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A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles

A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles

Recently, the cytotoxicity effects of 5 and/or 15 nm GNPs 5 and 15 nm in vitro on Balb/3T3 mouse fibroblasts have been investigated. In order to understand the observed differences in cytotoxicity of two sizes of GNPs, Gioria et al. examined the uptake and the intracellular distribution of the NPs. The results indicated cytotoxicity effects only for the cells treated with 5 nm GNPs but no toxicity was revealed on Balb/3T3 for 15 nm GNPs. This observation is due to high number of 5 nm GNPs taken-up by cells in comparison to the larger particles (15 nm particles). 78
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Toxicity of manufactured copper nanoparticles - A review

Toxicity of manufactured copper nanoparticles - A review

The gastrointestinal tract is also considered as a possible admission portal [1]. There are many ways in which NP can be ingested in the gastrointestinal tract. The absorption of particles of different sizes through the gastrointestinal tract can also end up in various toxic effects [43]. Although NP may contact the respiratory organs, however, other organs such as the gastrointestinal tract should be considered because NP can enter the gastrointestinal tract in many ways and indirectly through the mucosa or directly via the oral route. [44, 45]. There are few reports on the toxicological study of the gastrointestinal tract of nanomaterials. In a study in which only a few mice exhibited spectral symptoms, all mice treated with nano-copper clearly showed symptoms of food channel dysfunction, loss of appetite, diarrhea and vomiting. [1] Nano-copper can be translocated light intestinal tract containing lymphatic intestinal tissue (Peyer’s plaques (PP)) and M cells (specialized phagocytosis enterocytes). Furthermore, it can promote phagocytosis in the gastrointestinal mucosa and produce immune responses mediated by antigens [46]. Consistency can be directly linked to the route of exposure and the physico-chemical properties of the nanosustancia (for example, type, size, structure, surface modification, crystalline phase). The oral route is a relatively simple toxicological process compared to the pulmonary routine [7]. Once introduced into the stomach, NP copper will react drastically with hydrogen ions (H +) of gastric juice and can quickly become ionic. This chemical process undoubtedly causes an ionic copper overload in vivo. Because the ultrafine NPs of copper nanoparticles are highly active in the biological system when they are in the stomach. Nano-particles cause the accumulation of copper highly alkaloscentes heavy substances and excessive copper ions concludes with metabolic alkalosis and copper overload [16]. When nano-copper reacts to the acidic substance in the stomach, many proton ions are consumed. Metabolic alkalosis, such as poisoned copper ions, ends with a higher mortality than microcirculation in the same dose [16].
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Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β - (TGF- β -) and tumor necrosis factor-alpha (TNF- α ) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.
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A review of mammalian toxicity of ZnO nanoparticles

A review of mammalian toxicity of ZnO nanoparticles

metal oxide NPs tested, in vivo and in vitro toxicity could be predicted by their band-gap energy, ZnO (and CuO) NP toxicity is determined by its solubility. In fact, the first deci- sion in the proposed strategy for toxicity prediction is based on whether the solubility of the metal oxide NP is above a certain threshold (as is the case for ZnO NPs); the second decision is based on whether the band-gap energy overlaps with the cellular redox potential.

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Applications of Upconversion Nanoparticles in Molecular Imaging: A Review of Recent Advances and Future Opportunities

Applications of Upconversion Nanoparticles in Molecular Imaging: A Review of Recent Advances and Future Opportunities

Fluorescent nanoparticles have excellent photostability, chemical stability and low toxicity. advantages of these NPs over visible QDs and organic dye doped NPs is their ability to be excited in the NIR region, where autoûuorescence is minimal, tissue penetration is maximum and there is minimum photodamage. They also do not exhibit photoblinking, which is a phenomenon observed in QDs. The upconversion ûuorescence output of UCNs is also higher than that of QDs. These particles can be applied for drug and gene delivery due to the ability to protect their encapsulated content and physical properties.
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Molecular Mechanisms Involved in Inflammatory Cascade: A Review

Molecular Mechanisms Involved in Inflammatory Cascade: A Review

antioxidants are the synthetic compounds, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). The antioxidants are used as food additives and supplements to prevent and or remove oxidative species. However, despite being effective as antioxidants, the two compounds have been found have adverse effects that include carcinogenesis, liver and kidney toxicity. Long term regular long-term use of low dose NSAIDs has been associated with a significant reduction in the incidence of colon cancers by approximately 40% (Lam et al., 2004). Therefore, the ultimate goal would be to obtain anti-inflammatory agents that are effective with minimal to no adverse effects when administered over a long-term period. The agents would have the dual role of treating inflammation and preventing development of chronic and degenerative diseases. Plants have been considered to be sources of the new anti-inflammatory agents due to their extensive use in folk medicine globally to treat various ailments (Boukhatem et al., 2013).
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Characterisation of molecular mechanisms involved in nevirapine- induced hypersensitivity

Characterisation of molecular mechanisms involved in nevirapine- induced hypersensitivity

The variety of HLA genotyping techniques used (such as serological and sequence based HLA typing), genotype resolution and partial reporting of genotypes may all contribute to the differences in associations described. Low resolution typing refers to HLA-alleles reported at a two-digit level (e.g.: C*04) that represents a wide group of alleles. In addition, ambiguous results generated by high resolution HLA typing may not lead to the identification of two specific alleles but rather in a list of possibilities, e.g. HLA-C*04:01/04:05/04:07. The majority of studies had to be grouped at two-digit level to allow a comprehensive analysis of sub-group specificities. But this does not support the identification of individual alleles associated with NVP-induced ADRs. In addition, bias due to the selective reporting of statistically significant risk alleles and investigated genotypes cannot be excluded. Six of the twelve studies included in this review analysed both MHC class I and class II alleles (C ARR et al.,
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Cellular and molecular mechanisms involved in the establishment of HIV 1 latency

Cellular and molecular mechanisms involved in the establishment of HIV 1 latency

approaches to reactivation and depletion of the latent reservoir have been attempted clinically, but full depletion of this compartment remains a long-term goal. Compared to the mechanisms involved in the maintenance of HIV-1 latency and the pathways leading to viral reactivation, less is known about the establishment of latent infection. This review focuses on how HIV-1 latency is established at the cellular and molecular levels. We first discuss how latent infection can be established following infection of an activated CD4 T-cell that undergoes a transition to a resting memory state and also how direct infection of a resting CD4 T-cell can lead to latency. Various animal, primary cell, and cell line models also provide insights into this process and are discussed with respect to the routes of infection that result in latency. A number of molecular mechanisms that are active at both transcriptional and post-transcriptional levels have been associated with HIV-1 latency. Many, but not all of these, help to drive the establishment of latent infection, and we review the evidence in favor of or against each mechanism specifically with regard to the establishment of latency. We also discuss the role of immediate silent integration of viral DNA versus silencing of initially active infections. Finally, we discuss potential approaches aimed at limiting the establishment of latent infection.
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HIV protease inhibitors: a review of molecular selectivity and toxicity

HIV protease inhibitors: a review of molecular selectivity and toxicity

Abstract: Highly active antiretroviral therapy (HAART) is recognized as the most effective treatment method for AIDS, and protease inhibitors play a very important role in HAART. However, poor bioavailability and unbearable toxicity are their common disadvantages. Thus, the development of safer and potentially promising protease inhibitors is eagerly needed. In this review, we introduced the chemical characteristics and associated side effects of HIV pro- tease inhibitors, as well as the possible off-target mechanisms causing the side effects. From the chemical structures of HIV protease inhibitors and their possible off-target molecules, we could obtain hints for optimizing the molecular selectivity of the inhibitors, to provide help in the design of new compounds with enhanced bioavailability and reduced side effects. Keywords: off-target, side effect, glucose transporter-4, proteasome
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Comparative Characteristic of Toxicity of Nanoparticles using the test of Bacterial Bioluminescence

Comparative Characteristic of Toxicity of Nanoparticles using the test of Bacterial Bioluminescence

In its turn, electrostatic contact between the positively charged aggregates of copper nanoparticles (æ = +15.9±8.63 MB) with the negatively charged surface of E. coli K12 MG1655 pSoxS::lux and pKatG::lux with the inducible nature of the illumination (æ=-50.0±9.35 mV) showed the development of oxidative stress in model microorganisms. It was presumably determined by the transport of electrons through copper nanoparticles integrated with cytoplasmic membrane to molecular oxygen. The final result of this process was damage to DNA by reactive oxygen species. It was detected using the reporter strain E. coli pRecA::lux leading to the development of bactericidal effect 30 .
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<p>Molecular Mechanisms of Anticancer Activities of Puerarin</p>

<p>Molecular Mechanisms of Anticancer Activities of Puerarin</p>

Cancer is a major cause of mortality worldwide; therefore, the development of cancer treatment is highly important. Natural products (NPs) are widely used in cancer treatment because of their low toxicity and high level of success. 1 Medicinal plants proven to get active compounds contain NPs. 2 In the recent era, medicinal plants have been explored for the treatment of a wide spectrum of physiological diseases. 3–8 Common medicinal plant-derived NPs are iso fl avones with a 3-phenylchroman skeleton. 9 Legumes of the Leguminosae and Fabaceae families, including lupine, kudzu, barley, cauli fl ower, soy, and fava beans, are a major source of plant-based iso fl avones. 9,10 Puerarin (Pue), depicted in Figure 1, is an important bioactive iso fl a- vone glycoside. 11,12 Pue has been isolated from several leguminous plants of the genus Pueraria, including Pueraria tuberosa (Willd.), 13 – 15 Pueraria lobata (Willd.) Ohwi (Gegen in Chinese), 16,17 and Pueraria thomsoniiBenth. 13,18,19 Pueraria plants have been interlinked with Asian culture because of their use in decoration, cooking, and disease treatment. 13 Systematic biology is an emerging approach that focuses on molecular interactions with biological systems. 20 Pue has molecular weight 416, 21 possesses several pharmacological activities against osteoporosis, 22 cardiovascular diseases, 23 fever, 24 neurological dysfunction, 25 liver injury, 26 and hangover, and they have been used in clinical treatments and experimental research. 27 Pue injections are used extensively in China, 16,28,29 but their effects on human health remain unclear to
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Molecular mechanisms of circadian clock functioning

Molecular mechanisms of circadian clock functioning

Було встановлено, що під впливом тривалої дії різних доз метил­третбутилового ефіру (від 0,5 до 500 мг на кг маси тіла щурів протягом 1–2 місяців) значно порушується експресія генів [r]

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Molecular mechanisms of phosphate and sulphate transport in plants

Molecular mechanisms of phosphate and sulphate transport in plants

Similar transcriptional regulation of phosphate transporters by negative feedback has been reported. Genes encoding the APT1 and APT2 phosphate transporters of Arabidopsis are only expressed in roots and their expression is considerably enhanced by phosphate deprivation [12]. Root phosphate transporters isolated from potato [13], tomato [14,15], Medicago [17], and barley [18] are similarly regulated. These data have been summarised in a recent review by Mimura [29]. Localisation experi- ments with the tomato LePT1 phosphate transporter [14] revealed that, although mRNA for this trans- porter could be detected in all vegetative organs of tomato seedlings, it was primarily expressed in the peripheral cell layers of the root including the root cap, root hairs, epidermis, and outer layers of the cortex. When plants were deprived of phosphate, LePT1 was also expressed in some cells in the stelar region. Using a speci¢c antibody to LePT1 it has been shown that LePT1 protein levels also increase in response to phosphate deprivation [34]. Further, enriched levels of LePT1 protein were associated with plasma membrane preparations from phosphate starved roots in these studies. These data indicate that the enhanced levels of mRNA that result from phosphate deprivation are translated into LePT1 protein and this protein is targeted to the plasma membrane. Thus there is an increase in the total number of phosphate transporters in the plasma membranes of root cells in close proximity to the soil solution. This gives rise to the increased capacity of phosphate starved plants to take up phosphate [36^39].
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Molecular mechanisms of lymphangiogenesis in development and cancer

Molecular mechanisms of lymphangiogenesis in development and cancer

2006b). Silencing of the VEGF-C/VEGF-D/VEGFR3 signaling axis is achieved either through ligand sequestration by soluble receptor constructs (trap constructs), small molecular weight inhibitors and monoclonal antibodies against VEGFR3, or through repression of ligand expression by RNAi-technology (Sleeman et al., 2009). In most of these experimental approaches, blockade of the VEGFR3 signaling axis has efficiently repressed tumor lymphangiogenesis and with it metastasis to regional lymph nodes and distant organs. As discussed above, the contribution of the VEGF-A/VEGFR2 signaling axis to tumor lymphangiogenesis is less well defined. Blockade of VEGFR2 signaling activities in the tumor context substantially represses tumor angiogenesis, yet inhibits lympha- tic metastasis only in combination with anti-VEGFR3 treatment (Burton et al., 2008; Roberts et al., 2006; Shibata et al., 2008). From animal experiments, targeting the VEGFR3 axis seems to be the most promising approach. However the failure in blocking tumor lymphangiogenesis by VEGFR3 inhibition in some mouse models indicates that tumor lymphangiogenesis may also rely on other signaling pathways and can become independent of VEGFR3 signaling (Schomber et al., 2009; Cao et al., 2004).
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<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

Macropinocytosis has been known as a primary method for the cellular intake of fl uid-phase and mem- brane-bound bulk cargo. And recent researches show that direct roles for macropinocytosis within tumorigenesis. 113 Uptake of nutrients in the tumor microenvironment by macropinocytosis has recently been named as an emerging hallmark of cancer metabolism. 114,115 In lung cancer cell line A549, it has been demonstrated the extracellular ATP was internalized by macropinocytosis and induced intra- cellular ATP increase and drug resistance. 116 In addition, there are several researches associated with macropinocy- tosis and drug resistance in pancreatic cancer and breast cancer. 117,118 The mechanisms and effects of micropino- cytosis in gastric cancer need further study, and it may lead to a new way to solve the multi-drug resistance in gastric cancer.
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<p>Effect of superparamagnetic nanoparticles coated with various electric charges on &alpha;-synuclein and &beta;-amyloid proteins fibrillation process</p>

<p>Effect of superparamagnetic nanoparticles coated with various electric charges on &alpha;-synuclein and &beta;-amyloid proteins fibrillation process</p>

used for measurement. To prepare a solution of MTT, 5 mg of this compound was dissolved in 1 mL of PBS. The cells were cultured in 96 wells microtiter plate with 10,000 cells per well and incubated at 37 ° C for 24 hours. Then differ- ent charged nanoparticles with 2.5, 5 and 10 mg/mL were added to the culture medium, and the control well with a culture medium containing no effect of nanoparticles was considered. After incubation for 24, 48 and 72 hours in 5% CO 2 , 100 µ L MTT was added and incubated for 2 hours and then the culture medium was discarded. The reaction was stopped by adding ZAAZDMSO. As this solution dis- solves the purple colored formazan sediment in live cells, the absorption rate was measured by the ELISA device at 570 nm. In this study, to analyze the data, SPSS software (IBM Corporation, Armonk, NY, USA) was applied and the results were analyzed by ANOVA test and the significance level was measured on P,0.05.
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Molecular mechanisms of cisplatin resistance in cervical cancer

Molecular mechanisms of cisplatin resistance in cervical cancer

The molecular mechanisms underlying CPR are complex and usually associated with the following features: 1) reduction in the intracellular accumulation of the platinum compounds; 2) increase in DNA damage repair; 3) inactivation of apoptosis; 4) activation of epithelial–mesenchymal transition (EMT); 5) alteration in DNA methylation, microRNA profile, cancer stem cell characteristics, and expression of stress- response chaperones (Figure 1).

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Environmental Toxicity of Nanoparticles Environmental Toxicity of Nanoparticles

Environmental Toxicity of Nanoparticles Environmental Toxicity of Nanoparticles

mortality of Daphnia magna during 24 and 48 hours to calculate the acute toxicity (OECD 202, 2004). According to fish (lepistes – Poecllia reticula) acute toxicity test, acclimated fish was used this toxicity study. Synthetic dilution water as the volume of distilled water and 25 ml of each stock solution is made up to 2 liters and 5 fish were added. The pH of the water 7 ± 0.2, dissolved oxygen 4-6 mg/l will be adjusted. After 24 and 48 hour incubation fish deaths recorded (OECD 203, 1992). Bio- degradability test was conducted, where a 2-liter glass beaker. 10 and 100 mg/l initial COD was adjust using glucose (For 10 mg/l-COD: 0,1 g ; for 100 mg/l-COD: 0,5 g) and 10 and 100 mg/l NPs solutions were added (Before added ; NPs was stirred with sonicator). The pH of the water 7 ± 0.2, dissolved oxygen 4-6 mg/l (1N NaOH and 1 N HCl) will be adjusted. 30 mg/l-anaerobic sludge was added into the 2 liter baeker and test was started. During 28 days decreasing COD values were noted (OECD 301, 1992). Bioaccumulation test is performed in two stages. The first stage of contaminant uptake by fish are monitored in a 28- day incubation period. Aquarium 10 liter fill with water dilution in the pH 6.8 to 8.5, dissolved oxygen value of 2-3 mg/l so that ventilation is performed between. Nanoparticles concentration of 10-100 mg/l is set to be 2 different aquariums. 30 mg/l activated sludge and 10 fish was added aquariums. During this time, COD concentrations measured 0- 5-10-15 th days (OECD 305, 2012).
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Antiproliferative effects and molecular mechanisms of troglitazone in human cervical cancer in vitro

Antiproliferative effects and molecular mechanisms of troglitazone in human cervical cancer in vitro

functional role in HPV16-mediated cervical carcinogenesis. A recent study demonstrated that the activation of PPAR γ has a suppressive effect on STAT3. PPAR γ agonists negatively modulate STAT3 through direct and/or indirect mechanisms in cancer cells. In addition, STAT3 is known to be involved in the development and progression of many tumors, includ- ing cervical adenocarcinoma. The activation of STAT3 has a functional role in HPV16-mediated cervical carcinogenesis. Interestingly, a recent paper demonstrated that the activation of PPAR γ has a suppressive activity on STAT3. In fact, PPAR γ agonists negatively modulate STAT3 through direct and/or indirect mechanisms in cancer cells, and it could also be one of the mechanisms of TGZ. 30–33 However, more in-depth studies
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Ultrasound Techniques for Treatment of Bone Fractures: A Review of Mechanisms of Actions

Ultrasound Techniques for Treatment of Bone Fractures: A Review of Mechanisms of Actions

The databases of PubMed (1990-2016), EMBASE (1990-2016), Web of Sciences (1990-2016), and Google Scholar (1990-2016) were searched using the set terms. The search terms included "ultrasound wave", "bone fractures", "mechanisms of action", and "biological interactions". The obtained records were reviewed for the title and abstract by two authors and they came to consensus whether the studies are related to the review. Animal and human studies in both in vivo and in vitro designs that evaluate the therapeutic effects and/or mechanisms of action of US waves on different bone fractures were included for further evaluations. Any studies that evaluate the effects of US waves on one of the physiological, metabolic, morphological, or physical characteristic of wounds were reviewed. Because of the immense body of literature and variance in the methodology, this study aimed to provide a comprehensive and descriptive overview of the recent advances in applications of US waves for treatment of bone fractures and their mechanisms of action and biological interactions with living tissues.
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