Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats.

Cisplatin (CIS) is a platinum-derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti-inflammatory properties, in cisplatin-induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), IL-6 and IL-10 were measured to determine inflammatory activity. In addition, 8-OHdG and caspase-3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF-α, IL-1ß and IL-6 obtained in CIS-treated groups increased as well as IL-10 decreased, thereby elevating the inflammatory response. In addition, 8-OHdG and caspase-3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity-induced apoptosis. This study shows that tangeretin has beneficial effects on CIS-induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti-inflammatory properties of tangeretin.

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

Monitoring of Organochlorine Pesticides (OCP) in Hair Samples of Wild Herbivorous Mammals Living in Remote and Protected Areas of the Far East and Siberia of Russia.

Monitoring wildlife exposure to biological hazards is a critical component of the wildlife risk assessment. In this study 38 hair samples were collected from 8 different species from ten districts of Russian Far East and Siberia and analysed for the presence of organochlorine pesticides (OCP). 50% of the samples were contaminated with - p, p'-DDT, α-HCH and DDD. DDT was the main contaminant found in 13 sample at concentrations range of 14.3 to 369.5 pg/mg hair, mean 91.9 ± 89.7 pg/mg. α-HCH was detected in three samples with the concentrations range 29.9-180.2 pg/mg. The p, p'-DDD was found only in one hair sample of Siberian roe deer from Altai region at 52.6 pg/mg. The exposure level is depended on animals habitat location. The most contaminated region is Terney district which is in the proximity to the borders with China and North Korea where OCP are still in use.

New method for risk assessment in environmental health: The paradigm of heavy metals in honey.

The release of heavy metals into the natural environment creates problems due to their persistence. They can accumulate in the food chain presenting a dangerous sign for ecosystems and human health. The metals in honey could be of agrochemical or industrial origin. Regular consumption of honey and bee products contaminated with various pollutants in high concentrations can cause serious health problems due accumulation of toxic substances in the body. In the current study, we aimed to determine the concentrations of chromium, cadmium, zinc, copper, lead and nickel in four types of honey (linden, acacia, rapeseed and polyfloral honey) and soil collected from three regions with different degrees of pollution. For the risk characterization, we used a new methodology that calculated the corrected estimated daily intake and the source hazard quotient for each metal and the adversity-specific hazard index. There was a strong influence of the degree of environmental pollution on the level of contaminants in the honey samples. In the case of a single chemical assessment, an HQ above 10 was obtained for Cd in linden, rapeseed and polyfloral honey from area 1 and an HQ above 1 was obtained for Cd in the other honey samples from the 3 areas, for Cu in all honey samples from all the 3 areas, for Pb in linden, rapeseed and polyfloral honey from area 1 and for Cr in linden honey for area 2. HIA calculated as a sum of all HQS of heavy metals in food reveals an increase and moderate risk for nephrotoxicity, bone demineralisation, cardiotoxicity, developmental toxicity, small decrease in body weight or body weight gain after consumption of honey impurified with heavy metals. A strict monitorization of heavy metals in honey samples from farmers should be done in order to protect the consumers.

Evaluation of perinatal exposure of glyphosate and its mixture with 2,4-D and dicamba οn liver redox status in Wistar rats.

Wide-scale emergence of glyphosate-resistant weeds has led to an increase in the simultaneous application of herbicide mixtures exacerbated by the introduction of crops tolerant to glyphosate plus dicamba or glyphosate plus 2,4-D. This raises serious concerns regarding the environmental and health risks resulting from increased exposure to a mixture of herbicide active ingredients. We evaluated hepatotoxic effects following perinatal exposure to glyphosate alone or in combination with 2,4-D and dicamba from gestational day-6 until adulthood in Wistar rats. Animals were administered with glyphosate at the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day) and no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day). A mixture of glyphosate with 2,4-D (0.3 mg/kg bw/day) and dicamba (0.02 mg/kg bw/day) with each at their EU ADI was evaluated. Redox status was determined by measuring levels of reduced glutathione, decomposition rate of Η2Ο2, glutathione reductase, glutathione peroxidase, total antioxidant capacity, thiobarbituric reactive substances, and protein carbonyls. Gene expression analysis of Nr1d1, Nr1d2, Clec2g, Ier3, and Gadd45g associated with oxidative damage to DNA, was also performed. Analysis of liver samples showed that exposure to the mixture of the three herbicides induced a marked increase in the concentration of glutathione and malondialdehyde indicative of a disturbance in redox balance. Nevertheless, the effect of increased lipid peroxidation was not discernible following a 3-month recuperation period where animals were withdrawn from pesticide exposure post-weaning. Interestingly, toxic effects caused by prenatal exposure to the glyphosate NOAEL were present after the same 3-month recovery period. No statistically significant changes in the expression of genes linked with genotoxicity were observed. Our findings reinforce the importance of assessing the combined effects of chemical pollutants at doses that are asserted by regulatory agencies to be safe individually.

Comprehensive study of health effects of plasma technology occupational environment: Exposure to high frequency and intensity noise and toxic gases.

OBJECTIVES: To evaluate on animal models the health effects of the combined or separate exposure to main chemical and physical hazards of plasma-based material processing technology environment. MATERIALS AND METHODS: Male Wistar rats were exposed to actual levels of hazardous factors in plasma technology occupational environment: i.e., ozone and nitrogen oxides (O3 and NOx) in respective concentrations of 0.5 mg/m3 and 1.0 mg/m3 and high-frequency (1000-1600 Hz) of 112 dB intensity noise for 3 h/day, 5 days/week for 12 weeks, with a recovery period of 1 month. RESULTS: Exposure to noise or its combination with chemical factors (ozone, nitrogen oxides) causes non-specific CNS changes testifying for significant excitation dominance, especially in the case of joint exposure. Histological examination of rats' brain in experimental revealed a pronounced increase in blood filling of small vessels on the tenth day of the experiment, with subsequent intensification of vascular alterations and eventually to cerebral edema. The exposure to noise significantly reduced total thymus, bone marrow and spleen cell numbers and these was also more pronounced under the joint impact of noise and toxic gases. Thymus, but not bone marrow or spleen, mitotic activity was as well reduced under the same modes of exposure. Cytological investigation of film preparations of subcutaneous connective tissue revealed that joint exposure led to microcirculatory disorders, increased number of dark mast cells and reduced degranulation processes indicative of increased autoregulatory processes effective at microvasculature level. CONCLUSIONS: High-frequency and intensity noise is main stressor factor that has negative impact on CNS and immune system, morphology and functioning of hematopoietic organs (spleen, bone marrow, thymus) and connective tissue. Its negative impact is significantly potentiated by concurrent exposure to ozone and nitrogen oxide, while exposure only to these toxic gases has no significant effect on the above targets.

Pesticides and tremor: An overview of association, mechanisms and confounders.

Pesticides are a heterogeneous class of chemicals mainly used for the protection of crops from pests. Because of their very widespread use, acute or/and chronic exposure to these chemicals can lead to a plethora of sequelae inflicting diseases, many of which involve the nervous system. Tremor has been associated with pesticide exposure in human and animal studies. This review is aimed at assessing the studies currently available on the association between the various types of pesticides/insecticides and tremor, while also accounting for potential confounding factors. To our knowledge, this is the first coherent review on the subject. After appraising the available evidence, we call for more intensive research on this topic, as well as intonate the need of implementing future preventive measures to protect the exposed populations and to reduce potential disabilities and social drawbacks.

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.

Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.

A mixture of 13 pesticides, contaminants, and food additives below individual NOAELs produces histopathological and organ weight changes in rats.

The current approach for the risk assessment of chemicals does not account for the complex human real-life exposure scenarios. Exposure to chemical mixtures in everyday life has raised scientific, regulatory, and societal concerns in recent years. Several studies aiming to identify the safety limits of chemical mixtures determined hazardous levels lower than those of separate chemicals. Following these observations, this study built on the standards set by the real-life risk simulation (RLRS) scenario and investigated the effect of long-term exposure (18 months) to a mixture of 13 chemicals (methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, butylparaben, bisphenol A and acacia gum) in adult rats. Animals were divided into four dosing groups [0xNOAEL (control), 0.0025xNOAEL (low dose-LD), 0.01xNOAEL (medium dose-MD) and 0.05xNOAEL (high dose-HD) (mg/kg BW/day)]. After 18 months of exposure, all animals were sacrificed, and their organs were harvested, weighed, and pathologically examined. While organ weight tended to be higher in males than in females, when sex and dose were taken into account, lungs and hearts from female rats had significantly greater weight than that of males. This discrepancy was more obvious in the LD group. Histopathology showed that long-term exposure to the chemical mixture selected for this study caused dose-dependent changes in all examined organs. The main organs that contribute to chemical biotransformation and clearance (liver, kidneys, and lungs) consistently presented histopathological changes following exposure to the chemical mixture. In conclusion, exposure to very low doses (below the NOAEL) of the tested mixture for 18 months induced histopathological lesions and cytotoxic effects in a dose and tissue-dependent manner.

US regulations to curb alleged cancer causes are ineffectual and compromised by scientific, constitutional and ethical violations.

The 1958 Delaney amendment to the Federal Food Drug and Cosmetics Act prohibited food additives causing cancer in animals by appropriate tests. Regulators responded by adopting chronic lifetime cancer tests in rodents, soon challenged as inappropriate, for they led to very inconsistent results depending on the subjective choice of animals, test design and conduct, and interpretive assumptions. Presently, decades of discussions and trials have come to conclude it is impossible to translate chronic animal data into verifiable prospects of cancer hazards and risks in humans. Such conclusion poses an existential crisis for official agencies in the US and abroad, which for some 65 years have used animal tests to justify massive regulations of alleged human cancer hazards, with aggregated costs of $trillions and without provable evidence of public health advantages. This article addresses suitable remedies for the US and potentially worldwide, by critically exploring the practices of regulatory agencies vis-á-vis essential criteria for validating scientific evidence. According to this analysis, regulations of alleged cancer hazards and risks have been and continue to be structured around arbitrary default assumptions at odds with basic scientific and legal tests of reliable evidence. Such practices raise a manifold ethical predicament for being incompatible with basic premises of the US Constitution, and with the ensuing public expectations of testable truth and transparency from government agencies. Potential remedies in the US include amendments to the US Administrative Procedures Act, preferably requiring agencies to justify regulations compliant with the Daubert opinion of the Daubert ruling of the US Supreme Court, which codifies the criteria defining reliable scientific evidence. International reverberations are bound to follow what remedial actions may be taken in the US, the origin of current world regulatory procedures to control alleged cancer causing agents.

Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo.

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

DNA Damage Estimation after Chronic and Combined Exposure to Endocrine Disruptors: An In Vivo Real-Life Risk Simulation Approach.

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26-13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50-45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend.

Rapamycin-induced autophagy in osteosarcoma cells is mediated via the biglycan/Wnt/ß-catenin signaling axis.

Biglycan is a class I secreted small leucine-rich proteoglycan (SLRP), which regulates signaling pathways connected to bone pathologies. Autophagy is a vital catabolic process with a dual role in cancer progression. Here, we show that biglycan inhibits autophagy in two osteosarcoma cell lines (P ≤ 0.001), while rapamycin-induced autophagy decreases biglycan expression in MG63 osteosarcoma cells and abrogates the biglycan-induced cell growth increase (P ≤ 0.001). Rapamycin also inhibits ß-catenin translocation to the nucleus, inhibiting the Wnt pathway (P ≤ 0.001) and reducing biglycan's colocalization with the Wnt coreceptor LRP6 (P ≤ 0.05). Furthermore, biglycan exhibits protective effects against the chemotherapeutic drug doxorubicin in MG63 OS cells through an autophagy-dependent manner (P ≤ 0.05). Cotreatment of these cells with rapamycin and doxorubicin enhances cells response to doxorubicin by decreasing biglycan (P ≤ 0.001) and ß-catenin (P ≤ 0.05) expression. Biglycan deficiency leads to increased caspase-3 activation (P ≤ 0.05), suggesting increased apoptosis of biglycan-deficient cells treated with doxorubicin. Computational models of LRP6 and biglycan complexes suggest that biglycan changes the receptor's ability to interact with other signaling molecules by affecting the interdomain bending angles in the receptor structure. Biglycan binding to LRP6 activates the Wnt pathway and ß-catenin nuclear translocation by disrupting ß-catenin degradation complex (P ≤ 0.01 and P ≤ 0.05). Interestingly, this mechanism is not followed in moderately differentiated, biglycan-nonexpressing U-2OS OS cells. To sum up, biglycan exhibits protective effects against the doxorubicin in MG63 OS cells by activating the Wnt signaling pathway and inhibiting autophagy.

Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems.

This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.

Dysregulation of mitochondrial sirtuin genes is associated with human male infertility.

Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) are post-translational modifiers that regulate energy production, body homeostasis and mitochondrial activities via different substrates in response to environmental stressors. The present study aimed at assessing the expression of SIRT3, SIRT4, and SIRT5 in the semen of infertile men. Expression analysis was performed using q-RT PCR. All mitochondrial sirtuin genes were significantly down-regulated in the semen of infertile men compared to fertile men. Mitochondrial sirtuin genes expression levels were correlated with mitochondrial HSP90 expression. HSP90 expression was positively correlated with SIRT3, SIRT4 and SIRT5 expression in the semen of fertile men, while a negative correlation was observed between HSP90 in the semen of infertile men and mitochondrial sirtuin genes in the semen of fertile men. These data suggest that dysregulation of mitochondrial sirtuin genes causes mitochondrial dysfunction due to stress, which appears to be associated with human male infertility by compromising functional and structural sperm integrity.

Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing.

Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.

In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model.

An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid-namely, p(VP-AA)-OD6000 (p(VP-AA))-was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells' viability at the higher concentrations of 0.033 and 0.066 mg/mL (p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized (p = NS) did not affect individual adhesion molecules' expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.

Back to basics in COVID-19: Antigens and antibodies-Completing the puzzle.

The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia.

An integrated approach for assessing the in vitro and in vivo redox-related effects of nanomaterials.

Over the last few decades, nanotechnology has risen to the forefront of both the research and industrial interest, resulting in the manufacture and utilization of various nanomaterials, as well as in their integration into a wide range of fields. However, the consequent elevated exposure to such materials raises serious concerns regarding their effects on human health and safety. Existing scientific data indicate that the induction of oxidative stress, through the excessive generation of Reactive Oxygen Species (ROS), might be the principal mechanism of exerting their toxicity. Meanwhile, a number of nanomaterials exhibit antioxidant properties, either intrinsic or resulting from their functionalization with conventional antioxidants. Considering that their redox properties are implicated in the manifestation of their biological effects, we propose an integrated approach for the assessment of the redox-related activities of nanomaterials at three biological levels (in vitro-cell free systems, cell cultures, in vivo). Towards this direction, a battery of translational biomarkers is recommended, and a series of reliable protocols are presented in detail. The aim of the present approach is to acquire a better understanding with respect to the biological actions of nanomaterials in the interrelated fields of Redox Biology and Toxicology.