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1.
Bioorg Med Chem ; 102: 117671, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452407

RESUMO

The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.


Assuntos
Antineoplásicos , Neoplasias da Mama , Naftoquinonas , Humanos , Feminino , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Triazóis/farmacologia , Naftoquinonas/farmacologia , Proteínas Quinases Ativadas por AMP , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais
2.
An. R. Acad. Nac. Farm. (Internet) ; 90(1): 21-44, Ene-Mar, 2024. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-232333

RESUMO

La esquizofrenia es un trastorno neuropsiquiátrico crónico que afecta a 21 millones de personas en todo el mundo. Actualmente, los fármacos antipsicóticos de segunda generación o atípicos (FASG) son los medicamentos de elección para el tratamiento de esta enfermedad. Sin embargo, a pesar de su alta eficacia en contrarrestar la sintomatología neuropsiquiátrica de la esquizofrenia, observaciones clínicas recientes en pacientes tratados con FASG evidencian un aumento en la prevalencia de diferentes alteraciones metabólicas, entre las que se incluyen el aumento de peso corporal, la hiperglucemia y la dislipidemia. A pesar de que no se conocen en detalle los mecanismos moleculares responsables de estos efectos secundarios, cada vez más investigaciones apuntan a una relación entre los tratamientos con FASG y las alteraciones en los diferentes depósitos de tejido adiposo blanco, marrón y beige. En esta revisión analizamos el conocimiento actual en esta área destacando aspectos moleculares de la biología de los adipocitos, entre los que se encuentran los procesos de diferenciación, metabolismo lipídico, función termogénica y el proceso de pardeamiento o beiging.(AU)


Schizophrenia is a chronic neuropsychiatric disorder that affects 21 million people worldwide. Currently, second-generation or atypical antipsychotics (SGAs) are the first-line medications for the treatment of this disease. However, despite its high efficacy in counteracting the neuropsychiatric symptoms of schizophrenia, recent clinical investigations in patients treated with SGAs show an increase in the prevalence of pivotal metabolic alterations, including increased body weight, hyperglycemia and dyslipidemia. Although the molecular mechanisms responsible for these side effects are not fully understood, cumulative evidences associate SGA administration with alterations in the different adipose tissue depots of white, brown and beige adipocytes. In this review, we have recapitulated the current knowledge in this area with a particular focus on the molecular aspects of the adipocyte biology, including differentiation, lipid metabolism, thermogenic function and browning processes.(AU)


Assuntos
Humanos , Masculino , Feminino , Esquizofrenia/tratamento farmacológico , Metabolismo , Termogênese , Antipsicóticos , Tecido Adiposo/efeitos dos fármacos , Neuropsiquiatria , Farmácia
3.
Int J Parasitol Drugs Drug Resist ; 24: 100525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359731

RESUMO

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.


Assuntos
Antiprotozoários , Leishmania , Leishmaniose Cutânea , Naftoquinonas , Compostos Organometálicos , Humanos , Animais , Camundongos , Antimoniato de Meglumina/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Camundongos Endogâmicos BALB C
4.
Port J Card Thorac Vasc Surg ; 30(4): 51-58, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38345882

RESUMO

INTRODUCTION: Commonly used chronic limb-threatening ischemia (CLTI) classifications lack granularity and detail to precisely stratify patients according to risk of limb loss, expected revascularization benefit and mortality. The aim of this study is to evaluate in a Portuguese population the prognostic value of an updated CLTI classification based on Wound, Ischemia, and foot Infection (WIfI) proposed by the Society for Vascular Surgery. MATERIALS AND METHODS: Single-center retrospective evaluation of prospectively collected data of consecutive patients with CLTI submitted to lower limb revascularization from January to December of 2017. All consecutive patients with chronic peripheral artery disease with ischemic rest pain or tissue loss were included. The exclusion criteria were patients with intermittent claudication, vascular trauma, acute ischemia, non-atherosclerotic arterial disease and isolated iliac intervention. The primary end-point was major limb amputation, mortality and amputation-free survival (AFS) at 30 days, 1 year and 2 year follow-up. Secondary end-points were minor amputation, wound healing time (WHT) and rate (WHR). RESULTS: A total of 111 patients with CLTI were submitted to infra-inguinal revascularization: 91 endovascular and 20 open surgery. After categorizing them according to the WIfI: 20 had stage 1 (18.52%), 29 stage 2 (26.85%), 38 stage 3 (35.19%) and 21 stage 4 (19.44%). Overall mortality rate was 1.8%, 17% and 22.3% at 30 days, 1 year and 2 years follow-up. Major amputation rate was 0.9%, 2.7% and 2.7% at 30 days, 1 year and 2 years follow-up. AFS rate was 97.3%, 82.1%, and 76.8% at 30 days, 1 year, 2 years follow-up. In multi-variable analysis, higher WIfI score was the only predictive factor for mortality and AFS. WIfI 3 and 4 were also associated with increased risk of non-healing ulcer. CONCLUSION: This study proved the prognostic value of the WIfI classification in a Portuguese population by showing an association between higher scores and increased mortality, lower AFS and non-healing ulcer.


Assuntos
Infecção Focal , Doença Arterial Periférica , Infecção dos Ferimentos , Humanos , Resultado do Tratamento , Fatores de Risco , Salvamento de Membro/efeitos adversos , Estudos Retrospectivos , Portugal/epidemiologia , Úlcera/etiologia , Infecção dos Ferimentos/diagnóstico , Amputação Cirúrgica , Doença Arterial Periférica/diagnóstico , Infecção Focal/etiologia , Isquemia/diagnóstico , Isquemia Crônica Crítica de Membro
5.
Cuad. psicol. deporte ; 24(1): 257-274, Ene 2, 2024. tab, graf
Artigo em Inglês | IBECS | ID: ibc-229631

RESUMO

La observación sistemática es un método que permite obtener numerosas informaciones sobre el comportamiento del entrenador, incluida la comunicación, que es parte integral del proceso de eficacia pedagógica. Tras revisar varios sistemas de observación y comprobar su potencial, pero principalmente sus debilidades, surge el Sistema de Análisis de Información del Entrenador de Fútbol en Competición (SAITFC) desde una perspectiva de evolución y aportación científica. Un sistema flexible que incluye dimensiones, categorías y subcategorías, que hacen referencia a la información en un intento de hacer inclusivos todos los comportamientos relacionados con la información emitida por el entrenador, ayudando a elaborar un perfil de comportamiento en competición. El cálculo de los porcentajes de concordancia, complementando con las estadísticas Kappa de Cohen, mostró altos niveles de fidelidad de las observaciones para ser utilizadas como herramienta científica. Con este estudio piloto, los resultados obtenidos en esta investigación sugieren que los entrenadores emiten cada vez más información, no solo a los atletas, en forma de instrucción y feedback, sino a todos los agentes deportivos involucrados en la competencia, es decir, el arbitraje, el oponente y el equipo técnico en forma de conversaciones. El feedback tiende a ser prescriptive, auditive, dirigido al atleta, táctico y afectivamente neutral. Es importante destacar la expresividad de los feedbacks relacionados con esquemas tácticos y velocidad de reacción. El SAITFC, como herramienta para ayudar a sistematizar el comportamiento del entrenador, demostró ser un método eficaz, contribuyendo así a la formación de los entrenadores, pero también a nivel científico, ayudándolos en el campo.(AU)


Systematic observation is a method that allows obtaining numerous information about the coach ́s behavior, including communication, whichis an integral part of the process of pedagogical effectiveness. After reviewing several observation systems and verifying their potential, mainly their weaknesses, the Information Analysis System for Football Coaches in Competition (SAITFC) emerges from a perspective of evolution andscientific contribution. A flexible system that includes dimensions, categories, and subcategories, which refer to the information in an attempt to make all behaviors related to the information issued by the coach inclusive, helping to elaborate a behavioral profile in the competition. The calculation of agreement percentages, complemented by Cohen ́s Kappa statistics, showed substantial levels of reliability for the observations to be used as a scientific tool. With this pilotstudy, the results obtainedin this investigation suggest that coaches issue more and more information, not only to athletes, in the form of instruction and feedback but to all sports agents involved in the competition, namely arbitration, opponent, and technical team in the form of conversations. Feedback tends to be prescriptive, auditory, addressed to the athlete, tactical, and effectively neutral. It is essential to emphasize the expressiveness of the feedback related to tactical schemes and reaction speed. The SAITFC, as a tool tohelp systematize the coach ́s behavior, proved to be an effective method, thus contributing tothe training of coaches, but also at a scientific level, helping them in the field.(AU)


A observação sistemática é um método que permite obter inúmeras informações sobre o comportamento do treinador, entre elas a comunicação, a qual é parte integrante do processo de eficácia pedagógica.Após revisão de vários sistemas de observação e constatação das suas potencialidades, mas principalmente das suas fragilidades, surge assim numa perspetiva de evolução e de contributo científico, o Sistema de Análise da Informação do Treinador de Futebol em Competição (SAITFC). Um sistema flexível que inclui dimensões, categorias e subcategorias, as quais remetem para a informação numa tentativa de tornar inclusivo todos os comportamentos relacionadoscom a informação emitida pelo treinador, ajudando a umaelaboração de um perfil comportamental emcompetição. O cálculo de percentagens de acordos, complementada pela estatística de Kappa de Cohen, mostrou níveis fortes de fidelidade para as observações serem utilizadas como ferramenta científica. Com este estudo piloto, os resultados obtidos nesta investigação sugerem que os treinadores emitam cada vez mais informação, não só para os atletas, em forma de instrução e feedback, mas para todos os agentes desportivos envolvidos na competição, nomeadamente equipas de arbitragem, adversária e técnica em forma de conversas. O feedback tende a ser prescritivo, auditivo, dirigido ao atleta, tático e de afetividade neutra. De realçar a expressividade dos feedbacks relacionados com esquemas táticos e de velocidade de reação. O SAITFC enquanto ferramenta de auxílio à sistematização do comportamento do treinador, mostrou ser um método eficaz, contribuindo assim para a formação de treinadores, mas também a nível científico, auxiliando-os no terreno.(AU)


Assuntos
Humanos , Masculino , Feminino , Atletismo/normas , Futebol , Retroalimentação , Mentores , Comunicação , Observação , Psicologia do Esporte , Medicina Esportiva , Esportes/psicologia , Projetos Piloto
6.
Cureus ; 15(11): e49021, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38111399

RESUMO

Tuberculous spondylodiscitis (Pott's spine) is a complex extrapulmonary manifestation of tuberculosis (TB) that poses significant medical challenges, characterized by vertebral destruction affecting approximately 2% of all TB cases. The management of this condition involves a multidisciplinary approach, with surgical intervention indicated for specific cases, including those with neurological complications, spinal instability, and kyphosis. We report a case of a 49-year-old female with a confirmed diagnosis of tuberculous spondylodiscitis who had undergone eight months of tuberculostatic therapy. She was referred for neurosurgical consultation due to uncontrollable axial pain, despite favorable clinical and imaging responses, which had rendered her immobile for six months. Imaging revealed a complete collapse of the L5 vertebral body, and a complementary dual x-ray absorptiometry (DEXA) scan demonstrated severe osteoporosis. A two-stage surgical approach was chosen to address her condition, involving corpectomy through an anterior approach, followed by lumbopelvic stabilization. Postoperative recovery was uneventful, with progressive improvement in pain and mobility. This case highlights the challenges of managing tuberculous spondylodiscitis and underscores the significance of early detection to prevent complications like severe osteoporosis. In this case, delayed referral for surgery following an extended period of immobility added complexity to an already difficult case. The severe osteoporosis, with a t-score of -5.7, had a substantial impact on surgical planning, leading to a more robust approach to arthrodesis with substantial lumbopelvic instrumentation in order to mitigate the risks associated with implant failure. This case shows that timely intervention and a comprehensive multidisciplinary approach are essential for the effective management of tuberculous spondylodiscitis, especially in cases complicated by severe osteoporosis.

7.
RSC Adv ; 13(49): 34852-34865, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38035251

RESUMO

This study presents a comprehensive analysis encompassing the synthesis, structural elucidation, photophysical behavior, and electrochemical properties of a novel series of chalcogen-naphthoquinone-1,2,3-triazole hybrids. Employing a meticulously designed protocol, the synthesis of these hybrids, denoted as 11a-j, was achieved with remarkable efficiency (yielding up to 81%). This synthesis used a regioselective copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Furthermore, a detailed investigation into the photophysical characteristics, TDDFT calculations, electrochemical profiles, and photobiological attributes of compounds 11a-j was conducted. This exploration aimed to unravel insights into the excited state behaviors of these molecules, as well as their redox properties. Such insights are crucial for future applications of these derivatives in diverse biological assays.

8.
Neurosci Biobehav Rev ; 154: 105407, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37769929

RESUMO

Animal domestication leads to diverse behavioral, physiological, and neurocognitive changes in domesticated species compared to their wild relatives. However, the widely held belief that domesticated species are inherently less "intelligent" (i.e., have lower cognitive performance) than their wild counterparts requires further investigation. To investigate potential cognitive disparities, we undertook a thorough review of 88 studies comparing the cognitive performance of domesticated and wild animals. Approximately 30% of these studies showed superior cognitive abilities in wild animals, while another 30% highlighted superior cognitive abilities in domesticated animals. The remaining 40% of studies found similar cognitive performance between the two groups. Therefore, the question regarding the presumed intelligence of wild animals and the diminished cognitive ability of domesticated animals remains unresolved. We discuss important factors/limitations for interpreting past and future research, including environmental influences, diverse objectives of domestication (such as breed development), developmental windows, and methodological issues impacting cognitive comparisons. Rather than perceiving these limitations as constraints, future researchers should embrace them as opportunities to expand our understanding of the complex relationship between domestication and animal cognition.


Assuntos
Animais Domésticos , Domesticação , Animais , Cognição
9.
Molecules ; 28(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37764459

RESUMO

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C-H, N-H, O-H, S-H, and Si-H bonds. Typically, reactions from diazo compounds are catalyzed by transition metals with various ligands that modulate the capacity and selectivity of the catalyst. These ligands can modify and enhance chemoselectivity in the substrate, regioselectivity and enantioselectivity by reflecting these preferences in the products. Porphyrins have been used as catalysts in several important reactions for organic synthesis and also in several medicinal applications. In the chemistry of diazo compounds, porphyrins are very efficient as catalysts when complexed with low-cost metals (e.g., Fe and Co) and, therefore, in recent years, this has been the subject of significant research. This review will summarize the advances in the studies involving the field of diazo compounds catalyzed by metalloporphyrins (M-Porph, M = Fe, Ru, Os, Co, Rh, Ir) in the last five years to provide a clear overview and possible opportunities for future applications. Also, at the end of this review, the properties of artificial metalloenzymes and hemoproteins as biocatalysts for a broad range of applications, namely those concerning carbene-transfer reactions, will be considered.

10.
Sci Rep ; 13(1): 11402, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452079

RESUMO

Inferring causal relationships from observational data is a key challenge in understanding the interpretability of Machine Learning models. Given the ever-increasing amount of observational data available in many areas, Machine Learning algorithms used for forecasting have become more complex, leading to a less understandable path of how a decision is made by the model. To address this issue, we propose leveraging ensemble models, e.g., Random Forest, to assess which input features the trained model prioritizes when making a forecast and, in this way, establish causal relationships between the variables. The advantage of these algorithms lies in their ability to provide feature importance, which allows us to build the causal network. We present our methodology to estimate causality in time series from oil field production. As it is difficult to extract causal relations from a real field, we also included a synthetic oil production dataset and a weather dataset, which is also synthetic, to provide the ground truth. We aim to perform causal discovery, i.e., establish the existing connections between the variables in each dataset. Through an iterative process of improving the forecasting of a target's value, we evaluate whether the forecasting improves by adding information from a new potential driver; if so, we state that the driver causally affects the target. On the oil field-related datasets, our causal analysis results agree with the interwell connections already confirmed by tracer information; whenever the tracer data are available, we used it as our ground truth. This consistency between both estimated and confirmed connections provides us the confidence about the effectiveness of our proposed methodology. To our knowledge, this is the first time causal analysis using solely production data is employed to discover interwell connections in an oil field dataset.


Assuntos
Algoritmos , Algoritmo Florestas Aleatórias , Fatores de Tempo , Causalidade , Previsões
11.
J Bioenerg Biomembr ; 55(3): 233-248, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37442875

RESUMO

The subclass naphthoquinone represents a substance group containing several compounds with important activities against various pathogenic microorganisms. Accordingly, we evaluated O-allyl-lawsone (OAL) antiparasitic and antifungal activity free and encapsulated in 2-hydroxypropyl-ß-cyclodextrin (OAL MKN) against Trypanosoma cruzi and Sporothrix spp. OAL and OAL MKN were synthesized and characterized by physicochemical methods. The IC50 values of OAL against T. cruzi were 2.4 µM and 96.8 µM, considering epimastigotes and trypomastigotes, respectively. At the same time, OAL MKN exhibited a lower IC50 value (0.5 µM) for both trypanosome forms and low toxicity for mammalian cells. Additionally, the encapsulation showed a selectivity index approximately 240 times higher than that of benznidazole. Regarding antifungal activity, OAL and OAL MKN inhibited Sporothrix brasiliensis growth at 16 µM, while Sporothrix schenckii was inhibited at 32 µM. OAL MKN also exhibited higher selectivity toward fungus than mammalian cells. In conclusion, we described the encapsulation of O-allyl-lawsone in 2-hydroxypropyl-ß-cyclodextrin, increasing the antiparasitic activity compared with the free form and reducing the cytotoxicity and increasing the selectivity towardSporothrix yeasts and the T. cruzi trypomastigote form. This study highlights the potential development of this inclusion complex as an antiparasitic and antifungal agent to treat neglected diseases.


Assuntos
Doença de Chagas , Naftoquinonas , Trypanosoma cruzi , Animais , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/uso terapêutico , Antiparasitários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Mamíferos , Naftoquinonas/uso terapêutico
13.
Chem Rev ; 123(14): 9094-9138, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37379327

RESUMO

Biomolecular condensates, membrane-less entities arising from liquid-liquid phase separation, hold dichotomous roles in health and disease. Alongside their physiological functions, these condensates can transition to a solid phase, producing amyloid-like structures implicated in degenerative diseases and cancer. This review thoroughly examines the dual nature of biomolecular condensates, spotlighting their role in cancer, particularly concerning the p53 tumor suppressor. Given that over half of the malignant tumors possess mutations in the TP53 gene, this topic carries profound implications for future cancer treatment strategies. Notably, p53 not only misfolds but also forms biomolecular condensates and aggregates analogous to other protein-based amyloids, thus significantly influencing cancer progression through loss-of-function, negative dominance, and gain-of-function pathways. The exact molecular mechanisms underpinning the gain-of-function in mutant p53 remain elusive. However, cofactors like nucleic acids and glycosaminoglycans are known to be critical players in this intersection between diseases. Importantly, we reveal that molecules capable of inhibiting mutant p53 aggregation can curtail tumor proliferation and migration. Hence, targeting phase transitions to solid-like amorphous and amyloid-like states of mutant p53 offers a promising direction for innovative cancer diagnostics and therapeutics.


Assuntos
Neoplasias , Ácidos Nucleicos , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Agregados Proteicos , Neoplasias/metabolismo , Amiloide/química
14.
Zookeys ; 1165: 155-182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304571

RESUMO

The New Caledonian Archipelago is a hot spot for biodiversity and endemism. Whereas popular groups such as birds and plants are well-studied, invertebrate groups such as ostracods remain ill-known. Here, Caledromusrobinsmithigen. et sp. nov. is described from a single locality on 'Grande Terre', the main island of the archipelago. The new genus belongs to the Psychrodromini, one of the four tribes in the subfamily Herpetocypridinae (family Cyprididae). Caledromusgen. nov. can be distinguished from all other herpetocypridinids by a combination of the following factors: the absence of marginal septa in both valves, the mildly developed marginal valve structures, the small Rome organ on the A1, the total reduction of the five natatory setae on the A2, the rectangular second palp segment of the Mx1, the broad and asymmetrical palp on the female T1, the absence of additional postlabyrinthal coils in the Hp and the seta Sp of the CR which is a fixed spine. Because of the close similarity to the genus Psychrodromus, the new genus is thought to have Palaearctic affinities, contrary to other ostracod species in New Caledonia, which are either circumtropical or with Australian zoogeographical connections.

15.
Redox Biol ; 63: 102741, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230004

RESUMO

Olanzapine (OLA), a widely used second-generation antipsychotic (SGA), causes weight gain and metabolic alterations when administered orally to patients. Recently, we demonstrated that, contrarily to the oral treatment which induces weight gain, OLA administered via intraperitoneal (i.p.) in male mice resulted in body weight loss. This protection was due to an increase in energy expenditure (EE) through a mechanism involving the modulation of hypothalamic AMPK activation by higher OLA levels reaching this brain region compared to those of the oral treatment. Since clinical studies have shown hepatic steatosis upon chronic treatment with OLA, herein we further investigated the role of the hypothalamus-liver interactome upon OLA administration in wild-type (WT) and protein tyrosine phosphatase 1B knockout (PTP1B-KO) mice, a preclinical model protected against metabolic syndrome. WT and PTP1B-KO male mice were fed an OLA-supplemented diet or treated via i.p. Mechanistically, we found that OLA i.p. treatment induces mild oxidative stress and inflammation in the hypothalamus in a JNK1-independent and dependent manner, respectively, without features of cell dead. Hypothalamic JNK activation up-regulated lipogenic gene expression in the liver though the vagus nerve. This effect concurred with an unexpected metabolic rewiring in the liver in which ATP depletion resulted in increased AMPK/ACC phosphorylation. This starvation-like signature prevented steatosis. By contrast, intrahepatic lipid accumulation was observed in WT mice treated orally with OLA; this effect being absent in PTP1B-KO mice. We also demonstrated an additional benefit of PTP1B inhibition against hypothalamic JNK activation, oxidative stress and inflammation induced by chronic OLA i.p. treatment, thereby preventing hepatic lipogenesis. The protection conferred by PTP1B deficiency against hepatic steatosis in the oral OLA treatment or against oxidative stress and neuroinflammation in the i.p. treatment strongly suggests that targeting PTP1B might be also a therapeutic strategy to prevent metabolic comorbidities in patients under OLA treatment in a personalized manner.


Assuntos
Fígado Gorduroso , Transdução de Sinais , Masculino , Animais , Camundongos , Olanzapina/metabolismo , Transdução de Sinais/fisiologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteínas Quinases Ativadas por AMP/metabolismo , Fígado/metabolismo , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Camundongos Knockout , Inflamação/metabolismo , Ácido Graxo Sintases/metabolismo , Aumento de Peso , Hipotálamo/metabolismo , Camundongos Endogâmicos C57BL
16.
Curr Top Med Chem ; 23(11): 957-969, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37198981

RESUMO

Pharmaceutical chemistry has many industrial processes that must be studied and adapted to a new reality where the environment must be the focus of all production chains. Thus, new technologies that are cleaner and use renewable sources of raw materials still need to be developed and applied to materials that go to the market, and they need to reach a level that is less harmful to the environment. This applies especially in areas related to the pharmaceutical industries since chemical products are used in the production of medicines and used in many other areas of everyday life and are included in the Sustainable Development Goals proposed by the United Nations. This article intends to provide insight into some relevant topics that can stimulate researchers toward medicinal chemistry that can contribute to a sustainable future of the biosphere. This article is structured around four interconnected themes that influence how green chemistry can be important for a future where science, technology and innovation are key to mitigating climate change and increasing global sustainability.


Assuntos
Química Farmacêutica , Desenvolvimento Sustentável
17.
Zootaxa ; 5231(1): 79-92, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-37044817

RESUMO

With 53 formally described species, the genus Cypretta is one of the most common freshwater ostracod genera in the world. It has a mainly circumtropical distribution. The type species, Cypretta tenuicauda (Vávra, 1895), was described from Zanzibar (Africa) in a superficial way. Therefore, the morphology and identity of this species and of the genus remained problematic until today. Here, we redescribe Cypretta tenuicauda from the original type material and discuss the morphology of the species and the diagnosis of the genus. The species is characterized by the presence of anterior marginal septa in both valves, the sub-triangular carapace shape in lateral view, the right valve overlapping the left valve, the generally wide carapace and the presence of a serrated posteroventral inner list in the right valve. In addition, both α and ß setae on the mandibular palp are long and thin, claws Ga and Gp on the caudal ramus are elongated and seta-like, while the caudal ramus itself is equally slender. The caudal ramus attachment is reduced to a simple branch. The present redescription of the type species will assist in creating order in what is now a taxonomically confused genus.


Assuntos
Crustáceos , Água Doce , Animais , Distribuição Animal , Mandíbula
18.
Zootaxa ; 5237(1): 1-88, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37045115

RESUMO

We describe seven new species in two new genera of the Physocypria sensu latu clade (Cyclocypridinae) from three of the main Brazilian floodplains. Brasilocypria pea gen. et spec. nov. and Brasilocypria ricardopintoi gen. et spec. nov. occur in the Upper Paraná River floodplain and the South Matogrossense Pantanal, Claudecypria mesquitai gen. et spec. nov., Brasilocypria alisonae gen. et spec. nov. and Claudecypria rochei gen. et spec. nov. were found in the South Matogrossense Pantanal, and Brasilocypria lordi gen. et spec. nov. and Brasilocypria namiotkoi gen. et spec. nov. occur in the Amazon River floodplain. All new species here described were found as sexual populations. Generally, they have a short and suboval carapace, with the left valve overlapping the right valve on all sides, except for the dorsal side in some species. The morphology of the hemipenis and the prehensile palps, together with the shape of the valves, were the most important characters to distinguish the species. Size differences between species can be substantial. Several characters, such as the absence in all new species of the short accompanying seta of the five natatory setae on the antenna; the presence in all new species of a long seta next to the two a-setae on the first thoracopod, and the presence/absence or differences in length of specific setae on the second and third thoracopod, are relevant for the generic diagnoses. We also redefine Keysercypria Karanovic, 2011.


Assuntos
Crustáceos , Rios , Animais , Brasil
19.
Foods ; 12(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37048318

RESUMO

Beetroot is a tuber rich in antioxidant compounds, i.e., betanin and saponins, and is one of the main sources of dietary nitrate. The aim of the present study was to microencapsulate a ready-to-eat beetroot soup by lyophilization using different encapsulating agents, which supply the required amount of bioactive nutrients. Particle size distributions ranged from 7.94 ± 1.74 to 245.66 ± 2.31 µm for beetroot soup in starch and from 30.56 ± 1.66 to 636.34 ± 2.04 µm in maltodextrin. Microparticle yields of powdered beetroot soup in starch varied from 77.68% to 88.91%, and in maltodextrin from 75.01% to 80.25%. The NO3- and total betalain contents at a 1:2 ratio were 10.46 ± 0.22 mmol·100 g-1 fresh weight basis and 219.7 ± 4.92 mg·g-1 in starch powdered beetroot soup and 8.43 ± 0.09 mmol·100 g-1 fresh weight basis and 223.9 ± 4.21 mg·g-1 in maltodextrin powdered beetroot soup. Six distinct minerals were identified and quantified in beetroot soups, namely Na, K, Mg, Mn, Zn and P. Beetroot soup microencapsulated in starch or maltodextrin complied with microbiological quality guidelines for consumption, with good acceptance and purchase intention throughout 90 days of storage. Microencapsulated beetroot soup may, thus, comprise a novel attractive strategy to offer high contents of bioaccessible dietary nitrate and antioxidant compounds that may aid in the improvement of vascular-protective effects.

20.
Polymers (Basel) ; 15(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36987212

RESUMO

Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H2O), EtOH:H2O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery.

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