Psoralen attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7th to 21st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM-induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM-induced expression of α-smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor-ß1, interleukin-1ß, and tumor necrosis factor-α in the lungs of BLM-stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM-induced murine model.

Effects of RNA m6A writer METTL3 and hDPSCs on the peripheral nerve regeneration: In vitro and in vivo study.

PURPOSE: This study aimed to investigate whether RNA m6A participated in the differentiation and proliferation of dental pulp stem cells and improved peripheral nerve regeneration using a rat model of crushed mental nerve injury. MATERIALS AND METHODS: The components of RNA m6A were analyzed through qRT-PCR, while cell proliferation of different groups, including over-expression METTL3 (OE-METTL3) hDPSCs group, knock-down METTL3 (KD-METTL3) hDPSCs group and hDPSCs group in vitro, was clarified by MTT assay. Five groups were designed, namely, Control group, Sham group, hDPSCs group, OE-METTL3 group and KD-METTL3 group. After crushed right mental nerve injury, cells of different groups were transplanted into the lesion area (6 ul in volume). At one, two and three weeks later, histomorphometric analysis and sensory test were conducted in vivo. RESULTS: qRT-PCR results showed that "METTL3" was participated in the differentiation of dental pulp stem cells. There were differences (P < 0.05) between OE-METTL3 group and control group in MTT results in the third, fourth and sixth days. Moreover, the sensory test revealed significant differences (P < 0.05) in difference score and gap score between OE-METTL3 group and KD-METTL3 group in the first and third weeks. The axon counts and retrograde labeled neurons significantly increased in OE-METTL3 group compared with KD-METTL3 group. CONCLUSIONS: These results demonstrated that RNA m6A participated in the differentiation and proliferation of dental pulp stem cells, and that OE-METTL3 group exhibited the greater ability to improve peripheral nerve regeneration than KD-METTL3 group and hDPSCs group.

[Responses of net ecosystem carbon exchange to diffuse radiation in an alpine meadow on the Qinghai-Tibetan Plateau, China.] / 青藏高原高寒草甸净生态系统碳交换对散射辐射变化的响应.

Qinghai-Tibetan Plateau, one of the regions on the earth that receives the most solar radiation, is the world's highest alpine meadow ecosystem, with significance to regional and global carbon cycles. To examine the effects of solar radiation on ecosystem carbon dynamics in an alpine meadow, the net ecosystem CO2 exchange (NEE), solar radiation, diffuse radiation, and related environmental variables were measured using eddy-covariance technique and micro-meteorological system. Sky conditions were divided into three categories of clear days (CI≥0.7), cloudy days (0.315 ℃. Under clear sky day conditions, Re increased with increasing CI due to the increases of air temperature, with negative effects on NEE. NEE increased with the increases of VPD up to 0.6 kPa, then slowly decreased when VPD>0.6 kPa, illustrating that NEE was reduced due to the relatively high VPD. Our results suggested that strong solar radiation on clear days would not increase carbon uptake capacity of alpine meadow, while cloudy days with clearness index of 0.6-0.7 would help increase carbon sequestration on the Qinghai-Tibetan Plateau.

Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation.

Vasoactive intestinal peptide (VIP) is one of the most abundant neuropeptides in the lungs with various biological characters. We have reported that VIP inhibited the expressions of TREM-1 and IL-17A, which are involved in the initiation and amplification of inflammation in acute lung injury (ALI). However, the overall effect of VIP on ALI remains unknown. The aim of this study is to investigate the therapeutic effect of VIP mediated by lentivirus (Lenti-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lenti-VIP. Lenti-VIP increased the respiratory rate, lung compliance, and tidal volume, while decreased airway resistance in ALI mice, detected by Buxco system. Lenti-VIP significantly reduced inflammatory cell infiltration and maintained the integrity of the alveolar septa. Lenti-VIP also remarkably decreased the total protein level, the number of neutrophil and lactate dehydrogenase activity in the bronchoalveolar lavage fluid of LPS-induced ALI mice. In addition, Lenti-VIP down-regulated pro-inflammatory tumor necrosis factor (TNF)-α mRNA and protein expression, while up-regulated anti-inflammatory interleukin-10 mRNA and protein expression in lungs of ALI mice. Furthermore, we observed that VIP reduced the TNF-α expression in murine macrophages under LPS stimulation through protein kinase C and protein kinase A pathways. Together, our findings show that in vivo administration of lentivirus expressing VIP exerts a potent therapeutic effect on LPS-induced ALI in mice via inhibiting inflammation.

[Comparison of eddy covariance and static chamber/gas chromatogram methods in measuring ecosystem respiration].

Based on the measurement of carbon flux by the methods of eddy covariance and static chamber/gas chromatogram, a comparison was made between the two methods in evaluating ecosystem respiration over winter wheat (Triticum aestivum)--summer maize (Zea mays) double cropland and Kobresia humilis alpine meadow. The results showed that under the conditions of obtained data having good quality, nighttime ecosystem respiration from eddy covariance measurement was significantly agreed with that from static chamber/gas chromatogram measurement, with the correlation coefficients ranging from 0.95 to 0.98, and the daytime ecosystem respiration from these two measurements also had a good consistency though the static chamber/gas chromatogram measurement often produced higher values. The daily mean value of ecosystem respiration was significantly different between these two measurements, but the seasonal pattern was similar. For winter wheat-summer maize double cropland, the difference of mean air temperature inside and outside the chamber was 1.8 degrees C, and the daily mean value of ecosystem respiration across the whole study period was 30.3% lower in eddy covariance measurement than in static chamber/gas chromatogram measurement; while for alpine meadow, the difference of the mean air temperature was 1.9 degrees C, and the daily mean value of ecosystem respiration was 31.4% lower in eddy covariance measurement than in static chamber/gas chromatogram measurement. The variance between the daily mean values of ecosystem respiration obtained from the two measurements was higher in growing season than in dormant season.