Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention

CYP1A1 is one of the main cytochrome P450 enzymes, examined extensively for its capacity to activate compounds with carcinogenic properties. Continuous exposure to inhalation chemicals and environmental carcinogens is thought to increase the level of CYP1A1 expression in extrahepatic tissues, through the aryl hydrocarbon receptor (AhR). Although the latter has long been recognized as a ligand-induced transcription factor, which is responsible for the xenobiotic activating pathway of several phase I and phase II metabolizing enzymes, recent evidence suggests that the AhR is involved in various cell signaling pathways critical to cell cycle regulation and normal homeostasis. Disregulation of these pathways is implicated in tumor progression. In addition, it is becoming increasingly evident that CYP1A1 plays an important role in the detoxication of environmental carcinogens, as well as in the metabolic activation of dietary compounds with cancer preventative activity. Ultimately the contribution of CYP1A1 to cancer progression or prevention may depend on the balance of procarcinogen activation/detoxication and dietary natural product extrahepatic metabolism

Orthodeoxia and platypnoea after acute organophosphorus poisoning reversed by CPAP: a newly described cause and review of the literature

AbstractThe case of a 60-year-old male patient, who survived severe organophosphorus poisoning, and subsequently developed platypnoea and orthodeoxia is described. The patient was mechanically ventilated for a long period of time in the intensive care unit. During the weaning trial, he developed platypnoea and orthodeoxia (PaO2 85 mmHg in recumbency, and 40 mmHg in upright position). Interestingly, the patient's orthodeoxia was alleviated on continuous positive airway pressure (CPAP) treatment. This is a newly described cause of the platypnoea-orthodeoxia syndrome. The possible pathophysiological mechanisms are discussed and a review of the reported abnormal states associated with this condition is presented

The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age

BACKGROUND: This paper assess the relationship between the quantity of three anti-seizure medications in hair and the color of the analyzed hair, while controlling for the effects of dose, dose duration, and patient age for 140 clinical patients undergoing anti-seizure therapy. Three drugs are assessed: carbamazepine (40 patients), valproic acid (40 patients), and phenytoin (60 patients). The relationship between hair assay results, hair color, dose, dose duration, and age is modeled using an analysis of covariance. The covariance model posits the hair assay results as the dependent variable, the hair color as the qualitative categorical independent variable, and dose, dose duration, and age as covariates. The null hypothesis assessed is that there is a no relationship between hair color and the quantity of analyte determined by hair assay such that darker colored hair will demonstrate higher concentrations of analyte than lighter colored hair. RESULTS: The analysis reveals that there is a significant relationship between dose and concentration for all hair color categories independent of the other covariates or the categorical independent variable. CONCLUSION: There does not appear to be any relationship between carbamazepine concentration and hair color. There is a weak relationship between hair color and valproic acid concentration, which the data suggest may be mediated by age. There is a significant, moderate relationship between phenytoin concentration and hair color such that darker colored hair has greater concentration values than lighter colored hair

Classification of cancer cell lines using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and statistical analysis

Over the past decade, matrix-assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF MS) has been established as a valuable platform for microbial identification, and it is also frequently applied in biology and clinical studies to identify new markers expressed in pathological conditions. The aim of the present study was to assess the potential of using this approach for the classification of cancer cell lines as a quantifiable method for the proteomic profiling of cellular organelles. Intact protein extracts isolated from different tumor cell lines (human and murine) were analyzed using MALDI‑TOF MS and the obtained mass lists were processed using principle component analysis (PCA) within Bruker Biotyper® software. Furthermore, reference spectra were created for each cell line and were used for classification. Based on the intact protein profiles, we were able to differentiate and classify six cancer cell lines: two murine melanoma (B16‑F0 and B164A5), one human melanoma (A375), two human breast carcinoma (MCF7 and MDA‑MB‑231) and one human liver carcinoma (HepG2). The cell lines were classified according to cancer type and the species they originated from, as well as by their metastatic potential, offering the possibility to differentiate non‑invasive from invasive cells. The obtained results pave the way for developing a broad‑based strategy for the identification and classification of cancer cell

Health risk assessment of environmental selenium: Emerging evidence and challenges (Review)

New data have been accumulated in the scientific literature in recent years which allow a more adequate risk assessment of selenium with reference to human health. This new evidence comes from environmental studies, carried out in populations characterized by abnormally high or low selenium intakes, and from high-quality and large randomized controlled trials with selenium recently carried out in the US and in other countries. These trials have consistently shown no beneficial effect on cancer and cardiovascular risk, and have yielded indications of unexpected toxic effects of selenium exposure. Overall, these studies indicate that the minimal amount of environmental selenium which is source of risk to human health is much lower than anticipated on the basis of older studies, since toxic effects were shown at levels of intake as low as around 260 µg/day for organic selenium and around 16 µg/day for inorganic selenium. Conversely, populations with average selenium intake of less than 13-19 µg/day appear to be at risk of a severe cardiomyopathy, Keshan disease. Overall, there is the need to reconsider the selenium standards for dietary intake, drinking water, outdoor and indoor air levels, taking into account the recently discovered adverse health effects of low-dose selenium overexposure, and carefully assessing the significance of selenium-induced proteomic changes

Toxicological effects of selenium nanoparticles in laboratory animals: A review

This paper provides a comprehensive summary of the main toxicological studies conducted on selenium nanoparticles (NPs) using laboratory animals, up until February 28, 2023. A literature search revealed 17 articles describing experimental studies conducted on warm-blooded animals. Despite some uncertainties, in vivo studies have demonstrated that selenium NPs have an adverse effect on laboratory animals, as evidenced by several indicators of general toxic action. These effects include reductions of body mass, changes in hepatotoxicity indices (increased enzyme activity and accumulation of selenium in the liver), and the possibility of impairment of fatty acid, protein, lipid, and carbohydrate metabolisms. However, no specific toxic action attributable solely to selenium has been identified. The LOAEL and NOAEL values are contradictory. The NOAEL was 0.22 mg/kg body weight per day for males and 0.33 mg/kg body weight per day for females, while the LOAEL was assumed to be a dose of 0.05 mg/kg of nanoselenium. This LOAEL value is much higher for rats than for humans. The relationship between the adverse effects of selenium NPs and exposure dose is controversial and presents a wide typological diversity. Further research is needed to clarify the absorption, metabolism, and long-term toxicity of selenium NPs, which is critical to improving the risk assessment of these compounds

Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka

AbstractMeasuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure

COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence

Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)–B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics

Towards effective COVID\u201119 vaccines: Updates, perspectives and challenges (Review)

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS\u2011COV\u20112, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID\u201119 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale