Photobiomodulation, alone or combined with adipose-derived stem cells, reduces inflammation by modulation of microRNA-146a and interleukin-1ß in a delayed-healing infected wound in diabetic rats.

Diabetic wounds are categorized by chronic inflammation, leading to the development of diabetic foot ulcers, which cause amputation and death. Herewith, we examined the effect of photobiomodulation (PBM) plus allogeneic diabetic adipose tissue-derived stem cells (ad-ADS) on stereological parameters and expression levels of interleukin (IL)-1ß and microRNA (miRNA)-146a in the inflammatory (day 4) and proliferation (day 8) stages of wound healing in an ischemic infected (with 2×107 colony-forming units of methicillin-resistant Staphylococcus aureus) delayed healing wound model (IIDHWM) in type I diabetic (TIDM) rats. There were five groups of rats: group 1 control (C); group 2 (CELL) in which rat wounds received 1×106 ad-ADS; group 3 (CL) in which rat wounds received the ad-ADS and were subsequently exposed to PBM(890 nm, 80 Hz, 3.5 J/cm2, in vivo); group 4 (CP) in which the ad-ADS preconditioned by the PBM(630 nm + 810 nm, 0.05 W, 1.2 J/cm2, 3 times) were implanted into rat wounds; group 5 (CLP) in which the PBM preconditioned ad-ADS were implanted into rat wounds, which were then exposed to PBM. On both days, significantly better histological results were seen in all experimental groups except control. Significantly better histological results were observed in the ad-ADS plus PBM treatment correlated to the ad-ADS alone group (p<0.05). Overall, PBM preconditioned ad-ADS followed by PBM of the wound showed the most significant improvement in histological measures correlated to the other experimental groups (p<0.05). On days 4 and 8, IL-1 ß levels of all experimental groups were lower than the control group; however, on day 8, only the CLP group was different (p<0.01). On day 4, miR-146a expression levels were substantially greater in the CLP and CELL groups correlated to the other groups, on day 8 miR-146a in all treatment groups was upper than C (p<0.01). ad-ADS plus PBM, ad-ADS, and PBM all improved the inflammatory phase of wound healing in an IIDHWM in TIDM1 rats by reducing inflammatory cells (neutrophils, macrophages) and IL-1ß, and increasing miRNA-146a. The ad-ADS+PBM combination was better than either ad-ADS or PBM alone, because of the higher proliferative and anti-inflammatory effects of the PBM+ad-ADS regimen.

Effects of Sambucus ebulus Extract on Cell Proliferation and Viability of Triple- Negative Breast Cancer: An In Vitro and In Vivo Study.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer (BC) cases and is a severe type of BC. Since medicinal herbs containing biocompatible substances that are accepted by patient more than chemical therapeutics, they can be considered a safe option for treating BC. OBJECTIVE: This study evaluated the effect of Sambucus Ebulus (S. ebulus) extract on a model of TNBC. METHODS: S. ebulus extract was prepared using petroleum ether, ethyl acetate, and methanol. The petroleum ether extract was fractionated and analyzed using vacuum liquid chromatography and GC-MS, respectively. MDAMB- 231 and MCF-10A were used as TNBC and normal breast cells, respectively. Flowcytometry and MTT assays were performed to evaluate cell cycle, apoptosis, and viability of the cells. Gene expression analysis was performed using RT-qPCR. Nude mouse allograft tumor models were used, and pathological sections were evaluated. RESULTS: The findings indicated that S. ebulus extract remarkably decreased cell proliferation and viability. The extract had no toxicity to the normal breast cells but efficiently killed the cancer cells. Cell cycle- and apoptosisrelated gene expression showed that fraction 4 of S. ebulus extract significantly increased the expression of Bax, Bak, P53, and c-MYC. CONCLUSION: This study showed satisfactory results of the effect of S. ebulus extract on clearing BC cells both in vitro and in vivo. Thus, S. ebulus extract may be a safe herbal compound for eliminating BC cells without toxicity to host cells.