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This study evaluated the efficacy of personalized neuromodulation, where treatment modalities are chosen based on the patient's responses in a pilot trial. A total of 71 patients with tinnitus were divided into two groups: a personalized group and a randomized neuromodulation group. In the personalized group (n = 35), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) were assessed in a pilot trial, and responsive modalities were administered to 16 patients, while the non-responders (n = 19) were randomly assigned to rTMS, tDCS, or combined modalities. Patients in the randomized group (n = 36) were randomly allocated to rTMS, tDCS, or combined modalities. The Tinnitus Handicap Inventory (THI) score improvement after 10 sessions of each neuromodulation was significantly greater in the personalized group than in the randomized group (p = 0.043), with no significant differences in tinnitus loudness, distress, or awareness. The treatment success rate was highest in the personalized responder subgroup (92.3%), and significantly greater than that in the non-responder subgroup (53.0%; p = 0.042) and the randomized group (56.7%; p = 0.033). Personalized neuromodulation, where the treatment modality is chosen based on the patient's responses in a pilot trial, is an advantageous strategy for treating tinnitus.
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Although several previous studies have confirmed that listeners find it difficult to perceive the speech of face-mask-wearing speakers, there has been little research into how masks affect hearing-impaired individuals using hearing aids. Therefore, the aim of this study was to compare the effects of masks on the speech perception in noise of hearing-impaired individuals and normal-hearing individuals. We also investigated the effect of masks on the gain conferred by hearing aids. The hearing-impaired group included 24 listeners (age: M = 69.5, SD = 8.6; M:F = 13:11) who had used hearing aids in everyday life for >1 month (M = 20.7, SD = 24.0) and the normal-hearing group included 26 listeners (age: M = 57.9, SD = 11.1; M:F = 13:13). Speech perception in noise was measured under no mask-auditory-only (no-mask-AO), no mask-auditory-visual (no-mask-AV), and mask-AV conditions at five signal-to-noise ratios (SNRs; -16, -12, -8, -4, 0 dB) using five lists of 25 monosyllabic Korean words. Video clips that included a female speaker's face and sound or the sound only were presented through a monitor and a loudspeaker located 1 m in front of the listener in a sound-attenuating booth. The degree of deterioration in speech perception caused by the mask (no-mask-AV minus mask-AV) was significantly greater for hearing-impaired vs. normal-hearing participants only at 0 dB SNR (Bonferroni's corrected p < 0.01). When the effects of a mask on speech perception, with and without hearing aids, were compared in the hearing-impaired group, the degree of deterioration in speech perception caused by the mask was significantly reduced by the hearing aids compared with that without hearing aids at 0 and -4 dB SNR (Bonferroni's corrected p < 0.01). The improvement conferred by hearing aids (unaided speech perception score minus aided speech perception score) was significantly greater at 0 and -4 dB SNR than at -16 dB SNR in the mask-AV group (Bonferroni's corrected p < 0.01). These results demonstrate that hearing aids still improve speech perception when the speaker is masked, and that hearing aids partly offset the effect of a mask at relatively low noise levels.
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Background: : This study aimed to investigate the efficacy of P. oleracea in the management of patients with functional constipation. Methods: : A total of 60 patients with functional constipation as defined by the Rome IV criteria were enrolled in this randomized, double-blind, placebo-controlled study; 70% ethanol extracts of the aerial parts of P. oleracea were used for the intervention. Patients were randomly assigned to the P. oleracea or placebo groups. Treatment response, quality of life, and changes in colonic transit time (CTT) were evaluated. Results: : Complete spontaneous bowel movement (CSBM) improved significantly in the P. oleracea group compared with that in the placebo group over 8 weeks of treatment (P = 0.003). Overall Patient Assessment of Constipation Quality of Life (PAC-QOL) and Patient Assessment of Constipation Symptoms (PAC-SYM) score improvements were observed in the P. oleracea group (P < 0.05). Moreover, CTT decreased from 44.5 ± 22.0 h to 33.7 ± 22.7 h in the P. oleracea group after 7 weeks of treatment (P = 0.04). There were no significant differences in the Bristol Stool Form Scale (BSFS) or adverse events between the groups. Conclusions: : Compared to placebo, the use of P. oleracea in patients with functional constipation significantly improved CSBM, severity of symptoms, and quality of life. Further large studies are required to assess the benefits of P. oleracea in the treatment of functional constipation.
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Portulaca , Calidad de Vida , Estreñimiento/tratamiento farmacológico , Método Doble Ciego , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Lithium use causes goiter by increasing serum thyroid-stimulating hormone levels through the inhibition of thyroid hormone release. However, there are no reports of poorly differentiated thyroid carcinoma resulting from lithium-induced goiter. Herein, we report the case of a patient with schizophrenia who developed poorly differentiated thyroid carcinoma arising from a lithium-induced goiter. CASE PRESENTATION: A 61-year-old woman who was taking lithium for schizophrenia, visited the thyroid-endocrine center with a 10 × 12 cm anterior neck mass. She had a slowly growing goiter approximately 30 years ago; however, when she came to the hospital for diabetes diagnosis 2 years ago, she had no accompanying symptoms and refused evaluation. Three months before her visit, her dysphagia and dyspnea worsened as the size of her goiter increased rapidly. A neck ultrasound and enhanced thyroid computed tomography (CT) examination revealed a 10.9 × 9.2 × 12.8 cm size multi-lobulated mass on the right thyroid gland, leading to a leftward deviation of the trachea. Diagnostic total thyroidectomy was performed, and microscopic findings and immunohistochemical staining results indicated poorly differentiated thyroid carcinoma (PDTC) in the right thyroid mass. Mutation analyses for BRAF and the telomerase reverse transcriptase (TERT) promoter was performed. No BRAF gene mutations were detected; however, TERT promoter C228T point mutation was present in the PDTC. The patient underwent radioactive iodine therapy two months after the surgery. At a recent follow-up 4 months postoperatively, she was taking thyroid hormone replacement and remained in a relatively good health with a serum thyroglobulin level of 0.55 ng/ml. CONCLUSIONS: Thyroid examination of psychiatric patients who develop goiter due to long-term lithium treatment should be monitored regularly, and appropriate investigations and surgery should be performed in a timely manner if the goiter is growing rapidly.
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BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) protein has been implicated in phagocytosis of apoptotic cells, cell migration, neurite outgrowth, cancer cell invasion and metastasis, and poor prognosis in various cancers. We investigated the role of ELMO1 in mediating the oncogenic behavior of gastric cancer (GC) cells. We also investigated the correlation between expression of ELMO1 in GC tissues and various clinicopathological parameters. METHODS: We studied the impact of ELMO1 on tumor cell behavior using the pcDNA-myc vector and small interfering RNA in AGS and SNU1750 GC cell lines. We performed western blotting and immunohistochemistry to investigate the expression of ELMO1 in GC cells and tissues. RESULTS: ELMO1 overexpression inhibited apoptosis via the modulation of PARP, caspase-3 and caspase-7 in GC cells. ELMO1 overexpression led to significant increase in the number of migrating and invading GC cells. The expression of E-cadherin decreased and that of Snail increased in GC cells upon ELMO1 overexpression. Phosphorylation of PI3K/Akt and GSK-3ß was increased and that of ß-catenin was decreased upon ELMO1 overexpression in GC cells. These results were reversed after ELMO1 knockdown. ELMO1 expression was significantly associated with tumor size, cancer stage, lymph node metastasis and survival. ELMO1-positive tumors had significantly higher mean of Ki-67 labeling index than ELMO1-negative tumors. There was no significant relationship between ELMO1 expression and the mean value of the apoptotic index. CONCLUSIONS: Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.
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Forkhead box A1 (FOXA1) functions as a tumor suppressor gene or an oncogene in various types of cancer; however, the distinct function of FOXA1 in colorectal cancer is unclear. The present study aimed to evaluate whether FOXA1 affects the oncogenic behavior of colorectal cancer cells, and to investigate its prognostic value in colorectal cancer. The impact of FOXA1 on tumor cell behavior was investigated using small interfering RNA and the pcDNA6myc vector in human colorectal cancer cell lines. To investigate the role of FOXA1 in the progression of human colorectal cancer, an immunohistochemical technique was used to localize FOXA1 protein in paraffinembedded tissue blocks obtained from 403 patients with colorectal cancer. Tumor cell apoptosis and proliferation were evaluated using a terminal deoxynucleotidyl transferasemediated dUTP nickend labeling assay and Ki67 immunohistochemical staining, respectively. FOXA1 knockdown inhibited tumor cell invasion in colorectal cancer cells, and induced apoptosis and cell cycle arrest. FOXA1 knockdown activated cleaved caspasepoly (ADPribose) polymerase, upregulated the expression of p53 upregulated modulator of apoptosis, and downregulated BH3 interacting domain death agonist and myeloid cell leukemia1, leading to the induction of apoptosis. FOXA1 knockdown increased the phosphorylation level of signal transducer and activator of tran-scription3. By contrast, these results were reversed following the overexpression of FOXA1. The overexpression of FOXA1 was associated with differentiation, lymphovascular invasion, advanced tumor stage, depth of invasion, lymph node metastasis and poor survival rate. The mean Ki67 labeling index value of FOXA1positive tumors was significantly higher than that of FOXA1negative tumors. However, no significant association was observed between the expression of FOXA1 and the mean apoptotic index value. These results indicate that FOXA1 is associated with tumor progression via the modulation of tumor cell survival in human colorectal cancer.
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Neoplasias Colorrectales/patología , Factor Nuclear 3-alfa del Hepatocito/genética , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Regulación hacia Arriba , Células CACO-2 , Diferenciación Celular , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Pronóstico , Transducción de Señal , Análisis de SupervivenciaRESUMEN
Reversine, a 2,6diaminosubstituted purine analogue, has been reported to be effective in tumor suppression via induction of cell growth arrest and apoptosis of cancer cells. However, it remains unclear whether reversine exerts anticancer effects on human colorectal cancer cells. In the present study, in vitro experiments were conducted to investigate the anticancer properties of reversine in human colorectal cancer cells. The effect of reversine on human colorectal cancer cell lines, SW480 and HCT116, was examined using a WST1 cell viability assay, fluorescence microscopy, flow cytometry, DNA fragmentation, small interfering RNA (siRNA) and western blotting. Reversine treatment demonstrated cytotoxic activity in human colorectal cancer cells. It also induced apoptosis by activating poly(ADPribose) polymerase, caspase3, 7 and 8, and increasing the levels of the proapoptotic protein second mitochondriaderived activator of caspase/direct inhibitor of apoptosisbinding protein with low pI. The pancaspase inhibitor ZVADFMK attenuated these reversineinduced apoptotic effects on human colorectal cancer cells. Additionally, reversine treatment induced cell cycle arrest in the subG1 and G2/M phases via increase in levels of p21, p27 and p57, and decrease in cyclin D1 levels. The expression of Fas and death receptor 5 (DR5) signaling proteins in SW480 and HCT116 cells was upregulated by reversine treatment. Reversineinduced apoptosis and cell cycle arrest were suppressed by inhibition of Fas and DR5 expression via siRNA. In conclusion, Reversine treatment suppressed tumor progression by the inhibition of cell proliferation, induction of cell cycle arrest and induction of apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells. The present study indicated that reversine may be used as a novel anticancer agent in human colorectal cancer.
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Neoplasias Colorrectales/metabolismo , Morfolinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Purinas/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Receptor fas/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HCT116 , Humanos , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
RATIONALE: Radiofrequency ablation (RFA) is a safe and effective local treatment modality with a low complication rate and is commonly used to treat hepatocellular carcinoma (HCC). The clinical outcome of RFA may be closely related to the location, size, and shape of index tumors, and major complications, including hemorrhage, liver abscess, infarction, visceral organ perforation, hemothorax, pneumothorax, tumoral seeding, and hepatic failure. Cardiac tamponade is a rare and serious life-threatening complication associated with RFA. To date, a review of the medical literature reported 5 cases of cardiac tamponade after RFA for HCC. Herein, we report another case of cardiac tamponade after RFA for HCC in a 56-year-old man. PATIENT CONCERNS: He had suffered from liver cirrhosis due to alcohol abuse. He had chronic obstructive pulmonary disease. Magnetic resonance imaging showed a 3.0-cm exophytic subcapsular HCC in segment IVa of left hepatic lobe. As the patient was at high risk for surgery because of poor lung function, RFA was selected as the treatment of choice. The index tumor was located in the vicinity of the diaphragm and colon. During RFA procedure, thermal injury to the adjacent diaphragm and colon was minimized by introducing artificial ascites. Bleeding or tumoral seeding was prevented by ablating the electrode track during electrode retraction. DIAGNOSIS: Two hours after RFA, the patient presented with dyspnea, chest discomfort, and low blood pressure (80/60 mm Hg), suggesting cardiac tamponade. Immediate follow-up contrast-enhanced computed tomography image depicted the slightly high attenuated hemopericardium. Transthoracic echocardiography (TTE) showed a moderate amount of pericardial effusion with tamponade and a large hematoma. INTERVENTIONS: Under fluoroscopy and portable echocardiography guidance, a cardiologist immediately inserted a 7-French pigtail catheter into the pericardial space and collected more than 200 cc of bloody pericardial fluid. OUTCOMES: After pericardiocentesis, the patient's symptoms and hemodynamic status were dramatically improved. Follow-up TTE showed scanty amount of pericardial effusion and the drainage catheter was removed. The patient was discharged. LESSONS: When treating HCC in the left lobe (especially segments II and IVa), attention should be paid to cardiac tamponade. The early diagnosis and immediate treatment of cardiac tamponade may increase the chance of cure.
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Carcinoma Hepatocelular/cirugía , Taponamiento Cardíaco/diagnóstico , Taponamiento Cardíaco/etiología , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Ablación por Radiofrecuencia , Taponamiento Cardíaco/terapia , Diagnóstico Precoz , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The effects of different ganjangs (also designated as kanjang), including acid-hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame sauce (FSeS), on azoxymethane (AOM, 10 mg/kg)/dextran sulfate sodium (DSS, 2%)-induced colorectal carcinogenesis in C57BL/6J mice were studied. Low doses (4 mL/kg) of both FSeS and FSS significantly increased colon length, suppressed AOM/DSS-induced increases in colon weight/length ratios, and induced colorectal neoplasia compared with AHSS-treated and control mice. Fermented sauces, particularly low doses of FSeS and FSS, showed activity against AOM/DSS-induced colorectal carcinogenesis by abrogating serum and mRNA levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and IL-17α as well as by reducing mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2 in colon mucosa. FSeS significantly increased colonic p53 expression compared with other sauces. However, AHSS showed weak activity against AOM/DSS-induced colonic carcinogenesis. Overall, FSeS showed the strongest anticancer effect, followed by FSS and AHSS. Thus, fermentation with microorganisms rather than chemical processes is important, and raw materials are another factor influencing anticancer activity.
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Azoximetano/efectos adversos , Neoplasias del Colon/dietoterapia , Sulfato de Dextran/efectos adversos , Sesamum/metabolismo , Alimentos de Soja/análisis , Animales , Carcinogénesis , Colon/metabolismo , Colon/patología , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Fermentación , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Sesamum/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The origins and validity of the term "superficial musculoaponeurotic system" (SMAS) is reviewed. Gray stated the superficial fascia connects the skin with the deep or aponeurotic fascia and consists of fibro-areolar tissue. Hollinshead wrote superficial fascia exists throughout the body and contains a variable amount of fat. In the head and neck, it encloses voluntary muscles in its deep portion. Skoog found superficial fascia was fixed to the dense, deep fascia by fibrous adhesions in the temporal, preauricular, and parotid area. Mitz stated "There is a 'superficial muscular and aponeurotic system' (SMAS) in the parotid and cheek areas." SMAS has an intimate relationship with the entire superficial fascia of the head and neck and divides the subcutaneous fat into 2 layers. Wassef found a continuous fibromuscular layer at the deep limit of the "subcutis," which corresponded to the "superficial fascia." Nakajima reported the subcutaneous adipofascial tissue was made up of 2 adipofascial layers. Macchi found 2 different fibroadipose connective layers bounded to the laminar connective tissue layer (SMAS). In the cheek, Hwang found horizontal fibrous connective tissues (membranous layer of superficial fascia) divided the superficial fascia into the superficial fatty layer and the deep fatty layer. Recently, Mitz explained the reason for the term SMAS. The "musculo+aponeurotic" component is based on histology of muscle cells, including the risorius, in the same structure to be surgically consistent. The aponeurotic cells belong to the same surgical layer. SMAS is not sufficient to replace the old term "superficial fascia" of the cheek area.
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Mejilla/anatomía & histología , Fascia/anatomía & histología , Tejido Subcutáneo/anatomía & histología , Sistema Músculo-Aponeurótico Superficial/anatomía & histología , Tejido Adiposo/anatomía & histología , Tejido Conectivo/anatomía & histología , Músculos Faciales/anatomía & histología , Humanos , Cuello , Glándula Parótida , Terminología como AsuntoRESUMEN
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on ADlike skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4dinitrochlorobenzene (DNCB)induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dosedependent manner. Elevated serum histamine, total and DFEspecific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcriptionquantitative polymerase chain reaction (RTqPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)4, IL13, IL31 and IL17A was reduced in ear skin following AXE administration in AD mice. Fluorescenceactivated cell sorting demonstrated that the population of CD4+/IL4+, CD4+/IFNγ+ and CD4+/IL17A+ cells in draining lymph nodes was also significantly decreased in AXEtreated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNFα and IFNγ exhibited increased gene expression of proinflammatory cytokines and chemokines, including TNFα, IL1ß, IL6, IL8, CC motif chemokine ligand (CCL)17 and CCL22, as determined by RTqPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD.
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Amomum/química , Antiinflamatorios/farmacología , Dermatitis Atópica/inmunología , Extractos Vegetales/farmacología , Animales , Línea Celular , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Modelos Animales de Enfermedad , Histamina/sangre , Histamina/inmunología , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Piel/metabolismo , Piel/patologíaRESUMEN
We previously reported the inhibitory effect of chrysin, a natural flavonoid plentifully contained in propolis, vegetables and fruits, on the mast cell-mediated allergic reaction. In this study, we evaluated the effect of chrysin on atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae extract, DFE) to the ears. Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions. Oral administration of chrysin diminished AD symptoms such as ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. Chrysin decreased infiltration of mast cells, and reduced serum histamine level. Chrysin also suppressed AD by inhibiting the inflammatory responses of Th1, Th2, and Th17 cells in mouse lymph node and ear. Interestingly, chrysin significantly inhibited the production of cytokines, Th2 chemokines, CCL17 and CCL22 by the down-regulation of p38 MAPK, NF-κB, and STAT1 in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT). Chrysin also inhibited TNF-α/IFN-γ-stimulated IL-33 expression in HaCaT cells and mouse primary keratinocytes. Taken together, the results indicate that chrysin suppressed AD symptoms, suggesting that chrysin might be a candidate for the treatment of AD and skin allergic diseases.
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Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Flavonoides/administración & dosificación , Queratinocitos/efectos de los fármacos , Animales , Citocinas/genética , Citocinas/inmunología , Dermatitis Atópica/genética , Femenino , Histamina/inmunología , Humanos , Inmunoglobulina E/inmunología , Queratinocitos/inmunología , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
This study investigated the chemical composition changes of Salvia plebeia R.Br. cultivated under different light sources, including florescent light and sunlight. The plants were exposed to fluorescent light for four months and sunlight and then examined for the next 5-7 months. Plants were harvested monthly during the seven months, and we examined whether the difference in light source affected the phenolic and flavonoid contents and antioxidant activity. A simple and reliable HPLC method using a PAH C18 column was applied for the quantitative analysis of two triterpenoids from the S. plebeia groups. Oleanolic acid (OA) and ursolic acid (UA) showed good linearity (R² > 0.9999) within the test ranges (0.005-0.05 mg/mL), and the average percentage recoveries of the OA and UA were 95.1-104.8% and 97.2-107.1%, respectively. The intra- and inter-day relative standard deviations (RSDs) were less than 2.0%. After exposure to sunlight, the phenolic contents, including rosmarinic acid, showed a reduced tendency, whereas the flavonoid contents, including homoplantaginin and luteolin 7-glucoside, were increased. The content of the triterpenoids also showed an increased tendency under sunlight irradiation, but the variance was not larger than those of the phenolic and flavonoid contents. Among experimental groups, the group harvested at six months, having been exposed to sunlight for two months, showed the most potent antioxidant activity. Therefore, these results showed that the chemical composition and antioxidant activities of S. plebeia R.Br. was affected from environmental culture conditions, such as light source. Our studies will be useful for the development of functional materials using S. plebeia R.Br.
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Extractos Vegetales/química , Salvia/efectos de la radiación , Luz Solar , Animales , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Flavonoides/química , Humanos , Ratones , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Fenoles/química , Fotosíntesis , Células RAW 264.7 , Salvia/química , Salvia/crecimiento & desarrollo , Triterpenos/química , Triterpenos/farmacología , Ácido UrsólicoRESUMEN
OBJECTIVE: We aimed to determine whether combinations of multiplex cytokine responses could differentiate Mycobacterium tuberculosis (Mtb) infection states. METHODS: Mtb-specific antigen-induced and unstimulated cytokines were measured by Luminex assay in supernatants of QuantiFERON® Gold In-Tube assay (QFT) in 48 active pulmonary TB patients (TB), 15 latent TB infection subjects (LTBI), and 13 healthy controls (HCs). RESULTS: Among the 29 cytokines, eight Mtb antigen-specific biomarkers (GM-CSF, IFN-γ, IL-1RA, IL-2, IL-3, IL-13, IP-10, and MIP-1ß) in the Mtb-infected group were significantly different from those of the HCs. Five Mtb-specific biomarkers (EGF, GM-CSF, IL-5, IL-10, and VEGF), two unstimulated biomarkers (TNF-α[Nil] and VEGF[Nil]), and one Mtb-specific biomarker ratio (IL-2/IFN-γ) showed significant differences between active TB and LTBI. Three unstimulated biomarkers (IL-8[Nil], IL-13[Nil], and VEGF[Nil]) and 5 Mtb-specific biomarkers (IFN-γ, IL-2, IL-3, IP-10, and VEGF) were significantly different between active TB and non-active TB groups. Combinations of three cytokine biomarkers resulted in the accurate prediction of 92.1-93.7% of Mtb-infected cases and 92.3-100% of HCs, respectively. Moreover, combinations of five biomarkers accurately predicted 90.9-100% of active TB cases and 80-100% of LTBI subjects, respectively. In discriminating between active TB and non-active TB regardless of QFT results, combinations of six biomarkers predicted 79.2-95.8% of active TB cases and 67.9-89.3% of non-active TB subjects. CONCLUSIONS: Taken together, our data suggest that combinations of whole blood Mtb antigen-dependent cytokines could serve as biomarkers to determine TB disease states. Especially, VEGF is highlighted as a key biomarker for reflecting active TB, irrespective of stimulation.
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Biomarcadores/sangre , Citocinas/sangre , Tuberculosis Latente/diagnóstico , Tuberculosis/diagnóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Bacterianos/inmunología , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/sangre , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Tuberculosis/sangre , Tuberculosis/microbiología , Adulto JovenRESUMEN
The interleukin-6 (IL-6) family of cytokines plays a key role in the pathogenesis of rheumatoid arthritis and osteoporosis through the regulation of bone formation and resorption. In this study, it was observed that ethanol extract of Salvia plebeia R.Br. (S.P-EE) inhibited IL-6-induced signaling cascade including phosphorylation of JAK2/STAT3 and ERK. Subsequently, it was examined whether S.P-EE treatment could recover bone loss in ovariectomized (OVX) mice. Indeed, S.P-EE exhibited both preventive and therapeutic effect on OVX-induced bone loss in trabecular microarchitecture along with significant increase in bone mineral density and content. To understand the mechanism of action of S.P-EE in bone metabolism, the effect of S.P-EE on osteoclast differentiation and activity was investigated. S.P-EE significantly inhibited RANKL-induced osteoclast differentiation by suppressing phosphorylation of MAPK and Akt, and expression of NFATc1 and osteoclast marker genes. S.P-EE also inhibited bone-resorbing activity of osteoclasts. Furthermore, isolation and identification of the active compounds which are responsible for the inhibitory effect of S.P-EE on osteoclast differentiation was carried out. Six major flavonoids and plebeiolide A-C were isolated and examined their effects on osteoclast differentiation. Luteolin and hispidulin, and plebeiolide A and C, not B exhibited potent inhibitory activity on RANKL-induced osteoclast formation.
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Resorción Ósea/prevención & control , Interleucina-6/antagonistas & inhibidores , Osteogénesis/efectos de los fármacos , Ovariectomía/efectos adversos , Extractos Vegetales/uso terapéutico , Salvia , Animales , Resorción Ósea/etiología , Resorción Ósea/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Osteogénesis/fisiología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
A nickel-phosphorus-alumina xerogel catalyst was prepared by a carbon-templating epoxide-driven sol-gel method (denoted as CNPA catalyst), and it was applied to the hydrogen production by steam reforming of liquefied natural gas (LNG). For comparison, a nickel-phosphorus-alumina xerogel catalyst was also prepared by a similar method in the absence of carbon template (denoted as NPA catalyst). The effect of carbon template addition on the physicochemical properties and catalytic activities of the catalysts in the steam reforming of LNG was investigated. Both CNPA and NPA catalysts showed excellent textural properties with well-developed mesoporous structure. However, CNPA catalyst retained a more reducible nickel aluminate phase than NPA catalyst. XRD analysis of the reduced CNPA and NPA catalysts revealed that nickel sintering on the CNPA catalyst was suppressed compared to that on the NPA catalyst. From H2-TPD and CH4-TPD measurements of the reduced CNPA and NPA catalysts, it was also revealed that CNPA catalyst with large amount of hydrogen uptake and strong hydrogen-binding sites showed larger amount of methane adsorption than NPA catalyst. In the hydrogen production by steam reforming of LNG, CNPA catalyst with large methane adsorption capacity showed a better catalytic activity than NPA catalyst.
RESUMEN
A series of oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6-induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 µM which was much better than (+)-Madindoline A (IC50=21 µM), a known inhibitor of IL-6.
Asunto(s)
Interleucina-6/metabolismo , Oxazolidinonas/química , Transducción de Señal/efectos de los fármacos , Sitios de Unión , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Cristalografía por Rayos X , Células Hep G2 , Humanos , Indoles/química , Concentración 50 Inhibidora , Interleucina-6/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Oxazolidinonas/síntesis química , Oxazolidinonas/farmacología , Estructura Terciaria de Proteína , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Relación Estructura-ActividadRESUMEN
BACKGROUND/AIMS: Percutaneous coronary intervention (PCI) is often performed therapeutically, and antithrombotic treatment is required for at least 12 months after stent implantation. However, the development of post-PCI upper gastrointestinal bleeding (UGIB) increases morbidity and mortality. We investigated the incidence and risk factors for UGIB in Korean patients within 1 year after PCI. METHODS: The medical records of 3,541 patients who had undergone PCI between January 2006 and June 2012 were retrospectively reviewed. We identified 40 cases of UGIB. We analyzed the incidence and clinical risk factors associated with UGIB occurring within 1 year after PCI by comparing the results for each case to matched controls. The propensity score matching method using age and sex was utilized. RESULTS: UGIB occurred in 40 patients (1.1%). Two independent risk factors for UGIB were a history of peptic ulcer disease (odds ratio [OR], 12.68; 95% confidence interval [CI], 2.70 to 59.66; p=0.001) and the use of anticoagulants (OR, 7.76; 95% CI, 2.10 to 28.66; p=0.002). CONCLUSIONS: UGIB after PCI occurred at a rate of 1.1% in the study population. Clinicians must remain vigilant for the possibility of UGIB after PCI and should consider performing timely endoscopy in patients who have undergone PCI and are suspected of having an UGIB.
Asunto(s)
Hemorragia Gastrointestinal/etiología , Intervención Coronaria Percutánea/efectos adversos , Complicaciones Posoperatorias , Anciano , Anticoagulantes/efectos adversos , Estudios de Casos y Controles , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Úlcera Péptica/complicaciones , Puntaje de Propensión , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Constrictive pericarditis is an uncommon post-inflammatory disorder characterized by a variably thickened, fibrotic, and frequently calcified, pericardium. Etiology of the constriction can occur for many reasons. Although foreign bodies are not the common cause of constrictive pericarditis, the long-term presence of foreign bodies, like bullets, is presumed to cause chronic constrictive pericarditis even after a very long asymptomatic period. A 69-year-old patient with atrial flutter was admitted to the hospital. A cardiac computed tomography showed a bullet located adjacent to the right atrium. The transthoracic echocardiography showed a thickened pericardium and septal bouncing motion, which were compatible with constrictive pericarditis. The history of the patient revealed an injury by gunshot during the Korean War in 1950. Radiofrequency ablation of the atrial flutter was performed, and after ablation, the bullet was removed surgically. The patient was discharged home after surgery without complications.