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1.
An Acad Bras Cienc ; 96(1): e20231201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38451600

RESUMEN

Biotechnology offers solutions and opportunities to meet various societal demands, thereby contributing to significant scientific advancements. This study aimed to characterize the technological development of biotechnology in the healthcare sector in the state of Rio Grande do Sul, Brazil, from 2016 to 2022 by analyzing patents filed by and granted to public and private Higher Education institutions. For data collection, a quantitative exploratory approach was employed using statistical methods and a patent analysis of institutions in the patent database of the Brazilian National Institute of Industrial Property (INPI), focusing on patents related to the healthcare field. Data were collected in October, November, and December. A total of 580 patent records were collected from the INPI, belonging to Sections A and C of the International Patent Classification (IPC) related to educational institutions. Furthermore, this study highlighted that higher education institutions have a higher number of patents in the healthcare field. These results provide an understanding of the strategic areas for technological development in biotechnology in Rio Grande do Sul, Brazil.


Asunto(s)
Academias e Institutos , Biotecnología , Brasil , Universidades , Bases de Datos Factuales
2.
Eur J Med Chem ; 263: 115935, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37989057

RESUMEN

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Quinasas Janus , Purinas/farmacología , Línea Celular Tumoral , Proliferación Celular
3.
Inflammopharmacology ; 31(6): 2939-2954, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37740887

RESUMEN

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Stimulant medication is the main pharmacological treatment for ADHD. However, the traditional pharmacological treatments may have significant side effects; therefore, non-pharmacological approaches are needed. Thus, there has been growing interest in alternative herbal treatments. The aim of this review was to comprehensively assess the current evidence for plant-based treatment of ADHD in human and animal models, as well as their ability to modulate the inflammatory process. METHODS: This study was an integrative review of the current evidence for the plant-based treatment of ADHD. The research involved using literature available on PubMed and Scopus databases. FINDINGS: Spontaneously hypersensitive rats treated with baicalin exhibited significant reductions in locomotion, increased spatial learning skills, and increased levels of dopamine in the striatum. Supplementation with Sansonite improved memory and attention capacity. In human studies, Ginkgo biloba significantly improved the symptoms of inattention and reduced memory impairment. In studies conducted using Korean Red ginseng, Klamath, and Crocus sativus L., the patients showed significant improvements in symptoms of inattention and hyperactivity/impulsivity. Furthermore, we demonstrated that the identified plants modulate the inflammatory process through pro-inflammatory and anti-inflammatory cytokines, nitric oxide, Th cells, Toll-like receptor 4, and mitogen-activated protein kinases. CONCLUSION: All the studies included in this review focused on plants with demonstrated potential against inflammatory processes, positioning them as promising candidates for ADHD treatment, due to their potential to attenuate or even prevent neuroinflammatory mechanisms.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Humanos , Ratas , Animales , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Atención , Aprendizaje Espacial , Inflamación/tratamiento farmacológico
4.
J Appl Microbiol ; 134(8)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37533216

RESUMEN

AIMS: To evaluate the adhesion capacity and anti-inflammatory activity of lactic acid bacteria (LAB) isolated from raw cow milk and artisan cheese in Southern Brazil, investigating their effect on the release of cytokines such as TNF-α and IL-10 and their influence on the activation of the p38/MAPK pathway. METHODS AND RESULTS: Lentilactobacillus parabuchneri ML4, Lacticaseibacillus paracasei ML33, Lactiplantibacillus pentosus ML82, Lactiplantibacillus plantarum CH131, and L. paracasei CH135 demonstrated high adhesion potential in an in vitro model of the intestinal epithelium, as well as anti-inflammatory activity. After a 4-hour treatment, the strains significantly increased TNF-α levels, while a 24-hour treatment led to a significant decrease in TNF-α release. Moreover, IL-10 levels significantly increased after 24-hour and 48-hour treatments with LAB. The inhibition of p38/MAPK phosphorylation was identified as one of the mechanisms by which the L. paracasei ML33 and L. plantarum CH131 strains suppressed the production and release of TNF-α. CONCLUSIONS: We identified LAB strains with potential anti-inflammatory properties that could adhere to the intestinal mucosa and alleviate the inflammatory response by reducing the production and release of TNF-α through the inhibition of the p38/MAPK pathway, while promoting the production of IL-10.


Asunto(s)
Lactobacillales , Probióticos , Animales , Factor de Necrosis Tumoral alfa , Interleucina-10 , Brasil , Leche/microbiología , Antiinflamatorios
5.
J Toxicol Environ Health A ; 86(18): 678-695, 2023 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-37482814

RESUMEN

Hymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC50 of 3.12 µg/ml. The extract at concentrations of 400 and 800 µg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 µg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 µg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 µl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.


Asunto(s)
Caenorhabditis elegans , Hymenaea , Ratones , Humanos , Animales , Extractos Vegetales/toxicidad , Corteza de la Planta , Línea Celular
7.
Int J Mol Sci ; 23(24)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36555275

RESUMEN

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.


Asunto(s)
Antiulcerosos , Ceiba , Extractos Vegetales , Úlcera Gástrica , Animales , Humanos , Ratas , Antiulcerosos/farmacología , Antioxidantes/farmacología , Carragenina/efectos adversos , Ceiba/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , Úlcera
8.
Front Pharmacol ; 13: 975197, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36299892

RESUMEN

Gliomas are extremely debilitating malignant brain tumors with very limited response to therapies. The initiation and progression of gliomas can be attributed to several molecular abnormalities, such as mutations in important regulatory networks. In this regard, the mitogen-activated protein kinases (MAPKs) arise as key signaling pathways involved in cell proliferation, survival, and differentiation. MAPK pathway has been altered in most glial tumors. In glioma cells, the activation of p38 MAPK contributes to tumor invasion and metastasis and is positively correlated with tumor grade, being considered a potential oncogenic factor contributing to brain tumorigenesis and chemotherapy resistance. Hence, a better understanding of glioma pathogenesis is essential to the advancement of therapies that provide extended life expectancy for glioma patients. This review aims to explore the role of the p38 MAPK pathway in the genesis and progression of malignant brain tumors.

9.
Molecules ; 27(19)2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36235032

RESUMEN

The growing knowledge about the harmful effects caused by some synthetic ingredients present in skincare products has led to an extensive search for natural bioactives. Thus, this study aimed to investigate the dermatological potential of five fractions (F1-F5), obtained by a sequential extraction procedure, from the brown seaweed Saccorhiza polyschides. The antioxidant (DPPH, FRAP, ORAC and TPC), anti-enzymatic (collagenase, elastase, hyaluronidase and tyrosinase), antimicrobial (Staphylococcus epidermidis, Cutibacterium acnes and Malassezia furfur), anti-inflammatory (nitric oxide, tumor necrosis factor-α, interleukin-6 and interleukin-10) and photoprotective (reactive oxygen species) properties of all fractions were evaluated. The ethyl acetate fraction (F3) displayed the highest antioxidant and photoprotective capacity, reducing ROS levels in UVA/B-exposed 3T3 fibroblasts, and the highest anti-enzymatic capacity against tyrosinase (IC50 value: 89.1 µg/mL). The solid water-insoluble fraction (F5) revealed the greatest antimicrobial activity against C. acnes growth (IC50 value: 12.4 µg/mL). Furthermore, all fractions demonstrated anti-inflammatory potential, reducing TNF-α and IL-6 levels in RAW 264.7 macrophages induced with lipopolysaccharides. Chemical analysis of the S. polyschides fractions by NMR revealed the presence of different classes of compounds, including lipids, polyphenols and sugars. The results highlight the potential of S. polyschides to be incorporated into new nature-based skincare products.


Asunto(s)
Antiinfecciosos , Phaeophyceae , Antiinfecciosos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Colagenasas , Hialuronoglucosaminidasa , Interleucina-10 , Interleucina-6 , Lipopolisacáridos , Monofenol Monooxigenasa , Óxido Nítrico , Elastasa Pancreática , Extractos Vegetales/química , Especies Reactivas de Oxígeno , Azúcares , Factor de Necrosis Tumoral alfa , Agua
10.
Nutrition ; 103-104: 111772, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35930916

RESUMEN

Gastrointestinal tract diseases are characterized by an imbalance in physiological functions, which may involve inflammatory and metabolic pathways and trigger chronic, multifactorial, and idiopathic inflammatory disorders. The association of probiotics with prebiotics has the potential to remedy these afflictive conditions, because they attenuate or even block the adhesion of pathogenic microorganisms in the enteric environment. This article highlights the importance of using probiotics associated with fibers from Psyllium as prebiotics to maintain a healthy intestinal microbiota. We also present the technologies and encapsulating materials involved in coating to increase the survival rate of these strains when exposed to the gastrointestinal tract. The importance of products containing probiotics and fibers from Psyllium as prebiotics becomes increasingly evident when there is a health bias. Emerging health challenges and advances in research will drive selective approaches in biotechnology to discover and evaluate new probiotics and prebiotics that can potentially contribute to human health.


Asunto(s)
Microbioma Gastrointestinal , Probióticos , Psyllium , Humanos , Prebióticos , Probióticos/farmacología , Tracto Gastrointestinal/metabolismo
11.
Int J Mol Sci ; 23(6)2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35328335

RESUMEN

Luteolin is one of the most common flavonoids present in edible plants and its potential benefits to the central nervous system include decrease of microglia activation, neuronal damage and high antioxidant properties. The aim of this research was to evaluate the neuroprotective, antioxidant and anti-inflammatory activities of luteolin-7-O-glucoside (Lut7). Undifferentiated and retinoic acid (RA)-differentiated SH-SY5Y cells were pretreated with Lut7 and incubated with 6-hydroxydopamine (6-OHDA). Cytotoxic and neuroprotective effects were determined by MTT assay. Antioxidant capacity was determined by DPPH, FRAP, and ORAC assays. ROS production, mitochondrial membrane potential (ΔΨm), Caspase-3 activity, acetylcholinesterase inhibition (AChEI) and nuclear damage were also determined in SH-SY5Y cells. TNF-α, IL-6 and IL-10 release were evaluated in LPS-induced RAW264.7 cells by ELISA. In undifferentiated SH-SY5Y cells, Lut7 increased cell viability after 24 h, while in RA-differentiated SH-SY5Y cells, Lut7 increased cell viability after 24 and 48 h. Lut7 showed a high antioxidant activity when compared with synthetic antioxidants. In undifferentiated cells, Lut7 prevented mitochondrial membrane depolarization induced by 6-OHDA treatment, decreased Caspase-3 and AChE activity, and inhibited nuclear condensation and fragmentation. In LPS-stimulated RAW264.7 cells, Lut7 treatment reduced TNF-α levels and increased IL-10 levels after 3 and 24 h, respectively. In summary, the results suggest that Lut7 has neuroprotective effects, thus, further studies should be considered to validate its pharmacological potential in more complex models, aiming the treatment of neurodegenerative diseases.


Asunto(s)
Neuroblastoma , Fármacos Neuroprotectores , Acetilcolinesterasa/metabolismo , Antioxidantes/metabolismo , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Flavonas , Glucósidos , Humanos , Interleucina-10/metabolismo , Lipopolisacáridos/farmacología , Potencial de la Membrana Mitocondrial , Neuroblastoma/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxidopamina/toxicidad , Tretinoina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
12.
Inflammopharmacology ; 30(2): 565-577, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35165808

RESUMEN

Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides. In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.


Asunto(s)
Etanol , Myrtaceae , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Anticoagulantes/farmacología , Lipopolisacáridos , FN-kappa B/metabolismo , Óxido Nítrico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas
13.
Pharmaceuticals (Basel) ; 14(9)2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34577633

RESUMEN

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) affects the central nervous system (CNS), which is shown in a significant number of patients with neurological events. In this study, an updated literature review was carried out regarding neurological disorders in COVID-19. Neurological symptoms are more common in patients with severe infection according to their respiratory status and divided into three categories: (1) CNS manifestations; (2) cranial and peripheral nervous system manifestations; and (3) skeletal muscle injury manifestations. Patients with pre-existing cerebrovascular disease are at a higher risk of admission to the intensive care unit (ICU) and mortality. The neurological manifestations associated with COVID-19 are of great importance, but when life-threatening abnormal vital signs occur in severely ill COVID-19 patients, neurological problems are usually not considered. It is crucial to search for new treatments for brain damage, as well as for alternative therapies that recover the damaged brain and reduce the inflammatory response and its consequences for other organs. In addition, there is a need to diagnose these manifestations as early as possible to limit long-term consequences. Therefore, much research is needed to explain the involvement of SARS-CoV-2 causing these neurological symptoms because scientists know zero about it.

14.
Phytother Res ; 35(10): 5647-5667, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34165846

RESUMEN

There is a trend toward the use of natural substances present in plants and vegetables. In general, foods rich in antioxidants are complex matrices; therefore, understanding its absorption effects is extremely relevant to know its bioactive potential. Thus, this systematic review focused on clinical trials involving plants (or compounds) registered on the National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) with antioxidant properties. Following the reporting guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes studies of interest indexed in the PubMed and ClinicalTrials.gov databases were analyzed. Of the 59 clinical trials found, Allium sativum and Curcuma longa are the plant species with the highest percentage of clinical research. Prevention/attenuation of oxidative stress was one of the main antioxidant mechanisms indicated in the studies. The most tested compounds of the RENISUS plants in clinical trials were curcumin and soy isoflavone. In this review, we selected studies in advanced stages that highlight plants' value in optimizing antioxidant status; however, even with high-quality studies, it is not prudent to overstate the clinical efficacy of these plants.


Asunto(s)
Allium , Curcumina , Plantas Medicinales , Antioxidantes/farmacología , Estrés Oxidativo
15.
Sci Rep ; 11(1): 11998, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099808

RESUMEN

Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.


Asunto(s)
COVID-19/genética , Mutación/genética , SARS-CoV-2/genética , Proteínas Virales/genética , Brasil , Genoma Viral , Genómica , Humanos , SARS-CoV-2/patogenicidad , Índice de Severidad de la Enfermedad
16.
Inflammopharmacology ; 29(3): 595-615, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34046798

RESUMEN

OBJECTIVE: One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed. METHODS: We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy". RESULTS: All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided. CONCLUSIONS: Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.


Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de las Cinasas Janus/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/enzimología , Azetidinas/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Quimioterapia Combinada , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/diagnóstico , Metotrexato/administración & dosificación , Piperidinas/administración & dosificación , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Sulfonamidas/administración & dosificación , Resultado del Tratamiento
17.
Expert Rev Clin Pharmacol ; 14(6): 735-747, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33884948

RESUMEN

INTRODUCTION: The chronic metabolic disorder diabetes mellitus is a fast-growing global problem with huge social, health, and economic consequences, having one of the highest morbidities and mortality rates. Prolonged use of many available medications can produce undesirable side effects. Thus, plants appear as an important source of bioactive resources for the discovery of new treatments for diabetes. AREAS COVERED: In this sense, this systematic review focused on clinical trials involving plants of National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) (or compounds) with antidiabetic properties. We analyzed indexed studies in PubMed following the reporting guidelines of PRISMA. EXPERT OPINION: Of the 51 clinical trials found, Curcuma longa, Glycine max, Zingiber officinale, Punica granatum, Aloe vera, Momordica charantia are the species with the greatest amount of clinical trials and the attenuation of insulin resistance, decreased fasting blood glucose and glycosylated hemoglobin levels are some of the main mechanisms by which these plants exert hypoglycemic effects. Thus, we speculate that the Clinical Pharmacology should explore the field of plant-based compounds that will keep concentrating the attention of researchers, and therefore, we gathered studies in advanced stages that highlight the role of plants in the diabetes therapy.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Plantas Medicinales/química , Glucemia/efectos de los fármacos , Diabetes Mellitus/fisiopatología , Humanos , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Fitoterapia/métodos , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología
18.
Cancers (Basel) ; 13(9)2021 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-33923030

RESUMEN

The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor suppressor or tumor promoter according to cancer and cell type studied. In this review, we outline the current understanding of p38δ roles in each cancer type, to define whether it is possible to delineate new cancer therapies based on small-molecule p38δ inhibitors. We also highlight recent advances made in the design of molecules with potential to inhibit p38 isoforms and discuss structural approaches to guide the search for p38δ inhibitors.

19.
Int J Mol Sci ; 22(7)2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33918172

RESUMEN

Current treatments for neurodegenerative diseases (ND) are symptomatic and do not affect disease progression. Slowing this progression remains a crucial unmet need for patients and their families. c-Jun N-terminal kinase 3 (JNK3) are related to several ND hallmarks including apoptosis, oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. JNK inhibitors can play an important role in addressing neuroprotection. This research aims to evaluate the neuroprotective, anti-inflammatory, and antioxidant effects of a synthetic compound (FMU200) with known JNK3 inhibitory activity in SH-SY5Y and RAW264.7 cell lines. SH-SY5Y cells were pretreated with FMU200 and cell damage was induced by 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2). Cell viability and neuroprotective effect were assessed with an MTT assay. Flow cytometric analysis was performed to evaluate cell apoptosis. The H2O2-induced reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) were evaluated by DCFDA and JC-1 assays, respectively. The anti-inflammatory effect was determined in LPS-induced RAW264.7 cells by ELISA assay. In undifferentiated SH-SY5Y cells, FMU200 decreased neurotoxicity induced by 6-OHDA in approximately 20%. In RA-differentiated cells, FMU200 diminished cell death in approximately 40% and 90% after 24 and 48 h treatment, respectively. FMU200 reduced both early and late apoptotic cells, decreased ROS levels, restored mitochondrial membrane potential, and downregulated JNK phosphorylation after H2O2 exposure. In LPS-stimulated RAW264.7 cells, FMU200 reduced TNF-α levels after a 3 h treatment. FMU200 protects neuroblastoma SH-SY5Y cells against 6-OHDA- and H2O2-induced apoptosis, which may result from suppressing the JNK pathways. Our findings show that FMU200 can be a useful candidate for the treatment of neurodegenerative disorders.


Asunto(s)
Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteína Quinasa 10 Activada por Mitógenos/antagonistas & inhibidores , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Humanos , Ratones , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7
20.
Molecules ; 26(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806445

RESUMEN

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Diterpenos/farmacología , Fibroblastos/efectos de los fármacos , Rhodophyta/química , Animales , Antineoplásicos/química , Neoplasias de la Mama/patología , Proliferación Celular , Células Cultivadas , Daño del ADN , Diterpenos/química , Femenino , Humanos , Peróxido de Hidrógeno/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones
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