The unique physicochemical characteristics of nanoparticles have recently gained increasing attention in a diverse set of applications, particularly in the biomedical field. However, concerns about ...the potential toxicological effects of nanoparticles remain, as they have a higher tendency to generate excessive amounts of reactive oxygen species (ROS). Due to the strong oxidation potential, the excess ROS induced by nanoparticles can result in the damage of biomolecules and organelle structures and lead to protein oxidative carbonylation, lipid peroxidation, DNA/RNA breakage, and membrane structure destruction, which further cause necrosis, apoptosis, or even mutagenesis. This review aims to give a summary of the mechanisms and responsible for ROS generation by nanoparticles at the cellular level and provide insights into the mechanics of ROS-mediated biotoxicity. We summarize the literature on nanoparticle toxicity and suggest strategies to optimize nanoparticles for biomedical applications.
BACKGROUNDPrevious studies have found that blueberry anthocyanin extract (BAE) could prevent diabetic retinopathy (DR) development, but the underlying molecular mechanism is still a mystery. ...METHODSHuman retinal pigment epithelium cell line ARPE-19 cells were exposed to high concentration glucose (H-Glu) with 25 mM for 24 h, and the cell viability and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The endoplasmic reticulum stress (ERS) markers were determined by western blotting. Dual luciferase assay was applied to investigate the relationship between miR-182 and 8-oxoguanine-DNA glycosylase (OGG1). Furthermore, experiments in vivo were also performed to confirm the function of BAE in DR. RESULTSThe increase of apoptosis, reactive oxygen species (ROS) level and ERS in ARPE-19 cells induced by H-Glu was notably restored by BAE. Meanwhile, BAE greatly inhibited H-Glu-induced miR-182 expression in ARPE-19 cells, and OGG1 was identified to be one of the downstream target moleculars of miR-182. Furthermore, miR-182 overexpression or OGG1 knockdown restored the impact of BAE on H-Glu-treated APRE-19 cells. Even more important, BAE was further confirmed to alleviated the development of DR in diabetes rat models. CONCLUSIONSBAE significantly inhibited the progression of DR via molecular regulation function between miR-182/OGG1 axis and ROS/ERS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pathological cardiac hypertrophy involves excessive protein synthesis, increased cardiac myocyte size and ultimately the development of heart failure. Thus, pathological cardiac hypertrophy is a ...major risk factor for many cardiovascular diseases and death in humans. Extensive research in the last decade has revealed that post‐translational modifications (PTMs), including phosphorylation, ubiquitination, SUMOylation, O‐GlcNAcylation, methylation and acetylation, play important roles in pathological cardiac hypertrophy pathways. These PTMs potently mediate myocardial hypertrophy responses via the interaction, stability, degradation, cellular translocation and activation of receptors, adaptors and signal transduction events. These changes occur in response to pathological hypertrophy stimuli. In this review, we summarize the roles of PTMs in regulating the development of pathological cardiac hypertrophy. Furthermore, PTMs are discussed as potential targets for treating or preventing cardiac hypertrophy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Selective laser melting is an advanced manufacturing process which can control the microstructure evolution and mechanical properties of as-manufactured products via various processing parameters. In ...this study, the porosity/relative density, surface quality, microstructure and mechanical properties were investigated on the selective laser melted Ti-6Al-4V alloy specimens fabricated with a wide range of laser energy inputs. It was found that the microstructure of selected laser melted Ti-6Al-4V alloys is typical of acicular martensites α′. Quantitative analysis reveals that the relative density, martensitic lath size and microhardness increase with the laser energy input. The surface quality is also substantially affected by the energy input.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and ...tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein-protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bulk Ti–6Al–4V material and its lattice structures with rhombic dodecahedron unit cells are fabricated by electron beam melting (EBM) and selective laser melting (SLM) method respectively. The effect ...of part size on the compressive properties and failure modes of the material is taken into consideration. Electronic universal testing machine and Split Hopkinson pressure bar (SHPB) system are adopted for experiments, and the compressive behavior of the additively manufactured materials is investigated accordingly. Meanwhile, multiscale observations are conducted to reveal the macro- and microscopic deformation mechanism. The results showed that the mechanical response of the dense struts as well as micro-lattice structures manufactured by the two processes are quite different. The geometric imperfections are considered to reduce the strength of the undersized struts prepared by EBM. The specimens fabricated by both of the two approaches exhibit elastic-plastic deformation. Besides, the SLM made material is found to be more sensitive to strain rate especially for that below 1000/s than the EBM parts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC patients are commonly diagnosed at an advanced stage, for which highly effective therapies are ...limited. Moreover, the five-year survival rate of HCC patients remains poor due to high frequency of tumor metastasis and recurrence. These challenges give rise to the emergent need to discover promising biomarkers for HCC diagnosis and identify novel targets for HCC therapy. Circular RNAs (circRNAs), a class of long-overlook non-coding RNA, have been revealed as multi-functional RNAs in recent years. Growing evidence indicates that circRNA expression alterations have a broad impact in biological characteristics of HCC. Most of these circRNAs regulate HCC progression by acting as miRNA sponges, suggesting that circRNAs may function as promising diagnostic biomarkers and ideal therapeutic targets for HCC. In this review, we summarize the current progress in studying the functional role of circRNAs in HCC pathogenesis and present their potential values as diagnostic biomarkers and therapeutic targets. In-depth investigations on the function and mechanism of circRNAs in HCC will enrich our knowledge of HCC pathogenesis and contribute to the development of effective diagnostic biomarkers and therapeutic targets for HCC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Although machine learning (ML) techniques are increasingly used in rainfall-runoff models, most of them are based on one-dimensional datasets. In this study, a rainfall-runoff model with deep ...learning algorithms (CNN-LSTM) was proposed to compute runoff in the watershed based on two-dimensional rainfall radar maps directly. The model explored a convolutional neural network (CNN) to process two-dimensional rainfall maps and long short-term memory (LSTM) to process one-dimensional output data from the CNN and the upstream runoff in order to calculate the flow of the downstream runoff. In addition, the Elbe River basin in Sachsen, Germany, was selected as the study area, and the high-water periods of 2006, 2011, and 2013, and the low-water periods of 2015 and 2018 were used as the study periods. Via the fivefold validation, we found that the Nash–Sutcliffe efficiency (NSE) and Kling–Gupta efficiency (KGE) fluctuated from 0.46 to 0.97 and from 0.47 to 0.92 for the high-water period, where the optimal fold achieved 0.97 and 0.92, respectively. For the low-water period, the NSE and KGE ranged from 0.63 to 0.86 and from 0.68 to 0.93, where the optimal fold achieved 0.86 and 0.93, respectively. Our results demonstrate that CNN-LSTM would be useful for estimating water availability and flood alerts for river basin management.
Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial ...method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 μg/mL and 16 μg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exosomes are a type of extracellular vesicles (EVs) secreted by almost all cells, with a diameter range of 30–150 nm and a lipid bilayer membrane. Exosomes are now considered as vital mediators of ...intercellular communication and participate in multiple cellular processes, such as signal transduction and antigen presentation. Recently, circular RNAs (circRNAs), a novel class of noncoding RNAs (ncRNAs), have been found to be abundant and stable in exosomes. Increasing evidence indicates that exosome-derived circRNAs act as signaling molecules to regulate cancer growth, angiogenesis, invasion, metastasis, and sensitivity to chemotherapy. Moreover, circulating exosomal circRNAs can reflect the progression and malignant characteristics of cancer, implying their great potential as promising, non-invasive biomarkers for cancer diagnosis and prognosis. In this review, we summarize the recent progress on the functional roles of exosomal circRNAs in cancer progression, discussing their potential as promising biomarkers and therapeutic targets in cancer. Comprehensive elucidation of molecular mechanisms relevant to the implications of exosomal circRNAs in cancer progression will be conducive to the development of innovative diagnostic and therapeutic approaches in cancer.
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Exosomal circular RNAs (circRNAs) are involved in tumor cell growth, angiogenesis, invasion, metastasis, and chemoresistance. However, many gaps in our understanding of the relationship between exosomal circRNAs and cancer biology exist. This review gathers current knowledge regarding the origination, expression, functions, and clinical implications of exosomal circRNAs in cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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