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Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases, and they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for the treatment of age-related neurodegenerative diseases. Emerging evidence suggests that mitochondrial dysfunction and reactive oxygen species (ROS) generation play central roles in the onset and progression of neurodegenerative diseases. Mitochondria are key regulators of respiratory function, cellular energy adenosine triphosphate production, and the maintenance of cellular redox homeostasis, which are essential for cell survival. Mitochondrial morphology and function are tightly regulated by maintaining a balance among mitochondrial fission, fusion, biogenesis, and mitophagy. In this review, we provide an overview of the main functions of mitochondria, with a focus on recent progress highlighting the critical role of ROS-induced oxidative stress, dysregulated mitochondrial dynamics, mitochondrial apoptosis, mitochondria-associated inflammation, and impaired mitochondrial function in the pathogenesis of age-related neurodegenerative diseases, such as AD and PD. We also discuss the potential of mitochondrial fusion and biogenesis enhancers, mitochondrial fission inhibitors, and mitochondria-targeted antioxidants as novel drugs for the treatment of these diseases.
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Mitocôndrias , Dinâmica Mitocondrial , Doenças Neurodegenerativas , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Animais , Dinâmica Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologiaRESUMO
Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of 'Hair growth' on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/ß-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/ß-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.
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Obesity is caused by the accumulation of excess lipids due to an energy imbalance. Differentiation of pre-adipocytes induces abnormal lipid accumulation, and reactive oxygen species (ROS) generated in this process promote the differentiation of pre-adipocytes through mitogen-activated protein kinase (MAPK) signaling. Peroxiredoxin (Prx) is a potent antioxidant enzyme, and peroxiredoxin 5 (Prx5), which is mainly expressed in cytosol and mitochondria, inhibits adipogenesis by regulating ROS levels. Based on previous findings, the present study was performed to investigate whether cytosolic Prx5 (CytPrx5) or mitochondrial Prx5 (MtPrx5) has a greater effect on the inhibition of adipogenesis. In this study, MtPrx5 decreased insulin-mediated ROS levels to reduce adipogenic gene expression and lipid accumulation more effectively than CytPrx5. In addition, we found that p38 MAPK mainly participates in adipogenesis. Furthermore, we verified that MtPrx5 overexpression suppressed the phosphorylation of p38 during adipogenesis. Thus, we suggest that MtPrx5 inhibits insulin-induced adipogenesis more effectively than CytPrx5.
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Adipogenia , Insulina , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Camundongos , Células 3T3-L1 , Diferenciação Celular , Insulina/metabolismo , Lipídeos/farmacologia , Mitocôndrias/metabolismo , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Peroxirredoxinas/farmacologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
INTRODUCTION: Allergic rhinitis and asthma share a common inflammatory mechanism and are closely related, recognized as "one airway disease." Thus, the guidelines recommend allergic rhinitis and asthma be treated together, and leukotriene antagonists and antihistamines have been administered simultaneously; however, there are few reports of the use of combination drugs so far. METHODS: The aim of the study was to evaluate the treatment effects and adverse events of Monterizine® (a combination of montelukast and levocetirizine); a total of 2,254 patients with perennial allergic rhinitis and asthma were prospectively enrolled from 60 hospitals nationwide in Korea. They were followed up for 3 (Period 1) or 6 months (Period 2). Total nasal symptom score (TNSS), satisfaction, and safety data were collected and compared to baseline. RESULTS: TNSS scores were analyzed for 2,254 subjects. At Period 1 (n = 2,024) and 2 (n = 1,861), the scores decreased significantly from baseline (-1.20 ± 2.49 and -1.63 ± 2.78, p < 0.001). The mean quality of life (QoL) was significantly improved at Period 1 and 2 relative to baseline (-3.75 ± 6.58, -4.83 ± 7.11, both p < 0.0001). There were no serious adverse drug reactions, but there were some minor reactions including nasopharyngitis (2.92%), rhinitis (0.37%), and somnolence (0.34%). CONCLUSIONS: TNSS score and QoL were significantly improved by 3-6 months' treatment with Monterizine without significant adverse reactions. These results indicate that Monterizine, as a combination drug, is effective and safe for improving nasal symptoms and quality of life in patients with allergic rhinitis who also have asthma.
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Asma , Quinolinas , Rinite Alérgica , Humanos , Qualidade de Vida , Acetatos/efeitos adversos , Quinolinas/efeitos adversos , Ciclopropanos/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/induzido quimicamente , Asma/tratamento farmacológico , Asma/induzido quimicamente , Combinação de Medicamentos , Resultado do TratamentoRESUMO
Banhasasim-tang (BST), a herbal medicine, has been used for nausea and fever from cold damage. This study aimed to investigate the protective effects of BST in cold restraint stress-induced gastric ulcers. Male Sprague Dawley rats were orally treated with various doses of BST including 0.25, 0.5, 1, 3, 6, 9, 12 and 18g/kg based on the human daily intake dose. After treatment once per day for 3 days, rats were restrained into the cold stress chamber for 12h at 4°C to induce gastric ulcers. Gastric hemorrhagic ulcer area was evaluated and serum adrenocorticotropic hormone (ACTH), corticosterone, epinephrine and dopamine levels were determined. Compared to cold stress-induced gastric ulcer rats, hemorrhage ulcer areas were reduced in BST-treated stomach tissues at all concentrations. Increased serum ACTH, corticosterone and epinephrine levels were significantly decreased by BST treatment in cold stress-induced gastric ulcer rats. Moreover, there were increments of serum dopamine levels in 3 and 6g/kg of BST-treated groups. Taken together, BST positively ameliorated cold restraint stress-induced gastric hemorrhage with decrease in serum stress-related biomarkers such as ACTH, corticosterone, epinephrine and dopamine. The 3-6-fold of human daily intake dose of BST exhibited protective effects as a herbal medicine for gastric ulcers.
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Temperatura Baixa/efeitos adversos , Fitoterapia , Úlcera Gástrica/tratamento farmacológico , Estresse Fisiológico , Animais , Dopamina/metabolismo , Medicina Herbária , Masculino , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , República da Coreia , Úlcera Gástrica/etiologiaRESUMO
Phlomis umbrosa has been traditionally used for bone diseases in traditional Korean Medicine. Sweroside (SOS), marker compounds of P. umbrosa, has been known to promote osteoblast differentiation. In this study, ameliorative effects of SOS on osteoporosis and potential target pathway were investigated. Ovariectomized mice were administered three doses of SOS three times a week for 4 weeks after inducing osteoporosis. Bone mineral content (BMC) and bone mineral density (BMD) were analyzed by dual energy X-ray absorptiometry. A human osteosarcoma cell line (SaOS-2) was differentiated to clarify the promoting effects of SOS on osteoblast differentiation and bone formation. Osteoblastic bone-forming markers were evaluated in lumbar vertebrae (LV) and mineralized SaOS-2 cells. SOS markedly elevated BMC and BMD levels and attenuated the bone marrow adipocytes in the femoral shaft. SOS increased the formation of bone matrix in SaOS-2 cells. Bone morphogenetic protein-2 (BMP2) and runt-related transcription factor 2 (CBFA1) in LV and SaOS-2 cells were up-regulated by SOS. SOS increased alkaline phosphatase (ALPL), osteopontin (SPP1), and bone sialoprotein-1 (BSPH1). In conclusion, SOS induced the formation of mineralized bone matrix by regulating BMP2/CBFA1-mediated molecules. Therefore, SOS could be a therapeutic compound of treatment for osteoporosis by producing the new bone matrix.
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Proteína Morfogenética Óssea 2 , Glucosídeos Iridoides/farmacologia , Osteoporose/tratamento farmacológico , Proteínas Secretadas pela Vesícula Seminal , Animais , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Osteoblastos , Osteogênese , Osteoporose Pós-Menopausa , Transdução de SinaisRESUMO
Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as Astragalus membranaceus BUNGE, Schizonepeta tenuifolia Briq., Cryptotympana pustulata Fabr., Angelica sinensis Diels, Arctium lappa L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.
Assuntos
Dermatite Atópica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Pele/efeitos dos fármacos , Animais , Dermatite Atópica/patologia , Proteínas Filagrinas , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Plantas Medicinais/química , Pele/patologiaRESUMO
Obesity was originally considered a disease endemic to developed countries but has since emerged as a global health problem. Obesity is characterized by abnormal or excessive lipid accumulation (World Health Organization, WHO) resulting from pre-adipocyte differentiation (adipogenesis). The endoplasmic reticulum (ER) produces proteins and cholesterol and shuttles these compounds to their target sites. Many studies have implicated ER stress, indicative of ER dysfunction, in adipogenesis. Reactive oxygen species (ROS) are also known to be involved in pre-adipocyte differentiation. Prx4 specific to the ER lumen exhibits ROS scavenging activity, and we thereby focused on ER-specific Prx4 in tracking changes in adipocyte differentiation and lipid accumulation. Overexpression of Prx4 reduced ER stress and suppressed lipid accumulation by regulating adipogenic gene expression during adipogenesis. Our results demonstrate that Prx4 inhibits ER stress, lowers ROS levels, and attenuates pre-adipocyte differentiation. These findings suggested enhancing the activity of Prx4 may be helpful in the treatment of obesity; the data also support the development of new therapeutic approaches to obesity and obesity-related metabolic disorders.
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Adipócitos/metabolismo , Adipogenia/genética , Estresse do Retículo Endoplasmático/genética , Insulina/farmacologia , Obesidade/metabolismo , Peroxirredoxinas/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/enzimologia , Adipogenia/efeitos dos fármacos , Animais , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Metabolismo dos Lipídeos/genética , Camundongos , Obesidade/genética , Peroxirredoxinas/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Reactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2-3T3-L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS-based therapeutic solutions for the treatment of obesity and obesity-related metabolic disorders.
Assuntos
Adipócitos , Adipogenia , Tecido Adiposo Branco/citologia , Metabolismo dos Lipídeos , Peroxirredoxinas/fisiologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Diferenciação Celular , Camundongos , Obesidade/metabolismo , Obesidade/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. Banhahubak-tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 µm (PM10)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM10, BALB/c mice were sensitized and challenged with OVA and PM10, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.
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Antiasmáticos/farmacologia , Asma , Janus Quinase 1/imunologia , Fator de Transcrição STAT6/imunologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antiasmáticos/química , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Comprimidos , Células Th2/imunologia , Células Th2/patologiaRESUMO
Both direct- and evanescent-field interactions with carbon nanotubes (CNTs) are applied to achieve stable Q-switched operation of Yb:KYW planar waveguide lasers. The performance characteristics were investigated in a same cavity configuration and analyzed in detail in the following three cases, CNTs deposited onto end mirror (M-coating), output coupler (OC-coating) and top surface of the planar waveguide (WG-coating). Maximum output powers, repetition rates, and minimum pulse durations are 61 mW, 1103 kHz and 215 ns for OC-coating, 39 mW, 1052 kHz and 275 ns for WG-coating, and 26 mW, 1119 kHz and 217 ns for M-coating, respectively. From the calculation of the configuration-dependent stability range, the beam size and the electric field distribution in the Yb:KYW planar waveguide, it is confirmed that the evanescent-field interaction scheme makes stable Q-switching possible with much lower intensities at saturable absorber compared to the direct-field interaction scheme in the presented waveguide laser operation.
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OBJECTIVE: Natural products are well known as the source of drugs in the treatment of allergic inflammation. Chrysophanol, an anthraquinone from the AST2017-01 extract, showed a beneficial anti-inflammatory effect on activated human mast cells in our previous study. However, a regulatory effect of AST2017-01 and chrysophanol on mast cell proliferation induced by thymic stromal lymphopoietin (TSLP) remains unclear. The present study determined the anti-proliferative effect and the fundamental mechanism of AST2017-01 and chrysophanol in mast cells. METHODS: We evaluated an anti-proliferative effect of AST2017-01 and chrysophanol in TSLP-stimulated human mast cell line, HMC-1. RESULTS: Without cytotoxicity, AST2017-01 and chrysophanol decreased mast cells growth and Ki67 mRNA expression increased by TSLP. AST2017-01 and chrysophanol enhanced expressions of p53 and Bax, whereas inhibited expression of Bcl-2. AST2017-01 and chrysophanol restored caspase-3 activity which was decreased by TSLP. AST2017-01 and chrysophanol suppressed expressions of murine double minute-2 protein and phosphorylated-signal transducer and activator of transcription six which are associated with the regulation of p53 protein. AST2017-01 and chrysophanol decreased levels of interleukin (IL)-13, IL-6, and tumor necrosis factor-α. Moreover, AST2017-01 and chrysophanol reduced mRNA expressions of TSLP receptor and IL-7 receptor α. CONCLUSIONS: Therefore, this study proposes that AST2017-01 and chrysophanol may be promising candidates for the development of potent anti-inflammatory or health functional foods.
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Antraquinonas/farmacologia , Anti-Inflamatórios/farmacologia , Misturas Complexas/farmacologia , Cordyceps/química , Mastócitos/efeitos dos fármacos , Rumex/química , Proteína Supressora de Tumor p53/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas , Humanos , Mastócitos/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fator de Transcrição STAT6/metabolismo , Linfopoietina do Estroma do TimoRESUMO
Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.
Assuntos
Morte Celular/efeitos dos fármacos , Fraxinus/química , Iridoides/farmacologia , Doenças Mitocondriais/tratamento farmacológico , Neurônios/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Dinaminas/genética , Dinaminas/metabolismo , Regulação da Expressão Gênica , Ácido Glutâmico , Hipocampo/citologia , Glucosídeos Iridoides , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Schisandra chinenesis (SC) has been reported to have ameliorative effect on osteoporosis. However, the mechanisms underlying the anti-osteoporosis activity of SC have not been clearly elucidated. In the present study, we determined the effects of SC on The receptor activator of NF-kB ligand (RANKL)-induced osteoclastogenesis and its potential mechanism. METHODS: Raw 264.7 cells were treated with 0.6, 6 and 60 µg/mL SC in the presence of 100 ng/mL RANKL for 7 days. RANKL-induced osteoclast formation was analyzed by tartrate resistant acid phosphatase (TRAP) staining. The osteoclast differentiation-related factors were confirmed along with TNF-α. RESULTS: SC inhibits the RANKL-induced osteoclast differentiation in dose-dependent manner within non-toxic concentrations. The supernatant concentrations of TNF-α were significantly decreased by SC treatment. In addition, osteoclastogenesis-related factors, TRAP6 and NF-κB, were markedly decreased by SC in RANKL-induced osteoclasts. Mechanistically, SC reduced the RANKL-triggered NFATc1 and c-fos expressions. CONCLUSIONS: Taken together, our data suggest that SC can modulate bone metabolism by suppressing RANKL-induced osteoclast differentiation.
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Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/genética , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/genética , Ligante RANK/metabolismo , Schisandra/química , Animais , Regulação para Baixo/efeitos dos fármacos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Oligopeptídeos/metabolismo , Osteoclastos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Dementia has been shown to be closely related with neuronal degeneration and/or a decrease in the activity of neural stem cells in many brain regions, including the hippocampus. It has been recently established that Neogenin is involved in the cell fate determination by regulating Oct3/4, SOX and Nanog, notable embryonic cell markers, expressions in pre-implantation mouse embryos. Further, Neogenin expression at both mRNA and protein levels is manifest in many brain regions in mice, but it remains unclear whether Neogenin expression is prerequisite for the maintenance of neural stem cells, particularly, playing a critical role in the hippocampus, a brain region known to be involved in memory generation and consolidation. Here, we provide evidence that supports that Neogenin is implicated in the maintenance of neural stem cells in the hippocampus by enhancing PCNA expressions. We have performed RT-PCR analysis, Western blotting, and immunohistochemistry with fetal rat brain tissues at E18 for Neogenin mRNA and protein profiling. Neuronal cells obtained from the hippocampus were subjected to FACS analysis for the identification of Neogenin-positive and/or neuronal stem cell marker-positive cells. Western blotting results showed that Neogenin expression was higher in the hippocampal region compared to the cortical region. FACS analysis results indicated that a significant population of fetal rat neuronal cells exhibiting Neogenin expression also displayed SOX2 expression, implying co-expression of Neogenin and SOX2 in the hippocampus. Next, we investigated the role of Neogenin through gain- and loss-of-function studies with cultured rat hippocampal neurons. Neogenin down-regulation by small hairpin RNAs led to a dramatic decrease in SOX2 expression while its up-regulation by overexpression caused an increase in PCNA expression, a cell proliferation marker, compared with none-transfected cells. From this study, we propose a model whereby Neogenin could maintain neural stem cell population and control cell proliferation.
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Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/embriologia , Proteínas de Membrana/genética , Células-Tronco Neurais/metabolismo , Fatores de Transcrição SOXB1/genética , Animais , Células Cultivadas , Hipocampo/citologia , Hipocampo/metabolismo , Proteínas de Membrana/análise , Células-Tronco Neurais/citologia , Antígeno Nuclear de Célula em Proliferação/análise , Antígeno Nuclear de Célula em Proliferação/genética , Ratos , Fatores de Transcrição SOXB1/análiseRESUMO
OBJECTIVE: To study the anti-inflammatory properties of OJ. CONTEXT: Ojayeonjonghwan (OJ) is a traditional Korean prescription, which has been widely used for the treatment of prostatitis. However, no scientific study has been performed of the anti-inflammatory effects of OJ. MATERIALS AND METHODS: Peritoneal macrophages were isolated 3-4 days after injecting a C57BL/6J mouse with thioglycollate. They were then treated with OJ water extract (0.01, 0.1, and 1 mg/mL) for 1 h and stimulated with lipopolysaccharide (LPS) for different times. Nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and proinflammatory cytokine levels were determined by NO assay, Western blotting, RT-PCR and ELISA. RESULTS: NO generation and iNOS induction were increased in the LPS-activated mouse peritoneal macrophages. However, NO generation and iNOS induction by LPS were suppressed by treatment with OJ for the first time. The IC50 value of OJ with respect to NO production was 0.09 mg/mL. OJ did not influence LPS-stimulated COX-2 induction, but did significantly decrease LPS-stimulated secretions and mRNA expressions of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Inhibition rates of TNF-α, IL-6, and IL-1ß at an OJ concentration of 1 mg/mL were 77%, 88%, and 50%, respectively. OJ also suppressed the LPS-induced nuclear translocation of NF-κB. High-performance liquid chromatography showed schizandrin and gomisin A are major components of OJ. CONCLUSIONS: OJ reduces inflammatory response, and this probably explains its positive impact on the prostatitis associated inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lignanas/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Compostos Policíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Células Cultivadas , Ciclo-Octanos/análise , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dioxóis/análise , Etnofarmacologia , Lignanas/análise , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Medicina Tradicional Coreana , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/química , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Compostos Policíclicos/análise , Prostatite/tratamento farmacológico , Prostatite/imunologia , Prostatite/metabolismo , Prostatite/patologia , TioglicolatosRESUMO
We demonstrate an all-fiber Tm-doped soliton laser with high power by using a monolayer graphene saturable absorber (SA). Large area, uniform monolayer graphene was transferred to the surface of the side-polished fiber (SPF) to realize an in-line graphene SA that operates around 2 µm wavelength. To increase the nonlinear interaction with graphene, we applied an over-cladding onto the SPF, where enhanced optical absorption at monolayer graphene was observed. All-fiber Tm-doped mode-locked laser was built including our in-line graphene SA, which stably delivered the soliton pulses with 773 fs pulse duration. The measured 3-dB spectral bandwidth was 5.14 nm at the wavelength of 1910 nm. We obtained the maximum average output power of 115 mW at a repetition rate of 19.31 MHz. Corresponding pulse energy was estimated to be 6 nJ, which is the highest value among all-fiber Tm-doped soliton oscillators using carbon-material-based SAs.
RESUMO
Graphene has proved to be an excellent broadband saturable absorber for mode-locked operation of ultrafast lasers. However, for the mid-infrared (mid-IR) range where broadly tunable sources are in great needs, graphene-based broadly tunable ultrafast mid-IR lasers have not been demonstrated so far. Here, we report on passive mode-locking of a mid-IR Cr:ZnS laser by utilizing a transmission-type monolayer graphene saturable absorber and broad spectral tunability between 2120 nm and 2408 nm, which is the broadest tuning bandwidth ever reported for graphene mode-locked mid-IR solid-state lasers. The recovery time of the saturable absorber is measured to be ~2.4 ps by pump-probe technique at a wavelength of 2350 nm. Stably mode-locked Cr:ZnS laser delivers Fourier transform-limited 220-fs pulses with a pulse energy of up to 7.8 nJ.
RESUMO
Formononetin is one of the main components of red clover plants and its role on hair regrowth against hair loss has not been established yet. In the present study, we assessed the potential effects of formononetin on alopecia, along with impaired hair cycles by induction of apoptosis-regression.Depilated C57BL/6 mice were used for monitoring the hair cycles. Formononetin (1 and 100 µM) was topically treated to the dorsal skin for 14 days. Topical formononetin treatment induced miniaturized hair follicles to recover to normal sizes. Tapering hair shaft began to grow newly, emerging from the hair follicles by formononetin. In addition, formononetin inhibited the activation of caspase-8 and decreased the procaspase-9 expression. As a result of formononetin treatment, anti-apoptotic Bcl-2 was up-regulated, whereas pro-apoptotic Bax and p53 were down-regulated, resulting in a decrease of caspase-3 activation. Formononetin showed the obvious inhibition of apoptosis under terminal deoxynucleotidyl transferase dUTP nick end labeling staining thereafter.Taken together, our findings demonstrate that formononetin exerted the hair regrowth effect on hair loss, in which the underlying mechanisms were associated with Fas/Fas L-induced caspase activation, thus inhibiting apoptosis.
Assuntos
Alopecia/tratamento farmacológico , Apoptose/efeitos dos fármacos , Isoflavonas/uso terapêutico , Administração Tópica , Alopecia/patologia , Animais , Caspase 8/metabolismo , Caspase 9/metabolismo , Inibidores de Caspase/uso terapêutico , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
We demonstrate a diode-pumped femtosecond-laser-inscribed Yb:YAG channel waveguide laser, Q-switched by using single-walled carbon nanotubes (SWCNTs) near 1029 nm. We used saturable absorber mirrors (SAMs) fabricated by depositing SWCNTs on three different output couplers. Best performance of the 9.3-mm-long ultra-compact Q-switched waveguide laser is obtained with an output coupling transmission of 20%. In this case, a maximum average output power of 60 mW with a corresponding pulse energy of 37.7 nJ and a pulse duration of 88 ns at 1.59-MHz repetition rate were achieved. The highest pulse energy of 39.2 nJ and the shortest pulse duration of 78 ns were obtained with 30% and 10% output couplers, respectively.