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Objective: The objective of this work is to compare our outcomes using thulium laser enucleation of prostate (ThuLEP) to the single-port robot-assisted simple prostatectomy (SP RASP) in the surgical management of benign prostatic hyperplasia (BPH)., Methods: A retrospective cohort study was conducted from January 2017 through December 2021 of men who underwent SP RASP and ThuLEP performed by a single surgeon with an enucleation experience of >300 cases and extensive robotic experience. The primary outcome was changed in International Prostate Symptom Score (IPSS) postoperatively. Secondary outcomes were operative time, length of stay (LOS), change in post-void residuals (PVR), de novo stress- or urge-urinary incontinence (SUI, UUI), and rate of complications., Results: One hundred two patients underwent surgery during the study period: 33 RASP and 69 ThuLEP. There was no difference in preoperative characteristics, including age and body mass index, between both groups. Changes in IPSS scores postoperatively were not significant between SP RASP versus ThuLEP (-17 vs. -14, p  = 0.2956). SP RASP had a longer operative time (180 vs. 90 min, p  < 0.0001). There was no difference in LOS (0 vs. 0 days, p  = 0.2904). There was no difference in change in PVR (-96 vs. -91 mL, p  = 0.8504). SP RASP patients had significantly less postoperative SUI than ThuLEP (0 vs. 13 patients, p  = 0.0083), while there was no difference in UUI between both groups (4 vs. 2 patients, p  = 0.0843). There was no difference in 30-day complication rate (21.2% vs. 21.7%, p  = 0.9517), although there were three ThuLEP patients with Clavien-Dindo Class III or higher complication., Conclusions: There was no difference in change in IPSS scores between the two groups. ThuLEP is associated with shorter postoperative catheter days and decreased operative times. Hospital LOS was equivalent. SP RASP demonstrates significantly improved continence rates. Though SP RASP is within the initial learning curve at our institution, early results demonstrate the role for this modality alongside ThuLEP in the treatment of large gland BPH., Competing Interests: Dr. Simone Crivellaro is a consultant for Intuitive Surgical, Inc. All other authors have nothing to disclose., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O 2 • -), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H 2 O 2 instead of O 2 • -, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity. Altogether these results suggest that O 2 • - generated during NPs induced mitochondrial collapse is rapidly dismutated to H 2 O 2 , which in the presence of iron ions undergoes a Fenton reaction to produce an extremely reactive hydroxyl radical ( • OH). Clarification of the mechanism of NPs-dependent generation of • OH and demonstration of the crucial role of iron ions in NPs toxicity will facilitate our understanding of NPs toxicity and the design of safe nanomaterials., (Copyright © 2018. Published by Elsevier B.V.)

Application of nanomaterials in nearly every single branch of industry results in their accumulation in both abiotic environment and tissues of living organisms. Despite the common use of nanomaterials, we are not able to precisely define their toxicity towards humans and surrounding biota. Although we were able to determine final effects of chronic exposure to nanoparticles which consist of many pathologies such as respiratory diseases, allergies, diseases of cardiovascular system, disorders in embryonic life differentiation and growth disorders, toxic effects on the immune system and cancers. The most predominantly investigated feature of most nanoparticles is their ability to induce oxidative stress on cellular level. Imbalance in redox state of cells can lead to various malfunctions in their internal metabolism, which in turn can lead to mentioned pathologies on the organismal level if the exposure is persistent and spread wide enough. Imbalance in redox state translate into production of reactive oxygen species in amounts impossible to be scavenged in given time. Many reactive oxygen species play crucial role in physiological processes in properly functioning cells. It was proven on numerous occasions that abundance of ROS, aside from oxidative damage, can lead to more subtle adverse effects tied to disturbances in intra- and intercellular signaling pathways. In this chapter we would like to address the nanoparticle-induced redox imbalance in cells and its effects.

Biodiesels represent more carbon-neutral fuels and are introduced at an increasing extent to reduce emission of greenhouse gases. However, the potential impact of different types and blend concentrations of biodiesel on the toxicity of diesel engine emissions are still relatively scarce and to some extent contradictory. The objective of the present work was to compare the toxicity of diesel exhaust particles (DEP) from combustion of two 1st-generation fuels: 7% fatty acid methyl esters (FAME; B7) and 20% FAME (B20) and a 2nd-generation 20% FAME/HVO (synthetic hydrocarbon biofuel (SHB)) fuel. Our findings indicate that particulate emissions of each type of biodiesel fuel induce cytotoxic effects in BEAS-2B and A549 cells, manifested as cell death (apoptosis or necrosis), decreased protein concentrations, intracellular ROS production, as well as increased expression of antioxidant genes and genes coding for DNA damage-response proteins. The different biodiesel blend percentages and biodiesel feedstocks led to marked differences in chemical composition of the emitted DEP. The different DEPs also displayed statistically significant differences in cytotoxicity in A549 and BEAS-2B cells, but the magnitude of these variations was limited. Overall, it seems that increasing biodiesel blend concentrations from the current 7 to 20% FAME, or substituting 1st-generation FAME biodiesel with 2nd-generation HVO biodiesel (at least below 20% blends), affects the in vitro toxicity of the emitted DEP to some extent, but the biological significance of this may be moderate.

We have reported previously that glucose availability can modify toxicity of silver nanoparticles (AgNPs) via elevation of antioxidant defence triggered by increased mitochondrial generation of reactive oxygen species. In this study, we examined the effect of glucose availability on the production of reactive nitrogen species in HepG2 cells and modification of nitrative stress by AgNPs. We found that lowering the glucose concentration increased expression of genes coding for inducible nitric oxide syntheas, NOS2 and NOS2A resulting in enhanced production of nitric oxide. Surprisingly, AgNPs decreased the level of nitric oxide accelerated denitration of proteins nitrated by exogenous peroxynitrite in cells grown in the presence of lowered glucose concentration, apparently due to further induction of protective proteins., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to compare the antioxidant activities of six atypical antipsychotic drugs: clozapine (CLZ), quetiapine, olanzapine (OLA), risperidone, ziprasidone, aripiprazole (ARI), as well as a typical antipsychotic drug, haloperidol. Several tests of antioxidant activity were used: protection of thiol groups against oxidation by peroxynitrite (PN) and 3-morpholinosydnonimine (SIN-1, generator of PN), oxidation of dihydrorhodamine 123 by PN, SIN-1 and hypochlorite (NaOCl), bleaching of fluorescein fluorescence by PN, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH, generator of peroxyl radicals) and NaOCl, radical-scavenging activity with respect to 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) radical, 2,2-diphenyl-1-picrylhydrazyl free radical and the Ferric Reducing Antioxidant Potential. In most of the tests, OLA showed the highest antioxidant activity, followed by CLZ and in some cases ARI, other compounds being much less active or not active. OLA and CLZ exerted limited toxicity on mouse neuroblastoma Neuro-2A (N2A) cells and protected the cells against the toxic action of SIN-1, AAPH and NaOCl in the physiologically relevant concentration range of these oxidants. Both drugs reduced the PN-induced nitration of intracellular proteins. Given that schizophrenia is associated with oxidative and nitrosative stress, the direct antioxidant activity OLA and CLZ may contribute to the therapeutic action of these compounds., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT₁R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4. We used Ang II (200 ng/kg/min) infusion in mice and Ang II (10(-8) M) treatment of T35OK-AT₁R proximal tubule cells to test our hypothesis. Ang II-infused mouse kidneys displayed increases in DPP4 activity and decreases in megalin. In proximal tubule cells, Ang II stimulated DPP4 activity concurrent with suppression of megalin. MK0626, a DPP4 inhibitor, partially restored megalin expression similar to U0126, a mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) kinase kinase (MEK) 1/2 inhibitor and AG1478, an epidermal growth factor receptor (EGFR) inhibitor. Similarly, Ang II-induced ERK phosphorylation was suppressed with MK0626 and Ang II-induced DPP4 activity was suppressed by U0126. Therefore, our study reveals a cross talk between AT₁R signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression.

Background: The increasing body of evidence suggest that nanomaterials toxicity is associated with generation of oxidative stress. In this paper we investigated the role of respiration in silver nanoparticles (AgNPs) generated oxidative stress and toxicity. Since cancer cells rely on glucose as the main source of energy supply, glucose availability might be an important determinant of NPs toxicity., Methods: AgNPs of 20 nm nominal diameter were used as a model NPs. HepG2 cells were cultured in the media with high (25 mM) or low (5.5 mM) glucose content and treated with 20 nm AgNPs. AgNPs-induced toxicity was tested by neutral red assay. Generation of H2O2 in mitochondria was evaluated by use of mitochondria specific protein indicator HyPer-Mito. Expression of a 77 oxidative stress related genes was assessed by qPCR. The activity of antioxidant enzymes was estimated colorimetrically by dedicated methods in cell homogenates., Results: AgNPs-induced dose-dependent generation of H2O2 and toxicity was observed. Toxicity of AgNPs towards cells maintained in the low glucose medium was significantly lower than the toxicity towards cells growing in the high glucose concentration. Scarceness of glucose supply resulted in upregulation of the endogenous antioxidant defence mechanisms that in turn alleviated AgNPs dependent ROS generation and toxicity., Conclusion: Glucose availability can modify toxicity of AgNPs via elevation of antioxidant defence triggered by oxidative stress resulted from enhanced oxidative phosphorylation in mitochondria and associated generation of ROS. Presented results strengthen the idea of strong linkage between NPs toxicity and intracellular respiration and possibly other mitochondria dependent processes.

We examined the relation between DNA damage and the clonogenic potential of 3 human cell lines, HepG2, HT29 and A549, treated with bare 20 nm or 200 nm silver nanoparticles (AgNPs). The endpoints examined were the DNA breakage estimated by the comet assay, the oxidative base damage recognized by formamido-pyrimidine glycosylase (FPG) and estimated with the FPG+comet assay, and the frequencies of histone γH2AX foci and micronuclei. Each cell line studied had a different pattern of DNA breakage and base damage versus the NPs concentration and time of treatment. The overall pattern of DNA breakage and base damage induction corresponded to the intracellular generation of reactive oxygen species. There was no increase in the frequencies of histone γH2AX foci and micronuclei as compared to those in the untreated cells. The reported experiments suggest that only the oxidative DNA damage corresponds to the loss of the clonogenic ability of cells treated with AgNPs., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)