Combination of retinoids and narrow-band ultraviolet B inhibits matrix metalloproteinase 13 expression in HaCaT keratinocytes and a mouse model of psoriasis.

Matrix metalloproteinase13 (MMP13) can be released by keratinocytes and fibroblasts and involved in the pathogenesis of skin disorders. Retinoic acid derivative drugs include tazarotene and acitretin. Tazarotene/acitretin and narrow-band ultraviolet B (NB-UVB) irradiation are common treatment options for psoriasis. However, their impact on MMP13 expression in the context of psoriasis has yet to be determined. The expression of MMP13 was analyzed in patients with psoriasis. The effects of tazarotene/acitretin and NB-UVB on MMP13 expression were also investigated in a mouse model of psoriasis. Human HaCaT keratinocytes were exposed to acitretin or NB-UVB and then assayed for cell proliferation and MMP13 expression levels. We showed that patients with psoriasis had increased levels of MMP13 protein in skin lesions and serum samples. Exposure to acitretin and NB-UVB irradiation alone or in combination led to reduction of cell proliferation and MMP13 expression in HaCaT cells. Consistently, tazarotene treatment or NB-UVB irradiation attenuated imiquimod-induced psoriasis-like dermatitis and decreased MMP13 expression in a mouse model. Based on these from HaCaT keratinocytes cells and animal experiments, we suggest that tazarotene/acitretin and NB-UVB irradiation can inhibit the expression of MMP13 in HaCaT keratinocytes and psoriasis mouse models. Blockade of MMP13 activity may have therapeutic potential in improving symptoms of psoriasis.

Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma.

BACKGROUND: Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. METHODS: Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. RESULTS: The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting ß-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or ß-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. CONCLUSION: miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

Improved Polarizable Dipole-Dipole Interaction Model for Hydrogen Bonding, Stacking, T-Shaped, and X-H···π Interactions.

The polarizable dipole-dipole interaction model was formulated in our laboratory to rapidly simulate hydrogen bonding in biosystems. In this paper, this model is improved and further parametrized for stacking, T-shaped, and X-H···π interactions by adding the orbital overlap term and fitting to 19 CCSD(T)/CBS interaction energy curves of training dimers. The performance of our model is assessed through its application to more than 100 complexes, including hydrogen-bonded, stacked, T-shaped, and X-H···π complexes. For 124 relatively small testing complexes, our model reproduces benchmark equilibrium intermolecular distances with a root-mean-square deviation (RMSD) of 0.08 Å, and it reproduces benchmark interaction energies with a 0.64 kcal/mol RMSD. For 14 large noncovalent complexes, our model reproduces benchmark equilibrium intermolecular distances with a RMSD of 0.05 Å, and it reproduces benchmark interaction energies with a 0.80 kcal/mol RMSD. Extensive comparisons are made to interaction energies calculated via the M06-2X and M06-2X-D3 methods, via the well-known nonpolarizable AMBER99 force field method, via the popular polarizable AMOEBA force field method, and via semiempirical quantum mechanical (SQM) methods. Our statistical evaluations show that our model outperforms the AMBER99, AMOEBA, and SQM methods and is as accurate as the M06-2X and M06-2X-D3 methods. In summary, the model developed in this work is reasonable, and the newly introduced orbital overlap term is effective in the accurate modeling of the noncovalent interactions. Our testing results also indicate that the polarization interaction term is important in the evaluation of hydrogen bonding, whereas the orbital overlap is important in examining short hydrogen bonding, T-shaped, and X-H···π interactions. Our model may serve as a new tool for modeling biological systems where hydrogen bonding, stacking, T-shaped, and X-H···π interactions are of general importance.

How shall we design the future vehicle for Chinese market.

Surface transportation system is developing very fast in China and the number of vehicles is increasing quickly as well. This development creates a lot of problems on traffic safety and the number of accident is also increasing. In this paper, we made deep analysis of different possible causes of safety problems through three aspects: the traffic environment and infrastructure, in-vehicle information system design and the characteristics of drivers. There are many factors in each aspects may contribute to the transportation safety problems. Problems with infrastructure design and traffic design contribute over 50% of the traffic accident. Another important factor is that people has very little traffic safety concept and very weak on understanding the important of right behavior on the road. This paper has pointed the urgent needs to study the human factors in road and transportation system and vehicle HMI design, as there are very few such studies available in literature based on Chinese situation. The paper also proposed the needs to develop proactive educational system that can promote driver's understanding of traffic safety and to take the right action during drive.

[Effects of salt-alkali stress on osmoregulation substance and active oxygen metabolism of Qingshan poplar (Populus pseudo-cathayana x P. deltoides)].

Aimed to examine the adaptability of Qingshan poplar (Populus pseudo-cathayana x P. deltoides) to salt-alkali stress, two-year-old cutting seedlings of the poplar were treated with 28 combinations of salt-alkali stress. With increasing salt concentration, the leaf electrolyte leakage and MDA and proline contents of test seedlings all showed an increasing trend, while the leaf soluble sugar content and SOD and POD activities increased first but decreased afterwards. The increase of substrate pH made the electrolyte leakage, MDA content, and POD activity increased and the proline and soluble sugar contents decreased after an initial increase, but had lesser effects on the SOD activity. When the salinity was <100 mmol x L(-1) and the pH was increasing, all test physiological indices had a slight change while SOD activity kept at a higher level; when the salinity was >200 mmol x L(-1) and the pH was higher than 8.99, the electrolyte leakagewas higher than 50%, POD activity and MDA content increased obviously, proline and soluble sugar contents declined, and SOD activity was lower. It was concluded that a salt-alkali condition with salinity >200 mmol x L(-1) and pH > 8.99 was not appropriate to the growth of Qingshan poplar.