Theophylline enhances melanogenesis in B16F10 murine melanoma cells through the activation of the MEK 1/2, and Wnt/ß-catenin signaling pathways.

Theophylline is a kind of methyl xanthine, which has been suggested to inhibit the activity of phosphodiesterase and increase the intracellular level of cyclic adenine monophosphate (cAMP). Theophylline has also been reported to increase the length and complexity of the dendritic process in melanocytes. However, the mode of action of theophylline in melanogenesis has never been reported. In this study, the effects of theophylline on melanogenesis were evaluated spectrophotometrically by the mushroom tyrosinase activity assay and by the determination of the intracellular tyrosinase activity and melanin content. The expression levels of melanogenesis-related proteins were analyzed by Western blot. The results indicated that theophylline (100-500 µM) effectively enhanced melanogenesis in the B16F10 murine melanoma cells. Moreover, theophylline increased the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 (TRP-1), and the level of phosphorylated extracellular regulated protein kinase (p-ERK) and phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) were also increased. In summary, the results revealed that theophylline promoted melanogenesis in B16F10 cells by upregulating the mitogen-activated protein kinase kinase 1 (MEK 1/2) and Wnt/ß-catenin signaling pathways.

Prehospital Predictors of Initial Shockable Rhythm in Out-of-Hospital Cardiac Arrest: Findings From the Taichung Sudden Unexpected Death Registry (THUNDER).

OBJECTIVE: To identify the incidence and prehospital predictors of ventricular tachycardia/ventricular fibrillation (VT/VF) as the initial arrhythmia in patients with out-of-hospital cardiac arrest (OHCA) in central Taiwan. PATIENTS AND METHODS: The Taichung Sudden Unexpected Death Registry program encompasses the Taichung metropolitan area in central Taiwan, with a population of 2.7 million and 17 destination hospitals for patients with OHCA. We performed a detailed analysis of demographic characteristics, circumstances of cardiac arrest, and emergency medical service records using the Utstein Style. RESULTS: From May 1, 2013, through April 30, 2014, resuscitation was attempted in 2013 individuals with OHCA, of which 384 were excluded due to trauma and noncardiac etiologies. Of the 1629 patients with presumed cardiogenic OHCA, 7.9% (n=129) had initial shockable rhythm; this proportion increased to 18.8% (61 of 325) in the witnessed arrest subgroup. Male sex (odds ratio [OR], 2.45; 95% CI, 1.46-4.12; P<.001), age younger than 65 years (OR, 2.39, 95% CI, 1.58-3.62; P<.001), public location of arrest (OR, 4.61; 95% CI, 2.86-7.44; P<.001), and witnessed status (OR, 3.98; 95% CI, 2.62-6.05; P<.001) were independent predictors of VT/VF rhythm. CONCLUSION: The proportion of patients with OHCA presenting with VT/VF was generally low in this East Asian population. Of the prehospital factors associated with VT/VF, public location of OHCA was the strongest predictor of VT/VF in this population, which may affect planning and deployment of emergency medical services in central Taiwan.

Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways.

The mode of action of spent coffee grounds supercritical fluid CO2 extract (SFE) in melanogenesis has never been reported. In the study, the spent coffee grounds were extracted by the supercritical fluid CO2 extraction method; the chemical constituents of the SFE were investigated by gas chromatography-mass spectrometry (GC-MS). The effects of the SFE and its major fatty acid components on melanogenesis were evaluated by mushroom tyrosinase activity assay and determination of intracellular tyrosinase activity and melanin content. The expression level of melanogenesis-related proteins was analyzed by western blotting assay. The results revealed that the SFE of spent coffee grounds (1-10 mg/mL) and its major fatty acids such as linoleic acid and oleic acid (6.25-50 µM) effectively suppressed melanogenesis in the B16F10 murine melanoma cells. Furthermore, the SFE decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). The SFE also decreased the protein expression levels of p-JNK, p-p38, p-ERK, and p-CREB. Our results revealed that the SFE of spent coffee grounds attenuated melanogenesis in B16F10 cells by downregulation of protein kinase A (PKA), phosphatidylinositol-3-kinase (PI3K/Akt), and mitogen-activated protein kinases (MAPK) signaling pathways, which may be due to linoleic acid and oleic acid.