The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.

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Characterization of the human proliferating cell nuclear antigen physico-chemical properties: aspects of double trimer stability

Biochemistry and Cell Biology ◽

10.1139/o06-037 ◽

2006 ◽

Vol 84 (5) ◽

pp. 669-676 ◽

Cited By ~ 17

Author(s):

Stanislav N. Naryzhny ◽

Leroi V. DeSouza ◽

K.W. Michael Siu ◽

Hoyun Lee

Keyword(s):

Proliferating Cell Nuclear Antigen ◽

Wide Spectrum ◽

Gel Filtration ◽

Chemical Properties ◽

Nuclear Antigen ◽

Physico Chemical ◽

The Stability ◽

Proliferating Cell

Its toroidal structure allows the proliferating cell nuclear antigen (PCNA) to wrap around and move along the DNA fiber, thereby dramatically increasing the processivity of DNA polymerization. PCNA is also involved in the regulation of a wide spectrum of other biological functions, including epigenetic inheritance. We have recently reported that mammalian PCNA forms a double trimer complex, which may be critically important in coordinating DNA replication and other cellular functions. To gain a better understanding of the stability of PCNA complexes, we characterized the physico-chemical properties of the PCNA structure by in vivo and in vitro approaches. The data obtained by gel filtration and nondenaturing gel electrophoresis of native PCNA molecules confirm our previous observations, obtained using formaldehyde crosslinking, in which PCNA exists in the cell as a double trimer. We have also found that optimal pH (pH 6.5–7.5) is critical for the stability of the PCNA structure. The presence or absence of ATP, dithiothreitol, and Mg2+ does not affect the stability of the PCNA trimer or double trimer. However, 0.02% SDS can effectively inhibit PCNA double trimer, but not single trimer, formation. Interestingly, glycerol and ammonium sulfate significantly destabilize both PCNA trimer and double trimer structures.

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Mining a Nanoparticle Dataset, Compiled Within the MODENA-COST Action

Research Anthology on Synthesis, Characterization, and Applications of Nanomaterials ◽

10.4018/978-1-7998-8591-7.ch071 ◽

2021 ◽

pp. 1706-1724

Author(s):

Sabine Van Miert ◽

Jan Creylman ◽

Geert R. Verheyen

Keyword(s):

Chemical Properties ◽

In Vitro Testing ◽

Cost Action ◽

Robust Model ◽

Physico Chemical ◽

Classification And Regression ◽

Toxic Potential ◽

Sheer Number

Engineered nanomaterials (ENM) have new or enhanced physico-chemical properties compared to their micron-sized counterparts, but may also have an increased toxic potential. Animal and in vitro testing are typically employed to investigate the toxic effects of (nano)materials. The sheer number of ENMs and their physico-chemical parameters make it impossible to only use in vivo and in vitro testing, and modelling technologies are also deployed to find relationships between ENM parameters and toxicity. A heterogenous dataset containing information on 192 nanoparticle endpoints was compiled within the MODENA COST-Action consortium. Here, the available data was mined to identify relationships between nanoparticle properties and cell-death as measured with four cytotoxicity assays. ANOVA, collinearity analyses and classification and regression trees gave indications on potential relations between the NP-properties and toxicity, but could not deliver a robust model. More information and datapoints are necessary to build well-validated models.

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In Vitro Physico-Chemical Characterization and Standardized In Vivo Evaluation of Biocompatibility of a New Synthetic Membrane for Guided Bone Regeneration

Materials ◽

10.3390/ma12071186 ◽

2019 ◽

Vol 12 (7) ◽

pp. 1186

Author(s):

Lívia da Costa Pereira ◽

Carlos Fernando de Almeida Barros Mourão ◽

Adriana Terezinha Neves Novellino Alves ◽

Rodrigo Figueiredo de Brito Resende ◽

Marcelo José Pinheiro Guedes de Uzeda ◽

...

Keyword(s):

Bone Regeneration ◽

Chemical Properties ◽

Chemical Characterization ◽

Guided Bone Regeneration ◽

Tissue Reaction ◽

In Vivo Evaluation ◽

Physico Chemical ◽

Tissue Reactions

This study’s aim was to evaluate the biocompatibility and bioabsorption of a new membrane for guided bone regeneration (polylactic-co-glycolic acid associated with hydroxyapatite and β-tricalcium phosphate) with three thicknesses (200, 500, and 700 µm) implanted in mice subcutaneously. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and the quantification of carbon, hydrogen and nitrogen were used to characterize the physico-chemical properties. One hundred Balb-C mice were divided into 5 experimental groups: Group 1—Sham (without implantation); Group 2—200 μm; Group 3—500 μm; Group 4—700 μm; and Group 5—Pratix®. Each group was subdivided into four experimental periods (7, 30, 60 and 90 days). Samples were collected and processed for histological and histomorphometrical evaluation. The membranes showed no moderate or severe tissue reactions during the experimental periods studied. The 500-μm membrane showed no tissue reaction during any experimental period. The 200-μm membrane began to exhibit fragmentation after 30 days, while the 500-μm and 700-µm membranes began fragmentation at 90 days. All membranes studied were biocompatible and the 500 µm membrane showed the best results for absorption and tissue reaction, indicating its potential for clinical guided bone regeneration.

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Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis

Pharmaceutics ◽

10.3390/pharmaceutics11060263 ◽

2019 ◽

Vol 11 (6) ◽

pp. 263 ◽

Cited By ~ 4

Author(s):

Maria Letizia Manca ◽

Iris Usach ◽

José Esteban Peris ◽

Antonella Ibba ◽

Germano Orrù ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Chemical Properties ◽

Chemical Characterization ◽

Yeast Cells ◽

Unilamellar Vesicles ◽

Transmission Electron ◽

Physico Chemical

New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.

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Knockdown of Leptin Receptor Affects Macrophage Phenotype in the Tumor Microenvironment Inhibiting Breast Cancer Growth and Progression

Cancers ◽

10.3390/cancers12082078 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2078

Author(s):

Luca Gelsomino ◽

Giuseppina Daniela Naimo ◽

Rocco Malivindi ◽

Giuseppina Augimeri ◽

Salvatore Panza ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Leptin Receptor ◽

Macrophage Phenotype ◽

In Vivo Models ◽

Monocyte Chemoattractant Protein 1 ◽

Arginase 1 ◽

The Impact

Aberrant leptin (Ob) signaling, a hallmark of obesity, has been recognized to influence breast cancer (BC) biology within the tumor microenvironment (TME). Here, we evaluated the impact of leptin receptor (ObR) knockdown in affecting BC phenotype and in mediating the interaction between tumor cells and macrophages, the most abundant immune cells within the TME. The stable knockdown of ObR (ObR sh) in ERα-positive and ERα-negative BC cells turned the tumor phenotype into a less aggressive one, as evidenced by in vitro and in vivo models. In xenograft tumors and in co-culture experiments between circulating monocytes and BC cells, the absence of ObR reduced the recruitment of macrophages, and also affected their cytokine mRNA expression profile. This was associated with a decreased expression and secretion of monocyte chemoattractant protein-1 in ObR sh clones. The loss of Ob/ObR signaling modulated the immunosuppressive TME, as shown by a reduced expression of programmed death ligand 1/programmed cell death protein 1/arginase 1. In addition, we observed increased phagocytic activity of macrophages compared to control Sh clones in the presence of ObR sh-derived conditioned medium. Our findings, addressing an innovative role of ObR in modulating immune TME, may open new avenues to improve BC patient health care.

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Potential Applications of Biphosphonates in Dental Surgical Implants

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200702000304 ◽

2007 ◽

Vol 20 (3) ◽

pp. 455-465 ◽

Cited By ~ 6

Author(s):

D. Berardi ◽

T. Carlesi ◽

F. Rossi ◽

M. Calderini ◽

R. Volpi ◽

...

Keyword(s):

Alveolar Bone ◽

Chemical Properties ◽

Osteonecrosis Of The Jaw ◽

In Vivo Experiments ◽

Surgical Implants ◽

Physico Chemical ◽

Potential Applications ◽

Collateral Effect

Biphosphonates are largely used for their unquestionable properties of inhibiting bone resorption by osteoclast in the treatment of various osteometabolic illnesses such as osteoporosis, multiple myeloma, tumors which metastasize to the bone and malignant hypercalcemia. In this literature review the physico-chemical properties, biologic activities and the mechanisms of action of biphosphonates are described. The use of these drugs is discussed, analyzing the quantity of results which have emerged through in vitro and in vivo experiments on animal models. In this study the efficiency of these drugs is demonstrated in contrasting the osteolitic processes of the alveolar bone, in promoting the neoformation and in bettering the quality of bone implants. However, it is important to draw attention to a worrying correlation which has emerged during the last 3–4 years, between osteonecrosis of the jaw (ONJ) and the systemic administration of aminobiphosphonates. This collateral effect did not emerge following the use of non-aminobiphosphonates. The aim of this revie w is to identify the guidelines for the use of biphosphonates in oral implant surgery.

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Adverse biological effects of Milan urban PM looking for suitable molecular markers of exposure

Chemical Industry and Chemical Engineering Quarterly ◽

10.2298/ciceq120206114m ◽

2012 ◽

Vol 18 (4-2) ◽

pp. 635-641 ◽

Cited By ~ 5

Author(s):

Paride Mantecca ◽

Maurizio Gualtieri ◽

Eleonora Longhin ◽

Giuseppina Bestetti ◽

Paola Palestini ◽

...

Keyword(s):

Molecular Markers ◽

Chemical Composition ◽

Biological Effects ◽

Detailed Knowledge ◽

Biological Responses ◽

Physico Chemical ◽

Biological Hazard ◽

The Impact

The results presented summarise the ones obtained in the coordinated research project Tosca, which extensively analysed the impact of Milan urban PM on human health. The molecular markers of exposure and effects of seasonally and size-fractionated PMs (summer and winter PM10, PM2.5) were investigated in in vitro (human lung cell lines) and in vivo (mice) systems. The results obtained by the analyses of cytotoxic, pro-inflammatory and genotoxic parameters demonstrate that the biological responses are strongly dependent upon the PM samples seasonal and dimensional variability, that ultimately reflect their chemical composition and source. In fact summer PM10, enriched in crustal elements and endotoxins, was the most cytotoxic and pro-inflammatory fraction, while fine winter PMs induced genotoxic effects and xenobiotic metabolizing enzymes (like CYP1B1) production, likely as a consequence of the higher content in combustion derived particles reach in PAHs and heavy toxic metals. These outcomes outline the need of a detailed knowledge of the PMs physico-chemical composition on a local scale, coupled with the biological hazard directly associated to PM exposure. Apparently this is the only way allowing scientists and police-makers to establish the proper relationships between the respirable PM quantity/quality and the health outcomes described by clinicians and epidemiologists.

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Advances on Quinazoline Based Congeners for Anticancer Potential

Current Organic Chemistry ◽

10.2174/1385272825666210212121056 ◽

2021 ◽

Vol 25 ◽

Author(s):

Parul Grover ◽

Monika Bhardwaj ◽

Garima Kapoor ◽

Lovekesh Mehta ◽

Roma Ghai ◽

...

Keyword(s):

Anticancer Agents ◽

Medicinal Chemistry ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

Anticancer Compounds ◽

In Vivo Models ◽

Appropriate Treatment

: The heterocyclic compounds have a great significance in medicinal chemistry because they have extensive biological activities. Cancer is globally the leading cause of death and it is a challenge to develop an appropriate treatment for the management of cancer. Continuous efforts are being made to find a suitable medicinal agent for cancer therapy. Nitrogen-containing heterocycles have received noteworthy attention due to their wide and distinctive pharmacological activities. One of the most important nitrogen-containing heterocycles in medicinal chemistry is ‘quinazoline’ that possesses a wide spectrum of biological properties. This scaffold is an important pharmacophore and is considered a privileged structure. The various substituted quinazolines displayed anticancer activity against different types of cancer. This review highlights the recent advances in quinazoline based molecules as anticancer agents. Several in-vitro and in-vivo models used along with the results are also included. A subpart briefing natural quinazoline containing anticancer compounds is also incorporated in the review.

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Chagas Disease Drug Discovery

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057114550585 ◽

2014 ◽

Vol 20 (1) ◽

pp. 22-35 ◽

Cited By ~ 152

Author(s):

Eric Chatelain

Keyword(s):

Chagas Disease ◽

New Technologies ◽

Low Cost ◽

Screening Strategy ◽

New Drugs ◽

In Vivo Models ◽

The Right ◽

The Impact

American trypanosomiasis, or Chagas disease, is the result of infection by the Trypanosoma cruzi parasite. Endemic in Latin America where it is the major cause of death from cardiomyopathy, the impact of the disease is reaching global proportions through migrating populations. New drugs that are safe, efficacious, low cost, and adapted to the field are critically needed. Over the past five years, there has been increased interest in the disease and a surge in activities within various organizations. However, recent clinical trials with azoles, specifically posaconazole and the ravuconazole prodrug E1224, were disappointing, with treatment failure in Chagas patients reaching 70% to 90%, as opposed to 6% to 30% failure for benznidazole-treated patients. The lack of translation from in vitro and in vivo models to the clinic observed for the azoles raises several questions. There is a scientific requirement to review and challenge whether we are indeed using the right tools and decision-making processes to progress compounds forward for the treatment of this disease. New developments in the Chagas field, including new technologies and tools now available, will be discussed, and a redesign of the current screening strategy during the discovery process is proposed.

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