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Teucrifarides A–D (1–4), four previously unreported neo-clerodane-type diterpenoids, combined with sixteen known analogs (5–20), were purified from Teucrium quadrifarium. The absolute forma of compounds 1–4 were determined via spectroscopic and ECD calculation methods, together with X-ray crystallography experiments. Among them, compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo [5.3.2.01,6]undecane skeleton. Meanwhile, 2 incorporated a 6,20-epoxy ring with a novel 12-oxatricyclo [6.2.2.02,7]undecane skeleton. Compounds 1 and 12 exhibited significant inhibitory effects against HT-22 cells ferroptosis induced by RSL3, with EC50 values of 11.8 ± 1.0 μM, and 4.52 ± 1.24 μM, respectively. Moreover, ROS accumulation in HT22 cells treated with compound 1 was also observed. [ABSTRACT FROM AUTHOR]

Background: Environmental pollutants, particularly heavy metals, have been frequently connected to male infertility. Cadmium was previously shown to reduce male fertility by causing oxidative stress. Anacyclus pyrethrum is a well-known medicinal plant. Most of its parts, notably the roots, have excellent antioxidant and anti-inflammatory properties. The present study investigated the potential ability of Anacyclus pyrethrum to protect male rats against cadmium reproductive toxicity. Methods: Twenty-eight adult Wistar male rats (8 weeks old) weighing (170-200g) were randomly divided into four groups (n = 7): group (1) the control, group (2) was orally administrated with Anacyclus pyrethrum extract (100mg/kg) for 56 consecutive days, group (3) received a single intraperitoneal (IP) injection of cadmium chloride (1mg/kg), and group (4) received a single IP dose of CdCl2 followed by 8 weeks of oral Anacyclus extract treatment. Results: Cadmium Cd toxicity resulted in a significant decrease in the concentration of antioxidant enzymes (superoxide dismutase SOD and glutathione peroxidase GPx) in the semen coupled with a significant rise in malondialdehyde MDA level. Consequently, sperm analysis parameters were significantly affected showing decreased motility, viability, concentration and increased morphological aberrations. DNA fragmentation was also detected in the sperms of rats exposed to Cd using comet assay. Serum levels of testosterone T, follicle stimulating hormone FSH, and luteinizing hormone LH were significantly decreased. The mRNA expression levels of sex hormone receptors (FSHR, LHR and AR) in the testis of the Cd exposed rats were significantly decreased. Expression levels of Bax and Bcl2 genes in the sperms of Cd intoxicated rats were also affected shifting the Bax/Bcl2 ratio towards the induction of apoptosis. Co-treatment with the Anacyclus pyrethrum extract restored the oxidative enzymes activities and decreased the formation of lipid peroxidation byproduct, which in turn ameliorated the effect of Cd on sperm parameters, sperm DNA damage, circulating hormone levels, gene expression and apoptosis. These results indicate that Anacyclus pyrethrum could serve as a protective agent against cadmium-induced sperm toxicity. Conclusion: Taken together, it can be concluded that the antioxidant activities of Anacyclus pyrethrum restored the semen quality and enhanced fertility in Cd-intoxicated male rats. [ABSTRACT FROM AUTHOR]

The GluN3A subunit of N-methyl-D-aspartate receptors (NMDARs) plays an established role in synapse development, but its contribution to neural circuits in the adult brain is less clear. Recent work has demonstrated that in select cell populations, GluN3A assembles with GluN1 to form GluN1/GluN3A receptors that are insensitive to glutamate and instead serve as functional excitatory glycine receptors (eGlyRs). Our understanding of these eGlyRs, and how they contribute to intrinsic excitability and synaptic communication within relevant networks of the developing and the mature brain, is only beginning to be uncovered. Here, using male and female mice, we demonstrate that GluN3A subunits are enriched in the adult ventral hippocampus (VH), where they localize to synaptic and extrasynaptic sites and can assemble as functional eGlyRs on CA1 pyramidal cells. GluN3A expression was barely detectable in the adult dorsal hippocampus (DH). We also observed a high GluN2B content in the adult VH, characterized by slow NMDAR current decay kinetics and a high sensitivity to the GluN2B-containing NMDAR antagonist ifenprodil. Interestingly, the GluN2B enrichment in the adult VH was dependent on GluN3A as GluN3A deletion accelerated NMDAR decay and reduced ifenprodil sensitivity in the VH, suggesting that GluN3A expression can regulate the balance of conventional NMDAR subunit composition at synaptic sites. Lastly, we found that GluN3A knock-out also enhanced both NMDAR-dependent calcium influx and NMDAR-dependent long-term potentiation in the VH. Together, these data reveal a novel role for GluN3A and eGlyRs in the control of ventral hippocampal circuits in the mature brain. [ABSTRACT FROM AUTHOR]

Background: Orthodontics is a speciality of dentistry that uses a plethora of devices made from myriad materials to manage various malocclusions. Prolonged contact of orthodontic appliances with oral tissues can lead to cellular damage, highlighting the need for biocompatible materials to mitigate health risks. Objectives: To analyze the genotoxicity and cytotoxicity produced by metal brackets and coated metallic brackets with polymeric and nanoparticle coatings in oral mucosal cells. Materials & methods: The current study compares the toxicity of 3 different types of orthodontic brackets with control groups of oral mucosal cells. Each of the three treatment groups consisted of 10 samples of orthodontic brackets: stainless steel brackets(Group 1), nanoparticle-coated brackets(Group 2), and polymeric-coated brackets(Group 3) exposed to corrosion eluates employing an oral biomimicry model. Two types of oral mucosal cells- Human Gingival Fibroblasts and Buccal Epithelial Cells were used to study the cytotoxic and/or genotoxic effects of the elutes. Intergroup comparisons were conducted using one-way analysis of variance, while scanning electron microscopy evaluated surface characteristic. Results: The interaction between metal ions and oral mucosal cells showed no statistically significant difference for toxicity assays between the three groups(p > 0.005). However, polymeric and nanoparticle-coated groups showed reduced cellular differentiation when compared with conventional stainless-steel brackets. Conclusion: This in-vitro study shows that polymeric or nanoparticle coating of conventional metal brackets aids in enhancing corrosion-resistant characteristics of orthodontic appliances and reduces the toxic oral environment created by metal release in the oral cavity. [ABSTRACT FROM AUTHOR]

This study evaluates the anesthetic effectiveness and potential reduction of toxicity in Nile tilapia (Oreochromis niloticus) through the use of clove, cinnamon, and tea tree essential oils. We evaluated genetic damage, enzymatic activity, and gene expression. We conducted two experiments. In experiment 1, we individually evaluated the anesthetic efficiency and genotoxicity of these essential oils. In experiment 2, we assessed their combined effects at different concentrations. Clove oil, particularly at the highest concentration (200 µL/L), induced genotoxic effects and oxidative stress in fish, leading to alterations in gene expression regulation and enzymatic activity. Tea tree and cinnamon oils, at concentrations of 75 and 100 µL/L, required longer times to induce fish to the anesthesia stage and were less efficient in achieving deep anesthesia stage. Notably, combining tea tree and cinnamon essential oils to clove oil showed promise as an alternative to using clove oil alone. This combination demonstrated potential as an effective anesthetic and may help mitigate the genotoxic effects associated with clove essential oil. Our findings suggest a viable option to minimize potential physiological damage during the anesthesia process in aquaculture, thereby promoting a balance between this necessary procedure and animal welfare. [ABSTRACT FROM AUTHOR]

Ectoparasites Dactylogyrus spp. mainly infest fish gills and severely damage the host's gill tissues. Correspondingly, the explanation of the interaction of fish with Dactylogyrus spp. infection is still insufficient. The present study describes the changes in hemato-biochemical, immune, antioxidant, genotoxic, and pathological indices response of Nile tilapia (Oreochromis niloticus) severely (n > 50), mildly infected (n = 1–50), and uninfected with Dactylogyrus spp. Data showed the adverse effect of hemato-biochemical indices in infected fish compared to uninfected, notably in severely infected O. niloticus. Compared to uninfected fish, there is a significantly decreased serum lysozyme and complement C3 and increased IgM and phagocytic activity along with significant upregulation of (COX-2), (IL-1β), (TNF-α), and (IL-10) genes in infected fish partially, in severely infected fish. Concisely, indices of antioxidants in the liver and gills marked an increased level of MDA in the infected fish compared to the uninfected fish. Conversely, levels of SOD, CAT, and GSH were decreased significantly with damaged DNA in the gills and liver of infected groups, particularly in severely infected (P < 0.05). Histopathologically investigating livers and gills in infected Nile tilapia indicated damaging and degenerative alterations, particularly with severe infection. Findings showed that Dactylogyrus spp.–infected Nile tilapia were effective in improving our knowledge of fish-pathogen interactions, which may be essential for fish defense against parasite infection. [ABSTRACT FROM AUTHOR]

Abamectin, a widely used pesticide with insecticidal, anthelmintic, and acaricidal properties, has raised safety concerns due to its toxic effects on certain non-target organisms. The toxicity of abamectin, the active ingredient in the commercial pesticide formulation Alopec® EC, was evaluated using cytogenetic and comet assays on Allium cepa root tips. Mitotic index (MI) and phase index (PI) values were used for cytotoxicity assessment. Chromosomal aberration (CA) frequencies in the dividing cells and comet data were used for genotoxicity assessment. The root growth test showed a significant concentration-based decline in root growth after abamectin exposure, with a median effective concentration (EC50) of 2.50 mg/L. Following 96-hour exposure to three concentrations of abamectin (1.25, 2.50, and 5.00 mg/L), cytogenetic and comet analyses indicated a significant concentration- and time-dependent decrease in the MI, alongside an increase in DNA damage. Additionally, there was a significant concentration-dependent rise in the total frequency of CAs. These findings show that abamectin is a pesticide with lethal effects on A. cepa root tip meristematic cells, even at lower concentrations, over prolonged exposure times, with CA-forming and DNA-damaging effects, and that it is highly cytotoxic and genotoxic. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to investigate the changes induced by Tartrazine (T) and Thymoquinone (TQ) in rat lung tissues. Materials and Methods: Thirty-two rats were divided into four groups, 8 animals in each group: Control, T, TQ and T. The experiments were conducted for 21 days. Oxidant-antioxidant parameters were determined in rat lung tissues. Results: An increase was observed in Malondialdehyde (MDA) parameters in the lung tissues of rats in the T-treatment group when compared to all other groups, a significant decrease was observed in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels. It was observed that TQ administration led to a significant increase in antioxidant capacity when compared to other groups. Coadministration of T and TQ led to improvements in oxidant and antioxidant parameters when compared to the T group. Conclusion: In this first study on the correlation between T and TQ, T administration led to damages in lung tissues. It induced oxidative stress via the increase in oxidant capacity. TQ led to an increase in antioxidant capacity. We recommend TQ consumption to maintain strong antioxidant capacity against oxidative stress damage and T toxicity. [ABSTRACT FROM AUTHOR]

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection neurons, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition. Inhibitory circuits in the mammalian olfactory bulb shape information as it propagates from peripheral receptors to the downstream cortex. This study reveals that fast-spiking interneurons perisomatically inhibit projection neurons in the mammalian olfactory bulb via synaptic detonation. [ABSTRACT FROM AUTHOR]

In this study, a new ZnO/BaMg2 nanocomposite was synthesized, using the green synthesis method in which lemon peel extract was used as a reducing agent to form ZnO/BaMg2 nanocomposites. The synthesized nanoparticles were characterized by visible and ultraviolet light spectroscopy showing absorption peaks at around 277 nm. The chemical bond configurations of ZnO/BaMg2 were confirmed by Fourier transform infrared (FT-IR) spectroscopy analyses. The results of X-ray diffraction (XRD) analysis revealed the formation of a hexagonal crystal structure, and the particle SEM analyses showed irregular shapes around 35.89 nm for the synthesized nanoparticles. The catalytic activity of synthesized ZnO/BaMg2 in the decomposition of methyl orange (MO) and rose bengal (RB) dyes was studied by visible and UV–vis spectroscopy and compared with the catalytic activity of ZnO NPs. The decolorization ratios of both dyes for ZnO/BaMg2 composite were 90.2% and 98.71% of RB and MO, respectively, while for ZnO NPs 75.57% of MO and 88.69% of RB within 120 min. [ABSTRACT FROM AUTHOR]

Antibiotics are crucial in the control of bacterial infections on fish farms. However, the influence of licensed antibiotics on DNA damage, histological changes, and protein differentiation in some farmed fish species is unidentified. The current study aimed to investigate the effect of therapeutic (80 mg/kg body weight/day) and high doses (160 mg/kg body weight/day) of oxytetracycline (OTC) on some biological indices, protein differentiation, histological changes, and DNA damage in Oreochromis niloticus (n = 360; 40 ± 3.5 g) and the potential positive effects of dietary ascorbic acid (AA) and whether it is capable of reducing the deleterious impacts of OTC and working synergistically to increase fish disease resistance and decrease morbidity and mortality rates. In the current study, fish were fed diets with or without OTC (80 or 160 mg/kg body weight/day) and AA (100 mg/kg diet/day) for 28 days, followed by a bacterial stress test with two different virulent strains for 14 days. Treatments include CTR (control; without additives), AA, OTC80, OTC160, OTC80 + AA, and OTC160 + AA. The results revealed that the AA group had the best antioxidative (significant increase in SOD, CAT, and GPx) and immunomodulatory effects (an increase in IgM, nitroblue tetrazolium, and total leucocytic count). Furthermore, the hematological parameters, immune indices (NBT), and antioxidant enzymes were significantly reduced by OTC160 (p ≤ 0.05). The results also showed that OTC160 notably augmented the activity of liver (ALT, AST, and LDH) and kidney (creatinine and urea) damage markers (p ≤ 0.05). OTC160 revealed considerable hepatic and renal tissue damage and significantly higher hepatocyte DNA damage. Pathological changes and DNA damage were directly correlated to the dosage of OTC exposure, where they were more severe in OTC160. OTC80 showed insignificant changes in most parameters. Compared to CTR, the inclusion of AA in the O. niloticus diet significantly restored the biological indices, histological changes, and DNA damage in OTC-treated groups. The morbidity and mortality percentages after bacterial challenge were significantly lower in the OTC80 + AA group, followed by the OTC160 + AA group than in the CTR. These results corroborate the use of AA as a potent antioxidant and immune stimulant and a potential co-adjuvant to OTC in the diet of O. niloticus to reach optimal resistance to disease. [ABSTRACT FROM AUTHOR]

Normal cell and body functions need to be maintained and protected against endogenous and exogenous stress conditions. Different cellular stress response pathways have evolved that are utilized by mammalian cells to recognize, process and overcome numerous stress stimuli in order to maintain homeostasis and to prevent pathophysiological processes. Although these stress response pathways appear to be quite different on a molecular level, they all have in common that they integrate various stress inputs, translate them into an appropriate stress response and eventually resolve the stress by either restoring homeostasis or inducing cell death. It has become increasingly appreciated that non-protein-coding RNA species, such as long noncoding RNAs (lncRNAs), can play critical roles in the mammalian stress response. However, the precise molecular functions and underlying modes of action for many of the stress-related lncRNAs remain poorly understood. In this review, we aim to provide a framework for the categorization of mammalian lncRNAs in stress response and homeostasis based on their experimentally validated modes of action. We describe the molecular functions and physiological roles of selected lncRNAs and develop a concept of how lncRNAs can contribute as versatile players in mammalian stress response and homeostasis. These concepts may be used as a starting point for the identification of novel lncRNAs and lncRNA functions not only in the context of stress, but also in normal physiology and disease. [ABSTRACT FROM AUTHOR]

Background: This study investigates the impact of acute and chronic exposure to gaseous pollutants, specifically sulfur dioxide (SO), nitrogen dioxide (NO), and their combination (SO +NO), on the physiological and genetic integrity of Centropristis striata (sea bass). The research focuses on understanding the adverse effects on gill, liver, and kidney tissues over a 96-hour acute exposure period and during long-term chronic exposure at sub-lethal concentrations. Methods: The study determined lethal concentrations (LC, LC, LC) for SO, NO and their combination. Gill and liver health were evaluated using scoring systems. Total carotenoid and beta -carotene content in liver tissue were quantified. Comet assays were employed to measure DNA damage in gill, liver, and kidney tissues. Results: The findings indicate a dose-dependent increase in mortality rates with escalating concentrations of pollutants. Significant damage to gill and liver tissues was observed, with higher pollutant concentrations resulting in more severe damage. A notable depletion of carotenoid levels in the liver was detected with increasing pollutant exposure. Genotoxic analysis revealed significant DNA damage, particularly in liver tissue, suggesting a mechanistic link between pollutant exposure and genetic injury. Conclusion: The research highlights the detrimental effects of gaseous pollutants on the health and genetic integrity of sea bass. The dose-dependent adverse effects, including increased mortality, tissue damage, and DNA integrity disruption, underscore the necessity of implementing effective pollution control measures to preserve aquatic ecosystems. [ABSTRACT FROM AUTHOR]

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Introduction: Radiation‐induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial–mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) exhibits strong repair capacity when cells undergo radiation‐induced damage; whether DNA‐PKcs regulates EMT during RIPF remains unclear. Objectives: To investigate the role and molecular mechanism of DNA‐PKcs in RIPF and provide an important theoretical basis for utilising DNA‐PKcs‐targeted drugs for preventing RIPF. Methods: DNA‐PKcs knockout (DPK−/−) mice were generated via the Cas9/sgRNA technique and subjected to whole chest ionizing radiation (IR) at a 20 Gy dose. Before whole chest IR, the mice were intragastrically administered the DNA‐PKcs‐targeted drug VND3207. Lung tissues were collected at 1 and 5 months after IR. Results: The expression of DNA‐PKcs is low in pulmonary fibrosis (PF) patients. DNA‐PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA‐PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA‐PKcs and Twist1. High Twist1 expression and EMT‐associated changes caused by DNA‐PKcs deletion were blocked by insulin‐like growth factor‐1 (IGF‐1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR‐induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA‐PKcs. Conclusion: Our study clarified the critical role and mechanism of DNA‐PKcs in RIPF and showed that it could be a potential target for preventing RIPF. [ABSTRACT FROM AUTHOR]

Purpose: To compare the DNA damage in granulosa cells (GCs) of women undergoing ovarian-stimulated cycles with four widely used recombinant human follicle-stimulating hormones (rhFSH) in in vitro fertilization (IVF) protocols (Corneumon®, Gonal-F®, Pergoveris® and Puregon®). Methods: A randomized trial was carried out at a Mexican hospital. GCs were isolated from 18 women with infertility undergoing assisted reproductive techniques (ART). Four controlled ovarian stimulation (COS) protocols including Corneumon®, Gonal-F®, Pergoveris® or Puregon® were used. GCs DNA damage was assessed by the Comet assay. Two parameters were measured: comet tail length (CTL), and Olive tail moment (OTM, the percentage of DNA in the tail multiplied by the distance between the center of the tail and head). Results: Use of the different hrFSH in COS caused variable and statistically significant levels of DNA damage in GCs of infertile women. CTL was similar in the Corneumon® and Pergoveris® groups (mean values of 48.73 and 55.18, respectively) and Corneumon® CTL was significantly lower compared to the Gonal-F® and Puregon® groups (mean values of 61.98 and 91.17, respectively). Mean OTM values were significantly lower in Corneumon® and Pergoveris® groups, compared to Gonal-F® and Puregon® groups (25.59, 27.35, 34.76, and 47.27, respectively). Conclusion: Use of Corneumon® and Pergoveris® in COS caused statistically significantly lower levels of DNA damage in GCs of infertile women undergoing ART, which could potentially correlate with better reproductive outcomes. [ABSTRACT FROM AUTHOR]

Background: Phytoestrogens have been praised for their beneficial health effects, whereas synthetic xenoestrogens have been connected to ailments. Aims: To ascertain whether the toxicities of natural and synthetic estrogens differ, we examined the potent phytoestrogen 8-prenylnaringenin (8-PN), the common synthetic xenoestrogen tartrazine, and the physiological estrogen 17β-estradiol (E2). Methods: These three compounds were tested for cytotoxicity, cell proliferation and genotoxicity in human HepG2 and rat H4IIE hepatoma cells. Results: All three estrogens elicited cytotoxicity at high concentrations in both cell lines. They also inhibited cell proliferation, with E2 being the most effective. They all tended to increase micronuclei formation. Conclusion: Natural estrogens were no less toxic than a synthetic one. [ABSTRACT FROM AUTHOR]

Purpose: Genetic polymorphisms have been associated with the adaptation to training in maximal oxygen uptake ( V ˙ O 2 max). However, the genotype distribution of selected polymorphisms in athletic cohorts is unknown, with their influence on performance characteristics also undetermined. This study investigated whether the genotype distributions of 3 polymorphisms previously associated with V ˙ O 2 max training adaptation are associated with elite athlete status and performance characteristics in runners and rugby athletes, competitors for whom aerobic metabolism is important. Methods: Genomic DNA was collected from 732 men including 165 long-distance runners, 212 elite rugby union athletes, and 355 nonathletes. Genotype and allele frequencies of PRDM1 rs10499043 C/T, GRIN3A rs1535628 G/A, and KCNH8 rs4973706 T/C were compared between athletes and nonathletes. Personal-best marathon times in runners, as well as in-game performance variables and playing position, of rugby athletes were analyzed according to genotype. Results: Runners with PRDM1 T alleles recorded marathon times ∼3 minutes faster than CC homozygotes (02:27:55 [00:07:32] h vs 02:31:03 [00:08:24] h, P =.023). Rugby athletes had 1.57 times greater odds of possessing the KCNH8 TT genotype than nonathletes (65.5% vs 54.7%, χ2 = 6.494, P =.013). No other associations were identified. Conclusions: This study is the first to demonstrate that polymorphisms previously associated with V ˙ O 2 max training adaptations in nonathletes are also associated with marathon performance (PRDM1) and elite rugby union status (KCNH8). The genotypes and alleles previously associated with superior endurance-training adaptation appear to be advantageous in long-distance running and achieving elite status in rugby union. [ABSTRACT FROM AUTHOR]

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ -radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100's protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5 Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation's severe damage to important organs. [ABSTRACT FROM AUTHOR]

The ecotoxic effect of Zn species arising from the weathering of the marmatite-like sphalerite ((Fe, Zn)S) in Allium cepa systems was herein evaluated in calcareous soils and connected with its sulfide oxidation mechanism to determine the chemical speciation responsible of this outcome. Mineralogical analyses (X-ray diffraction patterns, Raman spectroscopy, scanning electron microscopy and atomic force microscopy), chemical study of leachates (total Fe, Zn, Cd, oxidation–reduction potential, pH, sulfates and total alkalinity) and electrochemical assessments (chronoamperometry, chronopotentiometry, cyclic voltammetry, and electrochemical impedance spectroscopy) were carried out using (Fe, Zn)S samples to elucidate interfacial mechanisms simulating calcareous soil conditions. Results indicate the formation of polysulfides (Sn2−), elemental sulfur (S0), siderite (FeCO3)-like, hematite (Fe2O3)-like with sorbed CO32− species, gunningite (ZnSO4·H2O)-like phase and smithsonite (ZnCO3)-like compounds in altered surface under calcareous conditions. However, the generation of gunningite (ZnSO4·H2O)-like phase was predominant bulk-solution system. Quantification of damage rates ranges from 75 to 90% of bulb cells under non-carbonated conditions after 15–30 days, while 50–75% of damage level is determined under neutral-alkaline carbonated conditions. Damage ratios are 70.08 and 30.26 at the highest level, respectively. These findings revealed lower ecotoxic damage due to ZnCO3-like precipitation, indicating the effect of carbonates on Zn compounds during vegetable up-taking (exposure). Other environmental suggestions of the (Fe, Zn)S weathering and ecotoxic effects under calcareous soil conditions are discussed. [ABSTRACT FROM AUTHOR]

Background: D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. Results: We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. Conclusions: The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes. [ABSTRACT FROM AUTHOR]

In this work, we investigated the reaction of cyclamate with hypochlorous acid (HOCl) in simulated gastric juice. The reaction products were detected by high-performance liquid chromatography diode array detection (HPLC-DAD) and ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). We also explored the changes in product concentration as a function of reaction time, cyclamate and HOCl concentrations. Cyclamate reacted with hypochlorous acid instantly in the simulated gastric fluid. N, N-dichlorcyclohexylamine and cyclohexylamine were both detected when the HOCl concentration was at millimole. Cyclohexylamine can only be found when HOCl concentration was at micromole. N, N-dichlorcyclohexylamine and cyclohexylamine concentrations both increased when cyclamate concentration increased under the millimole level of HOCl. As an important reactive oxygen species, hypochlorous acid (HClO) is produced in various physiological processes. The abnormal rise of the HClO level is associated with many inflammatory diseases. Chronic gastritis associated with Helicobacter pylori is a multistep, progressive, life-long inflammation. So, chronic gastritis infected with H. pylori may cause cyclamate metabolizing into cyclohexylamine in vivo. [ABSTRACT FROM AUTHOR]

Spike timing-based representations of sensory information depend on embedded dynamical frameworks within neuronal networks that establish the rules of local computation and interareal communication. Here, we investigated the dynamical properties of olfactory bulb circuitry in mice of both sexes using microelectrode array recordings from slice and in vivo preparations. Neurochemical activation or optogenetic stimulation of sensory afferents evoked persistent gamma oscillations in the local field potential. These oscillations arose from slower, GABA(A) receptor-independent intracolumnar oscillators coupled by GABA(A)- ergic synapses into a faster, broadly coherent network oscillation. Consistent with the theoretical properties of coupled-oscillator networks, the spatial extent of zero-phase coherence was bounded in slices by the reduced density of lateral interactions. The intact in vivo network, however, exhibited long-range lateral interactions that suffice in simulation to enable zero-phase gamma coherence across the olfactory bulb. The timing of action potentials in a subset of principal neurons was phase-constrained with respect to evoked gamma oscillations. Coupled-oscillator dynamics in olfactory bulb thereby enable a common clock, robust to biological heterogeneities, that is capable of supporting gamma-band spike synchronization and phase coding across the ensemble of activated principal neurons. NEW & NOTEWORTHY Odor stimulation evokes rhythmic gamma oscillations in the field potential of the olfactory bulb, but the dynamical mechanisms governing these oscillations have remained unclear. Establishing these mechanisms is important as they determine the biophysical capacities of the bulbar circuit to, for example, maintain zero-phase coherence across a spatially extended network, or coordinate the timing of action potentials in principal neurons. These properties in turn constrain and suggest hypotheses of sensory coding. [ABSTRACT FROM AUTHOR]

Copper (Cu) toxicity is a pressing concern for several soils, especially in organic viticulture. The objective of this work was to assess Cu toxicity on the non-target organism Eisenia fetida, employing both traditional and novel tools for early identification of Cu-induced damages. In addition to traditional tests like avoidance and reproductive toxicity experiments, other tests such as the single cell gel electrophoresis (SCGE) and gut microbiome analysis were evaluated to identify early and more sensitive pollution biomarkers. Four sub-lethal Cu concentrations were studied, and the results showed strong dose-dependent responses by the earthworm avoidance test and the exceeding of habitat threshold limit at the higher Cu doses. An inverse proportionality was observed between reproductive output and soil Cu concentration. Bioaccumulation was not detected in earthworms; soil concentrations of potentially bioavailable Cu were not affected by E. fetida presence or by time. On the contrary, the SCGE test revealed dose-dependent genotoxicity for the 'tail length' parameter already at the second day of Cu exposition. Gut microbiome analysis a modulation of microbial composition, with the most aboundant families being Pectobateriaceae, Comamonadaceae and Microscillaceae. Bacillaceae increased over time and showed adaptability to copper up to 165 mg/kg, while at the highest dose even the sensitive Acetobacteriaceae family was affected. The research provided new insights into the ecotoxicity of Cu sub-lethal doses highlighting both alterations at earthworms' cellular level and changes in their gut microbiota. [ABSTRACT FROM AUTHOR]

Global estimates exhibit that one million people have end-stage renal disease, a disease-state characterized by irreversible loss of kidney structure and function, thus necessitating renal replacement therapy. The disease-state, oxidative stress, inflammatory responses, as well as the treatment procedure can have damaging effects on the genetic material. Therefore, the present study was carried out to investigate DNA damage (basal and oxidative) using the comet assay in peripheral blood leukocytes of patients (n = 200) with stage V Chronic Kidney Disease (on dialysis and those recommended but yet to initiate dialysis) and compare it to that in controls (n = 210). Basal DNA damage was significantly elevated (1.13x, p ≤ 0.001) in patients (46.23 ± 0.58% DNA in tail) compared to controls (40.85 ± 0.61% DNA in tail). Oxidative DNA damage was also significantly (p ≤ 0.001) higher in patients (9.18 ± 0.49 vs. 2.59 ± 0.19% tail DNA) compared to controls. Twice-a-week dialysis regimen patients had significantly elevated % tail DNA and Damage Index compared to the non-dialyzed and to the once-a-week dialysis group implying dialysis- induced mechanical stress and blood–dialyzer membrane interactions as probable contributors to elevated DNA damage. The present study with a statistically significant power implies higher disease-associated as well as maintenance therapy (hemodialysis)-induced basal and oxidatively damaged DNA, which if not repaired has the potential to initiate carcinogenesis. These findings mark the need for improvement and development of interventional therapies for delaying disease progression and associated co-morbidities so as to improve life expectancy of patients with kidney disease. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders on a disease spectrum that are characterized by the cytoplasmic mislocalization and aberrant phase transitions of prion-like RNA-binding proteins (RBPs). The common accumulation of TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), and other nuclear RBPs in detergent-insoluble aggregates in the cytoplasm of degenerating neurons in ALS/FTD is connected to nuclear pore dysfunction and other defects in the nucleocytoplasmic transport machinery. Recent advances suggest that beyond their canonical role in the nuclear import of protein cargoes, nuclear-import receptors (NIRs) can prevent and reverse aberrant phase transitions of TDP-43, FUS, and related prion-like RBPs and restore their nuclear localization and function. Here, we showcase the NIR family and how they recognize cargo, drive nuclear import, and chaperone prion-like RBPs linked to ALS/FTD. We also discuss the promise of enhancing NIR levels and developing potentiated NIR variants as therapeutic strategies for ALS/FTD and related neurodegenerative proteinopathies. [ABSTRACT FROM AUTHOR]

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC. [ABSTRACT FROM AUTHOR]

Purpose: This paper introduces a complete in vitro investigation of cytotoxic and genotoxic effects of Phyllanthus niruri extract loaded chitosan nanoparticles (PNNP) on mouse Sertoli cell line (TM4), as well as their impact on spermatogenesis. Methods: Chitosan nanoparticles (ChNP) and PNNP were prepared using an ionic gelation process, while their cytotoxicity on TM4 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Comet and fast halo assays were used to quantify single-strand DNA breaks in TM4 cells. To detect changes in cell morphology during apoptosis, nuclear staining with Hoechst 33342 was performed. An immunofluorescence assay was employed to examine the expression level of proteins connexin 43 and Claudin 11 in TM4 cells after exposure to PNNP concentration of 125 µg/mL. Results: The synthesized PNNP had a size of 170.6 nm, a polydispersity index of 0.269, a zeta potential of +37.8 mV, and a good entrapment efficiency of 71.0%. Encapsulation of Phyllanthus niruri into ChNP induced DNA damage in TM4 cells as determined by alkaline comet and fast halo assay (FHA). Additionally, it stimulated apoptosis, as determined by changes in cell morphology by Hoechst 33342 staining. There was significant down regulation of blood-testis barrier (BTB) proteins in TM4 cells after exposure to PNNP which could compromise the integrity of BTB and subsequently disrupt spermatogenesis process in male. Conclusion: Our investigation confirms the cytotoxic and genotoxic effects of PNNP in TM4 cells, which could lead to spermatogenesis disruption and male infertility. [ABSTRACT FROM AUTHOR]

This study investigated the genotoxic risk of chronic exposure of hemolymph’s cells of Drosophila melanogaster (Insecta, Diptera) to water samples from Boqueirão de Parelhas Dam and from Lucrécia Dam in the semiarid region of Brazil. The dams are located over the Pegmatite Province of Borborema, with rocks rich in uranium and thorium. Water samples hydrated a culture medium composed of mashed potatoes, where larvae of D. melanogaster fed for 24 h, before be underwent to the Comet assay. The same water was evaluated for the presence of dissolved Radon gas (222Rn) and concentrations of 11 toxic metals (Ag, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn). The results indicated a genotoxic effect resulting from exposure to the waters of the Parelhas dam, in the samples of August 2018; and in Lucrécia dam, in January 2019. D. melanogaster stood out for its high sensitivity to monitor the genotoxic effects of compounds dissolved in public dams. And unlike to other essentially aquatic sentinel organisms, this species stood out as a model to concomitant studies of air and water possible contaminated, in a scenario of natural environmental radioactivity present in semiarid of Brazil. [ABSTRACT FROM AUTHOR]

In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis? The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting. A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak. In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions. [ABSTRACT FROM AUTHOR]

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 μM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Colorectal cancer, which is the third leading cause of cancer‐related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel‐forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1−/−) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1−/− female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2‐dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub‐acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH‐induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase‐3) in colonic crypts. Of note, at week 37, Panx1−/− animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease with aggregation of α-synuclein (α-syn) in substantia nigra (SN). The association between the α-syn and ferroptosis in PD remains unclear. GSE49036 was obtained from the Gene Expression Omnibus (GEO) database and intersected with ferroptosis genes. Bioinformatics analysis was used to identify the potential differentially expressed genes (DEGs) included the development of Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network. We screened 8 key genes were modulated and crosslinked by 238 miRNAs. Additionally, 5 hub genes were predicted and 38 lncRNAs targeting 3 key miRNAs were revealed. Finally, 3 hub genes (PIK3CA, BRD4, ATM) and the key lncRNA (NEAT1) were verified in neurotoxic PD models. The in vitro experiments showed that PIK3CA and ATM were significantly upregulated or the BRD4 was downregulated in the rotenone treatment and they could be rescued by the specific ferroptosis inhibitor, liproxstatin-1. The expression of the key lncRNA NEAT1 were consistent with the hub genes in same models. This study identified the proposed NEAT1-PIK3CA/ATM ceRNA network may be a specific biomarker in α-syn driving ferroptosis as well as to predict clinical outcomes and therapeutic targets in PD patients. [ABSTRACT FROM AUTHOR]

The Kidneys remove toxins from the blood and move waste products into the urine. However, the accumulation of toxins and fluids in the body leads to kidney failure. For example, the overuse of acrylamide and titanium dioxide nanoparticles (TiO2NPs) in many food and consumer products increases human exposure and risks; however, there are almost no studies available on the effect of TiO2NPs coadministration with acrylamide on the integrity of genomic and mitochondrial DNA. Accordingly, this study was conducted to estimate the integrity of genomic and mitochondrial DNA in the renal tissue of mice given acrylamide and TiO2NPs. To achieve this goal, mice were administrated orally TiO2NPs or/and acrylamide at the exposure dose levels (5 mg/kg b.w) and (3 mg/kg b.w), respectively, five times per week for two consecutive weeks. Concurrent oral administration of TiO2NPs with acrylamide caused remarkable elevations in the tail length, %DNA in tail and tail moment with higher fragmentation incidence of genomic DNA compared to those detected in the renal tissue of mice given TiO2NPs alone. Simultaneous coadministration of TiO2NPs with acrylamide also caused markedly high elevations in the reactive oxygen species (ROS) production and p53 expression level along with a loss of mitochondrial membrane potential and high decreases in the number of mitochondrial DNA copies and expression level of β catenin gene. Therefore, from these findings, we concluded that concurrent coadministration of acrylamide with TiO2NPs augmented TiO2NPs induced genomic DNA damage and mitochondrial dysfunction through increasing intracellular ROS generation, decreasing mitochondrial DNA Copy, loss of mitochondrial membrane potential and altered p53 and β catenin genes expression. Therefore, further studies are recommended to understand the biological and toxic effects resulting from TiO2NPs with acrylamide coadministration. [ABSTRACT FROM AUTHOR]

The unregulated expulsion of untreated textile water into water bodies is a major hazard to aquatic ecosystems. The present investigation was contrived to estimate the impact of textile dye bath effluent (untreated and microbially treated) on fish Channa punctata. Untreated effluent–exposed fish showed extremely altered behaviour (air gulping, erratic and speedy movements, increased opercular activity) and morphology (deposition of dyes on skin and scales, high pigmentation, mucus exudation). Significantly increased micronuclei (1.61-, 1.28-, 1.38-fold) and aberrant cell frequency (1.37-, 1.45-, 1.28-fold) was observed in untreated group as compared to treated group after 15, 30, and 45 days of exposure. Tail length, % tail intensity, tail moment and olive tail moment were also enhanced in all the exposed tissues. However, maximum damage was noticed in gill tissues showing 1.19-, 1.37-, 1.34- and 1.50-fold increased TL, %TI, TM and OTM in untreated group as compared to treated group after 45 days of exposure. On comparing untreated and treated groups, increased blood parameters and significantly reduced white blood cell count (WBC) were noticed in treated group. Significantly enhanced alterations in biochemical parameters were also analysed in untreated group. Reduced alterations in enzymological levels of fishes exposed to treated effluent indicate lesser toxic nature of the degraded metabolites of dye. Histological analysis in fishes exposed to untreated effluent showed several deformities in liver (necrosis, congestion, fusion of cells and melanomacrophage infiltration) and gill tissues (necrosis, bending of lamellae and severe aneurysm). Scanning electron microscopy (SEM) analysis further reaffirmed the pathologies observed in histological analysis. Fewer structural alterations were noticed in treated effluent fishes. The results concluded that untreated effluent inflicted toxicity potential on morphology as well as physiological defects in fish, and the severity increased with increasing duration of exposure, whereas reduction in toxicity in microbially treated groups can be analysed for aquacultural purposes owing to their lesser toxic nature. [ABSTRACT FROM AUTHOR]

Colors have been added to food naturally and artificially for centuries to make them look more appetizing. According to the Food and Drug Organization, eight artificial colors were registered for the nutrition application, one of them, is tartrazine, which is widely used in foods and cosmetics. Food colors significantly decrease weight and increase proteins, liver enzymes, thyroid hormones, total cholesterol, and triglyceride. Onion, as an antioxidant, can reduce the harmful effects of artificial food colors on weight gain, antioxidant activity, and blood biochemical factors. The present study aimed to evaluate the effects of the onion's antioxidant properties on serum biochemical factors and antioxidants in Wistar rats after consuming tartrazine. Eighty Rats were divided into four groups, 20 mice in each. The first group received water without additives and was considered the control, the second group received tartrazine, the third group received tartrazine with onion juice, and the fourth group received only onion juice through gastric gavage. This experiment was performed for 60 days, and then the antioxidant activities of superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx), and the biochemical parameters of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were measured. Tartrazine decreased the antioxidant activities of SOD, CAT, GPx, and the biochemical parameters of HDL and LDL. The results showed that the consumption of tartrazine causes the production of free radicals, which is the reason for the significant reduction of antioxidant activities and serum biochemical factors. Onion, as an antioxidant in this study, reduces the effects of tartrazine on antioxidant activities and serum biochemical factors. [ABSTRACT FROM AUTHOR]

RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification of intra- and intermolecular RNA-RNA interactions mediated by a specific RNA-binding protein (RBP). Using lhCLIP, we have uncovered a diverse landscape of intermolecular RNA interactions recognized by hnRNPK in human cells, involving all major classes of noncoding RNAs (ncRNAs) and mRNA. Notably, hnRNPK selectively binds with snRNA U4, U11, and U12, and shapes the secondary structure of these snRNAs, which may impact RNA splicing. Our study demonstrates the potential of lhCLIP as a user-friendly and widely applicable method for discovering RNA-RNA interactions mediated by a particular protein of interest and provides a valuable tool for further investigating the role of RBPs in gene expression and biological processes. Author summary: RBPs play a crucial role in post-transcriptional regulation of RNAs by modulating RNA-RNA interactions, encompassing processes like pre-mRNA splicing and mRNA degradation. Existing techniques for exploring RNA interactions associated with specific RBPs require some troublesome experimental procedures, including the use of radioisotopes to visualize RBP-RNA complexes and the introduction of exogenous expression of the target protein. In this context, we introduce lhCLIP, a novel method designed for capturing RNA-RNA interactions mediated by a specific protein. Diverging from other approaches reliant on radioisotopes, lhCLIP eliminates the need for their use. Moreover, its heightened sensitivity enables the capture of RNA-RNA interactions mediated by endogenously expressed RBPs, making it an intuitive and competitive option for researchers. We utilized lhCLIP to investigate RNA hybrids that are directly bound by hnRNPK, unveiling a complex array of intra- and intermolecular RNA interactions with the potential to exert influence over RNA splicing. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) accounts for considerable mortalities worldwide. Several modifiable risk factors, including a high intake of certain foods and beverages can cause CRC. This review summarized the latest findings on the intake of various foods, nutrients, ingredients, and beverages on CRC development, with the objective of classifying them as a risk or protective factor. High-risk food items include red meat, processed meat, eggs, high alcohol consumption, sugar-sweetened beverages, and chocolate candy. Food items that are protective include milk, cheese and other dairy products, fruits, vegetables (particularly cruciferous), whole grains, legumes (particularly soy beans), fish, tea (particularly green tea), coffee (particularly among Asians), chocolate, and moderate alcohol consumption (particularly wine). High-risk nutrients/ingredients include dietary fat from animal sources and industrial trans-fatty acids (semisolid/solid hydrogenated oils), synthetic food coloring, monosodium glutamate, titanium dioxide, and high-fructose corn sirup. Nutrients/ingredients that are protective include dietary fiber (particularly from cereals), fatty acids (medium-chain and odd-chain saturated fatty acids and highly unsaturated fatty acids, including omega-3 polyunsaturated fatty acids), calcium, polyphenols, curcumin, selenium, zinc, magnesium, and vitamins A, C, D, E, and B (particularly B6, B9, and B2). A combination of micronutrients and multi-vitamins also appears to be beneficial in reducing recurrent adenoma incidence. [ABSTRACT FROM AUTHOR]

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC–MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations. [ABSTRACT FROM AUTHOR]

Studies on adverse health consequences of azo dyes are limited and conflicting. Coenzyme Q10 (CoQ10) supplementation has been shown to have benefits associated with antioxidant and anti-inflammatory characteristics on several body systems. This work investigates the possible toxic effects of the widely used food additive sunset yellow and the probable protective effects of CoQ10 on testicular tight and gap junctions in rats by assessing molecular, immunohistochemical, and histopathological changes. Sixty Sprague–Dawley male weanling rats were randomly divided into six groups (n = 10). The rats received their treatments via daily oral gavages for 6 weeks. The treatments included as follows: low dose of sunset yellow (SY-LD) (2.5 mg/kg/day), high dose of sunset yellow (SY-HD) (70 mg/kg/day), CoQ10 (10 mg/kg/day), CoQ10 with low dose of sunset yellow (CoQ10 + LD), CoQ10 with high dose of sunset yellow (CoQ10 + HD), and distilled water as the control treatment. At the end of the experiment, the rats were anesthetized, and the testes were removed for molecular (real-time quantitative PCR), immunohistochemical, and histopathological (H & E staining) assessments. Claudin 11 and occludin gene expression significantly decreased in HD and CoQ10 + HD groups compared with the controls. Connexin 43 (Cx43) expression in the control and CoQ10 groups was significantly higher than in the HD group. The immunohistochemical and histopathological data were largely in line with these findings. The results showed that exposure to a high dose of sunset yellow led to disturbances in cell-to-cell interactions and testicular function. Simultaneous treatment with CoQ10 had some beneficial effects but did not completely improve these undesirable effects. [ABSTRACT FROM AUTHOR]

Plant polyphenols have poor water solubility, resulting in low bioavailability. In order to overcome this limitation, the drug molecules can be coated with multiple layers of polymeric materials. Microcrystals of quercetin and resveratrol coated with a (PAH/PSS)4 or (CH/DexS)4 shell were prepared using the layer-by-layer assembly method; cultured human HaCaT keratinocytes were treated with UV-C, and after that, cells were incubated with native and particulate polyphenols. DNA damage, cell viability, and integrity were evaluated by comet assay, using PrestoBlueTM reagent and lactate dehydrogenase (LDH) leakage test. The data obtained indicate that both native and particulate polyphenols added immediately after UV-C exposure increased cell viability in a dose-dependent manner; however, the efficiency of particulate quercetin was more pronounced than that of the native compound; also quercetin coated with a (CH/DexS)4 shell more effectively than the native compound reduced the number of DNA lesions in the nuclei of keratinocytes exposed to UV-C radiation; native and particulate resveratrol were ineffective against DNA damage. Quercetin reduces cell death caused by UV-C radiation and increases DNA repair capacity. Coating quercetin with (CH/DexS)4 shell markedly enhanced its impact on DNA repair. [ABSTRACT FROM AUTHOR]

In 2020, during the COVID-19 pandemic, containment measures were applied inducing potential changes in air pollutant concentrations and thus in air toxicity. This study evaluates the role of restrictions on biological effects of particulate matter (PM) in different Northwest Italy sites: urban background, urban traffic, rural, and incinerator. Daily PM samples collected in 2020 were pooled according to restrictions: January/February (no restrictions), March and April (first lockdown), May/June and July/August/September (low restrictions), October/November/December (second lockdown). The 2019 samples (pre-pandemic period) were pooled as 2020 for comparison. Pools were extracted with organic solvents and extracts were tested to assess cytotoxicity (WST-1 assay) and genotoxicity (comet assay) on BEAS-2B cells, mutagenicity (Ames test) on TA98 and TA100 Salmonella typhimurium strains, and estrogenic activity (gene reporter assay) on MELN cells. Pollutant concentrations were also analyzed (PM10, PM2.5, polycyclic aromatic hydrocarbons). No difference was observed for PM and polycyclic aromatic hydrocarbon concentrations between 2020 and 2019. During lockdown months (2020), PM cytotoxicity/genotoxicity was significantly lower in some sites than during 2019, while considering PM mutagenicity/estrogenic activity some differences were detected but without statistical significance. PM extract effects decreased in some sites during 2020; this may be due to lockdowns that reduced/modified pollutant emissions and may be related also to complex PM origin/formation and to meteorological conditions. In conclusion, the study confirms that PM biological effects cannot be assessed considering only the PM concentration and suggests to include a battery of bioassay for air quality monitoring in order to protect human health from air pollution effects. [ABSTRACT FROM AUTHOR]