Excessive Oxidative Stress in the Synergistic Effects of Shikonin on the Hyperthermia-Induced Apoptosis.

BACKGROUND: Hyperthermia (HT) has been used widely for cancer therapy, and the development of modern devices has made it more efficient. Shikonin (SHK) is a natural naphthoquinone derivative from a Chinese herb. Although the anticancer properties of SHK are evident, the underlying molecular mechanisms are not fully understood. OBJECTIVE: In this study, the effects of combining low doses of SHK with mild HT were investigated in the U937 cell line. METHODS: The cells were subjected to HT at 44°C for 10 min with or without SHK pretreatment, and parameters reflecting apoptosis, ROS generation and intracellular calcium elevation were evaluated by using DNA fragmentation, flow cytometry, and western blot analyses. RESULTS: SHK 0.5 µM significantly enhanced HT-induced apoptosis as indicated by DNA fragmentation and caspase-3 activation with increased generation of ROS and elevation of intracellular calcium. The combined treatment also synergistically activated proapoptotic proteins and inactivated anti-apoptotic proteins. Furthermore, the phosphorylation of JNK and PKC- δ and the dephosphorylation of ERK and AKT were the upstream effects that may have compounded the induction of apoptosis. The modulatory effects of HT and SHK were abrogated with the employment of NAC and JNK-IN-8 by inactivating the MAPK pathway and cleavage of caspase-3. Intracellular calcium was also elevated and was found to be responsible for the induction of cell death evident by the DNA fragmentation with or without the employment of BAPTA-AM. CONCLUSION: Conclusively, this study provides persuasive evidence that SHK in combination with HT is a propitious therapeutic way for augmentation of apoptosis and hence suggest a novel strategy for treating cancers.

[Changes of brain pain center and default mode network an electro acupuncture in Weizhong and Dachangshu acupoints: a task-fMRI study].

OBJECTIVE: To investigate the functional brain pain center and default mode network response to electro acupuncture stimulate in weizhong acupoints(BL40) and dachangshu acupoints(BL25). METHODS: During January to February 2015, volunteers were enrolled in this study from the staff and student interns of Gansu Province Traditional Chinese Medicine Hospital. A total of 20 healthy, right-handed subjects, male 9, female 11, age (23±3) years, participated in this study. Block design task functional magnetic resonance imaging(fMRI) 3.0 T was performed in all subjects by electro acupuncture stimulating at BL40 and BL25 from the same experienced acupuncturist.The needle connected electric acupuncture apparatus through tow long coaxial-cable. A block design with five 120 s blocks of rest time (OFF block, electric acupuncture turn off ) interspersed between five 60 s blocks of stimulation (ON block, electric acupuncture turn on) fMRI scan. Magnetic resonance data of brain function was collected and FSL(fMRI Software Library) software was used to analyze the data. RESULTS: All subjects' data were analyzed except 2 cases whose head movement were more than 2 mm. Activated brain function regions by electro acupuncture stimulate included temporal lobe lateral sulcus, lobus insularis, thalamus, supramarginal gyrus, prefrontal medial frontal gyrus. Negative activated brain regions included middle frontal gyrus, parahippocampal gyrus, cingulate cortex abdominal segment, parietal cortex.The functional pain central and default mode network were changed when electro acupuncture stimulate in(BL40) and(BL25). CONCLUSION: There are several brain activation regions and negative activated brain regions when administering electro acupuncture stimulation at BL40 and BL25.

[Effect of sodium ferulate on leucocyte spontaneous activation and surface adhesion molecule expression in arteriosclerosis obliterans patients].

OBJECTIVE: To explore the effect of sodium ferulate (SF) on leucocyte spontaneous activation rate (LSAR) and the surface expression of adhesion molecule (SEAM) in patients with arteriosclerosis obliterans (ASO). METHODS: Forty-two patients with ASO were treated by SF, LSAR and SEAM in them were determined qualitatively before and after SF treatment, as well as in 36 healthy subjects for control. RESULTS: Therapeutic effect of SF in the treated 42 patients was short-term cured in 17 cases (40.5%), markedly effective in 21 (50%), effective in 2 (4.8%), ineffective in 2(4.8%), and the total effective rate being 95.2%. LSAR and SEAM in ASO patients before treatment was 14.84 +/- 7.54% and 47.94 +/- 13.48% respectively, which was obviously higher than 4.96 +/- 2.04% and 24.12 +/- 9.35% in healthy subjects (P < 0.01) respectively, but markedly reduced to 8.19 +/- 4.09% and 28.63 +/- 7.91% after SF treatment (P < 0.01). CONCLUSION: SF could not only obviously lower both LSAR and SEAM but also exert a good therapeutic effect on patients with ASO.