GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFß1/Smad-Mediated Epithelial-to-Mesenchymal Transition.

Objective: Idiopathic pulmonary fibrosis is an irreversible and progressive fibrotic lung disease that leads to declines in pulmonary function and, eventually, respiratory failure and has no effective treatment. Gly-His-Lys (GHK) is a tripeptide involved in the processes of tissue regeneration and wound healing and has significant inhibitory effects on transforming growth factor (TGF)-ß1 secretion. The effect of GHK on fibrogenesis in pulmonary fibrosis and the exact underlying mechanism have not been studied previously. Thus, this study investigated the effects of GHK on bleomycin (BLM)-induced fibrosis and identified the pathway that is potentially responsible for these effects. Methods: Intratracheal injections of 3 mg/kg BLM were administered to induce pulmonary fibrosis in C57BL/6 mice. GHK was administered intraperitoneally at doses of 2.6, 26, and 260 µg/ml/day every other day from the 4th to the 21st day after BLM instillation. Three weeks after BLM instillation, pulmonary injury and pulmonary fibrosis was evaluated by the hematoxylin-eosin (HE) and Masson's trichrome (MT) staining. Chronic inflammation index was used for the histological assessments by two pathologists blindly to each other. Tumor necrosis factor (TNF)-α and IL-6 levels in BALF and myeloperoxidase (MPO) activity in lung extracts were measured. For the pulmonary fibrosis evaluation, the fibrosis index calculated based on MT staining, collagen deposition and active TGF-ß1 expression detected by ELISA, and the expression of TGF-ß1, α-smooth muscle actin (SMA), fibronectin, MMP-9, and TIMP-1 by western blotting. The epithelial mesenchymal transition index, E-cadherin, and vimentin was also detected by western blot. The statistical analysis was performed by one-way ANOVA and the comparison between different groups were performed. Results: Treatment with GHK at all three doses reduced inflammatory cell infiltration and interstitial thickness and attenuated BLM-induced pulmonary fibrosis in mice. GHK treatment significantly improved collagen deposition, and MMP-9/TIMP-1 imbalances in lung tissue and also reduced TNF-α, IL-6 expression in bronchoalveolar lavage fluid (BALF) and MPO in lung extracts. Furthermore, GHK reversed BLM-induced increases in TGF-ß1, p-Smad2, p-Smad-3 and insulin-like growth factor-1 (IGF-1) expression. Conclusion: GHK inhibits BLM-induced fibrosis progression, the inflammatory response and EMT via the TGF-ß1/Smad 2/3 and IGF-1 pathway. Thus, GHK may be a potential treatment for pulmonary fibrosis.

[Reactive nitrogen loss pathways and their effective factors in paddy field in southern China].

Based on the literature data, the N20 emission, N leaching, N runoff and NH3 volatilization were compared from different rice production regions and their effective factors were evaluated. The results showed that N2 0 emission, N leaching and N runoff in single rice in Yangtze River basin were higher than in other rice production regions, with N loss of 1.89, 6.4 and 10.4 kg N · hm(-2), and N loss rate of 0.8%, 3.8% and 5.3%, respectively. The high N20 emission, N leaching and N runoff in these regions might be attributed to high-rate N application and dry-wet alternation. The NH3 volatilization was the highest in late rice in southern China, with N loss of 54.9 kg N · hm(-2) and N loss rate of 35.2% due to higher temperature at late rice growing stage. In the field, the practice often decreased one reactive N loss but increased another one, indicating that intergated practical management is necessary to reduce reactive N loss. Reactive N loss often increase with increasing grian yield, which is associed with the high-rate N application. The N20 emission, N leaching and N runoff decreased with increasing the partial factor productivity of applied N (PFP). Therefore, reducing N losses per unit of yield is necessary for integrating higher yield with minimum environmental pollution.

Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats.

Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.

[Effects of nitrogen fertilization on population dynamics and yield of high-yielding wheat and on alteration of soil nitrogen].

Taking wheat varieties Yumai 49-198 (multi-spike phenotype) and Lankao Aizao 8 (large-spike phenotype) as test materials, field experiments were conducted at Wenxian and Lankao sites of Henan Province to study the effects of nitrogen fertilization on their population dynamics and yield and on the alteration of soil nitrogen. Five nitrogen application rates, i. e., 0, 90, 180, 270, and 360 N kg x hm(-2) were installed. The population amount of the two test varieties were all increased after emergence, reached the highest at jointing stage, and decreased afterwards. As for Yumai 49-198, its population amount had no significant differences at wintering and turning-green stages among the five nitrogen application rates and two experimental sites, but differed significantly after jointing stage with the nitrogen application rates. For Lankao Aizao 8, its population amount had no significant differences among the nitrogen application rates during whole growth period. The grain yield of the two varieties increased with the increase of nitrogen fertilization rate, but excessive nitrogen fertilization decreased the grain yield. Yumai 49-198 had the highest yield at 270 N kg x hm(-2), being 9523 and 9867 kg x hm(-2) at Wenxian and Lanako sites, respectively, while Lankao Aizao 8 had the highest yield at 180 N kg x hm(-2), being 9258 and 9832 kg x hm(-2) at Wenxian and Lanako sites, respectively. With the increase of nitrogen fertilization rate, soil nitrate N concentration and apparent nitrogen loss increased. At Wenxian and Lankao sites, the apparent soil nitrogen loss for Yumai 49-198 was 32.56% - 51.84% and - 16.7% - 42.6% of fertilized nitrogen, and that for Lankao Aizao 8 was 18.58% - 52.94% and - 11.5% - 45.8% of fertilized nitrogen, respectively. Considering the yield and environmental effect comprehensively, the nitrate N concentration in 0-90 cm soil layer in our case should not be exceeded 120 - 140 kg x hm(-2), and the maximal nitrogen application rate should not be exceeded 180 kg x hm(-2).

[FTIR spectroscopic study on the stress effect of compositions of macromolecular structure in tectonically deformed coals].

Fourier transform infrared spectroscopy (FTIR) was applied to the study of the stress effect of compositions of macromolecular structure in tectonically deformed coals. The results showed that in different kinds of tectonically deformed coals, the absorption band of aromatic structure, aliphatic structure and oxygen functional groups nearly consistent in the peak wave number, but the intensity of the peak is different which is justly influenced by different deformation degree and deformation mechanism of tectonically deformed coals under tectonic stress. In the metamorphic and deformed environments of the low, middle and high coal rank, for tectonically deformed coals, with the increasing stress, hydrogen-enriched degree and oxygen-enriched degree decrease, while the degree of ring condensation increases. But there are differences in the change of compositions contents of macromolecular structure. This might indicate that the FTIR could be used in the stress effect of compositions of macromolecular structure in tectonically deformed coals.