The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Extraction, bioactive function and application of wheat germ protein/peptides: A review.

The aging population and high incidence of age-related diseases are major global societal issues. Consuming bioactive substances as part of our diet is increasingly recognized as essential for ensuring a healthy life for older adults. Wheat germ protein has a reasonable peptide structure and amino acid ratio but has not been fully utilized and exploited, resulting in wasted wheat germ resources. This review summarizes reformational extraction methods of wheat germ protein/peptides (WGPs), of which different methods can be selected to obtain various WGPs. Interestingly, except for some bioactive activities found earlier, WGPs display potential anti-aging activity, with possible mechanisms including antioxidant, immunomodulatory and intestinal flora regulation. However, there are missing in vitro and in vivo bioactivity assessments of WGPs. WGPs possess physicochemical properties of good foamability, emulsification and water retention and are used as raw materials or additives to improve food quality. Based on the above, further studies designing methods to isolate particular types of WGPs, determining their nutritional and bioactive mechanisms and verifying their activity in vivo in humans are crucial for using WGPs to improve human health.

Spermiogenesis toxicity of imidacloprid in rats, possible role of CYP3A4.

This study evaluated the adverse effects of low-dose imidacloprid (IMI) on the characteristics of sperm from male Wistar rats. Thirty mature male rats were equally divided into three groups and orally administered vehicle (Control Group), acceptable daily intake (ADI) concentration of IMI (Group 1), and IMI at a dose 10-fold that of the ADI (Group 2) for 90 days. The findings revealed that IMI caused abnormalities in sperm concentrations and morphologies, accompanied by an imbalance of the gonadal hormone testosterone. Histopathological damage and decrease of testosterone levels were observed in testes from rats treated with IMI. However, estradiol and gonadotropin levels were unchanged after IMI treatment. IMI inhibited the activity of cytochrome P450 3A4 (CYP3A4) and left itself existed in the organism of rats. The indicators relating to sperms and CYP3A4 activity were recovered when rats were co-treated with IMI and CYP3A4 inducer rifampicin together. These results indicated that low-dose IMI exposure caused sperm abnormalities through affecting on the spermiogenesis in testis. Inhibition of CYP3A4 activity by IMI largely contributed to its sperm toxicity. Thus, IMI exposure at doses close to real-world settings resulted in sperm toxicity on rats, which might be a potential risk factor for human reproductive diseases.

Triazophos and its metabolite diethyl phosphate have different effects on endocrine hormones and gut health in rats.

Organophosphorus pesticide (OP) residues present in food can be metabolized into diethylphosphate (DEP) in vivo. Epidemiological studies of OPs have usually focused on these metabolites, while animal studies mainly assessed the OPs. Here, we compared the health risks of a frequently detected OP, triazophos (TAP), and its major metabolite, DEP, in rats. Levels of serum lipids and, sex hormones were measured using immunoassay kits. Gut hormones and inflammatory cytokines were assessed using a multiplexing kit, and the gut microbiota was evaluated by 16S rRNA gene sequencing. After a 24-week exposure period, both TAP and DEP significantly decreased serum levels of triglycerides, cholesterol, low-density lipoprotein cholesterol, and IL-6 (p < 0.05). However, DEP exposure had a stronger effect on serum estradiol (p < 0.05) than TAP, whereas only TAP inhibited the secretion of gut hormones. Both TAP and DEP enriched the pathogenic genera Oscillibacter, Peptococcus and Paraprevotella in the gut, and TAP also enriched enteritis-related genera Roseburia and Oscillibacter, which may affect the secretion of gut hormones. These findings indicate that the use of dialkyl phosphates as markers of OPs to examine the correlations of OP exposure with diseases may only provide partial information, especially for diseases related to gut health and the endocrine system.

Toxicities of Neonicotinoid-Containing Pesticide Mixtures on Nontarget Organisms.

Neonicotinoids are a widely used class of pesticides. Co-exposure to neonicotinoids and other classes of pesticides can exert potentiating or synergistic effects, and these mixtures have been detected in human bodily fluids. The present review summarizes studies into the effects of neonicotinoid-containing pesticide mixtures on humans and other nontarget organisms. Exposure to these mixtures has been reported to result in reproductive and hormonal toxicity, genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in vertebrates. Mortality of pollinators and toxicity in other organisms has also been reported. The underlying mechanism of pesticide mixture toxicity may be associated with impairment of cytochrome 450 enzymes, which are involved in metabolizing pesticides. However, a comprehensive explanation of the adverse effects of neonicotinoid-containing pesticide mixtures is still required so that effective prevention and control measures can be formulated. Environ Toxicol Chem 2020;39:1884-1893. © 2020 SETAC.

Assessment of the endocrine-disrupting effects of diethyl phosphate, a nonspecific metabolite of organophosphorus pesticides, by in vivo and in silico approaches.

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related enzymes/proteins, interfering with the production and signal regulation of thyroid hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

Assessment of the endocrine-disrupting effects of organophosphorus pesticide triazophos and its metabolites on endocrine hormones biosynthesis, transport and receptor binding in silico.

Triazophos (TAP) was a widely used organophosphorus insecticide in developing countries. TAP could produce specific metabolites triazophos-oxon (TAPO) and 1-phenyl-3-hydroxy-1,2,4-triazole (PHT) and non-specific metabolites diethylthiophosphate (DETP) and diethylphosphate (DEP). The objective of this study involved computational approaches to discover potential mechanisms of molecular interaction of TAP and its major metabolites with endocrine hormone-related proteins using molecular docking in silico. We found that TAP, TAPO and DEP showed high binding affinity with more proteins and enzymes than PHT and DETP. TAP might interfere with the endocrine function of the adrenal gland, and TAP might also bind strongly with glucocorticoid receptors and thyroid hormone receptors. TAPO might disrupt the normal binding of androgen receptor, estrogen receptor, progesterone receptor and adrenergic receptor to their natural hormone ligands. DEP might affect biosynthesis of steroid hormones and thyroid hormones. Meanwhile, DEP might disrupt the binding and transport of thyroid hormones in the blood and the normal binding of thyroid hormones to their receptors. These results suggested that TAP and DEP might have endocrine disrupting activities and were potential endocrine disrupting chemicals. Our results provided further reference for the comprehensive evaluation of toxicity of organophosphorus chemicals and their metabolites.

Organophosphorus pesticide triazophos: A new endocrine disruptor chemical of hypothalamus-pituitary-adrenal axis.

The organophosphorus pesticide, triazophos (TAP) was banned to use in agriculture in several countries due to its high toxicity. However, TAP was still widely used and frequently detected in foods. Recently, many studies reported the endocrine-disrupting effect of pesticides, especially the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis. In this study, adult male Wistar rats were exposed to TAP at the dose of 0.164 and 1.64 mg/kg bodyweight (~1/500th and 1/50th of LD50) for 24 weeks and serum contents of hormones were measured. TAP exposure significantly reduced serum contents of adrenocorticotropic hormone, corticosterone and epinephrine in rats (p < .05), leading to the delay in glucose homeostasis during the insulin tolerance test and decrease in serum contents of total cholesterol, triglyceride and low density lipoprotein. Molecular docking results suggested TAP may be an antagonist of glucocorticoid receptor which decreased significantly in the liver of rats, resulting in the decreased expression of 11ß-hydroxysteroid dehydrogenase 1 and PEPCK1. This study revealed that TAP is a potential endocrine disruptor, especially in the hypothalamus-pituitary-adrenal system and may disturb the metabolism by affecting glucocorticoid receptor. This study provided new evidence about the toxicity of TAP and it was necessary to strictly control the usage of TAP in food.

[Effects of Freezing and Thawing Treatments on Beef Protein Secondary Structure Analyzed with ATR-FTIR].

In order to further clarify the influence mechanism of different freezing temperature on meat quality in meat industry. The effects of freezing at -18, -23 and -38 ℃ on the stability of protein secondary structures of beef were studied. The attenuated total reflectance Fourier transfer infrared spectroscopy(ATR-FTIR)technique and automatic deconvolution, curve fitting and other calculation and analysis methods were used to analyze the changes of beef myofibrillar protein infrared spectra and secondary structures during -18, -23 and -38 ℃ freezing-thawing processes. ATR-FTIR results showed that the peak high and peak area of infrared spectra of beef myofibrillar protein in the freezing-thawing processes were changed, and the red shift or blue shift of wavenumbers occurred. The intensities of the absorption peak of 3 500~3 300 cm-1 in the infrared spectra of the frozen-thawed beef were reduced or even disappeared. This indicated that the intramolecular and intermolecular hydrogen bonding interactions, which formed by the bound water O­H group and the amino acid CO group, in thawed beef myofibrillar protein were broken. In other words, freezing can result in the destruction of beef myofibrillar protein secondary structures and protein advanced structures unfolded. Once the beef is thawed, the unfolded protein would reaggregation, and protein renaturation. Freezing could affect the stability of beef myofibrillar protein, the relative content of α-helix, ß-sheet, and ß-turn of beef myofibrillar protein were decreased, and the α-helix and ordered structures changed to the randon coil and disordered structures. After thawing, the increase of ß-sheet relative content of beef myofibrillar protein at -38 ℃ was greater than that of -23 and -18 ℃. The stability of -38 ℃ frozen beef myofibrillar protein was the best, and the protein renaturation was also the best after thawing. That is, the lower the freezing temperature, the lower the measure of freezing denaturation of beef myofibrillar protein, and the better the secondary structures stability of beef myofibrillar protein. The experimental study based on the actual production condition of the meat industry. And the effect of freezing temperatures on beef protein denaturation and the possible mechanism were revealed at the micro-aspect. It can be seen that the ATR-FTIR technology can reflect the changes of protein secondary structures in the process of freezing-thawing of beef, and reveal the regularity of beef protein denaturation, which can be used to identify and evaluate the quality of frozen meat. The experimental results provide a reference for the freezing preservation process and a method for the quality evaluation of meat.

Quantification of Forces During a Neurosurgical Procedure: A Pilot Study.

OBJECTIVE: Knowledge of tool-tissue interaction is mostly taught and learned in a qualitative manner because a means to quantify the technical aspects of neurosurgery is currently lacking. Neurosurgeons typically require years of hands-on experience, together with multiple initial trial and error, to master the optimal force needed during the performance of neurosurgical tasks. The aim of this pilot study was to develop a novel force-sensing bipolar forceps for neurosurgery and obtain preliminary data on specific tasks performed on cadaveric brains. METHODS: A novel force-sensing bipolar forceps capable of measuring coagulation and dissection forces was designed and developed by installing strain gauges along the length of the bipolar forceps prongs. The forceps was used in 3 cadaveric brain experiments and forces applied by an experienced neurosurgeon for 10 surgical tasks across the 3 experiments were quantified. RESULTS: Maximal peak (effective) forces of 1.35 N and 1.16 N were observed for dissection (opening) and coagulation (closing) tasks, respectively. More than 70% of forces applied during the neurosurgical tasks were less than 0.3 N. Mean peak forces ranged between 0.10 N and 0.41 N for coagulation of scalp vessels and pia-arachnoid, respectively, and varied from 0.16 N for dissection of small cortical vessel to 0.65 N for dissection of the optic chiasm. CONCLUSIONS: The force-sensing bipolar forceps were able to successfully measure and record real-time tool-tissue interaction throughout the 3 experiments. This pilot study serves as a first step toward quantification of tool-tissue interaction forces in neurosurgery for training and improvement of instrument handling skills.

Forces exerted during microneurosurgery: a cadaver study.

BACKGROUND: A prerequisite for the successful design and use of robots in neurosurgery is knowledge of the forces exerted by surgeons during neurosurgical procedures. The aim of the present cadaver study was to measure the surgical instrument forces exerted during microneurosurgery. METHODS: An experimental apparatus was set up consisting of a platform for human cadaver brains, a Leica microscope to provide illumination and magnification, and a Quanser 6 Degrees-Of-Freedom Telepresence System for tissue manipulation and force measurements. RESULTS: The measured forces varied significantly depending on the region of the brain (P = 0.016) and the maneuver performed (P < 0.0001). Moreover, blunt arachnoid dissection was associated with greater force exertion than sharp dissection (0.22 N vs. 0.03 N; P = 0.001). CONCLUSIONS: The forces necessary to manipulate brain tissue were surprisingly low and varied depending on the anatomical structure being manipulated, and the maneuver performed. Knowledge of such forces could well increase the safety of microsurgery.

Toward robot-assisted neurosurgical lasers.

Despite the potential increase in precision and accuracy, laser technology is not widely used in neurological surgery. This in part relates to challenges associated with the early introduction of lasers into neurosurgery. Considerable advances in laser technology have occurred, which together with robotic technology could create an ideal platform for neurosurgical application. In this study, a 980-nm contact diode laser was integrated with neuroArm. Preclinical evaluation involved partial hepatectomy, bilateral nephrectomy, splenectomy, and bilateral submandibular gland excision in a Sprague-Dawley rat model (n = 50). Total surgical time, blood loss as weight of surgical gauze before and after the procedure, and the incidence of thermal, vascular, or lethal injury were recorded and converted to an overall performance score. Thermal damage was evaluated in the liver using tissue samples stained with hematoxylin and eosin. Clinical studies involved step-wise integration of the 980-nm laser system into four neurosurgical cases. Results demonstrate the successful integration of contact laser technology into microsurgery, with and without robotic assistance. In preclinical studies, the laser improved microsurgical performance and reduced thermal damage, while neuroArm decreased intra- and intersurgeon variability. Clinical studies demonstrate dutility in meningioma resection (n = 4). Together, laser and robotic technology offered a more consistent, expedient, and precise tool for microsurgery.