Ching-Hsein Chen

The safety profile of ustekinumab in the treatment of patients with psoriasis and concurrent hepatitis B or C

Ustekinumab, an interleukin (IL)‐12 and IL‐23 blocker, has emerged as a new therapeutic option for patients with psoriasis. It is generally well tolerated but safety data on the use of ustekinumab in patients with viral hepatitis are limited.

Anticancer Activity of Isoobtusilactone A from Cinnamomum kotoense : Involvement of Apoptosis, Cell-Cycle Dysregulation, Mitochondria Regulation, and Reactive Oxygen Species

In this study, we investigate the anticancer effect of isoobtusilactone A (IOA), a constituent isolated from the leaves of Cinnamomum kotoense, on human non-small cell lung cancer (NSCLC) A549 cells. IOA was found to induce the arrest of G2-M phase, induce apoptosis, increase sub-G1, and inhibit the growth of these cells. Further investigation revealed that IOAs blockade of the cell cycle was associated with increased levels of p21/WAF1, p27 (kip1), and p53. In addition, IOA triggered the mitochondrial apoptotic pathway, as indicated by an increase in Bax/Bcl-2 ratios, resulting in a loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. We also found the generation of reactive oxygen species (ROS) to be a critical mediator in IOA-induced inhibition of A549 cell growth. In antioxidant and NO inhibitor studies, we found that by pretreating A549 cells with either N-acetylcystenine (NAC), catalase, mannitol, dexamethasone, trolox, or L-NAME we could significantly decrease IOA production of ROS. Moreover, using NAC to block ROS, we could significantly suppress IOA-induced antiproliferation, antimigration, and anti-invasion. Finally, we found that IOA inhibited the migration and invasion of A549 cell migration and invasion. Taken together, these results suggest that IOA has anticancer effects on A549 cells.

Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 Cells.

This study investigated the effect of baicalein, silymarin, and their combination, on two human liver-derived cell lines, HepG2 (hepatocellular carcinoma) and Chang liver (non-tumor liver cells). It was found that 6.75 microg/ml baicalein or 100 microg/ml silymarin alone significantly inhibited the growth of HepG2. When baicalein was used in combination with silymarin on HepG2, an additive effect at 24 h and a synergistic effect at 48 h were observed. The viability at 48 h was 85.62% from 6.75 microg/ml baicalein treatment; but the viability reduced to 49.67%, 38.56%, and 19.61% when 25, 50, and 100 microg/ml silymarin respectively, was added to the treatment. By contrast, each treatment had little or no effect on Chang liver. Compared to treatment of baicalein or silymarin alone on HepG2, combination of both drugs synergistically increased the percentages of cells in G0/G1 phase and decreased those in S-phase, which were associated with up-regulation of Rb, p53, p21(Cip1) and p27(Kip1) and down-regulation of cyclin D1, cyclin E, CDK4 and phospho-Rb. The results indicate that the combination of baicalein and silymarin eradicates tumor cells efficiently, has minimal deleterious effects to the surrounding normal cells, and offers mechanistic insight for further exploitation of HCC treatment.

Baicalein, a Novel Apoptotic Agent for Hepatoma Cell Lines:A Potential Medicine for Hepatoma

This study has demonstrated that baicalein has anticancer effectiveness against human hepatoma cells. The dose response of baicalein in Hep G2 and Hep J2 cells indicates that baicalein decreased viability >90%. In comparison, baicalein had only minimal effects on the viability of control Chang liver cells. Flow cytometric analysis showed that baicalein inhibited the cell cycle of Hep G2 cells in the S phase. In addition, baicalein treatment resulted in a decreased mitochondrial transmembrane potential and damaged the integrity of the cell membrane. The TdT-mediated dUTP-biotin nick end labeling assay results indicated that baicalein elicited a significant increase of DNA fragmentation in Hep G2 cells after incubation for 48 hours. These results indicate that baicalein is an effective antihepatoma agent with minimal influence on noncancer cells. The effects of baicalein on Hep G2 cells include inhibition of the S phase of the cell cycle, dysfunction of mitochondria, and initiation of apoptosis.

Mapping of psoriasis to 17q terminus

Psoriasis is a chronic, inflammatory, hyperproliferative disease of the skin, scalp, nails, and joints, with a prevalence of up to 2% in Caucasians1,2 but well under 1% in the Mongoloid races of the Far East.3 The disease varies in severity. Some patients display mild disease with isolated scaling erythematous plaques on the elbows or knees, whereas for others most of their cutaneous surface can be affected. At the cellular level, psoriasis is characterised by markedly increased epidermal proliferation and incomplete differentiation, elongation, dilation, and leakiness of the superficial plexus of dermal capillaries, and by a mixed inflammatory and immune cell infiltrate of the epidermis and papillary dermis.1,2 Dermal infiltrates comprised of T cells and macrophages typically appear in early lesions before epidermal changes.4 The therapeutic effect of immunosuppressive agents suggests psoriasis has a primary immune pathogenic basis.5 Susceptibility to the development of psoriasis is likely to have a significant genetic component. Accumulating evidence is consistent with the idea that psoriasis is a multifactorial disorder caused by the concerted action of multiple disease genes in a single individual and triggered by environmental factors.6 Some of these genes control the severity of a variety of diseases, via their regulation of the inflammatory and immune processes (severity genes), whereas others are unique to psoriasis (specific genes). A number of genetic studies have sought to identify the psoriasis susceptibility loci. Associations between psoriasis and human lymphocyte antigen alleles were first described in 1990.7 Subsequently, genome-wide linkage scans have mapped psoriasis to several chromosomal regions including PSORS1 at 6p21,8,9 PSORS2 at 17q,8–10 PSORS3 at 4q,11 PSORS4 at 1q,12 PSORS5 at 3q,13 PSORS6 at 19p,14 and PSORS7 at 1p.15 Recently, the International Psoriasis Genetics Consortium reassessed these candidate …

Application of Cesàro mean and the L-curve for the deconvolution problem

In this paper, the Cesaro mean technique is applied to regularize the divergent problem which occurs in ground motion deconvolution analysis in geotechnical engineering. To deal with this ill-posed problem, we use the corner of the L-curve as the compromise point to determine the optimal order of Cesaro mean so that the high frequency content can be suppressed instead of engineering judgement using the concept of a cutoff frequency. The fractional order of Cesaro mean has been derived and used to fulfill this purpose. From the examples shown, it is found that the wave form including maximum acceleration can be accurately predicted and that both the high frequency content and divergent results can be avoided by using the proposed regularization technique.

(−)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells.

(-)-Anonaine has been shown to have some anticancer activities, but the mechanisms of (-)-anonaine inducing cell death of human cancer cells is not fully understood. We investigated the mechanisms of apoptosis induced by (-)-anonaine in human HeLa cancer cells. Treatment with (-)-anonaine induces dose-dependent DNA damage that is correlated with increased intracellular nitric oxide, reactive oxygen species, glutathione depletion, disruptive mitochondrial transmembrane potential, activation of caspase 3, 7, 8, and 9, and poly ADP ribose polymerase cleavage. Our data indicate that (-)-anonaine up-regulated the expression of Bax and p53 proteins in HeLa cancer cells. The apoptosis and expression of Bax induced by (-)-anonaine could be inhibited when the HeLa cells were pretreated with Boc-Asp(OMe)-fmk, which is a broad caspases inhibitor. There was no obvious DNA damage in the (-)-anonaine-treated Madin-Darby canine kidney and Vero cell lines. Both Madin-Darby canine kidney and Vero cell lines are kidney epithelial cellular morphology. These results suggest that (-)-anonaine might be considered a potent compound for chemotherapy against cervical cancer or a health food supplement for cancer chemoprevention.

Novel multiple apoptotic mechanism of shikonin in human glioma cells.

BackgroundShikonin is the main naphthoquinone compound of the root of Lithospermum erythrorhizon. Our previous study demonstrated that shikonin possesses anticancer activity in human hepatoma cells. However, the anticancer mechanism of shikonin in human glioma cells is unclear at present. In the present study, we demonstrated that shikonin induces apoptosis in three human glioma cell lines: U87MG, Hs683, and M059K cells.MethodsCell cycle, generation of reactive oxygen species (ROS), depletion of glutathione (GSH), and disruption of mitochondrial transmembrane potential in shikonin-treated cells were determined by flow cytometry. Apoptosis-related proteins, catalase, and superoxide dismutase-1 (SOD-1) were determined by Western blot testing. N-acetylcysteine (NAC), pifithrin-α (PFT-α), or cyclosporin A were applied to evaluate the molecular mechanism of shikonin in apoptosis.ResultsShikonin induces the generation of ROS, depletion of GSH, disruption of mitochondrial transmembrane potential, upregulation of p53, and cleavage of PARP [poly(ADP-ribose) polymerase] in U87MG glioma cells. Moreover, shikonin causes catalase downregulation and SOD-1 upregulation as well as decreased Bcl-2 and increased Bax expression. Pretreatment with NAC, PFT-α, or cyclosporin A causes the recovery of shikonin-induced apoptosis. The ROS generation and GSH depletion induced by shikonin trigger mitochondrial transmembrane potential disruption. ROS production was partially dependent on the upregulation of p53 upon shikonin treatment.ConclusionsThese studies are the first to show that shikonin-induced apoptosis occurs through multiple pathways in human glioma cells. We conclude that shikonin may be used as a potential chemotherapeutic agent against human glioma.

[6]-gingerol induces Ca2+ mobilization in Madin-Darby canine kidney cells.

[6]-gingerol, a major phenolic compound derived from ginger (Zingiber officinale), is a potential chemopreventive compound that can induce stress in cancer cells and cause apoptotic cell death. This study examines the early signaling effects of [6]-gingerol on renal cells. It was found that [6]-gingerol caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [6]-gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 80%. Depletion of intracellular Ca2+ stores with CCCP, a mitochondrial uncoupler, did not affect the action of [6]-gingerol. In a Ca2+-free medium, the [6]-gingerol-induced [Ca2+]i rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). The elevation of [6]-gingerol-caused [Ca2+]i in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [6]-gingerol-induced Ca2+ influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not [6]-gingerol)-induced [Ca2+]i rise. These findings suggest that [6]-gingerol induces a significant rise in [Ca2+]i in MDCK renal tubular cells by stimulating both extracellular Ca2+ influx and thapsigargin-sensitive intracellular Ca2+ release via as yet unidentified mechanisms.

Para-phenylenediamine induced DNA damage and apoptosis through oxidative stress and enhanced caspase-8 and -9 activities in Mardin–Darby canine kidney cells

Para-phenylenediamine (p-PD), a suspected carcinogen, is a component of permanent hair dyes. In this study we examined the mechanism of cytotoxicity and genotoxicity in Mardin-Darby canine kidney cells (MDCK)-treated with p-PD. Our results showed that p-PD decreased cell viability in a dose- and time-dependent manner. In addition, p-PD induced DNA damage was confirmed by the comet and TUNEL assays. Pre-treatment of MDCK cells with antioxidants vitamin C or E significantly inhibited p-PD induced cytotoxicity and reactive oxygen species (ROS) generation. Furthermore, p-PD induced apoptosis through activated initiator caspase-8 and -9, and effector caspase-3/7. Based on these results, we suggested that p-PD induce apoptosis which was mediated with caspase-8, caspase-9 and caspase-3/7 activation via the involvement of ROS.