Application of Nanoparticles in Cancer Treatment: A Concise Review

Timely diagnosis and appropriate antitumoral treatments remain of utmost importance, since cancer remains a leading cause of death worldwide. Within this context, nanotechnology offers specific benefits in terms of cancer therapy by reducing its adverse effects and guiding drugs to selectively target cancer cells. In this comprehensive review, we have summarized the most relevant novel outcomes in the range of 2010–2023, covering the design and application of nanosystems for cancer therapy. We have established the general requirements for nanoparticles to be used in drug delivery and strategies for their uptake in tumor microenvironment and vasculature, including the reticuloendothelial system uptake and surface functionalization with protein corona. After a brief review of the classes of nanovectors, we have covered different classes of nanoparticles used in cancer therapies. First, the advances in the encapsulation of drugs (such as paclitaxel and fisetin) into nanoliposomes and nanoemulsions are described, as well as their relevance in current clinical trials. Then, polymeric nanoparticles are presented, namely the ones comprising poly lactic-coglycolic acid, polyethylene glycol (and PEG dilemma) and dendrimers. The relevance of quantum dots in bioimaging is also covered, namely the systems with zinc sulfide and indium phosphide. Afterwards, we have reviewed gold nanoparticles (spheres and anisotropic) and their application in plasmon-induced photothermal therapy. The clinical relevance of iron oxide nanoparticles, such as magnetite and maghemite, has been analyzed in different fields, namely for magnetic resonance imaging, immunotherapy, hyperthermia, and drug delivery. Lastly, we have covered the recent advances in the systems using carbon nanomaterials, namely graphene oxide, carbon nanotubes, fullerenes, and carbon dots. Finally, we have compared the strategies of passive and active targeting of nanoparticles and their relevance in cancer theranostics. This review aims to be a (nano)mark on the ongoing journey towards realizing the remarkable potential of different nanoparticles in the realm of cancer therapeutics.info:eu-repo/semantics/publishedVersio

Dendrimers in tissue engineering

Dendrimers are highly branched and multivalent, and monodispersive making them perfect candidates for a myriad of controlled drug delivery applications. Dendrimers possess many other advantages, such as the possibility of modulating surface chemistry and charge, and biodegradation rate and to be processed as scaffolds that can emulate natural extracellular matrices thus opening up unique applications in tissue engineering. The combination of dendrimers and other macromolecules (proteins and carbohydrates), as well as other traditional scaffold polymers, has led to the creation of hybrid scaffolds with new physical, mechanical, and biochemical properties. However, despite the widespread use of dendrimers in biomedical applications, their use in the fabrication of tissue engineering scaffolds remains some-how narrow. The most promising applications of dendritic macromolecules in TE area such as drug delivery strategies, cell differentiation and/or tissue regeneration, 3D/Dynamic platforms and ex vivo/in vivo testing are overviewed and discussed herein.JMO for the financial support provided under the program “Investigador FCT” (IF/01285/2015). MCR acknowledges the IET Institution of Engineering and Technology for the financial support provided under the IET Harvey Research Prize 2017. IMO thanks the financial support under the Norte2020 project (“NORTE-08-5369-FSE-000044”)

Social Dominance Orientation Boosts Collective Action Among Low-Status Groups

We propose that low-status group members' support for group-based hierarchy and inequality (i.e., social dominance orientation; SDO) may represent an ideological strategy to guarantee the legitimacy of future ingroup status-enhancement. Specifically, we argue that, under unstable social structure conditions, SDO serves as an ideological justification for collective action tendencies aimed at competing for a higher status. In such context, SDO should be positively related with actions aimed to favor the ingroup (i.e., collective actions) by increasing group members' motivation to engage in direct competition with a relevant higher-status outgroup. We conducted two studies under highly competitive and unstable social structure contexts using real life groups. In Study 1 (N = 77), we induced Low vs. High Ingroup (University) Status and in Study 2 (N = 220) we used competing sports groups. Overall, results showed that, among members of low-status groups, SDO consistently increased individuals' motivation to get involved in actions favoring the ingroup, by boosting their motivation to compete with the opposing high-status outgroup. We discuss the results in light of the social dominance and collective action framework.info:eu-repo/semantics/publishedVersio

Human phenylalanine hydroxylase as the case study

Funding Information: Authors acknowledge Sofarimex, Indústria Química e Farmacêutica SA, Portugal, for all the support concerning freeze-drying studies. This work was supported by FEDER and Fundação para a Ciência e a Tecnologia, I. P. through iMED.ULisboa (Projects UIDB/04138/2020 and UIDP/04138/2020), iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and research project PTDC/EBB-BIO/101237/2008 and research grant SFRH/BD/47946/2008 (to Paulo R. Lino). This work has also received funding from the National PKU Alliance, USA. The authors would like to thank Luís Miguel Ramos and Cátia Nascimento who contributed to the exploratory research that culminated in the work herein presented. Funding Information: Authors acknowledge Sofarimex, Indústria Química e Farmacêutica SA, Portugal, for all the support concerning freeze-drying studies. This work was supported by FEDER and Fundação para a Ciência e a Tecnologia, I. P. through iMED.ULisboa (Projects UIDB/04138/2020 and UIDP/04138/2020), iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and research project PTDC/EBB-BIO/101237/2008 and research grant SFRH/BD/47946/2008 (to Paulo R. Lino). This work has also received funding from the National PKU Alliance, USA. Publisher Copyright: © 2023 The Author(s)The structural maintenance of therapeutic proteins during formulation and/or storage is a critical aspect, particularly for multi-domain and/or multimeric proteins which usually exhibit intrinsic structural dynamics leading to aggregation with concomitant loss-of-function. Protein freeze-drying is a widely used technique to preserve protein structure and function during storage. To minimize chemical/physical stresses occurring during this process, protein stabilizers are usually included, their effect being strongly dependent on the target protein. Therefore, they should be screened for on a time-consuming case-by-case basis. Herein, differential scanning fluorimetry (DSF) and isothermal denaturation fluorimetry (ITDF) were employed to screen, among different classes of freeze-drying additives, for the most effective stabilizer of the model protein human phenylalanine hydroxylase (hPAH). Correlation studies among retrieved DSF and ITDF parameters with recovered enzyme amount and activity indicated ITDF as the most appropriate screening method. Biochemical and biophysical characterization of hPAH freeze-dried with ITDF-selected stabilizers and a long-term storage study (12 months, 5 ± 3 °C) showed that the selected compounds prevented protein aggregation and preserved hPAH structural and functional properties throughout time storage. Our results provide a solid basis towards the choice of ITDF as a high-throughput screening step for the identification of protein freeze-drying protectors.publishersversionpublishe

Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability

Human phenylalanine hydroxylase (hPAH) hydroxylates l-phenylalanine (l-Phe) to l-tyrosine, a precursor for neurotransmitter biosynthesis. Phenylketonuria (PKU), caused by mutations in PAH that impair PAH function, leads to neurological impairment when untreated. Understanding the hPAH structural and regulatory properties is essential to outline PKU pathophysiological mechanisms. Each hPAH monomer comprises an N-terminal regulatory, a central catalytic and a C-terminal oligomerisation domain. To maintain physiological l-Phe levels, hPAH employs complex regulatory mechanisms. Resting PAH adopts an auto-inhibited conformation where regulatory domains block access to the active site. l-Phe-mediated allosteric activation induces a repositioning of the regulatory domains. Since a structure of activated wild-type hPAH is lacking, we addressed hPAH l-Phe-mediated conformational changes and report the first solution structure of the allosterically activated state. Our solution structures obtained by small-angle X-ray scattering support a tetramer with distorted P222 symmetry, where catalytic and oligomerisation domains form a core from which regulatory domains protrude, positioning themselves close to the active site entrance in the absence of l-Phe. Binding of l-Phe induces a large movement and dimerisation of regulatory domains, exposing the active site. Activated hPAH is more resistant to proteolytic cleavage and thermal denaturation, suggesting that the association of regulatory domains stabilises hPAH.publishe

Investigation of hypovitaminosis D in patients infected with SARS-CoV-2 and its relationship with clinical worsening: a cross-sectional observational retrospective clinical study

Numerous studies have demonstrated the profile of infection and symptoms related to COVID-19 that occur with pulmonary manifestations (such as Acute Respiratory Syndrome), digestive symptoms, anosmia, and ageusia. Many comorbidities have been associated with deaths and severe cases of the disease, such as diabetes, hypertension, obesity, and heart disease. However, many questions remain unanswered, especially the association of disease severity with hypovitaminosis D. Vitamin D deficiency is widely found in patients in Intensive Care Units, and recent studies have shown that it has been suggested that patients with severe manifestations of COVID-19 have hypovitaminosis D. Therefore, the present study aims to associate the presence of hypovitaminosis D in patients with the acute respiratory syndrome, positive for SARS-COV-2, admitted to the José Alencar Regional Hospital in Uberaba/Brazil and the evolution of the disease (days of hospitalization, hospitalization in the ICU, discharge and death) through the analysis of vitamin D (25(OH)D) hospitalized patients clinical records. The incidence of hypovitaminosis D among the patients was also assessed. The results may contribute to the understanding of the disease, as well as the need for vitamin supplementation

Multiple origins of green coloration in frogs mediated by a novel biliverdin-binding serpin

Many vertebrates have distinctive blue-green bones and other tissues due to unusually high biliverdin concentrations—a phenomenon called chlorosis. Despite its prevalence, the biochemical basis, biology, and evolution of chlorosis are poorly understood. In this study, we show that the occurrence of high biliverdin in anurans (frogs and toads) has evolved multiple times during their evolutionary history, and relies on the same mechanism—the presence of a class of serpin family proteins that bind biliverdin. Using a diverse combination of techniques, we purified these serpins from several species of nonmodel treefrogs and developed a pipeline that allowed us to assemble their complete amino acid and nucleotide sequences. The described proteins, hereafter named biliverdinbinding serpins (BBS), have absorption spectra that mimic those of phytochromes and bacteriophytochromes. Our models showed that physiological concentration of BBSs fine-tune the color of the animals, providing the physiological basis for crypsis in green foliage even under near-infrared light. Additionally, we found that these BBSs are most similar to human glycoprotein alpha-1-antitrypsin, but with a remarkable functional diversification. Our results present molecular and functional evidence of recurrent evolution of chlorosis, describe a biliverdin-binding protein in vertebrates, and introduce a function for a member of the serpin superfamily, the largest and most ubiquitous group of protease inhibitors.Fil: Taboada, Carlos Alberto. University of Duke; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidade de Sao Paulo; BrasilFil: Brunetti, Andrés Eduardo. Universidade de Sao Paulo; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Lucio Lyra, Mariana. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fitak, Robert R.. University of Duke; Estados Unidos. University of Central Florida; Estados UnidosFil: Faigon Soverna, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Ron, Santiago R.. Pontificia Universidad Católica del Ecuador; EcuadorFil: Lagorio, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Baptista Haddad, Célio Fernando. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Peporine Lopes, Norberto. Universidade de Sao Paulo; BrasilFil: Johnsen, Sönke. University of Duke; Estados UnidosFil: Faivovich, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Chemes, Lucia Beatriz. Universidad Nacional de San Martín; ArgentinaFil: Bari, Sara Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Negative MR4·0 chronic myeloid leukaemia and its possible implications for treatment-free remission

© 2019 British Society for Haematology and John Wiley & Sons Ltd.ABL1 tyrosine kinase inhibitors (TKI) have dramatically improved the outcome for chronic myeloid leukaemia (CML) patients, resulting in a life expectancy that approaches that of the general population. Nevertheless, lifelong TKI therapy may have consequences, including chronic adverse events that can substantially impact patients’ quality of life, adherence to therapy and treatment success. Recently, several clinical discontinuation trials have demonstrated that 40–60% of chronic phase CML patients (CP-CML) who have achieved a stable deep molecular response (DMR) can stop therapy without relapsing (Breccia & Foà, 2018). Laboratory recommendations for scoring DMR were previously defined as MR4·0 [either detectable disease ⩽0·01% BCR-ABLIS (MR4·0 positive) or undetectable disease in cDNA with 10 000–31 999 ABL1 transcripts or 24 000–76 999 GUSB transcripts (MR4·0 negative)], MR4·5 [either detectable disease ⩽0·0032% BCR-ABLIS (MR4·5 positive) or undetectable disease in cDNA with 32 000–99 999 ABL1 transcripts or 77 000–239 999 GUSB transcripts (MR4·5 negative)], and MR5·0 [either detectable disease ⩽0·001% BCR-ABLIS (MR5·0 positive) or undetectable disease in cDNA with ⩾100 000 ABL1 transcripts or ⩾240 000 GUSB transcripts (MR5·0 negative)] (Cross et al, 2015).info:eu-repo/semantics/publishedVersio

Curcumin encapsulation in nanostructures for cancer therapy: a 10-year overview

Journal pre-proofsCurcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.This study was funded by the Coordination for Higher Level Graduate Improvements (CAPES/Brazil, finance code 001), National Council for Scientific and Technological Development (CNPq/Brazil, PIBIC process #123483/2020-4), State of São Paulo Research Foundation (FAPESP/Brazil, processes #2017/10789-1, #2018/10799-0, #2018/06475-4, #2018/07707-6, #2019/08549-8, and #2020/03727-2). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and the project AgriFood XXI (NORTE-01-0145-FEDER-000041) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Our Figures were created with BioRenderinfo:eu-repo/semantics/publishedVersio

Fixed and volatile constituents oF genus Croton plants: C. adenoCalyx Baill -euphorBiaceae

aBstract This work describes the phytochemical analysis of Croton adenocalyx Baill (Euphorbiaceae), a plant that is representative of the species from Ceará State (Brazil). The GC-MS analysis of the essential oil, obtained by hydrodistillation of the leaves from C. adenocalyx, allowed the identification of eleven volatile constituents; the main components were identified as α-pinene (32.63%); bicyclogermacrene (13.96%); trans-caryophyllene (10.23%); germacrene D (10.14%); β-pinene (10.11%) and β-elemene (8.31%). The chromatographic purification of the ethanolic extract from the trunk bark, allowed the isolation and identification of the 6-methoxy-7-hydroxycoumarin (1) and 3´,5-dihydroxy-3,4´,7-trimethoxyflavone (2). Keywords: Euphorbiaceae, Croton adenocalyx, Essential oil, GC-MS, Flavonoid, Coumarin. resumen Este trabajo describe el análisis fitoquímico de Croton adenocalyx Baill (Euphorbiaceae), una planta representativa de las especies del Estado de Ceará-Brasil. El análisis por CG-EM del aceite esencial, obtenido por hidrodestilación de las hojas de C. adenocalyx Baill, permitió la identificación de diez constituyentes volátiles. Los componentes mayoritarios fueron identificados como α-pineno (32.63%), biciclogermacreno (13.96%), trans-cariofileno (10.23%), germacreno D (10.14%), β-pineno (10.11%) y β-elemeno (8.31%). La purificación cromatográfica del extracto etanólico de la corteza del tronco, permitió aislar e identificar la coumarina 6-metoxi-7-hidroxicumarina (1) y el 3´,5-dihidroxi-3,4´,7-trimetoxiflavona (2)