Various source-derived mesenchymal stem cells (MSCs) with multipotent capabilities were considered for cell therapeutics of incurable diseases. The applicability of MSCs depends on the cellular source and on their different in vivo functions, despite having similar phenotypic and cytological characteristics. We characterized MSCs from different sources, including human bone marrow (BM), placenta (PL), and adipose tissue (AT), in terms of the phenotype, surface antigen expression, differentiation ability, proteome reference map, and blood flow recovery in a hindlimb ischemic disease model. The MSCs exhibit different differentiation potentials depending on the cellular source despite having similar phenotypic and surface antigen expression. We identified approximately 90 differentially regulated proteins. Most up- or down-regulated proteins show cytoskeletal or oxidative stress, peroxiredoxin, and apoptosis roles according to their functional involvement. In addition, the PL-MSCs retained a higher therapeutic efficacy than the BM- and AT-MSCs in the hindlimb ischemic disease model. In summary, we examined differentially expressed key regulatory factors for MSCs that were obtained from several cellular sources and demonstrated their differentially expressed proteome profiles. Our results indicate that primitive PL-MSCs have biological advantages relative to those from other sources, making PL-MSCs a useful model for clinical applications of cell therapy.

Previously, we identified annexin A4 (ANXA4) as a candidate substrate of caspase-3. Proteomic studies were performed to identify interacting proteins with a view to determining the roles of ANXA4. ANXA4 was found to interact with the p105. Subsequent studies revealed that ANXA4 interacts with NF-kappaB through the Rel homology domain of p50. Furthermore, the interaction is markedly increased by elevated Ca(2+) levels. NF-kappaB transcriptional activity assays demonstrated that ANXA4 suppresses NF-kappaB transcriptional activity in the resting state. Following treatment with TNF-alpha or PMA, ANXA4 also suppressed NF-kappaB transcriptional activity, which was upregulated significantly early after etoposide treatment. This difference may be due to the intracellular Ca(2+) level. Additionally, ANXA4 translocates to the nucleus together with p50, and imparts greater resistance to apoptotic stimulation by etoposide. Our results collectively indicate that ANXA4 differentially modulates the NF-kappaB signaling pathway, depending on its interactions with p50 and the intracellular Ca(2+) ion level.

Tongue diagnosis is an essential process to noninvasively assess the condition of a patient's internal organs in traditional medicine. To obtain quantitative and objective diagnostic results, image acquisition and analysis devices called tongue diagnosis systems (TDSs) are required. These systems consist of hardware including cameras, light sources, and a ColorChecker, and software for color correction, segmentation of tongue region, and tongue classification. To improve the performance of TDSs, various types TDSs have been developed. Hyperspectral imaging TDSs have been suggested to acquire more information than a two-dimensional (2D) image with visible light waves, as it allows collection of data from multiple bands. Three-dimensional (3D) imaging TDSs have been suggested to provide 3D geometry. In the near future, mobile devices like the smart phone will offer applications for assessment of health condition using tongue images. Various technologies for the TDS have respective unique advantages and specificities according to the application and diagnostic environment, but this variation may cause inconsistent diagnoses in practical clinical applications. In this manuscript, we reviewed the current trends in TDSs for the standardization of systems. In conclusion, the standardization of TDSs can supply the general public and oriental medical doctors with convenient, prompt, and accurate information with diagnostic results for assessing the health condition.

Among brain tumors, glioblastoma (GBM) is the most aggressive type and is associated with the lowest patient survival rate. Numerous lines of evidence have established that omega-3-polyunsaturated fatty acids (ω3-PUFAs) have potential for the prevention and therapy of several types of cancers. Docosahexaenoic acid (DHA), an ω3-PUFA, was reported to inhibit growth and induce apoptotic and autophagic cell death in several cancer cell lines; however, its effects on GBM cells are still unknown. in the present study, we examined the cytotoxic effect of DHA on the GBM cell lines, D54MG, U87MG, U251MG and GL261. Treatment of GBM cells with DHA induced PARP cleavage, increased the population of sub-G1 cells, and increased the number of TUNEL-positive cells, which are all indicative of apoptosis. Furthermore, treatment of GBM cells with DHA resulted in a significant increase in autophagic activity, as revealed by increased LC3-II levels, GFP-LC3 puncta, and autophagic flux activation, accompanied by activation of 5'-AMP-activated protein kinase (AMPK) and decreases in phosphorylated Akt (p-AktSer473) levels and mTOR activity. In vivo, endogenous expression of Caenorhabditis elegans ω3-desaturase, which converts ω6-PUFAs to ω3-PUFAs, in fat-1 transgenic mice yielded a significant decrease in tumor volume following subcutaneous injection of mouse glioma cells (GL261), when compared with wild-type mice. TUNEL-positive cell numbers and LC3-II levels were elevated in tumor tissue from the fat-1 transgenic mice compared with tumor tissue from the wild-type mice. In addition, p-Akt levels were decreased and p-AMPK levels were increased in tumor tissue from the fat-1 transgenic mice. These results indicate that ω3-PUFAs induce cell death through apoptosis and autophagy in GBM cells; thus, it may be possible to use ω3-PUFAs as chemopreventive and therapeutic agents for GBM.

An accurate assessment of the pulse depth in pulse diagnosis is vital to determine the floating and sunken pulse qualities (PQs), which are two of the four most basic PQs. In this work, we proposed a novel model of assessing the pulse depth based on sensor displacement (SD) normal to the skin surface and compared this model with two previous models which assessed the pulse depth using contact pressure (CP). In contrast to conventional stepwise CP variation tonometry, we applied a continuously evolving tonometric mechanism at a constant velocity and defined the pulse depth index as the optimal SD where the largest pulse amplitude was observed. By calculating the pulse depth index for 18 volunteers, we showed that the pulse was deepest at Cheok (significance level: P < 0.01), while no significant difference was found between Chon and Gwan. In contrast, the two CP-based models estimated that the pulse was shallowest at Gwan (P < 0.05). For the repeated measures, the new SD-based model showed a smaller coefficient of variation (CV ≈ 7.6%) than the two CP-based models (CV ≈ 13.5% and 12.3%, resp.). The SD-based pulse depth assessment is not sensitive to the complex geometry around the palpation locations and temperature variation of contact sensors, which allows cost-effective sensor technology.

Honokiol (HK), a novel plant-derived natural product, is a physiologically activated compound with polyphenolic structure, and has been identified to function as an anticancer agent. It has been widely used in several diseases as a traditional medicine for a long time. We investigated whether HK could show anticancer effects on two oral squamous cell lines (OSCCs), HN-22 and HSC-4. We demonstrated that HK-treated cells showed dramatic reduction in cell growth and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly inhibited by HK in a dose-dependent manner. Furthermore, we checked changes in cell cycle regulatory proteins and anti-apoptotic proteins at the molecular level, which are known as Sp1 target genes. The important key regulators in the cell cycle such as p27 and p21 were up-regulated by HK-mediated down-regulation of Sp1, whereas anti-apoptotic proteins including Mcl-1 and survivin were decreased, resulting in caspase-dependent apoptosis. Taken together, results from this study suggest that HK could modulate Sp1 transactivation and induce apoptotic cell death through the regulation of cell cycle and suppression of anti‑apoptotic proteins. In addition, HK may be used in cancer prevention and therapies to improve the clinical outcome as an anticancer drug.

DNA double-strand breaks (DSBs) can cause either cell death or genomic instability. The Ku heterodimer Ku70/80 is required for the NHEJ (non-homologous end-joining) DNA DSB repair pathway. The INHAT (inhibitor of histone acetyltransferases) complex subunit, SET/TAF-Iβ, can inhibit p300- and PCAF-mediated acetylation of both histone and p53, thereby repressing general transcription and that of p53 target genes. Here, we show that SET/TAF-Iβ interacts with Ku70/80, and that this interaction inhibits CBP- and PCAF-mediated Ku70 acetylation in an INHAT domain-dependent manner. Notably, DNA damage by UV disrupted the interaction between SET/TAF-Iβ and Ku70. Furthermore, we demonstrate that overexpressed SET/TAF-Iβ inhibits recruitment of Ku70/80 to DNA damage sites. We propose that dysregulation of SET/TAF-Iβ expression prevents repair of damaged DNA and also contributes to cellular proliferation. All together, our findings indicate that SET/TAF-Iβ interacts with Ku70/80 in the nucleus and inhibits Ku70 acetylation. Upon DNA damage, SET/TAF-Iβ dissociates from the Ku complex and releases Ku70/Ku80, which are then recruited to DNA DSB sites via the NHEJ DNA repair pathway.

Background:Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells.Methods:We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4′,6-diamidino-2-phenylindole staining and Western blotting.Results:Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells.Conclusions:Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti-proliferative agent that induces apoptotic cell death in G361 HMM cells.