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1.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473857

RESUMO

Anticancer agents are playing an increasing role in the treatment of gastric cancer (GC); however, novel anticancer agents have not been fully developed. Therefore, it is important to investigate compounds that improve sensitivity to the existing anticancer drugs. We have reported that pterostilbene (PTE), a plant stilbene, enhances the antitumor effect of low doses of sunitinib in gastric cancer cells accumulating mitochondrial iron (II) (mtFe) at low doses. In this study, we investigated the relationship between the mtFe deposition and the synergistic effect of PTE and different anticancer drugs. For this study, we used 5-fluorouracil (5FU), cisplatin (CPPD), and lapatinib (LAP), which are frequently used in the treatment of GC, and doxorubicin (DOX), which is known to deposit mtFe. A combination of low-dose PTE and these drugs suppressed the expression of PDZ domain-containing 8 (PDZD8) and increased mtFe accumulation and mitochondrial H2O2. Consequently, reactive oxygen species-associated hypoxia inducible factor-1α activation induced endoplasmic reticulum stress and led to apoptosis, but not ferroptosis. In contrast, 5FU and CDDP did not show the same changes as those observed with PTE and DOX or LAP, and there was no synergistic effect with PTE. These results indicate that the combination of PTE with iron-accumulating anticancer drugs exhibits a strong synergistic effect. These findings would help in developing novel therapeutic strategies for GC. However, further clinical investigations are required.


Assuntos
Antineoplásicos , Estilbenos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Peróxido de Hidrogênio/metabolismo , Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Apoptose , Mitocôndrias/metabolismo , Estilbenos/farmacologia , Estresse do Retículo Endoplasmático , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
2.
J Drugs Dermatol ; 23(3): 192-194, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443116

RESUMO

Plaque psoriasis is a chronic, immune-mediated, cutaneous, and systemic inflammatory dermatosis. Its pathogenesis involves the dysregulation of the interleukin (IL)-23/IL-17 signaling pathway. There are a range of treatment options available, encompassing topical agents, biologics, oral systemic therapy, and phototherapy. The utility of combination treatment has also been described and is a budding field of research. Here we describe the first case of adult severe generalized plaque psoriasis treated with once-daily oral deucravacitinib 6 mg combined with tapinarof cream 1% applied once daily. To our knowledge, the combination of these agents has not yet been described in the literature. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8091.


Assuntos
Compostos Heterocíclicos , Psoríase , Estilbenos , Adulto , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Terapia Combinada , Resorcinóis , Emolientes
3.
Enzyme Microb Technol ; 176: 110425, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479200

RESUMO

Cytochrome P450s (CYPs) regulate plant growth and stress responses by producing diverse primary and secondary metabolites. However, the function of many plant CYPs remains unknown because, despite their structural similarity, predicting the enzymatic activity of CYPs is difficult. In this study, one member of the CYP736A subfamily (CYP736A61) from tomatoes was isolated and characterized its enzymatic functions. CYP736A61 was successfully expressed in Escherichia coli through co-expression with molecular chaperones. The purified CYP736A61 showed hydroxylation activity toward 7-ethoxycoumarin, producing 7-hydroxycoumarin or 3-hydroxy 7-ethoxycoumarin. Further substrate screening revealed that dihydrochalcone and stilbene derivates (resveratrol and polydatin) are the substrates of CYP736A61. CYP736A61 also mediated the hydroxylation of resveratrol and polydatin, albeit with low activity. Importantly, CYP736A61 mediated the cleavage of resveratrol and polydatin as well as pinostilbene and pterostilbene. Interestingly, CY736A61 also converted phloretin to naringenin chalcone. These results suggest that CYP736A61 is a novel CYP enzyme with stilbene cleavage activity.


Assuntos
Glucosídeos , Solanum lycopersicum , Estilbenos , Resveratrol , Estilbenos/química , Estilbenos/metabolismo , Catálise
4.
Biochem Biophys Res Commun ; 705: 149756, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38460440

RESUMO

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI.


Assuntos
Infarto do Miocárdio , Estilbenos , Ratos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Resveratrol/farmacologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Lipopolissacarídeos/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Ratos Wistar , Infarto do Miocárdio/tratamento farmacológico , Dieta
5.
Food Funct ; 15(5): 2381-2405, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38376230

RESUMO

Hyperglycemia has become a global health problem due to changes in diet and lifestyle. Most importantly, persistent hyperglycemia can eventually develop into type II diabetes. While the usage of current drugs is limited by their side effects, stilbenes derived from fruits and herbal/dietary plants are considered as important phytochemicals with potential hypoglycemic properties. Herein, the most common stilbenoids in consumed foods, i.e. resveratrol, pterostilbene, piceatannol, oxyresveratrol, and 2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucopyranoside (THSG), are reviewed in this paper. These stilbenes are found to regulate glucose homeostasis via (a) modulation of feeding behaviour and nutrition absorption; (b) restoration of insulin signalling by enhancing insulin production/insulin sensitivity; (c) improvement of gut permeability, gut microbial profile and resulting metabolomes; and (d) amelioration of circadian rhythm disruption. In this review, we have summarized the underlying mechanisms for the hypoglycemic effects of the five most common dietary stilbenoids listed above, providing a comprehensive framework for future study and applications.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Insulinas , Estilbenos , Humanos , Hipoglicemiantes/farmacologia , Resveratrol/farmacologia , Dieta , Estilbenos/farmacologia , Estilbenos/química
6.
J Enzyme Inhib Med Chem ; 39(1): 2315227, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38421003

RESUMO

Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It is also a natural dietary compound with a wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, and so on. Structural modifications based on the chemical scaffold of the pterostilbene skeleton are of great importance for drug discovery. In this study, pterostilbene skeletons were used to design novel anti-inflammatory compounds with high activity and low toxicity. A total of 30 new were found and synthesised, and their anti-inflammatory activity and safety were screened. Among them, compound E2 was the most active (against NO: IC50 = 0.7 µM) than celecoxib. Further studies showed that compound E2 exerted anti-inflammatory activity by blocking LPS-induced NF-κB/MAPK signalling pathway activation. In vivo experiments revealed that compound E2 had a good alleviating effect on acute colitis in mice. In conclusion, compound E2 may be a promising anti-inflammatory lead compound.


Assuntos
Transdução de Sinais , Estilbenos , Camundongos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Estilbenos/farmacologia , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia
7.
J Nucl Med ; 65(3): 453-461, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302152

RESUMO

We investigated the longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients in the Alzheimer disease (AD) continuum using 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI-2620) PET. Methods: We prospectively enrolled 52 participants (age, 69.7 ± 8.4 y; 18 men and 34 women): 7 with normal cognition, 28 with mild cognitive impairment, and 17 with AD. They all completed the [18F]PI-2620 and [18F]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [18F]florbetaben PET, at the 1-y follow-up. Amyloid-ß (Aß) PET images were visually scored as positive (+) or negative (-). Patients on the AD continuum, including Aß+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (≥65 y old) groups. [18F]PI-2620 PET SUV ratios (SUVRs) were determined by calculating the cerebral-to-inferior cerebellar ratio. Cortical volumes were calculated using 3-dimensional T1-weighted MRI. The correlation between tau accumulation progression and cognitive decline was also investigated. Results: The global [18F]PI-2620 PET SUVRs were 1.04 ± 0.07 in 15 Aß- patients, 1.18 ± 0.21 in 20 LO+ patients (age, 76.7 ± 3.8 y), and 1.54 ± 0.38 in 17 EO+ patients (age, 63.4 ± 5.4 y; P < 0.001) at baseline. The global SUVR increased over 1 y by 0.05 ± 0.07 (3.90%) and 0.13 ± 0.22 (8.41%) in the LO+ and EO+ groups, respectively, whereas in the Aß- groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the Aß- and LO+ groups (P < 0.05 for each) and rapid accumulation in Braak stage V (0.15 ± 0.25; 9.10% ± 12.27%; P = 0.016 and 0.008), Braak stage VI (0.08 ± 0.12; 7.16% ± 10.06%; P < 0.006 and 0.005), and global SUVR (P = 0.013) compared with the Aß- group. In the EO+ group, the changes in SUVR in Braak stages II-VI were strongly correlated with the baseline and changes in verbal memory (P < 0.03). The LO+ group showed higher tau accumulation in Braak stage I-IV areas than did the Aß- group (P < 0.001 for each). In the LO+ group, the change in SUVR in Braak stages III and IV moderately correlated with the change in attention (P < 0.05), and the change in SUVR in Braak stages V and VI moderately correlated with the change in visuospatial function (P < 0.005). Conclusion: These findings suggest that [18F]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum.


Assuntos
Doença de Alzheimer , Compostos de Anilina , Piridinas , Estilbenos , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons
8.
Biochem Biophys Res Commun ; 700: 149598, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38308910

RESUMO

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PURPOSE: This study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. METHODS: An ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. RESULTS: During ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. CONCLUSIONS: PCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.


Assuntos
Ferroptose , Traumatismo por Reperfusão Miocárdica , Fator 2 Relacionado a NF-E2 , Traumatismo por Reperfusão , Estilbenos , Animais , Camundongos , Isquemia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Estilbenos/farmacologia
10.
Bioorg Chem ; 145: 107178, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359708

RESUMO

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.


Assuntos
Antineoplásicos , Neoplasias do Colo , Flavanonas , Iohexol/análogos & derivados , Estilbenos , Masculino , Humanos , Via de Sinalização Wnt , Estilbenos/farmacologia , Antineoplásicos/farmacologia , Células HCT116 , Flavanonas/farmacologia , Apoptose , Neoplasias do Colo/tratamento farmacológico , Proliferação de Células , Linhagem Celular Tumoral , beta Catenina/metabolismo
11.
J Ethnopharmacol ; 326: 117865, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38369066

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucopyranoside (TSG) as the primary constituent of Polygonum multiflorum Thumb. (PM) possesses anti-oxidative, antihypercholesterolemic, anti-tumor and many more biological activities. The root of PM has been used as a tonic medicine for thousands of years. However, cases of PM-induced liver injury are occasionally reported, and considered to be related to the host immune status. AIM OF THE STUDY: The primary toxic elements and specific mechanisms PM causing liver damage are still not thoroughly clear. Our study aimed to investigate the influences of TSG on the immune response in idiosyncratic hepatotoxicity of PM. MATERIALS AND METHODS: The male C57BL/6 mice were treated with different doses of TSG and the alterations in liver histology, serum liver enzyme levels, proportions of T cells and cytokines secretion were evaluated by hematoxylin and eosin (HE), RNA sequencing, quantitative real time polymerase chain reaction (qRT-PCR), Flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA), respectively. Then, primary spleen cells from drug-naive mice were isolated and cultured with TSG in vitro. T cell subsets proliferation and cytokines secretion after treated with TSG were assessed by CCK8, FCM and ELISA. In addition, mice were pre-treated with anti-CD25 for depleting regulatory T cells (Tregs), and then administered with TSG. Liver functions and immunological alterations were analyzed to evaluate liver injury. RESULTS: Data showed that TSG induced liver damage, and immune cells infiltration in the liver tissues. FCM results showed that TSG could activate CD4+T and CD8+T in the liver. Results further confirmed that TSG notably up-regulated the levels of inflammatory cytokines including TNF-α, IFN-γ, IL-18, perforin and granzyme B in the liver tissues. Furthermore, based on transcriptomics profiles, some immune system-related pathways including leukocyte activation involved in inflammatory response, leukocyte cell-cell adhesion, regulation of interleukin-1 beta production, mononuclear cell migration, antigen processing and presentation were altered in TSG treated mice. CD8+T/CD4+T cells were also stimulated by TSG in vitro. Interestingly, increased proportion of Tregs was observed after TSG treatment in vitro and in vivo. Foxp3 and TGF-ß1 mRNA expressions were up-regulated in the liver tissues. Depletion of Tregs moderately enhanced TSG induced the secretion of inflammatory cytokines in serum. CONCLUSIONS: Our findings showed that TSG could trigger CD4+T and CD8+T cells proliferation, promote cytokines secretion, which revealed that adaptive immune response associated with the mild liver injury cause by TSG administration. Regulatory T cells (Tregs) mainly sustain immunological tolerance, and in this study, the progression of TSG induced liver injury was limited by Tregs. The results of our investigations allow us to preliminarily understand the mechanisms of PM related idiosyncratic hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Fallopia multiflora , Polygonum , Estilbenos , Camundongos , Masculino , Animais , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Camundongos Endogâmicos C57BL , Citocinas/genética , Imunidade , Estilbenos/toxicidade , Estilbenos/uso terapêutico
12.
Leuk Res ; 138: 107464, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422882

RESUMO

Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.


Assuntos
Linfoma , Fitoalexinas , Estilbenos , Humanos , Resveratrol/uso terapêutico , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Linfoma/tratamento farmacológico
13.
Talanta ; 272: 125752, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354543

RESUMO

The reported organic electrochemiluminescence (ECL) luminophors for the detection of various markers often suffer from intermolecular π-π stacking-induced luminophore quenching. Herein, we demonstrate one-pot synthesis of a new aggregation-induced electrochemiluminescence (AIECL) emitter (i.e., TPE@SiO2/rGO composite) for sensitive measurement of microcystin-leucine arginine (MC-LR). The TPE@SiO2/rGO composite is constructed by embedding the silica-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) in the reduced graphene oxide. In comparison with the monomer TPE, this composite exhibit high luminescence efficiency and strong ECL emission, because the AIECL phenomenon triggered by the spatial confinement effect in the SiO2 cage induces the restriction of the internal motion and vibration of molecules. Notably, this composite has distinct advantages of easy preparation, simple functionalization, and stable luminescence. Especially, the TPE@SiO2/rGO-based ECL-RET system exhibits a high quenching efficiency (ΦET) of 69.7%. When target MC-LR is present, it triggers DNA strand displacement reaction (SDR), inducing the quenching of the ECL signal of TPE@SiO2/rGO composite due to ECL resonance energy transfer between TPE@SiO2/rGO composite and methylene blue (MB). The proposed biosensor enables highly sensitive, low-cost, and robust measurement of MC-LR with a large dynamic range of 7 orders of magnitude and a detection limit of 3.78 fg/mL, and it displays excellent detection performance in complex biological matrices, holding potential applications in food safety and water monitoring.


Assuntos
Técnicas Biossensoriais , Toxinas Marinhas , Microcistinas , Dióxido de Silício , Estilbenos , Vibração , Transferência de Energia , Medições Luminescentes , Técnicas Eletroquímicas , Limite de Detecção
14.
Mol Biol Rep ; 51(1): 366, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409545

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is one of the most prevalent brain injuries in humans which has poor prognosis and high mortality rates. Due to several medical or surgical treatment methods, a gold standard method doesn't exist for SAH treatment. Piceatannol (PCN), a natural analog of resveratrol, was reported to reduce inflammation and apoptosis promising a wide range of therapeutic alternatives. In this study, we aimed to investigate the effects of PCN in an experimental SAH model. The alleviating effects of PCN in the hippocampus in an experimental SAH model were investigated for the first time. METHODS AND RESULTS: In this study, 27 Wistar Albino male rats (200-300 g; 7-8 week) were used. Animals were divided into three groups; SHAM, SAH, and SAH + PCN. SAH model was created with 120 µl of autologous arterial tail blood to prechiasmatic cisterna. 30 mg/kg PCN was administered intraperitoneally at 1st h after SAH. Neurological evaluation was performed with Garcia's score. RT-PCR was performed for gene expression levels in the hippocampus. Pyknosis, edema, and apoptosis were evaluated by H&E and TUNEL staining. Our results indicated that PCN administration reduced apoptosis (P < 0.01), cellular edema, and pyknosis (P < 0.05) in the hippocampus after SAH. Moreover, PCN treatment significantly decreased the expression levels of TNF-α (P < 0.01), IL-6 (P < 0.05), NF-κB (P < 0.05), and Bax (P < 0.05) in the hippocampus. CONCLUSIONS: Our results demonstrated that PCN might be a potential therapeutic adjuvant agent for the treatment of early brain injury (EBI) following SAH. Further studies are required to clarify the underlying mechanisms and treatment options of SAH.


Assuntos
Lesões Encefálicas , Fármacos Neuroprotetores , Estilbenos , Hemorragia Subaracnóidea , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Ratos Wistar , Lesões Encefálicas/tratamento farmacológico , Apoptose , Edema/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
15.
Molecules ; 29(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398607

RESUMO

Deoxynivalenol (DON) is a common mycotoxin that is widely found in various foods and feeds, posing a potential threat to human and animal health. This study aimed to investigate the protective effect of the natural polyphenol piceatannol (PIC) against DON-induced damage in porcine intestinal epithelial cells (IPEC-J2 cells) and the underlying mechanism. The results showed that PIC promotes IPEC-J2 cell proliferation in a dose-dependent manner. Moreover, it not only significantly relieved DON-induced decreases in cell viability and proliferation but also reduced intracellular reactive oxygen species (ROS) production. Further studies demonstrated that PIC alleviated DON-induced oxidative stress damage by increasing the protein expression levels of the antioxidant factors NAD(P)H quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM), and the mRNA expression of catalase (CAT), Superoxide Dismutase 1 (SOD1), peroxiredoxin 3 (PRX3), and glutathione S-transferase alpha 4 (GSTα4). In addition, PIC inhibited the activation of the nuclear factor-B (NF-κB) pathway, downregulated the mRNA expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) to attenuate DON-induced inflammatory responses, and further mitigated DON-induced cellular intestinal barrier injury by regulating the protein expression of Occludin. These findings indicated that PIC had a significant protective effect against DON-induced damage. This study provides more understanding to support PIC as a feed additive for pig production.


Assuntos
Células Epiteliais , NF-kappa B , Estilbenos , Tricotecenos , Suínos , Animais , Humanos , NF-kappa B/metabolismo , Linhagem Celular , RNA Mensageiro/metabolismo
16.
J Drugs Dermatol ; 23(2): 23-28, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306128

RESUMO

Atopic dermatitis (AD) is a chronic relapsing–remitting disease with a multifactorial etiology involving epidermal barrier and immunologic dysfunction. Topical therapies form the mainstay of AD treatment, but options are limited by adverse effects and restrictions on application site, duration, and extent of use. Tapinarof (VTAMA; Dermavant Sciences, Inc.) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis. AhR is a ligand-dependent transcription factor with wide-ranging roles, including regulation of homeostasis and immune response in skin cells. AhR expression and signaling are altered in many inflammatory skin diseases, and clinical trials with tapinarof have validated AhR as a therapeutic target capable of delivering significant efficacy. Tapinarof cream 1% once daily demonstrated efficacy versus vehicle in adults and adolescents with AD and is being investigated in the ADORING trials for the treatment of AD in adults and children down to 2 years of age. J Drugs Dermatol. 2024;23(2):23-28.  doi:10.36849/JDD.8026.


Assuntos
Dermatite Atópica , Estilbenos , Humanos , Dermatite Atópica/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/agonistas , Resorcinóis , Pele
17.
Chem Biol Drug Des ; 103(2): e14458, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38383061

RESUMO

JNK3, a neuronal kinase activated by stress, plays a role in stress-induced apoptosis, leading to neuronal cell death following cerebral ischemia. This study investigates the neuroprotective effects of piceatannol (PCT) in SHSY-5Y neuroblastoma cells after hypoxic injury and its interaction with JNK3. We analyzed the crystal coordinates, interaction energies, and amino acid interactions to determine PCT's selectivity for JNK3. The electrostatic potential was computed using density functional theory, while molecular dynamics assessed the stability and structural consistency of the JNK3-PCT complex. We used SP600125 (SP6), a JNK3 inhibitor, as a reference compound. Additionally, we performed cell-free JNK 1, 2, and 3 kinase assays to evaluate the isoform selectivity of PCT. Cytotoxicity and cell viability were determined by an MTT test. To assess apoptosis, we used acridine orange/ethidium bromide dual fluorescent labeling and ANNEXIN A5-FITC flow cytometry. Western blot was used to evaluate the attenuation of JNK3 and apoptotic proteins. In silico studies revealed a stronger binding affinity between PCT and JNK3 compared to JNK1 and JNK2, which was further supported by the in vitro kinase assay. PCT-treated cells exhibited a decrease in Cyt-c and caspase-3 expression and an increase in Bcl-2 level, compared to hypoxic control (p < .001). PCT also demonstrated superior efficacy over SP6 in inhibiting JNK3 phosphorylation (p < .001). Furthermore, PCT significantly increased the expression of neuronal genes, including NgN1, neuroD2, and survivin (p < .001). In conclusion, PCT is a potential JNK3 inhibitor, since it inhibited phosphorylation and the Bcl-2/Cyt-C/caspase-3-dependent apoptotic pathway after ischemic/hypoxic insult.


Assuntos
Caspases , Oxigênio , Estilbenos , Caspase 3 , Caspases/farmacologia , Proteína Quinase 10 Ativada por Mitógeno/genética , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Apoptose , Linhagem Celular
18.
J Orthop Trauma ; 38(3): 134-142, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385973

RESUMO

OBJECTIVES: The aims of this study were to compare the patient and fracture characteristics, radiological, functional, and quality of life outcomes; the need for a lateral window approach and requirement of total hip arthroplasty; and complications in patients with simple and complex acetabular fractures who underwent a modified Stoppa approach through vertical and Pfannenstiel incisions. DESIGN: This was a retrospective comparison study. SETTING: Level 1 trauma center. PATIENT SELECTION CRITERIA: Patients with acetabular fractures (A-O-/-O-T-A type 62A-B-C) treated with vertical (group V) or Pfannenstiel (group P) incision-modified Stoppa approach between 2010 and 2020 were included. OUTCOME MEASURES AND COMPARISONS: Patient characteristics, radiological evaluations (reduction quality and posttraumatic osteoarthritis), patient functional outcomes [12-item Short-Form Survey (SF-12) physical component score, SF-12 mental component score, Harris Hip Score, and Merle d'Aubigné-Postel], approach modifications and stratification by fracture type and complications were compared between those treated with vertical or Pfannenstiel incisions. RESULTS: One hundred four patients (mean age of 38.5 ± 14.3 years) were included. There was no significant difference between the Pfannenstiel or vertical groups regarding patient and fracture characteristics (P = 0.137), postoperative reduction quality (P = 0.130), or the mean functional and quality of life outcome scores at the last follow-up (P = 0.483 for the Harris Hip Score, P = 0.717 for the Merle d'Aubigné-Postel score, P = 0.682 for the SF-12 physical component score, and P = 0.781 for the SF-12 mental component score). In group P, significantly more patients needed additional lateral incisions (40.8% vs. 10.9%; P 0.001) and total hip replacement procedures (12.2% vs. 1.8%; P = 0.049). The total, early, and late complication rates were significantly higher in group P (P 0.001, P = 0.034, and P = 0.049, respectively). CONCLUSIONS: Pfannenstiel incision was associated with higher complication rates than vertical incision in acetabular fractures treated through a modified Stoppa approach. Fracture complexity is associated with the need for a lateral window approach and total hip arthroplasty, as well as a worse functional and radiological outcome regardless of incision type. However, it was not associated with the development of intraoperative or postoperative complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas do Quadril , Compostos Organometálicos , Osteoartrite , Fraturas da Coluna Vertebral , Estilbenos , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos
19.
Clin Exp Dent Res ; 10(1): e845, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345478

RESUMO

OBJECTIVE: The tooth loss has a significant impact on the positioning of the condyle in the glenoid fossa and joint spaces of the temporomandibular joint (TMJ). The aim of this study was to assess the association between tooth loss and TMJ spaces using cone beam computed tomography (CBCT) images. MATERIALS AND METHODS: This retrospective investigation involved the evaluation of CBCT images of the bilateral TMJs in a cohort of 111 individuals, comprising 68 males and 43 women. The dentition of the patients was categorized into three categories, including A (65.4%), B (19.1%), and C (16.4%), based on the Eichner index. Anterior, superior, and posterior joint spaces were then measured in sagittal views. The Kruskal-Wallis test and Mann-Whitney test were employed to identify significant differences among the three Eichner groups. RESULTS: The findings of the present study suggested that there was no statistically significant variation in the anterior joint space among different Eichner groups within the general population (p = .781). Nevertheless, the superior and posterior joint spaces exhibited statistically significant alterations, as indicated by p-values of .039 and .010, respectively. It was detected that condyles were positioned inferiorly and posteriorly in group C when compared to groups A and B. CONCLUSION: The present study indicated that greater loss of tooth-supporting zones is associated with posterior and inferior displacement of condyles. Understanding these relationships helps emphasize how crucial it is to replace missing teeth to enhance occlusion support and, in turn, stop the progression and further deterioration of temporomandibular disorders.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Estilbenos , Perda de Dente , Masculino , Humanos , Feminino , Côndilo Mandibular/diagnóstico por imagem , Estudos Retrospectivos , Perda de Dente/diagnóstico por imagem , Articulação Temporomandibular/diagnóstico por imagem
20.
Food Funct ; 15(6): 2996-3007, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38411214

RESUMO

Resveratrol has profound benefits against diabetes. However, whether its methylated derivative 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) also plays a protective role in glucose metabolism is not characterized. We aimed to study the anti-diabetic effects of 3,4',5-TMS in vitro and in vivo. Insulin-resistant HepG2 cells (IR-HepG2) were induced by high glucose plus dexamethasone whilst six-week-old male C57BL/6J mice received a 60 kcal% fat diet for 14 weeks to establish an obese diabetic model. 3,4',5-TMS did not reduce the cell viability of IR-HepG2 cells at concentrations of 0.5 and 1 µM, which enhanced the capability of glycogen synthesis and glucose consumption in IR-HepG2 cells. Four-week oral administration of 3,4',5-TMS at 10 mg kg-1 day-1 ameliorated insulin sensitivity and glucose tolerance of diet-induced obese (DIO) mice. 3,4',5-TMS activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway by inhibiting phosphorylation of insulin receptor substrate (IRS)-1 at Ser307 and increasing the protein levels of IRS-1 and IRS-2 to restore the insulin signaling pathway in diabetes. 3,4',5-TMS also upregulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at Ser9. 3,4',5-TMS suppressed oxidative stress by increasing the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H : quinone oxidoreductase 1 (NQO1) and antioxidant enzyme activity. In summary, 3,4',5-TMS alleviated hepatic insulin resistance in vitro and in vivo, by the activation of the insulin signaling pathway, accomplished by the suppression of oxidative stress.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Estilbenos , Animais , Camundongos , Masculino , Insulina/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos Obesos , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Glucose/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Obesidade/tratamento farmacológico
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