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International Journal of Molecular... Oct 2023In recent years, interest in nanotechnology has increased exponentially due to enhanced progress and technological innovation. In tissue engineering, the development of... (Review)
Review
In recent years, interest in nanotechnology has increased exponentially due to enhanced progress and technological innovation. In tissue engineering, the development of metallic nanoparticles has been amplified, especially due to their antibacterial properties. Another important characteristic of metal NPs is that they enable high control over the features of the developed scaffolds (optimizing their mechanical strength and offering the controlled release of bioactive agents). Currently, the main concern related to the method of synthesis of metal oxide NPs is the environmental impact. The physical and chemical synthesis uses toxic agents that could generate hazards or exert carcinogenicity/environmental toxicity. Therefore, a greener, cleaner, and more reliable approach is needed. Green synthetic has come as a solution to counter the aforementioned limitations. Nowadays, green synthesis is preferred because it leads to the prevention/minimization of waste, the reduction of derivatives/pollution, and the use of non-toxic (safer) solvents. This method not only uses biomass sources as reducing agents for metal salts. The biomolecules also cover the synthesized NPs or act as in situ capping and reducing agents. Further, their involvement in the formation process reduces toxicity, prevents nanoparticle agglomeration, and improves the antimicrobial activity of the nanomaterial, leading to a possible synergistic effect. This study aims to provide a comprehensive review of the green synthesis of metal and metal oxide nanoparticles, from the synthesis routes, selected solvents, and parameters to their latest application in the biomedical field.
Topics: Oxides; Reducing Agents; Nanoparticles; Metal Nanoparticles; Anti-Bacterial Agents; Metals; Plant Extracts; Solvents; Green Chemistry Technology
PubMed: 37895077
DOI: 10.3390/ijms242015397 -
Proceedings of the National Academy of... Mar 2024Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia...
Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia beating by densely grouping mitochondria just beneath the apical membrane. However, this efficient localization comes at a cost because electrons leaked during oxidative phosphorylation react with molecular oxygen to form superoxide, and thus, the cluster of mitochondria creates a hotspot for oxidant production. The relatively high oxygen concentration overlying airway epithelia further intensifies the risk of generating superoxide. Thus, airway ciliated cells face a unique challenge of producing harmful levels of oxidants. However, surprisingly, highly ciliated epithelia produce less reactive oxygen species (ROS) than epithelia with few ciliated cells. Compared to other airway cell types, ciliated cells express high levels of mitochondrial uncoupling proteins, UCP2 and UCP5. These proteins decrease mitochondrial protonmotive force and thereby reduce production of ROS. As a result, lipid peroxidation, a marker of oxidant injury, decreases. However, mitochondrial uncoupling proteins exact a price for decreasing oxidant production; they decrease the fraction of mitochondrial respiration that generates ATP. These findings indicate that ciliated cells sacrifice mitochondrial efficiency in exchange for safety from damaging oxidation. Employing uncoupling proteins to prevent oxidant production, instead of relying solely on antioxidants to decrease postproduction oxidant levels, may offer an advantage for targeting a local area of intense ROS generation.
Topics: Humans; Reactive Oxygen Species; Mitochondrial Uncoupling Proteins; Superoxides; Ion Channels; Oxidative Stress; Adenosine Triphosphate; Epithelial Cells; Oxidants; Oxygen; Mitochondrial Proteins
PubMed: 38416686
DOI: 10.1073/pnas.2318771121 -
Environmental Science and Pollution... Feb 2024The European Union requires environmental monitoring of the antidepressant drug venlafaxine. Advanced oxidation processes provide a remedy against the spread of...
The European Union requires environmental monitoring of the antidepressant drug venlafaxine. Advanced oxidation processes provide a remedy against the spread of micropollutants. In this study, the photoinduced and electrochemical decompositions of venlafaxine were investigated in terms of mechanism and efficacy using high-performance liquid chromatography coupled to high-resolution multifragmentation mass spectrometry. Kinetic analysis, structure elucidation, matrix variation, and radical scavenging indicated the dominance of a hydroxyl-mediated indirect mechanism during photodegradation and hydroxyl and direct electrochemical oxidation for electrochemical degradation. Oxidants, sulfate, and chloride ions acted as accelerants, which reduced venlafaxine half-lives from 62 to 25 min. Humic acid decelerated degradation during ultra-violet irradiation up to 50%, but accelerated during electrochemical oxidation up to 56%. In silico quantitative structure activity relationship analysis predicted decreased environmental hazard after advanced oxidation process treatment. In general, photoirradiation proved more efficient due to faster decomposition and slightly less toxic transformation products. Yet, matrix effects would have to be carefully evaluated when potential applications as a fourth purification stage were to be considered.
Topics: Venlafaxine Hydrochloride; Kinetics; Oxidants; Oxidation-Reduction; Hydroxyl Radical; Water Pollutants, Chemical
PubMed: 38252206
DOI: 10.1007/s11356-024-32018-5 -
Redox Biology Sep 2023Diabetes mellitus currently affects ∼10% of the population worldwide, with Type 2 predominating, and this incidence is increasing steadily. Both Type 1 and 2 are...
Diabetes mellitus currently affects ∼10% of the population worldwide, with Type 2 predominating, and this incidence is increasing steadily. Both Type 1 and 2 are complex diseases, involving β-cell death and chronic inflammation, but the pathways involved are unresolved. Chronic inflammation is characterized by increased oxidant formation, with this inducing protein modification, altered function and immunogenicity. Amylin, a peptide hormone co-secreted with insulin by β-cells, has attracted considerable interest for its amyloidogenic properties, however, the effects that oxidants have on amylin aggregation and function are poorly understood. Amylin was exposed in vitro to hypochlorous acid, hydrogen peroxide and peroxynitrous acid/peroxynitrite to investigate the formation of post-translational oxidative modifications (oxPTMs, via mass spectrometry) and fibril formation (via transmission electron microscopy). Amylin free acid (AFA) was also examined to investigate the role of the C-terminal amide in amylin. Oxidant exposure led to changes in aggregate morphology and abundance of oxPTMs in a concentration-dependent manner. The toxicity and immunogenic potential of oxidant-modified amylin or AFA on pancreatic islet cells (INS-1E), human monocyte cell line (THP-1) and monocyte-derived dendritic cells (moDCs) were examined using metabolic activity and cytokine assays, and flow cytometry. No significant changes in vitality or viability were detected, but exposure to oxidant-modified amylin or AFA resulted in altered immunogenicity when compared to the native proteins. THP-1 and moDCs show altered expression of activation markers and changes in cytokine secretion. Furthermore, oxidant-treated amylin and AFA promoted maturation of THP-1 and pre-mature moDCs, as determined by changes in size, and maturation markers.
Topics: Humans; Islet Amyloid Polypeptide; Oxidants; Amyloid; Islets of Langerhans; Myeloid Cells; Cytokines
PubMed: 37544243
DOI: 10.1016/j.redox.2023.102835 -
Journal of Chromatography. B,... Jan 2024Polysorbates (PS) are the most frequently used surfactants to stabilize biologicals. Ironically, these excellent stabilizing non-ionic surfactants have inherent...
Polysorbates (PS) are the most frequently used surfactants to stabilize biologicals. Ironically, these excellent stabilizing non-ionic surfactants have inherent structural properties, which lead to instabilities of their own. Such PS degradation can be triggered by multiple root-causes, like chemical and enzymatic hydrolysis or oxidative degradation. This can on the one hand reduce the concentration of surface-active PS and on the other hand lead to the formation of unfavorable degradants, like poorly soluble free fatty acids (FFA), which may phase separate and form visible FFA particles. Due to the potential criticality of PS degradation in biopharmaceutical formulations, various analytics have been established in recent years not only to monitor the PS content but also to evaluate specific PS markers and crucial degradants. However, in most cases sample preparations and several analytical assays have to be conducted to obtain a comprehensive picture of potential PS degradation root-causes. Here we show a novel approach for PS degradation UPLC-QDa based root-cause analytics, which utilizes previously established analytics for (i) most relevant polysorbate 20 (PS20) esters, (ii) PS20 free fatty acids and (iii) a newly developed method for the evaluation of PS20 specific oxidation markers. Thereby, this triad of analytical methods uses the same sample preparation and detector, which reduces the overall necessary effort, time investment and sample volume. Furthermore, the innovative PS20 oxidation marker method allows to quantify specific concentrations of the determined markers by external calibration and possible perception of oxidative degradation processes prior to relevant losses of PS20 esters, which could serve as an early indication during formulation development. The applicability of this method set was verified using several PS20 containing stress samples, which cover the most relevant root-causes, including acidic and alkaline hydrolysis, enzyme mediated hydrolysis, oxidative AAPH stress and Fe/HO mediated degradation as well as autoxidation via long-term storage at elevated temperatures. Overall, this analytical setup has shown to deliver in-depth data about PS20 degradation, which can be used to narrow down the causative stress without the necessity of fundamentally different methods. Therefore, it can be seen as all-in-one solution during sometimes troublesome development of biopharmaceutical formulations, that supports the elucidation of the PS degradation mechanism(s) and thus establish mitigation strategies.
Topics: Polysorbates; Fatty Acids, Nonesterified; Chromatography, High Pressure Liquid; Hydrogen Peroxide; Surface-Active Agents; Biological Products
PubMed: 38128165
DOI: 10.1016/j.jchromb.2023.123955 -
Journal of Bacteriology Oct 2023To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and...
To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is the antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acid side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenic (UPEC), the primary causative agent of urinary tract infections, have developed sophisticated defense systems to protect themselves from HOCl. We recently identified the RcrR regulon as a novel HOCl defense strategy in UPEC. Expression of the operon is controlled by the HOCl-sensing transcriptional repressor RcrR, which is oxidatively inactivated by HOCl resulting in the expression of its target genes, including . The gene encodes a hypothetical membrane protein, deletion of which substantially increases UPEC's susceptibility to HOCl. However, the mechanism behind protection by RcrB is unclear. In this study, we investigated whether (i) its mode of action requires additional help, (ii) expression is induced by physiologically relevant oxidants other than HOCl, and (iii) expression of this defense system is limited to specific media and/or cultivation conditions. We provide evidence that RcrB expression is sufficient to protect from HOCl. Furthermore, RcrB expression is induced by and protects from several RCS but not from ROS. RcrB plays a protective role for RCS-stressed planktonic cells under various growth and cultivation conditions but appears to be irrelevant for UPEC's biofilm formation. IMPORTANCE Bacterial infections pose an increasing threat to human health, exacerbating the demand for alternative treatments. Uropathogenic (UPEC), the most common etiological agent of urinary tract infections (UTIs), are confronted by neutrophilic attacks in the bladder, and must therefore be equipped with powerful defense systems to fend off the toxic effects of reactive chlorine species. How UPEC deal with the negative consequences of the oxidative burst in the neutrophil phagosome remains unclear. Our study sheds light on the requirements for the expression and protective effects of RcrB, which we recently identified as UPEC's most potent defense system toward hypochlorous acid (HOCl) stress and phagocytosis. Thus, this novel HOCl stress defense system could potentially serve as an attractive drug target to increase the body's own capacity to fight UTIs.
Topics: Humans; Hypochlorous Acid; Uropathogenic Escherichia coli; Chlorine; Urinary Tract Infections; Oxidants; Escherichia coli Proteins; Escherichia coli Infections
PubMed: 37791752
DOI: 10.1128/jb.00064-23 -
PLoS Genetics Feb 2024Misfolded proteins are usually refolded to their functional conformations or degraded by quality control mechanisms. When misfolded proteins evade quality control, they...
Misfolded proteins are usually refolded to their functional conformations or degraded by quality control mechanisms. When misfolded proteins evade quality control, they can be sequestered to specific sites within cells to prevent the potential dysfunction and toxicity that arises from protein aggregation. Btn2 and Hsp42 are compartment-specific sequestrases that play key roles in the assembly of these deposition sites. Their exact intracellular functions and substrates are not well defined, particularly since heat stress sensitivity is not observed in deletion mutants. We show here that Btn2 and Hsp42 are required for tolerance to oxidative stress conditions induced by exposure to hydrogen peroxide. Btn2 and Hsp42 act to sequester oxidized proteins into defined PQC sites following ROS exposure and their absence leads to an accumulation of protein aggregates. The toxicity of protein aggregate accumulation causes oxidant sensitivity in btn2 hsp42 sequestrase mutants since overexpression of the Hsp104 disaggregase rescues oxidant tolerance. We have identified the Sup35 translation termination factor as an in vivo sequestrase substrate and show that Btn2 and Hsp42 act to suppress oxidant-induced formation of the yeast [PSI+] prion, which is the amyloid form of Sup35. [PSI+] prion formation in sequestrase mutants does not require IPOD (insoluble protein deposit) localization which is the site where amyloids are thought to undergo fragmentation and seeding to propagate their heritable prion form. Instead, both amorphous and amyloid Sup35 aggregates are increased in btn2 hsp42 mutants consistent with the idea that prion formation occurs at multiple intracellular sites during oxidative stress conditions in the absence of sequestrase activity. Taken together, our data identify protein sequestration as a key antioxidant defence mechanism that functions to mitigate the damaging consequences of protein oxidation-induced aggregation.
Topics: Protein Aggregates; Prions; Saccharomyces cerevisiae Proteins; Molecular Chaperones; Saccharomyces cerevisiae; Oxidative Stress; Amyloid; Oxidants; Peptide Termination Factors
PubMed: 38422160
DOI: 10.1371/journal.pgen.1011194 -
Ecotoxicology and Environmental Safety Sep 2023Copper oxide nanoparticles (CuO NPs) were regarded as the versatile materials in daily life and the in-depth evaluation of their biological effects is of great concern....
Copper oxide nanoparticles (CuO NPs) were regarded as the versatile materials in daily life and the in-depth evaluation of their biological effects is of great concern. Herein the female and male zebrafishes were chosen as the model animals to analyze the reproductive toxicity caused by CuO NPs at low concentration (10, 50 and 100 μg/L) After 20-days exposure, the structure of zebrafish ovary and testis were impaired. Moreover, the contents of 17β-estradiol (E2) in both females and males were increased, while the contents of testosterone (T) were decreased, indicating the imbalanced sex hormones caused by CuO NPs. The expression of genes along the hypothalamic pituitary-gonad (HPG) axis, were examined with quantitative real-time PCR to further evaluate the toxic mechanisms. Meanwhile, the levels of erα/er2β and cyp19a in female zebrafishes and erα/er2β, lhr, hmgra/hmgrb, 3βhsd and 17βhsd in male zebrafishes were obviously up-regulated. While, the level of αr was obviously down-regulated in female and male zebrafishes. Thus, the obtained data uncovered that long-term exposure of CuO NPs with low dose could trigger the endocrine disorder, resulting in the disturbance of E2 and T level, inhibition of gonad development, and alteration of HPG axis genes. In brief, this study enriched the toxicological data of NPs on aquatic vertebrates and provided the theoretical support for assessing the environmental safety of NPs.
Topics: Animals; Male; Female; Zebrafish; Gonads; Copper; Estrogen Receptor alpha; Oxides; Water Pollutants, Chemical
PubMed: 37467561
DOI: 10.1016/j.ecoenv.2023.115252 -
Journal of Biological Inorganic... Oct 2023Superoxide dismutases (SODs) are enzymes that catalyze the dismutation of the superoxide radical anion into O and HO in a two-step reaction. They are ubiquitous to all...
Superoxide dismutases (SODs) are enzymes that catalyze the dismutation of the superoxide radical anion into O and HO in a two-step reaction. They are ubiquitous to all forms of life and four different types of metal centers are detected, dividing this class of enzymes into Cu-/Zn-, Ni-, Mn-, and Fe-SODs. In this study, a superoxide dismutase from the thermophilic bacteria Thermobifida fusca (TfSOD) was cloned and expressed before the recombinant enzyme was characterized. The enzyme was found to be active for superoxide dismutation measured by inhibition of cytochrome c oxidation and the inhibition of the autoxidation of pyrogallol. Its pH-optimum was determined to be 7.5, while it has a broad temperature optimum ranging from 20 to 90 °C. Combined with the T that was found to be 78.5 ± 0.5 °C at pH 8.0, TfSOD can be defined as a thermostable enzyme. Moreover, the crystal structure of TfSOD was determined and refined to 1.25 Å resolution. With electron paramagnetic resonance spectroscopy, it was confirmed that iron is the metal co-factor of TfSOD. The cell potential (E) for the TfSOD-Fe/TfSOD-Fe redox couple was determined to be 287 mV.
Topics: Superoxide Dismutase; Superoxides; Hydrogen Peroxide; Thermobifida
PubMed: 37725277
DOI: 10.1007/s00775-023-02019-9 -
Environmental Science & Technology Dec 2023The use of household bleach cleaning products results in emissions of highly oxidative gaseous species, such as hypochlorous acid (HOCl) and chlorine (Cl). These species...
Gas-Phase and Surface-Initiated Reactions of Household Bleach and Terpene-Containing Cleaning Products Yield Chlorination and Oxidation Products Adsorbed onto Indoor Relevant Surfaces.
The use of household bleach cleaning products results in emissions of highly oxidative gaseous species, such as hypochlorous acid (HOCl) and chlorine (Cl). These species readily react with volatile organic compounds (VOCs), such as limonene, one of the most abundant compounds found in indoor enviroments. In this study, reactions of HOCl/Cl with limonene in the gas phase and on indoor relevant surfaces were investigated. Using an environmental Teflon chamber, we show that silica (SiO), a proxy for window glass, and rutile (TiO), a component of paint and self-cleaning surfaces, act as a reservoir for adsorption of gas-phase products formed between HOCl/Cl and limonene. Furthermore, high-resolution mass spectrometry (HRMS) shows that the gas-phase reaction products of HOCl/Cl and limonene readily adsorb on both SiO and TiO. Surface-mediated reactions can also occur, leading to the formation of new chlorine- and oxygen-containing products. Transmission Fourier-transform infrared (FTIR) spectroscopy of adsorption and desorption of bleach and terpene oxidation products indicates that these chlorine- and oxygen-containing products strongly adsorb on both SiO and TiO surfaces for days, providing potential sources of human exposure and sinks for additional heterogeneous reactions.
Topics: Humans; Hypochlorous Acid; Limonene; Chlorine; Halogenation; Silicon Dioxide; Terpenes; Gases; Oxygen; Air Pollution, Indoor
PubMed: 38010858
DOI: 10.1021/acs.est.3c06656