To explore the role of heme oxygenase (HO)-1 experimental system in dachengqitang (DD) ameliorating ALI induced by lipopolysaccharide (LPS) in mice. Seventy-five male Kunming mice were randomly divided into control group (normal saline was instilled intratracheally(50 microL/per mouse), LPS group (LPS was instilled intratracheally to replicate ALI model), DD + LPS group, DD + LPS + ZnPP (ZnPP, HO-1 specific inhibitor) group and the DD group. Mice were killed at 6 h after administration. Lung indexes were tested; lung histomorphological changes were observed under microscope, and neutrophils (PMN) number and protein content of bronchoalveolar lavage fluid (BALF) were measured; HO-1 mRNA and protein expression in lung tissue were detected by RT-PCR and Western blot. The results showed that intratracheal instillation of LPS in mice can cause significant morphological changes in lung tissue. Both PMN numbers and protein content in BALF were increased. meanwhile the expressions of HO-1 mRNA and protein in lung tissue were increased. Pretreated with DD and then intratracheally instillated LPS coulde ameliorat lung tissue injury, reduced PMN BALF number and protein content, but increase HO-1 mRNA and protein expression in the lung tissue when compared with LPS. HO-1 inhibitor ZnPP coulde inhibite the ameliorative effect of DD. The results suggest that the ameliorative effect of DD on ALI induced by LPS in mice were related with upregulation HO-1 mRNA and protein.
Acute Lung Injury ; chemically induced ; prevention & control ; Animals ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Gene Expression Regulation, Enzymologic ; drug effects ; Heme Oxygenase-1 ; antagonists & inhibitors ; genetics ; metabolism ; Leukocyte Count ; Lipopolysaccharides ; Lung ; drug effects ; enzymology ; pathology ; Male ; Mice ; Neutrophils ; cytology ; drug effects ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Proteins ; metabolism ; Protoporphyrins ; pharmacology ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome

Objective To encode the protein cystatin M with CST6 gene and construct a CST6-overexpression vector,and transfect it into the gastric cancer cells SGC-7901 in order to observe the effect of cystatin M on the proliferation and migration abilities of SGC-7901 cells.Methods There were three groups in the experiment:pcDNA3.1(+)-CST6 group,pcDNA3.1 (+)group and non-transfected group.RT-PCR and Western blot were used to identify the RNA expression of CST6 in SGC-7901/CST6 cells.The proliferation and migration abilities of the transfected cells were detected by MTT and cell wound healing assay,respectively.Results SGC-7901/CST6 cells stably expressed CST6 gene RNA and cystatin M protein.The proliferation and migration of pcDNA3 .1 (+)-CST6 group cells were reduced compared with those of cells in the other two groups (P<0.05).Conclusion Cystatin M can inhibit the proliferation and migration of SGC-7901 cells.

Objective To investigate the change of plasma ghrelin level and explore the related factors of ghrelin alteration in elderly hypertensive patients with psychological distress. Methods A total of 300 elders, who were screened with Hamilton Anxiety Scale (HAMA), Hamilton Rating Scale for Depression (HAMD), and the Symptom Checklist-90 (SCL-90) for psychological stress and somato-psychological manifestations respectively, were divided into hypertension group (n=148) and non-hypertension group (n=152). Their blood samples were collected to measure the plasma level of ghrelin and total cortisol on the same day. Results The incidences of anxiety and depression were 27.7% and 11.7%, respectively, in all the enrolled elders. However, the rates of psychological distress, particularly anxiety, were significantly higher in the hypertensive elders than in the non-hypertensive ones (43.2% vs. 12.5%). Anxiety was positively related to the cortisol level but negatively related to the plasma ghrelin level, and the latter two were negatively correlated with each other. Conclusion Chronic increase of plasma cortisol induced by long-term anxiety can lead to the reduction of ghrelin level, which then adversely affects blood pressure in elders with psychological distress. Therefore, ghrelin might be a selective antihypertensive medicine for hypertensive elders with anxiety.

Objective To investigate whether the expression of metal matrix protease-9 (MMp-9) changes with altitude in severe acute pancreatitis (SAP) lung injury by establishing SAP model in rats.The related indexes of pancreas and lung injury and MMp-9 were measured.Methods 280 SPF male Wistar rats were randomly assigned to different altitude groups to establish SAP model,then the serum amylase (AMY) content of each group were detected.The degree of pancreatic injury and pancreatic pathological score were observed under light microscope.The expression level of MMP-9 in lung tissues was measured and analyzed by statistical methods.Results (1) At the same altitude,the expression of MMP-9 in each time group increased with time,with statistically significant difference (P ≤ 0.05).(2) AMY value,pathological score of pancreas and expression of MMP-9 in lung tissue increased with the altitude in the same time group at different altitudes,with statistically significant difference (P ≤ 0.05).Conclusions The higher the altitude,the more severe the damage of SAP and lung,and the higher the expression level of MMP-9.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.