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1.
Polymers (Basel) ; 16(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000760

RESUMO

Most polymeric food packaging materials are non-biodegradable and derived from petroleum, thus recent studies have focused on evaluating alternative biodegradable materials from renewable sources, with polysaccharides and proteins as the main types of employed biopolymers. Therefore, this study aimed to develop biopolymeric films based on sunflower proteins and galactomannans from locust bean gum. The influence of the galactomannan amount (0.10%, 0.30%, 0.50%, and 0.75% w/v) on the physicochemical, thermal, and mechanical properties of cast sunflower protein-based films was studied. Sunflower proteins gave rise to yellowish, shining, and translucid films. With the incorporation of locust bean gum-derived galactomannans, the films became more brown and opaque, although they still maintained some translucency. Galactomannans significantly changed the proteins' secondary structures, giving rise to films with increased tensile resistance and stretchability. Nevertheless, the increase in the galactomannan amount did not have a significant effect on the film's thermal stability. The protein/galactomannan-based films showed values of water vapor and oxygen permeability that were slightly higher than those of the pristine materials. Overall, blending locust bean gum galactomannans with sunflower proteins was revealed to be a promising strategy to develop naturally colored and translucid films with enhanced mechanical resistance while maintaining flexibility, fitting the desired properties for biodegradable food packaging materials.

2.
Chem Biodivers ; : e202400668, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763894

RESUMO

The cytochrome P450 is a superfamily of hemoproteins mainly present in the liver and are versatile biocatalysts. They participate in the primary metabolism and biosynthesis of various secondary metabolites. Chemical catalysts are utilized to replicate the activities of enzymes. Metalloporphyrins and Salen complexes can contribute to the products' characterization and elucidate biotransformation processes, which are investigated during pre-clinical trials. These catalysts also help discover biologically active compounds and get better yields of products of industrial interest. This review aims to investigate which natural product classes are being investigated by biomimetic chemical models and the functionalities applied in the use of these catalysts. A limited number of studies were observed, with terpenes and alkaloids being the most investigated natural product classes. The research also revealed that Metalloporphyrins are still the most popular in the studies, and the identity and yield of the products obtained depend on the reaction system conditions.

3.
J Fungi (Basel) ; 10(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38667948

RESUMO

The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus Scedosporium apiospermum. Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density. The mean diameter of the EVs, evaluated by the light scattering technique, was 179.7 nm. Overall, the structural stability of S. apiospermum EVs was preserved during incubation under various storage conditions. The lipid, carbohydrate and protein contents were quantified, and the EVs' protein profile was evidenced by SDS-PAGE, revealing proteins with molecular masses ranging from 20 to 118 kDa. Through immunoblotting, ELISA and immunocytochemistry assays, antigenic molecules were evidenced in EVs using a polyclonal serum (called anti-secreted molecules) from a rabbit inoculated with conditioned cell-free supernatant obtained from S. apiospermum mycelial cells. By Western blotting, several antigenic proteins were identified. The ELISA assay confirmed that the anti-secreted molecules exhibited a positive reaction up to a serum dilution of 1:3200. Despite transporting immunogenic molecules, S. apiospermum EVs slightly induced an in vitro cytotoxicity effect after 48 h of contact with either macrophages or lung epithelial cells. Interestingly, the pretreatment of both mammalian cells with purified EVs significantly increased the association index with S. apiospermum conidia. Furthermore, EVs were highly toxic to Galleria mellonella, leading to larval death in a typically dose- and time-dependent manner. Collectively, the results represent the first report of detecting EVs in the S. apiospermum filamentous form, highlighting a possible implication in fungal pathogenesis.

4.
Biomed Pharmacother ; 173: 116290, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458010

RESUMO

Jatropha mollissima (Pohl) Baill. (Euphorbiaceae) is widely used in traditional medicine to treat inflammatory disorders. So, a topical gel containing the hydroethanolic extract of its leaves was developed and evaluated for its anti-inflammatory, wound healing, and antiophidic properties in mice. First, the chemical profile of different parts of the plant was characterized by liquid chromatography coupled to mass spectrometry (LC-MS) using molecular networking. In the leaf extract, 11 compounds were characterized, with a particular emphasis on the identification of flavonoids. The gel efficiently inhibited carrageenan-induced paw edema, as well as acute and chronic croton oil-induced ear edema models, thereby reducing inflammatory and oxidative parameters in inflamed tissues. Besides anti-inflammatory activity, the herbal gel showed significant wound healing activity. The edematogenic, hemorrhagic and dermonecrotic activities induced by Bothrops jararaca snake venom were effectively inhibited by the treatment with J. mollissima gel. The association with the herbal gel improved in up to 90% the efficacy of commercial snake antivenom in reduce venom-induced edema. Additionally, while antivenom was not able to inhibit venom-induced dermonecrosis, treatment with herbal gel reduced in 55% the dermonocrotic halo produced. These results demonstrate the pharmacological potential of the herbal gel containing J. mollissima extract, which could be a strong candidate for the development of herbal products that can be used to complement the current antivenom therapy against snake venom local toxicity.


Assuntos
Venenos de Crotalídeos , Euphorbiaceae , Jatropha , Mordeduras de Serpentes , Animais , Camundongos , Euphorbiaceae/química , Antivenenos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Jatropha/química , Composição de Medicamentos , Mordeduras de Serpentes/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Veneno de Bothrops jararaca , Cicatrização
5.
Sci Rep ; 14(1): 4682, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409185

RESUMO

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.


Assuntos
Antimaláricos , Malária Cerebral , Animais , Camundongos , Humanos , Malária Cerebral/tratamento farmacológico , Malária Cerebral/prevenção & controle , Malária Cerebral/parasitologia , Angiotensina II/farmacologia , Angiotensina II/uso terapêutico , Modelos Animais de Doenças , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Plasmodium berghei/fisiologia , Camundongos Endogâmicos C57BL
6.
iScience ; 27(2): 108984, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38327800

RESUMO

Olaparib is a pioneering PARP inhibitor (PARPi) approved for treating castration-resistant prostate cancer (CRPC) tumors harboring DNA repair defects, but clinical resistance has been documented. To study acquired resistance, we developed Olaparib-resistant (OlapR) cell lines through chronic Olaparib treatment of LNCaP and C4-2B cell lines. Here, we found that IGFBP3 is highly expressed in acquired (OlapR) and intrinsic (Rv1) models of Olaparib resistance. We show that IGFBP3 expression promotes Olaparib resistance by enhancing DNA repair capacity through activation of EGFR and DNA-PKcs. IGFBP3 depletion enhances efficacy of Olaparib by promoting DNA damage accumulation and subsequently, cell death in resistant models. Mechanistically, we show that silencing IGFBP3 or EGFR expression reduces cell viability and resensitizes OlapR cells to Olaparib treatment. Inhibition of EGFR by Gefitinib suppressed growth of OlapR cells and improved Olaparib sensitivity, thereby phenocopying IGFBP3 inhibition. Collectively, our results highlight IGFBP3 and EGFR as critical mediators of Olaparib resistance.

7.
Fertil Steril ; 121(6): 1031-1039, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38316207

RESUMO

OBJECTIVE: To report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo-retrieved mature oocytes from a woman with bilateral ovarian carcinoma. DESIGN: Case report. SETTING: Fertility clinic. PATIENT: A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy of 96.1% according to International Ovarian Tumor Analysis Group recommendations for adnexal tumors, who desired fertility preservation before definitive surgical treatment. INTERVENTION(S): Cryopreservation of ex vivo-retrieved mature metaphase II oocytes is followed by fertilization with donor sperm and embryo transfer to a gestational carrier. MAIN OUTCOME MEASURE(S): Fertility preservation. RESULTS: After controlled ovarian stimulation, 12 metaphase II oocytes were retrieved from oophorectomized specimens and vitrified. Intracytoplasmic sperm injection with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, 2 of which were transferred to a gestational carrier, resulting in a normal, healthy singleton pregnancy, and the live birth of a healthy infant. CONCLUSION(S): Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies.


Assuntos
Preservação da Fertilidade , Nascido Vivo , Metáfase , Recuperação de Oócitos , Neoplasias Ovarianas , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Gravidez , Adulto , Preservação da Fertilidade/métodos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Criopreservação , Oócitos , Transferência Embrionária , Ovariectomia , Resultado do Tratamento
8.
Future Microbiol ; 19: 385-395, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38381028

RESUMO

Background: New chemotherapeutics are urgently required to treat Candida infections caused by drug-resistant strains. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different Candida species. Results: Proliferation of Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis and Candida tropicalis was inhibited by three of six Cu(II) (MICs 1.52-21.55 µM), three of three Ag(I) (MICs 0.11-12.74 µM) and seven of seven Mn(II) (MICs 0.40-38.06 µM) complexes. Among these [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O, where oda = octanedioic acid, exhibited effective growth inhibition (MICs 0.4-3.25 µM), favorable activity indexes, low toxicity against Vero cells and good/excellent selectivity indexes (46.88-375). Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O represents a promising chemotherapeutic option for emerging, medically relevant and drug-resistant Candida species.


Candida species are widespread fungi that can cause a variety of infections in humans, and some of them exhibit resistance profile to existing antifungal drugs. Consequently, it is imperative to discover novel treatments for these clinically relevant human infections. Complexes are chemical compounds containing metal ion components that are well-known for their antimicrobial properties, including antifungal activity. In the present study, we investigated the effects of 16 novel complexes against ten medically relevant Candida species, including some strains resistant to commonly used clinical antifungals. Our findings revealed that all complexes containing manganese and silver metals effectively inhibited the growth of all Candida species tested, albeit to varying extents. Some of these complexes exhibited superior antifungal activity and lower toxicity to mammalian cells compared to traditional antifungals, such as fluconazole. In conclusion, these new complexes hold promise as a potential novel approach for treating fungal infections, especially those caused by drug-resistant Candida strains.


Assuntos
Antifúngicos , Cobre , Fenantrolinas , Animais , Chlorocebus aethiops , Cobre/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Prata/farmacologia , Manganês/farmacologia , Células Vero , Candida , Candida albicans , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica
9.
Foods ; 13(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38254503

RESUMO

Natural polysaccharides are among the renewable sources with great potential for replacing petroleum-derived chemicals as precursors to produce biodegradable films. This study aimed to prepare biopolymeric films using starch extracted from the periderm and cortex of cassava roots (waste from cassava root processing), locust bean galactomannan, and cellulose nanofibers also obtained from cassava waste. The films were prepared by casting, and their physicochemical, mechanical, and biodegradability properties were evaluated. The content of cellulose nanofibers varied from 0.5 to 2.5%. Although the addition of cellulose nanofibers did not alter the mechanical properties of the films, it significantly enhanced the vapor barrier of the films (0.055 g mm/m2 h kPa-2.5% nanofibers) and their respective stabilities in aqueous acidic and alkaline media. All prepared films were biodegradable, with complete degradation occurring within five days. The prepared films were deemed promising alternatives for minimizing environmental impacts caused by the disposal of petroleum-derived materials.

10.
Clin Infect Dis ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170196

RESUMO

BACKGROUND: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated. METHODS: A prospective study was performed to investigate the association between Xpert® MTB/RIF Ct values and Mtb transmission to close contacts of patients with culture-confirmed pulmonary TB in a multi-center Brazilian cohort. We evaluated clinical and laboratory data, such as age, sex, race, smoking habits, drug use, alcohol use, chest radiograph, Xpert® MTB/RIF results among pulmonary tuberculosis cases, and QuantiFERON(QFT)-Plus results at baseline and after six months for close contacts who had a negative result at baseline. RESULTS: A total of 1,055 close contacts of 382 pulmonary tuberculosis cases were included in the study. The median Ct values from pulmonary tuberculosis cases of QFT-Plus positive (at baseline or six months) close contacts were lower compared with those who were QFT-Plus negative. An adjusted logistic regression demonstrated that reduced Ct values from the index cases were independently associated with QFT-Plus conversion from negative to positive (OR: 1.61, 95% CI: 1.12-2.32) after adjusting for clinical characteristics. CONCLUSION: Close contacts of pulmonary TB index cases exhibiting low Xpert MTB/RIF Ct values displayed higher rates of TB infection, reflecting Mtb transmission.

11.
Am J Cardiol ; 214: 18-24, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104755

RESUMO

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.


Assuntos
COVID-19 , Síndrome do QT Longo , Humanos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/tratamento farmacológico , Azitromicina/efeitos adversos , Tratamento Farmacológico da COVID-19 , Eletrocardiografia/métodos , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
12.
Brain Res ; 1822: 148669, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37951562

RESUMO

Cerebral malaria (CM) pathogenesis is described as a multistep mechanism. In this context, monocytes have been implicated in CM pathogenesis by increasing the sequestration of infected red blood cells to the brain microvasculature. In disease, endothelial activation is followed by reduced monocyte rolling and increased adhesion. Nowadays, an important challenge is to identify potential pro-inflammatory stimuli that can modulate monocytes behavior. Our group have demonstrated that bradykinin (BK), a pro-inflammatory peptide involved in CM, is generated during the erythrocytic cycle of P. falciparum and is detected in culture supernatant (conditioned medium). Herein we investigated the role of BK in the adhesion of monocytes to endothelial cells of blood brain barrier (BBB). To address this issue human monocytic cell line (THP-1) and human brain microvascular endothelial cells (hBMECs) were used. It was observed that 20% conditioned medium from P. falciparum infected erythrocytes (Pf-iRBC sup) increased the adhesion of THP-1 cells to hBMECs. This effect was mediated by BK through the activation of B2 and B1 receptors and involves the increase in ICAM-1 expression in THP-1 cells. Additionally, it was observed that angiotensin-converting enzyme (ACE) inhibitor, captopril, enhanced the effect of both BK and Pf-iRBC sup on THP-1 adhesion. Together these data show that BK, generated during the erythrocytic cycle of P. falciparum, could play an important role in adhesion of monocytes in endothelial cells lining the BBB.


Assuntos
Barreira Hematoencefálica , Bradicinina , Adesão Celular , Malária Cerebral , Malária Falciparum , Plasmodium falciparum , Humanos , Bradicinina/metabolismo , Adesão Celular/fisiologia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Eritrócitos/parasitologia , Malária Cerebral/metabolismo , Malária Cerebral/parasitologia , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Monócitos/fisiologia , Plasmodium falciparum/fisiologia , Barreira Hematoencefálica/fisiopatologia
13.
Methods Protoc ; 6(5)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37736960

RESUMO

Fungi are well-known producers of chemically diverse and biologically active secondary metabolites. However, their production yields through fermentation may hamper structural analysis and biological activity downstream investigations. Herein, a systematic experimental design that varies multiple cultivation parameters, followed by chemometrics analysis on HPLC-UV-MS or UHPLC-HRMS/MS data, is presented to enhance the production yield of fungal natural products. The overall procedure typically requires 3-4 months of work when first developed, and up to 3 months as a routine procedure.

14.
Front Psychol ; 14: 1196794, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538999

RESUMO

The development of critical thinking in higher education is fundamental, preparing students to think well, find explanations, make decisions and solve problems. Given the importance of its promotion, its assessment is crucial, since the two are inseparable. Moreover, the number of instruments that are validated to assess critical thinking in the Portuguese language and culture are scarce. We present the validation psychometric study of the PENCRISAL test (short version) to the Portuguese language, a critical thinking assessment test for higher education students, designed and validated in Spain (full and short version), which presents adequate reliability and validity psychometric characteristics to assess key-dimensions of critical thinking. A sample of 225 Portuguese higher education students from three universities (two public and one private) performed a reduced version of the PANCRISAL test. The results obtained allowed replicating the Spanish reduced version in Portugal (only changing one of the six items), and the confirmatory factorial analysis permits to identify two factors intercorrelated, legitimizing the combination of the six items in a global score. This short version can be used as a screening test, and its potential is pointed out to assess students critical thinking to support teaching and research in higher education.

15.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569517

RESUMO

The Aedes aegypti mosquito is a vector of severe diseases with high morbidity and mortality rates. The most commonly used industrial larvicides have considerable toxicity for non-target organisms. This study aimed to develop and evaluate liquid and solid carrier systems to use pentyl cinnamate (PC), derived from natural sources, to control Ae. aegypti larvae. The liquid systems consisting of nanoemulsions with different lecithins systems were obtained and evaluated for stability over 30 days. Microparticles (MPs) were obtained by the spray drying of the nanoemulsions using maltodextrin as an adjuvant. Thermal, NMR and FTIR analysis indicated the presence of PC in microparticles. Indeed, the best nanoemulsion system was also the most stable and generated the highest MP yield. The PC larvicidal activity was increased in the PC nanoemulsion system. Therefore, it was possible to develop, characterize and obtain PC carrier systems active against Ae. aegypti larvae.


Assuntos
Aedes , Inseticidas , Animais , Inseticidas/química , Mosquitos Vetores , Cinamatos/farmacologia , Larva
16.
Trop Med Infect Dis ; 8(8)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37624333

RESUMO

Chagas disease is an emerging and neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, estimated to infect 8 to 10 million people worldwide, according to the World Health Organization [...].

17.
J Hum Resour ; 58(4): 1273-1306, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37484544

RESUMO

This paper studies distributional effects of education on health. In 1972, England, Scotland, and Wales raised their minimum school-leaving age from 15 to 16 for students born after 9/1/1957. Using a regression discontinuity design and objective health measures for 129,000 individuals, we find that education reduced body size and increased blood pressure in middle age. The reduction in body size was concentrated at the upper tail of the distribution with an 8 percentage point reduction in obesity. The increase in blood pressure was concentrated at the lower tail of the distribution with no effect on stage 2 hypertension.

18.
Foods ; 12(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37444258

RESUMO

Most polymeric materials are synthetic and derived from petroleum, hence they accumulate in landfills or the ocean, and recent studies have focused on alternatives to replace them with biodegradable materials from renewable sources. Biodegradable wastes from food and agroindustry, such as spent coffee grounds (SCGs), are annually discarded on a large scale and are rich in organic compounds, such as polysaccharides, that could be used as precursors to produce films. Around 6.5 million tons of SCGs are discarded every year, generating an environmental problem around the world. Therefore, it was the aim of this work to develop films from the SCGs polysaccharide fraction, which is comprised of cellulose, galactomannans and arabinogalactans. Two types of crosslinking were performed: the first forming coordination bonds of calcium ions with polysaccharides; and the second through covalent bonds with 1,4-phenylenediboronic acid (PDBA). The films with Ca2+ ions exhibited a greater barrier to water vapor with a reduction of 44% of water permeability vapor and 26% greater tensile strength than the control film (without crosslinkers). Films crosslinked with PDBA presented 55-81% higher moisture contents, 85-125% greater permeability to water vapor and 67-150% larger elongations at break than the films with Ca2+ ions. Film biodegradability was demonstrated to be affected by the crosslinking density, with the higher the crosslinking density, the longer the time for the film to fully biodegrade. The results are promising and suggest that future research should focus on enhancing the properties of these films to expand the range of possible applications.

19.
J Biol Chem ; 299(8): 104973, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380074

RESUMO

Prostate cancer is initially regulated by the androgen receptor (AR), a ligand-activated, transcription factor, and is in a hormone-dependent state (hormone-sensitive prostate cancer (HSPC)), but eventually becomes androgen-refractory (castration-resistant prostate cancer (CRPC)) because of mechanisms that bypass the AR, including by activation of ErbB3, a member of the epidermal growth factor receptor family. ErbB3 is synthesized in the cytoplasm and transported to the plasma membrane for ligand binding and dimerization, where it regulates downstream signaling, but nuclear forms are reported. Here, we demonstrate in prostatectomy samples that ErbB3 nuclear localization is observed in malignant, but not benign prostate, and that cytoplasmic (but not nuclear) ErbB3 correlated positively with AR expression but negatively with AR transcriptional activity. In support of the latter, androgen depletion upregulated cytoplasmic, but not nuclear ErbB3, while in vivo studies showed that castration suppressed ErbB3 nuclear localization in HSPC, but not CRPC tumors. In vitro treatment with the ErbB3 ligand heregulin-1ß (HRG) induced ErbB3 nuclear localization, which was androgen-regulated in HSPC but not in CRPC. In turn, HRG upregulated AR transcriptional activity in CRPC but not in HSPC cells. Positive correlation between ErbB3 and AR expression was demonstrated in AR-null PC-3 cells where stable transfection of AR restored HRG-induced ErbB3 nuclear transport, while AR knockdown in LNCaP reduced cytoplasmic ErbB3. Mutations of ErbB3's kinase domain did not affect its localization but was responsible for cell viability in CRPC cells. Taken together, we conclude that AR expression regulated ErbB3 expression, its transcriptional activity suppressed ErbB3 nuclear translocation, and HRG binding to ErbB3 promoted it.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Receptores Androgênicos , Humanos , Masculino , Androgênios/metabolismo , Linhagem Celular Tumoral , Ligantes , Neuregulina-1/genética , Neoplasias da Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Proteína Tirosina Quinases , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
20.
Trop Med Infect Dis ; 8(5)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37235336

RESUMO

Chagas disease is derived from the infection by the protozoan Trypanosoma cruzi. In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu2+, namely, cis-aquadichloro(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper (3a) and its glycosylated ligand cis-dichloro (N-{[4-(2,3,4,6-tetra-O-acetyl-ß-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (3b), are effective against T. cruzi trypomastigote forms. With this result in mind, the present work aimed to investigate the effects of both compounds on trypomastigotes physiology and on the interaction process with host cells. Apart from loss of plasma membrane integrity, an increased generation of reactive oxygen species (ROS) and decreased mitochondrial metabolism were observed. Pretreatment of trypomastigotes with these metallodrugs inhibited the association index with LLC-MK2 cells in a typical dose-dependent manner. Both compounds showed low toxicity on mammalian cells (CC50 > 100 µM), and the IC50 values calculated for intracellular amastigotes were determined as 14.4 µM for 3a and 27.1 µM for 3b. This set of results demonstrates the potential of these aminopyridines complexed with Cu2+ as promising candidates for further antitrypanosomal drug development.

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