Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Critical role of heme oxygenase-1 in chaetoglobosin A by triggering reactive oxygen species mediated mitochondrial apoptosis in colorectal cancer.

The incidence rate of colorectal cancer (CRC) has been increasing and poses severe threats to human health worldwide and developing effective treatment strategies remains an urgent task. In this study, Chaetoglobosin A (ChA), an endophytic fungal metabolite from the medicinal herb-derived fungus Chaetomium globosum Km1126, was identified as a potent and selective antitumor agent in human CRC. ChA induced growth inhibition of CRC cells in a concentration-dependent manner but did not impair the viability of normal colon cells. ChA triggered mitochondrial intrinsic and caspase-dependent apoptotic cell death. In addition, apoptosis antibody array analysis revealed that expression of Heme oxygenase-1 (HO-1) was significantly increased by ChA. Inhibition of HO-1 increased the sensitivity of CRC cells to ChA, suggesting HO-1 may play a protective role in ChA-mediated cell death. ChA induced cell apoptosis via the induction of reactive oxygen species (ROS) and ROS scavenger (NAC) prevented ChA-induced cell death, mitochondrial dysfunction, and HO-1 activation. ChA promoted the activation of c-Jun N-terminal kinase (JNK), and co-administration of JNK inhibitor or siRNA markedly reversed ChA-mediated apoptosis. ChA significantly decreased the tumor growth without eliciting any organ toxicity or affecting the body weight of the CRC xenograft mice. This is the first study to demonstrate that ChA exhibits promising anti-cancer properties against human CRC both in vitro and in vivo. ChA is a potential therapeutic agent worthy of further development in clinical trials for cancer treatment.

Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human HCC cells. In this study, we found that cryptocaryone potently induced growth inhibition by apoptotic cell death in HCC cells. Cryptocaryone also suppressed the ATP synthesis, lactate production and glycolytic capacity of HCC cells. Mechanistic investigations showed that phosphorylation of Akt and c-Src, as well as the expression of HK1 were impeded by cryptocaryone. Moreover, cryptocaryone markedly increased the expression level of transcription factor FoxO1. Importantly, clinical database analysis confirmed the negative correlation between HK1 and FoxO1. High expression levels of HK-1 were positively correlated with poorer survival in patients with HCCs. These results suggest that cryptocaryone may promote cell apoptosis by inhibiting FoxO1-mediated aerobic glycolysis through Akt and c-Src signaling cascades in human HCC cells. This is the first study to indicate that cryptocaryone exerts anti-cancer property against human HCC cells. Cryptocaryone is a potential natural product worthy of further development into a promising candidate for HCC treatment.

Dynamic analysis of lathe bed of woodworking CNC machining center based on the modeling of joint surface.

Based on the finite element theory, a joint-plane modeling method is employed to connect the corresponding nodes at the joint surface of the woodworking computer numerical control (CNC) machining center bed with a 2-node 12-degree-of-freedom unit. A spatial element model is established, which can show the state of the nodes between joint surfaces when they are stretched, compressed, or twisted; and it can help build a woodworking CNC machining center on a finite element model of bed with the characteristics of the joint surface. The simulated analysis is performed on the model and is compared with the result of simulated analysis on the bed model that ignores the characteristics of the joint surface and modal experiment. The comparison verifies the effectiveness of the modeling method based on the characteristics of the joint surface. The weak link of the machine bed structure is analyzed and optimized. The natural frequency of the bed is improved by2.55% ~ 11.3%. The displacement is reduced by a maximum of 19.4%, and dynamic performance of the bed is improved.

[Antipyretic effect of active components of Mahuang Decoction and its correlation with pharmacokinetics in febrile rats].

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1ß and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.

The efficacy and safety of a Chinese herbal product (Xiao-Feng-San) for the treatment of refractory atopic dermatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Severe and widespread atopic dermatitis often fails to respond adequately to topical steroids and oral antihistamines and requires immunomodulatory drugs which, although effective, have undesirable toxic effects. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, 71 patients with severe intractable atopic dermatitis were given an 8-week treatment with oral Xiao-Feng-San (XFS; 47 patients) or placebo (24 patients). Total lesion score, erythema score, surface damage score, pruritus score and sleep score were measured at 4-week intervals. RESULTS: Fifty-six patients completed both the treatment and follow-up periods. The decrease in the total lesion score in the treatment group at 8 weeks was significantly greater than that of the placebo group (79.7 ± 5.8% vs. 13.5 ± 7.64%; p < 0.001). There was also a statistically significant difference between the treatment and placebo groups with regard to erythema, surface damage, pruritus and sleep scores. The difference between the 2 groups was still significant for all outcome measures except the erythema score at the 12-week follow-up, 4 weeks after the 8-week treatment had ended. Patients reported no side effects from treatment, although some commented on the unpalatability of the medication. CONCLUSION: Our study results suggest that the traditional Chinese herbal medicine XFS may be an alternative choice of therapy for severe, refractory, extensive and nonexudative atopic dermatitis.

Stereoselective synthesis of desloratadine derivatives as antagonist of histamine.

A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H(1) antihistamine activity. For the evaluation of H(1) antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7, 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with gamma-alkylidene butenolide. Their H(1) antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7, 8a and 8g display potent activity inhibiting histamine-induced effects.

Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells.

The cytotoxicity of berberine on C6 rat glioma cells indicated that berberine induced morphological changes and caused cell death through G2/M arrest and apoptosis. While undergoing apoptosis, there was a remarkable accumulation of G2/M cells with the upregulatoin of Wee1 but it also inhibited cyclin B, CDK1 and Cdc25c that led to G2/M arrest. Along with cytotoxicity in C6 cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3 and -8 and DNA fragmentation were induced. Berberine increased the levels of GADD153 and GRP 78 in C6 cells based on the examination of Western blotting and this is a major hallmark of endoplasmic reticulum (ER) stress. We also found that berberine promoted the production of reactive oxygen species and Ca2+ in C6 cells. Western blotting assay also showed that berberine inhibited the levels of anti-apoptotic protein Bcl-2 but increased the levels of pro-apoptotic protein Bax before leading to a decrease in the levels of mitochondrial membrane potential (DeltaPsim) followed by cytochrome c release that caused the activations of capase-9 and -3 for apoptotic occurrence. The caspase-8, -9 and -3 were activated by berberine in C6 cells based on the substrate solution (PhiPhiLux-G1D1, CaspaLux 8-L1D2, CaspaLux 9-M1D2 for caspase-3, -8 and -9, respectively) and analyzed by flow cytometer and each inhibitor of caspase-8, -9 and -3 led to increase the percentage of viable C6 cells after exposure to berberine. This finding was also confirmed by Western blot assay which showed that berberine promoted the active form of caspase-8, -9 and -3. These results demonstrate that the cytotoxicity of berberine in C6 rat glioma cells is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2.

The roles of endoplasmic reticulum stress and Ca2+ on rhein-induced apoptosis in A-549 human lung cancer cells.

Although rhein has been shown to induce apoptosis in several cancer cell lines, the mechanism of action of rhein-induced cell cycle arrest and apoptosis at the molecular level is not well known. In this study, the mechanism of rhein action on A-549 human lung cancer cells was investigated. Rhein induced G0/G1 arrest through inhibition of cyclin D3, Cdk4 and Cdk6. The efficacious induction of apoptosis was observed at 50 microM for 12 h and up to 72 h as examined by a flow cytometric method. Flow cytometric analysis demonstrated that rhein increased the levels of GADD153 and GRP78, both hallmarks of endoplasmic reticulum stress, promoted ROS and Ca2+ production, induced the loss of mitochondrial membrane potential (delta psi(m)), promoted cytochrome c release from mitochondria, promoted capase-3 activation and led to apoptosis. Rhein also increased the levels of p53, p21 and Bax but reduced the level of Bcl-2. The Ca2+ chelator BAPTA was added to the cells before rhein treatment, thus blocking the Ca2+ production and inhibiting rhein-induced apoptosis in A-549 cells. Our data demonstrate that rhein induces apoptosis in A-549 cells via a Ca2+ -dependent mitochondrial pathway.

Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways.

Emodin was isolated from Rheum palmatum L. and exhibits an anticancer effect on human cancer cell lines, however, the molecular mechanisms of emodin-mediated apoptosis in human tongue cancer cells have not been fully investigated. In this study, treatment of human tongue cancer SCC-4 cells with various concentrations of emodin led to G2/M arrest through promoted p21 and Chk2 expression but inhibited cyclin B1 and cdc2; it also induced apoptosis through the pronounced release of cytochrome c from mitochondria and activations of caspase-9 and caspase-3. These events were accompanied by the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (delta psi(m)) and a decrease in the ratio of mitochondrial Bcl-2 and Bax content; emodin also promoted the levels of GADD153 and GRP78. The free radical scavenger N-acetylcysteine and caspase inhibitors markedly blocked emodin-induced apoptosis. Taken together, these findings suggest that emodin mediated oxidative injury (DNA damage) based on ROS production and ER stress based on the levels of GADD153 and GRP78 that acts as an early and upstream change in the cell death cascade to caspase- and mitochondria-dependent signaling pathways, triggers mitochondrial dysfunction from Bcl-2 and Bax modulation, mitochondrial cytochrome c release and caspase activation, consequently leading to apoptosis in SCC-4 cells.

Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways.

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.

Inhibition of lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production by menthone through nuclear factor-kappaB signaling pathway in HaCat cells.

Menthone, the Chinese old remedy extracted from genus Mentha, has been widely used as a cooling agent, a counterirritant for pain relief, and for the treatment of pruritus. However, its detail mechanisms for interfering inflammatory reaction remain unknown. In this study, we found that menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as nuclear factor kappaB (NF-kappaB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide. Furthermore, our data also demonstrated that the translocation of NF-kappaB activated by LPS into the nucleus was suppressed by menthone, and I-kappaB and beta-transducin repeat containing protein (beta-TrCP) were both involved in this suppression. To sum up, this study has provided molecular evidence for menthone effect on the LPS-induced cytokine production, NF-kappaB activation, and the involvement of I-kappaB and beta-TrCP.

Growth inhibition and apoptosis induction by tanshinone I in human colon cancer Colo 205 cells.

Tanshinone I (Tan-I) and tanshinone IIA (Tan-IIA) were isolated from Danshen (Salviae Miltiorrhizae Radix), a widely prescribed traditional herbal medicine that is used to treat cardiovascular and dysmenorrhea diseases. In our previous study, Tan-IIA was demonstrated to induce apoptosis in human colon cancer Colo 205 cells. However, the effect of Tan-I on human colon cancer cells is not clearly understood yet. In this study, the anti-growth and apoptosis-eliciting effects of Tan-I, as well as its cellular mechanisms of actions, were investigated in Colo 205 human colon cancer cells. Tan-I reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and in cells in the sub-G1 fraction. The expression of p53, p21, bax and caspase-3 increased in Tan-I-treated cells. In addition, the cell cycle analysis showed G0/G1 arrest. These findings suggest that Tan-I induces apoptosis in Colo 205 cells through both mitochondrial-mediated intrinsic cell-death pathways and p21-mediated G0/G1cell cycle arrest. Accordingly, the therapeutic potential of Tan-I for colon cancer deserves further study.

Growth inhibition and apoptosis induction by tanshinone IIA in human colon adenocarcinoma cells.

Tanshinone IIA is the most abundant diterpene quinone in Danshen, Salviae miltiorrhizae Radix, a widely prescribed traditional herbal medicine that is used to treat cardiovascular and inflammatory diseases. Recently, tanshinone IIA was demonstrated to induce cell death and apoptosis in a variety of tumors. However, the effect of tanshinone IIA on human colon cancer cells is not clearly understood yet. In this study, the antigrowth and apoptosis-eliciting effects of tanshinone IIA, as well as its cellular mechanisms of actions, were investigated in Colo-205 human colon cancer cells. Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction. The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA. Tanshinone IIA-induced catalytic activation of caspases was confirmed by cleavage of caspase-8 and caspase-3. These findings suggest that tanshinone IIA induces apoptosis in Colo-205 cells through both mitochondrial-mediated intrinsic and Fas-mediated extrinsic caspase cell-death pathways. Accordingly, the chemotherapeutic potential of tanshinone IIA for colon cancer warrants further study.

Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205).

The effects of the crude extract of Solanum lyratum (SLE) on human colon cancer colo 205 cells were investigated. The cell viability, morphological changes of the cells, cell cycle arrest, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (deltapsi(m)) and cell cycle- and apoptosis-associated protein levels and gene expressions were examined in colo 205 cells after exposure to various concentrations of SLE for different time periods. The results indicated that SLE decreased the percentage of viable colo 205 cells accompanied by morphological changes. The most effective concentration of SLE was 300 pg/ml (SLE 300) and this concentration was used for further investigations. SLE induced S-phase arrest and apoptosis (sub-G1) in the colo 205 cells and those effects were dose- and time-dependent. DAPI staining and DNA gel electrophoresis confirmed that SLE induced apoptosis in colo 205 cells. Flow cytometric analysis also showed that SLE 300 promoted ROS production and decreased the deltapsi(m). Western blotting analysis indicated that SLE 300 increased Bax levels and decreased Bcl-2 levels, which caused the loss of deltapsi(m) followed by cytochrome c release and caspase-9 and -3 activation, finally leading to apoptosis. SLE 300 also promoted p53 and p27, but decreased the levels of cyclin B1 thus causing S-phase arrest. The gene expression associated with those proteins was also confirmed by PCR methods. The findings show that SLE might be used as a colon cancer therapeutic agent in the future.

Gypenosides induced G0/G1 arrest via inhibition of cyclin E and induction of apoptosis via activation of caspases-3 and -9 in human lung cancer A-549 cells.

Gynostemma pentaphyllum Makino is known in Asia for its effect on the treatment of hepatitis and cardiovascular diseases. Gypenosides (Gyp) are the major components extracted from Gynostemma pentaphyllum Makino. However, the molecular mechanism underlying the Gyp-induced cell cycle arrest and apoptotic process is unclear. In this study, the chemopreventive role of Gyp in human lung cancer (A549) cells in vitro was evaluated by studying the regulation of the cell cycle and apoptosis. Gyp induced GO/G1 arrest and apoptosis in the human lung cancer A549 cells. Investigation of the cyclin-dependent protein kinase inhibitors by Western blotting showed that p16, p21, p27 and p53 proteins were increased with the increasing time of incubation with Gyp in the A549 cells. This increase may be the major factor by which Gyp caused GO/G1 arrest in the examined cells. Flow cytometric assay and gel electrophoresis of DNA fragmentation also confirmed that Gyp induced apoptosis in the A549 cells. Our data demonstrated that Gyp-induced apoptotic cell death was accompanied by up-regulation of Bax, caspase-3 and caspase-9, but down-regulation of the Bcl-2 levels. Taken together, Gyp appears to exert its anticancer properties by inducing GO/GI-phase arrest and apoptosis via activation of caspase-3 in human lung A549 cancer cells.

The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells.

Our previous studies have shown that bee venom (BV) can induce apoptosis in human cervical cancer Ca Ski cells, but it can also affect human breast cancer cells, though its molecular mechanisms are not precisely known. In this study, the molecular mechanisms of apoptosis induced by BV in human breast cancer MCF7 cells were investigated. BV induced morphological changes (examined by phase-contrast microscopy) and inhibited the proliferation (examined by MTT assay) of MCF7 cells; both effects occurred in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species (ROS) and dysfunction of the mitochondrial membrane potential (Azm), and led to cytochrome c release, an increase in the levels of caspase-9 and Poly (ADP-ribose) polymerase (PARP) and then apoptosis. It also showed that BV induced S-phase arrest in MCF7 cells which may occur through the promotion of p53, p21, p27 and the exhibition of Cdk2. Western blotting demonstrated that BV reduced Bcl-2 and increased Bax protein levels which may have caused the changes of delta psi m. BV treatment led to ROS production up to but after treatment led to a decrease in the levels of ROS, which may be associated with the observations of BVaffecting glutathion S-transferase (GST), Zn-superoxide dismutase (Zn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase. The Comet assay also showed that BV induced DNA damage while DAPI staining also confirmed that BV induced apoptosis in examined MCF7 cells. Our results also showed that BV increased the levels of AIF and EndoG in MCF7 cells. In conclusion, our data demonstrated that BV induced apoptosis via a mitochondria-dependent pathway based on the changes of delta psi m, AIF and EndoG release in MCF7 cells.

Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro.

Berberine, a yellow benzylisoquinoline alkaloid, is a constituent of Coptis chines and is commonly used in Chinese herbal medicine for patients with gastrointestinal disorders. The pharmacological effects of berberine include anti-inflammation, antidiarrhetic, antimalarial, and even antimicrobial activities. However, its mechanism of action on the cell migration of human gastric cancer SNU-5 cells is not fully understood. The effects of berberine on the percentage of viable cells were examined first and it was found that berberine induced dose-dependent inhibition in human gastric cancer SNU-5 cells. The effect of berberine on the levels of reactive oxygen species (ROS) and matrix metalloproteinase-1, -2, -7 and -9 was then examined using Western blotting and the results showed that berberine induced ROS production for up to 6 hours of incubation. It was also found that berberine induced downregulation of MMP-1 -2, and -9 but did not affect the level of MMP-7. The mRNA levels of MMPs in SNU-5 cells after treatment with berberine for 24 hours were investigated using a polymerase chain reaction and the results showed that berberine inhibited the gene expression of MMP-1, -2 and -9 in human SNU-5 cells but it did not affect MMP-7. In conclusion, berberine appears to exert its anticancer properties by inducing ROS production and prevention of cell migration via inhibition of the gene expression of MMP-1, -2 and -9 in human gastric cancer SNU-5 cancer cells.

[Development of traditional Chinese medicine in Taiwan before 1960s].

It is important for people to view the early development of traditional Chinese medicine in Taiwan from a historical perspective as the World Health Organization (WHO) has already confirmed that traditional Chinese medicine is a great contribution to human civilization. In this article, we will introduce the early development of traditional Chinese medicine in Taiwan chronologically.

Differential gene expression in hemodialysis patients with "cold" zheng.

The aim of the present study was to search for the differential gene expression and measure the serum level of a number of biochemical parameters in the cold zheng (CZ) and non-cold zheng (NCZ) in patients receiving hemodialysis. Hemodialysis (HD) patients were randomly selected from the CZ and NCZ groups. The between-group differences in gene expression were assessed using complementary DNA (cDNA) microarray. Differential gene expression was further validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Our results demonstrated that the up-regulation of the inflammation-associated genes, ALOX5AP, S100A8 and S100A12, down-regulation of the genes related to immunity (DEFA4), metabolism (GNG11, PYGB, PRKAR2B), and growth/proliferation (HSF2, DDR2, TK1) were found in the CZ group. Furthermore, the CZ HD patients had significantly lower serum albumin levels compared with their NCZ counterparts (3.31 +/- 0.08 g/dL versus 4.18 +/- 0.12 g/dL). It appears reasonable to conclude that up-regulated inflammatory-gene expression (ALOX5AP, S100A8 and S100A12) may play an important role in CZ HD patients.