HBG gene modified autologous CD34+ hematopoietic stem cells(Guangzhou Ruifeng)

We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-alpha (TNF-alpha)-stimulated mature DC. PCa cells and DC were co-incubated for 24-48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-alpha resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-alpha treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-alpha-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients.Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

Dengue virus (DENV), a mosquito-borne flavivirus, leads to over 390 million annual infections worldwide, and there are no approved antivirals so far. Rhododendron mariae (RM), a traditional Chinese herb abundant in flavonoids and triterpenoids, is used to treat respiratory disorders, yet its antiviral potential has been little explored. This study sought to assess the activity and mechanism of RM-1, an extract from RM, against DENV.

In vitro, plaque reduction assays in BHK-21 cells were used to determine RM-1’s half-maximal effective concentration (EC50) against DENV-2. Its broad-spectrum activity against the four DENV serotypes was tested in Vero and Huh7 cells. In vivo, DENV-infected suckling mice were given RM-1 (10 mg/kg), with monitoring of viral loads, histology, and survival. Mechanistic studies included attachment assays and molecular docking to find potential targets.

RM-1 strongly inhibited DENV-2 (EC50=2.24 μg/mL) and showed dose-dependent activity against all four serotypes by blocking viral attachment. In infected mice, RM-1 lessened disease severity, reduced tissue lesions, lowered viral loads in serum, brain and spleen, and boosted survival rates. It targeted DENV envelope protein domain III (ED III), which is critical for host attachment.

This is the first report that RM-1 acts as a novel DENV attachment inhibitor by targeting ED III. These findings show RM-1’s promise as an anti-dengue therapeutic, supporting traditional herbs as sources of antivirals for flavivirus drug development.