Prevalence of Cardiovascular Disease and Comparison of Risk Category Predictions of Systemic Coronary Risk Evaluation Score-2 and 4 Other Cardiovascular Disease Risk Assessment Tools Among People Living with Human Immunodefficiency Virus in Türkiye.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among people living with HIV (PLWH). We aimed to assess the prevalence of diagnosed CVD and the risk of CVD among PLWH using 5 different tools. METHODS: This retrospective, cross-sectional study was conducted in 20 tertiary centers in Türkiye between October 2021 and March 2022, among 1425 PLWH aged 40-75 years. About 82.7% were male, with a median age of 51. Web-based tools for each score were used for CVD risk calculations. RESULTS: Of 1425 PLWH enrolled, 10.8% had confirmed CVD, and 1132 had their risk scores evaluated. Of those participants, 42.8% had a higher risk of CVD (10-year risk of atherosclerotic CVD risk score (ASCVD) above 7.5%), and according to the European Society of Cardiology systemic coronary risk evaluation 2 (SCORE2), 71.7% had a high- to very high-risk rate. The agreement between various CVD risk tools varied, with Framingham heart study risk score (FRS), modified FRS, data collection on adverse effects of anti-HIV drugs (DAD), and SCORE2 for high-risk countries showing overall agreement rates of 82%, 94%, 91%, and 36%, respectively, compared to ASCVD. According to the 2021 European and 2019 American Cardiology guidelines, 75.3% and 47.1% of PLWH would be eligible for lipid-lowering agents, respectively. CONCLUSION: The diagnosed CVD prevalence highlighted the importance of monitoring cardiovascular health and comorbidities in this population. SCORE2 identified a greater number of individuals at high/very high risk compared to other prediction tools. The implementation of CVD prevention through lipid-lowering therapy was far from desired levels in our cohort.

Observational study of immunosuppressive treatment patterns and outcomes in primary membranous nephropathy: a multicenter retrospective analysis.

BACKGROUND: We evaluated the efficacy of different immunosuppressive regimens in patients with primary membranous nephropathy in a large national cohort. METHODS: In this registry study, 558 patients from 47 centers who were treated with at least one immunosuppressive agent and had adequate follow-up data were included. Primary outcome was defined as complete (CR) or partial remission (PR). Secondary composite outcome was at least a 50% reduction in estimated glomerular filtration (eGFR), initiation of kidney replacement therapies, development of stage 5 chronic kidney disease, or death. RESULTS: Median age at diagnosis was 48 (IQR: 37-57) years, and 358 (64.2%) were male. Patients were followed for a median of 24 (IQR: 12-60) months. Calcineurin inhibitors (CNIs) with or without glucocorticoids were the most commonly used regimen (43.4%), followed by glucocorticoids and cyclophosphamide (GC-CYC) (39.6%), glucocorticoid monotherapy (25.8%), and rituximab (RTX) (9.1%). Overall remission rate was 66.1% (CR 26.7%, PR 39.4%), and 59 (10.6%) patients reached secondary composite outcome. Multivariate logistic regression showed that baseline eGFR (OR 1.011, 95% CI: 1.003-1.019, p = 0.007), serum albumin (OR 1.682, 95% CI: 1.269-2.231, p < 0.001), and use of RTX (OR 0.296, 95% CI: 0.157-0.557, p < 0.001) were associated with remission rates; whereas only lower baseline hemoglobin was significantly associated with secondary composite outcome (OR: 0.843, 95% CI: 0.715-0.993, p = 0.041). CYC use was significantly associated with higher remission (OR 1.534, 95% CI: 1.027-2.290, p = 0.036). CONCLUSIONS: Higher baseline eGFR and serum albumin levels correlated with increased remission rates. Remission rates were lower in patients treated with RTX, while those on GC-CYC showed higher rates of remission. Due to the study's retrospective nature and multiple treatments used, caution is warranted in interpreting these findings.

Comparative Analysis of Surgical and Endovascular Approaches for Isolated Aortic Coarctation Repair across Age Groups: Outcomes and Long-Term Efficacy.

Background: Aortic coarctation, a condition characterized by localized narrowing of the aorta, can be managed with either surgical or endovascular techniques. This study aims to compare these approaches concerning long-term outcomes, particularly re-coarctation rates and late arterial hypertension. Methods: We retrospectively analyzed data from patients with native, isolated aortic coarctation treated by surgical or endovascular methods between 2015 and 2024. Clinical and demographic data were collected from electronic health records. Blood pressure was measured using oscillometric devices, and transthoracic echocardiography (TTE) was performed by an experienced sonographer. The primary endpoint was to identify which treatment predicted re-coarctation during follow-up, while the secondary endpoint assessed the incidence of late arterial hypertension. Results: Sixty-nine patients were included, with a mean age of 18.14 ± 8.18 years (median 16 years; range 8 to 37 years) and a median follow-up of 3 years (range 6 months to 8 years). Of these, 67 (97.1%) underwent elective repairs. Repair techniques included endovascular treatment (24.6%), surgical end-to-end anastomosis (47.8%), and surgical patchplasty (27.5%). The endovascular group was significantly older (29.82 ± 5.9 years vs. 14.33 ± 4.25 years, p = 0.056) and had shorter procedure durations and hospital stays. One-year freedom from reintervention was significantly higher in the surgical group (98.7%) compared to the endovascular group (88.23%) (p < 0.001). Conclusions: Both techniques effectively treat aortic coarctation, but surgical repair offers better long-term outcomes, while endovascular repair provides shorter recovery times. These findings should inform the choice of treatment modality based on patient-specific factors and clinical priorities.

Antigenotoxic and Life-Prolonging Effects of Flavoured Kombuchas on Drosophila melanogaster.

Research background: Kombucha is a fermented beverage with several health benefits; however, to improve its antioxidant activity, new raw materials such as hop, madimak and hawthorn were included in the present study. Experimental approach: The somatic mutation and recombination test (SMART) was performed on the fruit fly (Drosophila melanogaster) to evaluate the antigenotoxic potential of black tea-flavoured kombucha and three other flavours of kombuchas (hop, madimak and hawthorn) against H2O2- and K2Cr2O7-induced genotoxicity. Furthermore, a lifespan assay was performed to assess the effects of kombuchas on the longevity of the fruit fly. Results and conclusions: According to the results obtained from the SMART assay, hop-flavoured kombucha attenuated genotoxicity induced by H2O2, and madimak-flavoured kombucha reduced genotoxicity induced by H2O2 and K2Cr2O7. Black tea- and hop-flavoured kombucha prolonged the lifespan of the fruit fly (Drosophila melanogaster) after the treatment with H2O2 and K2Cr2O7. Novelty and scientific contribution: Hop-flavoured kombucha is a promising antioxidant that protects the genome and extends the lifespan of the fruit fly. This study sheds light on novel beverages that can combat ageing and protect against genotoxicity.

Biopsy-proven BK virus nephropathy in renal transplant recipients: A multi-central study from Turkey (BK-TURK STUDY).

AIM: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. MATERIALS AND METHODS: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. RESULTS: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2. In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. CONCLUSION: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Risk Factors Associated with Osteopenia/Osteoporosis in Antiretroviral Therapy Naive HIV Patients.

INTRODUCTION/OBJECTIVES: Different ART (antiretroviral therapy) options may affect the risk of osteopenia/osteoporosis in people living with HIV (PLWH) having increased life expectancy. Current guidelines recommend bone mineral density (BMD) measurement only in patients at risk. In our study, we investigated the prevalence of osteopenia/osteoporosis and associated risk factors in naive patients not receiving ART. METHODS: This study included 116 newly diagnosed, ART naive HIV-positive patients who were studied retrospectively. Vitamin D level, BMD measurement, CD4 and CD8 count, CD4/CD8 ratio, HIV RNA level, body mass index and other risk parameters of ART naive patients were included in our study. RESULTS: Of 116 patients, 103 were male and 13 female. 47.4% (osteoporosis in 4.3%, osteopenia in 43.1%) of patients had osteopenia/osteoporosis. The patients with osteopenia/osteoporosis had older age (39.2±11.0 vs. 32.0±8.6, p=0.0001), lower vitamin D levels (16.0±5.0 vs. 24.4±6.3, p=0.0001), lower BMI (body mass index) (23.0±4.0 vs. 24.6±4.6 p<0.05), lower CD4 and CD8 counts (405.1±885.0 vs. 467.3± 695.1; 849.9570.4 vs. 1012.0±629.4, respectively, p<0.05). 41.8% had CD4 count ≤200/µL (vs. 18.0%, p=0.005). No statistically significant differences were observed in terms of gender distribution, smoking, alcohol and drug use, comorbidities and, additional drug use and HIV RNA >100 000 copies/ml. In multivariate analysis, age and vitamin D level were significant and independent (p<0.05) risk factors with osteoporosis/osteopenia. CONCLUSION: Being over 40 years of age, CD4 count ≤200/µL, vitamin D level <20 ng/mL and low BMI are the most important risk factors for osteopenia/osteoporosis in ART naive patients. Among these parameters, age and vitamin D level were significant and independent risk factors. These factors may guide the determination of the need for dual-energy x-ray absorptiometry (DXA) testing in ART naive patients and drug choices in the treatment plan.

Primary cutaneous nocardiosis of the ankle caused by N. brasiliensis: a case report.

Nocardia is a genus of aerobic, Gram-positive bacteria known for their filamentous and branching morphology. N. brasiliensis is the most common species causing cutaneous nocardiosis. We present a 67-year-old woman who developed abscesseson the back of her right ankle after walking barefoot on soil. Cultures from the cutaneous lesions grew N. brasiliensis. Antibiotic therapy with trimethoprim-sulfamethoxazole given for a month provided near-complete resolution of her lesions.

In vivo assessment of the toxic impact of exposure to magnetic iron oxide nanoparticles (IONPs) using Drosophila melanogaster.

Iron oxide nanoparticles (IONPs) have useful properties, such as strong magnetism and compatibility with living organisms which is preferable for medical applications such as drug delivery and imaging. However, increasing use of these materials, especially in medicine, has raised concerns regarding potential risks to human health. In this study, IONPs were coated with silicon dioxide (SiO2), citric acid (CA), and polyethylenimine (PEI) to enhance their dispersion and biocompatibility. Both coated and uncoated IONPs were assessed for genotoxic effects on Drosophila melanogaster. Results showed that uncoated IONPs induced genotoxic effects, including mutations and recombinations, while the coated IONPs demonstrated reduced or negligible genotoxicity. Additionally, bioinformatic analyses highlighted potential implications of induced recombination in various cancer types, underscoring the importance of understanding nanoparticle-induced genomic instability. This study highlights the importance of nanoparticle coatings in reducing potential genotoxic effects and emphasizes the necessity for comprehensive toxicity assessments in nanomaterial research.

Alcohol-free synthesis, biological assessment, in vivo toxicological evaluation, and in silico analysis of novel silane quaternary ammonium compounds differing in structure and chain length as promising disinfectants.

Quaternary ammonium compounds (QACs) are commonly used as disinfectants for industrial, medical, and residential applications. However, adverse health outcomes have been reported. Therefore, biocompatible disinfectants must be developed to reduce these adverse effects. In this context, QACs with various alkyl chain lengths (C12-C18) were synthesized by reacting QACs with the counterion silane. The antimicrobial activities of the novel compounds against four strains of microorganisms were assessed. Several in vivo assays were conducted on Drosophila melanogaster to determine the toxicological outcomes of Si-QACs, followed by computational analyses (molecular docking, simulation, and prediction of skin sensitization). The in vivo results were combined using a cheminformatics approach to understand the descriptors responsible for the safety of Si-QAC. Si-QAC-2 was active against all tested bacteria, with minimal inhibitory concentrations ranging from 13.65 to 436.74 ppm. Drosophila exposed to Si-QAC-2 have moderate-to-low toxicological outcomes. The molecular weight, hydrophobicity/lipophilicity, and electron diffraction properties were identified as crucial descriptors for ensuring the safety of the Si-QACs. Furthermore, Si-QAC-2 exhibited good stability and notable antiviral potential with no signs of skin sensitization. Overall, Si-QAC-2 (C14) has the potential to be a novel disinfectant.

Central sensitization: its prevalence and impact on quality of life among hemodialyzed patients.

BACKGROUND/AIM: Data on the role of central sensitization in hemodialyzed patients are scarce. The aim was to identify the impact of central sensitization on quality of life and elucidate the risk factors for the development of central sensitization in patients receiving hemodialysis. METHODS: Central sensitization, quality of life, psychological well-being, and sleep were assessed by the Central Sensitization Inventory (CSI), abbreviated version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Evaluation Scale (JSS), respectively. The effect of central sensitization on quality of life and the predictors of the development of central sensitization were assessed by regression analyses. RESULTS: The frequency of central sensitization was 48% in the study population (n = 100). Patients with central sensitization had significantly higher pain intensity, worse sleep quality, and more impaired psychological status (p < 0.05 for all). The CSI score negatively affected all quality of life domains on its own (p < 0.001 for all, adjusted R2 ranged from 0.17 to 0.47). Dialysis vintage (OR, 0.8; 95% CI, 0.7 to 1.0), pain (OR, 1.5; 95% CI, 1.1 to 2.0), JSS (OR, 1.3; 95% CI, 1.1 to 1.5), and HADS-total (OR, 1.1; 95% CI, 1.0 to 1.2) were determined as the independent risk factors for central sensitization (p < 0.05 for all). CONCLUSION: This study confirms that given the high frequency of central sensitization and its significant negative impact on quality of life, the presence of central sensitization should be investigated in patients undergoing hemodialysis.

Morphologically different hydroxyapatite nanoparticles exert differential genotoxic effects in Drosophila.

Hydroxyapatite (HAP) occurs naturally in sedimentary and metamorphic rocks and constitutes the hard structures in many organisms. Since synthetic nano-sized HAP (HAP-NPs) are used in orthopedic applications and for heavy metal remediation in aquatic and terrestrial media, both environment and humans are exposed to them. Due to the concerns about their potential hazards, the genotoxic effects that round/rod forms of HAP-NPs were investigated in Drosophila using the wing-spot and the comet assays. Furthermore, caspase activities were evaluated to examine the activation of cell death pathways. As a novelty, the expression of 36 genes involved in DNA repair was investigated, as a tool to indirectly determine DNA damage induction. Obtained sizes were 35-60 nm (roundHAP-NPs) and 45-90 nm (rodHAP-NPs) with a low Zeta-potential (-1.65 and 0.37 mV, respectively). Genotoxicity was detected in the wing-spot (round form), and in the comet assay (round and rod-like HA-NPs). In addition, increased expression of Caspases 3/7, 8, and 9 activities were observed. For both HAP forms, increased changes in the expression were observed for mismatch repair genes, while decreased expression was observed for genes involved in ATM, ATR, and cell cycle pathways. The observed changes in the repair pathways would reinforce the view that HAP-NPs have genotoxic potential, although more markedly in the round form. Thus, the environmental presence of engineered nanoparticles, including HAPs, raises concerns about potential effects on human health. It is essential that the effects of their use are carefully assessed and monitored to ensure safety and to mitigate any potential adverse effects.

Comparative evaluation of natural and artificial sweeteners from DNA damage, oxidative stress, apoptosis, to development using Drosophila melanogaster.

The overconsumption of added sugars makes people vulnerable to a myriad of diseases. Several biochemical and developmental assays were performed in the current study to assess the effect of fructose on Drosophila melanogaster and to find substitutes for fructose by comparing it to well-known sweeteners. Drosophila was exposed separately to the same ratio of sugar 9.21% (w/v) of several types of sweeteners (sucrose, fructose, glucose syrup, high-fructose corn syrup and stevia). Results revealed that fructose might induce recombination, whereas stevia lacks genotoxic potential. No developmental delay, growth defects, or neurotoxic effects were recorded for any of the sweeteners. We also observed no striking differences in reactive oxygen species levels. Thus, stevia seems to be an alternative sweetener to fructose that can be consumed to reduce fructose-induced anomalies.

Increased expression of ubiquitin C-terminal hydrolase L1 in astrocytomas of ascending grades.

BACKGROUND: The ubiquitin-proteasome pathway controls the monitoring and degradation of important proteins and is involved in several cellular processes, such as development, differentiation, and transcriptional regulation. Recent evidence has shown that ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), a member of the deubiquitinating enzyme family that removes ubiquitin from protein substrates, is overexpressed in many types of cancer. AIM: This study thus examined the expression of UCH-L1 in human astrocytoma tissues. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded astrocytoma samples were obtained from 40 patients, after which histopathological examination, typing, and grading were performed. The study group included 10 histologically normal brain tissues, which served as the control group, and 10 WHO grade II, 10 WHO grade III, and 10 WHO grade IV (glioblastoma) samples. Normal brain tissue samples were obtained from the histologically normal, non-tumoral portion of the pathology specimens. UCH-L1 expression was evaluated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: Astrocytoma tissues exhibited higher UCH-L1 expression compared to the control group. UCH-L1 overexpression increased significantly together with the increase in astrocytoma grades (from II to IV). CONCLUSION: UCH-L1 could be a good diagnostic and therapeutic marker for determining astrocytoma development and progression.

C-Reactive Protein to Albumin Ratio is Associated with Disease Activity in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis.

Objective/Aim: C-reactive protein to albumin ratio (CAR) has recently been recognized as an independent prognostic marker for vasculitides. This study aims to investigate CAR and its relationship with disease activity and damage in prevalent ANCA associated vasculitis (AAV) patients. Methods: Fifty-one patients with AAV and 42 age-sex-matched healthy controls were enrolled in this cross-sectional study. Birmingham vasculitis score (BVAS) was used to assess vasculitis activity and vasculitis damage index (VDI) to provide information on disease damage. Results: The median (25th-75th) age of the patients were 55 (48-61) years. CAR was significantly higher in AAV patients than controls (1.9±2.7 vs 0.7±0.4; p=0.006). The 75th percentile of BVAS was defined as high BVAS (BVAS≥5) and ROC curve analysis showed that CAR≥0.98 predicted BVAS≥5 with 70.0% sensitivity and 68.0% specificity (AUC:0.660, CI: 0.482-0.837, p=0.049). When patients with CAR≥0.98 were compared to those without, BVAS [5.0 (3.5-8.0) vs. 2.0 (0-3.25), p<0.001], BVAS≥5 [16 (64.0%) vs 4 (15.4%) patients, p:0.001], VDI [4.0 (2.0-4.0) vs. 2.0 (1.0-3.0), p=0.006], and CAR [1.32 (1.07-3.78) vs. 0.75 (0.60-0.83), p<0.001] were higher whereas albumin [3.8 (3.1-4.3) vs. 4.1 (3.9-4.4) g/dL, p=0.025] and haemoglobin [12.1 (10.4-13.4) vs. 13.0 (12.5-14.2) g/dL, p=0.008] were lower. Multivariate analysis revealed that BVAS [OR(95% CI):1.313 (1.003-1.719), p=0.047] was an independent factor associated with CAR≥0.98 in patients with AAV. Furthermore, correlation analysis showed that CAR significantly correlated with BVAS (r: 0.466, p=0.001). Conclusion: In this study, we observed that CAR was significantly associated with disease activity in AAV patients and can be used to monitor disease activity.

Antioxidant, Antimicrobial, and Neurotoxicity (in Sh-Sy5y Cell Lines) Properties of Mg Nanoparticle System (BP@MgNPs) Prepared by Green Synthesis with Bee Pollen.

Due to their distinct characteristics and possible uses in a variety of disciplines, nanoparticles have attracted a lot of attention recently. One area of interest is the synthesis of nanoparticles using natural sources such as bee pollen. The research aims to evaluate the usability of bee pollen extract-based magnesium nanoparticles (MgNPs). First, a palynological study was used to determine the plant source of bee pollen. The nanoparticle was characterized using scanning electron microscopy, energy dispersive X-ray analysis, transmission electron microscopy, X-ray diffractometry, and Fourier transform infrared spectroscopy. The results revealed cubic-shaped MgNPs with an average size range of 36-40 nm. Afterward, nanoparticles were evaluated for their antioxidant, antimicrobial, and neurotoxic properties. It was determined that the total antioxidant capacity, phenolic (TPC), flavonoid (TFC) content, DPPH radical scavenging, and antimicrobial activity of the nanoparticles were lower than pollen extract. At the same time, nanoparticles have less toxicity than bee pollen.

Computational assessment of the biological response of curcumin to type 2 diabetes mellitus induced by metal exposure.

The current study aimed to identify the molecular mechanisms of a metal mixture (cadmium, nickel, and lead) involved in type 2 diabetes mellitus (T2DM) development and the therapeutic effect of curcumin in this metal mixture-induced T2DM. To accomplish this, SwissADME assessed the physicochemical and pharmacokinetic properties of curcumin and the Prediction of Activity Spectra for Substances evaluates its biological activities. The Comparative Toxicogenomics Database, Cytoscape, AutoDock Vina, and MicroRNA ENrichment TURned NETwork were used as tools to perform data-mining approaches and molecular docking. Curcumin properties were fitted within the acceptable range to be a promising drug candidate. The mixed metal altered 23 genes linked to T2DM development and targeted by curcumin. Curcumin had a dual-natured effect or antagonistic effect for most of the involved genes in T2DM and metal mixture. The most prominent biological processes were identified as ''response to external stimulus'', ''regulation of programmed cell death'', ''programmed cell death'', ''cell death'', and ''response to stress''. Three highly interacted miRNAs related to metal mixture-induced T2DM and targeted by curcumin (hsa-miR-98-5p, hsa-miR-34a-5p, and hsa-miR-155-5p) were identified. These findings could pave the way for further studies to evaluate the link between these genes and T2DM.

Avascular Necrosis in Renal Transplant Patients.

OBJECTIVES: Kidney transplant recipients are at increased risk for avascular necrosis due to steroid use and accompanying comorbidities. Concerning risk factors, uncertainty still exists. We evaluated the clinical characteristics and risk factors of avascular necrosis in kidney transplant recipients. MATERIALS AND METHODS: Symptomatic avascular necrosis was found by magnetic resonance imaging in 33 of 360 kidney transplant patients between 2005 and 2021. The patients' clinical characteristics, biochemical testing, and medications were evaluated. RESULTS: We found the frequency of avascular necrosis to be 9.7% during the follow-up period. If the total steroid dosage used was more than 4 g in the first 3 months, the risk of developing avascular necrosis increased 4.08 times, and the presence of cytomegalovirus disease increased the risk by 4.03 times. Avascular necrosis was observed bilaterally in 60.6% of cases and at the femoral head in 66.7%. The frequency of avascular necrosis was highest in the first and second years posttransplant. CONCLUSIONS: We found that avascular necrosis appears most frequently in the first 2 years after kidney transplant and the most important risk factors are cumulative steroid dose and cytomegalovirus disease. In the follow-up of kidney transplant patients, it is important to use low-dose steroid doses if possible. Of note, preventing the development of cytomegalovirus disease by screening and prophylaxis for cytomegalovirus is also important in reducing the development of avascular necrosis.

Genotoxic and genoprotective effects of phytoestrogens: a systematic review.

Phytoestrogens are xenoestrogens found in plants with a myriad of health benefits. However, various studies reported the genotoxic effects of these substances. Thus, we reviewed in vitro and in vivo studies published in PubMed, Scopus, and Web of Science to evaluate the genotoxic and the genoprotective potential of phytoestrogens. Only studies written in English and intended to study commercially available phytoestrogens were included. The screening was performed manually. Moreover, the underlying mechanism of action of phytoestrogens was described. Around half of those studies (43%) reported genoprotective results. However, several studies revealed positive results for genotoxicity with specific model organisms and with dose/concentration dependence. The assessment of the selected articles showed substantial differences in the used concentrations and a biphasic response was recorded in some phytoestrogens. As far as we know, this is the first study to assess the genotoxic and genoprotective effects of phytoestrogens systematically.

Genotoxic potential of different nano-silver halides in cultured human lymphocyte cells.

Most antibacterial applications in nanotechnology are carried out using silver nanoparticles (AgNPs). However, there is a dearth of information on the biological effects of AgNPs on human blood cells. In this study, the cytotoxic and genotoxic potentials of ionic silver (Ag+), AgNP, silver bromide (AgBr), silver chloride (AgCl), and silver iodide (AgI) were evaluated through chromosome aberration (CA) test and cytokinesis-blocked micronucleus (CBMN) test in human cultured lymphocytes in vitro. Furthermore, the potential damages that can cause to DNA were evaluated through alkaline single cell gel electrophoresis (Comet) assay on isolated lymphocytes. The results showed that AgNPs exerted cytotoxic effects by reducing the cytokinesis-block proliferation index and mitotic index at 24 and 48 h. AgNPs also increased micronucleus (MN) formation at both exposure times in the cultured cells. Meanwhile, AgCl had no genotoxic effects on the human lymphocyte cultured cells but had a cytotoxic effect at high doses. AgNP, Ag+, AgBr, and AgI caused substantial DNA damage by forming DNA strand breaks. They may also have clastogenic, genotoxic and cytotoxic effects on human lymphocyte cells. Based on the foregoing findings, silver nanomaterials may have genotoxic and cytotoxic potentials on human peripheral lymphocytes in vitro.

Genotoxic hazard assessment of cerium oxide and magnesium oxide nanoparticles in Drosophila.

The use of metal oxide nanoparticles (NPs) is steadily spreading, leading to increased environmental exposures to many organisms, including humans. To improve our knowledge of this potential hazard, we have evaluated the genotoxic risk of cerium oxide (CeO2NPs) and magnesium oxide (MgONPs) nanoparticle exposures using Drosophila as an in vivo assay model. In this study, two well-known assays, such as the wing somatic mutation and recombination test (wing-spot assay) and the single-cell gel electrophoresis test (comet assay) were used. As a novelty, and for the first time, changes in the expression levels of a wide panel of DNA repair genes were also evaluated. Our results indicate that none of the concentrations of CeO2NPs increased the total spot frequency in the wing-spot assay, while induction was observed at the highest dose of MgONPs. Regarding the comet assay, both tested NPs were unable to induce single DNA strand breaks or oxidative damage in DNA bases. Nevertheless, exposure to CeO2NPs induced significant increases in the expression levels of the Mlh1 and Brca2 genes, which are involved in the double-strand break repair pathway, together with a decrease in the expression levels of the MCPH1 and Rad51D genes. Regarding the effects of MgONPs exposure, the expression levels of the Ercc1, Brca2, Rad1, mu2, and stg genes were significantly increased, while Mlh1 and MCPH1 genes were decreased. Our results show the usefulness of our approach in detecting mild genotoxic effects by evaluating changes in the expression of a panel of genes involved in DNA repair pathways.