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1.
Braz. j. biol ; 84: e253084, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345551

RESUMO

Abstract Repeatedly frying process of dietary edible oil has a potential role in the generation of free radicals. Therefore, questions have always been raised as to whether, there is an efficient and economical method to reduce the harmful effects of repeated use of frying edible oil. Since hibiscus has been stated to have a wide variety of therapeutic effects, it was important to investigate its properties against harmful effects of free radicals. The current study aspires to find out whether irradiated powder of hibiscus has a protective role against adverse effects of repeated use of frying edible oil. Thirty-five adult male albino rats were equally assigned into five groups. First group"G1" was fed with normal diet as control group, meanwhile, group"G2" the diet mixed with fresh oil, "G3" diet mixed with repeatedly frying oil only, "G4" diet mixed with frying oil treated with hibiscus and "G5" diet mixed with frying oil treated with irradiated hibiscus. Feeding duration was six weeks. Fatty acid analyses of oil as well as peroxide values were determined. Blood and liver samples were collected for biochemical analyses as well as histological study. Repeatedly heated cooked oil has significant increases in peroxide value, acid value, free fatty acid and both conjugated diene and triene compared with repeatedly frying oil treated with hibiscus. Also there are significant increases in cholesterol and triglyceride and impaired in liver functions in "G3"compared with others. In addition, relative to the hibiscus groups, there is a substantial reduction in oxygen consumption in "G3". Both hibiscus as well as irradiated hibiscus attract attention in order to play a vital and economical role against harmful effects of frequent use of frying edible oil on some biological functions but, irradiated hibiscus was more effective.


Resumo O processo de fritura repetida de óleo comestível da dieta tem papel potencial na geração de radicais livres que podem ter efeitos prejudiciais em algumas funções biológicas. Portanto, sempre se questionou se existe uma maneira eficiente e econômica de prevenir ou pelo menos reduzir os efeitos nocivos do uso repetido de óleo comestível para fritar. Como o hibisco tem ampla variedade de efeitos terapêuticos, foi importante investigar suas propriedades como agente antioxidante contra os efeitos nocivos dos radicais livres. O presente estudo pretende descobrir se o pó irradiado de hibisco tem papel protetor contra os efeitos adversos do uso repetido de óleo comestível para fritar. Trinta e cinco ratos albinos machos adultos foram divididos igualmente em cinco grupos. O primeiro grupo "G1" foi alimentado com dieta normal como grupo controle, enquanto o grupo "G2" dieta misturada com óleo fresco, dieta "G3" misturada com óleo de fritura repetida, dieta "G4" misturada com óleo de fritura tratada com hibisco e dieta "G5" misturada com óleo de fritura tratada com hibisco irradiado. A duração da alimentação foi de seis semanas. Foram determinadas as análises de ácidos graxos de óleo, bem como os valores de peróxidos. Amostras de sangue e fígado foram coletadas para análises bioquímicas e estudo histológico. O óleo cozido repetidamente aquecido tem aumentos significativos no valor de peróxido, valor de ácido, ácido graxo livre e dieno e trieno conjugados em comparação com óleo de fritura repetidamente tratado com hibisco. Também há aumentos significativos no colesterol e triglicérides e comprometimento das funções hepáticas no "G3" em comparação com outros. Além disso, em relação aos grupos de hibiscos, há uma redução substancial no consumo de oxigênio no "G3". Tanto o hibisco como o hibisco irradiado chamam atenção por desempenhar papel vital e econômico contra os efeitos nocivos do uso frequente de óleo comestível para fritar em algumas funções biológicas, mas o hibisco irradiado foi mais eficaz.


Assuntos
Animais , Ratos , Hibiscus , Óleos Vegetais/farmacologia , Colesterol , Culinária , Temperatura Alta
2.
Braz. j. biol ; 84: e253696, 2024. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355862

RESUMO

Abstract Transplanting time and genotype contribute to improving crop yield and quality of eggplant (Solanum melongena L.). A field experiment was conducted to investigate the impact of foliar applied of triacontanol (TRIA) and eggplant genotypes 25919, Nirala, 28389 and Pak-10927,transplanted on 1 March,15 March, and 1 April on exposure to high air temperature conditions. The experiment was performed according to Randomized Complete Block Design and the data was analyzed by using Tuckey,s test . The TRIA was applied at 10µM at flowering stage; distilled water was used as the control. Rate of photosynthesis and transpiration, stomatal conductance, water use efficiency, and effects on antioxidative enzymes (superoxide dismutase, catalase and peroxidase) were evaluated. The 10µM TRIA increased photosynthesis rate and water use efficiency and yield was improved in all genotypes transplanted at the different dates. Foliar application of 10µM TRIA increased antioxidative enzyme activities (SOD, POD & CAT) and improved physiological as well as biochemical attributes of eggplant genotypes exposed to high heat conditions. Highest activity of dismutase enzyme 5.41mg/1g FW was recorded in Nirala genotype in second transplantation. Whereas, lowest was noted in PAK-10927 (2.30mg/g FW). Maximum fruit yield was found in accession 25919 (1.725kg per plant) at 1st transplantation with Triacontanol, whereas accession PAK-10927 gave the lowest yield (0.285 kg per plant) at control treatment on 3rd transplantation. Genotype, transplanting date and application of TRIA improved growth, yield and quality attributes under of heat stress in eggplant.


Resumo O tempo de transplante e o genótipo contribuem para melhorar a produtividade e a qualidade da cultura da berinjela (Solanum melongena L.). Um experimento de campo foi conduzido para investigar o impacto da aplicação foliar de triacontanol (TRIA) e genótipos de berinjela 25919, Nirala, 28389 e Pak-10927, transplantados em 1 de março, 15 de março e 1 de abril de exposição a condições de alta temperatura do ar. O experimento foi realizado de acordo com o Randomized Complete Block Design e os dados foram analisados pelo teste de Tuckey. O TRIA foi aplicado a 10 µM na fase de floração; água destilada foi utilizada como controle. Taxa de fotossíntese e transpiração, condutância estomática, eficiência do uso da água e efeitos sobre as enzimas antioxidantes (superóxido dismutase, catalase e peroxidase) foram avaliados. O TRIA 10 µM aumentou a taxa de fotossíntese e a eficiência do uso da água e o rendimento foi melhorado em todos os genótipos transplantados nas diferentes datas. A aplicação foliar de TRIA 10µM aumentou as atividades das enzimas antioxidantes (SOD, POD e CAT) e melhorou os atributos fisiológicos e bioquímicos de genótipos de berinjela expostos a condições de alto calor. A atividade mais elevada da enzima dismutase 5,41mg / 1g FW foi registrada no genótipo Nirala no segundo transplante. Considerando que o mais baixo foi observado em PAK-10927 (2,30 mg / g FW). A produtividade máxima de frutos foi encontrada no acesso 25919 (1,725 ​​kg por planta) no 1º transplante com Triacontanol, enquanto o acesso PAK-10927 deu a menor produção (0,285 kg por planta) no tratamento de controle no 3º transplante. Genótipo, data de transplante e aplicação de TRIA, melhoramento do crescimento, rendimento e atributos de qualidade sob estresse térmico em berinjela.


Assuntos
Solanum melongena/genética , Solanum melongena/metabolismo , Fotossíntese , Resposta ao Choque Térmico , Álcoois Graxos , Antioxidantes/metabolismo , Antioxidantes/farmacologia
3.
Braz. j. biol ; 84: e253616, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355880

RESUMO

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.


Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.


Assuntos
Animais , Ratos , Óleos Voláteis/farmacologia , Colágeno/metabolismo , Alpinia/química , Caveolina 1/metabolismo , Músculos/efeitos dos fármacos , Fibrose , Óleos Vegetais/farmacologia , Brasil , Ratos Wistar , Modelos Animais de Doenças , Músculos/patologia
4.
Braz. j. biol ; 84: e254479, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355910

RESUMO

Abstract Earias vittellaFabricius, 1794 (Noctuidae: Lepidoptera) is deliberated to be one of the most destructive pests of cotton and okra vegetation in the world including Asia. The pest has established resistance to various synthetic insecticides. The use of bio-pesticide is one of the unconventional approaches to develop a vigorous ecosystem without harming non- target pests and beneficial natural insect fauna. In the present study, the toxicity levels of Citrullus colocynthis seed extract have been evaluated against the populations of E. vittellaunder standardized laboratory conditions. The toxic effects of C. colocynthis on development periods, protein contents and esterase activity of the life stages of E. vittella were also evaluated. The toxicity levels of methanol, ethanol, hexane, water and profenofos were evaluated on the 1st instar larvae of E. vittella. LC30 and LC80 concentrations exhibited the effectiveness of methanol-based C. colocynthis seed extract against 1st instar larvae of E. vitella. The enhanced larval and pupal periods were revealed in treated samples during the comparison with untreated samples. The intrinsic rate of increase, net reproductive rate in the LC30 and LC80 concentrations exposed larvae remained less than the control treatment. Fecundity, the esterase activity and protein contents were declined in LC30 and LC80 treated samples as compared to the control. The present findings suggest that C. colosynthis extracts based botanical insecticides are beneficial, ecosystem sustainable and can be integrated with insect management programs from environment safety perspective.


Resumo Earias vittella Fabricius, 1794 (Noctuidae: Lepidoptera) é considerada uma das pragas mais destrutivas de algodão e quiabo no mundo, incluindo a Ásia. Essa praga estabeleceu resistência a vários inseticidas sintéticos. O uso de biopesticidas é uma das abordagens não convencionais para desenvolver um ecossistema saudável sem prejudicar as pragas não alvo e a fauna natural benéfica de insetos. No presente estudo, os níveis de toxicidade do extrato de semente de Citrullus colocynthis foram avaliados nas populações de E. vittella em condições de laboratório padronizadas. Os efeitos tóxicos de C. colocynthis nos períodos de desenvolvimento, conteúdo de proteína e atividade esterase das fases de vida de E. vittella também foram avaliados. Os níveis de toxicidade de metanol, etanol, hexano, água e profenofós foram avaliados em larvas de 1º instar de E. vittella. As concentrações de LC30 e LC80 apresentaram eficácia do extrato de sementes de C. colocynthis à base de metanol contra larvas de 1º instar de E. vittella. Os períodos larval e pupal aumentados foram revelados nas amostras tratadas durante a comparação com as amostras não tratadas. A taxa intrínseca de aumento e a taxa reprodutiva líquida nas concentrações de larvas expostas LC30 e LC80 permaneceram menores do que o tratamento controle. A fecundidade, a atividade da esterase e o conteúdo de proteína diminuíram nas amostras tratadas com LC30 e LC80 em comparação com o controle. As presentes descobertas sugerem que os extratos de C. colocynthis à base de inseticidas botânicos são benéficos, sustentáveis ​​para o ecossistema e podem ser integrados com programas de manejo de insetos do ponto de vista da segurança ambiental.


Assuntos
Animais , Citrullus colocynthis , Inseticidas , Mariposas , Extratos Vegetais/farmacologia , Ecossistema , Larva
5.
Sci Rep ; 13(1): 98, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596856

RESUMO

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.


Assuntos
Neoplasias Ovarianas , Vacinas , Animais , Camundongos , Humanos , Feminino , Células-Tronco Hematopoéticas , Interleucina-12/metabolismo , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/metabolismo , Células Dendríticas , Vacinas/farmacologia , Camundongos Endogâmicos C57BL
6.
Sci Rep ; 13(1): 101, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596838

RESUMO

Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1's role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure. Moreover, PA-mediated downregulation of PDX-1, MafA, and insulin expression was attenuated by tranilast. PA-induced oxidative and ER stress were also reduced in the presence of tranilast. These protective effects were accompanied by increased phosphorylation and decreased nuclear translocation of FoxO-1. Conversely, the effects of tranilast were diminished when treated in transfected cells with FoxO-1 phosphorylation mutant (S256A), suggesting that the tranilast-mediated effects are associated with inactivation of FoxO-1. Examination of the in vivo effects of tranilast using wild type and diabetic db/db mice showed improved glucose tolerance along with FoxO-1 inactivation in the pancreas of the tranilast-treated groups. Thus, we report here that tranilast has protective effects against PA-induced lipotoxic stress in INS-1 cells, at least partly, via FoxO-1 inactivation, which results in improved glucose tolerance in vivo.


Assuntos
Células Secretoras de Insulina , Ácido Palmítico , Camundongos , Animais , Ácido Palmítico/farmacologia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Apoptose , Glucose/metabolismo
7.
Trials ; 24(1): 4, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597128

RESUMO

BACKGROUND: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells. METHODS: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion. RESULTS: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination. CONCLUSIONS: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated. TRIAL REGISTRATION: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Linfoma não Hodgkin , Adulto , Humanos , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/efeitos adversos , Citocinas , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Linfócitos T
8.
PLoS One ; 18(1): e0280023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598909

RESUMO

BACKGROUND: Cytokine-induced killer (CIK) cells are heterogeneous lymphocytes from human peripheral blood mononucleated cells (PBMCs) co-cultured with several cytokines. The main purpose of this study is to evaluate the functional characteristics and anticancer ability of CIK cells from hepatocarcinoma (HCC) patients. METHODS: CIK cells were activated ex-vivo and expanded from PBMCs from HCC patients. The immunophenotype and the ex-vivo killing ability of CIK cells were evaluated. Human CIK cells were intravenously injected into NOD/SCID mice to evaluate the in vivo anticancer ability. RESULTS: More than 70% of CIK cells were CD3+CD8+, and 15%-30% were CD3+CD56+. These cells expressed an increased number of activated natural killer (NK) receptors, such as DNAM1 and NKG2D, and expressed low-immune checkpoint molecules, including PD-1, CTLA-4, and LAG-3. Among the chemokine receptors expressed by CIKs, CXCR3 and CD62L were elevated in CD8+ T cells, representing the trafficking ability to inflamed tumor sites. CIK cells possess the ex-vivo anticancer activity to different cell lines. To demonstrate in vivo antitumor ability, human CIK cells could significantly suppress the tumor of J7 bearing NOD/SCID mice. Furthermore, human immune cells could be detected in the peripheral blood and on the tumors after CIK injection. CONCLUSIONS: This study revealed that CIK cells from HCC patients possess cytotoxic properties, and express increased levels of effector NK receptors and chemokine molecules and lower levels of suppressive checkpoint receptors. CIK cells can suppress human HCC ex-vivo and in vivo. Future clinical trials of human CIK cell therapy for HCC are warranted.


Assuntos
Carcinoma Hepatocelular , Células Matadoras Induzidas por Citocinas , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/patologia , Células Matadoras Induzidas por Citocinas/patologia , Neoplasias Hepáticas/patologia , Camundongos SCID , Camundongos Endogâmicos NOD , Citocinas/farmacologia , Citotoxicidade Imunológica
9.
PLoS One ; 18(1): e0280112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598916

RESUMO

Ischemic stroke (IS) is one of the major global causes of death and disability. Because blood clots block the neural arteries provoking ischemia and hypoxia in the brain tissue, IS results in irreversible neurological damage. Available IS treatments are currently limited. Curcumin has gained attention for many beneficial effects after IS, including neuroprotective and anti-inflammatory; however, its precise mechanism of action should be further explored. With network pharmacology, molecular docking, and molecular dynamics (MD), this study aimed to comprehensively and systematically investigate the potential targets and molecular mechanisms of curcumin on IS. We screened 1096 IS-related genes, 234 potential targets of curcumin, and 97 intersection targets. KEGG and GO enrichment analyses were performed on these intersecting targets. The findings showed that the treatment of IS using curcumin is via influencing 177 potential signaling pathways (AGE-RAGE signaling pathway, p53 signaling pathway, necroptosis, etc.) and numerous biological processes (the regulation of neuronal death, inflammatory response, etc.), and the AGE-RAGE signaling pathway had the largest degree of enrichment, indicating that it may be the core pathway. We also constructed a protein-protein interaction network and a component-target-pathway network using network pharmacology. From these, five key targets were screened: NFKB1, TP53, AKT1, STAT3, and TNF. To predict the binding conformation and intermolecular affinities of the key targets and compounds, molecular docking was used, whose results indicated that curcumin exhibited strong binding activity to the key targets. Moreover, 100 ns MD simulations further confirmed the docking findings and showed that the curcumin-protein complex could be in a stable state. In conclusion, curcumin affects multiple targets and pathways to inhibit various important pathogenic mechanisms of IS, including oxidative stress, neuronal death, and inflammatory responses. This study offers fresh perspectives on the transformation of curcumin to clinical settings and the development of IS therapeutic agents.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , AVC Isquêmico , Humanos , Farmacologia em Rede , Curcumina/farmacologia , Curcumina/uso terapêutico , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
10.
RMD Open ; 9(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36599629

RESUMO

OBJECTIVES: Macrophage subsets, activated by T cells, are increasingly recognised to play a central role in rheumatoid arthritis (RA) pathogenesis. Janus kinase (JAK) inhibitors have proven beneficial clinical effects in RA. In this study, we investigated the effect of JAK inhibitors on the generation of cytokine-activated T (Tck) cells and the production of cytokines and chemokines induced by Tck cell/macrophage interactions. METHODS: CD14+ monocytes and CD4+ T cells were purified from peripheral blood mononuclear cells from buffy coats of healthy donors. As representative JAK inhibitors, tofacitinib or ruxolitinib were added during Tck cell differentiation. Previously validated protocols were used to generate macrophages and Tck cells from monocytes and CD4+ T cells, respectively. Cytokine and chemokine including TNF, IL-6, IL-15, IL-RA, IL-10, MIP1α, MIP1ß and IP10 were measured by ELISA. RESULTS: JAK inhibitors prevented cytokine-induced maturation of Tck cells and decreased the production of proinflammatory cytokines TNF, IL-6, IL-15, IL-1RA and the chemokines IL-10, MIP1α, MIP1ß, IP10 by Tck cell-activated macrophages in vitro (p<0.05). CONCLUSIONS: Our findings show that JAK inhibition disrupts T cell-induced macrophage activation and reduces downstream proinflammatory cytokine and chemokine responses, suggesting that suppressing the T cell-macrophage interaction contributes to the therapeutic effect of JAK inhibitors.


Assuntos
Artrite Reumatoide , Inibidores de Janus Quinases , Humanos , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Membrana Sinovial/patologia , Interleucina-15/farmacologia , Interleucina-15/uso terapêutico , Interleucina-6 , Leucócitos Mononucleares/patologia , Ativação de Macrófagos , Quimiocina CXCL10/farmacologia , Quimiocina CXCL10/uso terapêutico , Macrófagos , Artrite Reumatoide/tratamento farmacológico , Citocinas , Linfócitos T
11.
Drug Deliv ; 30(1): 2162158, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36587626

RESUMO

Genistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon®90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, in vitro dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon®90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon®90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon®90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.


Assuntos
Produtos Biológicos , Genisteína , Genisteína/farmacologia , Genisteína/química , Disponibilidade Biológica , Solubilidade , Anti-Inflamatórios/farmacologia , Administração Oral , Tamanho da Partícula , Varredura Diferencial de Calorimetria
12.
Drug Deliv ; 30(1): 2162157, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36587813

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of -39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 µg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Células CACO-2 , Resveratrol/farmacologia , Antivirais/farmacologia , RNA Viral , Polietilenoglicóis , Permeabilidade , Tamanho da Partícula
13.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678315

RESUMO

Disrupted biological function, manifesting through the hallmarks of aging, poses one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease in nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds, to restore NAD+ levels present in youth. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through the inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NAD+ precursor supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.


Assuntos
NAD , Sirtuína 1 , Humanos , Adolescente , NAD/metabolismo , Senoterapia , Niacinamida/farmacologia , Niacinamida/metabolismo , Mononucleotídeo de Nicotinamida , Nucleotídeos , Suplementos Nutricionais
14.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678320

RESUMO

Essential oils (EO) are promising feed additives for their antibacterial, antioxidant, and immune-enhancing abilities with low toxicity. Carvacrol, thymol, and cinnamaldehyde are commonly used to synthesize EO. However, few studies focus on combining these three EO in early-weaned piglets. In the present study, 24 piglets weaned at 21 d of age were randomly divided into 2 groups (6 replicate pens per group, 2 piglets per pen). The piglets were fed a basal diet (the control group) and a basal diet supplemented with 400 mg/kg EO (a blend consisting of carvacrol, thymol, and cinnamaldehyde, the EO group) for 28 days. At the end of the experiment, one piglet per pen was randomly chosen to be sacrificed. Growth performance, hematology, plasma biochemical indices, antioxidant capacity, intestinal epithelial development and immunity, colonic volatile fatty acids (VFA), and microbiota were determined. The results indicated that the diet supplemented with EO significantly improved average daily feed intake (ADFI, p < 0.01) and average daily gain (ADG, p < 0.05) in the day 0 to 28 period. EO supplementation led to a significant decrease in plasma lysozyme (p < 0.05) and cortisol levels (p < 0.01). Additionally, EO significantly promoted jejunal goblet cells in the villus, jejunal mucosa ZO-1 mRNA expression, ileal villus height, and ileal villus height/crypt depth ratio in piglets (p < 0.05). The ileal mucosal TLR4 and NFκB p-p65/p65 protein expression were significantly inhibited in the EO group (p < 0.05). Colonic digesta microbiota analysis revealed that bacteria involving the Erysipelotrichaceae family, Holdemanella genus, Phascolarctobacterium genus, and Vibrio genus were enriched in the EO group. In conclusion, these findings indicate that the EO blend improves ADG and ADFI in the day 0 to 28 period, as well as intestinal epithelial development and intestinal immunity in early-weaned piglets, which provides a theoretical basis for the combined use of EO in weaned piglets.


Assuntos
Microbiota , Óleos Voláteis , Animais , Suínos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Óleos Voláteis/farmacologia , Timol/farmacologia , Suplementos Nutricionais
15.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678322

RESUMO

Neurodegenerative diseases are known for their wide range of harmful conditions related to progressive cell damage, nervous system connections and neuronal death. These pathologies promote the loss of essential motor and cognitive functions, such as mobility, learning and sensation. Neurodegeneration affects millions of people worldwide, and no integral cure has been created yet. Here, bioactive compounds have been proven to exert numerous beneficial effects due to their remarkable bioactivity, so they could be considered as great options for the development of new neuroprotective strategies. Phenolic bioactives have been reported to be found in edible part of plants; however, over the last years, a large amount of research has focused on the phenolic richness that plant by-products possess, which sometimes even exceeds the content in the pulp. Thus, their possible application as an emergent neuroprotective technique could also be considered as an optimal strategy to revalorize these agricultural residues (those originated from plant processing). This review aims to summarize main triggers of neurodegeneration, revise the state of the art in plant extracts and their role in avoiding neurodegeneration and discuss how their main phenolic compounds could exert their neuroprotective effects. For this purpose, a diverse search of studies has been conducted, gathering a large number of papers where by-products were used as strong sources of phenolic compounds for their neuroprotective properties. Finally, although a lack of investigation is quite remarkable and greatly limits the use of these compounds, phenolics remain attractive for research into new multifactorial anti-neurodegenerative nutraceuticals.


Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fenóis/farmacologia , Fenóis/química , Antioxidantes/farmacologia , Antioxidantes/química , Doenças Neurodegenerativas/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Plantas/química
16.
Nutrients ; 15(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36678330

RESUMO

BACKGROUND: Oxidative stress and impaired autophagy are directly and indirectly implicated in exercise-mediated muscle injury. Trehalose, spermidine, nicotinamide, and polyphenols possess pro-autophagic and antioxidant properties, and could therefore reduce exercise-induced damage to skeletal muscle. The aim of this study was to investigate whether a mixture of these compounds was able to improve muscle injury biomarkers in endurance athletes through the modulation of oxidative stress and autophagic machinery. METHODS AND RESULTS: sNOX2-dp; H2O2 production; H2O2 breakdown activity (HBA); ATG5 and p62 levels, both markers of autophagic process; and muscle injury biomarkers were evaluated in five endurance athletes who were allocated in a crossover design study to daily administration of 10.5 g of an experimental mixture or no treatment, with evaluations conducted at baseline and after 30 days of mixture consumption. Compared to baseline, the mixture intake led to a remarkable reduction of oxidative stress and positively modulated autophagy. Finally, after the 30-day supplementation period, a significant decrease in muscle injury biomarkers was found. CONCLUSION: Supplementation with this mixture positively affected redox state and autophagy and improved muscle injury biomarkers in athletes, allowing for better muscle recovery. Moreover, it is speculated that this mixture could also benefit patients suffering from muscle injuries, such as cancer or cardiovascular patients, or elderly subjects.


Assuntos
Peróxido de Hidrogênio , Estresse Oxidativo , Humanos , Idoso , Projetos Piloto , Antioxidantes/farmacologia , Atletas , Músculo Esquelético , Biomarcadores , Autofagia
17.
Nutrients ; 15(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36678328

RESUMO

Hypertension (HTN) is the leading cause of premature deaths worldwide and the main preventable risk factor for cardiovascular diseases. Therefore, there is a current need for new therapeutics to manage this condition. In this regard, protein hydrolysates containing antihypertensive bioactive peptides are of increasing interest. Thus, agri-food industry byproducts have emerged as a valuable source to obtain these hydrolysates as they are rich in proteins and inexpensive. Among these, byproducts from animal origin stand out as they are abundantly generated worldwide. Hence, this review is focused on evaluating the potential role of chicken slaughterhouse byproducts as a source of peptides for managing HTN. Several of these byproducts such as blood, bones, skins, and especially, chicken feet have been used to obtain protein hydrolysates with angiotensin-converting enzyme (ACE)-inhibitory activity and blood pressure-lowering effects. An increase in levels of endogenous antioxidant compounds, a reduction in ACE activity, and an improvement of HTN-associated endothelial dysfunction were the mechanisms underlying their effects. However, most of these studies were carried out in animal models, and further clinical studies are needed in order to confirm these antihypertensive properties. This would increase the value of these byproducts, contributing to the circular economy model of slaughterhouses.


Assuntos
Anti-Hipertensivos , Hipertensão , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Galinhas/metabolismo , Matadouros , Hidrolisados de Proteína/farmacologia , Peptídeos/farmacologia , Hipertensão/tratamento farmacológico
18.
Nutrients ; 15(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36678327

RESUMO

Efforts to decrease the deleterious effects of renal ischemia-reperfusion injury (IRI) are ongoing. Recently, there has been increasing interest in using natural phytochemical compounds as alternative remedies in several diseases. Nerolidol is a natural product extracted from plants with floral odors and has been proven to be effective for the treatment of some conditions. We investigated the effect of nerolidol in a rat model of renal IRI. Nerolidol was dissolved in a vehicle and administered orally as single daily dose of 200 mg/kg for 5 days prior to IRI and continued for 3 days post IRI. G-Sham (n = 10) underwent sham surgery, whereas G-IRI (n = 10) and G-IRI/NR (n = 10) underwent bilateral warm renal ischemia for 30 min and received the vehicle/nerolidol, respectively. Renal functions and histological changes were assessed before starting the medication, just prior to IRI and 3 days after IRI. Nerolidol significantly attenuated the alterations in serum creatinine and urea, creatinine clearance, urinary albumin and the urinary albumin-creatinine ratio. Nerolidol also significantly attenuated the alterations in markers of kidney injury; proinflammatory, profibrotic and apoptotic cytokines; oxidative stress markers; and histological changes. We conclude that nerolidol has a renoprotective effect on IRI-induced renal dysfunction. These findings might have clinical implications.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Ratos , Animais , Injúria Renal Aguda/patologia , Creatinina , Rim , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Albuminas/farmacologia
19.
Nutrients ; 15(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36678340

RESUMO

We studied the activities of Siraitia grosvenorii extracts (SGE) on airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), as well as in LPS-treated human bronchial epithelial cell line (BEAS-2B). SGE improved the viability of LPS-incubated BEAS-2B cells and inhibited the expression and production of inflammatory cytokines. SGE also attenuated the mitogen-activated protein kinase (MAPK)-nuclear factor-kappa B (NF-κB) signaling activated by LPS stimulation in BEAS-2B cells. In mice stimulated by CSE and LPS, we observed the infiltration of immune cells into the airway after COPD induction. SGE reduced the number of activated T cells, B cells, and neutrophils in bronchoalveolar fluid (BALF), lung tissue, mesenteric lymph node, and peripheral blood mononuclear cells, as well as inhibited infiltration into organs and mucus production. The secretion of cytokines in BALF and the expression level of pro-inflammatory cytokines, mucin 5AC, Transient receptor potential vanilloid 1, and Transient receptor potential ankyrin 1 in lung tissue were alleviated by SGE. In addition, to investigate the activity of SGE on expectoration, we evaluated phenol red secretions in the trachea of mice. SGE administration showed the effect of improving expectoration through an increase in phenol red secretion. Consequently, SGE attenuates the airway inflammatory response in CSE/LPS-stimulated COPD. These findings indicate that SGE may be a potential herbal candidate for the therapy of COPD.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Camundongos , Humanos , Animais , Lipopolissacarídeos/farmacologia , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Leucócitos Mononucleares/metabolismo , Fenolsulfonaftaleína/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pulmão/patologia , Inflamação/metabolismo , Citocinas/metabolismo , Tabaco
20.
Sensors (Basel) ; 23(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36679772

RESUMO

This review summarizes the literature data reported from 2000 up to the present on the development of various electrochemical (voltammetric, amperometric, potentiometric and photoelectrochemical), optical (UV-Vis and IR) and luminescence (chemiluminescence and fluorescence) methods and the corresponding sensors for rifamycin antibiotics analysis. The discussion is focused mainly on the foremost compound of this class of macrocyclic drugs, namely rifampicin (RIF), which is a first-line antituberculosis agent derived from rifampicin SV (RSV). RIF and RSV also have excellent therapeutic action in the treatment of other bacterial infectious diseases. Due to the side-effects (e.g., prevalence of drug-resistant bacteria, hepatotoxicity) of long-term RIF intake, drug monitoring in patients is of real importance in establishing the optimum RIF dose, and therefore, reliable, rapid and simple methods of analysis are required. Based on the studies published on this topic in the last two decades, the sensing principles, some examples of sensors preparation procedures, as well as the performance characteristics (linear range, limits of detection and quantification) of analytical methods for RIF determination, are compared and correlated, critically emphasizing their benefits and limitations. Examples of spectrometric and electrochemical investigations of RIF interaction with biologically important molecules are also presented.


Assuntos
Mycobacterium tuberculosis , Rifamicinas , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Rifamicinas/farmacologia , Antituberculosos
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