-1 supplementation performed in two experiments (#01 on the oocyte maturation - IVM medium supplemented and experiment #2 on culture step IVC, supplemented SOF medium). There were IVP commercial procedures done, with 3 IVP batches per experiment and distributed the oocytes in four groups of treatment (one control group and three different dosages of rHGAL-1 to supplement both IVM and SOF mediums, using (2, 20 and 40µg.mL-1 respectively). A total of 962 (experiment 1) and 1,213 (experiment 2) oocytes were aspirated and submitted to IVP procedure. There was no damage to in vitro bovine embryos growth, considering cleavage percentage (%CLE), blastocysts development on day 7 (BlD7, BxD7, BhD7), or hatching blastocysts maturation on day 8 (BhD8%), regardless of rHGAL-1 supplementation. The immunohistochemistry assay with D8 embryos cultivated with rHGAL-1 supplementation on the culture medium (SOF medium) could demonstrate the presence of exogenous GAL-1, distributed in mass cell and trophoblastic cells, and the profile observed is dependent of exogenous supplementation and it was more evident in hatched embryos. The findings reassure the use of a reasonable amount of rHGAL-1 for in vitro embryonic development and make using rHGAL-1 in assisted reproduction in humans more reliable and safer.
ARTICLE | doi:10.20944/preprints202305.0332.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Ophthalmology; Toxicology Pharmacology and therapeutics; Drug interactions; Pharma-cology and therapeutics
Online: 5 May 2023 (08:56:37 CEST)
A clinical case of atypical endophthalmitis in an 82-year-old patient who underwent complicated cataract phacoemulsification. Clinical manifestations showed signs of a bacterial process, however, the treatment was not effective. Antifungal therapy had yielded positive results, despite the low probability of a fungal etiology of the process.
ARTICLE | doi:10.20944/preprints202303.0250.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Aedes aegypti; Musca domestica; house fly; toxicology; natural products; insecticide synergists
Online: 14 March 2023 (06:34:58 CET)
With widespread resistance to a limited number of insecticides available for medical and veterinary pests, new insecticides and insecticide synergists are desperately needed in this market space. We assessed the topical toxicity of carvone, menthone, and fenchone compared to permethrin and methomyl against the yellow fever mosquito, Aedes aegypti, and the house fly, Musca domestica. We also evaluated the synergistic potential of the monoterpenoids with permethrin and methomyl. Additionally, we assessed the acetylcholinesterase inhibitory potential of each monoterpenoid compared to methomyl. While all three monoterpenoids performed relatively poorly as topical insecticides (LD50 > 4000 ng/mg on M. domestica; > 6000 ng/mg on Ae. aegypti), they synergized both permethrin and methomyl as well as or better than piperonyl butoxide (PBO). Carvone and menthone yielded synergistic co-toxicity factors (23 and 29, respectively), which were each higher than PBO at 24 h. Acetylcholinesterase inhibition did not appear to explain the toxic or synergistic effects of the three monoterpenoids with IC50 values greater than 1 mM for all, compared to the 2.5 and 1.7 µM for methomyl on Aedes aegypti and Musca domestica, respectively. This study provides valuable monoterpenoid toxicity and synergism data on two pestiferous insects and highlights potential for these chemistries in future pest control formulations.
REVIEW | doi:10.20944/preprints202204.0277.v2
Subject: Environmental And Earth Sciences, Environmental Science Keywords: Agriculture; agri-food sector; analytical methods; Colombia; pesticides residues, toxicology effects
Online: 27 May 2022 (09:02:52 CEST)
The role that Colombia will play in terms of food supply in the coming years has generated a discussion on the agricultural practices implemented, specifically in the use of pesticides. Therefore, this article aims to provide a comprehensive and complete review of the status of pesticide use in the agricultural sector, highlighting the agri-food industry in Colombia. Currently, the use of pesticides has intensified throughout the world, generating a call for attention by governmental entities in terms of regulation. Colombia for the year 2019 presented a rate of use of 7.8 kg/ha of pesticides, placing it among the twenty countries with the highest rate. On the other hand, the quantities and economic benefits of exports and imports are growing steadily. Several organizations have focused their efforts on determining the health consequences that people exposed to chronic and/or acute intoxication may suffer. This has led to cases of cytogenetic, neurocognitive and physical effects, prompting governmental organizations to regulate the use of pesticides. Finally, the need to design pesticide management and handling systems that respond to the needs of producers and the sector, integrating international food safety guidelines, is identified.
ARTICLE | doi:10.20944/preprints202208.0504.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Amphetamine-related drugs; Forensic Toxicology; blood; UPLC-qTOF-MS; MMSPE; Validation; SWGTOX
Online: 30 August 2022 (04:09:57 CEST)
Abuse of amphetamine-related drugs (ARDs) causes traffic accidents, violence, and overdose. In forensic toxicology, analysis for ARDs in biological samples can help identify those driving or performing other tasks under the influence of drugs, clarify the cause of death, and identify recent drug users. In this study, we validated a pseudo-isocratic UPLC-qTOF-MS method following mixed mode cation exchange (MMSPE) extraction for analysis of ARDs in blood. The procedure requires 250 μL of blood to achieve a limit of quantification (LOQ) and detection (LOD) of 20 ng/mL for all analytes. In aged animal blood samples, extraction recoveries of 63-90% and matrix effects of 9-21% were observed. Precision and accuracy for all analytes were within 20% and 89–118%, respectively. The analytical method was developed and validated in accordance with the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard. It has acceptable accuracy and precision for use in doping control and forensic toxicology.
ARTICLE | doi:10.20944/preprints202309.0417.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: adenylosuccinic acid; Duchenne muscular dystrophy; myopathy; metabolic disease; skeletal muscle; toxicology; drug development
Online: 7 September 2023 (05:09:43 CEST)
Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.
ARTICLE | doi:10.20944/preprints202308.0052.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: COVID-19; therapeutic antibody; SARS-CoV-2 Delta; SARS-CoV-2 Omicron; toxicology
Online: 1 August 2023 (11:27:40 CEST)
We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.
REVIEW | doi:10.20944/preprints202304.1245.v1
Subject: Biology And Life Sciences, Toxicology Keywords: Fluorescence; Image Cytometry; Cytomics; Reactive Oxygen Species; Antioxidants; Oxydative Stress; In Vitro Toxicology
Online: 30 April 2023 (03:08:04 CEST)
Oxidative stress has been implicated in cellular senescence and aging, as well as in the onset and progression of many diverse genetic and acquired diseases and conditions. The search for biomarkers of oxidative stress has become relevant to many biomedical fields using many different methods and approaches. Fluorescence methodology is advantageous because of its simplicity and high sensitivity. Fluorescent probes are frequently used to investigate the role of reactive oxygen species in oxidative stress in experimental or clinical settings, often involving the use of flow cytometry and related single-cell based technologies. To assess the specific role of reactive oxygen species in oxidative stress studies by cytometric methodologies, it is essential to detect and characterize these species accurately. However, the detection and quantitation of individual intracellular ROS is still a challenge, but different and complementary strategies may focus on other endpoints of oxidative stress. In this review we present and discuss briefly the limitations and perspectives of such approaches. Based on our results, we also provide recommendations for proper design of cytometric studies of oxidative stress in order to prevent or minimize experimental errors..
ARTICLE | doi:10.20944/preprints201901.0062.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: small molecule; ligand; receptor; docking; molecular dynamics; DNA repair; inhibition; PCNA; ADME; toxicology
Online: 8 January 2019 (11:10:26 CET)
Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.
REVIEW | doi:10.20944/preprints202010.0086.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: antioxidant defenses; human health; environmental pollution; oxidative stress; epidemiology; perfluorinated substances; reactive oxygen species; toxicology
Online: 5 October 2020 (12:58:24 CEST)
Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.
ARTICLE | doi:10.20944/preprints202305.0269.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: forensic toxicology; amphetamine-related fatalities; brain; omega-3 fatty acids; docosahexaenoic acid; Comparative Toxicogenomic Database (CTD)
Online: 4 May 2023 (13:28:44 CEST)
Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/ml), medium (>0.5 to 1.5 g/ml), and high (>1.5 g/ml) based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid, docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predict an association between docosahexaenoic and arachidonic acids and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, supplement therapy may necessitate preventing omega-3 fatty acid deficiency.
ARTICLE | doi:10.20944/preprints202204.0107.v1
Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: atmospheric aerosol; chemical composition; secondary aerosol; source apportionment; ultrafine particles; oxidative potential; exposure; toxicology; forecasting; micrometeorology
Online: 12 April 2022 (09:54:57 CEST)
The RHAPS project was launched in 2019 with the major objective to identify specific properties of the fine atmospheric aerosol from combustion sources that are responsible for toxicological effects and can be used as new metrics for health-related outdoor pollution studies. In this paper, we present the overall methodology of RHAPS, and introduce the phenomenology and the first data observed. A comprehensive physico-chemical aerosol characterization has been achieved by means of high-time resolution measurements (e.g. number size distributions, refractory chemical components, elemental composition,) and low-time resolution analyses (e.g. oxidative potential, toxicological assays, chemical composition,…). Preliminary results show a high complexity in the relations observed, the link between air quality and toxicological endpoints being not obvious. We explore data from different points of view: source apportionment of PM1 and the role of source emissions on aerosol toxicity, the oxidative potential as a predictive variable for PM1 toxicity with focus on the secondary organic aerosol possessing redox-active capacity, exposure-response relationships for PM1, and air quality models to forecast PM1 toxicity. We provide a synthesis of results with the outlook to companion papers where data are analyzed in more detail.
ARTICLE | doi:10.20944/preprints202301.0415.v2
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Psychological Health; Drugs; Twitter; Machine Learning; Big Data; Drug Abuse; Toxicology; Social Factors; Economic Factors; Environmental Factors
Online: 27 February 2023 (13:31:40 CET)
Mental health issues can have significant impacts on individuals and communities and hence on social sustainability. There are several challenges facing mental health treatment, however, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring. This requires a holistic approach to understanding mental health issues that are missing from the existing research. Mental health should be understood in the context of social and environmental factors. More research and awareness are needed, as well as interventions to address root causes. The effectiveness and risks of medications should also be studied. This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters related to mental health from Twitter data. The parameters are discovered from three different perspectives, Drugs & Treatments, Causes & Effects, and Drug Abuse. We used Twitter to gather 1,048,575 tweets in Arabic about psychological health in Saudi Arabia. We built a big data machine learning software tool for this work. A total of 52 parameters were discovered for all three perspectives. We defined 6 macro-parameters (Diseases & Disorders, Individual Factors, Social & Economic Factors, Treatment Options, Treatment Limitations, and Drug Abuse) to aggregate related parameters. We provide a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse, as seen on Twitter, discussed by the public and health professionals. Moreover, we identify their associations with different drugs. The work will open new directions for social media-based identification of drug use and abuse for mental health, as well as other micro and macro factors related to mental health. The methodology can be extended to other diseases and provides a potential for discovering evidence for forensics toxicology from social and digital media.