Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis.

Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca2+/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca2+/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.

Comparing the Effectiveness of Electroacupuncture with Different Grades of Knee Osteoarthritis: A Prospective Study.

BACKGROUND: The electroacupuncture (EA) with different number of points significantly affected its efficacy on knee osteoarthritis (KOA), and the severity of KOA also influenced its response to treatments. Hence, we prospectively compared the clinical efficacy of EA on KOA with different severities. METHODS: A total of 132 KOA patients recruited from 181st Central Hospital of The Chinese People's Liberation Army between March 2014 and March 2015 were classified into 4 KOA stages according to Kellgren Lawrence grading scale. They were allocated into three treatment groups, including two-point group, four-point group and six-point group. Patients in the six-point group received treatment at six-points including ST34, SP10, SP9, ST36, ST35 and EX-LE4. Patients in the four-point group received treatment at ST34, SP10, ST35 and EX-LE5, while patients in the two-point group received treatment at ST35 and EX-LE4. Visual Analog Scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC) and self-assessment questionnaire of patients were assessed after treatment. RESULTS: Three kinds of EA treatments all have significant clinical effects on KOA patients with down-regulated scores of VAS and WOMAC. Regarding post-treatment efficacy, the six point group exhibited lower VAS score and higher WOMAC score compared with the other two groups. For patients with different KOA grades, patients with higher KOA grades were associated with lower grade of treatment efficacy. CONCLUSIONS: Patients with KOA, especially those with lower KOA stages, could gain beneficial efficacies from EA treatments with two, four and six points, respectively.

Improved immune response to an attenuated pseudorabies virus vaccine by ginseng stem-leaf saponins (GSLS) in combination with thimerosal (TS).

Vaccination using attenuated vaccines remains an important method to control animal infectious diseases. The present study evaluated ginseng stem-leaf saponins (GSLS) and thimerosal (TS) for their adjuvant effect on an attenuated pseudorabies virus (aPrV) vaccine in mice. Compared to the group immunized with aPrV alone, the co-inoculation of GSLS and/or TS induced a higher antibody response. Particularly, when administered together with GSLS-TS, the aPrV vaccine provoked a higher serum gB-specific antibody, IgG1 and IgG2a levels, lymphocyte proliferative responses, as well as production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) from lymphocytes, and more importantly provided an enhanced cytotoxicity of NK cells and protection against virulent field pseudorabies virus challenge. Additionally, the increased expression of miR-132, miR-146a, miR-147 and miR-155 was found in murine macrophages cultured with GSLS and/or TS. These data suggest that GSLS-TS as adjuvant improve the efficacy of aPrV vaccine in mouse model and have potential for the development of attenuated viral vaccines.

Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals.

Increased humoral immune responses of pigs to foot-and-mouth disease vaccine supplemented with ginseng stem and leaf saponins.

Vaccination is a conventional approach against foot-and-mouth disease (FMD) in pigs. However, failure to elicit an immune response to vaccine has been reported. Our previous investigation showed that ginseng stem and leaf saponins (GSLS) and mineral oil acted synergistically to promote Th1/Th2 immune responses to FMD vaccine in mice. This study was designed to i) find the optimal doses of GSLS in oil-emulsified FMD vaccines to induce immune responses in mice and pigs and ii) to evaluate the effect of oil-emulsified FMD vaccine supplemented with GSLS on the immune responses in pigs, by measuring the serum indirect hemagglutination (IHA) titer and IgG and IgG subclass levels. The GSLS-enhanced immune response to FMD oil-emulsion vaccine depended on the dose of GSLS added to the vaccine. Addition of GSLS at a dose of 40 µg to 2 ml of FMD oil-emulsified vaccine significantly enhanced the humoral immune responses in pigs, when compared to the vaccine without GSLS (P<0.05). The increased antibodies included IgG1 and IgG2. Hence, GSLS and oil adjuvant synergistically promoted the immune responses to vaccination against FMD in pigs, and GSLS could be a promising vaccine additive to improve oil-emulsified veterinary vaccines.

Effect of oral administration of ginseng stem-and-leaf saponins (GSLS) on the immune responses to Newcastle disease vaccine in chickens.

This study was designed to evaluate the effect of oral administration of ginseng stem-and-leaf saponin (GSLS) on immune responses in chickens vaccinated with live Newcastle disease (ND) vaccines. In experiment 1, chickens were orally administered GSLS (2.5, 5, 10, and 20mg/kg) in drinking water for 3 days, and then intranasally vaccinated with ND vaccine. Hemagglutination inhibition (HI) test showed that the optimal dose of GSLS for enhancing HI titers was 5mg/kg. In experiment 2, chickens were fed with GSLS (5mg/kg) for 7, 5 or 3 days before vaccination. Result indicated that GSLS enhanced HI titers in a time-dependent manner. The order of the duration for drinking GSLS on increasing HI titers was 7 days>5 days>3 days. In experiment 3, chickens were fed with GSLS before or after immunization. Serum was sampled at a week interval for 5 weeks for HI test, splenic lymphocytes were prepared at weeks 2 and 4 after the booster immunization for lymphocyte proliferation test (LPT) and intestinal tissues were sampled at week 4 after the booster immunization for immunohistochemistry and histological examination. Results showed that HI titer, LPT, IgA+ cells and intestinal intraepithelial lymphocytes (iIELs) were significantly higher in chickens drinking GSLS before vaccination than those after vaccination. Therefore, oral administration of GSLS in drinking water at a dose of 5mg/kg for 7 days significantly increased systemic as well as gut mucosal immunity in chickens immunized with ND vaccine. Considering the immune potentiating effect of GSLS on ND vaccine, GSLS should be evaluated for its oral adjuvant effect on the immune response against other diseases such avian influenza and infectious bursal disease.