Down-regulation of exosomal miR-200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis.

Vitiligo is a refractory disfiguring skin disease. However, the aetiology and pathogenesis of vitiligo have not been fully defined. Previous studies have shown that exosomes from normal human keratinocytes improve melanogenesis by up-regulating the expression of melanogenesis-related proteins. Several microRNAs (miRNAs) have been demonstrated to be effective in modulating melanogenesis via exosomes. In the present study, it was found that the effect of exosomes derived from keratinocytes in vitiligo lesions in regulating melanin synthesis is weakened. Furthermore, miR-200c was detected to be significantly down-regulated in exosomes from keratinocytes in vitiligo lesions. In addition, miR-200c enhanced the expression of melanogenesis-related genes via suppressing SOX1 to activate ß-catenin. In conclusion, our study revealed that the effect of exosomes secreted by keratinocytes in vitiligo lesions exhibited a weaker capacity in promoting melanogenesis of melanocytes. Moreover, the expression of miR-200c, which mediates melanogenesis in exosomes secreted by keratinocytes in vitiligo lesions, is down-regulated, which may be one of the pathogenesis in vitiligo. Therefore, keratinocyte-derived exosomal miR-200c may be a potential target for the treatment of vitiligo.

Increased HERV-E clone 4-1 expression contributes to DNA hypomethylation and IL-17 release from CD4+ T cells via miR-302d/MBD2 in systemic lupus erythematosus.

BACKGROUND: Increased human endogenous retroviruses E clone 4-1 (HERV-E clone 4-1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity. In this study, we want to further investigate the mechanism of HERV-E clone 4-1 mRNA upregulation and its roles in SLE progression. METHODS: CD4+ T cells were isolated from venous blood of SLE patients or healthy controls and qRT-PCR was used to detect HERV-E clone 4-1 mRNA expression. We then investigated the regulation of Nuclear factor of activated T cells 1 (NFAT1) and Estrogen receptor-α (ER-α) on HERV-E clone 4-1 transcription and the functions of HERV-E clone 4-1 3' long terminal repeat (LTR) on DNA hypomethylation and IL-17 release. RESULTS: We found HERV-E clone 4-1 mRNA expression was upregulated in CD4+ T cells from SLE patients and positively correlated with SLE disease activity. This is associated with the activation of Ca2+/calcineurin (CaN)/NFAT1 and E2/ER-α signaling pathway and DNA hypomethylation of HERV-E clone 4-1 5'LTR. HERV-E clone 4-1 also takes part in disease pathogenesis of SLE through miR-302d/Methyl-CpG binding domain protein 2 (MBD2)/DNA hypomethylation and IL-17 signaling via its 3'LTR. CONCLUSIONS: HERV-E clone 4-1 mRNA upregulation is due to the abnormal inflammation/immune/methylation status of SLE and it could act as a potential biomarker for diagnosis of SLE. HERV-E clone 4-1 also takes part in disease pathogenesis of SLE via its 3'LTR and the signaling pathways it involved in may be potential therapeutic targets of SLE.

[Review on Application of Optical Scattering Spectroscopy for Elastic Wave Velocity Study on Materials in Earth's Interior].

In-situ experimental results on the elastic wave velocity of Earth materials at high pressure and high temperature in combination with data from seismic observation can help to inverse the chemical composition, state and migration of materials in Earth's interior, providing an important approach to explore information of deep earth. Applying the Brillouin scattering into the Diamond Anvil Cell (DAC) to obtain the in situ elastic wave velocities of minerals, is the important approach to investigate elastic properties of Earth's Interior. With the development of DAC technology, on the one hand, the high temperature and high pressure experimental environment to simulate different layers of the earth can be achieved; on the other hand, the optical properties of DAC made many kinds of optical analysis and test methods have been widely applied in this research field. In order to gain the elastic wave velocity under high temperature and high pressure, the accurate experimental pressure and heating temperature of the sample in the cavity should be measured and calibrated first, then the scattering signal needs to dealt with, using the Brillouin frequency shift to calculate the velocity in the sample. Combined with the lattice constants obtained from X ray technique, by a solid elastic theory, all the elastic parameters of minerals can be solved. In this paper, firstly, application of methods based on optical spectrum such as Brillouin and Raman scattering in elasticity study on materials in Earth's interior, and the basic principle and research progress of them in the velocity measurement, pressure and temperature calibration are described in detail. Secondly, principle and scope of application of two common methods of spectral pressure calibration (fluorescence and Raman spectral pressure standard) are analyzed, in addition with introduce of the application of two conventional means of temperature calibration (blackbody radiation and Raman temperature scale) in temperature determination. Lastly, geophysical applications of mineral elasticity are discussed on the basis of the recent research results derive from Brillouin scattering system of wave velocities for major minerals in Earth's lower mantle (perovskite, ferropericlase, etc.), and the future research work is inspected.

Variation of biophysical parameters of the skin with age, gender, and lifestyles.

BACKGROUND: Sweet, spicy or greasy food, staying up late, and using electronic products for a long time are common bad habits nowadays. Their role in skin diseases has been paid much attention. OBJECTIVE: The aim of this study was to investigate whether unhealthy lifestyles would affect the skin sebum content, SC hydration, and pH and how do they affect. METHODS: A total of 300 volunteers were enrolled, and a multifunctional skin physiology monitor measured the three skin biophysical properties on the forehead and dorsal hand. Lifestyle factors were evaluated by a self-administered questionnaire. RESULTS: Eating oily, sweet, spicy food, and staying up late increased the sebum content of the forehead significantly. Dorsal hand SC hydration was higher in people eating more sweet food and oily food, and forehead SC hydration was higher in people eating more sweet food and go to bed earlier. Eating sweet food could increase pH in both forehead and dorsal hand. The forehead pH decreased in using electronic products over 6 hours a day or staying up late. There are significant differences in sebum, hydration, and pH value among different age groups. In males, the pH was lower than females, but the sebum was higher. CONCLUSION: Sebum content, SC hydration, and pH are affected by unhealthy lifestyles, age, and gender.

Deep carbon cycle constrained by carbonate solubility.

Earth's deep carbon cycle affects atmospheric CO2, climate, and habitability. Owing to the extreme solubility of CaCO3, aqueous fluids released from the subducting slab could extract all carbon from the slab. However, recycling efficiency is estimated at only around 40%. Data from carbonate inclusions, petrology, and Mg isotope systematics indicate Ca2+ in carbonates is replaced by Mg2+ and other cations during subduction. Here we determined the solubility of dolomite [CaMg(CO3)2] and rhodochrosite (MnCO3), and put an upper limit on that of magnesite (MgCO3) under subduction zone conditions. Solubility decreases at least two orders of magnitude as carbonates become Mg-rich. This decreased solubility, coupled with heterogeneity of carbon and water subduction, may explain discrepancies in carbon recycling estimates. Over a range of slab settings, we find aqueous dissolution responsible for mobilizing 10 to 92% of slab carbon. Globally, aqueous fluids mobilise [Formula: see text]% ([Formula: see text] Mt/yr) of subducted carbon from subducting slabs.

Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2.

Hypoxia is commonly observed in solid tumors and contributes to the resistance of DNA damage drugs. However, the mechanisms behind this resistance are still unclear. In this study, we aimed to explore the effects of hypoxia-induced exosomes on non-small cell lung cancer (NSCLC). Methods: NSCLC cells were subjected to either normoxic or hypoxic conditions to assess cell survival and changes in the expression levels of key proteins. Comparative proteomics were performed to identify exosomal PKM2 in normoxic or hypoxic cisplatin-resistant NSCLC cells-derived exosomes. Functions of hypoxia induced-exosomal PKM2 in promoting cisplatin resistance to NSCLC cells were evaluated both in vitro and in vivo experiments and the molecular mechanisms of hypoxia induced-exosomal PKM2 were demonstrated using flow cytometry, immunoblotting, oxidative stress detection and histological examination. A series of in vitro experiments were performed to evaluate the function of hypoxia-induced exosomes on cancer-associated fibroblasts (CAFs). Results: Hypoxia exacerbated the cisplatin resistance in lung cancer cells due to the increased expression of PKM2 that was observed in the exosomes secreted by hypoxic cisplatin-resistance cells. We identified that hypoxia-induced exosomal PKM2 transmitted cisplatin-resistance to sensitive NSCLC cells in vitro and in vivo. Mechanistically, hypoxia-induced exosomal PKM2 promoted glycolysis in NSCLC cells to produce reductive metabolites, which may neutralize reactive oxygen species (ROS) induced by cisplatin. Additionally, hypoxia-induced exosomal PKM2 inhibited apoptosis in a PKM2-BCL2-dependent manner. Moreover, hypoxia-induced exosomal PKM2 reprogrammed CAFs to create an acidic microenvironment promoting NSCLC cells proliferation and cisplatin resistance. Conclusions: Our findings revealed that hypoxia-induced exosomes transmit cisplatin resistance to sensitive NSCLC cells by delivering PKM2. Exosomal PKM2 may serve as a promising biomarker and therapeutic target for cisplatin resistance in NSCLC.