RESUMO
BACKGROUND: Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community. METHOD: This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes. RESULTS: 7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate. CONCLUSION: In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.
Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Adipogenia/efeitos dos fármacos , Obesidade/metabolismo , Camundongos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Masculino , PPAR gama/metabolismo , PPAR gama/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genética , Camundongos Obesos , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Adipocinas/metabolismo , Fármacos Antiobesidade/farmacologia , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAATRESUMO
Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we investigated the effects of n-trans-hibiscusamide (NHA) and its derivative 4-O-(E)-feruloyl-N-(E)-hibiscusamide (HAD) on receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL)-induced osteoclast differentiation and an ovariectomized osteoporosis mouse model. NHA and HAD significantly inhibited the differentiation of osteoclasts from bone marrow-derived macrophages (BMMs) and the expression of osteoclast differentiation-related genes. At the molecular level, NHA and HAD significantly downregulated the phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules. However, Akt and NF-κB phosphorylation was inhibited only after NHA or HAD treatment. In the ovariectomy (OVX)-induced osteoporosis model, both NHA and HAD effectively improved trabecular bone structure. C-terminal telopeptide (CTX), a bone resorption marker, and RANKL, an osteoclast stimulation factor, were significantly reduced by NHA and HAD. The tartrate-resistant acid phosphatase (TRAP)-stained area, which indicates the osteoclast area, was also decreased by these compounds. These results show the potential of NHA and HAD as therapeutic agents for osteoporosis.
Assuntos
Acrilamidas/farmacologia , Guaiacol/análogos & derivados , Osteoporose/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica/efeitos dos fármacos , Guaiacol/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.
Assuntos
Alpinia/química , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Inflamação/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/metabolismo , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Formaldeído/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolissacarídeos/efeitos adversos , Camundongos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação , Fator de Necrose Tumoral alfa/genéticaRESUMO
Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.
Assuntos
Amidas/farmacologia , Orelha/patologia , Edema/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Piper/química , Amidas/química , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Xilenos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Many studies have identified and described various medicinal effects of cirsiliol. Here, we investigated the signaling pathway involved in the anti-inflammatory effects of cirsiliol on IL-6-induced activity. Cirsiliol showed no cytotoxicity and inhibited pSTAT3-induced luciferase activity. At the molecular level, cirsiliol suppressed the expression of IL-6-induced inflammatory marker genes such as CRP, IL-1ß, ICAM-1 and SOCS3, IL-6-induced activation of Jak2, gp130, STAT3 and ERK and nuclear translocation of STAT3, as measured by PCR, immunofluorescence staining and western blot analysis. However, the interaction between IL-6 and its receptor was not affected by cirsiliol treatment. These results indicate that cirsiliol attenuates IL-6-induced cellular signaling by regulating Jak2 phosphorylation. Therefore, cirsiliol could be a therapeutic agent for IL-6-related inflammatory diseases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Flavonas/uso terapêutico , Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Anti-Inflamatórios/farmacologia , Flavonas/farmacologia , Humanos , Técnicas In VitroRESUMO
Three new sesquiterpenoids (compounds 4, 5, and 26), along with 23 known sesquiterpenoids (compounds 1-3 and 6-25) and two diterpenoids (compounds 27 and 28), were obtained from Curcuma phaeocaulis, and their chemical structures were determined through nuclear magnetic resonance (NMR), circular dichroism (CD), and high-resolution electrospray ionization (HRESIMS) spectroscopic data, which were compared to the data from previous studies. All isolates were tested for inhibitory activity against interleukin (IL)-6-stimulated STAT3 expression using a luciferase reporter assay, and curzerenone (21) and 8-epi-galanolactone (28) displayed promising signal transducer and activator of transcription (STAT3)-inhibitory activities with IC50 values of 4.8 and 4.1⯵M, respectively. In addition, these candidates significantly suppressed the mRNA expression levels of the proinflammatory genes IL-1ß and C-reactive protein (CRP) via blockade of the IL-6-activated Janus kinase 2 (JAK2)/STAT3 and ERK-MAPK signaling pathways. These results suggest that curzerenone (21) and 8-epi-galanolactone (28) may be potential candidates for ameliorating severe inflammatory diseases.
Assuntos
Curcuma/química , Diterpenos/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Diterpenos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/farmacologia , Modelos Moleculares , Compostos Fitoquímicos , Sesquiterpenos/químicaRESUMO
Three undescribed diarylheptanoids (3: -5: ) and six known curcuminoids (1, 2: , and 6: -9: ) were obtained from the ethyl acetate-soluble fraction of an ethanolic extract of Curcuma phaeocaulis. Their chemical structures and absolute configurations were elucidated by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy, and the modified Mosher's method. Previous studies constructed Hep3B cells stably transfected with pSTAT3-Luc plasmid containing STAT3 binding site to discover STAT3 inhibitors from natural products. The STAT3 inhibitory activities of all isolates were measured in transfected Hep3B cells after treatment with IL-6. Compound 5: ((5R)-1,7-Bis(3,4-dimethoxyphenyl)-3-methoxy-1-hepten-5-ol), demethoxycurcumin (7: ), and curcumin (8: ) exhibited significant inhibitory activity (IC50 values: 11.1, 1.9, and 1.6 µM, respectively). Furthermore, IL-6-induced phosphorylation of STAT3, and the mRNA expression levels of inflammation-related genes such as CRP, IL-1ß, ICAM-1, and SOCS3 were significantly reduced by exposure to compound 5: . These data suggested that the inhibitory activity of 5: is associated with the suppression of STAT3 phosphorylation. Thus, compound 5: may be a promising candidate for the treatment of cancer or inflammatory diseases related to the IL-6/STAT3 signaling pathway.
Assuntos
Curcuma , Diarileptanoides/farmacologia , Interleucina-6/farmacologia , Fator de Transcrição STAT3/efeitos dos fármacos , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Curcuma/química , Diarileptanoides/isolamento & purificação , Humanos , Interleucina-6/antagonistas & inibidores , Espectroscopia de Ressonância Magnética , Plantas Medicinais/química , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Oleanolic acid acetate (OAA), a major triterpenoid compound of Vigna angularis (azuki bean, V. angularis), has been shown to downregulate inflammatory responses in macrophages. Here, we show the molecular basis for the effect of OAA on Toll-like receptor (TLR) downstream signaling. OAA treatment significantly inhibited the secretion of embryonic alkaline phosphatase (SEAP) induced by polyinosinic acid (poly(I), TLR3 ligand) in a dose-dependent manner and without cytotoxicity in THP1-XBlue cells. In addition, OAA downregulated the gene expression of poly(I) induced pro-inflammatory cytokines and chemokines genes such as MCP-1, IL-1ß, IL-8, VCAM-1 and ICAM-1. Furthermore, we found that the inhibition activity of OAA was accompanied by decreased activation of not only nuclear factor-kappa B (NF-κB) signaling but also mitogen-activated protein kinase (MAPK) signaling upon stimulation with the TLR3 agonist. Interestingly, the interaction of OAA with IκB kinase α/ß (IKKα/ß) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα), extracellular regulated kinases (ERK), and p38, in an in vitro model. The action of OAA was regulated by TLR3, demonstrating that TLR3 plays a critical role in mediating the physiologically-relevant anti-inflammatory action of OAA and that the interaction with IKKα/ß is modulated through TLR3. These results reveal new insight into the understanding of the regulatory mechanisms of the downstream TLR3 signaling pathway and consequent inflammatory responses that are involved in the development and progression of inflammatory diseases.
Assuntos
Acetatos/farmacologia , Anti-Inflamatórios/farmacologia , Quinase I-kappa B/metabolismo , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Receptor 3 Toll-Like/metabolismo , Linhagem Celular , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Nine new sesquiterpenoid lactones and 11 known analogues were isolated from the aerial parts of Salvia plebeia R.Br. Their structures were elucidated via HRESIMS and NMR data, and their absolute configurations were defined via electronic circular dichroism data, X-ray crystallographic analysis, and the modified Mosher's ester method. Compounds 1-20 were investigated for their ability to inhibit LPS-stimulated nitric oxide production in murine macrophage cells. Of the isolates, epi-eudebeiolide C (20) showed the highest inhibitory effect (IC50 of 17.9 µM). mRNA and protein expression of inducible nitric oxide synthase (iNOS), but not that of cyclooxygenase-2 (COX-2), was dose-dependently decreased by 20 in LPS-activated RAW 264.7 cells. Based on a mechanistic study involving the nuclear factor-κB (NF-κB) signaling pathway, the anti-inflammatory effect of 20 was attributed to NF-κB activation blockade via inhibition of NF-κB (IκB) phosphorylation. Therefore, 20 might be a potential candidate for relieving inflammatory diseases.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Lactonas/isolamento & purificação , Lactonas/farmacologia , Componentes Aéreos da Planta/química , Salvia/química , Sesquiterpenos de Eudesmano/isolamento & purificação , Sesquiterpenos de Eudesmano/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Proteínas I-kappa B/metabolismo , Lactonas/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ressonância Magnética Nuclear Biomolecular , República da Coreia , Sesquiterpenos de Eudesmano/química , Transdução de Sinais/efeitos dos fármacosRESUMO
In this study, a reference-free damage characterization technique is developed not only to identify but also to locate and quantify damage in composite structures subject to varying temperature conditions. First, damage is characterized in terms of a damage index (m-value) defined as the ratio of damage size to the wavelength of the A0 mode within the damage. Then, a feasible solution space defining all possible combinations of the damage location and size are estimated without using any prior baseline data obtained from the pristine condition of a structure or different paths. When additional information such as the A0 mode group velocity within the pristine region of the structure becomes available, the estimates for the damage location and size are updated with better accuracy. The uniqueness of this study lies in that damage localization and quantification as well as identification are all performed without comparing current Lamb wave signals with the ones obtained from the pristine condition of the target structure, making the proposed technique more attractive for online monitoring. Numerical and experimental tests are presented to demonstrate the effectiveness of the proposed damage detection technique under varying temperature.
RESUMO
This paper presents a spectral noise and data reduction technique based on long short-term memory (LSTM) network for nonlinear ultrasonic modulation-based fatigue crack detection. The amplitudes of the nonlinear modulation components created by a micro fatigue crack are often very small and masked by noise. In addition, the collection of large amounts of data is often undesirable owing to the limited power, data storage, and data transmission bandwidth of monitoring systems. To tackle the issues, an LSTM network was applied to ultrasonic signals to reduce the noise level and the amount of data. The proposed technique offers the following benefits: (1) spectral noise reduction using the LSTM network for ultrasonic signals and (2) data reduction without compromising the spectral density amplitude of the existing nonlinear modulation components. Finally, the performance evaluation was conducted using the data obtained from complex geometry and real structure under external noises, indicating that the proposed method can be applied to various structures.
RESUMO
Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-ß (IFN-ß) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-ß effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-ß, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-ß plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-ß upregulated SIRT1 protein expression in endothelial cells in a protein synthesisindependent manner. IFN-ß plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-ß plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-ß plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway. [BMB Reports 2023; 56(5): 314-319].
Assuntos
Sepse , Sirtuína 1 , Humanos , Animais , Camundongos , Sirtuína 1/metabolismo , Interferon beta , Células Endoteliais/metabolismo , Glicocálix/metabolismo , Heparina Liase , Sepse/tratamento farmacológico , Sepse/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Vigna angularis is an edible crop and herbal medicine that is known to have antipyretic, anti-inflammatory, and anti-edema effects. Many studies have been conducted on the 95% ethanol extract of V. angularis, but there is little research on the 70% ethanol extract and hemiphloin, which is a new indicator component of the 70% ethanol extract of V. angularis. To investigate the in vitro anti-atopic effect and verify the mechanism action of 70% ethanol extract of V. angularis (VAE), TNF-α/IFN-γ-induced HaCaT keratinocytes were used. The VAE treatment alleviated TNF-α/IFN-γ-induced IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC gene expressions and productions. VAE also inhibited the phosphorylation of MAPKs, including p38, ERK, JNK, STAT1, and NF-κB in TNF-α/IFN-γ-induced HaCaT cells. 2,4-dinitochlorobenzene (DNCB)-induced skin inflammation mice model, and HaCaT keratinocytes were used. In the DNCB-induced mouse model, VAE treatment alleviated ear thicknesses and IgE levels. Furthermore, VAE decreased IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC gene expressions of DNCB-applied ear tissue. Additionally, we investigated the anti-atopic and anti-inflammatory effects of hemiphloin using TNF-α/IFN-γ-induced HaCaT keratinocytes and LPS-induced J774 macrophages. Treatment hemiphloin decreased gene expressions and productions of IL-1ß, IL-6, IL-8, CCL17/TARC, and CCL22/MDC in TNF-α/IFN-γ-induced HaCaT cells. The phosphorylations of p38, ERK, STAT1, and NF-κB were inhibited by hemiphloin in TNF-α/IFN-γ-induced HaCaT cells. Finally, hemiphloin showed anti-inflammatory activities in LPS-induced J774 cells. It decreased LPS-induced NO productions and iNOS and COX-2 expressions. Treatment of hemiphloin also inhibited LPS-induced TNF-α, IL-1ß, and IL-6 gene expressions. These results suggest that VAE is an anti-inflammatory agent for inflammatory skin diseases and that hemiphloin could be a therapeutic candidate for inflammatory skin diseases.
RESUMO
Ampelopsis brevipedunculata (Maxim.) Trautv. has been used for a long time as a folk remedy. According to studies, it possesses anti-inflammatory, antioxidant, and antibacterial properties. However, its effects on atopic dermatitis (AD) are poorly studied. Thus, we investigated the therapeutic effect of A. brevipedunculata (Maxim.) Trautv. extract (ABE-M) on 2,4-dinitrochlorobenzene (DNCB)-induced AD. For in vitro analysis, keratinocytes cell lines (HaCaT cells) were used. To evaluate the gene and protein expression levels of cytokines and chemokines, TNF-α/IFN-γ-stimulated HaCaT cells were treated with ABE-M. The cells and the supernatant were collected, then gene and protein levels were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay analysis. For in vivo analysis, BALB/c mice (6 weeks) were randomly separated into five groups (n = 5). The mice were applied DNCB and phosphate-buffered saline, dexamethasone (DX) or ABE-M (50, 100, and 200 mg/kg) was orally administrated for 28 days. At the end, ear tissues and blood were collected for histological analysis and evaluation of cytokines and chemokines. In keratinocytes, ABE-M inhibited the protein and mRNA levels of chemokines, and cytokines exposed by TNF-α/IFN-γ. Similarly, the expression of chemokines was suppressed by ABE-M in AD animal model induced by DNCB and the level of pro-inflammatory cytokines was decreased in a dose-dependent manner. Our research indicates that ABE-M could be a candidate material that can be used to improve skin immunity enhancement, health, and beauty.
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Lycium barbarum and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes (HaCaT) were induced by skin diseases caused by 2,4-dinitrochlorobenzene (DNCB) and tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ). The inhibitory activity of L. barbarum EtOH extract (LBE) and scopoletin on proinflammatory cytokines and chemokines was investigated. In the DNCB-induced animal model, oral administration of LBE inhibited skin lesions and proinflammatory cytokines and chemokines and showed inhibitory effects in vitro. Additionally, as a result of examining the efficacy of scopoletin isolated from L. barbarum, scopoletin in HaCaT cells showed inhibitory effects on proinflammatory cytokines and chemokines. It shows promise in the treatment of chronic skin diseases.
Assuntos
Dermatite Atópica , Lycium , Animais , Anti-Inflamatórios/farmacologia , Quimiocinas , Citocinas/farmacologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dinitroclorobenzeno/efeitos adversos , Humanos , Inflamação/patologia , Interferon gama/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/uso terapêutico , Escopoletina/farmacologia , Pele/patologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Leukemia inhibitory factor (LIF) is a stem cell growth factor that maintains selfrenewal of mouse embryonic stem cells (mESCs). LIF is a cytokine in the interleukin6 family and signals via the common receptor subunit gp130 and ligandspecific LIF receptor. LIF causes heterodimerization of the LIF receptor and gp130, activating the Janus kinase/STAT and MAPK pathways, resulting in changes in protein phosphorylation. The present study profiled LIFmediated protein phosphorylation changes in mESCs via proteomic analysis. mESCs treated in the presence or absence of LIF were analyzed via twodimensional differential ingel electrophoresis and protein and phosphoprotein staining. Protein identification was performed by matrixassisted laser desorption/ionizationtime of flight mass spectrophotometry. Increased phosphorylation of 16 proteins and decreased phosphorylation of 34 proteins in response to LIF treatment was detected. Gene Ontology terms enriched in these proteins included 'organonitrogen compound metabolic process', 'regulation of mRNA splicing via spliceosome' and 'nucleotide metabolic process'. The present results revealed that LIF modulated phosphorylation levels of nucleotide metabolismassociated proteins, thus providing insight into the mechanism underlying LIF action in mESCs.
Assuntos
Fator Inibidor de Leucemia/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Nucleotídeos/metabolismo , Animais , Linhagem Celular , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Camundongos , Fosforilação , Ligação Proteica , Proteômica , Receptores de OSM-LIF/metabolismoRESUMO
In Asia, Vigna angularis (azuki bean) has been used as a traditional medicine to treat various diseases because of its biological properties. Osteoarthritis (OA) and osteoporosis (OP) are common regenerative bone diseases that are characterized by deterioration of joint and bone structure. In this study, we evaluated the effects of Vigna angularis extract (VAE) on monosodium iodoacetate (MIA)-induced OA and ovariectomy (OVX)-induced OP models. In the MIA-induced OA results, severe OA was alleviated by the administration of VAE. Extensive local damage in the cartilage and hemorrhagic and edematous of surrounding tissues were decreased by VAE treatment. Articular cartilage was almost intact except for a focal mild abrasion, and the surface was glistening, similar to that of the normal joint. In the OVX-induced OP results, bone mineral content (BMC) and bone mineral density (BMD) were recovered by VAE treatment, and it improved the microstructures of bone. These results show that VAE could inhibit OA and OP symptoms.
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Eudebeiolide B is a eudesmane-type sesquiterpenoid compound isolated from Salvia plebeia R. Br., and little is known about its biological activity. In this study, we investigated the effects of eudebeiolide B on osteoblast differentiation, receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. Eudebeiolide B induced the expression of alkaline phosphatase (ALP) and calcium accumulation during MC3T3-E1 osteoblast differentiation. In mouse bone marrow macrophages (BMMs), eudebeiolide B suppressed RANKL-induced osteoclast differentiation of BMMs and bone resorption. Eudebeiolide B downregulated the expression of nuclear factor of activated T-cells 1 (NFATc1) and c-fos, transcription factors induced by RANKL. Moreover, eudebeiolide B attenuated the RANKL-induced expression of osteoclastogenesis-related genes, including cathepsin K (Ctsk), matrix metalloproteinase 9 (MMP9) and dendrocyte expressed seven transmembrane protein (DC-STAMP). Regarding the molecular mechanism, eudebeiolide B inhibited the phosphorylation of Akt and NF-κB p65. In addition, it downregulated the expression of cAMP response element-binding protein (CREB), Bruton's tyrosine kinase (Btk) and phospholipase Cγ2 (PLCγ2) in RANKL-induced calcium signaling. In an ovariectomized (OVX) mouse model, intragastric injection of eudebeiolide B prevented OVX-induced bone loss, as shown by bone mineral density and contents, microarchitecture parameters and serum levels of bone turnover markers. Eudebeiolide B not only promoted osteoblast differentiation but inhibited RANKL-induced osteoclastogenesis through calcium signaling and prevented OVX-induced bone loss. Therefore, eudebeiolide B may be a new therapeutic agent for osteoclast-related diseases, including osteoporosis, rheumatoid arthritis and periodontitis.
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INTRODUCTION: In the present study, an Adaptive Ground Control System for Multiple-UAV Operator Workload Decrement (AGCS) has been developed and the effectiveness of the system has been analyzed using eye-tracking and task performance data. The AGCS contained four more functions than the conventional GCS (CGCS) functions. The functions were based on real-time operator gaze information, multiple UAV operational state, and mission state information to help safe and efficient multiple UAV operation.METHODS: A total of 30 volunteers participated in the human-in-the-loop experiment to compare the performances of the newly developed AGCS and CGCS while executing reconnaissance and strike missions by operating multiple UAVs.RESULTS: According to the results, the AGCS demonstrates a statistically significant increase in mission performance, such as the mission completion rate (M = 97.3 vs. M = 95.4; SD = 3.1 vs. SD = 4.9) and mission success rate (M = 90.4 vs. M = 88.4; SD = 5.7 vs. SD = 5.6). In addition, the subjects' pupil diameter and gaze indicator show significant differences in the direction of workload reduction (α = 0.05). The subjects expressed positive opinions about using the AGCS.DISCUSSION: The originally developed AGCS showed a promising future extension based on the experimental data. After completion of the experiment, domain experts were interviewed and the next version will reflect their opinion.Lim H-J, Choi S-H, Oh J, Kim BS, Kim S, Yang JH. Adaptive ground control system of muliple-UAV operators in a simulated environment. Aerosp Med Hum Perform. 2019; 90(10):841-850.
Assuntos
Medicina Aeroespacial , Aeronaves , Militares , Carga de Trabalho , Adulto , Feminino , Humanos , Masculino , Treinamento por Simulação/métodos , Interface Usuário-Computador , Guerra , Adulto JovemRESUMO
Ampelopsis brevipedunculata (Maxim.) Trautv. (AB), a traditional East Asian medicine, exhibits protective effects against several inflammatory diseases. Our search for an inhibitor of IL-6-induced JAK2/STAT3 activation revealed that AB ethanolic extract (ABE) had a significant inhibitory effect on IL-6-induced STAT3 expression in Hep3B cells. The isolation and purification of an EtOAc-soluble fraction of ABE (ABEA) using reversed-phase high-performance liquid chromatography (RP-HPLC) afforded 17 compounds. The structures of these compounds (1-17) were elucidated based on 1H and 13C nuclear magnetic resonance (NMR) spectroscopy as well as electrospray-ionization mass spectrometry (ESI-MS) data. ABE and ABEA were screened by a luciferase assay using Hep3B cells transfected with the STAT3 reporter gene. ABEA exhibited potent inhibitory effects on IL-6-induced STAT3 expression; moreover, these effects arose from the inhibition of the phosphorylation of the STAT3, JAK2, and ERK proteins in U266 cells. In addition, the compounds isolated from ABEA were measured for their inhibitory effects on IL-6-stimulated STAT3 expression. Of the compounds isolated, betulin showed the greatest inhibitory effects on IL-6-induced STAT3 activation in the luciferase assay (IC50 value: 3.12 µM). Because of its potential for inhibiting STAT3 activation, A. brevipedunculata could be considered a source of compounds of pharmaceutical interest.