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1.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445327

RESUMO

The fight against cancer is one of the main challenges for medical research. Recently, nanotechnology has made significant progress, providing possibilities for developing innovative nanomaterials to overcome the common limitations of current therapies. In this context, silver nanoparticles (AgNPs) represent a promising nano-tool able to offer interesting applications for cancer research. Following this path, we combined the silver proprieties with Artemisia arborescens characteristics, producing novel nanoparticles called Artemisia-AgNPs. A "green" synthesis method was performed to produce Artemisia-AgNPs, using Artemisia arborescens extracts. This kind of photosynthesis is an eco-friendly, inexpensive, and fast approach. Moreover, the bioorganic molecules of plant extracts improved the biocompatibility and efficacy of Artemisia-AgNPs. The Artemisia-AgNPs were fully characterized and tested to compare their effects on various cancer cell lines, in particular HeLa and MCF-7. Artemisia-AgNPs treatment showed dose-dependent growth inhibition of cancer cells. Moreover, we evaluated their impact on the cell cycle, observing a G1 arrest mediated by Artemisia-AgNPs treatment. Using a clonogenic assay after treatment, we observed a complete lack of cell colonies, which demonstrated cell reproducibility death. To have a broader overview on gene expression impact, we performed RNA-sequencing, which demonstrated the potential of Artemisia-AgNPs as a suitable candidate tool in cancer research.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Artemisia/química , Nanopartículas Metálicas , Prata , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/genética , Artemisia/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Química Verde , Células HeLa , Humanos , Células MCF-7 , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Células PC-3 , Extratos Vegetais/química , Prata/química , Prata/uso terapêutico
2.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443602

RESUMO

The present work opens with an acknowledgement to the research activity performed by Luciana Naldini while affiliated at the Università degli Studi di Sassari (Italy), in particular towards gold complexes and clusters, as a tribute to her outstanding figure in a time and a society where being a woman in science was rather difficult, hoping her achievements could be of inspiration to young female chemists in pursuing their careers against the many hurdles they may encounter. Naldini's findings will be a key to introduce the most recent results in this field, showing how the chemistry of gold compounds has changed throughout the years, to reach levels of complexity and elegance that were once unimagined. The study of gold complexes and clusters with various phosphine ligands was Naldini's main field of research because of the potential application of these species in diverse research areas including electronics, catalysis, and medicine. As the conclusion of a vital period of study, here we report Naldini's last results on a hexanuclear cationic gold cluster, [(PPh3)6Au6(OH)2]2+, having a chair conformation, and on the assumption, supported by experimental data, that it comprises two hydroxyl groups. This contribution, within the fascinating field of inorganic chemistry, provides the intuition of how a simple electron counting may lead to predictable species of yet unknown molecular architectures and formulation, nowadays suggesting interesting opportunities to tune the electronic structures of similar and higher nuclearity species thanks to new spectroscopic and analytical approaches and software facilities. After several decades since Naldini's exceptional work, the chemistry of the gold cluster has reached a considerable degree of complexity, dealing with new, single-atom precise, materials possessing interesting physico-chemical properties, such as luminescence, chirality, or paramagnetic behavior. Here we will describe some of the most significant contributions.

3.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209468

RESUMO

Skin is the external part of the human body; thus, it is exposed to outer stimuli leading to injuries and damage, due to being the tissue mostly affected by wounds and aging that compromise its protective function. The recent extension of the average lifespan raises the interest in products capable of counteracting skin related health conditions. However, the skin barrier is not easy to permeate and could be influenced by different factors. In the last decades an innovative pharmacotherapeutic approach has been possible thanks to the advent of nanomedicine. Nanodevices can represent an appropriate formulation to enhance the passive penetration, modulate drug solubility and increase the thermodynamic activity of drugs. Here, we summarize the recent nanotechnological approaches to maintain and replace skin homeostasis, with particular attention to nanomaterials applications on wound healing, regeneration and rejuvenation of skin tissue. The different nanomaterials as nanofibers, hydrogels, nanosuspensions, and nanoparticles are described and in particular we highlight their main chemical features that are useful in drug delivery and tissue regeneration.


Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/uso terapêutico , Regeneração/efeitos dos fármacos , Rejuvenescimento , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Pele/metabolismo , Animais , Humanos
4.
Semin Cancer Biol ; 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34153434

RESUMO

Gold nanoparticles (AuNPS) represent one of the most studied classes of nanomaterials for biomedical applications, especially in the field of cancer research. In fact, due to their unique properties and high versatility, they can be exploited under all aspects connected to cancer management, from early detection to diagnosis and treatment. AuNPs have thus been tested with amazing results as biosensors, contrast agents, therapeutics. Their importance as potent theranostics is undoubted, but the translation to clinical practice has been hampered by a series of aspects, such as the unclear toxicity in humans and the lack of thorough studies on reliable animal models. Still, their potential action is so appealing and the results so impressive that an outstanding number of papers is being published every year, with the consequence that any review on this topic becomes obsolete within a few months. Here we would like to report the latest findings on AuNPs research addressing all their functions as theranostic agents.

5.
Semin Cancer Biol ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34182143

RESUMO

Although thousands of different nanoparticles (NPs) have been identified and synthesized to date, well-defined, consistent guidelines to control their exposure and evaluate their potential toxicity have yet to be fully established. As potential applications of nanotechnology in numerous fields multiply, there is an increased awareness of the issue of nanomaterials' toxicity among scientists and producers managing them. An updated inventory of customer products containing NPs estimates that they currently number over 5.000; ten years ago, they were one fifth of this. More often than not, products bear no information regarding the presence of NPs in the indicated list of ingredients or components. Consumers are therefore largely unaware of the extent to which nanomaterials have entered our lives, let alone their potential risks. Moreover, the lack of certainties with regard to the safe use of NPs is curbing their applications in the biomedical field, especially in the diagnosis and treatment of cancer, where they are performing outstandingly but are not yet being exploited as much as they could. The production of radical oxygen species is a predominant mechanism leading to metal NPs-driven carcinogenesis. The release of particularly reactive metal ions capable of crossing cell membranes has also been implicated in NPs toxicity. In this review we discuss the origin, behavior and biological toxicity of different metal NPs with the aim of rationalizing related health hazards and calling attention to toxicological concerns involved in their increasingly widespread use.

6.
Biomolecules ; 11(5)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33918997

RESUMO

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass-RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects' iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Ferro/deficiência , Obesidade/metabolismo , Anemia/etiologia , Anemia Ferropriva/etiologia , Suplementos Nutricionais , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Hepcidinas , Humanos , Ferro/metabolismo , Obesidade/fisiopatologia , Obesidade/cirurgia
7.
Molecules ; 26(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925725

RESUMO

Rhodium is one of the most used metals in catalysis both in laboratory reactions and industrial processes. Despite the extensive exploration on "classical" ligands carried out during the past decades in the field of rhodium-catalyzed reactions, such as phosphines, and other common types of ligands including N-heterocyclic carbenes, ferrocenes, cyclopentadienyl anion and pentamethylcyclopentadienyl derivatives, etc., there is still lively research activity on this topic, with considerable efforts being made toward the synthesis of new preformed rhodium catalysts that can be both efficient and selective. Although the "golden age" of homogeneous catalysis might seem over, there is still plenty of room for improvement, especially from the point of view of a more sustainable chemistry. In this review, temporally restricted to the analysis of literature during the past five years (2015-2020), the latest findings and trends in the synthesis and applications of Rh(I) complexes to catalysis will be presented. From the analysis of the most recent literature, it seems clear that rhodium-catalyzed processes still represent a stimulating challenge for the metalloorganic chemist that is far from being over.

8.
Arch Toxicol ; 95(8): 2605-2612, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33870439

RESUMO

The relatively widespread presence of environmental barium is raising a growing public awareness as it can lead to different health conditions. Its presence in humans may produce several effects, especially among those chronically exposed from low to moderate doses. Barium accumulation can mainly occur by exposure in the workplace or from drinking contaminated water. However, this element is also assumed with the diet, mainly from plant foods. The average amount of barium intake worldwide and its geographical variation is little known due to the lack of research attention. Barium was never considered as an essential nutrient for humans, although it is undoubtedly naturally abundant enough and distinctive in its chemical properties that it might well have some biochemical function, e.g., for regulatory purposes, both in animals and plants. The information on the potential health effects of barium exposure is primarily based on animal studies and reported as comprising kidney diseases, neurological, cardiovascular, mental, and metabolic disorders. The present paper considers exposure and potential health concerns on environmental barium, giving evidence to information that can be used in future epidemiological and experimental studies.

9.
Curr Med Chem ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761850

RESUMO

BACKGROUND: Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned and any concentration imbalance in form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes till death. Conversely, non-essential metals are not necessary for life and only noxious effects could arise after their exposure. Large environmental amounts of such chemicals come from both natural and anthropogenic sources, with the latter being predominant because of human activities. The dissipation of toxic metals contaminates water, air, soil, and food, causing a series of chronic and acute syndromes. OBJECTIVE: This review discusses the toxicity of non-essential metals considering their peculiar chemical characteristics such as different forms, hard-soft character, oxidation states, binding capabilities and solubility, which can influence their speciation in biological systems, and subsequently, the main cellular targets. Particular focus is given to selected toxic metals, major non-essential metals or semimetals related to toxicity such as mercury, lead, cadmium, chromium, nickel and arsenic. In addition, we provide indications on the possible treatments/interventions on metal poisoning based on chelation therapy. CONCLUSION: Toxic metal ions can exert their peculiar harmful effects in several ways. They strongly coordinate to important biological molecules on the basis of their chemical-physical characteristics (manly HSAB properties) or replace essential metal ions from their natural locations in proteins, enzymes or in hard structures such as bones or teeth. Metals with redox properties could be key inducers of reactive oxygen species, leading to oxidative stress and cellular damage. Therapeutic detoxification, through complexation of toxic metal ions by specific chelating agents, appears an efficacious clinical strategy mainly in acute cases of metal intoxication.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33370684

RESUMO

BACKGROUND: Many scientific contributions recognize polyamines as important biomarkers for the diagnosis and treatment of cancer. Several authors have suggested the use of LC/MS instruments as an elective method for their measurement, providing good detection limits and specificity; however, many of these procedures suffer from long chromatographic run times, high detection limits and lengthy and expensive sample pre-treatment steps. METHODS: UHPLC coupled with high-resolution Orbitrap mass spectrometry (UHPLC/Orbitrap) was set up for the identification and separation ofpolyamines, together with some of their metabolites and catabolites, in the plasma of healthy and prostate cancer human patients. Thirteen metabolites were measured in deproteinized plasma samples through a new analytical approach known as the parallel reaction monitoring (PRM) for targeted quantitative analysis. RESULTS: The calibration curves were linear and R2 ranged from 0.9913 to 0.9995 for all analytes. LOQ values are between 0.382 and 25 ng mL-1 and LOD values are between 0.109 and 7.421 ng mL-1. The method shows an accuracy and precision for intra-day and inter-day < 15% RSD and R.E.% for all the QC samples. The matrix effect calculated at different concentration levels did not exceed 15%. CONCLUSIONS: The method developed provides rapid, easy and robust identification and measurement of a wide range of polyamines, and some of their metabolites that can be evaluated as biomarkers to predict the clinical features of prostate cancer patients, avoiding invasive diagnostic procedures.


Assuntos
Poliaminas/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/sangue , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
11.
PLoS One ; 15(9): e0238532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870934

RESUMO

Malaria represents one of the most common infectious diseases which becoming an impellent public health problem worldwide. Antimalarial classical medications include quinine-based drugs, like chloroquine, and artesunate, a derivative of artemisinin, a molecule found in the plant Artemisia annua. Such therapeutics are very effective but show heavy side effects like drug resistance. In this study, "green" silver nanoparticles (AgNPs) have been prepared from two Artemisia species (A. abrotanum and A. arborescens), traditionally used in folk medicine as a remedy for different conditions, and their potential antimalarial efficacy have been assessed. AgNPs have been characterized by UV-Vis, dynamic light scattering and zeta potential, FTIR, XRD, TEM and EDX. The structural characterization has demonstrated the spheroidal shape of nanoparticles and dimensions under 50 nm, useful for biomedical studies. Zeta potential analysis have shown the stability and dispersion of green AgNPs in aqueous medium without aggregation. AgNPs hemocompatibility and antimalarial activity have been studied in Plasmodium falciparum cultures in in vitro experiments. The antiplasmodial effect has been assessed using increasing doses of AgNPs (0.6 to 7.5 µg/mL) on parasitized red blood cells (pRBCs). Obtained data showed that the hemocompatibility of AgNPs is related to their synthetic route and depends on the administered dose. A. abrotanum-AgNPs (1) have shown the lowest percentage of hemolytic activity on pRBCs, underlining their hemocompatibility. These results are in accordance with the lower levels of parasitemia observed after A. abrotanum-AgNPs (1) treatment respect to A. arborescens-AgNPs (2), and AgNPs (3) derived from a classical chemical synthesis. Moreover, after 24 and 48 hours of A. abrotanum-AgNPs (1) treatment, the parasite growth was locked in the ring stage, evidencing the effect of these nanoparticles to hinder the maturation of P. falciparum. The anti-malarial activity of A. abrotanum-AgNPs (1) on pRBCs was demonstrated to be higher than that of A. arborescens-AgNPs (2).


Assuntos
Antimaláricos/farmacologia , Artemisia , Nanopartículas Metálicas , Plasmodium falciparum/efeitos dos fármacos , Prata/farmacologia , Antimaláricos/química , Artemisia/química , Química Verde , Humanos , Malária Falciparum/tratamento farmacológico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Prata/química
12.
Inorg Chem ; 59(7): 4661-4684, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212645

RESUMO

A series of five rationally designed decapeptides [DEHGTAVMLK (DP1), THMVLAKGED (DP2), GTAVMLKDEH (Term-DEH), TMVLDEHAKG (Mid-DEH), and DEHGGGGDEH (Bis-DEH)] have been studied for their interactions with Cu(II) and Mn(II) ions. The peptides, constructed including the most prevalent amino acid content found in the cell-free extract of Deinococcus radiodurans (DR), play a fundamental role in the antioxidant mechanism related to its exceptional radioresistance. Mn(II) ions, in complex with these peptides, are found to be an essential ingredient for the DR protection kit. In this work, a detailed characterization of Cu(II) systems was included, because Cu(II)-peptide complexes have also shown remarkable antioxidant properties. All peptides studied contain in their sequence coordinating residues that can bind effectively Mn(II) or Cu(II) ions with high affinity, such as Asp, Glu, and His. Using potentiometric techniques, NMR, EPR, UV-vis, and CD spectroscopies, ESI-MS spectrometry, and molecular model calculations, we explored the binding properties and coordination modes of all peptides toward the two metal ions, were able to make a metal affinity comparison for each metal system, and built a structural molecular model for the most stable Cu(II) and Mn(II) complexes in agreement with experimental evidence.


Assuntos
Complexos de Coordenação/química , Cobre/química , Deinococcus/química , Manganês/química , Oligopeptídeos/química , Complexos de Coordenação/metabolismo , Cobre/metabolismo , Deinococcus/metabolismo , Manganês/metabolismo , Oligopeptídeos/metabolismo , Ligação Proteica
13.
J Inorg Biochem ; 195: 120-129, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30939379

RESUMO

The human body needs about 20 essential elements in order to function properly and among them, for certain, 10 are metal elements, though for every metal we do need, there is another one in our body we could do without it. Until about 1950 poor attention was given to the so-called "inorganic elements" and while researches on "organic elements" (C, N, O and H) and organic compounds were given high priority, studies on essential inorganic elements were left aside. Base on current knowledge it is ascertained today that metals such as Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn and Mo are essential elements for life and our body must have appropriate amounts of them. Here a brief overview to highlight their importance and current knowledge about their essentiality.


Assuntos
Metais/metabolismo , Oligoelementos/metabolismo , Animais , Humanos , Metais/toxicidade , Oligoelementos/deficiência , Oligoelementos/toxicidade , Desequilíbrio Hidroeletrolítico/metabolismo , Desequilíbrio Hidroeletrolítico/fisiopatologia
14.
J Inorg Biochem ; 193: 152-165, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30769225

RESUMO

This work presents the simple and low cost synthesis of a new tripodal ligand, in which three units of kojic acid are coupled to a tris(2-aminoethyl)amine (tren) backbone molecule. The protonation equilibria, together with the complex formation equilibria of this ligand with Fe3+, Al3+, Cu2+ and Zn2+ ions were studied. The complementary use of potentiometric, spectrophotometric and NMR techniques, and of Density Functional Theory (DFT) calculations, has allowed a thorough characterization of the different species involved in equilibrium. The stability of the formed complexes with Fe3+ and Al3+ are high enough to consider the new ligand for further studies for its clinical applications as a chelating agent. Biodistribution studies were carried out to assess the capacity the ligand for mobilization of gallium in 67Ga-citrate injected mice. These studies demonstrated that this ligand efficiently chelates the radiometal in our animal model, which suggests that it can be a promising candidate as sequestering agent of iron and other hard trivalent metal ions. Furthermore, the good zinc complexation capacity appears as a stimulating result taking into a potential use of this new ligand in analytical chemistry as well as in agricultural and environmental applications.


Assuntos
Quelantes de Ferro/farmacologia , Piranos/farmacologia , Pironas/farmacologia , Alumínio/química , Animais , Cobre/química , Teoria da Densidade Funcional , Feminino , Radioisótopos de Gálio/química , Ferro/química , Quelantes de Ferro/síntese química , Quelantes de Ferro/farmacocinética , Camundongos , Modelos Químicos , Piranos/síntese química , Piranos/farmacocinética , Pironas/síntese química , Pironas/farmacocinética , Distribuição Tecidual , Zinco/química
15.
J Med Chem ; 62(13): 5923-5943, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-30735392

RESUMO

Silver has no biological role, and it is particularly toxic to lower organisms. Although several silver formulations employed in medicine in the past century are prescribed and sold to treat certain medical conditions, most of the compounds, including those showing outstanding properties as antimicrobial or anticancer agents, are still in early stages of assessment, that is, in vitro studies, and may not make it to clinical trials. Unlike other heavy metals, there is no evidence that silver is a cumulative poison, but its levels can build up in the body tissues after prolonged exposure leading to undesired effects. In this review, we deal with the journey of silver in medicine going from the alternative or do-it-yourself drug to scientific evidence related to its uses. The many controversies push scientists to move toward a more comprehensive understanding of the mechanisms involved.


Assuntos
Prata/farmacologia , Prata/uso terapêutico , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Bactérias/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/toxicidade , Fungos/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Vírus/efeitos dos fármacos
16.
J Inorg Biochem ; 189: 103-114, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30243118

RESUMO

This paper presents an easy and low cost synthesis of chelating agents for potential medical and environmental applications, and the evaluation of the stability of their complexes with Fe3+, Al3+, Cu2+ and Zn2+. In the last years, we synthesized and characterized effective iron chelators based on two kojic acid units joined by different linkers in position 6. In this study, we preserved kojic acid (a cheap and non-toxic molecule) as the basic unit but joined the two kojic acid units through ethylene diamine, propylene diamine and butylene diamine by reacting them with the OH groups in position 2. The different anchoring position of the linker, as well as the linker length, can affect both protonation and complex formation equilibria. A thorough study of the protonation and complex formation equilibria of the three ligands toward the metal ions is presented based on combined potentiometric and spectroscopic studies, and 1H NMR. The obtained results allow remarking that the orientation of the oxygen atoms in the kojic acid units, related to the anchoring position of the linker, strongly affects the protonation constants, while the chelating ability is practically unaffected. The trivalent metal ions form stable complexes with a 2:3 metal to ligand stoichiometry through the oxygen donor atoms of the ligands, whereas divalent metal ions form binuclear complexes for which the nitrogen atoms from the linker might be involved in the coordination sphere. The stability of the complexes decreases with linker length, and the selectivity of the ligands toward metal ions grows in the order Zn2+ < Cu2+ < Al3+ < Fe3+.


Assuntos
Alumínio/química , Cobre/química , Compostos Férricos/química , Zinco/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
17.
Curr Med Chem ; 25(1): 65-74, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28464784

RESUMO

Tungsten or wolfram was regarded for many years as an enemy within the tin smelting and mining industry, because it conferred impurity or dirtiness in tin mining. However, later it was considered an amazing metal for its strength and flexibility, together with its diamond like hardness and its melting point which is the highest of any metal. It was first believed to be relatively inert and an only slightly toxic metal. Since early 2000, the risk exerted by tungsten alloys, its dusts and particulates to induce cancer and several other adverse effects in animals as well as humans has been highlighted from in vitro and in vivo experiments. Thus, it becomes necessary to take a careful look at all the most recent data reported in the scientific literature, covering the years 2001-2016. In fact, the findings indicate that much more attention should be devoted to thoroughly investigate the toxic effects of tungsten and the involved mechanisms of tungsten metal or tungsten metal ions.


Assuntos
Neoplasias/induzido quimicamente , Tungstênio/efeitos adversos , Animais , Humanos
18.
J Trace Elem Med Biol ; 44: 151-160, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28965571

RESUMO

Ni(II) stimulates innate immunity via the direct binding to human Toll Like Receptor 4 (hTLR4), the bacterial lypopolysaccharide receptor. The binding is specific for humans and causes nickel contact allergy. The protein sequence analysis of hTLR4 revealed that the ectodomain, the region supposed to coordinate the metal ions, contains a histidine-rich motif that is not conserved among all organisms. To elucidate the role of each histidine residue on the protein-nickel binding, we examined the formation of Ni(II) complexes with the model peptide NH2-FQHSNRKQMSERSVFRSRRNRIYRDISHTHTR-COO-, which encompasses the sequence 429-460 of hTLR4. The amino acid sequence of the peptide has been modified by the substitution of some selected lipophilic residues (Leu and Phe) with hydrophilic residues (Arg), aiming at increasing the peptide hydro solubility of the protein fragment. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) measurements demonstrate that the non-conserved histidines in the ectodomain cooperate in metal coordination and consequently enable the activation of the molecular mechanism of nickel hypersensitivity reaction.


Assuntos
Modelos Biológicos , Níquel/metabolismo , Peptídeos/metabolismo , Receptor 4 Toll-Like/metabolismo , Sequência de Aminoácidos , Dicroísmo Circular , Cristalografia por Raios X , Humanos , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Peptídeos/química , Prótons , Espectrofotometria Ultravioleta , Receptor 4 Toll-Like/química
19.
Int J Pharm ; 526(1-2): 254-270, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28450172

RESUMO

Malaria is one of the most common infectious diseases, which has become a great public health problem all over the world. Ineffectiveness of available antimalarial treatment is the main reason behind its menace. The failure of current treatment strategies is due to emergence of drug resistance in Plasmodium falciparum and drug toxicity in human beings. Therefore, the development of novel and effective antimalarial drugs is the need of the hour. Considering the huge biomedical applications of nanotechnology, it can be potentially used for the malarial treatment. Silver nanoparticles (AgNPs) have demonstrated significant activity against malarial parasite (P. falciparum) and vector (female Anopheles mosquito). It is believed that AgNPs will be a solution for the control of malaria. This review emphasizes the pros- and cons of existing antimalarial treatments and in depth discussion on application of AgNPs for treatment of malaria. The role of nanoparticles for site specific drug delivery and toxicological issues have also been discussed.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Nanopartículas Metálicas/química , Prata/farmacologia , Animais , Anopheles , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Plasmodium falciparum
20.
J Inorg Biochem ; 171: 18-28, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28343065

RESUMO

5-Hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one ligand, an iron chelator, was evaluated for its coordination ability toward Al(III), Cu(II) and Zn(II) ions by using potentiometric, NMR, EPR and UV-Vis techniques. The behavior of the ligand with the non-essential Al(III) ion has been examined, as well as its potential influence on the homeostatic equilibria of the essential Cu(II) and Zn(II) ions. Structural information on the complex formation equilibria have been obtained from 1D and 2D NMR study. The donor atoms involved in the coordination of Al(III), Cu(II) and Zn(II) ions are (O, O) the same as for Fe(III) at physiological pH value, even if from the complexation competition study the ligand appears to be more selective toward Fe(III) ions supporting that it can be used as an iron chelating agent. The involvement of N-donor atoms at high pH in Cu(II) coordination has been determined by using EPR and UV-Vis techniques.


Assuntos
Alumínio/química , Quelantes/química , Complexos de Coordenação/química , Cobre/química , Zinco/química , Complexos de Coordenação/farmacologia , Íons/química , Ligantes , Espectroscopia de Ressonância Magnética , Estrutura Molecular
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