Comparative Toxicity, Biodistribution and Excretion of Ultra-Small Gold Nanoclusters with Different Emission Wavelengths

2021 ◽  
Vol 17 (9) ◽  
pp. 1778-1787
Author(s):  
Na Li ◽  
Lina Chen ◽  
Chujie Zeng ◽  
Huanggen Yang ◽  
Silian He ◽  
...  
Keyword(s):  
Biomedical Application ◽  
Gold Nanoclusters ◽  
Potential Threat ◽  
Mechanisms Of Toxicity ◽  
Comparative Toxicity ◽  
Haemolytic Assay ◽  
High Concentrations ◽  
Living Organisms

The exponentially increased use of gold nanoclusters in diagnosis and treatment has raised serious concern about their potential threat to living organisms. However, the mechanisms of toxicity of gold nanoclusters in vitro and in vivo remain poorly understood. In this work, comparative toxicity studies, including biodistribution and excretion, were carried out with mildly and chemically synthesized ultra-small L-histidine-protected and bovine serum albumin (BSA)-protected gold nanoclusters in an all-aqueous process. These nanoclusters did not induce a remarkable impact on cell viability, even at relatively high concentrations (100 μg/mL). The haemolytic assay demonstrated that the gold nanoclusters could not destroy blood cell at 600 μg/mL. After intravenous injection with mice, the biocompatibility, biodistribution, and excretion were determined. Quantitative analysis results showed that accumulation varied in the liver, spleen, kidney, and lung, though primarily in the liver and spleen. They were excreted in urine and faeces, but mainly excreted through urine. In our study, no obvious abnormalities were found in body weight, behavioral changes, blood and serum biochemical indicators, and histopathology. These findings suggested that both gold nanoclusters showed similar effects in vivo and were safe and biocompatible, laying the foundation for safe biomedical application in the future.

scholarly journals Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure

2020 ◽  
Vol 21 (7) ◽  
pp. 2375 ◽  
Author(s):  
Zannatul Ferdous ◽  
Abderrahim Nemmar
Keyword(s):  
Silver Nanoparticles ◽  
Biomedical Application ◽  
Health Impact ◽  
Surgical Instruments ◽  
Wound Dressings ◽  
Mechanisms Of Toxicity ◽  
Biodistribution Studies ◽  
Exposure In Vivo

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs.

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

1992 ◽  
Vol 20 (1) ◽  
pp. 146-163
Author(s):  
Francis H. Kruszewski ◽  
Laura H. Hearn ◽  
Kyle T. Smith ◽  
Janice J. Teal ◽  
Virginia C. Gordon ◽  
...  
Keyword(s):  
Double Blind ◽  
Eye Irritation ◽  
Ocular Irritation ◽  
Rabbit Eye ◽  
Wide Range ◽  
High Concentrations ◽  
Alkaline Membrane ◽  
Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

Protein-templated gold nanoclusters as specific bio-imaging probes for the detection of Hg(ii) ions in in vivo and in vitro systems: discriminating between MDA-MB-231 and MCF10A cells

The Analyst ◽  
2021 ◽  
Author(s):  
Subhajit Chakraborty ◽  
Atanu Nandy ◽  
Subhadip Ghosh ◽  
Nirmal Kumar Das ◽  
Sameena Parveen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Serum Albumin ◽  
Gold Nanoclusters ◽  
Selective Detection ◽  
Imaging Probes ◽  
Bio Imaging ◽  
In Vitro Systems ◽  
Mcf10a Cells

Sub-nanomolar selective detection of Hg(ii) ions by protein (Human Serum Albumin, HSA) templated gold nanoclusters (AuNCs), both in in vitro as well as in vivo environments and specific endocytose behaviour towards breast cancer (BC) cell lines.

c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein

1994 ◽  
Vol 14 (9) ◽  
pp. 6021-6029
Author(s):  
R Metz ◽  
A J Bannister ◽  
J A Sutherland ◽  
C Hagemeier ◽  
E C O'Rourke ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Tata Box ◽  
Binding Motif ◽  
Protein Protein Interactions ◽  
High Concentrations ◽  
Tata Box Binding Protein

Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.

scholarly journals A Review on the Enhancement of Calcium Phosphate Cement with Biological Materials in Bone Defect Healing

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3075
Author(s):  
Sok Kuan Wong ◽  
Yew Hoong Wong ◽  
Kok-Yong Chin ◽  
Soelaiman Ima-Nirwana
Keyword(s):  
Calcium Phosphate ◽  
Calcium Phosphate Cement ◽  
Research Effort ◽  
Biological Materials ◽  
Biological Properties ◽  
Comprehensive Overview ◽  
Bone Defect Healing ◽  
Living Organisms

Calcium phosphate cement (CPC) is a promising material used in the treatment of bone defects due to its profitable features of self-setting capability, osteoconductivity, injectability, mouldability, and biocompatibility. However, the major limitations of CPC, such as the brittleness, lack of osteogenic property, and poor washout resistance, remain to be resolved. Thus, significant research effort has been committed to modify and reinforce CPC. The mixture of CPC with various biological materials, defined as the materials produced by living organisms, have been fabricated by researchers and their characteristics have been investigated in vitro and in vivo. This present review aimed to provide a comprehensive overview enabling the readers to compare the physical, mechanical, and biological properties of CPC upon the incorporation of different biological materials. By mixing the bone-related transcription factors, proteins, and/or polysaccharides with CPC, researchers have demonstrated that these combinations not only resolved the lack of mechanical strength and osteogenic effects of CPC but also further improve its own functional properties. However, exceptions were seen in CPC incorporated with certain proteins (such as elastin-like polypeptide and calcitonin gene-related peptide) as well as blood components. In conclusion, the addition of biological materials potentially improves CPC features, which vary depending on the types of materials embedded into it. The significant enhancement of CPC seen in vitro and in vivo requires further verification in human trials for its clinical application.

scholarly journals Antiparasitary Activity Of The Juglone Compound: A Narrative Review

2021 ◽  
pp. 13
Author(s):  
◽  
Keyword(s):  
Mortality Rate ◽  
Leishmania Donovani ◽  
Inhibitory Concentration ◽  
Narrative Review ◽  
Hymenolepis Nana ◽  
Compound A ◽  
Living Organisms ◽  
Nanomolar Range

Objective: To report, based on the literature, the action of the compound 5-hydroxy-1,4-naphthoquinone against parasites (protozoa and helminths) that affect humans. Methods: This is a narrative review that used Pubmed and Google Scholar as a data tool. This work included articles published until September 2020 that were directly related to the use of the compound juglone in antiparasitic trials. Results: The compound juglone demonstrated promising effects as a human and animal antiparasitic substance. In protozoa, the Apicomplexo Toxoplasma gondii parasite showed a high mortality rate in concentrations of juglone in the nanomolar range. The juglone showed an average inhibitory concentration (IC50) of 1.62 µM, >100 µM, and 2.02 µM µM for Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania donovani, respectively. Also, the juglone showed antihelmintic activity on Hymenolepis nana in mice, and on adult worms of Schistosoma mansoni (LE strain) with IC50 34.16 µM, 32.14 µM, and 25 µM in the 24h, 48h, and 72 h, respectively. Conclusion: The results published so far show the in vitro antiparasitic potential of juglone, and the need for further studies on the specific mode of action that interacts with parasites. Besides, the literature is still limited to studies that evaluate in vivo the compound juglone, requiring better information on its interaction with living organisms.

scholarly journals Pegylated arginase I: a potential therapeutic approach in T-ALL

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5214-5221 ◽  
Author(s):  
Claudia P. Hernandez ◽  
Kevin Morrow ◽  
Lluis A. Lopez-Barcons ◽  
Jovanny Zabaleta ◽  
Rosa Sierra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cyclin D3 ◽  
Chemotherapy Agent ◽  
High Concentrations ◽  
T Cell Lines ◽  
Arginase I ◽  
Malignant T Cells

Abstract Adult patients with acute lymphoblastic T cell leukemia (T-ALL) have a very poor prognosis and few effective therapeutic options. Therefore, novel therapies that increase the efficacy of the treatments and that prolong T-ALL patient survival are needed. Malignant T cells require high concentrations of nutrients to sustain their increased rate of proliferation. In this study, we determined whether L-Arginine depletion by the pegylated form of the L-Arginine-metabolizing enzyme arginase I (peg-Arg I) impairs the proliferation of malignant T cells. Our results show that peg-Arg I depleted L-Arginine levels in vitro and in vivo. In addition, treatment of malignant T-cell lines with peg-Arg I significantly impaired their proliferation, which correlated with a decreased progression into the cell cycle, followed by the induction of apoptosis. Furthermore, peg-Arg I impaired the expression of cyclin D3, a fundamental protein in T-ALL proliferation, through a global arrest in protein synthesis. Injection of peg-Arg I plus chemotherapy agent Cytarabine prolonged survival in mice bearing T-ALL tumors. This antitumoral effect correlated with an inhibition of T-ALL proliferation in vivo, a decreased expression of cyclin D3, and T-ALL apoptosis. The results suggest the potential benefit of L-Arginine depletion by peg-Arg I in the treatment of T-cell malignancies.

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