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109 result(s) for "nontoxic"
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Development of Biocompatible Ciprofloxacin-Loaded Zinc-Bovine Serum Albumin Nanoflowers as Nontoxic Platform for Local Drug Delivery
Osteomyelitis (OM) is an inflammation of bone and bone marrow and remains one of the most challenging infectious diseases to treat. This clinical difficulty highlights the need for alternative therapeutic strategies, including targeted local delivery of antibacterial agents. In this study, we report for the first time the use of zinc-bovine serum albumin (ZnBSA) hybrid nanoflowers as potential antibiotic carriers for osteomyelitis treatment. Hybrid nanoflowers are hierarchically structured nanomaterials composed of inorganic components (typically metal phosphates) and organic molecules (such as proteins or enzymes) that self-assemble into flower-like morphologies, exhibiting high surface area and synergistic physicochemical properties arising from organic-inorganic integration. ZnBSA hybrid nanostructures were synthesized through a rapid and optimized procedure and characterized using scanning electron microscopy, infrared spectroscopy and X-ray diffraction. Ciprofloxacin was loaded into the ZnBSA nanostructures, and drug release behavior was studied by ultraviolet-visable spectroscopy. Antibacterial activity was assessed using optical density measurements and disc diffusion assays. The biocompatibility of ZnBSA loaded with ciprofloxacin was evaluated through in vitro toxicity assays on human red blood cells and dermal fibroblasts, as well as in vivo testing using . The ZnBSA nanostructures demonstrated rapid formation and improved biocompatibility compared to conventional copper-based nanoflowers. Toxicity studies confirmed a favorable safety profile both in vitro and in vivo. Ciprofloxacin-loaded ZnBSA carriers exhibited sustained drug release and effective antibacterial activity against , and . These findings indicate that ZnBSA hybrid nanostructures represent a safe and effective localized drug delivery system for osteomyelitis treatment. Their biocompatibility, rapid synthesis, sustained antibiotic release, and broad-spectrum antibacterial activity highlight their potential as a promising alternative to existing nanocarrier systems for managing bone infections.
Targeting EGFR/HER2/HER3 with a Three-in-One Aptamer-siRNA Chimera Confers Superior Activity against HER2+ Breast Cancer
HER family members are interdependent and functionally compensatory. Simultaneously targeting EGFR/HER2/HER3 by antibody combinations has demonstrated superior treatment efficacy over targeting one HER receptor. However, antibody combinations have their limitations, with high immunogenicity and high cost. In this study, we have developed a three-in-one nucleic acid aptamer-small interfering RNA (siRNA) chimera, which targets EGFR/HER2/HER3 in one molecule. This inhibitory molecule was constructed such that a single EGFR siRNA is positioned between the HER2 and HER3 aptamers to create a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera (H2EH3). EGFR siRNA was delivered into HER2-expressing cells by HER2/HER3 aptamer-induced internalization. HER2/HER3 aptamers act as antagonist molecules for blocking HER2 and HER3 signaling pathways and also as tumor-targeting agents for siRNA delivery. H2EH3 enables down-modulation of the expression of all three receptors, thereby triggering cell apoptosis. In breast cancer xenograft models, H2EH3 is able to bind to breast tumors with high specificity and significantly inhibits tumor growth via either systemic or intratumoral administration. Owing to low immunogenicity, ease of production, and high thermostability, H2EH3 is a promising therapeutic to supplement current single HER inhibitors and may act as a treatment for HER2+ breast cancer with intrinsic or acquired resistance to current drugs.
Effective Biobased Phosphorus Flame Retardants from Starch-Derived bis-2,5-(Hydroxymethyl)Furan
A series of biobased phosphorus flame retardants has been prepared by converting starch-derived bis-2,5-(hydroxymethyl)furan to the corresponding diacrylate followed by Michael addition of phosphite to generate derivatives with phosphorus moieties attached via P–C bonds. All compounds behave as effective flame retardants in DGEBA epoxy resin. The most effective is the DOPO derivative, 2,5-di[(3-dopyl-propanoyl)methyl]furan. When incorporated into a DGEBA blend at a level to provide 2% phosphorus, a material displaying a LOI of 30, an UL 94 rating of V0 and a 40% reduction in combustion peak heat release rate compared to that for resin containing no additive is obtained. The analogous compounds generated from bisphenol A and tetrabromobisphenol A exhibit similar flame-retarding properties.
Gravimetric Separation of Heavy Minerals in Sediments and Rocks
The potential of heavy minerals studies in provenance analysis can be enhanced conspicuously by using a state-of-the-art protocol for sample preparation in the laboratory, which represents the first fundamental step of any geological research. The classical method of gravimetric separation is based on the properties of detrital minerals, principally their grain size and density, and its efficiency depends on the procedure followed and on the technical skills of the operator. Heavy-mineral studies in the past have been traditionally focused on the sand fraction, generally choosing a narrow grain-size window for analysis, an approach that is bound to introduce a serious bias by neglecting a large, and sometimes very large, part of the heavy-mineral spectrum present in the sample. In order to minimize bias, not only the largest possible size range in each sample should be considered, but also, the same quantitative analytical methods should be applied to the largest possible grain-size range occurring in the sediment system down to 5 μm or less, thus including suspended load in rivers, loess deposits, and shallow to deep-marine muds. Wherever the bulk sample cannot be used for practical reasons, we need to routinely analyze the medium silt to medium sand range (15–500 μm) for sand and the fine silt to sand range (5–63 or > 63 μm) for silt. This article is conceived as a practical handbook dedicated specifically to Master and PhD students at the beginning of their heavy-mineral apprenticeship, as to more expert operators from the industry and academy to help improving the quality of heavy-mineral separation for any possible field of application.
A non-toxic equinatoxin-II reveals the dynamics and distribution of sphingomyelin in the cytosolic leaflet of the plasma membrane
Sphingomyelin (SM) is a major sphingolipid in mammalian cells. SM is enriched in the extracellular leaflet of the plasma membrane (PM). Besides this localization, recent electron microscopic and biochemical studies suggest the presence of SM in the cytosolic leaflet of the PM. In the present study, we generated a non-toxic SM-binding variant (NT-EqtII) based on equinatoxin-II (EqtII) from the sea anemone Actinia equina , and examined the dynamics of SM in the cytosolic leaflet of living cell PMs. NT-EqtII with two point mutations (Leu26Ala and Pro81Ala) had essentially the same specificity and affinity to SM as wild-type EqtII. NT-EqtII expressed in the cytosol was recruited to the PM in various cell lines. Super-resolution microscopic observation revealed that NT-EqtII formed tiny domains that were significantly colocalized with cholesterol and N-terminal Lyn. Meanwhile, single molecule observation at high resolutions down to 1 ms revealed that all the examined lipid probes including NT-EqtII underwent apparent fast simple Brownian diffusion, exhibiting that SM and other lipids in the cytosolic leaflet rapidly moved in and out of domains. Thus, the novel SM-binding probe demonstrated the presence of the raft-like domain in the cytosolic leaflet of living cell PMs.
In vitro anticancer activity of Eclipta alba whole plant extract on colon cancer cell HCT-116
Backgrounds Colon cancer is the third most deadly and one of the most diagnosed diseases in the world. Although routine screening and early detection during last decades has improved the survival, colon cancer still claims hundreds of thousands lives each year worldwide. Surgery and chemotherapy is mainstay of current treatment, nevertheless toxicity associated with this treatment underscores the urgency of demand of a better therapeutics. Close to 50% of current chemotherapeutic drugs are direct or indirect descendants compounds isolated from medicinal plants, which indicate plants are great potential sources of novel therapeutics. In our literature review we found Eclipta alba to posses many pharmacological activities, including those with anticancer potentials. However, no study on anticancer activity of this kind has been reported. Methods Phytochemicals were extracted by maceration method from shade dried whole plant of Eclipta alba using methanol as a solvent. The anticancer effect of extract was investigated on various cancer cell lines like human colorectal carcinoma (HCT-116), human prostate cancer (PC-3), Michigan cancer foundation-breast cancer (MCF-7) and renal cell carcinoma (RCC-45). We have also studied the effects on normal human embryonic lung fibroblast cell (WI-38) using MTT (methyl thiazoldiphenyltetrazolium bromide) assay, clonogenic (colony formation) and migration assay. Finally obtained results were analyzed using ANNOVA and Dunnett’s test. Results Results obtained from MTT assay revealed that the methanolic extract of Eclipta alba carried significant ( p  < 0.005) specificity against HCT-116 cells as compared to the other cancer cells. This extract also showed minimal or nontoxicity to WI-38 cells. Migration as well as clonogenic assays also confirmed the anticancer potential of the extract against HCT-116 cells. Conclusion This is a unique finding of its kind because the specific anticancer effect with minimal toxicity on normal cells has not been reported on Eclipta alba extract. Finally this finding opens up a great possibility to develop a novel antitumor drug candidate against deadly colon cancer in the future.
Facile synthesis of uniform large-sized InP nanocrystal quantum dots using tris(tert-butyldimethylsilyl)phosphine
Colloidal III-V semiconductor nanocrystal quantum dots [NQDs] have attracted interest because they have reduced toxicity compared with II-VI compounds. However, the study and application of III-V semiconductor nanocrystals are limited by difficulties in their synthesis. In particular, it is difficult to control nucleation because the molecular bonds in III-V semiconductors are highly covalent. A synthetic approach of InP NQDs was presented using newly synthesized organometallic phosphorus [P] precursors with different functional moieties while preserving the P-Si bond. Introducing bulky side chains in our study improved the stability while facilitating InP formation with strong confinement at a readily low temperature regime (210°C to 300°C). Further shell coating with ZnS resulted in highly luminescent core-shell materials. The design and synthesis of P precursors for high-quality InP NQDs were conducted for the first time, and we were able to control the nucleation by varying the reactivity of P precursors, therefore achieving uniform large-sized InP NQDs. This opens the way for the large-scale production of high-quality Cd-free nanocrystal quantum dots.
Synthesis of antibacterial poly((2-methylsulfinyl)ethyl acrylate-co-acrylic acid)-based electrospun nanofibers
DMSO-inspired polymer is frequently applied in advanced biomedical aspects due to its highly hydrophilic, excellent biocompatibility, and negligible cytotoxicity nature. Herein, our study aimed for the first time to synthesize electrospun poly((2-methylsulfinyl)ethyl acrylate-co-acrylic acid) (PMSEA-AA) nanofibers as wound dressing materials. PAA was initially grafted through a steglich esterification reaction to obtain poly(2-(methylthio)ethyl acrylate-co-acrylic acid) copolymer (PMTEA-AA). Subsequently, the obtained copolymer was further oxidized and exposed to electrospinning to give PMSEA-AA nanofiber-containing sulfoxide groups. The chemical structure of as-obtained polymers was carefully confirmed by FTIR, UV–vis, 1 H-NMR, TGA, DSC, and GPC. Further, PMSEA-AA nanofibers were observed with remarkable mechanical, hydrophilic, cell viability, and antibacterial behaviors. The tensile strength and elongation at a break for PMSEA-AA nanofibers were recorded as 9 MPa and 30%, which are higher compared to PAA fibers (6.33, 20%). The cell growth of PMTEA-AA nanofiber was considerably increased concerning pure PAA nanofiber approving the nontoxic capability due to the hydrophobicity nature and high surface area that can lead to effective contact with the cancer cells. Also, PMSEA-AA nanofiber could achieve superior bacterial inhibition zones of 12 and 9 mm for S. aureus and E. coli , respectively, compared to PAA. PMSEA-AA nanofibers could discover biomedical and pharmaceutical applications for wound healing materials, tissue engineering, and transdermal drug delivery system for skin and oral.
Genome Streamlining, Plasticity, and Metabolic Versatility Distinguish Co-occurring Toxic and Nontoxic Cyanobacterial Strains of Microcoleus
Microcoleus autumnalis , and closely related Microcoleus species, compose a geographically widespread group of freshwater benthic cyanobacteria. Canine deaths due to anatoxin-a poisoning, following exposure to toxic proliferations, have been reported globally. Harmful cyanobacterial bloom occurrences have increased worldwide due to climate change and eutrophication, causing nuisance and animal deaths. Species from the benthic cyanobacterial genus Microcoleus are ubiquitous and form thick mats in freshwater systems, such as rivers, that are sometimes toxic due to the production of potent neurotoxins (anatoxins). Anatoxin-producing (toxic) strains typically coexist with non-anatoxin-producing (nontoxic) strains in mats, although the reason for this is unclear. To determine the genetic mechanisms differentiating toxic and nontoxic Microcoleus , we sequenced and assembled genomes from 11 cultures and compared these to another 31 Microcoleus genomes. Average nucleotide identities (ANI) indicate that toxic and nontoxic strains are distinct species (ANI, <95%), and only 6% of genes are shared across all 42 genomes, suggesting a high level of genetic divergence among Microcoleus strains. Comparative genomics showed substantial genome streamlining in toxic strains and a potential dependency on external sources for thiamine and sucrose. Toxic and nontoxic strains are further differentiated by an additional set of putative nitrate transporter (nitrogen uptake) and cyanophycin (carbon and nitrogen storage) genes, respectively. These genes likely confer distinct competitive advantages based on nutrient availability and suggest nontoxic strains are more robust to nutrient fluctuations. Nontoxic strains also possess twice as many transposable elements, potentially facilitating greater genetic adaptation to environmental changes. Our results offer insights into the divergent evolution of Microcoleus strains and the potential for cooperative and competitive interactions that contribute to the co-occurrence of toxic and nontoxic species within mats. IMPORTANCE Microcoleus autumnalis , and closely related Microcoleus species, compose a geographically widespread group of freshwater benthic cyanobacteria. Canine deaths due to anatoxin-a poisoning, following exposure to toxic proliferations, have been reported globally. While Microcoleus proliferations are on the rise, the mechanisms underpinning competition between, or coexistence of, toxic and nontoxic strains are unknown. This study identifies substantial genetic differences between anatoxin-producing and non-anatoxin-producing strains, pointing to reduced metabolic flexibility in toxic strains, and potential dependence on cohabiting nontoxic strains. Results provide insights into the metabolic and evolutionary differences between toxic and nontoxic Microcoleus , which may assist in predicting and managing aquatic proliferations.
New Smart Bioactive and Biomimetic Chitosan-Based Hydrogels for Wounds Care Management
Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels’ structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.