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1.
Arch Microbiol ; 206(6): 251, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727840

RESUMO

The prevalence of Candida albicans infection has increased during the past few years, which contributes to the need for new, effective treatments due to the increasing concerns regarding antifungal drug toxicity and multidrug resistance. Butyl isothiocyanate (butylITC) is a glucosinolate derivative, and has shown a significant antifungal effect contrary to Candida albicans. Additionally, how butylITC affects the virulence traits of C. albicans and molecular mode of actions are not well known. Present study shows that at 17.36 mM concentration butylITC inhibit planktonic growth. butylITC initially slowed the hyphal transition at 0.542 mM concentration. butylITC hampered biofilm development, and inhibits biofilm formation at 17.36 mM concentration which was analysed using metabolic assay (XTT assay) and Scanning Electron Microscopy (SEM). In addition, it was noted that butylITC inhibits ergosterol biosynthesis. The permeability of cell membranes was enhanced by butylITC treatment. Moreover, butylITC arrests cells at S-phase and induces intracellular Reactive Oxygen Species (ROS) accumulation in C. albicans. The results suggest that butylITC may have a dual mode of action, inhibit virulence factors and modulate cellular processes like inhibit ergosterol biosynthesis, cell cycle arrest, induces ROS production which leads to cell death in C. albicans.


Assuntos
Antifúngicos , Biofilmes , Candida albicans , Membrana Celular , Isotiocianatos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Biofilmes/efeitos dos fármacos , Antifúngicos/farmacologia , Isotiocianatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Sensibilidade Microbiana , Ciclo Celular/efeitos dos fármacos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Ergosterol/metabolismo
2.
Sci Rep ; 14(1): 10032, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693156

RESUMO

The primary objective of the present study was to produce metal complexes of H4DAP ligand (N,N'-((pyridine-2,6-diylbis(azanediyl))bis(carbonothioyl))dibenzamide) derived from 2,6-diaminopyridine and benzoyl isothiocyanate with either ML or M2L stoichiometry. There are three distinct coordination complexes obtained with the formulas [Co(H2DAP)]·H2O, [Ni2(H2DAP)Cl2(H2O)2]·H2O, and [Cu(H4DAP)Cl2]·3H2O. The confirmation of the structures of all derivatives was achieved through the utilization of several analytical techniques, including FT-IR, UV-Vis, NMR, GC-MS, PXRD, SEM, TEM analysis, and QM calculations. Aiming to analyze various noncovalent interactions, topological methods such as QTAIM, NCI, ELF, and LOL were performed. Furthermore, the capacity of metal-ligand binding was examined by fluorescence emission spectroscopy. An in vitro investigation showed that the viability of MDA-MB-231 and HepG-2 cells was lower when exposed to the manufactured Cu2+ complex, in comparison to the normal cis-platin medication. The compounds were further evaluated for their in vitro antibacterial activity. The Ni2+ complex has shown promising activity against all tested pathogens, comparable to the reference drugs Gentamycin and Ketoconazole. Furthermore, a computational docking investigation was conducted to further examine the orientation, interaction, and conformation of the recently created compounds on the active site of the Bcl-2 protein.


Assuntos
Cobalto , Complexos de Coordenação , Cobre , Isotiocianatos , Simulação de Acoplamento Molecular , Níquel , Níquel/química , Cobre/química , Humanos , Isotiocianatos/química , Isotiocianatos/farmacologia , Ligantes , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Cobalto/química , Linhagem Celular Tumoral , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química
3.
Food Funct ; 15(9): 4894-4904, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38597802

RESUMO

The contributions of cruciferous vegetables to human health are widely recognised, particularly at the molecular level, where their isothiocyanates play a significant role. However, compared to the well-studied isothiocyanate 4-(methylsulfinyl)butyl isothiocyanate (sulforaphane) produced from broccoli sprouts, less is known about the pharmacological effects of other isothiocyanates and the stage of vegetables preferable to obtain their benefits. We analysed the quantity and quality of isothiocyanates produced in both the sprouts and mature stages of eight cruciferous vegetables using gas chromatography-mass spectrometry (GC-MS). Additionally, we investigated the hepatoprotective effects of isothiocyanates in a mouse model of acute hepatitis induced by carbon tetrachloride (CCl4). Furthermore, we explored the detoxification enzyme-inducing activities of crude sprout extracts in normal rats. Among the eight cruciferous vegetables, daikon radish (Raphanus sativus L.) sprouts produced the highest amount of isothiocyanates, with 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) being the dominant compound. The amount of sulforaphene in daikon radish sprouts was approximately 30 times that of sulforaphane in broccoli sprouts. Sulforaphene demonstrated hepatoprotective effects similar to sulforaphane in ameliorating CCl4-induced hepatic injury in mice. A crude extract of 3-day-old daikon radish sprouts upregulated the detoxifying enzyme glutathione S-transferase (GST) in the liver, whereas the crude extract of broccoli sprouts showed limited upregulation. This study highlights that daikon radish sprouts and sulforaphene have the potential to serve as functional food materials with hepatoprotective effects. Furthermore, daikon radish sprouts may exhibit more potent hepatoprotective effects compared to broccoli sprouts.


Assuntos
Isotiocianatos , Fígado , Raphanus , Verduras , Isotiocianatos/farmacologia , Animais , Camundongos , Raphanus/química , Masculino , Verduras/química , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Sulfóxidos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Brassica/química , Humanos , Ratos Sprague-Dawley , Brassicaceae/química
4.
Mol Nutr Food Res ; 68(8): e2400063, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38600885

RESUMO

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.


Assuntos
Isotiocianatos , Neoplasias , Isotiocianatos/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , NF-kappa B/metabolismo , Antineoplásicos Fitogênicos/farmacologia
5.
Mol Nutr Food Res ; 68(8): e2400087, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581346

RESUMO

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.


Assuntos
Dieta , Isotiocianatos , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Isotiocianatos/farmacologia , Isotiocianatos/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Prospectivos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Arilamina N-Acetiltransferase/genética , Neoplasias não Músculo Invasivas da Bexiga
6.
Bioconjug Chem ; 35(5): 633-637, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38656148

RESUMO

Zirconium-89 is the most widely used radioisotope for immunoPET because its physical half-life (78.2 h) suits the one of antibodies. Desferrioxamine B (DFO) is the standard chelator for the complexation of zirconium(IV), and its bifunctional version, containing a phenylisothiocyanate function, is the most commonly used for the conjugation of DFO to proteins. However, preliminary results have shown that the thiourea link obtained from the conjugation of isothiocyanate and lysines is sensitive to the ionizing radiation generated by the radioisotope, leading to the rupture of the link and the release of the chelator/radiometal complex. This radiolysis phenomenon could produce nonspecific signal and prevent the detection of bone metastasis, as free zirconium accumulates into the bones. The aim of this work was to study the stability of a selection of conjugation linkers in 89Zr-labeled immunoconjugates. We have synthesized several DFO-based bifunctional chelators appended with an isothiocyanate moiety, a bicyclononyne, or a squaramate ester. Two antibodies (trastuzumab and rituximab) were conjugated and radiolabeled with zirconium-89. The effect of increasing activities of zirconium-89 on the integrity of the bioconjugate bearing thiourea links was evaluated as well as the impact of the presence of a radioprotectant. The stability of the radiolabeled antibodies was studied over 7 days in PBS and human plasma. Radioconjugates' integrity was evaluated using iTLC and size-exclusion chromatography. This study shows that the nature of the linker between the chelator and biomolecule can have a strong impact on the stability of the 89Zr-labeled conjugates, as well as on the aggregation of the conjugates.


Assuntos
Imunoconjugados , Isotiocianatos , Radioisótopos , Zircônio , Zircônio/química , Imunoconjugados/química , Isotiocianatos/química , Radioisótopos/química , Quelantes/química , Humanos , Desferroxamina/química
7.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612571

RESUMO

Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives.


Assuntos
Neoplasias Ósseas , Radioisótopos de Cálcio , Isotiocianatos , Osteossarcoma , Canais de Potencial de Receptor Transitório , Humanos , Animais , Camundongos , Canais de Potencial de Receptor Transitório/genética , Anquirinas , Capsaicina/farmacologia , Osteossarcoma/genética , Neoplasias Ósseas/genética
8.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612798

RESUMO

Brassica vegetables are widely consumed all over the world, especially in North America, Asia, and Europe. They are a rich source of sulfur compounds, such as glucosinolates (GLSs) and isothiocyanates (ITCs), which provide health benefits but are also suspected of having a goitrogenic effect. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on thyroid function, in terms of the potential risk for people with thyroid dysfunctions. We analyzed the results of 123 articles of in vitro, animal, and human studies, describing the impact of brassica plants and extracts on thyroid mass and histology, blood levels of TSH, T3, T4, iodine uptake, and the effect on thyroid cancer cells. We also presented the mechanisms of the goitrogenic potential of GLSs and ITCs, the limitations of the studies included, as well as further research directions. The vast majority of the results cast doubt on previous assumptions claiming that brassica plants have antithyroid effects in humans. Instead, they indicate that including brassica vegetables in the daily diet, particularly when accompanied by adequate iodine intake, poses no adverse effects on thyroid function.


Assuntos
Brassica , Bócio , Iodo , Animais , Humanos , Verduras , Isotiocianatos , Glucosinolatos
9.
Org Biomol Chem ; 22(16): 3249-3261, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38568016

RESUMO

A one-pot microwave assisted telescopic approach is reported for the chemo-selective synthesis of substituted 1,3-thiazetidines using readily available 2-aminopyridines/pyrazines/pyrimidine, substituted isothiocyanates and 1,2-dihalomethanes. The procedure involves thiourea formation from 2-aminopyridines/pyrazines/pyrimidine with the substituted isothiocyanates followed by a base catalysed nucleophilic attack of the CS bond on the 1,2-dihalomethane. Subsequently, a cyclization reaction occurs to yield substituted 1,3-thiazetidines. These four membered strained ring systems are reported to possess broad substrate scope with high functional group tolerance. The above synthetic sequence for the formation of four membered heterocycles is proven to be a modular and straightforward approach. Further the mechanistic pathway for the formation of 1,3-thiazetidines was supported by computational evaluations and X-ray crystallography analyses. The relevance of these thiazetidines in biological applications is evaluated by studying their ability to bind bio-macromolecules like proteins and nucleic acids.


Assuntos
Micro-Ondas , Pirimidinas/química , Pirimidinas/síntese química , Cristalografia por Raios X , Proteínas/química , Tiazóis/química , Tiazóis/síntese química , Modelos Moleculares , Estrutura Molecular , Ácidos Nucleicos/química , Ácidos Nucleicos/síntese química , Isotiocianatos/química , Isotiocianatos/síntese química , Aminopiridinas/química , Aminopiridinas/síntese química
10.
J Ethnopharmacol ; 328: 118108, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38574780

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a traditional folk medicine commonly used by ethnic minorities in the Guangxi Zhuang Autonomous Region, and has a traditional application in the treatment of liver disease. Polygala fallax Hemsl. polysaccharides (PFPs) are of interest for their potential health benefits. AIM OF THIS STUDY: This study explored the impact of PFPs on a mouse model of cholestatic liver injury (CLI) induced by alpha-naphthyl isothiocyanate (ANIT), as well as the potential mechanisms. MATERIALS AND METHODS: A mouse CLI model was constructed using ANIT (80 mg/kg) and intervened with different doses of PFPs or ursodeoxycholic acid. Their serum biochemical indices, hepatic oxidative stress indices, and hepatic pathological characteristics were investigated. Then RNA sequencing was performed on liver tissues to identify differentially expressed genes and signaling pathways and to elucidate the mechanism of liver protection by PFPs. Finally, Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to verify the differentially expressed genes. RESULTS: Data analyses showed that PFPs reduced the levels of liver function-related biochemical indices, such as ALT, AST, AKP, TBA, DBIL, and TBIL. PFPs up-regulated the activities of SOD and GSH, down-regulated the contents of MDA, inhibited the release of IL-1ß, IL-6, and TNF-α, or promoted IL-10. Pathologic characterization of the liver revealed that PFPs reduced hepatocyte apoptosis or necrosis. The RNA sequencing indicated that the genes with differential expression were primarily enriched for the biosynthesis of primary bile acids, secretion or transportation of bile, the reactive oxygen species in chemical carcinogenesis, and the NF-kappa B signaling pathway. In addition, the results of qRT-PCR and Western blotting analysis were consistent with those of RNA sequencing analysis. CONCLUSIONS: In summary, this study showed that PFPs improved intrahepatic cholestasis and alleviated liver damage through the modulation of primary bile acid production, Control of protein expression related to bile secretion or transportation, decrease in inflammatory reactions, and inhibition of oxidative pressure. As a result, PFPs might offer a hopeful ethnic dietary approach for managing intrahepatic cholestasis.


Assuntos
Colestase Intra-Hepática , Colestase , Polygala , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , 1-Naftilisotiocianato/toxicidade , China , Fígado/metabolismo , Colestase/induzido quimicamente , Colestase/tratamento farmacológico , Colestase/metabolismo , Colestase Intra-Hepática/induzido quimicamente , Isotiocianatos/efeitos adversos , Isotiocianatos/metabolismo , Ácidos e Sais Biliares/metabolismo
11.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673850

RESUMO

Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, the periparturient period, when dairy cows must rapidly adapt to the sudden metabolic demands of lactation, is a period when the production of damaging free radicals can overwhelm the natural antioxidant systems, potentially leading to tissue damage and reduced milk production. Central to the protection against free radical damage and antioxidant defense is the transcription factor NRF2, which activates an array of genes associated with antioxidant functions and cell survival. The objective of this study was to evaluate the effect that two natural NRF2 modulators, the NRF2 agonist sulforaphane (SFN) and the antagonist brusatol (BRU), have on the transcriptome of immortalized bovine mammary alveolar cells (MACT) using both the RT-qPCR of putative NRF2 target genes, as well as RNA sequencing approaches. The treatment of cells with SFN resulted in the activation of many putative NRF2 target genes and the upregulation of genes associated with pathways involved in cell survival, metabolism, and antioxidant function while suppressing the expression of genes related to cellular senescence and DNA repair. In contrast, the treatment of cells with BRU resulted in the upregulation of genes associated with inflammation, cellular stress, and apoptosis while suppressing the transcription of genes involved in various metabolic processes. The analysis also revealed several novel putative NRF2 target genes in bovine. In conclusion, these data indicate that the treatment of cells with SFN and BRU may be effective at modulating the NRF2 transcriptional network, but additional effects associated with cellular stress and metabolism may complicate the effectiveness of these compounds to improve antioxidant health in dairy cattle via nutrigenomic approaches.


Assuntos
Isotiocianatos , Fator 2 Relacionado a NF-E2 , Quassinas , Sulfóxidos , Transcriptoma , Animais , Bovinos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Isotiocianatos/farmacologia , Quassinas/farmacologia , Sulfóxidos/farmacologia , Transcriptoma/efeitos dos fármacos , Feminino , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Simulação por Computador , Estresse Oxidativo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos
12.
Cell Signal ; 119: 111181, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643946

RESUMO

Prohibitin (PHB) is a pleiotropic molecule with a variety of known functions and subcellular locations. PHB's function in breast cancer is poorly understood. Herein, we report that PHB is expressed in cancer types of diverse origin including breast cancer. The cancer patients with changes in PHB were reported to have significantly reduced 'overall survival' in comparison to the cases without alterations in PHB. The expression of PHB was increased by H2O2 and also by Moringin (MG), which is an isothiocyanate derived from the seeds of Moringa oleifera. MG interacted with PHB, DRP1, and SLP2 and inhibited the growth of MCF-7 and MDAMB-231 cells. The isothiocyanate triggered apoptosis in breast cancer cells as revealed by AO/PI assay, phosphatidylserine externalization, cell cycle analysis and DAPI staining. MG induced proapoptotic proteins expression such as cytochrome c, p53, and cleaved caspase-7. Further, cell survival proteins such as survivin, Bcl-2, and Bcl-xL were suppressed. A depolarization of membrane potential suggested that the apoptosis was triggered through mitochondria. The isothiocyanate suppressed the cancer cell migration and interacted with NF-κB subunits. MG suppressed p65 nuclear translocation induced by TNF-α. The reactive oxygen species generation was also induced by the isothiocyanate in breast cancer cells. MG also modulated the expression of lncRNAs. Collectively, the functions of PHB in breast cancer growth is evident from this study. The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets.


Assuntos
Apoptose , Neoplasias da Mama , Isotiocianatos , Proibitinas , Transdução de Sinais , Humanos , Isotiocianatos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Linhagem Celular Tumoral , Células MCF-7 , Movimento Celular/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos
13.
J Agric Food Chem ; 72(18): 10579-10583, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38683941

RESUMO

A 14C-based method was developed to study the rate and extent of covalent bond formation between ß-lactoglobulin and three model flavor compounds: a ketone (2-undecanone UDO), an aldehyde (decanal DAL), an isothiocyanate (2-phenylethyl isothiocyanate PEITC), and an unreactive "methods blank" (decane DEC). Aqueous protein solutions with one of the 14C-labeled model flavor compounds were placed in water baths at 25, 45, and 65 °C for 4 weeks measuring the amount of flavor: protein reaction at 1, 3, 7, 14, 21, and 28 days. UDO showed lowest reactivity (max of 0.9% of added compound reacted), DAL (max of 16.4% reacted), and PEITC (max of 71.8% reacted). All compounds showed a rapid initial reaction rate which slowed after ca. 7 days. It appears that only PEITC (at 65 °C) saturated all potential protein-reactive sites over the storage period.


Assuntos
Aromatizantes , Isotiocianatos , Cetonas , Lactoglobulinas , Lactoglobulinas/química , Aromatizantes/química , Isotiocianatos/química , Cetonas/química , Radioisótopos de Carbono/análise , Radioisótopos de Carbono/química , Aldeídos/química , Cinética
14.
Food Chem ; 449: 138939, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38599103

RESUMO

Glucosinolate-derived isothiocyanates are valuable for human health as they exert health promoting effects. As thermal food processing could affect their levels in a structure dependent way, the stability and reactivity of 12 Brassicaceae isothiocyanates during aqueous heating at 100 °C and pH 5-8 were investigated. The formation of their corresponding amines and N,N'-dialk(en)yl thioureas was quantified. Further, the potential to form odor active compounds was investigated by HRGC-MS-olfactometry. A strong structure-reactivity relationship was found and shorter side chains and electron withdrawing groups increase the reactivity of isothiocyanates. 3-(Methylsulfonyl)-propyl isothiocyanate was least stable. The main products are the corresponding amines (up to 69% recovery) and formation of N,N'-dialk(en)yl thioureas is only relevant at neutral to basic pH values. Apart from allyl isothiocyanate also 3-(methylthio)propyl isothiocyanate is precursor to many sulfur-containing odor active compounds. Thus, the isothiocyanate-structure affects their levels but also contributes to the flavor of boiled Brassicaceae vegetables.


Assuntos
Brassicaceae , Temperatura Alta , Isotiocianatos , Isotiocianatos/química , Brassicaceae/química , Odorantes/análise , Cromatografia Gasosa-Espectrometria de Massas , Manipulação de Alimentos
15.
Sci Rep ; 14(1): 6937, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521828

RESUMO

Keratoconus (KC) is a progressive degenerative disease that usually occurs bilaterally and is characterized by corneal thinning and apical protrusion of the cornea. Oxidative stress is an indicator of the accumulation of reactive oxygen species (ROS), and KC keratocytes exhibit increased ROS production compared with that of normal keratocytes. Therefore, oxidative stress in KC keratocytes may play a major role in the development and progression of KC. Here, we investigated the protective effect of sulforaphane (SF) antioxidants using a hydrogel-simulated model of the cell mechanical microenvironment of KC. The stiffness of the KC matrix microenvironment in vitro was 16.70 kPa and the stiffness of the normal matrix microenvironment was 34.88 kPa. Human keratocytes (HKs) were cultured for 24 h before observation or drug treatment with H2O2 in the presence or absence of SF. The levels of oxidative stress, nuclear factor E2-related factor 2 (Nrf-2) and antioxidant response element (ARE) were detected. The high-stress state of HKs in the mechanical microenvironment of KC cells compensates for the activation of the Nrf-2/ARE signaling pathway. H2O2 leads to increased oxidative stress and decreased levels of antioxidant proteins in KC. In summary, SF can reduce endogenous and exogenous oxidative stress and increase the antioxidant capacity of cells.


Assuntos
Isotiocianatos , Ceratocone , Sulfóxidos , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/metabolismo , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Elementos de Resposta Antioxidante , Peróxido de Hidrogênio/metabolismo , Córnea/metabolismo
16.
Eur J Pharmacol ; 969: 176477, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38438062

RESUMO

Polycystic ovarian syndrome (PCOS) has been associated with depression and suicidal ideations in females. Studies have highlighted the role of autophagic deficiency in depression pathogenesis. Sulforaphane (SFN) is a natural product that improved autophagic deficiency and showed antidepressant activity in depressed patients. Herein, the study aimed to evaluate the impact of using SFN on depression-associated with PCOS via hippocampal energy sensors and cellular bioenergetics. PCOS was induced by administering letrozole (1 mg/kg, p. o.) for 21 days, followed by SFN treatment (0.5 mg/kg, i. p.) for one week. Two days before euthanasia, PCOS rats showed anhedonic behavior in the sucrose preference test and increased immobility time in the forced swimming test. Depressed rats showed a reduction in nuclear SIRT1 and an elevated cytoplasmic one. This was associated with a reduction in phosphorylation of energy sensors, liver kinase B1 (LKB1), and adenosine monophosphate kinase (AMPK), along with an imbalance of autophagic markers such as Beclin-1, microtubule-associated protein I/II light chain 3, autophagy enzyme 7 and selective autophagy receptor P62. Additionally, Nrf2 and KEAP1 levels were decreased. These abnormalities were alleviated by SFN treatment, as evidenced by the nuclear translocation of SIRT1 and the repression of downstream proteins, including FOXO1, NF-κB, and TNF-α production. These changes were reflected in improved behavioral performance in the sucrose preference test (SPT) and forced swimming test (FST). The antidepressant effects of SFN were counteracted by an autophagic inhibitor, 3-methyladenine. Eventually, SFN, as a nutraceutical, has a promising antidepressant effect via restoring autophagic-related depression in the PCOS rat model.


Assuntos
Proteínas Quinases Ativadas por AMP , Isotiocianatos , Síndrome do Ovário Policístico , Sulfóxidos , Humanos , Feminino , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Depressão/tratamento farmacológico , Sirtuína 1/metabolismo , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Autofagia , Sacarose/farmacologia
18.
Biomolecules ; 14(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38540770

RESUMO

Sulforaphane (SFN) is one of the hydrolysates of glucosinolates (GSLs), primarily derived from Brassica vegetables like broccoli. In clinical therapy, SFN has been proven to display antimicrobial, anticancer, antioxidant, and anti-inflammatory properties. However, the antimicrobial effects and mechanism of SFN against plant pathogens need to be further elucidated, which limits its application in agriculture. In this study, the genetic factors involved in SFN biosynthesis in 33 B. oleracea varieties were explored. The finding showed that besides the genetic background of different B. oleracea varieties, myrosinase and ESP genes play important roles in affecting SFN content. Subsequently, the molecular identification cards of these 33 B. oleracea varieties were constructed to rapidly assess their SFN biosynthetic ability. Furthermore, an optimized protocol for SFN extraction using low-cost broccoli curds was established, yielding SFN-enriched extracts (SFN-ee) containing up to 628.44 µg/g DW of SFN. The antimicrobial activity assay confirmed that SFN-ee obtained here remarkably inhibit the proliferation of nine tested microorganisms including four plant pathogens by destroying their membrane integrity. Additionally, the data demonstrated that exogenous application of SFN-ee could also induce ROS accumulation in broccoli leaves. These results indicated that SFN-ee should play a dual role in defense against plant pathogens by directly killing pathogenic cells and activating the ROS signaling pathway. These findings provide new evidence for the antimicrobial effect and mechanism of SFN against plant pathogens, and suggest that SFN-ee can be used as a natural plant antimicrobial agent for crop protection and food preservation.


Assuntos
Anti-Infecciosos , Brassica , Isotiocianatos , Sulfóxidos , Brassica/metabolismo , Proteção de Cultivos , Espécies Reativas de Oxigênio/metabolismo , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo
19.
Nutrients ; 16(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542669

RESUMO

Isothiocyanates are biologically active products resulting from the hydrolysis of glucosinolates predominantly present in cruciferous vegetables belonging to the Brassicaceae family. Numerous studies have demonstrated the diverse bioactivities of various isothiocyanates, encompassing anticarcinogenic, anti-inflammatory, and antioxidative properties. Nature harbors distinct isothiocyanate precursors, glucosinolates such as glucoraphanin and gluconastrin, each characterized by unique structures, physical properties, and pharmacological potentials. This comprehensive review aims to consolidate the current understanding of Moringa isothiocyanates, mainly 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate), comparing this compound with other well-studied isothiocyanates such as sulforaphane and phenyl ethyl isothiocyanates. The focus is directed toward elucidating differences and similarities in the efficacy of these compounds as agents with anticancer, anti-inflammatory, and antioxidative properties.


Assuntos
Anticarcinógenos , Brassicaceae , Glucosinolatos/farmacologia , Brassicaceae/química , Isotiocianatos/farmacologia , Antioxidantes/farmacologia , Anti-Inflamatórios , Anticarcinógenos/farmacologia
20.
Int J Biol Macromol ; 265(Pt 2): 131011, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518947

RESUMO

Preserving fish meat poses a significant challenge due to its high protein and low fat content. This study introduces a novel approach that utilizes a common type of lanthanide metal-organic frameworks (Ln-MOFs), EuMOFs, in combination with 5-fluorescein isothiocyanate (FITC) and methylcellulose (MC) to develop fluorescent sensor arrays for real-time monitoring the freshness of fish meat. The EuMOF-FITC/MC fluorescence films were characterized with excellent fluorescence response, ideal morphology, good mechanical properties, and improved hydrophobicity. The efficacy of the fluorescence sensor array was evaluated by testing various concentrations of spoilage gases (such as ammonia, dimethylamine, and trimethylamine) within a 20-min timeframe using a smartphone-based camera obscura device. This sensor array enables the real-time monitoring of fish freshness, with the ability to preliminarily identify the freshness status of mackerel meat with the naked eye. Furthermore, the study employed four convolutional neural network (CNN) models to enhance the performance of freshness assessment, all of which achieved accuracy levels exceeding 93 %. Notably, the ResNext-101 model demonstrated a particularly high accuracy of 98.97 %. These results highlight the potential of the EuMOF-based fluorescence sensor array, in conjunction with the CNN model, as a reliable and accurate method for real-time monitoring the freshness of fish meat.


Assuntos
Aprendizado Profundo , Isotiocianatos , Elementos da Série dos Lantanídeos , Animais , Fluoresceína-5-Isotiocianato , Peixes , Corantes , Fluoresceína
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