7 research outputs found
Molecular docking analysis and in vivo assessment of zinc oxide nanoparticle toxicity in zebrafish larvae
No full textThe zinc oxide nanoparticles (ZnO-NPs) being widely employed in several industries and consumer products, are raising concerns about their safety on aquatic biota and human health. This study aims to investigate the possible toxicological effects of ZnO-NPs through a combined in vivo and in silico approach. Zebrafish embryos were exposed to several ZnO-NPs concentrations and morphological alterations and lipid peroxidation (MDA) were investigated. Furthermore, molecular docking simulations were applied to study the intermolecular interactions of ZnO-NPs against critical embryonic proteins namely zebrafish hatching enzyme1 (ZHE1) as well as the superoxide dismutase (SOD1). Treatment with ZnO-NPs resulted in an increase in MDA concentration and a decrease in antioxidant enzyme levels. Besides a significant decrease in mRNA expression of key enzymes of ROS detoxification genes, a modulation of inflammatory genes with a low downregulation of tnf-α, and an upregulation of il-1β were observed. Docking study suggests that the delayed hatching and increased cellular oxidative stress in zebrafish embryos may occur through a synergistic mechanism based on the ZnO-NP—dependent inhibition of ZHE1 and SOD1 enzymes. The integration of in vivo assessments with in silico computational modeling provided a more comprehensive evaluation of potential physiological risks in zebrafish embryos associated with nanomaterial exposure
LINKING NANOPARTICLES TO EMBRYONIC DEFORMITIES: EXPLORING THE TERATOGENICITY OF ZINC OXIDE NANOPARTICLES
No full textThe exponential growth of nanotechnology has led to significant advancements in engineered nanoparticles (ENPs) between 1 and 100 nm in size, with zinc oxide nanoparticles (ZnO-NPs) playing a prominent role across various industries and applications. Particularly in biomedicine, ZnO-NPs have emerged as versatile tools, serving as anti- bacterial agents, drug and gene delivery platforms for cancer treatment, cellular imaging enhancers, and high-performance biosensors. For these reasons the aim of this study is to explore their potential toxicity on zebrafish early life stage using a combined in vivo and in-silico approach. In the first phase by SEM-EDS analysis, the ZnO-NPs purity was confirmed. After the Fish Embryo Acute Toxicity Tests according to OECD test guideline No. 236 (OECD, 2013) were performed. The embryos were exposed to five con centrations of ZnO-NPs: 50, 100, 150, 200 and 250 mg/L. At 96 hours, LC20 of about 58.201 mg/L and NOED of <50 mg/L, were determined. The most common sub-lethal alterations were pericardial and yolk edema, blood stasis, reduced blood circulation, reduced heartbeat, skeletal alterations and delayed hatching. Later, to further assess the toxicity of ZnO nanoparticles, oxidative stress was evaluated by quantifying lipid peroxidation using the thiobarbituric Acid Reactive Substances assay. The results showed as the treatment with ZnO-NPs led to a significant increase in lipid peroxidation in zebrafish larvae, as evidenced by the elevated levels of MDA induced by the treatment, indicating a low detoxification capacity of reactive oxygen species. To further confirm these findings, the gene expression of key antioxidant enzymes such as catalase (cat), superoxide dismutase (sod), and glutathione S-transferase (gstm) was also evaluated via RT-PCR. The results demonstrated a decrease in the expression of all the enzymes, suggesting that nanoparticles may interfere with the redox state of zebrafish larvae. Furthermore, since the oxidative stress is often associated with inflammation also key genes related to inflammation tnfalpha and il1beta were assayed. Our results showed a modulation of inflammation’s genes, particularly treatment induced a low downregulation of tnfalpha and an opposite regulation of il1beta which expression increased at very high levels. Finally, molecular docking and dynamics approach were applied to further explore any potential molecular interactions between ZnO- NPs and critical embryonic proteins, such as hatching enzyme ZHE1, and superoxide dismutase, SOD 1, enzyme. Results shown that ZnO-NPs interfered with both enzymes inhibiting those activities, and causing a delayed hatching of zebrafish embryos most probably through a multi-modal mechanism. The integration of in silico and in vivo assessments provides a more comprehensive evaluation of the potential risks associated with exposure to nano- materials, contributing to the fields of nanotoxicology and developmental biology. However, we are discussing preliminary results that require further testing and examination to fully understand the molecular mechanisms and causes of ZnO-NP toxicity
Molecular docking analysis and in vivo assessment of zinc oxide nanoparticle toxicity in zebrafish larvae
No full text: The zinc oxide nanoparticles (ZnO-NPs) being widely employed in several industries and consumer products, are raising concerns about their safety on aquatic biota and human health. This study aims to investigate the possible toxicological effects of ZnO-NPs through a combined in vivo and in silico approach. Zebrafish embryos were exposed to several ZnO-NPs concentrations and morphological alterations and lipid peroxidation (MDA) were investigated. Furthermore, molecular docking simulations were applied to study the intermolecular interactions of ZnO-NPs against critical embryonic proteins namely zebrafish hatching enzyme1 (ZHE1) as well as the superoxide dismutase (SOD1). Treatment with ZnO-NPs resulted in an increase in MDA concentration and a decrease in antioxidant enzyme levels. Besides a significant decrease in mRNA expression of key enzymes of ROS detoxification genes, a modulation of inflammatory genes with a low downregulation of tnf-α, and an upregulation of il-1β were observed. Docking study suggests that the delayed hatching and increased cellular oxidative stress in zebrafish embryos may occur through a synergistic mechanism based on the ZnO-NP-dependent inhibition of ZHE1 and SOD1 enzymes. The integration of in vivo assessments with in silico computational modeling provided a more comprehensive evaluation of potential physiological risks in zebrafish embryos associated with nanomaterial exposure
Separating Thermodynamics from Kinetics: A New Understanding of the Transketolase Reaction
No full textTransketolase catalyzes asymmetric C−C bond formation of two highly polar compounds. Over the last 30 years, the reaction has unanimously been described in literature as irreversible because of the concomitant release of CO2 if using lithium hydroxypyruvate (LiHPA) as a substrate. Following the reaction over a longer period of time however, we have now found it to be initially kinetically controlled. Contrary to previous suggestions, for the non-natural conversion of synthetically more interesting apolar substrates, the complete change of active-site polarity is therefore not necessary. From docking studies it was revealed that water and hydrogen-bond networks are essential for substrate binding, thus allowing aliphatic aldehydes to be converted in the charged active site of transketolase
Substrate and cofactor binding to nitrile reductase: A mass spectrometry based study
No full textNitrile reductases catalyse a two-step reduction of nitriles to amines. This requires the binding of two NADPH molecules during one catalytic cycle. For the nitrile reductase from E. coli (EcoNR) mass spectrometry studies of the catalytic mechanism were performed. EcoNR is dimeric and has no Rossman fold. It was demonstrated that during catalysis each active site binds one substrate molecule. NADPH binds independent of the substrate. The PreQ0 binding pocket of the active site is not involved in the binding of NADPH; this is in conflict with an earlier hypothesis.<br/
Rhodococcus strains as source for ene-reductase activity
No full textRhodococcus strains are ubiquitous in nature and known to metabolise a wide variety of compounds. At the same time, asymmetric reduction of C=C bonds is important in the production of high-valued chiral building blocks. In order to evaluate if Rhodococci can be used for this task, we have probed several Rhodococcus rhodochrous and R. erythropolis strains for ene-reductase activity. A series of substrates including activated ketones, an aldehyde, an imide and nitro-compound were screened using whole cells of seven Rhodococcus strains. This revealed that whole cells of all Rhodococcus strains showed apparent (S)-selectivity towards ketoisophorone, while most other organisms show (R)-selectivity for this compound. Three putative ene-reductases from R. rhodochrous ATCC 17895 were heterologously expressed in Escherichia coli. One protein was purified and its biocatalytic and biochemical properties were characterised, showing typical (enantioselective) properties for class 3 ene-reductases of the old yellow enzyme family.BT/Biocatalysi
Vëzhgime nga festivali mbarëkombëtar shqiptar i folklorit Rapsha 2017, Tuz, Mali i Zi (18-20 gusht)
No full textOn August 18-20, 2017, the Albanian Folk Festival was held in Rapsha of Tuzi. The author was invited to the post of a jury member. The festival was attended by 22 Albanian folk groups, associations or troops representing seven countries: Albania, Kosovo, Macedonia, Montenegro, Italy, Serbia and the USA. According to the Festival Director, each troop had to perform for 15 minutes live rather than by play-back (CD playing). The program had to be as sourceful, echoing mainly local authenticity. Even the folk costumes were the most original. This Festival marked its 5th edition. As by the program, the seven participating troops performing the first evening gathered in Tuz for the Troops Kick-off Parade. In the first evening (August 18, 2017), the competing performers were SHKA “Rapsha”, Drume-Hot and the “Shota” National Ensemble, Prishtina – Kosovo. The following troops followed suit: “Krahu i Shqiponjës Taip Medani”, Vlora –Albania; SHKA “Sali Mani” Malësia e Madhe, Albania; “Burimet e Sharrit”, Tetovo – Macedonia; SHKA “Maja e karafilit”, Plavë-Guci, Montenegro; SHKA “Gryka e Kaçanikut”, Kaçanik – Kosovo. In the second evening, the competing troops were SHKA “Dedë Gjon Luli”, Traboin – Hot, Montenegro; “Shkëmbi” dhe “Shkëndija” from the Arbëresh provinces of Akuaformoza and San Benedeto Ullanova, Italy; the polyphonic troop “Lunxhëria”, Lunxhëri –Albania; the ethnocultural ensemble “Katerina Josipi”, Zym – Prizren, Kosovo; the cultural association “Skampa”, Elbasan –Albania; “Gurra e Kurbinit”, Laç – Albania; SHKA “Zëri i Luginës”, Bujanoc, Lugina e Preshevës – Serbia. In the second evening, the competing troops were: SHKA “Besa”, Triesh, Malësi e Madhe – Montenegro; “Gjergj Kastrioti – Skënderbeu”, Detroit – Michigan, USA; folk troop “Mati”, Mat – Albania; SHKA “Malësori”, Gjonaj – Prizren, Kosovo; the polyphonic troop “Bilbilat e Kolonjës”, Gjirokastra – Albania; SHKA “Jahi Hasani”, Çegran – Gostivar, Macedonia; the native troop “Rugova”, Rugovë – Peja, Kosovo; the folk troop “Bashkimi kombëtar”, New York– USA. In conclusion, the jury awarded the prizes to the three best troops. The author defined this event as a nationwide festival with a huge background. Based on its organization, this festival can be considered an international one similar to the ones I have attended for decades, in: Germany, Turkey, Italy, Romania, Hungary, Greece, Macedonia, Montenegro, France, Spain and recently in Slovenia.Më 18 – 20 gusht 2017 u zhvillua në Rapsha të Tuzit, Festivali Mbarëkombëtar Shqiptar i Folklorit. Autori ishte i ftuar me detyrën e antarit të jurisë. Në festival morën pjesë 22 grupe, shoqata apo ansamble folklorike fhqiptare, që përfaqësonin shtatë shtete: Shqipëria, Kosova, Maqedonia, Mali i Zi, Italia, Serbia, SHBA.Sipas rregullatorit të Drejtorisë së Festivalit, çdo ansambël do të konkurronte në 15 minuta dhe programi duhej të ishte me shoqërime muzikore të drejtpërdrejta dhe jo me incizime (CD). Përmbajtja e programit duhet të ishte sa më burimore, duke i bërë jehonë kryesisht autenticitetit vendës. Edhe kostumet popullore qenë më origjinale. Ky Festival shënoi edicionin e 5-të të mbajtjes së tij. Sipas programit, të shtatë ansamblet pjesëmarrëse të mbrëmjes së parë, u mblodhën në Tuz për të zhvilluar defilenë e ansambleve (apo “Paradën e nisjes”). Në mbrëmjen e parë (18 gusht 2017) dhanë koncerte SHKA “Rapsha”, Drume-Hot dhe Ansambli kombëtar “Shota”, Prishtinë – Kosovë. Në vijim konkuruan ansamblet: “Krahu i Shqiponjës Taip Medani”, Vlorë –Shqipëri; SHKA “Sali Mani” Malësia e Madhe, Shqipëri; “Burimet e Sharrit”, Tetovë – Maqedoni; SHKA “Maja e karafilit”, Plavë-Guci, Mali i Zi; SHKA “Gryka e Kaçanikut”, Kaçanik - Kosovë. Në mbrëmjen e dytë konkuruan ansamblet: SHKA “Dedë Gjon Luli”, Traboin - Hot, Mali i Zi; “Shkëmbi” dhe “Shkëndija” të katundeve arbëreshe Akuaformoza dhe San Benedeto Ullanova, Itali; Grupi polifonik “Lunxhëria”, Lunxhëri –Shqipëri; Ansambli etnokulturor “Katerina Josipi”, Zym - Prizren, Kosovë; Shoqata Kklturore “Skampa”, Elbasan –Shqipëri; “Gurra e Kurbinit”, Laç – Shqipëri; SHKA “Zëri i Luginës”, Bujanoc, Lugina e Preshevës – Serbi.Në përfundim, juria ndau çmimet për tre trupat më të mirë. Autori e përkufizoi këtë ngjarje si një festival mbarëkombëtar me një sfond të madh. Në bazë të organizimit të tij, ky mund të konsiderohet si festival ndërkombëtar i ngjashëm me ata që kam ndjekur prej dekadash, në: Gjermani, Turqi, Itali, Rumani, Hungari, Greqi, Maqedoni, Mal të Zi, Francë, Spanjë dhe së fundmi në Slloveni
