Increase In Aberrations Research Articles

Exogenous application of mycotoxin fusaric acid improve the morphological, cytogenetic, biochemical and anatomical parameters in salt (NaCl) stressed Allium cepa L.

Salinity is one of the most important abiotic stress factors that negatively affect plant growth and development. In contrast, fusaric acid (FA), a mycotoxin produced by Fusarium and Giberella fungal genera, has biological and metabolic effects in various plants. In this study, it was aimed to investigate the protective effect of externally applied FA (0.1 nM) against the damage caused by salt (0.15 M NaCl) stress in onion (Allium cepa L.) plant. Salt stress resulted in an increase in the chromosomal aberrations (CAs) and micronucleus (MN) frequency, a decrease in the mitotic index (MI), fresh weight, root number, germination percentage, and root length. It promoted CAs such as irregular mitosis, bilobulated nuclei, chromosome loss, bridge, unequal seperation of chromosome, vagrant chromosome and polar slip in root meristem cells. In addition, salt stress caused a enhancement in free proline (PR), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the roots of onion plant. Moreover, it revealed damage and changes that include the accumulation of some chemical substances such as proline and sugars in epidermis and cortex layer cells, epidermal cell injury, flattening of the cell nucleus, wall thickening in cortex cells, necrotic areas and indistinct transmission tissue in the anatomical structure of onion roots. On the other hand, FA application promoted bulb germination and mitotic activity, strengthened the antioxidant defense system, and reduced chromosome and anatomical structure damages. In conclusion; it has been revealed that exogenous FA application may have a positive effect on increasing the resistance of onion plants to salt stress.

Nano-graphene oxide particles induce inheritable anomalies through altered gene expressions involved in oocyte maturation

The inheritable impact of exposure to graphene oxide nanoparticles (GO NPs) on vertebrate germline during critical windows of gamete development remain undetermined to date. Here, we analyzed the transgenerational effects of exposure to nano-graphene oxide particles (nGO) synthesized in house with lateral dimensions 300–600 nm and surface charge of −36.8 mV on different developmental stages of germ cells (GCs): (1) during GCs undergoing early development and differentiation, and (2) during GCs undergoing gametogenesis and maturation in adulthood. Biocompatibility analyses in Japanese medaka embryos showed lethality above 1 µg/ml and also an aberrant increase in germ cell count of both males and females at doses below the lethal dose. However, no lethality or anomalies were evident in adults up to 45 µg/ml. Long term exposure of embryos and adults for 21 days resulted in reduced fecundity. This effect was transmitted to subsequent generations, F1 and F2. Importantly, the inheritable effects of nGO in adults were pronounced at a high dose of 10 µg/ml, while 1 µg/ml showed no impact on the germline indicating lower doses used in this study to be safe. Further, expressions of selected genes that adversely affected oocyte maturation were enhanced in F1 and F2 individuals. Interestingly, the inheritance patterns differed corresponding to the stage at which the fish received the exposure.

Cytosolic zinc mediates the cytotoxicity of thiol-reactive electrophiles in rat vascular smooth muscle cells

The aberrant increase or dysregulation of cytosolic Zn2+ concentration ([Zn2+]cyt) has been associated with cellular dysfunction and cytotoxicity. In this study, we postulated that Zn2+ mediates the cytotoxicity of thiol-reactive electrophiles. This notion was grounded on earlier research, which revealed that thiol-reactive electrophiles may disrupt Zn2+-binding motifs, consequently causing Zn2+ to be released from Zn2+-binding proteins, and leading to a surge in [Zn2+]cyt. The thiol-reactive electrophiles N-ethylmaleimide (NEM) and diamide were observed to induce an increase in [Zn2+]cyt, possibly through the impairment of Zn2+-binding motifs, and subsequent stimulation of reactive oxygen species (ROS) formation, resulting in cytotoxicity in primary cultured rat vascular smooth muscle cells. These processes were negated by the thiol donor N-acetyl-L-cysteine and the Zn2+ chelator TPEN. Similar outcomes were detected with co-treatment involving Zn2+ and Zn2+ ionophores such as pyrithione or disulfiram. Moreover, TPEN was found to inhibit cytotoxicity triggered by short-term exposure to various thiol-reactive electrophiles including hydrogen peroxide, acrylamide, acrylonitrile, diethyl maleate, iodoacetic acid, and iodoacetamide. In conclusion, our findings suggest that cytosolic Zn2+ acts as a universal mediator in the cytotoxic effects produced by thiol-reactive electrophiles.

The effect of p53 on the activity of NRF2 and NDRG2 genes through apoptotic pathway in IDH-wildtype glioblastoma

BackgroundTumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. MethodsA group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. ResultsThe mean patients’ age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. ConclusionsDuring cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant.

Biosecurity test of conjugated nanoparticles of chitosan-protoporphyrin IX-vitamin B9 for their use in photodynamic therapy.

The main obstacle of Photodynamic Therapy (PDT) to damage and destroy abnormal cells is that most photosensitizers (Ps) have a highly hydrophobic nature with a tendency to aggregate in aqueous solutions and the non-specificity towards target cells. Nanotechnology proposes new tactics for the development of monomeric Ps nanotransporters and active targeting molecules with the use of biodegradable polymeric nanoparticles to improve the specificity towards target cells. However, these products must comply with safety tests to be endorsed as therapeutic alternatives by regulatory organizations. The goal of this work was to optimize the synthesis of chitosan polymeric nanoparticles conjugated with protoporphyrin IX and vitamin B9 (CNPs-PpIX-B9) by the ionic gelation method from the established protocol previously carried out by our laboratory with 1.74 times fold of efficiency. They were characterized by ultraviolet light-visible light, infrared spectroscopy and transmission electron microscopy. In addition, in CHO-K1 cells the biosafety (cytotoxicity and genotoxicity) of conjugate was assessed following the recommendations of the chromosomal aberrations test by OEDC 473 (2016) guideline. The conjugate did not show evidence of genotoxicity (clastogenicity). Surprisingly, the significant differences between the treatments performed and the negative control do not represent increases in chromosomal aberrations, whereby the safe concentrations to use the conjugate without inducing cytotoxic or genotoxic effects are less than 0.25 mg / mL. Since it induced a significant decrease of structural chromosomal aberrations, generating a positive effect on the genomic stability of CHO-K1 cells cultured in this test system.

Cytogenetic Analysis of the Crustacean Pontogammarus robustoides (Amphipoda, Gammaridae) at Increased Water Temperature under Conditions of Microcosm

Adaptive reactions of <i>Pontogammarus robustoides</i>, a representative of the family Gammaridae, were studied at the cellular level at the increase in water temperature to its critical values under conditions of a model ecosystem - a microcosm. A cytogenetic analysis of its embryo cells was carried out and the activity of nucleoli of somatic cells was investigated. It has been shown that normal development of <i>P. robustoides</i> embryo cells was observed within the temperature range from 25.0°C to 27.5°C. The increase in water temperature up to 30.0-30.5°C resulted in such structural and functional changes in its cells as the increase in chromosome aberrations and the increase in the number of micronuclei. At the prolonged exposure to the increased water temperature, these indices approached critical levels. The number of embryo cells with nuclear fragmentation increased, which is evidence of the development of the processes directed to apoptosis. The destruction of embryo cell structures was registered at 32.0°C. The total volume of nucleoli in the somatic cells increased, which can be indicative of the increased synthesis of proteins probably involved in the processes of adaptation. A decrease in water temperature to the initial level of 25.0°C favored recovery of the structural and functional indices of Gammaridae genome. However, a high contribution of cell division disorders was still observed, which was accompanied by a significant decrease in the number of micronuclei.

Biomechanical properties of cornea and ocular aberrations in myopic eyes.

To study the correlation of corneal topography, corneal biomechanical properties, and ocular aberrations with the magnitude of refractive error in myopic eyes. All myopic patients attending the clinic for refractive surgery were recruited. Data recorded included visual acuity, axial length (AL), central corneal thickness (CCT), manifest refraction spherical equivalent (MRSE), topography (Pentacam - Oculus), corneal biomechanical factors [ocular response analyzer (ORA)], and optical aberrations (iTrace). They were further categorized into group 1 (suitable for femto-LASIK) and group 2 (unsuitable for femto-LASIK). Sixty eyes (30 myopes) of mean age 22.78 ± 2.71 years were enrolled. A negative correlation of refractive error was noted with AL (ρ = -0.9; P < 0.001), total aberrations (ρ = 0.53; P < 0.001), and lower-order aberrations (LOA) (ρ = 0.54; P < 0.001). A strongly positive correlation was noted between CCT and corneal hysteresis (CH) (ρ = 0.63; P < 0.001), CCT and CRF (ρ = 0.56; P < 0.001), CH and corneal resistance factor (CRF) (ρ = 0.83; P < 0.001), and Goldmann equivalent intraocular pressure (IOPg) and corneal compensated intraocular pressure (IOPcc) (ρ = 0.78; P < 0.001). An increase in higher-order aberrations (HOAs) as well as lower-order aberrations (LOAs) was noted with increasing sim-K [HOA (r = 0.73, P = 0.001); LOA (r = 0.601, P = 0.014)] and increasing CRF [HOA (r = 0.5, P = 0.006); LOA (r = 0.732, P = 0.001)] in group 2. The amount of refractive error, axial length, central corneal thickness, and sim-K were significantly different in the two groups. Increasing degree of myopia is associated with an increase in axial length, total aberrations, and lower-order aberrations. Corneal biomechanical parameters have a strong correlation with each other. Lower corneal biomechanics are noted in high myopes as they have weaker and thinner corneas. Corneal biomechanics and ocular aberrations do not differ significantly between cases suitable for femto-LASIK and cases unsuitable for femto-LASIK.

NLRP3 inflammasome-produced pro-inflammatory cytokines IL-1b and IL-18 are critical exacerbating factors of septic cardiomyopathy

Abstract Background Sepsis is life-threatening multiple organ failure due to systemic infection, and frequently causes septic cardiomyopathy (SCM). Recent evidence has established that cytokine storm, an aberrant increase in various cytokines leading to severe inflammation and tissue damage, plays a crucial role in SCM. However, it is unknown which cytokines are the most critical initiators and exacerbating factors of SCM. Purpose To investigate how IL-1β and IL-18 driven by NLRP3 inflammasome contribute to the pathophysiology of SCM, and to study whether blockage of these cytokines can ameliorate cardiac dysfunction in a murine model of lipopolysaccharide (LPS)-induced SCM. Methods Wild-type, Nlrp3-/-, Casp1/11-/-, and Il1b-/- mice were injected intraperitoneally with 6 mg/kg of LPS to induce SCM. To suppress IL-18, the adeno-associated virus (AAV) vectors encoding IL-18 binding protein (IL-18BP) were injected intramuscularly 14 days before LPS. Bone marrow transplantation (5 Gy x2) was performed 6 weeks prior to LPS. Results While 40% of wild-type mice died 48 h after LPS injection in our SCM model, none of Nlrp3-/- mice died. Cardiac function, as determined by echocardiography and BNP, was significantly decreased 6 h after LPS injection in WT mice but not in Nlrp3-/- or Casp1/11-/- mice. Serum CK-MB increase was also ameliorated in Nlrp3-/- or Casp1/11-/- mice. Serum levels of various pro-inflammatory cytokines including TNFα, IL-1β, IL-6, IL-18, and IFNγ were suppressed in Nlrp3-/- mice. These findings collectively indicated a critical role of NLRP3 inflammasome in LPS-induced SCM. However, unexpectedly, genetic deletion of IL-1β, the canonical effector molecule of NLRP3 inflammasome, in Il1b-/- mice failed to alleviate cardiac dysfunction and damage caused by LPS. In addition, IL-18 suppression by AAV-mediated overexpression of IL-18BP, a high-affinity IL-18 decoy receptor, only partially prevented LPS-induced SCM. On the other hand, intriguingly, dual inhibition of IL-1β and IL-18 successfully protected mice from LPS-induced SCM, demonstrating that concomitant blockage of two NLRP3 inflammasome products, IL-1β and IL-18, was necessary and sufficient to prevent SCM. Finally, while bone marrow transplantation experiments showed that cardiac dysfunction after LPS injection was suppressed in recipient Nlrp3-/- mice transplanted with wild-type bone marrow cells, cardiomyocyte-specific deletion of NLRP3 in αMHC-Cre;Nlrp3-/- mice did not prevent LPS-induced SCM. These data suggest that NLRP3 inflammasome in resident cells other than bone marrow-derived cells and cardiomyocytes is important in the pathophysiology of SCM. Conclusion The present study indicates that concomitant blockage of IL-1β and IL-18 driven by NLRP3 inflammasome is necessary and sufficient to prevent SCM. Our data provide fundamental evidence that combination therapy targeting both IL-1β and IL-18 could serve as a new approach to the treatment of SCM.

Evaluation of Corneal High Order Aberrations in Post Laser-Assisted in Situ Keratomileusis versus Photorefractive Keratectomy in Myope

Background Aberrations of the eye are the difference between two surfaces: the ideal and the actual wave front. Higher order aberrations are a relatively small component, comprising about 10% of the eye’s total aberrations. High order aberrations increase with age and minor symmetry exists between the right and the left eyes. Aim and objectives To Compare corneal high order aberrations in post laser-assisted in situ keratomileusis with corneal high order aberrations in post Photorefractive keratectomy in myope. Subjects and methods this study was designed as a prospective randomized intervention study that conducted on 40 myopic eyes. The eyes divided into two randomized groups. Group A: 20 myopic eyes corrected with laser-assisted in situ keratomileusis and Group B: 20 myopic eyes corrected with Photorefractive keratectomy. Cases were collected for LASIK and PRK at operative theater in Beni-Suef University Hospital and clear vision laser center in Cairo, from May 2019 till January 2022. Result There was clinically significant difference between pre- and post-operative visual acuity, vertical trefoil and vertical coma of LASIK group and there was clinically significant between pre- and post-operative visual acuity, vertical trefoil and vertical coma of PRK group. But there was no significant difference between LASIK and PRK in visual acuity, spherical aberration, higher order 5 mm and 6 mm, vertical coma and Vertical trefoil. Conclusion There is non-significant increase in higher order aberration and spherical aberration post LASIK and post PRK with lesser amount in PRK.

Comparative analysis of the correction of irregular postkeratoplastic astigmatism with scleral lenses and intrastromal ring implantation

Background. Many patients after penetrating keratoplasty (PK) experience induced postkeratoplastic astigmatism, which is often irregular and causes an increase in corneal aberrations that reduce visual acuity and quality. The aim of the study. To conduct a comparative analysis of the effect of rigid gas permeable scleral lenses and the MyoRing implantation method on clinical and functional parameters in patients with IPA. Material and methods. The clinical study included 60 patients (60 eyes). The age of patients with IPA was from 25 to 42 years. All patients underwent penetrating keratoplasty. All patients were divided into two groups depending on the method for irregular postkeratoplastic astigmatism correction. Group I included 30 patients (30 eyes) who were fitted with rigid gas permeable scleral lenses. Group II consisted of 30 patients (30 eyes) who underwent implantation of the MyoRing into a penetrating corneal graft. The observation period was 1 year. Results. After 12 months of observation, there was a greater increase in uncorrected visual acuity by an average of 3 lines, in corrected visual acuity – by 2 lines; a greater decrease in corneal aberrations in photo- (root mean square (RMS) of total aberrations (RMS total) by 0.30 ± 0.08 µm, RMS of higher order aberrations (RMS HOA) – by 1.01 ± 0.24 μm) and mesopic conditions (RMS total – by 0.33 ± 0.09 μm, RMS HOA – by 0.08 ± 0.03 μm) in patients wearing rigid gas permeable scleral lenses compared with patients after MyoRing implantation into a penetrating corneal graft. Conclusion. Patients of group I, wearing rigid gas permeable scleral lenses, showed a greater improvement in visual acuity and a decrease in corneal aberrations in photo- and mesopic conditions compared to the patients of group II (after MyoRing implantation) at a follow-up period of 12 months.

Evaluation of the Genotoxicity of the Aerial Parts of Iraqi Euphorbia cyathophora on Bone Marrow and Spleen Cells in Mice

The aim of the study was extraction of arial part of Euphorbia cyathophora constituents with methanol and evaluate its effect on mitotic index and total chromosomal aberration bone marrow cell and spleen cell in mice&#x0D; 200 gm of E. cyathophora fine powder was defatted then extracted by cold maceration 80% ethanol for seven days. The extract was filtered and dried in a rotary evaporator then the dried extract was suspended with water and consecutively extracted using chloroform, ethyl acetate for each. The aqueous layer was then mixed with 100ml methanol. These fractions are dried under reduced pressure to obtain the dry extract. Twenty-four Albino mice were used for the experiment. The animals were divided into four groups: Group 1: Mice were treated with distilled water. The dose was given daily for seven successive days. Group 2: Mice were treated with a single dose (20mg/kg) of methotrexate (positive control). Group 3: Mice were treated with (100mg/kg) of menthol fraction for seven successive days. Group 4: Mice were treated with (200mg/kg) of methanol fraction for seven successive days. Mice were sacrificed by (spinal dislocation). Samples of bone marrow cells and spleen cells were taken and genotoxic analyses.&#x0D; Methanol fraction of Euphorbia cyathophora at a dose of 100mg/kg demonstrated a significant decrease in mitotic index and a significant increase in total chromosomal aberrations as compared to distilled water in both bone marrow cells and spleen cells&#x0D; (p&lt;0.05). 100 mg/kg and 200 mg/kg of methanol fraction of Euphorbia cyathophora that showed to be significantly higher in mitotic index and significantly lower in total chromosomal aberration as compared to methotrexate (p&lt;0.05).&#x0D; In conclusion the current study revealed that the methanol fraction of aerial parts of Euphorbia cyathophora is genotoxic but its genotoxicity is less than that of methotrexate.

Quality of Vision and Ocular Higher Order Aberrations after SMILE for Myopia and Myopic Astigmatism

Background Previous studies have shown considerable amounts of higher order aberrations following SMILE. In our study we aim at accurately quantifying the higher order aberrations following SMILE in myopia and myopic astigmatism. Objective To detect the effect of SMILE on quality of vision and the incidence of higher order aberrations following SMILE. Patients and Methods This is a prospective study that included 30 eyes of 18 patients presented in the outpatient clinic seeking advice for myopic refractive surgical correction. The study was conducted in accordance with the ethical standards stated by the ethical committee of Ain shams university hospitals with informed consents obtained from all participants. Results On studying the post-operative corneal third order aberrations we detected increase in post-operative vertical and horizontal coma, and spherical aberrations with non-significant change in vertical and horizontal trefoil. According to our study results, SMILE is an effective refractive surgery that improves visual acuity. That causes decrease in quality of vision through modulation transfer ratio and increase in ocular higher order aberrations. Conclusion SMILE (small incision lenticule extraction) is an efficient modality for refractive surgical correction of myopia and myopic astigmatism, with significant post-operative improvement in unaided visual acuity detected post-operative increase in the ocular HOAs. Total coma, trefoil and sphere increase significantly in mesopic more than photopic pupil. The degree of myopia didn’t affect the ocular higher order aberrations except for modulation transfer ratio.

Organotypic culture model of mouse meibomian gland as a screening platform for risk factors related to meibomian gland dysfunction

PurposeMeibomian glands (MGs) are crucial for maintaining tear film stability and ocular surface health. Here, we aim to establish a novel organotypic culture model of MGs and explore the risk factors of MG dysfunction (MGD). MethodsWe developed a novel organotypic culture model for MGs at the air-liquid interface. The viability and cell proliferation of MGs were assessed using CCK-8, immunofluorescence, and qPCR. Lipid accumulation was evaluated by Nile red staining and microscopic examination. Protein expression levels were evaluated by immunofluorescence and Western blot assay. EdU assay was employed to track the proliferation of acinar cells. The validity of the model was confirmed through culturing MGs from mice of different ages and incorporating certain drugs (Dex) into the culture system. ResultsUtilizing the novel culture model, the MG tissue exhibited sustained viability, cellular division, and continuous production of lipids for a duration of 7 days. Lipid droplets formed were directly visualized using light field microscopy. Through the cultivation of aged mice's MGs, it was discovered that aging resulted in diminished proliferation and lipid synthesis, along with an aberrant increase in Krt10 expression. Further application of this model showed that Dex treatment diminished MG's proliferation and lipid synthesis. Finally, an in vivo study was conducted to provide additional confirmation of the phenomenon of Dex-induced abnormalities. ConclusionsIn this study, a stable organotypic culture model of the MGs was established. The organotypic culture model offers a valuable tool to investigate the pathophysiological mechanisms and facilitate drug screening for MG-related diseases.

Canagliflozin alleviates experimentally induced benign prostate hyperplasia in a rat model: exploring potential mechanisms involving mir-128b/EGFR/EGF and JAK2/STAT3 signaling pathways through in silico and in vivo investigations

Benign prostatic hyperplasia (BPH) poses a significant health concern amongst elderly males. Canagliflozin (Cana), a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has a powerful anti-inflammatory influence. Nevertheless, its role in treating BPH has not been clarified. Therefore, the study aimed to investigate the potential ameliorative effect of Cana on experimentally induced BPH in rats and explore the underlying mechanisms compared to the standard finasteride (Fin). The study employed histological analysis, biochemical assays using ELISA, and western blotting. Animals were categorized into four groups: Control (2.5 ml/kg CMC, orally + 3 ml/kg olive oil, subcutaneous), BPH (3 mg/kg testosterone, subcutaneous + CMC orally), Fin-treated BPH (5 mg/kg, orally), and Cana-treated BPH (5 mg/kg, orally), for 28 days. The BPH group showed obvious BPH manifestations including an increase in prostate weight (PW), prostate index (PI), dihydrotestosterone (DHT) level, and histological aberrations compared to control. Fin and Cana therapy had a comparable impact. Cana treatment significantly reduced PW and PI, besides it improved prostatic biochemical, and histopathological features compared to BPH, consistent with in silico study findings. Cana was associated with downregulation of the androgen axis, increased miR-128b expression, with a lowered expression of epidermal growth factor (EGF) and its receptor. Phosphorylation of STAT3 and its downstream proliferative markers were significantly reduced suggesting apoptotic activity. Cana markedly rescued the BPH-induced upregulation of IL-1β, and iNOS levels. Altogether, the current study demonstrates that Cana could impede BPH progression, possibly by modulating miR-128b/EGFR/EGF and JAK2/STAT3 pathways and downregulating AR, cyclin D1, and PCNA immunoreactivity.

Regulation of SELENOF translation by eIF4a3: Possible role in prostate cancer progression.

The levels of the SELENOF selenoprotein are dramatically reduced in prostate cancer compared to adjacent benign tissue and reducing SELENOF in prostate epithelial cells results in the acquisition of features of the transformed phenotype. It was hypothesized that the aberrant increase in the eiF4a3 translation factor, which has an established role in RNA splicing and the regulation of selenoprotein translation, contributes to the lower levels of SELENOF. Using the available databases, eIF4a3messenger RNA (mRNA) levels are elevated in prostate cancer compared to normal tissue as is the hypomethylation of the corresponding gene. Using a prostate cancer tissue microarray, we established that eiF4a3 levels are higher in prostate cancer tissue. Ectopic expression of eIF4a3 in prostate cancer cells reduced SELENOF levels and attenuated the readthrough of the UGA codon using a specialized reporter construct designed to examine UGA decoding, with the opposite effects observed using eIF4a3 knock-down constructs. Direct binding of eIF4a3 to the regulatory regions of SELENOF mRNA was established with pull-down experiments. Lastly, we show that an eIF4a3 inhibitor, eIF4a3-IN-2, increases SELENOF levels, UGA readthrough, and reduces binding of eIF4a3 to the SELENOF mRNA 3'-UTR in exposed cells. These data establish eIF4a3 as a likely prostate cancer oncogene and a regulator of SELENOF translation.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells

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.

5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system

The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably, the phase differences between structures were close to zero, corresponding to <1 ms delays. Likely, this hypersynchrony has major effects on the integration of information across neuronal systems and we propose that it is a key contributor to changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.

Evaluation of toxicity and genotoxicity of concrete cast with steel slags using higher terrestrial plants.

The potential impact of concrete mixtures containing steel slag (SS) as a partial replacement of natural aggregates on the terrestrial ecosystem was assessed using a battery of plant-based bioassays. Leaching tests were conducted on four concrete mixtures and one mixture containing only natural aggregates (reference concrete). Leachates were tested for phytotoxicity using seeds of Lepidium sativum, Cucumis sativus, and Allium cepa. Emerging seedlings of L. sativum and A. cepa were used to assess DNA damage (comet test). The genotoxicity of the leachates was also analysed with bulbs of A. cepa using the comet and chromosome aberration tests. None of the samples caused phytotoxic effects. On the contrary, almost all the samples supported the seedlings and two leachates, one from the SS-containing concrete and the other from the reference concrete, promoted the growth of C. sativus and A. cepa. The DNA damage of L. sativum and A. cepa seedlings was significantly increased only by the reference concrete sample. In contrast, the DNA damage in A. cepa bulbs was significantly enhanced by the reference concrete, but also by that of a concrete sample with SS. Furthermore, all leachates caused an increase in chromosomal aberrations in A. cepa bulbs. Despite some genotoxic effects of the concrete on plant cells, the partial replacement of SS does not seem to make the concrete more hazardous than the reference concrete, suggesting the potential use of SS as a reliable recycled material.

Cytotoxicity and Genotoxicity Evaluation of Zanthoxylum rhoifolium Lam and In Silico Studies of Its Alkaloids.

The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC-DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 μg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

(Re)Presenting War: A Study of Resilience in Tim O’ Brien’s the Things They Carried

War has registered itself as an inseverable reality of modern times. However, it has marked its presence since the inception of human civilization, and so have the narratives centring it. An investigation into the traditional mainstream narratives divulge the repeated construction of lofty perceptions around war. Per contra to the representation, there have been stories from the battlefield that have created cervix in the narration. Modern times, with the increasing number an intensity of war, resulted in the increase in aberrations in the traditional presentation and brought forth the not-so-glorious-and-glamourous aspects that had been shoved under the carpet by the authors. Tim O’ Brien, in his collection The Things They Carried, touches upon his own experiences and those of a few others during the Vietnam War. He presents the stories as fictional accounts and still manages to give words to the “unspeakable.” As an addition to the conventional presentation of wounds as physical, Brien and various other authors of modern times delve into exploring the emotional and psychological damage as well, that, no doubt, leaves indelible prints while on the field and clings on to some beyond war too. The research paper attempts to delve into exploring the role of resilience in veterans combatting the lone war in the midst of expectations that the traditional war narratives have given birth to. Through this, the paper also strives to locate truth in the portrayal of war.