Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.

The effects of topical aloe vera on an experimentally designed penile fracture model in rats.

BACKGROUND: This study assessed the histopathological and oxidative effects of topical Aloe Vera (AV) on penile fractures (PF) formed experimentally in a rat model. METHODS: Forty Wistar albino rats (220-250 g) were used. The PF model was created experimentally with a number 15 lancet. Then, the rats were randomly and equally divided into five groups. In the first group (C), no incision was formed. In the second group (P), an incision was formed. In the third group (PR), the incision line was closed primarily. In the fourth group (PA), AV was locally applied onto the incision without suturing for three days. In the last group (PRA), AV was applied to the primary repair region for three days. All groups were compared to each other according to histopathological and biochemical data. RESULTS: Hyperemia-bleeding was observed to be suppressed in the PRA group compared to the other groups (p<0.001). Inflammation was observed only in Groups PR and PRA (p<0.001). Significant fibrosis was observed in the PA and PRA groups compared to the other groups (p<0.001). Superoxide Dismutase (SOD) and Glutathione (GSH) values increased in favor of Group PRA (p=0.009 and p=0.035, respectively). Total Oxidative Status (TOS) and Malondialdehyde (MDA) values decreased in favor of Group PA (p=0.036 and p=0.026, respectively). Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1 beta (IL-1ß) levels decreased mostly in the PRA group, but these changes did not reach statistical significance (p>0.05). CONCLUSION: Topical AV application reduces tissue inflammation and oxidative stress but appears to increase the development of fibrosis after PF.

Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

BACKGROUND: Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. METHODS AND RESULTS: Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). CONCLUSION: The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

Abundance Trends and Nesting Biology of Green Turtles Chelonia mydas (Testudines: Cheloniidae) During Ten Consecutive Breeding Seasons (2012-2021) at Akyatan Beach, Turkey.

Data obtained from long-term survey studies are valuable for assessing the population status and trends in critical populations of threatened species, like sea turtles. Akyatan Beach is one of the most important green turtle nesting beaches in the Mediterranean and has been monitored since 2006 without interruption. The beach is 22 km long and more than 100 m wide at some points, and both loggerhead and green turtles nest on the beach. However, loggerhead nesting is very limited compared to green turtles. A total of 3866 C. mydas nests were recorded over ten consecutive years at Akyatan Beach, with a mean of 387 ± 127 nests (range = 201-559). The average nesting density was 17.6 nests km-1 (range = 9.1-25.4 nests km-1). In the 3309 nests, a total of 355,259 eggs were counted. The overall mean clutch size was 112 ± 26.10 eggs. Of these eggs, 50.80% hatched (depredated nests included), and 78.07% of them were able to reach the sea. The overall mean hatching success was 73.07 ± 26.20%. The overall mean incubation duration was 51.4 ± 3.5 days. The clutch sizes and hatching success differed between years, and there was a significant decreasing trend in mean incubation duration over the ten years of the study. A total of 1585 green turtle nests (41.02% of nests) were totally or partially depredated by golden jackals and wild boars, while other predators depredated 20.5% of hatchlings. The nesting data obtained since 2006 showed strong annual fluctuations ranging from 170 (in 2007) to 562 (in 2006) with a slightly increasing but statistically insignificant trend (r = 0.94, p > 0.05). The main threats to the population were depredation by jackals and wild boars.

In vitro and in silico evaluation of inhibitory effects of bisphenol derivatives on acetylcholinesterase of electric eel (Electrophorus electricus L.).

The inhibitory effects of bisphenol A (BPA) and bisphenol S (BPS), which are common pollutants, especially in marine and freshwater, on the electric eel acetylcholinesterase (AChE) activity were studied in vitro and in silico. Both produced full non-competitive inhibition, but the Ki value of BPA was half that of BPS. Molecular docking analyses revealed that both interact with residues W286, F297, Y337, F338 in the PAS and ABS regions in the middle and entrance of the active site gorge, and that BPS also has hydrogen bond with S203 of the catalytic triad. The surge at IC50 values of both compounds with an inflection point at pH: 8.2 suggested that Y124 and/or Y337 in the narrow gorge are primary structural factors in binding. Less effective inhibition of BPS, especially at 25-30 °C, the temperature at which enzyme activity peaks, was attributed to the conformation of the narrow gorge. Homology analyses for AChE initially revealed a significant degree of identity, particularly in the alpha/beta hydrolase domain, which also comprises the active site, with sequences from seven distinct teleost species of various environments. Finally, it was discovered for the first time that BPS, like BPA, is a significant inhibitor of AChE, and this was confirmed by in vitro and in silico analyses done at various pH and temperature levels. It was concluded that this effect might also apply to AChE of most other bony fish.

Periprocedural, Short-Term, and Long-Term Outcomes of Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy: A 20-Year Single-Center Experience.

BACKGROUND: Alcohol septal ablation is recommended for hypertrophic obstructive cardiomyopathy patients who had refractory symptoms despite optimal medical treatment. We compared the periprocedural, short-, and long-term clinical outcomes and mortality predictors in hypertrophic obstructive cardiomyopathy patients who underwent alcohol septal ablation. METHODS: Hypertrophic obstructive cardiomyopathy patients aged ≥18 years (63 females and 71 males) who underwent alcohol septal ablation were included. The primary endpoint was all-cause mortality. RESULTS: The mean patient age was 60.0 (standard deviation 13.7) years. The median follow-up time was 13 (7.6-18.5) years. During the procedure, 9, 2, and 1 patients developed ventricular fibrillation, remote site myocardial infarction, and pericardial tamponade, respectively, but none died. One patient died during hospitalization. During the long-term follow-up, 17, 5, 20, and 8 patients developed heart failure, myocardial infarction, chronic atrial fibrillation, and non-fatal stroke, respectively, and 24 died. There was no significant difference between the sexes (all P > .05). Age (hazard ratio=0.69, 95% CI=0.61‒0.78, P < .001), body mass index (hazard ratio=1.20, 95% CI=1.04-1.40, P=.01), age at diagnosis (hazard ratio=1.57, 95% CI=1.34-1.78, P < .001), and time from diagnosis to ablation (hazard ratio=1.57, 95% CI=1.35-1.84, P< .001) predicted all-cause mortality. In Kaplan‒Meier curves, long-term all-cause mortality was similar in men and women (P[log-rank]=.43). CONCLUSION: Alcohol septal ablation has similar short- and long-term outcomes for both sexes in hypertrophic obstructive cardiomyopathy patients. Risk factors for longterm mortality were age, body mass index, diagnosis age, and time delay to operation. Therefore, alcohol septal ablation timing is essential for better clinical outcomes. Our findings may contribute to the increased performance of alcohol septal ablation in hypertrophic obstructive cardiomyopathy patients in our country.

Revising the taxonomy of Darevskia valentini (Boettger, 1892) and Darevskia rudis (Bedriaga, 1886) (Squamata, Lacertidae): a Morpho-Phylogenetic integrated study in a complex Anatolian scenario.

Revealing biodiversity allows the accurate determination of the underlying causes of many biological processes such as speciation and hybridization. These processes contain many complex patterns, especially in areas with high species diversity. As two of the prominent zoogeographic areas, Anatolia and Caucasus are also home to the genus Darevskia, which has a complex morphological structure and parthenogenetic speciation. Darevskia valentini and D. rudis are two largely distributed taxa of this genus, both of which have a controversial taxonomic delimitation. Here we performed both a highly detailed morphological comparison and a molecular evaluation for the populations in both species groups. The most comprehensive taxonomic revision of this complex was carried out to determine the cases where the data obtained were compatible or not with each approach. As a result of the obtained outputs, it seems that D. spitzenbergerae stat. nov., D. mirabilis stat. nov. and D. obscura stat. nov. should be accepted as the species level, this later with subspecies D. o. bischoffi comb. nov. and D. o. macromaculata comb. nov.. Also, we propose two new taxa: D. josefschmidtleri sp. nov. and D. spitzenbergerae wernermayeri ssp. nov.. It has also been shown that "lantzicyreni" subspecies belong to D. rudis instead of D. valentini. The extensive revision has contributed to subsequent studies to more accurately understand the past histories of species in the genus Darevskia.

A Novel 4H-Chromen-4-One Derivative from Marine Streptomyces ovatisporus S4702T as Potential Antibacterial and Anti-Cancer Agent.

BACKGROUND: Marine actinomycetes are among indispensable sources of natural bioactive compounds with unique antimicrobial and anti-cancer activities. OBJECTIVE: Herein, it was aimed to elucidate the bioactive potential of a marine-derived Streptomyces ovatisporus S4702T, isolated previously. METHODS: Streptomyces ovatisporus S4702T was cultured in N-Z Amine broth, and extraction was carried out using different organic solvents. Bioassay-guided purification was followed by chemical characterization using NMR and LC-MS/MS. The compound was then evaluated for its antibacterial, antioxidant and cytotoxic activities. RESULTS: Etyl acetate extracts gave the highest antibacterial activity, and chemical characterization of this extract indicated the formula as C15H29O5N3 and the corresponding possible molecular structure as 4H-chromen-4-one derivative. It was found highly potent against Bacillus subtilis ATCC 6633 (MIC: 0.25 µg ml-1) and Micrococcus luteus ATCC 9341 (MBC: 0.5 µg ml-1). It has no remarkable antioxidant activity, but a higher EC50 value and less cytotoxicity against normal cells. The EC50 values of this chromen derivative were found as 9.68 µg ml-1 for human colon carcinoma, 9.93 µg ml-1 for human prostate adenocarcinoma and 25.5 µg ml-1 for human embryonic kidney cells. CONCLUSION: Overall, the presented 4H-chromen-4-one derivative is a remarkable bioactive compound with potent antibacterial and cytotoxic activity. With its high bioactive potential, it is proposed as a good candidate in medicine.

Bisphenol S leads to cytotoxicity-induced antioxidant responses and oxidative stress in isolated rainbow trout (Oncorhyncus mykiss) hepatocytes.

BACKGROUND: Bisphenol S (BPS) is a chemical compound that is utilized in the plastic industry as an alternative to bisphenol A (BPA). The toxic effects of BPS in fish is less known and limited. Therefore, in the present study, the influence of BPS on rainbow trout (Oncorhyncus mykiss) hepatocytes in vitro was investigated. METHODS AND RESULTS: For this purpose the fish hepatocytes were isolated, and then the cultured cells were treated with increasing concentrations of BPS (0, 15.63, 31.25, 62.50, 125, 250, and 500 µM) for 24 h. The cytotoxic impact of BPS was determined in the culture media using lactate dehydrogenase assay and then, the antioxidant defence indicators were assayed. The results showed that concentration-dependent increases were observed in the percentage of cytotoxicity. The superoxide dismutase activity was reduced, while the catalase and glutathione peroxidase activity increased with all of the BPS concentrations. The glutathione S-transferase (GST) activity significantly increased after a BPS concentration of 31.25 µM or higher, while GST Theta 1-1 activity was decreased by the same concentrations of BPS. The reduced glutathione content significantly decreased with a BPS concentration of 31.25 µM or higher, and the malondialdehyde content increased after BPS concentrations of 125, 250, and 500 µM. CONCLUSIONS: The findings determined herein suggested that BPS causes cytotoxicity in fish hepatocytes and can lead to oxidative stress, resulting hepatotoxic in fish. Thus, the utilization of BPS instead of BPA as safe alternative in industry should be re-evaluated in the future for environmental health.

Identification of 3-Bromo-1-Ethyl-1H-Indole as a Potent Anticancer Agent with Promising Inhibitory Effects on GST Isozymes.

BACKGROUND: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. OBJECTIVE: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3- bromo-1-ethyl-1H-indole (BEI) structure. METHODS: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur™ image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. RESULTS: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. CONCLUSION: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs.

Which factors can we control the transition from mild cognitive impairment to dementia?

Mild cognitive impairment (MCI) is a clinical condition in the transitional stage between healthy aging and dementia. In this study, we investigated the risk factors and the development of dementia in MCI patients. Seventy six patients who diagnosed MCI, according to the Petersen criteria, over sixty-years old, and risk factors in transition to dementia were investigated. Neurological examinations, laboratory tests, systemic comorbidities, mini-mental state examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale of the patients every 3-6 months were investigated. Dementia developed in 44.7% of MCI patients. Vascular risk factors were the most prominent risk factors in the transition from MCI to dementia (p = 0.000). Increased vascular risk factors and advancing age in MCI patients accelerate the transition to dementia. Therefore, modifiable vascular risk factors, which are significant factors in the transition to dementia, should be controlled and these patients should be closely monitored.

Glutathione S-transferase enzyme activity and protein expression in patients with recurrent tonsillitis and idiopathic tonsillar hypertrophy.

OBJECTIVES: The palatine tonsil is a significant part of the secondary immune system. Tonsillitis and idiopathic tonsillar hypertrophy (ITH) are the most common pathologies of this component. Although there are studies on their pathogenesis, there is insufficient study of the role of antioxidant agents. Glutathione S-transferase (GST) isozymes contribute to the antioxidation reactions in the tissue via the glutathione pathway. The purpose in this study was to reveal the levels of the GST enzyme activity and protein expression of GSTP1 and GSTA1 isozymes in patients with tonsillitis and tonsil hypertrophy, and to investigate their role in the pathogenesis of these diseases. MATERIALS AND METHODS: Sixteen patients with recurrent tonsillitis and 5 patients with ITH and were included in the study. Cytosolic extracts were prepared from post-tonsillectomy tissues of both patient groups and GST enzyme activities were measured. RESULTS: The expression of GSTP1 was found to be significantly higher than GSTA1 in tissue samples of patients with ITH and recurrent tonsillitis (P<0.001). Increased GST activity and GSTP1 isozyme expression were shown in patients with recurrent tonsillitis compared to the idiopathic tonsillar hypertrophy study group. There was a positive correlation between the expressions of GSTP1 (P=0.040; r=0.47). CONCLUSION: Increased GST activity and GSTP1 isozymes were demonstrated histologically in the pathogenesis of ITH and recurrent tonsillitis. We believe that the data of changes in antioxidant capacity, obtained from studies with more extensive and larger samples, would support our findings.

Geographic patterns of genetic variation in a broadly distributed marine vertebrate: new insights into loggerhead turtle stock structure from expanded mitochondrial DNA sequences.

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (∼800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology.