Objective:To compare serum level of β thromboglobulin in patients with coronary heart disease (CHD) complicated different complications.Methods:According to their complications,a total of 398 patients with unsta- ble angina pectoris (UAP)were divided into pure UAP group (UAP control group,n=82),hypertension group (n=89),diabetes mellitus (DM)group (n=133)and brain infarction group (n=94).Serum level of β thromboglobu- lin were measured and compared among four groups 6h after onset and before discharge.Incidence of myocardial in- farction within six months were followed up in four groups.Results:On 6h after onset,the serum level of β throm- boglobulin of brain infarction group,DM group,hypertension group,UAP control group was (61.13±3.32)ng/ml,(59.77±3.15)ng/ml,(52.12±3.27)ng/m, (48.55±3.14)ng/ml respectively,in which the level of brain infarction group was the highest,the difference between any two groups were significant (P<0.01 all);Compared with 6h after onset,there were significant reductions in serum levels of β thromboglobulin of four groups before dis- charge P<0.01 all,their ordering and difference significant degree were no change.The incidence of myocardial infarction (MI)in brain infarction group,DM group,hypertension group,UAP control group was 11.7%,6.0%, 3.4%,2.4% respectively,the MI incidence of brain infarction group was significant more than that of UAP con- trol group,the differences among other groups was no significant,P>0.05.Conclusion:β-thromboglobulin level during UAP onset is significant higher than that of remission period,and it rises most significantly in brain infarction group,and in this group the percentage of myocardial infarction occurred within six months is highest

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.