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1.
Nature ; 603(7901): 434-438, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35296844

RESUMO

Oxidation can deteriorate the properties of copper that are critical for its use, particularly in the semiconductor industry and electro-optics applications1-7. This has prompted numerous studies exploring copper oxidation and possible passivation strategies8. In situ observations have, for example, shown that oxidation involves stepped surfaces: Cu2O growth occurs on flat surfaces as a result of Cu adatoms detaching from steps and diffusing across terraces9-11. But even though this mechanism explains why single-crystalline copper is more resistant to oxidation than polycrystalline copper, the fact that flat copper surfaces can be free of oxidation has not been explored further. Here we report the fabrication of copper thin films that are semi-permanently oxidation resistant because they consist of flat surfaces with only occasional mono-atomic steps. First-principles calculations confirm that mono-atomic step edges are as impervious to oxygen as flat surfaces and that surface adsorption of O atoms is suppressed once an oxygen face-centred cubic (fcc) surface site coverage of 50% has been reached. These combined effects explain the exceptional oxidation resistance of ultraflat Cu surfaces.

2.
Circ Res ; 133(3): 200-219, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37350264

RESUMO

BACKGROUND: The mTOR (mechanistic target of rapamycin) pathway is a complex signaling cascade that regulates cellular growth, proliferation, metabolism, and survival. Although activation of mTOR signaling has been linked to atherosclerosis, its direct role in lesion progression and in plaque macrophages remains poorly understood. We previously demonstrated that mTORC1 (mTOR complex 1) activation promotes atherogenesis through inhibition of autophagy and increased apoptosis in macrophages. METHODS: Using macrophage-specific Rictor- and mTOR-deficient mice, we now dissect the distinct functions of mTORC2 pathways in atherogenesis. RESULTS: In contrast to the atheroprotective effect seen with blockade of macrophage mTORC1, macrophage-specific mTORC2-deficient mice exhibit an atherogenic phenotype, with larger, more complex lesions and increased cell death. In cultured macrophages, we show that mTORC2 signaling inhibits the FoxO1 (forkhead box protein O1) transcription factor, leading to suppression of proinflammatory pathways, especially the inflammasome/IL (interleukin)-1ß response, a key mediator of vascular inflammation and atherosclerosis. In addition, administration of FoxO1 inhibitors efficiently rescued the proinflammatory response caused by mTORC2 deficiency both in vitro and in vivo. Interestingly, collective deletion of macrophage mTOR, which ablates mTORC1- and mTORC2-dependent pathways, leads to minimal change in plaque size or complexity, reflecting the balanced yet opposing roles of these signaling arms. CONCLUSIONS: Our data provide the first mechanistic details of macrophage mTOR signaling in atherosclerosis and suggest that therapeutic measures aimed at modulating mTOR need to account for its dichotomous functions.


Assuntos
Aterosclerose , Serina-Treonina Quinases TOR , Camundongos , Animais , Alvo Mecanístico do Complexo 2 de Rapamicina , Serina-Treonina Quinases TOR/metabolismo , Macrófagos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fatores de Transcrição/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo
3.
Mod Pathol ; 37(4): 100449, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369185

RESUMO

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.


Assuntos
Adenocarcinoma Sebáceo , Carcinoma de Células Escamosas , Neoplasias Oculares , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Sebáceas , Humanos , Prognóstico , Linfócitos do Interstício Tumoral/patologia , Carcinoma de Células Escamosas/patologia , Biomarcadores/metabolismo , Neoplasias Oculares/patologia , Neoplasias de Cabeça e Pescoço/patologia , Papillomavirus Humano
4.
J Nat Prod ; 87(1): 58-67, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38159296

RESUMO

Phytochemical investigation of the MeOH extract of Pinus eldarica needles led to the isolation and identification of a new clerodane-type diterpene, pinuseldarone (1), along with a known flavonoid, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2), through HPLC purification. The structure of the new compound 1 was elucidated using spectroscopic methods, including 1D and 2D NMR, as well as HRESIMS. Its absolute configuration was established through NOESY analysis and computational methods, including electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ probability analysis. The metabolic implications of the isolated compounds were assessed using a cultured brown adipocyte model derived from murine brown adipose tissue. It was observed that treatment with dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2) downregulates the adipogenic marker C/EBPδ and fatty acid transporter CD36, resulting in a significant reduction in lipid accumulation during brown adipocyte differentiation. However, pinuseldarone (1) treatment did not affect brown adipocyte differentiation. Interestingly, pretreatment with pinuseldarone (1) potentiated the pharmacological stimulation of brown adipocytes, seemingly achieved by sensitizing their response to ß3-adrenoreceptor signaling. Therefore, our findings indicate that phytochemicals derived from P. eldarica needles could potentially serve as valuable compounds for adjusting the metabolic activity of brown adipose tissue, a vital component in maintaining whole-body metabolic homeostasis.


Assuntos
Diterpenos Clerodânicos , Pinus , Animais , Camundongos , Adipogenia , Adipócitos Marrons/metabolismo , Termogênese
5.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34815341

RESUMO

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.


Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Operante/fisiologia , Giro do Cíngulo/patologia , Tonsila do Cerebelo/metabolismo , Animais , Comportamento Animal , Tomada de Decisões/fisiologia , Masculino , Canais de Potássio/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Recompensa , Comportamento Social
6.
Health Commun ; 39(5): 937-944, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37038244

RESUMO

Applying fuzzy trace theory to misinformation related to COVID-19, the present study (a) examines the roles of gist knowledge in predicting misinformation acceptance, and (b) further examines whether a gist cue in fact checking scales affects the level of gist knowledge. Study 1 (a survey) showed that categorical gist knowledge was negatively related to misinformation acceptance, whereas ordinal gist knowledge was not, when both types of knowledge were included in the model. In addition, Study 2 (an experiment) showed that fact checking scales containing a categorical gist cue resulted in greater categorical gist knowledge.


Assuntos
Comunicação , Humanos , Inquéritos e Questionários
7.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39273406

RESUMO

Glehnia littoralis is a perennial herb found in coastal sand dunes throughout East Asia. This herb has been reported to have hepatoprotective, immunomodulatory, antioxidant, antibacterial, antifungal, anti-inflammatory, and anticancer activities. It may be effective against hepatocellular carcinoma (HCC). However, whether this has been proven through gene-level RNA-seq analysis is still being determined. Therefore, we are attempting to identify target genes for the cell death process by analyzing the transcriptome of Hep3B cells among HCC treated with GLE (Glehnia littoralis extract) using RNA-seq. Hep3B was used for the GLE treatment, and the MTT test was performed. Hep3B was then treated with GLE at a set concentration of 300 µg/mL and stored for 24 h, followed by RNA isolation and sequencing. We then used the data to create a plot. As a result of the MTT analysis, cell death was observed when Hep3B cells were treated with GLE, and the IC50 was about 300 µg/mL. As a result of making plots using the RNA-seq data of Hep3B treated with 300 µg/mL GLE, a tendency for the apoptotic process was found. Flow cytometry and annexin V/propidium iodide (PI) staining verified the apoptosis of HEP3B cells treated with GLE. Therefore, an increase or decrease in the DEGs involved in the apoptosis process was confirmed. The top five genes increased were GADD45B, DDIT3, GADD45G, CHAC1, and PPP1R15A. The bottom five genes decreased were SGK1, CX3CL1, ZC3H12A, IER3, and HNF1A. In summary, we investigated the RNA-seq dataset of GLE to identify potential targets that may be involved in the apoptotic process in HCC. These goals may aid in the identification and management of HCC.


Assuntos
Apoptose , Carcinoma Hepatocelular , Neoplasias Hepáticas , Extratos Vegetais , RNA-Seq , Humanos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos
8.
Int J Mol Sci ; 25(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255858

RESUMO

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.


Assuntos
Antioxidantes , Cirsium , Antioxidantes/farmacologia , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Polifenóis/farmacologia , Extratos Vegetais/farmacologia
9.
J Nat Prod ; 86(8): 1891-1900, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37506055

RESUMO

Streptomyces spp. are well-known symbiotic microorganisms that produce antimicrobial metabolites against various pathogens. We isolated actinomycetes from the body surface of the termite Odontotermes formosanus and identified it as Streptomyces neopeptinius BYF101 based on 16S rRNA phylogenetic analysis. Chemical analysis of the cultures of termite-associated S. neopeptinius BYF101 via HR-MS2 and GNPS analyses enabled the isolation and identification of 20 metabolites, including the unreported obscurolide-type metabolites (1-3). The chemical structures of unreported compounds (1-3) were elucidated using HR-ESI-MS and 1D and 2D NMR analysis, and their absolute configurations were determined via chemical reactions followed by the application of competing enantioselective acylation (CEA) and computational methods for ECD and DP4+ probability calculation. The isolated compounds (1-20) were tested to determine their antifungal activity against two human fungal pathogens, Candida albicans and Cryptococcus neoformans. Among the compounds tested, indole-3-carboxylic acid (9) displayed antifungal activity against C. neoformans, with an MIC value of 12 µg/mL.


Assuntos
Cryptococcus neoformans , Isópteros , Streptomyces , Animais , Humanos , Antifúngicos/química , Isópteros/microbiologia , RNA Ribossômico 16S/genética , Filogenia , Streptomyces/química , Testes de Sensibilidade Microbiana , Candida albicans
10.
Health Commun ; 38(3): 585-593, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34376089

RESUMO

The present study tests and extends the RISP model (a) by applying the model in the context of COVID-19 in South Korea and (b) by examining the impacts of information seeking and processing on misinformation exposure and acceptance. Based on a survey of 346 Korean adults, this study showed that information avoidance, but not information seeking, was a positive predictor of misinformation exposure. In addition, heuristic processing, but not systematic processing, moderated the relationship between misinformation exposure and misinformation acceptance, such that the relationship between misinformation exposure and misinformation acceptance was stronger among those who showed greater tendency for heuristic processing. In addition, information insufficiency was a negative predictor of both information avoidance and heuristic processing. Theoretical and practical implications are discussed.


Assuntos
COVID-19 , Adulto , Humanos , Comunicação , Inquéritos e Questionários , República da Coreia
11.
Health Commun ; 38(12): 2742-2749, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35968837

RESUMO

Based on the Risk Information Seeking and Processing Model, the present study examines whether COVID-19 message fatigue leads to greater information avoidance and heuristic processing, and consequently greater acceptance of misinformation. We conducted a survey of 821 Korean adults regarding their information seeking and processing regarding COVID-19 vaccination. Results of SEM analyses showed that COVID-19 message fatigue was (a) negatively related to information insufficiency and (b) positively related to information avoidance and heuristic processing. Information avoidance and heuristic processing were subsequently related to greater levels of misinformation acceptance. Theoretical and practical implications are discussed.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Comunicação , Comportamento de Busca de Informação , Adulto , Humanos , Povo Asiático/psicologia , COVID-19/epidemiologia , COVID-19/psicologia , Fadiga/psicologia
12.
Sensors (Basel) ; 23(13)2023 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-37447942

RESUMO

Cracks have a primary effect on the failure of a structure. Therefore, the development of crack sensors with high accuracy and resolution and cracks detection method are important. In this study, the crack sensors were fabricated, and the crack locations were detected with the electrical signal of the crack sensor. First, a metal grid-type micro-crack sensor based on silver was fabricated. The sensor is made with electrohydrodynamics (EHD) inkjet printing technology, which is well known as the next generation of printed electronics technology. Optimal printing conditions were established through experiments, and a grid sensor was obtained. After that, single cracks and multiple cracks were simulated on the sensor, and electrical signals generated from the sensor were measured. The measured electrical signal tracked the location of the cracks in three steps: simple cross-calculation, interpolation, and modified P-SPICE. It was confirmed that cracks could be effectively found and displayed using the method presented in this paper.


Assuntos
Sistemas Computacionais , Eletricidade , Eletrônica , Prata , Tecnologia
13.
Sensors (Basel) ; 23(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36904838

RESUMO

As the demands of various network-dependent services such as Internet of things (IoT) applications, autonomous driving, and augmented and virtual reality (AR/VR) increase, the fifthgeneration (5G) network is expected to become a key communication technology. The latest video coding standard, versatile video coding (VVC), can contribute to providing high-quality services by achieving superior compression performance. In video coding, inter bi-prediction serves to improve the coding efficiency significantly by producing a precise fused prediction block. Although block-wise methods, such as bi-prediction with CU-level weight (BCW), are applied in VVC, it is still difficult for the linear fusion-based strategy to represent diverse pixel variations inside a block. In addition, a pixel-wise method called bi-directional optical flow (BDOF) has been proposed to refine bi-prediction block. However, the non-linear optical flow equation in BDOF mode is applied under assumptions, so this method is still unable to accurately compensate various kinds of bi-prediction blocks. In this paper, we propose an attention-based bi-prediction network (ABPN) to substitute for the whole existing bi-prediction methods. The proposed ABPN is designed to learn efficient representations of the fused features by utilizing an attention mechanism. Furthermore, the knowledge distillation (KD)- based approach is employed to compress the size of the proposed network while keeping comparable output as the large model. The proposed ABPN is integrated into the VTM-11.0 NNVC-1.0 standard reference software. When compared with VTM anchor, it is verified that the BD-rate reduction of the lightweighted ABPN can be up to 5.89% and 4.91% on Y component under random access (RA) and low delay B (LDB), respectively.

14.
Int J Mol Sci ; 24(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37298192

RESUMO

Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer.


Assuntos
Antineoplásicos , Flavonas , Neoplasias da Próstata , Masculino , Humanos , Flavonas/farmacologia , Flavonas/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Apoptose , Apigenina/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico
15.
Allergy ; 77(7): 2131-2146, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35038351

RESUMO

BACKGROUND: NLRP3-driven inflammatory responses by circulating and lung-resident monocytes are critical drivers of asthma pathogenesis. Autophagy restrains NLRP3-induced monocyte activation in asthma models. Yet, the effects of autophagy and its master regulator, transcription factor EB (TFEB), on monocyte responses in human asthma remain unexplored. Here, we investigated whether activation of autophagy and TFEB signaling suppress inflammatory monocyte responses in asthmatic individuals. METHODS: Peripheral blood CD14+ monocytes from asthmatic patients (n = 83) and healthy controls (n = 46) were stimulated with LPS/ATP to induce NLRP3 activation with or without the autophagy inducer, rapamycin. ASC specks, caspase-1 activation, IL-1ß and IL-18 levels, mitochondrial function, ROS release, and mTORC1 signaling were examined. Autophagy was evaluated by LC3 puncta formation, p62/SQSTM1 degradation and TFEB activation. In a severe asthma (SA) model, we investigated the role of NLRP3 signaling using Nlrp3-/- mice and/or MCC950 administration, and the effects of TFEB activation using myeloid-specific TFEB-overexpressing mice or administration of the TFEB activator, trehalose. RESULTS: We observed increased NLRP3 inflammasome activation, concomitant with impaired autophagy in circulating monocytes that correlated with asthma severity. SA patients also exhibited mitochondrial dysfunction and ROS accumulation. Autophagy failed to inhibit NLRP3-driven monocyte responses, due to defective TFEB activation and excessive mTORC1 signaling. NLRP3 blockade restrained inflammatory cytokine release and linked airway disease. TFEB activation restored impaired autophagy, attenuated NLRP3-driven pulmonary inflammation, and ameliorated SA phenotype. CONCLUSIONS: Our studies uncover a crucial role for TFEB-mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA.


Assuntos
Asma , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Asma/metabolismo , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Inflamassomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Int J Mol Sci ; 23(14)2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35887080

RESUMO

Breast cancer is one of the top causes of death, particularly among women, and it affects many women. Cancer can also be caused by various factors, including acquiring genetic alteration. Doctors use radiation to detect and treat breast cancer. As a result, breast cancer becomes radiation-resistant, necessitating a new strategy for its treatment. The approach discovered by the researchers is a flavonoid, which is being researched to see if it might help treat radiation-resistant breast cancer more safely than an approved medicine already being used in the field. As a result, this study focuses on the role of flavonoids in breast cancer suppression, breast cancer gene anomalies, and the resulting apoptotic mechanism.


Assuntos
Neoplasias da Mama , Flavonoides , Apoptose , Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos
17.
Int J Mol Sci ; 23(10)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35628252

RESUMO

Inflammation is a multifaceted response of the immune system at the site of injury or infection caused by pathogens or stress via immune cells. Due to the adverse effects of chemical drugs, plant-based compounds are gaining interest in current research. Prunetinoside or prunetin-5-O-glucoside (PUG) is a plant-based active compound, which possesses anti-inflammatory effects on immune cells. In this study, we investigate the effect of PUG on mouse macrophage RAW264.7 cells with or without stimulation of lipopolysaccharide (LPS). Cytotoxicity results showed that PUG is non-cytotoxic to the cells and it reversed the cytotoxicity in LPS-stimulated cells. The levels of nitric oxide (NO) and interleukin-6 (IL-6) were determined using a NO detection kit and IL-6 ELISA kit, respectively, and showed a significant decrease in NO and IL-6 in PUG-treated cells. Western blot and qRT-PCR were performed for the expression of two important pro-inflammatory cytokines, COX2 and iNOS, and found that their expression was downregulated in a dose-dependent manner. Other pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNFα, had reduced mRNA expression after PUG treatment. Furthermore, a Western blot was performed to calculate the expression of NF-κB and MAPK pathway proteins. The results show that PUG administration dramatically reduced the phosphorylation of p-Iκbα, p-NF-κB 65, and p-JNK. Remarkably, after PUG treatment, p-P38 and p-ERK remain unchanged. Furthermore, docking studies revealed that PUG is covalently linked to NF-κB and suppresses inflammation. In conclusion, PUG exerted the anti-inflammatory mechanism by barring the NF-κB pathway and activating JNK. Thus, prunetinoside could be adopted as a therapeutic compound for inflammatory-related conditions.


Assuntos
Cumarínicos , Macrófagos , NF-kappa B , Animais , Anti-Inflamatórios/uso terapêutico , Cumarínicos/farmacologia , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7
18.
Int J Mol Sci ; 23(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36142874

RESUMO

Cancer is a horrific disease that, to date, has no cure. It is caused by various factors and takes many lives. Apoptosis is a programmed cell death mechanism and if it does not function correctly in cancer cells, it can lead to severe disease. There are various signaling pathways for regulating apoptosis in cancer cells. Flavonoids are non-artificial natural bioactive compounds that are gaining attention as being capable of for inducing apoptosis in cancer cells. Among these, in this study, we focus on flavones. Flavones are a subclass of the numerous available flavonoids and possess several bioactive functions. Some of the most reported and well-known critical flavones, namely apigenin, acacetin, baicalein, luteolin, tangeretin, and wogonin, are discussed in depth in this review. Our main aim is to investigate the effects of the selected flavones on apoptosis and cell signaling pathways that contribute to death due to various types of cancers.


Assuntos
Flavonas , Neoplasias , Apigenina/farmacologia , Apoptose , Flavonas/farmacologia , Flavonoides/farmacologia , Humanos , Luteolina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais
19.
Int J Mol Sci ; 23(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36012164

RESUMO

Kynurenic acid was included in the three compounds (caffeic acid, chlorogenic acid, and kynurenic acid) that showed high antioxidant and anti-inflammatory potential among the phenolic compounds contained in Gynura procumbens. In this study, the mechanism of cancer cell death induced by kynurenic acid (KYNA), which has the highest molecular binding affinity, in the gastric cancer cell line AGS was confirmed in molecular docking analysis. KYNA showed the most cancer cell death effect on AGS cells among several gastric cancer cell lines (MKN, AGS, and SNU). AGS cells were used for later experiments, and KYNA concentrations of 0, 150, 200, and 250 µM were used. KYNA inhibited cell migration and proliferation in AGS cells in a concentration-dependent manner. G2/M phase cell cycle arrest and reduction of related proteins (Cdc25C, CDK1 and CyclinB1) were confirmed in KYNA-treated AGS cells. Apoptosis of KYNA-treated AGS cells was confirmed by Annexin V/propidium iodide (PI) staining flow cytometry analysis. As a result of morphological chromatin condensation through DAPI (4',6-diamidino-2-phenylindole), intense blue fluorescence was confirmed. The mechanism of apoptosis induction of KYNA-treated AGS cells was confirmed by western blotting. In the extrinsic pathway, apoptosis induction markers FasL, Fas, and Caspase-3 and -8 were increased in a concentration-dependent manner upon KYNA treatment. In the intrinsic pathway, the expression of anti-apoptotic factors PI3K, AKT, and Bcl-xL was down-regulated, and the expression of apoptosis-inducing factors BAD, Bak, Bax, Cytochrom C, and Caspase-9 was up-regulated. Therefore, in the present study, we strongly imply that KYNA induces apoptosis in AGS gastric cancer cells. This suggests that KYNA, a natural compound, could be the basis for drug for the treatment of gastric cancer.


Assuntos
Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Ácido Cinurênico/farmacologia , Ácido Cinurênico/uso terapêutico , Simulação de Acoplamento Molecular , Neoplasias Gástricas/metabolismo
20.
Molecules ; 27(6)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35335230

RESUMO

As part of an ongoing natural product chemical research for the discovery of bioactive secondary metabolites with novel structures, wild fruiting bodies of Daedaleopsis confragosa were collected and subjected to chemical and biological analyses. We subjected the fractions derived from the methanol extract of the fruiting bodies of D. confragosa to bioactivity-guided fractionation because the methanol extract of D. confragosa showed antibacterial activity against Helicobacter pylori strain 51, according to our bioactivity screening. The n-hexane and dichloromethane fractions showed moderate to weak antibacterial activity against H. pylori strain 51, and the active fractions were analyzed for the isolation of antibacterial compounds. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that the n-hexane fraction contains several compounds which are absent in the other fractions, so the fraction was prioritized for further fractionation. Through chemical analysis of the active n-hexane and dichloromethane fractions, we isolated five ergosterol derivatives (1-5), and their chemical structures were determined to be demethylincisterol A3 (1), (20S,22E,24R)-ergosta-7,22-dien-3ß,5α,6ß-triol (2), (24S)-ergosta-7-ene-3ß,5α,6ß-triol (3), 5α,6α-epoxy-(22E,24R)-ergosta-7,22-dien-3ß-ol (4), and 5α,6α-epoxy-(24R)-ergosta-7-en-3ß-ol (5) by NMR spectroscopic analysis. This is the first report on the presence of ergosterol derivatives (1-5) in D. confragosa. Compound 1 showed the most potent anti-H. pylori activity with 33.9% inhibition, rendering it more potent than quercetin, a positive control. Compound 3 showed inhibitory activity comparable to that of quercetin. Distribution analysis of compound 1 revealed a wide presence of compound 1 in the kingdom Fungi. These findings indicate that demethylincisterol A3 (1) is a natural antibiotic that may be used in the development of novel antibiotics against H. pylori.


Assuntos
Agaricales , Antibacterianos/farmacologia , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Polyporaceae , República da Coreia , Esteróis/farmacologia , Espectrometria de Massas em Tandem
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