Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB.

It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.

Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt.

Apoptosis of implanted mesenchymal stem cells (MSCs) limits the efficiency of MSC therapy. Recent studies showed the ligands of Toll-like receptors (TLRs) could control the function of these cells. We have investigated the effect of lipopolysaccharides (LPS), a ligand of TLR4, on the survival of MSCs and explored the roles of TLR4 and PI3K/Akt. H(2)O(2)/serum deprivation(H(2)O(2)/SD) induced apoptosis of MSCs but LPS-preconditioning (1.0microg/ml) protected MSCs from H(2)O(2)/SD-induced apoptosis and promoted their proliferation. Western blotting showed that 1.0microg/ml LPS enhanced phosphorylation of both Akt at Ser 473 and nuclear factor-kappa B (NF-kappaB) p65 at Ser 536. However, the protective effects of LPS on survival were not observed in TLR4(lps-del) MSCs. The results suggest appropriate treatments with LPS can protect MSCs from oxidative stress-induced apoptosis and improve the survival of MSCs via the TLR4 and PI3K/Akt pathway.

Treatment with yiqi bushen koufuye combined with chemotherapy for preventing postoperative metastasis of stomach cancer--a clinical observation of 28 cases.

OBJECTIVE: To study the effect of yiqi bushen koufiuye (oral liquid for invigorating qi and tonifying the kidney) combined with chemotherapy on postoperative metastasis of stomach cancer. METHODS: The 47 cases of postoperative stomach cancer with the syndrome of deficiency of both the spleen and kidney were divided randomly into the treatment group (28 cases), and the control group (19 cases). The control group was treated simply by chemotherapy; while the treatment group, was treated with Yiqi Bushen Koufuye in addition to chemotherapy. The effect was observed 12 months later on local relapse and distal metastasis, the life quality, peripheral hemogram, and immunologic function. RESULTS: The rates of postoperative relapse and metastasis of the treatment group were obviously lower than those of the control group (P < 0.05). The Karnofasky scores, peripheral hemogram and immunologic function of the treatment group were obviously improved in comparison with the control group (P < 0.01 or P < 0.05). CONCLUSION: Yiqi bushen koufuye combined with chemotherapy is effective in preventing postoperative metastasis of stomach cancer, increasing sensitivity and decreasing toxins, and improving the life quality and immunologic function of the patient.