Toxicology data of graphene-family nanomaterials: an update.

Due to its unique physical structure and chemical properties, graphene family nanomaterials (GFNs) and derived commodities have been widely used in commercial products, particularly biomedical applications, which has significantly increased the risk of human exposure. There exists significant evidence that GFNs are accumulated in a number of tissues and organs through different exposure pathways, and further cause toxicity manifested as lesions or functional impairment. Moreover, GFNs can be internalized by varing cell types and induce cytoskeletal disorders, organelle dysfunction, and interact directly with biological macromolecules such as DNA, mRNA and proteins, ultimately resulting in greater rates of cell apoptosis, necrosis and autophagic cell death. The toxicological effect of GFN is closely related to its lateral size, surface structure, functionalization, and propensity to adsorb proteins. Using major data published over the past four years, this review presents and summarizes state of current understanding of GFN toxicology and identifies current deficiencies and challenges. This review aims to help improve evaluation of the biocompatibility of GFNs and provides theoretical guidance for their safe application.

Evaluating the safety and efficiency of nanomaterials: A focus on mitochondrial health.

Nanomaterials (NMs) have extensive application potential in drug delivery, tissue engineering, and various other domains, attributable to their exceptional physical and chemical properties. Nevertheless, an increasing body of literature underscores the diverse safety risks are associated with NMs upon interaction with the human body, including oxidative stress and programmed cell death. Mitochondria, serving as cellular energy factories, play a pivotal role in energy metabolism and the regulation of cell fate. Organs with substantial energy demands, including the heart and brain, are highly sensitive to mitochondrial integrity, with mitochondrial impairment potentially resulting in significant dysfunction and pathologies such as as heart failure and neurodegenerative disease. This review elucidates the pathways by which NMs translocate into mitochondria, their intracellular dynamics, and their impact on mitochondrial morphology, respiratory chain activity, and metabolic processes. We further investigate associated molecular mechanisms, including mitochondrial dynamic imbalance, calcium overload, and oxidative stress, and elucidate the pivotal roles of mitochondria in different forms of programmed cell death such as apoptosis and autophagy. Finally, we offer recommendations regarding the safety and efficacy of NMs for medical applications. By systematically analyzing the interactions and molecular mechanisms between NMs and mitochondria, this paper aims to enhance the toxicological evaluation framework of NMs and provide a foundational reference and theoretical basis for their clinical utilization.

Bayesian network analysis of long-term oncologic outcomes of open, laparoscopic, and robot-assisted radical cystectomy for bladder cancer.

BACKGROUND: To understand the long-term oncologic outcomes of open radical cystectomy (ORC) versus laparoscopic radical cystectomy (LRC) versus robot-assisted radical cystectomy (RARC) for bladder cancer (BCa). Therefore, we performed the conventional meta-analysis and network meta-analysis to evaluate the long-term oncologic outcomes of ORC, LRC, and RARC for BCa. METHODS: A systematic search of PubMed, Embase, Cochrane Library, Medline, and Web of science was performed up until July 1, 2021. Long-term oncologic outcomes include the 5-year overall survival (OS) rate, the 5-year recurrence-free survival (RFS) rate, and the 5-year cancer specific-survival (CSS) rate. The Bayesian network analysis has been registered in PROSPERO (CRD42020208396). RESULTS: We found that 10 articles (including 3228 patients) were included in our Bayesian network analysis. No significant differences were found between ORC, LRC, and RARC in long-term oncologic outcomes in either direct meta-analysis or network meta-analysis. Therefore, the clinical effects of 5-year OS, RFS, and CSS of RARC, LRC, and ORC are similar. But LRC may be ranked first in 5-year OS, RFS, and CSS compared to other surgical approaches by probabilistic analysis ranking via Bayesian network analysis. CONCLUSION: We found that there were no statistical differences in the 3 surgical approaches of RAPC, LPC, and OPC for Bca in long-term oncologic outcomes by direct meta-analysis. However, Subtle differences between these surgical approaches can be concluded that LRC may be a better surgical approach than RARC or ORC in long-term oncologic outcomes by probabilistic analysis ranking via Bayesian network analysis. Moreover, we need a large sample size and more high-quality studies to improve and verify further.

Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells.

Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.

Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes.

RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p <0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p <0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p <0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.

Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.

AIM: To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. MATERIALS & METHODS: Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. RESULTS: A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. CONCLUSION: These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.