Compound K (20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol) is an active metabolite of ginsenosides and induces apoptosis in various types of cancer cells. This study investigated the role of autophagy in compound K-induced cell death of human HCT-116 colon cancer cells. Compound K activated an autophagy pathway characterized by the accumulation of vesicles, the increased positive acridine orange-stained cells, the accumulation of LC3-II, and the elevation of autophagic flux. Whereas blockade of compound K-induced autophagy by 3-methyladenein and bafilomycin A1 significantly increased cell viability. In addition, compound K augmented the time-dependent expression of the autophagy-related proteins Atg5, Atg6, and Atg7. However, knockdown of Atg5, Atg6, and Atg7 markedly inhibited the detrimental impact of compound K on LC3-II accumulation and cell vitality. Compound K-provoked autophagy was also linked to the generation of intracellular reactive oxygen species (ROS); both of these processes were mitigated by the pre-treatment of cells with the antioxidant N-acetylcysteine. Moreover, compound K activated the c-Jun NH2-terminal kinase (JNK) signaling pathway, whereas downregulation of JNK by its specific inhibitor SP600125 or by small interfering RNA against JNK attenuated autophagy-mediated cell death in response to compound K. Compound K also provoked apoptosis, as evidenced by an increased number of apoptotic bodies and sub-G1 hypodiploid cells, enhanced activation of caspase-3 and caspase-9, and modulation of Bcl-2 and Bcl-2-associated X protein expression. Notably, compound K-stimulated autophagy as well as apoptosis was induced by disrupting the interaction between Atg6 and Bcl-2. Taken together, these results indicate that the induction of autophagy and apoptosis by compound K is mediated through ROS generation and JNK activation in human colon cancer cells.
Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson's disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD-like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration.
Although the T-helper type 9 (Th9) subset has recently been revisited, interleukin (IL)-9-producing invariant natural killer T (iNKT) cells remain poorly characterized. Moreover, whether IL-9-producing iNKT cells regulate colitis is unknown. Here, we investigated functions of IL-9-producing iNKT cells in dextran sulfate sodium (DSS)-induced colitis. Wild-type (WT) mice attenuated colitis compared to Jα18(-/-) mice, which were restored by the adoptive transfer of WT, but not IL-4-deficient iNKT cells. IL-4-deficient iNKT cells failed to produce IL-9, which was reversed by recombinant IL-4. Furthermore, iNKT cells, pre-incubated with anti-CD3+CD28 monoclonal antibodies and IL-4+tumor growth factor (TGF)-β (IL-9(+) iNKT), suppressed colitis in Jα18(-/-) mice, whereas pre-incubated IL-4-deficient iNKT cells did not. IL-9 blockade reversed IL-9(+) iNKT cell-mediated colitis by increasing colonic IL-17A and interferon (IFN)-γ transcripts, but decreasing IL-9, IL-10, TGF-β, PU.1, IFN regulatory factor 4, and signal transducer and activator of transcription 5 in Jα18(-/-) mice. In conclusion, IL-9-producing iNKT cells protect against DSS-induced colitis through IFN-γ and IL-17A suppression, but IL-10 and TGF-β enhancement, depending on the IL-4 production by iNKT cells.
The objective of this study was to determine if total laparoscopic hysterectomy using a uterine manipulator with an intrauterine balloon increases the risk of positive peritoneal washings in patients with endometrial cancer. Three sets of peritoneal washings were obtained during surgery from 46 women with endometrial cancer at the Center for Uterine Cancer, National Cancer Center, Korea, between May 2004 and July 2006: the first before the insertion of the uterine manipulator (premanipulator), the second after clipping the fallopian tubes and inserting the uterine manipulator (postmanipulator), and the third after the removal of the uterus through the vagina (posthysterectomy). The cytology samples were examined by the same cytopathologist for the presence of malignant cells. Two of 46 (4.3%) patients were upstaged to IIIA disease due to positive cytology conversion after the insertion of the uterine manipulator, one after the insertion of the uterine manipulator, and the other after the hysterectomy. However, during the follow-up for 3-28 months (median 18), neither of the 2 patients experienced a tumor recurrence. In conclusion, using a uterine manipulator with an intrauterine balloon during the laparoscopic surgery for endometrial cancer might be associated with positive cytologic conversion. Possible explanations are retrograde seeding of tumor cells into the peritoneal cavity, the pressure effect of the inflatable manipulator tip, and spillage of preexited tumor cells between the isthmus and the fimbriae. More effective preventive methods such as distal tubal clipping or coagulation of the fimbriae may be necessary in treating women with endometrial cancer.
As a smartphone is becoming very popular and its performance is being improved fast, a smartphone shows its potential as a low-cost physiological measurement solution which is accurate and can be used beyond the clinical environment. Because cardiac pulse leads the subtle color change of a skin, a pulsatile signal which can be described as photoplethysmographic (PPG) signal can be measured through recording facial video using a digital camera. In this paper, we explore the potential that the reliable heart rate can be measured remotely by the facial video recorded using smartphone camera. First, using the front facing-camera of a smartphone, facial video was recorded. We detected facial region on the image of each frame using face detection, and yielded the raw trace signal from the green channel of the image. To extract more accurate cardiac pulse signal, we applied independent component analysis (ICA) to the raw trace signal. The heart rate was extracted using frequency analysis of the raw trace signal and the analyzed signal from ICA. The accuracy of the estimated heart rate was evaluated by comparing with the heart rate from reference electrocardiogram (ECG) signal. Finally, we developed FaceBEAT, an iPhone application for remote heart rate measurement, based on this study.
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