Croton argyrophyllus Kunth essential oil-loaded solid lipid nanoparticles: evaluation of release profile, antioxidant activity and cytotoxicity in a neuroblastoma cell line

The essential oil from Croton argyrophyllus Kunth is known for its antiproliferative, anti-inflammatory, antinociceptive, and anticancer activities, and is recognized as a source of phytochemicals for potential use in pharmaceutic and food sectors. Solid lipid nanoparticles (SLN) have been produced to load Croton argyrophyllus (CA) Kunth essential oil (CAEO) and its antioxidant properties evaluated in vitro as a new approach for the treatment of neurodegenerative diseases. Cetyl palmitate SLN loading CAEO (CAEO-SLN) with a mean particle size of 201.4 ± 2.3 nm (polydispersity index 0.211) have been produced by hot high-pressure homogenisation. The release of the oil followed the Korsmeyers-Peppas model. The risk of lipid peroxidation has been determined by applying the production of thiobarbituric acid-reactive substances (TBARS) standard assay. The antioxidant activity was determined by the capacity of the antioxidants existing in CAEO to scavenge the stable radical DPPH•. The cytotoxicity of CA Kunth essential oil-loaded SLN (CAEO-SLN) was evaluated in a human cell line SH-SY5Y (derived from human neuroblastoma) by determining the reduction of the yellow dye 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). Both free essential oil (fEO) and loaded essential oil (CAEO-SLN) were demonstrated to inhibit the Fenton reaction. CAEO-SLN showed DPPH• radical scavenging capacity. The loading of the oil into cetyl palmitate SLN reduced the risk of cytotoxicity.This research was supported by the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES),Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC) CHAMADA MS/CNPq/FAPITEC/SE/SESN◦06/2018—PROGRAMA DE PESQUISA PARA O SUS: GESTÃO COMPARTILHADA EM SAÚDE—PPSUSSERGIPE 2017/2018, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). This research was also supported through the projects M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund),receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education(FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nelpaziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Schizophrenia and work: aspects related to job acquisition in a follow-up study

Objective: Work is considered one of the main forms of social organizationhowever, few individuals with schizophrenia find work opportunities. The purpose of this study was to evaluate the relationship between schizophrenia symptoms and job acquisition. Method: Fifty-three individuals diagnosed with schizophrenia from an outpatient treatment facility were included in an 18-month follow-up study. After enrollment, they participated in a prevocational training group. At the end of training (baseline) and 18 months later, sociodemographic, clinical data and occupational history were collected. Positive and negative symptoms (Positive and Negative Syndrome Scale - PANSS), depression (Calgary Depression Scale), disease severity (Clinical Global Impression - CGI), functionality (Global Assessment of Functioning - GAF), personal and social performance (Personal and Social Performance - PSP) and cognitive functions (Measurement and Treatment Research to Improve Cognition in Schizophrenia - MATRICS battery) were applied at baseline and at the end of the study. Results: Those with some previous work experience (n = 19) presented lower scores on the PANSS, Calgary, GAF, CGI and PSP scales (p < 0.05) than those who did not work. Among those who worked, there was a slight worsening in positive symptoms (positive PANSS). Conclusions: Individuals with less severe symptoms were more able to find employment. Positive symptom changes do not seem to affect participation at workhowever, this calls for discussion about the importance of employment support.Programa de Esquizofrenia (PROESQ)Centro de Atencao Integrada a Saude Mental (CAISM)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/50740-5]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)FAPESPConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CAPESUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Carlos UFSCar, Dept Med, Sao Carlos, SP, BrazilUniv Fed Sao Carlos, Dept Terapia Ocupac, Sao Carlos, SP, BrazilFac Ciencias Med Santa Casa Sao Paulo, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilFAPESP [2011/50740-5]Web of Scienc

Perillaldehyde 1,2-epoxide loaded SLN-tailored mAb: production, physicochemical characterization and in vitro cytotoxicity profile in MCF-7 cell lines

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 ± 4.78 nm and polydispersity index (PI) of 0.303 ± 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer–Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of cPa-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (cPa-SLN-SAb), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), cPa-SLN and cPa-SLN-SAb onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto cPa-SLN-SAb improved the cell viability in comparison to the cationic cPa-SLN.The authors wish to acknowledge the financial support from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and from FAPITEC/SE (Fundação de Apoio à Pesquisa e Inovação Tecnológica do Estado de Sergipe). E.B. Souto acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

In vitro characterization, modelling, and antioxidant properties of Polyphenon-60 from green tea in Eudragit S100-2 chitosan microspheres

Eudragit S100-coated chitosan microspheres (S100Ch) are proposed as a new oral delivery system for green tea polyphenon-60 (PP60). PP60 is a mixture of polyphenolic compounds, known for its active role in decreasing oxidative stress and metabolic risk factors involved in diabetes and in other chronic diseases. Chitosan-PP60 microspheres prepared by an emulsion cross-linking method were coated with Eudragit S100 to ensure the release of PP60 in the terminal ileum. Different corecoat ratios of Eudragit and chitosan were tested. Optimized chitosan microspheres were obtained with a chitosan:PP60 ratio of 8:1 (Ch-PP608:1), rotation speed of 1500 rpm, and surfactant concentration of 1.0% (m/v) achieving a mean size of 7.16 µm. Their coating with the enteric polymer (S100Ch-PP60) increased the mean size significantly (51.4 µm). The in vitro modified-release of PP60 from S100Ch-PP60 was confirmed in simulated gastrointestinal conditions. Mathematical fitting models were used to characterize the release mechanism showing that both Ch-PP608:1 and S100Ch-PP60 fitted the KorsmeyersPeppas model. The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 µg/mL and 154.4 µg/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.This research was supported by the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC) CHAMADA MS/CNPq/FAPITEC/SE/SES N◦ 06/2018 – PROGRAMA DE PESQUISA PARA O SUS: GESTÃO COMPARTILHADA EM SAÚDE – PPSUS SERGIPE 2017/2018, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). This work was also financed through the projects M-ERA-NET/0004/2015-PAIRED, UIDB/04469/2020 (strategic fund) and PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D).Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups.Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). the majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001).Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.Farmanguinhos/Fundacao Oswaldo Cruz/National Health MinistryBrazilian Diabetes SocietyFundacao do Amparo a Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estado Rio de Janeiro, Unit Diabet, BR-20551030 Rio de Janeiro, BrazilBaurus Diabet Assoc, São Paulo, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilFed Univ Hosp Porto Alegre, Porto Alegre, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilSanta Casa Misericordia, Belo Horizonte, MG, BrazilSanta Casa Misericordia São Paulo, São Paulo, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilHosp Geral de Bonsucesso, Rio de Janeiro, BrazilHosp Univ Clementino Fraga Filho IPPMG, Rio de Janeiro, BrazilUniv Hosp São Paulo, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, São Paulo, BrazilUniv São Paulo, Inst Crianca, Hosp Clin, São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilAmbulatorio Fac Estadual Med Sao Jose Rio Preto, Ribeirao Preto, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilClin Endocrinol Santa Casa Belo Horizonte, Belo Horizonte, MG, BrazilUniv Estadual Londrina, Londrina, BrazilUniv Fed Parana, Hosp Clin, Porto Alegre, RS, BrazilInst Crianca Com Diabet Rio Grande Sul, Rio Grande Do Sul, RS, BrazilGrp Hosp Conceicao, Inst Crianca Com Diabet, Porto Alegre, RS, BrazilHosp Univ Santa Catarina, Florianopolis, SC, BrazilInst Diabet Endocrinol Joinville, Joinville, BrazilHosp Reg Taguatinga, Brasilia, DF, BrazilHosp Geral Goiania, Goiania, Go, BrazilCtr Diabet & Endocrinol Estado Bahia, Goiania, Go, BrazilUniv Fed Maranhao, Sao Luis, BrazilCtr Integrado Diabet & Hipertensao Ceara, Fortaleza, Ceara, BrazilUniv Fed Sergipe, Aracaju, BrazilHosp Univ Alcides Carneiro, Campina Grande, BrazilHosp Univ Joao de Barros Barreto, Belem, Para, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, São Paulo, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilWeb of Scienc

Hypotensive effect and endothelium-dependent vascular action of leaves of Alpinia purpurata (Vieill) K. Schum

The aims of this study were to evaluate the chemical profile, vascular reactivity, and acute hypotensive effect (AHE) of the ethanolic extract of leaves of Alpinia purpurata (Vieill) K. Schum (EEAP). Its chemical profile was evaluated using HPLC-UV, ICP-OES, and colorimetric quantification of total flavonoids and polyphenols. The vascular reactivity of the extract was determined using the mesenteric bed isolated from WKY. AHE dose-response curves were obtained for both EEAP and inorganic material isolated from AP (IAP) in WKY and SHR animals. Cytotoxic and mutagenic safety levels were determined by the micronucleus test. Rutin-like flavonoids were quantified in the EEAP (1.8 ± 0.03%), and the total flavonoid and polyphenol ratios were 4.1 ± 1.8% and 5.1 ± 0.3%, respectively. We observed that the vasodilation action of EEAP was partially mediated by nitric oxide (·NO). The IAP showed the presence of calcium (137.76 ± 4.08 μg mg-1). The EEAP and IAP showed an AHE in WKY and SHR animals. EEAP did not have cytotoxic effects or cause chromosomic alterations. The AHE shown by EEAP could result from its endothelium-dependent vascular action. Rutin-like flavonoids, among other polyphenols, could contribute to these biological activities, and the calcium present in EEAP could act in a synergistic way