Toxicity Assessment of a No-Pain Pharmacopuncture Extract Using a Standard Battery of In Vitro Chromosome Aberration Tests.

Objectives: Genotoxicity is evaluated through a chromosomal aberration test using cultured mammalian cells to determine the toxicity of no-pain pharmacopuncture (NPP), which has recently been used to treat musculoskeletal pain disorders in Korean medical clinical practice. Methods: An initial test was performed to determine the dosage range of the NPP, followed by the main test. In this study, NPP doses of 10.0, 5.0, and 2.5%, and negative and positive controls were tested. An in vitro chromosome aberration test was performed using Chinese hamster lung cells under short-term treatment with or without metabolic activation and under continuous treatment without metabolic activation. Results: Compared with the saline negative control group, NPP did not significantly increase the frequency of chromosomal abnormalities in Chinese hamster lung cells, regardless of the presence or absence of metabolic activation. Additionally, the number of cells with structural chromosomal abnormalities was significantly higher in the positive control group than that in the negative control group that received saline. Conclusion: Based on the above results, the chromosomal abnormality-producing effect of NPP was determined to be negative under these test conditions.

Application of HepaRG cells for genotoxicity assessment: a review.

There has been growing interest in the use of human-derived metabolically competent cells for genotoxicity testing. The HepaRG cell line is considered one of the most promising cell models because it is TP53-proficient and retains many characteristics of primary human hepatocytes. In recent years, HepaRG cells, cultured in both a traditional two-dimensional (2D) format and as more advanced in-vivo-like 3D spheroids, have been employed in assays that measure different types of genetic toxicity endpoints, including DNA damage, mutations, and chromosomal damage. This review summarizes published studies that have used HepaRG cells for genotoxicity assessment, including cell model evaluation studies and risk assessment for various compounds. Both 2D and 3D HepaRG models can be adapted to several high-throughput genotoxicity assays, generating a large number of data points that facilitate quantitative benchmark concentration modeling. With further validation, HepaRG cells could serve as a unique, human-based new alternative methodology for in vitro genotoxicity testing.

The role of genetic polymorphisms for inducing genotoxicity in workers occupationally exposed to benzene: a systematic review.

Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen.

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.

Evaluation of biological selenium nanoparticles on growth performance, histopathology of vital organs and genotoxicity in Japanese quails (coturnix coturnix japonica).

Research on the effects of selenium nanoparticles (Se-NPs), particularly in Japanese quails, is lacking, especially regarding the potential for DNA damage. Therefore, this study aimed to investigate the impact of administering 0.2 and 0.4 mg/kg of Se-NPs on the growth performance, DNA integrity, and histopathological alterations of the liver, lung, kidney, and heart in quails. A total of 480 one-day-old Japanese quails were divided into three experimental groups as follows: Group 1 served as the control and received only basic feed, while Group 2 and 3 received 0.2 mg/kg and 0.4 mg/kg of Se-NPs via oral gavage. Our results suggested that, birds fed with Se-NPs at both levels significantly (p < .01) reduced feed intake, however, weight gain was significantly (p < .01) increased in quails supplemented with 0.2 mg/kg. Similarly, feed conversion ratio (FCR) was significantly (p < .01) reduced in group supplemented with 0.2 mg/kg Se-NPs. White blood cells increased significantly (P0.01) in 0.4 mg/kg while haemoglobin and red cell distribution width decreased (p < .01) in the same group. Both treatment regimens resulted in DNA damage and histopathological alterations; however, the adverse effects were more prominent in the group receiving the higher dose of 0.4 mg/kg. These findings indicate that the lower dose of 0.2 mg/kg may have beneficial effects on growth. However, the higher dose of 0.4 mg/kg not only negatively impacts growth but also leads to histopathological alterations in major organs of the body and DNA damage as well.

A pilot study exploring time- and dose-dependent DNA damage and chromosomal instability caused by benzo[a]pyrene in two urothelial cell types.

Environmental and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in humans. Uncertainty exists regarding the causation of urinary bladder cancer by benzo[a]pyrene (B[a]P) due to a lack of sufficient data. In this work, we focused on in-vitro DNA damage and the formation of micronuclei and chromosomal aberrations as predictors of cancer risk, applying a wide range of dosages and time periods to quantify the onset, intensity, and duration of the response. We chose two urothelial cell types to compare susceptibility and the ability to increase the malignity of a pre-existing bladder cancer: a cancer cell line (T24) and a pooled sample of primary urinary bladder epithelia cells (PUBEC) from pigs. The highest level of DNA damage assessed by comet assay was observed following 24-h treatment in both cell types, whereas PUBEC cells were clearly more susceptible. Even 4-h treatment induced DNA damage in PUBEC cells with benchmark doses of 0.0027 µM B[a]P and 0.00023 µM after 4-h and 24-h exposure, respectively. Nearly no effect was observed for periods of 48 h. The frequency of micronucleus formation increased more markedly in T24 cells, particularly with 24-h treatment. In PUBEC cells, 48-h exposure notably induced the formation of nucleoplasmic bridges and nuclear buds. Even though only one biological replicate was studied due to the sophisticated study design, our results give a strong indication of the potential of B[a]P to induce and increase malignity in human-relevant cell types.

Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts.

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage. Cytotoxicity, mutagenicity, and genotoxicity were assessed in the following respective assays: Neutral Red Uptake (NRU), Ames and Mouse Lymphoma Assay (MLA). Targeted analysis of phosphorylation signalling and inflammatory markers under non-toxic conditions was used to investigate any potential signalling pathways or inflammatory response. A reference snus (CRP1.1) and four NPs with various flavours and nicotine strengths were assessed. Test article extracts was generated by incubating one pouch in 20 mL of media (specific to each assay) with the inclusion of the pouch material. NP extracts did not induce any cytotoxicity or mutagenic response, genotoxic response was minimal and limited signalling or inflammatory markers were induced. In contrast, CRP1.1 induced a positive response in four toxicological endpoints in the absence of S9: Srxn1 (oxidative stress), Btg2 (cell stress), Ddit3 (protein damage) and Rtkn (DNA damage), and three endpoints in presence of S9: Srxn1, Ddit3 and Rtkn. CRP1.1 was genotoxic when assessed in MLA and activated signalling pathways involved in proliferation and cellular stress and specifically induced phosphorylation of c-JUN, CREB1, p53, p38 MAPK and to a lesser extent AKT1S1, GSK3α/ß, ERK1/2 and RSK1 in a dose-dependent manner. CRP 1.1 extracts resulted in the release of several inflammatory mediators including cytokines IL-1α, IL5, IL6, IL8, IL-1RA, MIF and TNF-ß, receptor IL-2RA, and growth factors FGF-basic, VEGF and M-CSF. In conclusion these assays contribute to the weight of evidence assessment of the potential comparative health risks of NPs and snus.

New Charged Cholinesterase Inhibitors: Design, Synthesis, and Characterization.

Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles 23-34, as well as 1,2,3-triazolium salts 44-51, were synthesized and tested. Triazolium salts 44-46 showed excellent activity while salts 47 and 49 showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules 24-27. The representative of newly prepared compounds, 45 and 50, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases' active sites identified cation-π interactions as the most responsible for the stability of the enzyme-ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed.

Investigation of multidirectional toxicity induced by high-dose molybdenum exposure with Allium test.

In this study, the multifaceted toxicity induced by high doses of the essential trace element molybdenum in Allium cepa L. was investigated. Germination, root elongation, weight gain, mitotic index (MI), micronucleus (MN), chromosomal abnormalities (CAs), Comet assay, malondialdehyde (MDA), proline, superoxide dismutase (SOD), catalase (CAT) and anatomical parameters were used as biomarkers of toxicity. In addition, detailed correlation and PCA analyzes were performed for all parameters discussed. On the other hand, this study focused on the development of a two hidden layer deep neural network (DNN) using Matlab. Four experimental groups were designed: control group bulbs were germinated in tap water and application group bulbs were germinated with 1000, 2000 and 4000 mg/L doses of molybdenum for 72 h. After germination, root tips were collected and prepared for analysis. As a result, molybdenum exposure caused a dose-dependent decrease (p < 0.05) in the investigated physiological parameter values, and an increase (p < 0.05) in the cytogenetic (except MI) and biochemical parameter values. Molybdenum exposure induced different types of CAs and various anatomical damages in root meristem cells. Comet assay results showed that the severity of DNA damage increased depending on the increasing molybdenum dose. Detailed correlation and PCA analysis results determined significant positive and negative interactions between the investigated parameters and confirmed the relationships of these parameters with molybdenum doses. It has been found that the DNN model is in close agreement with the actual data showing the accuracy of the predictions. MAE, MAPE, RMSE and R2 were used to evaluate the effectiveness of the DNN model. Collective analysis of these metrics showed that the DNN model performed well. As a result, it has been determined once again that high doses of molybdenum cause multiple toxicity in A. cepa and the Allium test is a reliable universal test for determining this toxicity. Therefore, periodic measurement of molybdenum levels in agricultural soils should be the first priority in preventing molybdenum toxicity.

Systematic literature review of heavy metal contamination of the Nigerian environment from E-waste management: associated health and carcinogenic risk assessment.

E-waste -the aftermath of large amount of electrical and electronic equipment ferried into Africa from which Nigeria receives a significant chunk, is composed of components known to be hazardous to health. Composition of series of heavy metals (HMs) in e-waste is traceable to many health conditions including cancer which is hitherto incompletely understood. This study harmonizes primary data on HMs from e-waste in different Nigerian environmental media including the air, soil, surface dust, water and plant. We estimated the possible health implications, single and aggregative soil and water pollution indices in adult and children, carcinogenic and non-carcinogenic risks secondary to HM exposure and mapped out the possible mechanism of carcinogenesis. Analysis showed that soil, water, surface dust and plant matrices in Nigerian environment are variedly but considerably contaminated with combination of HMs. The significantly high values of the hazard quotient and hazard index of both water and surface dust matrices are indicative of adverse health effect of the non-carcinogenic risk. The highest HQ is generated by Pb and Cr through dermal exposure to soil and surface dust with mean values of 1718.48, 1146.14, 1362.10 and 1794.61 respectively among Nigerian children followed by the oral exposure. This pattern of observation is similar to that obtained for adult category. HI due to Pb and Cr in soil constitutes the highest HI (2.05E+03 and 1.18E+03 respectively) followed by surface dust. However, this study precipitates the observation that children are more at health risk than adults in contaminated environment. Carcinogenic risk also follows the same pattern of expression in the Nigerian environment. We conclude that exposure to e-waste poses significant carcinogenic and non-carcinogenic health risks with the carcinogenesis and proposed that the toxicity may be mediated via DNA damage, oxidative stress and inflammatory/immune cells dysfunction in Nigerian environment.

Spirulina-based carbon materials as adsorbents for drinking water taste and odor control: Removal efficiency and assessment of cyto-genotoxic effects.

The sensory quality of drinking water, and particularly its taste and odor (T&O) is a key determinant of consumer acceptability, as consumers evaluate water by their senses. Some of the conventional treatment processes to control compounds which impart unpleasant T&O have limitations because of their low efficiency and/or high costs. Therefore, there is a great need to develop an effective process for removing T&O compounds without secondary concerns. The primary objective of this study was to assess for the first time the effectiveness of spirulina-based carbon materials in removing geosmin (GSM) and 2-methylisoborneol (2-MIB) from water, two commonly occurring natural T&O compounds. The efficiency of the materials to remove environmentally relevant concentrations of GSM and 2-MIB (ng L-1) from ultrapure and raw water was investigated using a sensitive headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC/MS) method. Moreover, the genotoxic and cytotoxic effects of the spirulina-based materials were assessed for the first time to evaluate their safety and their potential in the treatment of water for human consumption. Based on the results, spirulina-based materials were found to be promising for drinking water treatment applications, as they did not exert geno-cytotoxic effects on human cells, while presenting high efficiency in removing GSM and 2-MIB from water.

Cytotoxic, acute oral toxicity, genotoxic and mutagenic assessment of the essential oil from fresh leaves of Croton argyrophyllus (Kunth.).

ETHNOPHARMACOLOGICAL RELEVANCE: Croton argyrophyllus Kunth., commonly known as "marmeleiro" or "cassetinga," is widely distributed in the Brazilian Northeast region. Its leaves and flowers are used in traditional medicine as tranquilizers to treat flu and headaches. AIM OF THE STUDY: This study was conducted to determine the chemical composition and toxicological safety of essential oil from C. argyrophyllus leaves using in vitro and in vivo models. MATERIALS AND METHODS: The chemical composition of the essential oil was determined using a gas chromatograph coupled to a mass spectrometer. Cytotoxicity was tested in the HeLa, HT-29, and MCF-7 cell lines derived from human cells (Homo sapiens) and Vero cell lines derived from monkeys (Cercopithecus aethiops) using the MTT method. Acute toxicity, genotoxicity. Mutagenicity tests were performed in Swiss mice (Mus musculus), which were administered essential oil orally in a single dose of 2000 mg/kg by gavage. RESULTS: The main components of the essential oil were p-mentha-2-en-1-ol, α-terpineol, ß-caryophyllene, and ß-elemene. The essential oil exhibited more than 90% cytotoxicity in all cell lines tested. No deaths or behavioral, hematological, or biochemical changes were observed in mice, revealing no acute toxicity. In genotoxic and mutagenic analyses, there was no increase in micronuclei in polychromatic erythrocytes or in the damage and index in the comet assay. CONCLUSIONS: The essential oil was cytotoxic towards the tested cell lines but did not exert toxic effects or promote DNA damage when administered orally at a single dose of 2000 mg/kg in mice.

Tl(I) and Tl(III)-induce genotoxicity, reticulum stress and autophagy in PC12 Adh cells.

Thallium (Tl) and its two cationic species, Tl(I) and Tl(III), are toxic for most living beings. In this work, we investigated the effects of Tl (10-100 µM) on the viability and proliferation capacity of the adherent variant of PC12 cells (PC12 Adh cells). While both Tl(I) and Tl(III) halted cell proliferation from 24 h of incubation, their viability was ~ 90% even after 72 h of treatment. At 24 h, increased levels of γH2AX indicated the presence of DNA double-strand breaks. Simultaneously, increased expression of p53 and its phosphorylation at Ser15 were observed, which were associated with decreased levels of p-AKTSer473 and p-mTORSer2448. At 72 h, the presence of large cytoplasmic vacuoles together with increased autophagy predictor values suggested that Tl may induce autophagy in these cells. This hypothesis was corroborated by images obtained by transmission electron microscopy (TEM) and from the decreased expression at 72 h of incubation of SQSTM-1 and increased LC3ß-II to LC3ß-I ratio. TEM images also showed enlarged ER that, together with the increased expression of IRE1-α from 48 h of incubation, indicated that Tl-induced ER stress preceded autophagy. The inhibition of autophagy flux with chloroquine increased cell mortality, suggesting that autophagy played a cytoprotective role in Tl toxicity in these cells. Together, results indicate that Tl(I) or Tl(III) are genotoxic to PC12 Adh cells which respond to the cations inducing ER stress and cytoprotective autophagy.

DNA Damage in Bat Blood Leukocytes Using a Chromatin Dispersion Test (CDT): Biomarker of Environmental Genotoxicity.

Environmental pollutants produce adverse effects on organisms and ecosystems. Biomonitoring and biomarkers offer a reasonable approach to make these assessments. Induced genetic changes can be using as a biomarker in organisms that react to a given compound in the ecosystem. Monitoring environmental genotoxicity necessitates the choice of model animals known as "sentinels or biological monitors" and the suitability of validated tests for DNA damage evaluation. We aimed to estimate the DNA damage produced by thermal stress in the leukocytes of the Mexican free-tailed bat (Tadarida brasiliensis). The DNA damage in bat leukocytes exposed to different temperatures (35 °C, 45 °C, and 55 °C) was evaluated by the adapted chromatin dispersion test (CDT) and the results were confirmed by the alkaline comet test. The CDT permitted a clear representation of leukocytes with fragmented DNA and of nonfragmented DNA. In addition, we detected nuclear anomalies in relation to cell death cellular swelling, nuclear fragmentation, and chromatin lysis. The alkaline comet assay revealed that the halos of diffuse chromatin include fragmented DNA. The assay of the method employing the CDT is well established, precise, and cost-effective for the routine quantitative analysis of DNA damage on the effect of the leukocytes of bats exposed to thermal stress. This could also apply as a sensitive screening tool for the evaluation of genotoxicity in environmental protection programs.

Advancing environmental monitoring across the water continuum combining biomarker analysis in multiple sentinel species: A case study in the Seine-Normandie Basin (France).

Nowadays, biomarkers are recognized as valuable tools to complement chemical and ecological assessments in biomonitoring programs. They provide insights into the effects of contaminant exposures on individuals and establish connections between environmental pressure and biological response at higher levels. In the last decade, strong improvements in the design of experimental protocols and the result interpretation facilitated the use of biomarker across wide geographical areas, including aquatic continua. Notably, the statistical establishment of reference values and thresholds enabled the discrimination of contamination effects in environmental conditions, allowed interspecies comparisons, and eliminated the need of a reference site. The aim of this work was to study freshwater-estuarine-coastal water continua by applying biomarker measurements in multi-species caged organisms. During two campaigns, eight sentinel species, encompassing fish, mollusks, and crustaceans, were deployed to cover 25 sites from rivers to the sea. As much as possible, a common methodology was employed for biomarker measurements (DNA damage and phagocytosis efficiency) and data interpretation based on guidelines established using reference values and induction/inhibition thresholds (establishment of three effect levels). The methodology was successfully implemented and allowed us to assess the environmental quality. Employing multiple species per site enhances confidence in observed trends. The results highlight the feasibility of integrating biomarker-based environmental monitoring programs across a continuum scale. Biomarker results align with Water Framework Directive indicators in cases of poor site quality. Additionally, when discrepancies arise between chemical and ecological statuses, biomarker findings offer a comprehensive perspective to elucidate the disparities. Presented as a pilot project, this work contributes to gain insights into current biomonitoring needs, providing new questions and perspectives.

Toxicological effects of nanoparticles in plants: Mechanisms involved at morphological, physiological, biochemical and molecular levels.

The rapid advancement of nanotechnology has led to unprecedented innovations across diverse industries, including pharmaceuticals, agriculture, cosmetics, electronics, textiles, and food, owing to the unique properties of nanoparticles. The extensive production and unregulated release of synthetic nanoparticles may contribute to nanopollution within the ecosystem. In the agricultural sector, nanotechnology is increasingly utilized to improve plant productivity, enhance resistance to stressors, and reduce the usage of chemicals. However, the uncontrolled discharge of nanoparticles into the natural environment raises concerns regarding possible plant toxicological impacts. The review focuses on the translocation of these particles within the plants, emphasizing their phytotoxicological effects at morphological, physiological, biochemical, and molecular levels. Eventhough the beneficial aspects of these nanoparticles are evident, excessive usage of nanoparticles at higher concentrations may lead to potential adverse effects. The phytotoxicity resulting from excessive amounts of nanoparticles affects seed germination and biomass production, disrupts the photosynthesis system, induces oxidative stress, impacts cell membrane integrity, alters gene expression, causes DNA damage, and leads to epigenetic variations in plants. Nanoparticles are found to directly associate with the cell membrane and cell organelles, leading to the dissolution and release of toxic ions, generation of reactive oxygen species (ROS) and subsequent oxidative stress. The present study signifies and accumulates knowledge regarding the application of nanoparticles in agriculture and illustrates a clear picture of their possible impacts on plants and soil microbes, thereby paving the way for future developments in nano-agrotechnology. The review concludes by addressing current challenges and proposing future directions to comprehend and mitigate the possible biological risks associated with nanoparticles in agriculture.

Gut microbiota and their derivatives in the progression of colorectal cancer: Mechanisms of action, genome and epigenome contributions.

Gut microbiota interacts with host epithelial cells and regulates many physiological functions such as genetics, epigenetics, metabolism of nutrients, and immune functions. Dietary factors may also be involved in the etiology of colorectal cancer (CRC), especially when an unhealthy diet is consumed with excess calorie intake and bad practices like smoking or consuming a great deal of alcohol. Bacteria including Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli (E. coli) actively participate in the carcinogenesis of CRC. Gastrointestinal tract with chronic inflammation and immunocompromised patients are at high risk for CRC progression. Further, the gut microbiota is also involved in Geno-toxicity by producing toxins like colibactin and cytolethal distending toxin (CDT) which cause damage to double-stranded DNA. Specific microRNAs can act as either tumor suppressors or oncogenes depending on the cellular environment in which they are expressed. The current review mainly highlights the role of gut microbiota in CRC, the mechanisms of several factors in carcinogenesis, and the role of particular microbes in colorectal neoplasia.

Cytogenetic Bioindication in Root Meristems for Vitality Assessment of Trees.

Our method describes how to collect forest tree root tips in the field, to store them for transfer to the lab, to pretreat root tips in order to arrest cells in metaphase, fix root tips to preserve specific morphological organizations, to stain fixed root tips by Feulgen's Reaction in order to increase contrast, and to prepare the root meristem for analyzing mitotic stages and chromosomal aberrations via light microscopy. We further describe how to classify chromosomal abnormalities and quantify them via aberration indices.

Low Dose of Nickel and Benzo [a] Anthracene in Rat-Diet, Induce Apoptosis, Fibrosis, and Initiate Carcinogenesis in Liver via NF-Æ˜ß Pathway.

Environmental contaminants such as polycyclic aromatic hydrocarbon (PAH) and heavy metals are major contaminants of food such as fish thus serving as source of exposure to human. This study was designed to evaluate the carcinogenic risk and other risks associated with long-term consumption of environmentally relevant dose of nickel and benzo [a] anthracene in rats. Thirty-six (36) male rats weighing between 80 and 100 g were assigned into 6 groups of 6 animals each; normal, nickel-, and benzo [a] anthracene-exposed groups for 12 and 24 weeks, respectively. Micronucleus and comet analyses were done in the blood, liver, and bone marrow. Liver function, redox, and inflammatory markers (AST, ALT, GGT, SOD, GSH, MDA, protein carbonyl, protein thiol, total protein, IL-10, 1L-1ß, TNF-α, TGF-ß NF-Ƙß, and 8-oxodeoxyguansine) were analysed by standard methods. Immuno-histochemical quantification of Bax, Bcl2, and Erk 1/2 as well as mRNA expression of cyclin D1 was done in liver. From the results, weight gain was observed in varying degrees throughout the exposure period. The polychromatic erythrocytes/normochromatic erythrocytes ratio > 0.2 indicates no cytotoxic effects on the bone marrow. Percentage-MnPCE in blood significantly (p < 0.05) increased throughout exposure duration. Percentage tail DNA in blood was significantly (< 0.05) increased at weeks 20 and 24 in the exposed groups and in liver at weeks 12 (16.22 ± 0.47) and 24 (17.00 ± 0.36) of nickel-exposed rats. The aspartate amino transferase (AST):alanine amino transferase (ALT) ratio indicated fatty liver disease in the benzo [a] anthracene (0.90) and acute liver injury in the nickel (> 10 times greater than the upper limits of the reference group) exposed groups during the first 12 weeks. Observation from the histological and cytological data of the liver revealed the presence of inflammation, fibrosis, and high nuclear/cytoplasmic ratio, respectively, in the nickel and benzo [a] anthracene groups. Only benzo [a] anthracene induced liver oxidative stress with significant (p < 0.05) decrease in SOD (0.64 ± 0.02) activity and increase in protein carbonyl (7.60 ± 0.80 × 10-5) and MDA (57.10 ± 6.64) concentration after 24 weeks. Benzo [a] anthracene up-regulated the cyclin D1 expression and significantly (p < 0.05) increased the levels of the cytokines. Nickel and benzo [a] anthracene significantly (p < 0.05) increased the Bax (183.45 ± 6.50 and 199.76 ± 10.04) and Erk 1/2 (108.25 ± 6.41 and 136.74 ± 4.22) levels when compared with the control (37.43 ± 22.22 and 60.37 ± 17.86), respectively. Overall result showed that the toxic effects of nickel and benzo [a] anthracene might involve fibrosis, cirrhosis, apoptosis, and inflammation of the liver. As clearly demonstrated in this study, benzo [a] anthracene after the 24 weeks of exposure stimulates carcinogenic process by suppressing the liver antioxidant capacity, altering apoptotic, cell proliferation, and differentiation pathways.

Plant-nano interactions: A new insight of nano-phytotoxicity.

Whether nanoparticles (NPs) are boon or bane for society has been a centre of in-depth debate and key consideration in recent times. Exclusive physicochemical properties like small size, large surface area-to-volume ratio, robust catalytic activity, immense surface energy, magnetism and superior biocompatibility make NPs obligatory in many scientific, biomedical and industrial ventures. Nano-enabled products are newer entrants in the present era. To attenuate environmental stress and maximize crop yields, scientists are tempted to introduce NPs as augmented supplements in agriculture. The feasible approaches for NPs delivery are irrigation, foliar spraying or seed priming. Internalization of excessive NPs to plants endorses negative implications at higher trophic levels via biomagnification. The characteristics of NPs (dimensions, type, solubility, surface charge), applied concentration and duration of exposure are prime factors conferring nanotoxicity in plants. Several reports approved NPs persuaded toxicity can precisely mimic abiotic stress effects. The signature effects of nanotoxicity include poor root outgrowth, biomass reduction, oxidative stress evolution, lipid peroxidation, biomolecular damage, perturbed antioxidants, genotoxicity and nutrient imbalance in plants. NPs stress impels mitogen-activated protein kinase signaling cascade and urges stress responsive defence gene expression to counteract stress in plants. Exogenous supplementation of nitric oxide (NO), arbuscular mycorrhizal fungus (AMF), phytohormones, and melatonin (ME) is novel strategy to circumvent nanotoxicity. Briefly, this review appraises plants' physio-biochemical responses and adaptation scenarios to endure NPs stress. As NPs stress represents large-scale contaminants, advanced research is indispensable to avert indiscriminate NPs usage for synchronizing nano-security in multinational markets.