Feather pulp was analyzed by means of polyacrglamide gel electrophoresis for Landaise geese's prealbumin polymorphisms. The result showes that the method is recommendable for the study on protein polymorphisms of poultry, and harmless to bird. The electrophoretogram on prealbumin region exists 4～5 prealbumin bands, which is divided by 3 subregions. Paf and Pam are all exist 1 band. 2 phenotypes are found in Pas region. The frequency of type Pas1-2 is at most, reached 83.33%, and 16.67% for that of type pas1-1.
Atherosclerosis as the common disease has aroused many attentions worldwide. Gene target therapy has become the promising filed for atherosclerosis treatment. Herein, LncRNA AK094457 as a new promising therapy target is investigated in OX-LDL induced vascular smooth muscle cells. The Results showed that LncRNA AK094457 downregulated by shRNA-AK094457-1 have inhibiting effects on proliferation, migration, ROS level and inflammation level in OX-LDL induced vascular smooth muscle cells (VSMCs). In addition, the down regulation of lncRNA suppressed expressions of relevant proteins that are involved in TLR4/MyD88 signal pathway and enhanced expressions of relevant proteins in Nrf2/HO-1 pathway. Taken together, Down regulation of lncRNA AK094457 against effects induced by OXL-LDL in atherosclerosis via Nrf2/HO-1 and TLR4/MyD88 signal pathway is a promising avenue for atherosclerosis treatment.
Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization.
3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Polygalae Radix ("YuanZhi," the roots of Polygala tenuifolia WILLD.), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca2+ transients were recorded in myocytes loaded with the Ca2+ indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15–30 µM) significantly shortened action potential duration at 50% and 90% repolarization (APD50 and APD90) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (ICa,L), but showed effect on neither transient outward potassium current (Ito) nor steady-state potassium current (IK,SS). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of ICa,L and the suppression of intracellular Ca2+ transients, which consequently suppress the generation of transient inward current (Iti). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.
The current study was designed to investigate the effect of madecassoside, the major triterpene in CENTELLA ASIATICA, on burn wound healing and its possible mechanism of action. An oral administration of madecassoside (6, 12, 24 mg/kg) facilitated wound closure in a time-dependent manner and reached its peak effect, nearly completely wound closure, on day 20 in the group receiving the highest dose of 24 mg/kg of madecassoside. Further histopathological analysis revealed that madecassoside alleviated infiltration of inflammatory cells as well as enhanced epithelisation resulting from dermal proliferation of fibroblasts. Madecassoside at higher doses (12 and 24 mg/kg) decreased nitric oxide (NO) levels and malondialdehyde (MDA) content in the burn skin tissue. However, reduced glutathione (GSH) and hydroxyproline levels were increased in the same skin tissue. In addition, madecassoside promoted skin angiogenesis IN VIVO, correlating with our findings IN VITRO that it stimulated endothelial cell growth in a rat aortic ring assay. These data suggest that madecassoside has significant wound-healing activity and is one of the major reasons for the use of C. ASIATICA herbs in the successful treatment of burn injury. Moreover, the results from the present study indicate that the effect of madecassoside on wound healing may involve several mechanisms including antioxidative activity, collagen synthesis and angiogenesis.
Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum , has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen‐induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro‐inflammatory cytokines including IL‐1β, IL‐6, IL‐8 and TNFα, and downregulated the expression of MMP‐9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα‐induced activations of NF‐κB and MAPKs (p38 and JNK) leading to the downregulation of pro‐inflammatory cytokines, which was beneficial to the anti‐proliferative and anti‐migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA.
Low back pain (LBP) is a global health issue. Intervertebral disc degeneration (IDD) is a major cause of LBP. Although the explicit mechanisms underpinning IDD are unclear, endoplasmic reticulum (ER) stress caused by aberrant unfolded or misfolded proteins may be involved. The accumulation of unfolded/misfolded proteins may result in reduced protein synthesis and promote aberrant protein degradation to recover ER function, a response termed the unfolded protein response. A growing body of literature has demonstrated the potential relationships between ER stress and the pathogenesis of IDD, indicating some promising therapeutic targets. In this review, we summarize the current knowledge regarding the impact of ER stress on the process of IDD, as well as some potential therapeutic strategies for alleviating disc degeneration by targeting different pathways to inhibit ER stress. This review will facilitate understanding the pathogenesis and progress of IDD and highlights potential therapeutic targets for treating this condition.
Endoplasmic-reticulum-associated protein degradation
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