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Free radical is a marker in various inflammatory diseases. The antioxidant effect protects us from this damage, which also plays an essential role in preventing inflammation. Inflammation protects the body from biological stimuli, and pro-inflammatory mediators are negatively affected in the immune system. Inflammation caused by LPS is an endotoxin found in the outer membrane of Gram-negative bacteria, which induces immune cells to produce inflammatory cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. Based on this, the antioxidant and anti-inflammatory effects of plant extracts were investigated. First, the main phenolic compounds for the five peaks obtained from Stachys affinis extract (SAE) were identified. The antioxidant effect of each phenolic compound was confirmed through HPLC analysis before and after the competitive binding reaction between DPPH and the extract. Afterward, the anti-inflammatory effect of each phenolic compound was confirmed through competitive binding between COX2 and the extract in HPLC analysis. Lastly, the anti-inflammatory effect of SAE was confirmed through in vitro experiments and also confirmed in terms of structural binding through molecular docking. This study confirmed that phenolic compounds in SAE extract have potential antioxidant and anti-inflammatory effects, and may provide information for primary screening of medicinal plants.
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Anti-Inflamatórios , Antioxidantes , Simulação de Acoplamento Molecular , Extratos Vegetais , Polifenóis , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/química , Polifenóis/farmacologia , Polifenóis/química , Ciclo-Oxigenase 2/metabolismo , Cromatografia Líquida de Alta Pressão , AnimaisRESUMO
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.
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Antioxidantes , Cirsium , Antioxidantes/farmacologia , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Polifenóis/farmacologia , Extratos Vegetais/farmacologiaRESUMO
The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.
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Dermatitis is an inflammatory condition of the outer layer of the skin that causes itching, blisters, redness, swelling, and often exudation, scabs, and peeling. Among them, purulent inflammation is a symptom that often occurs on the skin and appears in the form of boils and acne. Various studies are being conducted to treat these inflammatory diseases. Accordingly, Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE), which uses herbal preparations such as Lonicera japonica, Citri Reticulatae Pericarpium, and Glycyrrhiza uralensis, has been used to suppress inflammation since ancient times, and its anti-inflammatory effect can be observed in skin keratinocytes after inducing inflammation. In this study, the major polyphenolic compounds in LCPE were quantitatively determined by analyzing the data through peak values using high-performance chromatography (HPLC-MS/MS) coupled with mass spectrometry. Additionally, bioactive compounds targeting 2,2-diphenyl-1-picrylhydrazyl (DPPH) were analyzed by ultrafiltration integrated with LC. Several compounds with the most significant effects were selected (chlorogenic acid, narirutin, and isorhamnetin). Skin keratinocytes induced by lipopolysaccharide (LPS) were treated with LCPE to show its anti-inflammatory effects. After LCPE treatment, inflammation-mediating cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were decreased. In addition, nuclear factor kappa (NF-кB) and mitogen-activated protein kinase (MAPK) were inhibited in important pathways related to inflammation. Lastly, molecular modeling was performed to determine binding scores with inflammation-related proteins using molecular docking for the selected compounds. According to these results, LCPE is effective in treating keratinocytes induced by LPS and reducing inflammation and has potential antioxidant effects, and the polyphenol components have been identified.
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Hepatocellular carcinoma (HCC) has a poor prognosis and a low survival rate. Drugs without side effects are desperately needed since chemotherapy has a negative effect on the host cells. Previous research has firmly established that plant-based compounds have significant bioactivities without a negative impact on the host. Flavonoids, in particular, are a class of compounds with both anti-inflammatory and anti-cancer properties. Prunetrin (PUR) is a glycosyloxyisoflavone (Prunetin 4'-O-glucoside) derived from Prunus sp., and its other form, called prunetin, showed optimistic results in an anti-cancerous study. Hence, we aimed to discover the anti-cancer ability of prunetrin in liver cancer Hep3B cells. Our cytotoxicity results showed that PUR can decrease cell viability. The colony formation assay confirms this strongly and correlates with cell cytotoxicity results. Prunetrin, in a dose-dependent manner, arrested the cell cycle in the G2/M phase and decreased the expression of cyclin proteins such as Cyclin B1, CDK1/CDC2, and CDC25c. Prunetrin treatment also promoted the strong cleavage of two important apoptotic hallmark proteins called PARP and caspase-3. It also confirms that apoptosis occurs through the mitochondrial pathway through increased expression of cleaved caspase-9 and increased levels of the pro-apoptotic protein Bak. Bak was significantly increased with the declining expression of the anti-apoptotic protein Bcl-xL. Next, it inhibits the mTOR/AKT signaling pathways, proving that prunetrin includes apoptosis and decreases cell viability by suppressing these pathways. Further, it was also observed that the activation of p38-MAPK was dose-dependent. Taken together, they provide evidence that prunetrin has an anti-cancerous ability in Hep3B liver cancer cells by arresting the cell cycle via p38 and inhibiting mTOR/AKT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Pontos de Checagem do Ciclo Celular , Transdução de Sinais , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Apigenina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Morte Celular , Apoptose , Proliferação de Células , Células Hep G2 , Linhagem Celular Tumoral , Receptores de Morte CelularRESUMO
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.
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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 farmacológicoRESUMO
Apigetrin (7-(ß-D-glucopyranosyloxy)-4',5-dihydroxyflavone), a glycoside bioactive dietary flavonoid derived from Taraxacum officinale and Teucrium gnaphalodes, is known to possess anticancer, antioxidant, and anti-inflammatory effects on numerous cancers. In the present study, we examined the effect of apigetrin in Hep3B hepatocellular cancer cell line (HCC). Apigetrin inhibited cell growth and proliferation of Hep3B cells, as confirmed by MTT and colony formation assay. We used apigetrin at concentrations of 0, 50, and 100 µM for later experiments. Of these concentrations, 100 µM of apigetrin showed a significant effect on cell inhibition. In apigetrin-treated Hep3B cells, cell cycle arrest occurred at the G2/M phase. Apoptosis and necroptosis of Hep3B cells treated with apigetrin were confirmed by Annexin V/propidium iodide (PI) staining and flow cytometry results. Morphological observation through 4',6-diamidino-2-phenylindole (DAPI) staining showed intense blue fluorescence representing chromatin condensation. Hematoxylin staining showed necroptotic features such as formation of vacuoles and swelling of organelles. Apigetrin increased reactive oxygen species (ROS) levels in cells, based on fluorescence imaging. Furthermore, the underlying mechanism involved in the apoptosis and necroptosis was elucidated through western blotting. Apigetrin up-regulated TNFα, but down-regulated phosphorylation of p-p65, and IκB. Apigetrin inhibited the expression of Bcl-xl but increased Bax levels. Up-regulation of cleaved PARP and cleaved caspase 3 confirmed the induction of apoptosis in apigetrin-treated Hep3B cells. Additionally, necroptosis markers RIP3, p-RIP3, and p-MLKL were significantly elevated by apigetrin dose-dependently, suggesting necroptotic cell death. Taken together, our findings strongly imply that apigetrin can induce apoptosis and necroptosis of Hep3B hepatocellular cancer cells. Thus, apigetrin as a natural compound might have potential for treating liver cancer.
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Apigenina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , NF-kappa B/metabolismo , Necroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
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.
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Flavonas , Neoplasias , Apigenina/farmacologia , Apoptose , Flavonas/farmacologia , Flavonoides/farmacologia , Humanos , Luteolina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de SinaisRESUMO
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.
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Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Ácido Cinurênico/farmacologia , Ácido Cinurênico/uso terapêutico , Simulação de Acoplamento Molecular , Neoplasias Gástricas/metabolismoRESUMO
Understanding the triggers and therapeutic targets for gastric cancer, one of the most common cancers worldwide, can provide helpful information for the development of therapeutics. RNA sequencing technology can be utilized to identify complex disease targets and therapeutic applications. In the present study, we aimed to establish the pharmacological target of Kynurenic acid (KYNA) for gastric cancer AGS cells and to identify the biological network. RNA sequencing identified differentially expressed genes (DEGs) between KYNA-treated and untreated cells. A total of 278 genes were differentially expressed, of which 120 genes were up-regulated, and 158 genes were down-regulated. Gene ontology results confirmed that KYNA had effects such as a reduction in genes related to DNA replication and nucleosome organization on AGS cells. Protein-protein interaction was confirmed through STRING analysis, and it was confirmed that cancer cell growth and proliferation were inhibited through KEGG, Reactome, and Wiki pathway analysis, and various signaling pathways related to cancer cell death were induced. It was confirmed that KYNA treatment reduced the gene expression of cancer-causing AP-1 factors (Fos, Jun, ATF, and JDP) in AGS cell lines derived from gastric cancer. Overall, using next-generation transcriptome sequencing data and bioinformatics tools, we confirmed that KYNA had an apoptosis effect by inducing changes in various genes, including factor AP-1, in gastric cancer AGS cells. This study can identify pharmacological targets for gastric cancer treatment and provide a valuable resource for drug development.
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Neoplasias Gástricas , Transcriptoma , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Ácido Cinurênico , Fator de Transcrição AP-1/genética , Biomarcadores , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão GênicaRESUMO
The objectives of this study were to evaluate antioxidant capacity of hot water extract from red maple leaf with different extraction times (experiment I) and to determine their impacts on color, free anthocyanin content, and hardness of gelatin gels (experiment II). In experiment I, hot water extraction time (30, 60, 120, 180, and 360 min at 60 °C) was fixed as a main effect. The different extraction times had no impacts on total polyphenol content and DPPH radical scavenging activity (p > 0.05). However, extraction time for 360 min could decrease anthocyanin content as well as ferric reducing antioxidant power (p < 0.05). In experiment II, 6%, 18%, and 30% gelatin gels were prepared without/with red maple leaf extract (1000 mg/L). The red maple leaf extract significantly increased redness, yellowness, and hardness, but decreased free anthocyanin content. Such impacts were obviously observed at high gelatin concentration. Thus, red maple leaf extract could be a novel anthocyanin source for improving antioxidant capacity and reddish color of gelatin gels. However, the addition amount of red maple leaf extract may be limited in the development of senior-friendly jelly food for soft texture in that it could increase the hardness of the gelatin gel.
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The aim of this study was to determine the relationship between in vitro antioxidant capacity of soy sauces and its impact on lipid oxidation in raw and cooked beef patties during 10â¯days of refrigerated storage. Three commercial soy sauces were used: industrially fermented soy sauce (IS), traditionally fermented Korean soy sauce (KS), and mixed soy sauce (MS). In vitro antioxidant capacity, KS showed the highest total phenol content, whereas IS and MS had a higher Fe2+ chelating activity than KS (Pâ¯<â¯.05). Heat treatment decreased total phenol content but increased Fe2+ chelating activity of soy sauces (Pâ¯<â¯.001). In both raw and cooked beef patties, the addition of IS or MS caused a lower 2-thiobarbituric acid reactive substances (TBARS) level than KS throughout the overall storage period (Pâ¯<â¯.05). This preliminary study suggests that the Fe2+ chelating activity of soy sauce may be one of the major mechanisms in preventing lipid oxidation in meat products.
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Antioxidantes/análise , Produtos da Carne/análise , Alimentos de Soja/análise , Animais , Bovinos , Fermentação , Armazenamento de Alimentos , Temperatura Alta , Quelantes de Ferro/análise , Oxirredução , Fenóis/análise , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
BACKGROUND/AIMS: The medial amygdala (MeA) responds to olfactory stimuli and alters reproductive physiology. However, the neuronal circuit that relays signals from the MeA to the reproductive axis remains poorly defined. This study aimed to test whether MeA kisspeptin (MeAKiss) neurons in male mice are sensitive to sexually relevant olfactory stimuli and transmit signals to alter reproductive physiology. We also investigated whether MeAKiss neurons have the capacity to elaborate glutamate and GABA neurotransmitters and potentially contribute to reproductive axis regulation. METHODS: Using female urine as a pheromone stimulus, MeAKiss neuronal activity was analysed and serum luteinizing hormone (LH) was measured in male mice. Next, using a chemogenetic approach, MeAKiss neurons were bi-directionally modulated to measure the effect on serum LH and evaluate the activation of the preoptic area. Lastly, using in situ hybridization, we identified the proportion of MeAKiss neurons that express markers for GABAergic (Vgat) and glutamatergic (Vglut2) neurotransmission. RESULTS: Male mice exposed to female urine showed a two-fold increase in the number of c-Fos-positive MeAKiss neurons concomitant with raised LH. Chemogenetic activation of MeAKiss neurons significantly increased LH in the absence of urine exposure, whereas inhibition of MeAKiss neurons did not alter LH. In situ hybridization revealed that MeAKiss neurons are a mixed neuronal population in which 71% express Vgat mRNA, 29% express Vglut2 mRNA, and 6% express both. CONCLUSIONS: Our results uncover, for the first time, that MeAKiss neurons process sexually relevant olfactory signals to influence reproductive hormone levels in male mice, likely through a complex interplay of neuropeptide and neurotransmitter signalling.
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Tonsila do Cerebelo/fisiologia , Kisspeptinas/fisiologia , Hormônio Luteinizante/sangue , Neurônios/fisiologia , Feromônios/farmacologia , Administração por Inalação , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Clozapina/análogos & derivados , Clozapina/farmacologia , Ácido Glutâmico/metabolismo , Kisspeptinas/genética , Masculino , Camundongos , Camundongos Transgênicos , Feromônios/administração & dosagem , Feromônios/urina , Área Pré-Óptica/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
A 12-year-old neutered male domestic shorthair cat was presented with a 3-year history of multiple nonpruritic, ulcerated, plaque-like skin lesions but no other clinical signs. A systemic examination revealed mild lymphadenopathy. Histopathologic analysis of the skin lesions revealed multicentric basosquamous carcinoma (BSC). Immunohistochemical analysis, PCR, and sequencing detected Felis catus papillomavirus type 2 (FcaPV-2) within the tumors. As BSC is rare in cats, clinical behavior has not been established. To our knowledge, this is the first case report to demonstrate detection of FcaPV-2 within a BSC in a domestic cat.
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Carcinoma Basoescamoso/veterinária , Doenças do Gato/virologia , Papillomaviridae/isolamento & purificação , Neoplasias Cutâneas/veterinária , Animais , Carcinoma Basoescamoso/virologia , Gatos , DNA Viral , Masculino , Neoplasias Cutâneas/virologiaRESUMO
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP3) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP3K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP3K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus. In the present study, to further elucidate the role of IP3K-A in the brain, we developed a transgenic (Tg) mouse line in which IP3K-A is conditionally overexpressed approximately 3-fold in the excitatory neurons of forebrain regions, including the hippocampus. The Tg mice showed an increase in both presynaptic release probability of evoked responses, along with bigger synaptic vesicle pools, and miniature excitatory postsynaptic current amplitude, although the spine density or the expression levels of the postsynaptic density-related proteins NR2B, synaptotagmin 1, and PSD-95 were not affected. Hippocampal-dependent learning and memory tasks, including novel object recognition and radial arm maze tasks, were partially impaired in Tg mice. Furthermore, (R,S)-3,5-dihydroxyphenylglycine-induced metabotropic glutamate receptor long-term depression was inhibited in Tg mice and this inhibition was dependent on protein kinase C but not on the IP3 receptor. Long-term potentiation and depression dependent on N-methyl-d-aspartate receptor were marginally affected in Tg mice. In summary, this study shows that overexpressed IP3K-A plays a role in some forms of hippocampus-dependent learning and memory tasks as well as in synaptic transmission and plasticity by regulating both presynaptic and postsynaptic functions.
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Região CA1 Hipocampal/citologia , Depressão Sináptica de Longo Prazo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Células Piramidais/citologia , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica , Animais , Região CA1 Hipocampal/fisiologia , Masculino , Aprendizagem em Labirinto , Memória , Camundongos , Camundongos Transgênicos , Plasticidade Neuronal , Fosfotransferases (Aceptor do Grupo Álcool)/análise , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Prosencéfalo/citologia , Prosencéfalo/fisiologia , Células Piramidais/metabolismo , Regulação para CimaRESUMO
In vivo tracking of transplanted stem cells has been a central aim of stem cell therapy. Although many tracking systems have been introduced, no method has yet been validated for clinical applications. We developed a novel sophisticated peptide (GV1001) that mimics hTERT (human telomerase reverse transcriptase) and analysed its ability to track and protect stem cells after transplantation. Ferrocenecarboxylic acid-conjugated GV1001 (Fe-GV1001) efficiently penetrated stem cells with no adverse effects. Moreover, Fe-GV1001 improved the viability, proliferation, and migration of stem cells under hypoxia. After Fe-GV1001-labelled stem cells were transplanted into the brains of rats after stroke, the labelled cells were easily tracked by MRI. Our findings indicate that Fe-GV1001 can be used for the in vivo tracking of stem cells after transplantation into the brain and can improve the efficacy of stem cell therapy by sustaining and enhancing stem cell characteristics under disease conditions.
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Compostos Ferrosos/química , Fragmentos de Peptídeos/química , Telomerase/química , Animais , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Metalocenos , Células-Tronco Neurais/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Ratos , Transplante de Células-TroncoRESUMO
The objectives of this study were conducted to characterize pepsin-soluble collagen (PSC) extracted from bones (PSC-B), skins (PSC-S), and tendons (PSC-T) of duck feet and to determine their thermal and structural properties, for better practical application of each part of duck feet as a novel source for collagen. PSC was extracted from each part of duck feet by using 0.5 M acetic acid containing 5% (w/w) pepsin. Electrophoretic patterns showed that the ratio between α1 and α2 chains, which are subunit polypeptides forming collagen triple helix, was approximately 1:1 in all PSCs of duck feet. PSC-B had slightly higher molecular weights for α1 and α2 chains than PSC-S and PSC-T. From the results of differential scanning calorimetry (DSC), higher onset (beginning point of melting) and peak temperatures (maximum point of curve) were found at PSC-B compared to PSC-S and PSC-T (p<0.05). Fourier transform infrared spectroscopy (FT-IR) presented that PSC-S and PSC-T had similar intermolecular structures and chemical bonds, whereas PSC-B exhibited slight difference in amide A region. Irregular dense sheet-like films linked by random-coiled filaments were observed similarly. Our findings indicate that PSCs of duck feet might be characterized similarly as a mixture of collagen type I and II and suggest that duck feet could be used for collagen extraction without deboning and/or separation processes.
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The objectives of this study were to determine efficacy of a membrane filtration in soy hull pectin purification and evaluate combined effects of soy hull pectin and pre-emulsified fiber/oil (PE) on chemical composition and technological properties of low fat and low salt meat emulsions. Soy hull pectin was purified through two different methods (alcohol-washed (ASP) and membrane-filtered (MSP)). Insoluble soy hull residues after pectin extraction were incorporated with sunflower oil and water for the PE preparation. Meat emulsion was formulated with 58 % pork, 20 % ice, 20 % pork backfat, and 2 % NaCl as control. A total of six low fat and low salt meat emulsions (1 % NaCl and 10 % backfat) was manufactured with 1 % pectin (with/without ASP or MSP) and 10 % PE (with/without). The pectin content of ASP and MSP was 0.84 and 0.64 g L-galacturonic acid/g dry sample, respectively. The inclusion of soy hull pectin caused similar results on chemical composition, color, cooking loss, and texture of the meat emulsions, regardless of the purification method. In addition, positive impacts of the combined treatments with soy hull pectin and PE compared to single treatments on cooking loss and texture of the meat emulsions were observed. Results suggest that membrane filtration could be an effective alternative method to purify pectin, instead of alcohol-washing, and both soluble pectin and insoluble fiber from soy hulls could be used as a functional non-meat ingredient to manufacture various low fat and low salt meat products.
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The brown soybean extract (BE, extracted by distilled water, 50%, 75%, and 95% ethanol) were analyzed for their total phenol, flavonoid, anthocyanin content, and DPPH radical-scavenging activity to determine antioxidant activities. Brown soybean extract with 75% ethanol showed significantly higher DPPH radical scavenging activity, total phenol and anthocyanin content compared to the other treatments (p<0.05). Then, brown soybean extract with 75% ethanol was applied to pork patties at different concentration (0.05%, 0.1%, and 0.2%) and lipid oxidation was evaluated during 15 d of refrigerated storage. Addition of BE significantly increased redness and pH values, respectively (p<0.05). Moreover, TBARS value of pork patties decreased significantly (p<0.05) as BE concentration increased. In sensory evaluation, pork patties with 0.1% BE had significantly higher score than other treatments in flavor and overall acceptability (p<0.05). Consequently, these results indicate that 0.1% BE could be an effective natural antioxidant to inhibit lipid oxidation in pork patties.