1,578 research outputs found

    Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

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    Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs

    Bestimmung von Antibiotika und ihr Verbleib zwischen der Wasser- und Sedimentphase

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    Antibiotika (ABs) werden in der Human- und Veterinärmedizin zur Behandlung von bakterieller Infektionen eingesetzt. Eines der drängendsten Probleme, das derzeit im Zusammenhang mit ABs diskutiert wird, sind Antibiotikaresistenzen (ARs). In den letzten Jahren ist die Verbreitung von ARs insbesondere durch die aquatische Umwelt zunehmend in den Fokus der Forschung gerückt. Unter anderem gelangen ABs durch behandeltes Abwasser in die aquatische Umwelt (Flüsse oder Seen). Ziel der Dissertation war die Untersuchung des Umweltverhaltens und des Verbleibs von 19 ABs, die den Klassen der Fluorchinolone, Makrolide, Sulfonamide und Tetracyclinen angehören. Ein Schwerpunkt lag dabei auf der Sedimentphase von Flüssen, die als Senke für anthropogene Spurenstoffe fungieren. Im ersten Teil der Dissertation wurde eine analytische Methode zur präzisen und simultanen Bestimmung von 19 ABs in der Sediment- und Wasserphase entwickelt. Zur Extraktion der ABs aus dem Sediment wurde die beschleunigte Lösungsmittelextraktion verwendet. Anschließend erfolgte eine Aufreinigung mittels Festphasenextraktion. Zur Bestimmung der ABs wurde die Flüssigkeitschromatographie gekoppelt mit der Massenspektrometrie eingesetzt. Dieses ermöglichte, auch sehr geringe Konzentrationen an ABs zu bestimmen (im ng/L-Bereich). Um das Verhalten der ABs in der aquatischen Umwelt zu untersuchen, wurde im zweiten Teil der Arbeit eine Mesokosmos-Studie durchgeführt. Dabei wurden die Bedingungen im Fluss im Labor mit Säulenversuchen (Sediment und Wasser) nachgestellt. Folgende Prozesse wurden betrachtet: Adsorption am Flusssediment, biologischer Abbau durch Mikroorganismen, Reaktion mit Wasser (Hydrolyse) und Zersetzung durch Sonnenlicht (Photoabbau). Mit dem gewählten Aufbau konnte unter kontrollierbaren Laborbedingungen, aber gleichzeitig umweltnahen Gegebenheiten, das Verhalten der ABs bestimmt werden. ABs derselben Klasse wiesen ein ähnliches Verhalten auf. Ihr Verhalten konnte auf ihre chemisch-physikalischen Eigenschaften zurück geführt werden (Kd_d-Werte für die Adsorptionsaffinität, log(KOW_{OW})-Wert für die Löslichkeit und Absorptionsmaximum für den Photoabbau). Der Verbleib der Fluorchinolone und Tetracycline (hohe Kd_d-Werte) wurde maßgeblich durch die Adsorption bestimmt (46 bis 80 %). Die Konzentration der Fluorchinolone und Tetracycline nahm in der Wasserphase schnell ab und sie persistierten nicht. Der Hauptprozess für die Sulfonamide (geringe Kd_d -Werte) war der biologische Abbau (50 bis 65 %), der jedoch sehr langsam ablief. Die Makrolide wurden von keinem der vier Prozesse abgebaut und persistierten, wie die Sulfonamide, in der Wasserphase. Im letzten Teil der Arbeit wurde am lokalen Fluss Alb in Karlsruhe die Konzentration an ABs in der Wasser- und Sedimentphase vor und nach Einleitung des Kläranlagenablaufs in den Fluss bestimmt. Durch die Anwendung der im ersten Teil entwickelten analytischen Methode wurden neun ABs von 19 möglichen im Konzentrationsbereich von 1,6 bis 396,3 ng/L im Kläranlagenablauf quantifiziert. Für das Oberflächenwasser nach Einleitung des Kläranlagenablaufs lagen die Konzentration bei 0,5 bis 134,9 ng/L . In den Sedimentproben wurden sechs der neun ABs aus der Wasserphase im unteren Mikrogramm je Kilogramm Bereich quantifiziert (0,07 bis 21,92 µg/kg bezogen auf die Trockenmasse des Sediments). Durch die Feldstudie konnte der anthropogene Eintrag von ABs und Antibiotikaresistenzgenen in die aquatische Umwelt (Wasser- und Sedimentphase) verdeutlicht werden. Die Kombination der Ergebnisse aus der Mesokosmosstudie und der Feldstudie zeigten, dass die chemisch-physikalischen Eigenschaften sowie die Struktur der ABs ihr Verhalten und Verbleib in der aquatischen Umwelt bestimmten. Mit dem log(KOW_{OW})-Wert, pKS_S-Wert, Kd_d-Wert und dem Absorptionsmaxima konnte das Verhalten der ABs begründet werden

    Biomedical and Pharmacological Applications of Marine Collagen

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    Biomimetic polymers and materials have been widely used in a variety of biomedical and pharmacological applications. Particularly, collagen-based biomaterials have been extensively applied in various biomedical fields, such as scaffolds in tissue engineering. However, there are many challenges associated with the use of mammalian collagen, including the issues of religious constrains, allergic or autoimmune reactions, and the spread of animal diseases. Over the past few decades, marine collagen (MC) has emerged as a promising biomaterial for biomedical and pharmacological applications. Marine organisms are a rich source of structurally novel and biologically active compounds, and to date, many biological components have been isolated from various marine resources. MC offers advantages over mammalian collagen due to its water solubility, low immunogenicity, safety, biocompatibility, antimicrobial activity, functionality, and low production costs. Due to its characteristics and physicobiochemical properties, it has tremendous potential for use as a scaffold biomaterial in tissue engineering and regenerative medicine, in drug delivery systems, and as a therapeutic. In this Special Issue, we encourage submissions related to the recent developments, advancements, trends, challenges, and future perspectives in this new research field. We expect to receive contributions from different areas of multidisciplinary research, including—but not restricted to—extraction, purification, characterization, fabrication, and experimentation of MC, with a particular focus on their biotechnological, biomedical and pharmacological uses

    Nanotechnology based drug delivery systems for the treatment of anterior segment eye diseases

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    Diseases affecting the anterior segment of the eye are the primary causes of vision impairment and blindness globally. Drug administration through the topical ocular route is widely accepted because of its user/patient friendliness - ease of administration and convenience. However, it remains a significant challenge to efficiently deliver drugs to the eye through this route because of various structural and physiological constraints that restrict the distribution of therapeutic molecules into the ocular tissues. The bioavailability of topically applied ocular medications such as eye drops is typically less than 5%. Developing novel delivery systems to increase the retention time on the ocular surfaces and permeation through the cornea is one of the approaches adopted to boost the bioavailability of topically administered medications. Drug delivery systems based on nanotechnology such as micelles, nanosuspensions, nanoparticles, nanoemulsions, liposomes, dendrimers, niosomes, cubosomes and nanowafers have been investigated as effective alternatives to conventional ocular delivery systems in treating diseases of the anterior segment of the eye. This review discussed different nanotechnology-based delivery systems that are currently investigated for treating and managing diseases affecting the anterior ocular tissues. We also looked at the challenges in translating these systems into clinical use and the prospects of nanocarriers as a vehicle for the delivery of phytoactive compounds to the anterior segment of the eye

    Biosynthesis of capsaicinoids by recombinant Saccharomyces cerevisiae

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    Throughout history, people have used products from different microorganisms and plants for many medicinal and nutritional applications. Chilli peppers have been used for spicing up food, but also for their pharmacological properties. They contain alkaloid molecules called capsaicinoids, which have been shown to activate and desensitise the heat receptor - Transient Receptor Potential Vanilloid type 1 (TRPV1) cation channel. The TRPV1 receptor is a target for pain relief treatments for a range of health conditions, therefore capsaicinoids are important drug candidates.Capsaicinoids can be manufactured by extraction directly from the chili pepper,which typically results in relatively small amounts and therefore requires large areas of land. Furthermore, capsaicinoids yield can be affected by environmental and genotypical factors. Another way of production can be through the use of synthetic biology and metabolic engineering strategies to introduce enzymatic reactions in a model microorganism. This way, plant-derived or novel capsaicinoids with potentially improved therapeutic properties can be produced from given precursors, simple sugars or renewable raw materials.The aim of this work was to engineer baker’s yeast Saccharomyces cerevisiae for a whole-cell biocatalytic production of capsaicinoids. The structure of thesecompounds is comprised of a vanilloid moiety and a fatty acyl chain joined by anamide bond. The last step for synthesis of these compounds in the plant is through condensation of the precursors vanillylamine (derived from vanillin) and a fatty acyl-CoA forming the amide bond. Amide forming reactions are very important in chemical synthesis and research has been directed towards finding efficient enzymes to perform them. Furthermore, yeast as a model microorganism has been modified to produce vanillin from glucose; however, reductive amination of vanillin to vanillylamine, or production of capsaicinoids in yeast has not been achieved previously.This thesis addresses how capsaicinoids can be produced, the challenges for in vivo reductive amination of vanillin to vanillylamine and the identification andcharacterisation of several heterologous N-acyltransferase (NAT) and CoA-ligase(CL) amide-forming enzymes. Vanillylamine was produced from vanillin, byoverexpressing a vanillin aminotransferase. The transamination reaction wasimproved by the co-expression of an alanine dehydrogenase, which also removed the need for amine donor supplementation. Cultivation conditions were shown to have an effect on the transamination, with anaerobic conditions and ethanol as a cosubstrate leading to decrease in by-product formation and improved reductive amination of vanillin to vanillylamine. Moreover, combinations of NAT and CL enzymes were evaluated for production of nonivamide (a model capsaicinoid) from vanillylamine and nonanoic acid. Finally, nonivamide, was successfully produced in vivo from precursors vanillin and nonanoic acid, after implementing strain engineering strategies and evaluating reaction conditions. Even though the NAT and CL enzyme cascade effectively produced nonivamide, the titres and yields of the process can be further improved, indicating that the amidation step is the current bottleneck in the production and requires further optimisation.Lastly, the potential of S. cerevisiae as a biosensor was evaluated by overexpressing the TRPV1 receptor and modulating its activation. This was done as a first step towards the goal of using yeast as a screening platform for strains producing capsaicinoids with activity on the TRPV1 receptor.Transferring the capsaicinoid enzyme cascade in a cell host is not straightforward and requires optimal expression of several heterologous enzymes, adjustments of reaction conditions and strategies in reducing inhibitory effects and by-products. However, biosynthesis in whole-cells may offer advantages due to simple cell derived generation of enzymes, intermediates and co-factors, positively affecting the cost and performing the reaction in aqueous environment as a more environmentally sustainable way of production

    RECENT ADVANCES IN MOLECULAR MEDICINE AND TRANSLATIONAL RESEARCH

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    ABSTRACT BOO

    Genomic insights for safety assessment of foodborne bacteria.

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    La sicurezza alimentare e l'accesso ad essa sono fondamentali per sostenere la vita e promuovere una buona salute. Gli alimenti non sicuri, contenenti microrganismi o sostanze chimiche nocive, sono causa di oltre 200 malattie, dalla diarrea al cancro, che colpiscono in particolare i neonati, i bambini piccoli, gli anziani e gli individui immunocompromessi. L'onere globale delle malattie di origine alimentare si ripercuote sulla salute pubblica, sulla società e sull'economia, pertanto è necessaria una buona collaborazione tra governi, produttori e consumatori per contribuire a garantire la sicurezza alimentare e sistemi alimentari più solidi. L'indagine più recente condotta dall'OMS (2015) ha evidenziato una stima di 600 milioni di individui malati e 420.000 decessi annui associati ad alimenti non sicuri. L'impatto economico è dovuto principalmente alla mancanza di alimenti sicuri nei Paesi a basso e medio reddito, con una perdita di 110 miliardi di dollari l'anno in termini di produttività e spese mediche. Le sfide principali per garantire la sicurezza alimentare rimangono legate alla nostra produzione alimentare e alla catena di approvvigionamento, dove fattori come la contaminazione ambientale, le preferenze dei consumatori, il rilevamento tempestivo e la sorveglianza dei focolai giocano un ruolo cruciale. Recentemente, le metodologie basate sul DNA per il rilevamento e l'indagine microbica hanno suscitato particolare interesse, soprattutto grazie allo sviluppo delle tecnologie di sequenziamento. Contrariamente ai metodi tradizionali dipendenti dalla coltura, le tecniche basate sul DNA, come il sequenziamento dell'intero genoma (WGS), mirano a risultati rapidi e sensibili a un prezzo relativamente basso e a tempi di elaborazione brevi. Inoltre, il WGS conferisce un elevato potere discriminatorio che consente di determinare importanti caratteristiche genomiche legate alla sicurezza alimentare, come la tassonomia, il potenziale patogeno, la virulenza e la resistenza antimicrobica e il relativo trasferimento genetico. La comprensione di queste caratteristiche è fondamentale per progettare strategie di rilevamento e mitigazione da applicare lungo l'intera catena alimentare secondo una prospettiva di "One Health", che porta ad acquisire conoscenze sul microbiota che influenza l'uomo, gli animali e l'ambiente. Lo scopo della tesi è quello di approfondire la genomica dei microbi di origine alimentare per la loro caratterizzazione e per creare o migliorare le strategie per la loro individuazione e i metodi di mitigazione. In particolare, questa tesi si concentra sulla valutazione del potenziale patogeno sulla base di analisi genomiche che includono studi di tassonomia, virulenza, resistenza agli antibiotici e mobiloma. Il secondo obiettivo è quello di trarre vantaggio dalle conoscenze genomiche per progettare dispositivi di rilevamento rapidi ed efficaci e metodi di mitigazione affidabili per affrontare i patogeni di origine alimentare. Più in dettaglio, saranno trattati i seguenti argomenti: La presenza di ceppi multiresistenti negli alimenti fermentati pronti al consumo rappresenta un rischio per la salute pubblica per la diffusione di determinanti AMR nella catena alimentare e nel microbiota intestinale dei consumatori. Le analisi genomiche hanno permesso di valutare accuratamente la sicurezza del ceppo UC7251 di E. faecium, in relazione alla sua virulenza e alla co-localizzazione dei geni di resistenza agli antibiotici e ai metalli pesanti in elementi mobili con capacità di coniugazione in diverse matrici. Questo lavoro sottolinea l'importanza di una sorveglianza della presenza di batteri AMR negli alimenti e di incitare lo sviluppo di strategie innovative per la mitigazione del rischio legato alla diffusione della resistenza antimicrobica negli alimenti. L'accuratezza dell'identificazione tassonomica guida le analisi successive e, per questo motivo, un metodo adeguato per identificare le specie è fondamentale. È stata studiata la riclassificazione delle specie di Enterococcus faecium clade B, utilizzando un approccio combinato di filogenomica, tipizzazione di sequenza multilocus, identità nucleotidica media e ibridazione digitale DNA-DNA. L'obiettivo è dimostrare come l'analisi del genoma sia più efficace e fornisca risultati più dettagliati riguardo alla definizione delle specie, rispetto all'analisi della sequenza del 16S rRNA. Ciò ha portato alla proposta di riclassificare tutto il clade B di E. faecium come E. lactis, riconoscendo che i due gruppi sono filogeneticamente separati, per cui è possibile definire una specifica procedura di valutazione della sicurezza, prima del loro utilizzo negli alimenti o come probiotici, compresa la considerazione per l'inclusione nella lista europea QPS. A partire da questa riclassificazione tassonomica, abbiamo sviluppato un metodo basato sulla PCR per la rapida individuazione e differenziazione di queste due specie e per discutere le principali differenze fenotipiche e genotipiche da una prospettiva clinica. A questo scopo, è stato utilizzato un allineamento del core-genoma basato sull'analisi del pangenoma. La differenza allelica tra alcuni geni del core ha permesso la progettazione di primer e l'identificazione della specie mediante PCR con una specificità del 100% e senza reattività crociata. Inoltre, i genomi clinici di E. lactis sono stati classificati come un rischio potenziale a causa della capacità di aumentare la traslocazione batterica. Gli agenti antimicrobici alternativi agli antibiotici sono una delle principali aree di sviluppo e miglioramento dell'attuale catena alimentare. Le nanoparticelle metalliche, come le nanoparticelle di platino (PtNPs), hanno suscitato interesse per le loro potenti attività catalitiche simili alle ossidasi e alle perossidasi che garantiscono forti effetti antimicrobici, e sono state proposte come potenziali candidati per superare gli inconvenienti degli antibiotici come la resistenza ai farmaci. L'obiettivo è studiare la modalità d'azione delle PtNPs in relazione alla capacità di formazione del biofilm, al meccanismo di contrasto delle specie reattive dell'ossigeno (ROS) e al quorum sensing utilizzando batteri di origine alimentare come Enterococcus faecium e Salmonella Typhimurium.Safe food and the access to it is key to sustaining life and promoting good health. Unsafe food containing harmful microorganisms or chemical substances causes more than 200 diseases, ranging from diarrhoea to cancers that particularly affect infants, young children, elderly and immunocompromised individuals. The global burden of foodborne disease affects public health, society, and economy, therefore good collaboration between governments, producers and consumers is needed to help ensure food safety and stronger food systems. The most recent survey conducted by WHO (2015) showed an estimated 600 million ill individuals and 420 000 yearly deaths associated to unsafe food. The economic impact is mainly due to the lack of safe food in low and middle income causing a US$ 110 billion is lost each year in productivity and medical expenses. The main challenges to assure food safety remain tied to our food production and supply chain, where factors like environmental contamination, consumer preferences, timely detection and surveillance of outbreaks play a crucial role. Recently, DNA-based methodologies for microbial detection and investigation have sparked special interest, mainly linked to the development of sequencing technologies. Contrary to the traditional culture-dependent methods, DNA-based techniques such as Whole Genome Sequencing (WGS) that targets fast and sensitive results at a relative low price and short processing time. Moreover, WGS confers high discriminatory power that allows to determine important genomic characteristics linked to food safety like taxonomy, pathogenic potential, virulence and antimicrobial resistance and the genetic transfer thereof. The understanding of these characteristics is fundamental to design detection and mitigation strategies to apply along the entire food-chain following a ‘One Health’ perspective, leading to gain knowledge about the microbiota that affect humans, animals, and environment. The aim of the thesis is to gain insight into the genomics of foodborne microbes for their characterization and to create or improve strategies for their detection and mitigation methods. Particularly, this thesis is focused on the assessment of the pathogenic potential based on genomic analyses including taxonomy, virulence, antibiotic resistance and mobilome studies. The second focus is to profit from the genomic insights to design rapid and time-effective detection devices and reliable mitigation methods to tackle foodborne pathogens. In more detail the following topics will be handled: The presence of multi-drug resistant strains in ready-to-eat fermented food represents a risk of public health for the spread of AMR determinants in the food chain and in the gut microbiota of consumers. Genomic analyses permitted to accurately assess the safety of E. faecium strain UC7251, with respect to its virulence and co-location of antibiotic and heavy metal resistance genes in mobile elements with conjugation capacity in different matrices. This work emphasizes the importance of a surveillance for the presence of AMR bacteria in food and to incite the development of innovative strategies for the mitigation of the risk related to antimicrobial resistance diffusion in food. The accuracy of taxonomic identification drives the subsequent analysis and, for this reason, a suitable method to identify species is crucial. The species re-classification of Enterococcus faecium clade B was investigated, using a combined approach of phylogenomics, multilocus sequence typing, average nucleotide identity and digital DNA–DNA hybridization. The goal is to show how the genome analysis is more effective and give more detailed results concerning the species definition, respect to the analysis of the 16S rRNA sequence. This led to the proposal to reclassify all the E. faecium clade B as E. lactis, recognizing the two groups are phylogenetically separate, where a specific safety assessment procedure can be designed, before their use in food or as probiotics, including the consideration for inclusion in the European QPS list. From this taxonomic re-classification, we developed a PCR-based method for rapid detection and differentiation of these two species and to discuss main phenotypic and genotypic differences from a clinical perspective. To this aim, core-genome alignment base on pangenome analysis was used. Allelic difference between certain core genes allowed primer design and species identification through PCR with 100% specificity and no cross-reactivity. Moreover, clinical E. lactis genomes categorised as a potential risk due to the ability of enhanced bacterial translocation. Antimicrobial agents alternative to antibiotics are one of the main areas of development and improvement in the current food chain. Metallic nanoparticles like Platinum nanoparticles (PtNPs), have awaken interest due to their potent catalytic activities similar to oxidases and peroxidases granting strong antimicrobial effects, have been proposed as potential candidates to overcome the drawbacks of antibiotics like drug resistance. The goal is to study the mode of action of PtNPs related to biofilm formation capacity, reactive oxygen species (ROS) coping mechanism and quorum sensing using foodborne bacteria like Enterococcus faecium and Salmonella Typhimurium

    Microalgae-enabled wastewater treatment : A sustainable strategy for bioremediation of pesticides

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    Pesticides have been identified as major contaminants of various waterways. Being classified as potential endocrine disrupting compounds, pesticides in aqueous system are highly hazardous to aquatic organisms and the ecosystem. The treatment of pesticide-containing wastewater can be performed through several means, but a wastewater treatment strategy which emphasizes both treatment efficiency and sustainability is a necessity of current time. In this context, bioremediation has been increasingly promoted as an alternative technique for the remediation of diverse pollutants. Particularly, bioremediation which involves the utilization of microalgae for the removal or conversion of pesticides to the harmless or less harmful compounds is becoming a trend. Exploiting microalgae as a tool for wastewater treatment presents multiple advantages over conventional treatment technologies, which include an opportunity to simultaneously treat pesticide-containing wastewater and nutrient recovery for microalgae cultivation as well as less formation of toxic sludge. This review discusses the roles of microalgae in mitigating pesticide pollution issue, while offering an opportunity for nutrient recovery from various wastewater sources. Based on the current laboratory studies, the use of microalgae bioremediation as a promising strategy for pesticide treatment has been rationalized. The establishment of more pilot scale studies is highly encouraged to further facilitate the implementation of this treatment approach for practical application

    Biomateriais para degradação catalítica e sequestro de organofosforados

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    Orientadora: Profª Drª.Elisa Souza OrthTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Exatas, Programa de Pós-Graduação em Química. Defesa : Curitiba, 03/04/2023Inclui referências: p. 122-138Resumo: A casca de arroz (CA) e a casca de camarão (CC) são resíduos contendo celulose e quitina, respectivamente, com grande potencial de aplicação, porém tendo o descarte como principal destino. Já os organofosforados são uma classe de compostos amplamente empregados como pesticidas e armas químicas e com alta estabilidade e toxicidade aguda. Esses compostos podem ser clivados por alfa-nucleófilos, como as amidoximas, a compostos menos tóxicos ou ainda sequestrados. Uma abordagem nesse sentido é a funcionalização covalente de materiais contendo polissacarídeos com grupos alfa-nucleófilos e seu uso na detoxificação de organofosforados em diferentes solventes. O objetivo desse trabalho foi obter materiais sustentáveis derivados da CA/CC funcionalizados com amidoximas para a degradação e sequestro de organofosforados em diferentes solventes. Para a síntese desses materiais, as hidroxilas da celulose da CA e da quitina da CC foram cianoetiladas pelo método NaOH/uréia/acrilonitrila. Por fim, as amostras com nitrilas foram funcionalizadas com amidoximas, gerando as amostras finais CAAMI e CCAMI, respectivamente. As amostras foram caracterizadas e as funcionalizações confirmadas por microscopia eletrônica de varredura, espectroscopia de raios-X por dispersão em energia, titulação potenciométrica, análise termogravimétrica, infravermelho por transformada de Fourier e ressonância magnética nuclear (RMN). A reatividade das amostras foi avaliada com os organofosforados 2,4-dinitrofenil fosfato (DEDNPP) e o pesticida Paraoxon e acompanhada por espectroscopia UV-Vis e RMN. O estudo do DEDNPP com a CAAMI/CCAMI foi feito nos solventes H2O, acetonitrila (ACN), dimetilsulfóxido (DMSO), acetona, etanol e n-hexano. Em H2O e nas frações H2O/ACN e H2O/DMSO, as CAAMI/CCAMI atuaram como catalisadores, com incrementos catalíticos da ordem de 10 3-10 4 vezes superiores que a reação não catalisada. A neutralização catalítica levou a produtos menos tóxicos por apenas um caminho reacional, i.e. sendo seletivo. Já em ACN e acetona as amostras se comportaram como sequestrantes com o DEDNPP, com uma capacidade de sequestro da ordem de 10-5 mol g-1 de fosforila sequestrada por grama de amostra. Ainda, o comportamento de sequestro foi reversível ao trocar o solvente da amostra sequestrada por H2O, o que permite a aplicação na separação do organofosforado e de seu grupo de saída de um meio reacional e posterior destinação final em outro. Por fim, as amostras CAAMI/CCAMI foram testadas com o pesticida real Paraoxon e foi observada uma reação envolvendo dois mecanismos diferentes: (i) o ataque majoritário ao centro de fósforo, algo desejado e esperado pra esse organofosforado; e (ii) um ataque a etila, mecanismo minoritário e incomum para este organofosforado. Em conclusão, os biomateriais atuaram com duas importantes funções: degradação e sequestro do DEDNPP e Paraoxon, sendo o comportamento da amostra modulado pela simples troca do solvente do meio reacional. Os resultados são promissores para área de segurança química ao permitir a degradação rápida de organofosforados ou sua separação mecânica de forma simples e barata do meio reacional líquido.Abstract: Rice husk (CA) and shrimp husk (CC) are residues containing cellulose and chitin, respectively, with great potential for application, but with disposal as the main destination. Regarding organophosphates, they belong to a class of compounds widely used as pesticides and chemical weapons with high stability and acute toxicity. These compounds can be cleaved by alpha-nucleophiles, such as amidoximes, to less toxic compounds or even scavenged by them. One approach in this context is the covalent functionalization of materials containing polysaccharides with alpha-nucleophilic groups and their use in the detoxification of organophosphates in different solvents. The objective of this work was to obtain sustainable materials derived from CA/CC functionalized with amidoximes for the detoxification/scavenging of organophosphates in different solvents. In order to synthesize these materials, the hydroxyls of cellulose in CA and of chitin in CC were cyanoethylated by the NaOH/urea/acrylonitrile method. Finally, the samples with nitriles were functionalized with amidoximes, generating the final samples CAAMI and CCAMI, respectively. The samples were characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, potentiometric titration, thermogravimetric analysis, Fourier transform infrared and nuclear magnetic resonance (RMN). The reactivity of the samples was evaluated with the organophosphates 2,4-dinitrophenyl phosphate (DEDNPP) and the pesticide Paraoxon and monitored by UV-Vis and NMR spectroscopy. The study of DEDNPP with CAAMI/CCAMI was carried out in the solvents H2O, acetonitrile (ACN), dimethyl sulfoxide (DMSO), acetone, ethanol and n-hexane. In H2O and in the H2O/ACN and H2O/DMSO fractions, the samples acted as catalysts, with catalytic increments in the order of 10 3-10 4-fold compared to non-catalyzed reactions. The catalytic neutralization led to less toxic products by only one reaction pathway, i.e. being selective. On the other hand, in ACN and acetone, the samples behaved as scavengers with DEDNPP, with a scavenging capacity of around 10-5 mol g-1 of phosphoryl scavenged per gram of sample. Furthermore, the scavenging behavior was reversible when changing the solvent of the scavenged sample for H2O, which allows its application in the separation of organophosphate and its leaving group from a reaction medium and subsequent final destination in another one. Finally, CAAMI and CCAMI were tested with the real pesticide Paraoxon and a reaction involving two different mechanisms was observed: (i) the major attack on the phosphorus center, a desired and expected mechanism for this organophosphate; and (ii) an attack on ethyl group, a minor and unusual mechanism for this organophosphate. In conclusion, the biomaterials acted with two important functions: degradation and sequestration of DEDNPP and Paraoxon, with the behavior of the sample being modulated by the simple change of solvent in the reaction medium. The results are promising for the area of chemical security, by allowing the rapid degradation of organophosphates or their mechanical separation in a simple and inexpensive way from the liquid reaction mediu

    Pullulan hydrogels as drug release platforms in biomedicine

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    It is increasingly urgent to develop new therapeutic systems to combat the spreading and evolution of various pathologies globally. Nonspecific therapies and/or insufficient medication biodistribution might hinder the patient's recovery. In this sense, a targeted and controlled delivery of various biomolecules allows overcoming the limitations of conventional delivery systems, taking the user one step closer to the successful treatment of a disease. Hydrogels have been highlighted for their drug delivery abilities, particularly for their tunable properties, like hydration capacity, biodegradability, release kinetics, etc., that can be adjusted to the desired needs. Additionally, they can be produced from either natural and/or synthetic polymers, with natural-origin sources providing exceptional features like biodegradation and acceptable integration in biological systems. One of those polymers is pullulan, a biodegradable, biocompatible and hemocompatible material, with multiple uses in biomedicine. Investigations into pullulan-based hydrogels have progressively increased over the last few decades. This review addresses the uses of pullulan in biomedical engineering, emphasizing its exceptional properties for drug delivery and its processing into hydrogel systems, either in its original or derivative forms.Authors acknowledge the Portuguese Foundation for Science and Technology (FCT), FEDER funds by means of Portugal 2020 Competitive Factors Operational Program (POCI) and the Portuguese Government (OE) for funding the project PEPTEX with reference PTDC/CTM-TEX/28074/2017 (POCI-01-0145-FEDER-028074) and 2C2T Strategic project UIDP/00264/2020. M.O.T. and H.P.F. also acknowledge FCT for funding PhD scholarship with reference 2021.06906.BD and auxiliary researcher contract via 2021.02720. CEEIND, respectively
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