Induction Of Aberrations Research Articles

In Silico Methods for Chromosome Damage.

Due to the link with serious adverse health effects, genotoxicity is an important toxicological endpoint in each regulatory setting with respect to human health, including for pharmaceuticals. To this extent, a compound potential to induce gene mutations as well as chromosome damage needs to be addressed. For chromosome damage, i.e., the induction of structural or numerical chromosome aberrations, several in vitro and in vivo test methods are available. In order to rapidly collect toxicological data without the need for test material, several in silico tools for chromosome damage have been developed over the last years. In this chapter, a battery of freely available in silico chromosome damage prediction tools for chromosome damage is applied on a dataset of pharmaceuticals. Examples of the different outcomes obtained with the in silico battery are provided and briefly discussed. Furthermore, results for coumarin are presented in more detail as a case study. Overall, it can be concluded that although they are in general less developed than those for mutagenicity, in silico tools for chromosome damage can provide valuable information, especially when combined in a battery.

Extension of the BIANCA biophysical model up to Fe-ions and applications for space radiation research

BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) is a biophysical model, implemented as a Monte Carlo code, which simulates the induction of chromosome aberrations and cell death by different monochromatic ion beams (i.e., different ion types and energy values), as well as photons. In previous works, the model predictions for cell survival and lymphocyte dicentrics along therapeutic-like ion beams have been successfully benchmarked against experimental data. With the aim of evaluating the biological damage induced by Galactic Cosmic Rays (GCR), in this study BIANCA was extended up to Fe-ions. A radiobiological database describing human skin fibroblast cell survival and lymphocyte dicentrics as a function of ion type (1≤Z≤26) and energy, as well as dose, was constructed. Afterwards, interfacing BIANCA with the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the Relative Biological Effectiveness (RBE) of Galactic Cosmic Rays, both for dicentrics and for cell survival; the results were discussed with respect to available space radiation protection limits. Following this work, BIANCA can now provide RBE predictions of cell killing, which can be related to deterministic effects, and lymphocyte dicentrics, more related to stochastic effects, for space radiation exposure.

Antimutagenic Activity of Cassia Auriculata Linn Fractions along with Anticancer Activity in Male Albino Mice

Background: In recent years, there has been a surge in interest in studying plant-derived materials and their impact on DNA. Herbal products include a number of natural substances that may help protect cells against mutagen-induced cell damage.
 Aim: The purpose of this research was to assess the genotoxic effects of Cassia Auriculata Linn flavonoids (CAF) and Cassia Auriculata Linn saponin (CAS) rich fractions on mouse bone marrow cells utilizing chromosomal aberration test and micronucleus assay.
 Methodology: The suppressive impact of CAF and CAS on 7, 12-dimethylbenz (α) anthracene (DMBA) and Croton oil induced skin tumor promotion in mice with topical administration twice weekly for 18 weeks is also investigated in this work. Three dosages of 100 and 200 mg/kg body weight were used. Single oral dosages of CAF and CAS Fraction at the three levels did not enhance the number of micronucleate polychromatic erythrocytes in the micronucleus experiment.
 Result: In mice bone marrow cells, a single oral treatment of CAF and CAS fraction revealed no significant alterations in mitotic indices or chromosomal aberration induction. The clastogenicity of CYP was considerably decreased by pretreatment with CAF and CAS fraction. As a result, it can be stated that CAF and CAS fraction had no genotoxic impact on mouse bone marrow cells.
 Conclusions: The portions of Cassia Auriculata have been shown to be non-genotoxic and non-clastogenic at the quantities utilized in this investigation. CAF and CAS Fraction might possibly be a promising skin tumor promotion reducing agent, according to this research.

NAMPT-derived NAD+ fuels PARP1 to promote skin inflammation through parthanatos cell death.

Several studies have revealed a correlation between chronic inflammation and nicotinamide adenine dinucleotide (NAD+) metabolism, but the precise mechanism involved is unknown. Here, we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation, and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD+ supplementation. Similarly, genetic and pharmacological inhibition of poly(ADP-ribose) (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases, and reactive oxygen species (ROS) scavenging all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased the expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of NAMPT and PARP activity, together with AIFM1 nuclear translocation, was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD+, mediates skin inflammation through parthanatos cell death.

Peripheral Refraction, Wave Front of the Eye and Visual Performance in the Correction of Myopia in Children with Bifocal Soft Contact Lenses with High Addition

Purpose: to study the effect of bifocal soft contact lens (BSCL) with an ADD of 4 diopters on peripheral refraction (PR), optical and ergonomic eye parameters in children with myopia.Patients and methods. 26 patients (52 eyes) with myopia –3.09 ± 1.13 diopters at the age of 10.04 ± 1.5 years without correction and with correction by BSCL Prima BIO Bi-focal ( Okay Vision Retail, Russia). All patients underwent a horizontal and vertical PR study on an open field autorefractometer Grand Seiko WAM-5500 (Japan), wavefront aberrations were studied on OPD-Scan III aberrometer (Nidek, Japan), contrast sensitivity under mesopic conditions were studied on a Mesotest 2 instrument (Oculus, Germany) and visual productivity was studied using test tables.Results. The visual acuity of the distance with a BSCL correction of 0.98 ± 0.04 did not differ (p = 0.26) from the maximum visual acuity corrected by spherocylindrical glasses of 0.99 ± 0.04. BSCL induces myopic defocus in all peripheral zones, with a maximum value of 15° and a sharp decrease of 30°. Peripheral myopic defocus induced by the lens at a horizontal and vertical angle of 15 degrees did not depend on the initial degree of myopia. BSCL increases the total RMS from 0.07 ± 0.02 μm to 0.19 ± 0.07 μm in the 3 mm zone (p < 0.01) and from 0.27 ± 0.09 μm to 1.18 ± 0, 23 μm in the 6 mm zone (p < 0.01), mainly due to an increase in spherical aberration from –0.0005 ± 0.006 μm to 0.06 ± 0.01 μm (p < 0.01) and from 0.01 ± 0.09 μm to 0.58 ± 0.14 μm (p < 0.01) in the 3 mm and 6 mm zones, respectively. An increase in the overall RMS in BSCL reduces the quality of eye optics and contrast sensitivity under mesopic conditions, but does not impair visual productivity.Conclusion. BSCLs with a high ADD of 4 diopters are capable of inducing significant myopic peripheral defocus due to the induction of spherical aberration, while maintaining high visual acuity and not changing ophthalmic ergonomics, which makes them a pathogenetically substantiated method for correcting myopia and preventing its progression in children and adolescents.

Cytotoxic and genotoxic evaluation of dipyridamole and its alternative therapeutic potential in cancer therapy: an in vitro and in vivo approach.

The molecular mechanism behind the anti-cancer potential of dipyridamole, an antiplatelet drug was investigated by examining the interaction of dipyridamole with DNA as well as the genotoxicity and cytotoxicity associated with dipyridamole . Interaction of dipyridamole with calf thymus DNA (Ct-DNA) was determined in order to ascertain the strength and mode of binding as well as the thermodynamic parameters involved. Dipyridamole interacts with Ct-DNA through a groove binding mechanism. Furthermore, a preliminary assessment of the genotoxic effect of dipyridamole was performed in vitro using the plasmid nicking assay and comet assay. Genotoxicity was also confirmed through DAPI nuclear staining of HeLa and HCT-116 cells. Cytotoxicity was assessed in vitro on HeLa, HCT-116 as well as HEK293 cells using the MTT assay as well as through inverted microscopy. Dipyridamole was selectively more toxic towards cancer cells. Dipyridamole demonstrated induction of micronucleus and chromosomal aberrations only at high concentrations in bone marrow cells of male Wistar rats, suggesting its safe usage at clinically relevant concentrations. These results indicated the existence of an intrinsic genotoxic potential of dipyridamole which may be contributing to its anti-cancer properties.

Impact of extreme (flat and steep) keratometry on the safety and efficacy of small incision lenticule extraction (SMILE)

Little is known about the connection between preoperative keratometry and postoperative results of myopic small-incision lenticule extraction (SMILE). To determine the influence of extreme (flat and steep) corneal keratometry on the safety and efficacy of SMILE, the databases of the Department of Ophthalmology, Ludwig-Maximilians-University Munich, Germany, and SMILE Eyes Linz, Austria, were screened for patients with steep and flat keratometry who had undergone SMILE. In this cross-sectional matched comparative cohort study, eyes with markedly flat (< 42.0 diopters; D) or steep (≥ 47.0D) preoperative corneal keratometry were matched to a cohort of eyes with regular keratometry (42.0–46.9D) by preoperative manifest refractive spherical equivalent and cylinder, age, corrected distance visual acuity and surgical SMILE parameters. The standardized graphs and terms for refractive surgery results were applied to compare the three groups. Changes in higher order aberrations (HOAs) were evaluated on Scheimpflug imaging. In total, 63 eyes (21 each) of 54 patients with a mean refractive spherical equivalent of − 5.21 ± 1.59 D were followed up for a mean of 9.2 ± 6.1 (minimum ≥ 3) months. Mean baseline keratometry was 41.3 ± 0.7D (flat), 45.5 ± 1.0D (regular) and 47.7 ± 0.6D (steep) (p < 0.0001). Compared to the regular group, the flat and the steep cornea group resulted in a non-inferior percentage of eyes within ± 0.50 D of target refraction (p = 0.20), uncorrected distance visual acuity (p = 0.95) and corrected distance visual acuity (p = 0.20). Flat corneas however experienced a stronger induction of spherical aberration (SA) compared to the steep group (p = 0.0005). In conclusion, non-inferior outcomes of SMILE can also be expected in eyes with steep (≥ 47D) or flat (< 42D) preoperative keratometry, while SMILE however induces more SA in eyes with a flat keratometry.

Two-Year Changes in Corneal Spherical Aberration After Laser-Assisted In Situ Keratomileusis and Photorefractive Keratectomy in Regular and Wavefront-Guided Ablations.

IntroductionThe aim of this study was to analyze the changes in corneal spherical aberration following regular ablation (RA) and wavefront-guided (WFG) ablations in photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK).MethodsA retrospective analysis was performed on the eyes that underwent femtosecond LASIK or PRK between January 2016 and December 2018. Changes in the corneal spherical aberration were measured preoperatively and postoperatively with a high-resolution Scheimpflug camera system, and they were correlated with the attempted correction and all other tomography parameters.ResultsOf the 3826 eyes that were reviewed, 484 eyes met the inclusion criteria and were enrolled in the study. Seventy-four eyes underwent PRK and 410 eyes underwent LASIK. The LASIK and PRK subgroups were similar in terms of the general demographics, preoperative higher-order aberrations, and manifest spherical equivalent. The changes in spherical aberration were significantly correlated with the attempted correction in both LASIK (y = –0.35x and R2 = 0.42 for myopic WFG; y = –0.18x and R2 = 0.19 for myopic RA; y = –0.44x and R2 = 0.49 for hyperopic WFG; y = –0.53x and R2 = 0.69 for hyperopic RA) and PRK (y = –0.20x and R2 = 0.25 for myopic WFG; y = –0.37x and R2 = 0.44 for myopic RA). No other preoperative parameters except corneal asphericity, axial length, and anterior chamber depth were significantly correlated with the changes in the spherical aberration.ConclusionsLASIK correction had a higher induction of spherical aberration compared with that of PRK, and the beneficial effect of the WFG treatment on spherical aberration was mainly visible in the PRK-treated eyes.

Alkaline-extracted cyanide from cassava wastewater and its sole induction of chromosomal aberrations in Allium cepa L. root tips

ABSTRACT Cassava, a staple crop in Nigeria, processed by numerous factories in rural and suburban locations is known to contain some level of cyano compounds. Lack of stringent environmental regulations on the management of cassava wastewater (CWW) from cassava-processing factories had led to its indiscriminate discharge on the environment. CWW samples were obtained from cassava-processing factories from selected states (Lagos (A), Oyo (B), Ogun 1 (C1), Ogun 2 (C2) and Cross River (D)) in Nigeria to determine the cytotoxic and genotoxic effects of extracted cyanide from the wastewaters. The cyanide was hydrolysed via chemical degradation utilizing 1.25 M NaOH and subsequently titrated using silver nitrate with p-dimethylaminobenzalrhodamine as indicator. Further, in order to explore the potential toxicity of this pollutant present in the effluent, a battery of short-term biological assay (Allium cepa chromosomal aberration test) was used. Bulbs with roots of Allium cepa L. were treated with different concentrations (0.05%, 0.1%, 0.2%, 0.4% and 0.8%) of CWW, and after 48 h, the root tips were processed for cytological studies by the aceto-orcein squash procedure. The results revealed that cyanide concentrations on re-fluxing were in the range of 1.0 and 1.3 mg/L. All concentrations induced a number of chromosomal aberrations in the root tip cells. The mitotic index decreased significantly (p < 0.05) with increasing concentration. The cytotoxic effects showed strong concentration-dependent root growth inhibition with EC50 values of 30%, 20%, 37%, 43% and 22% for A, B, C1, C2 and D, after 72 h. The findings thus indicate that alkali treatment is very efficient in degrading the cyanide content of CWW and has shown that the combination of physico-chemical analysis along with the sole toxicity assessment could provide valuable information about the sole toxicity of cyanide as a chemical pollutant present in the cassava effluent.

Localization matters: nuclear-trapped Survivin sensitizes glioblastoma cells to temozolomide by elevating cellular senescence and impairing homologous recombination

To clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) and in vivo, distinguishing between its nuclear and cytoplasmic localization. Expression of nuclear export sequence (NES)-mutated Survivin (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due to enhanced cell death but rather due to increased senescence. Nuclear-trapped Survivin reduced homologous recombination (HR)-mediated double-strand break (DSB) repair, as evaluated by γH2AX foci formation and qPCR-based HR assay leading to pronounced induction of chromosome aberrations. Opposite, clones, expressing free-shuttling cytoplasmic but not nuclear-trapped Survivin, could repair TMZ-induced DSBs and evaded senescence. Mass spectrometry-based interactomics revealed, however, no direct interaction of Survivin with any of the repair factors. The improved TMZ-triggered HR activity in Surv-GFP was associated with enhanced mRNA and stabilized RAD51 protein expression, opposite to diminished RAD51 expression in SurvNESmut cells. Notably, cytoplasmic Survivin could significantly compensate for the viability under RAD51 knockdown. Differential Survivin localization also resulted in distinctive TMZ-triggered transcriptional pathways, associated with senescence and chromosome instability as shown by global transcriptome analysis. Orthotopic LN229 xenografts, expressing SurvNESmut exhibited diminished growth and increased DNA damage upon TMZ, as manifested by PCNA and γH2AX foci expression, respectively, in brain tissue sections. Consequently, those mice lived longer. Although tumors of high-grade glioma patients expressed majorly nuclear Survivin, they exhibited rarely NES mutations which did not correlate with survival. Based on our in vitro and xenograft data, Survivin nuclear trapping would facilitate glioma response to TMZ.

Efficacy evaluation of Rauwolfia serpentina against Chromium (VI) toxicity in fish, Channa punctatus

Aim: To explore the efficacy potential of ethanolic root extract of Rauwolfia serpentina against Chromium (VI) toxicity in fish, Channa punctatus. Methodology: Acclimatized fish were divided into six groups, each having 15 specimens. Group I served as a control, while Group II and III fish were exposed to ethanolic root extract of Rauwolfia serpentina (3 mg l-1) and Cr (VI) (96 h LC50/10; 7.68 mg l-1), respectively. Groups IV, V and VI fish were exposed to three different concentrations of ethanolic root extract of Rauwolfia serpentina (1, 2 and 3 mg l-1), simultaneously with 7.68 mg l-1 of Cr (VI). The induction of micronuclei, chromosomal aberrations, protein levels and liver enzymes-SGOT, SGPT and ALP- were assessed in fish of all six groups after designated exposure periods. Results: A significant induction (p&lt;0.05) in chromosomal aberrations, micronuclei frequency and activities of liver enzymes (SGOT, SGPT and ALP) coupled with reduced protein level was recorded in Group III as compared to the control. Whereas, a significant (p&lt;0.05) decrease in the frequency of chromosomal aberrations, micronuclei induction and activities of liver enzymes together with an increase in protein level was observed in Group IV, V and VI with respect to control and Group III. Interpretation: Present investigation evince the ameliorative potential of ethanolic root extract of Rauwolfia serpentina against Cr (VI) induced chromosomal aberrations and micronuclei induction, changes in protein levels and biochemical alterations of liver enzymes in Channa punctatus. Thus would help present work helps in saving the aquatic biodiversity and increasing the production of protein rich food fish.

Synergistic Effects of Chronic Restraint-Induced Stress and Low-Dose 56Fe-particle Irradiation on Induction of Chromosomal Aberrations in Trp53-Heterozygous Mice.

Astronauts can develop psychological stress (PS) during space flights due to the enclosed environment, microgravity, altered light-dark cycles, and risks of equipment failure or fatal mishaps. At the same time, they are exposed to cosmic rays including high atomic number and energy (HZE) particles such as iron-56 (Fe) ions. Psychological stress or radiation exposure can cause detrimental effects in humans. An earlier published pioneering study showed that chronic restraint-induced psychological stress (CRIPS) could attenuate Trp53 functions and increase carcinogenesis induced by low-linear energy transfer (LET) γ rays in Trp53-heterozygous (Trp53+/-) mice. To elucidate possible modification effects from CRIPS on high-LET HZE particle-induced health consequences, Trp53+/- mice were received both CRIPS and accelerated Fe ion irradiation. Six-week-old Trp53+/- C57BL/6N male mice were restrained 6 h per day for 28 consecutive days. On day 8, they received total-body Fe-particle irradiation (Fe-TBI, 0.1 or 2 Gy). Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Induction of psychological stress in our experimental model was confirmed by increase in urinary corticosterone level on day 7 of restraint regimen. Regardless of Fe-TBI, CRIPS reduced splenocyte number per spleen at the end of the 28-day restraint regimen. At 2 Gy, Fe-TBI alone induced many aberrant chromosomes and no modifying effect was detected from CRIPS on induction of aberrant chromosomes. Notably, neither Fe-TBI at 0.1 Gy nor CRIPS alone induced any increase in the frequency of aberrant chromosomes, while simultaneous exposure resulted in a significant increase in the frequency of chromosomal exchanges. These findings clearly showed that CRIPS could enhance the frequency of chromosomal exchanges induced by Fe-TBI at a low dose of 0.1 Gy.

Effect of Phaulopsis falcisepala (Acanthaceae) Leaves and Stems on Mitotic Arrest and Induction of Chromosomal Changes in Meristematic Cells of Allium Cepa

Phaulopsis falcisepala is an herb found in the forest zone of West Africa. It is applied ethnomedicinally for treating wounds and cancer. This study investigated the chemical constituents, cytotoxicity, and antimitotic activity of P. falcisepala leaves and stems. Chemical constituents were evaluated using phytochemical methods. Cytotoxicity was investigated using brine shrimp lethality and Allium cepa root growth inhibition assays. Antimitotic activity and induction of chromosomal aberrations were assessed by cytological examination of treated A. cepa meristematic cells. Chemical investigation revealed the presence of diverse bioactive chemical groups, including alkaloids, terpenoids, tannins, flavonoids and saponins in various extracts of the leaves and stems of P. falcisepala. Aqueous and methanol extracts contained copious amounts of the phytochemicals while ethyl acetate and n-hexane extracts contained moderate to trace amounts. The extracts demonstrated toxicity against brine shrimps, with LC50 values in the range 13.1–52.2 µg/mL. The extracts significantly inhibited A. cepa root growth, with IC50 values in the range 63.91–87.4 µg/mL and 45.34– 81.15µg/mL for 24 and 48 h treatments. The extracts (IC50 values in the range 46.2–94.23 µg/mL and 30.79–75.81 µg/mL for 24 and 48 h treatments) produced significant antimitotic effect comparable to or greater than that of methotrexate (IC50 value >125 µg/mL). Cytological examinations revealed that the extracts induced mitotic arrest and chromosomal changes. This study reports for the first time the phytoconstituents and cytotoxic activity of P. falcisepala supporting its ethnomedicinal use and could serve as the basis for further pharmacological studies and isolation of bioactive principles.

Oral Administration of Probiotic Bifidobacterium breve Improves Facilitation of Hippocampal Memory Extinction via Restoration of Aberrant Higher Induction of Neuropsin in an MPTP-Induced Mouse Model of Parkinson's Disease.

We previously reported that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease (PD) model mice (PD mice) facilitate hippocampal memory extinction, which may be the cause of cognitive impairment in PD. Recent studies on the consumption of probiotics have reported a variety of beneficial effects on the central nervous system via the microbiota–gut–brain axis. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 [MCC1274] (B. breve A1) on the facilitation of hippocampal memory extinction observed in PD mice. We found that four-day consecutive oral administration of B. breve A1 restored facilitation of contextual fear extinction in PD mice. Hippocampal mRNA expression levels of postsynaptic density protein-95 and synaptophysin significantly decreased in the PD mice, but mRNA and protein expression levels of neuropsin increased. Furthermore, CA1 apical spine density was significantly reduced in PD mice. On the other hand, administration of B. breve A1 to PD mice recovered all these expression levels and the CA1 spine density to control levels. These results suggest that increased induction of neuropsin is involved in abnormal changes in hippocampal synaptic plasticity, and that B. breve A1 imposes reins on its expression, resulting in the restoration of abnormal hippocampal synaptic plasticity and the facilitation of fear extinction in PD mice.

Functional Optical Zone and Visual Quality After Small-Incision Lenticule Extraction for High Myopic Astigmatism.

IntroductionThe aim of this study was to compare the functional optical zone (FOZ) after correction of high myopic astigmatism and low myopic astigmatism by small-incision lenticule extraction (SMILE).MethodsIn this prospective study, 30 patients who received SMILE for high myopic astigmatism correction (cylinderical diopters ≤ − 2.0D) were enrolled in the high astigmatism group (HA). The control group comprised 40 patients who underwent SMILE for low myopic astigmatism correction (LA; cylinderical diopters ≥ − 0.5D). FOZ was delineated as the area outlined by a change of 0.5D relative to the power at the corneal vertex on the total corneal refractive power map. An ellipse-fitting program (MatLab) was used to calculate some parameters of the FOZ. Visual quality evaluations were also conducted, including evaluations of wavefront aberrations, optical quality, and intraocular scattering, and completion of a quality of life questionnaire. All of the right eyes were analyzed in the study.ResultsThe preoperative average treatment spherical equivalent (− 5.77 ± 1.86D vs. − 6.49 ± 1.49D; P = 0.074), lenticule thickness (120.87 ± 23.27 μm vs. 118.53 ± 21.66 μm; P = 0.666), and programmed optical zone (6.58 ± 0.17 mm vs. 6.65 ± 0.18 mm; P = 0.104) were comparable between the HA and LA groups. The long axes (6.99 ± 1.14 mm vs. 5.32 ± 0.61 mm; P < 0.001), short axes (4.66 ± 0.96 mm vs. 4.23 ± 0.64 mm; P = 0.047), and area (25.90 ± 8.03 mm2 vs. 17.92 ± 4.36 mm2; P < 0.001) of the FOZ were significantly larger in the HA group than in the LA group. The centration of the FOZ were comparable between the two groups (0.62 ± 0.25 mm vs. 0.70 ± 0.25 mm; P = 0.194). Postoperative spherical aberration was lower in the HA group than in the LA group (0.07 ± 0.05 μm vs. 0.14 ± 0.10 μm; P = 0.001). There was no significant difference in the ocular scatter index (0.80 ± 0.46 vs. 0.73 ± 0.46; P = 0.447), modulated transfer function (MTF)cutoff (37.89 ± 9.79 cpd vs. 39.78 ± 7.45 cpd; P = 0.363), and Strehl in two dimensions (Strehl2D) ratio (0.20 ± 0.04 vs. 0.20 ± 0.04; P = 0.363) between the HA group and the LA group. There were no significant differences in the scores on quality of life between the HA and LA groups (45.88 ± 2.15 vs. 45.64 ± 1.84; P = 0.423). Correlation analysis revealed that increase in the spherical aberration was significantly correlated with the long axes, short axes and area in the FOZ in both groups.ConclusionWith a comparable optical design and attempted correction in SMILE, the eyes with higher myopic astigmatism correction achieved larger FOZ than the eyes with lower myopic astigmatism correction. Consequently, less spherical aberration induction was created after higher myopic astigmatism correction. This result may be associated with less corneal volume sculpted by laser for the higher astigmatism treatment, leading to fewer biochemical responses and les change in corneal aspherity. Good retinal image quality and satisfied quality of life were achieved at a comparable level in both study groups.

Comparative assessment of functional outcomes of different endothelial keratoplasty techniques

Comparative analysis of the higher-order aberrations (HOA) of the cornea after endothelial keratoplasty (EK) using DSAEK and DMEK techniques; evaluation of the correlation between higher-order corneal aberrations and functional outcomes of the treatment. The study included 47 patients (59 eyes). The main group consisted of 35 patients (35 eyes) with bullous keratopathy and Fuchs' endothelial dystrophy; among them, 19 patients underwent endothelial keratoplasty using the DSAEK technique and 16 - DMEK technique. The control group included 12 patients (24 eyes) of corresponding age without corneal pathology. Standard and special examination tests were performed before, as well as 6 and 12 months after the operation, including computed tomography and aberrometry of the cornea using the Pentacam HR system. Same tests were performed in the control group. The values of the main HOA of the anterior corneal surface: RMS coma (Z3±1, Z5±1), RMS spherical aberration (SA; Z40, Z60) and RMS HOA (Z3-6) 6 months after different EK techniques were statistically significantly higher than in the control group. A statistically significantly lower induction of aberrations of the posterior corneal surface after DMEK technique was revealed. Analysis of the final aberration pattern 6 months after surgery did not reveal any statistically significant differences in the values of the main (RMS coma, RMS SA, RMS HOA) total corneal aberrations after DSAEK and DMEK. A negative correlation was revealed between the best corrected visual acuity (BCVA) and HOA; however, it was statistically significant only for individual aberration values: RMS HOA (Z3-6) of the posterior corneal aberrations after DMEK (r= -0.634, p=0.049), and RMS coma (Z3±1, Z5±1) of the cornea after DSAEK (r= -0.57, p=0.042). Comparative analysis of total corneal HOA did not reveal a statistically significant difference in the main parameters: RMS coma, RMS SA, RMS HOA in patients after DSAEK and DMEK surgeries. Correlation analysis did not reveal any statistically significant effects of most aberrations on the functional outcomes of the treatment.

Clinical Effectiveness of Laser-Induced Increased Depth of Field for the Simultaneous Correction of Hyperopia and Presbyopia.

To evaluate the visual outcomes of patients with presbyopic hyperopia, comparing the current standard of monovision treatment with a novel bilateral presbyopic LASIK (Custom-Q mode) technique. This prospective comparative study of consecutive eligible patients with presbyopic hyperopia undergoing a bilateral presbyopic laser in situ keratomileusis technique was conducted between January 2018 and February 2019. After contact lens-simulated monovision measurements were obtained, the non-dominant eyes had a negative aspheric ablation profile planned using the Custom-Q nomogram (Alcon Laboratories, Inc). The dominant eye was operated on with a positive aspheric ablation profile. Visual acuity testing, refraction, corneal asphericity (▵Q), higher order aberrations, and a satisfaction questionnaire (National Eye Institute Refractive Error Quality of Life) were evaluated after the monovision trial and postoperatively. Twenty-eight patients, with a mean age of 56.03 ± 4.31 years, were included in the study. At 6 months, 100% of patients achieved 20/20 or better binocular uncorrected distance visual acuity (UDVA) versus 57% in the monovision group, 100% of patients achieved 20/25 or better binocular uncorrected intermediate visual acuity versus 32% in the monovision group, and 92.86% of patients achieved 20/25 or better binocular uncorrected near visual acuity (UNVA) in both groups. In contact lens monovision simulation, no patient reached a UDVA of 20/50 or better, with only 3.6% having a UNVA of 20/40 or better. The questionnaire demonstrated high patient satisfaction. The outcomes confirm the superiority of increased depth of focus using negative spherical aberration modulation in the non-dominant eye compared with contact lens monovision. They also demonstrate the effectiveness of positive spherical aberration induction to improve intermediate and near vision in the dominant eye. [J Refract Surg. 2021;37(1):16-24.].

In Vivo Screening of Xanthones from Garcinia oligantha Identified Oliganthin H as a Novel Natural Inhibitor of Convulsions.

Epilepsy is a chronic neurological disorder, characterized by recurrent, spontaneous, and transient seizures, and affects more than 70 million people worldwide. Although two dozen antiepileptic drugs (AEDs) are approved and available in the market, seizures remain poorly controlled in one-third of epileptic patients who are suffering from drug resistance or various adverse effects. Recently, the xanthone skeleton has been regarded as an attractive scaffold for the discovery and development of emerging anticonvulsants. We had isolated several dihydroxanthone derivatives previously, including oliganthin H, oliganthin I, and oliganthin N, whose structures were similar and delicately elucidated by spectrum analysis or X-ray crystallographic data, from extracts of leaves of Garcinia oligantha. These xanthone analogues were evaluated for anticonvulsant activity, and a novel xanthone, oliganthin H, has been identified as a sound and effective natural inhibitor of convulsions in zebrafish in vivo. A preliminary structure-activity relationship analysis on the relationship between structures of the xanthone analogues and their activities was also conducted. Oliganthin H significantly suppressed convulsant behavior and reduced to about 25% and 50% of PTZ-induced activity, in 12.5 and 25 μM treatment groups (P < 0.01 and 0.001), respectively. Meanwhile, it reduced seizure activity, velocity, seizure duration, and number of bursts in zebrafish larvae (P < 0.05). Pretreatment of oliganthin H significantly restored aberrant induction of gene expressions including npas4a, c-fos, pyya, and bdnf, as well as gabra1, gad1, glsa, and glula, upon PTZ treatment. In addition, in silico analysis revealed the stability of the oliganthin H-GABAA receptor complex and their detailed binding pattern. Therefore, direct interactions with the GABAA receptor and involvement of downstream GABA-glutamate pathways were possible mechanisms of the anticonvulsant action of oliganthin H. Our findings present the anticonvulsant activity of oliganthin H, provide a novel scaffold for further modifications, and highlight the xanthone skeleton as an attractive and reliable resource for the development of emerging AEDs.

Protective Effects of Ginger extract against Methotrexate induced cytotoxicity in mice

Ginger (Zingiber officinalis) is one of the frequently used spices in the world and medicinal plant, which has been used all over the world. This study was designed to investigate the role of aqueous ginger extract to inhibit the genotoxicity of methotrexate (MTX) in female albino mice by using these parameters: mitotic index (MI), chromosome aberrations (CA) and micronuclei formation (MNPCE) in somatic cells (bone marrow). The cytological protection of aqueous ginger extract (AGE) was performed at doses (25, 50) mg \\ kg against MTX effects (0.5) mg/kg for three weeks exposure. The results revealed the high inhibitory effects of MTX for cell division in addition to induction of chromosome aberration with micronuclei formation, the absence of cytotoxicity for AGE at tested doses, and the inhibitory efficiency of AGE against the toxicity and mutagenicity of MTX, specially at the dose 50 mg\\kg. From the results we can concluded that the AGE has a promising role in the protection of somatic cells from cytotoxic effects of methotrexate.

Induction of chromosome aberrations in B14-150 cells following carbon ions irradiation at low doses

Dose-dependences of the chromosomal aberrations induction in B14-150 cells were studied for carbon ions (E ∼455 MeV/nucleon) with different values of the linear energy transfer (LET): 10-12 keV/μm (proximal region of the Bragg curve - plateau) and 25-27 keV/μm (tail of the Bragg curve). It is shown that the level of chromosome aberrations was higher for irradiation at tail of carbon beam. The dose relations were described by a modified linear-quadratic model and had a similar character in the studied dose range of 0.05-2.5 Gy. A sharp increase of the chromosome aberrations yield at the dose range up to 0.1 Gy (hyper-radiosensitivity, HRS), slowdown in it at the range of 0.1-0.3 Gy (induced radioresistance, IRR) and a further its’ growth above 0.3 Gy were observed with a transformation to linear and linear-quadratic dependences. The results obtained agree with the known literature data and indicates the likeness of the biological effect of hyper-radiosensitivity and induced radioresistance (HRS/IRR) for different cell lines.