Anti-metastatic mechanism of Tian-Xian Liquid (TXL) and its bioactive fractions in human colorectal cancer cells and xenograft models

Poster Session A: abstract no. 29Colorectal carcinoma is the second most prevalent cancer with an up-rising trend in Hong Kong (Hong Kong Cancer Registry). Traditional Chinese medicine acts as a complementary alternative for tumour therapy with minimal side-effects and traumatic injuries. Tian-Xian Liquid (TXL), one of the well-known natural medicinal herbal formulations, has been commercially used as an anticancer dietary supplement for a decade without known adverse effects. This study aimed to investigate the anti-metastatic property of TXL and its bioactive fractions [butanol fraction (BU), ethyl-acetate fraction (EA) and aqueous fraction (WA)] at molecular level on human colorectal cancer in vitro (HT-29 cancer cells) and in vivo (nude mice xenografts). For the cell model, TXL and its bioactive fractions have similar anti-proliferative effects by MTT assay. At 4-hour-incubation, IC50 values were obtained at 1% (V/V) TXL, 1.25% (V/V) BU, 5% (V/V) EA and 0.3125% (V/V) WA. At IC50, TXL and its bioactive fractions significantly reduced the MMP2 and MMP7 expressions at mRNA level by real-time PCR. At protein level, TXL, BU and EA correspondingly down-regulated MMP2 (active form) and MMP7 protein from 24 to 48 hours; TXL and BU also down-regulated VEGF protein expression; however, no such effect was found in WA-treated cells. Further, only TXL, EA and WA effectively inhibited the cell migration at 48 hours incubation by woundhealing assay. For the xenografts models, MMP2 and MMP7 mRNA expressions were reduced by TXL-, BU- and EA-treated xenografts; however no effects on MMP2 protein expression in all drug-treated xenografts. The VEGF protein expression was significantly down-regulated in TXL- and WA-treated xenografts. Further, TXL, BU and WA effectively inhibited the tumor growth without altering the body weight of the xenografts. In summary, the Chinese medicinal formulation, TXL, demonstrated the most effective anti-metastatic ability on human colorectal cancer in vitro and in vivo.published_or_final_versio

Topological susceptibility in full QCD: lattice results versus the prediction from the QCD partition function with granularity

Recent lattice data from CP-PACS, UKQCD, SESAM/TXL and the Pisa group regarding the quark mass dependence of the topological susceptibility in 2-flavour QCD are compared to each other and to theoretical expectations. The latter get specified by referring to the QCD finite-volume partition function with ``granularity'' which accounts for the entropy brought by instantons and anti-instantons. The chiral condensate in $N_f=2$ QCD, if determined by this method, turns out surprisingly large.Comment: 24 pages, 9 figures containing 21 graphs; v2: modifications to account for the changes in the SESAM/TXL data, otherwise minor alterations, except for 4 new references added; to appear in Nucl. Phys.

Tian Xian Liquid (TXL) induces apoptosis in HT-29 colon cancer cell in vitro and inhibits tumor growth in vivo

<p>Abstract</p> <p>Background</p> <p>Tian Xian Liquid (TXL) is a Chinese medicine decoction and has been used as an anticancer dietary supplement. The present study aims to investigate the effects of TXL on the apoptosis of HT-29 cells and tumor growth <it>in vivo</it>.</p> <p>Method</p> <p>HT-29 colon cancer cells were treated with gradient dilution of TXL. The mitochondrial membrane potential was measured by JC-1 assay. The release of cytochrome c from mitochondrial and apoptosis-related proteins <it>Bax</it>, <it>Bcl-2</it>, cleaved caspase-3, 9 were examined by Western blot analysis. HT-29 cells were implanted in nude mice to examine the effects of TXL on tumor growth.</p> <p>Result</p> <p>TXL inhibited HT-29 xenografted model and showed a strong and dose-dependent inhibitory effect on the proliferation of HT-29 cells. Mitochondrial membrane potential was reduced by TXL at the concentration of 0.5% above. For Western blot analysis, an increase in <it>Bax </it>expression and a decrease in <it>Bcl-2 </it>expression were observed in TXL-treated cells. TXL treatment increased the protein level of cleaved casepase-3 and caspase-9, and the release of cytochrome c in cytoplasm was up-regulated as well.</p> <p>Conclusion</p> <p>TXL significantly inhibits cell proliferation in the HT-29 cells and HT-29 xenografted model via the mitochondrial cell death pathway.</p

Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine Thiolactone In Vivo

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662. In vivo analysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks. Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress

Protective effects of a compound herbal extract (Tong Xin Luo) on free fatty acid induced endothelial injury: Implications of antioxidant system

<p>Abstract</p> <p>Background</p> <p>Tong-Xin-Luo (TXL) – a mixture of herbal extracts, has been used in Chinese medicine with established therapeutic efficacy in patients with coronary artery disease.</p> <p>Methods</p> <p>We investigated the protective role of TXL extracts on endothelial cells injured by a known risk factor – palmitic acid (PA), which is elevated in metabolic syndrome and associated with cardiovascular complications. Human aortic endothelial cells (HAECs) were preconditioned with TXL extracts before exposed to PA for 24 hours.</p> <p>Results</p> <p>We found that PA (0.5 mM) exposure induced 73% apoptosis in endothelial cells. However, when HAECs were preconditioned with ethanol extracted TXL (100 μg/ml), PA induced only 7% of the endothelial cells into apoptosis. Using antibody-based protein microarray, we found that TXL attenuated PA-induced activation of p38-MAPK stress pathway. To investigate the mechanisms involved in TXL's protective effects, we found that TXL reduced PA-induced intracellular oxidative stress. Through AMPK pathway, TXL restored the intracellular antioxidant system, which was depressed by the PA treatment, with an increased expression of thioredoxin and a decreased expression of the thioredoxin interacting protein.</p> <p>Conclusion</p> <p>In summary, our study demonstrates that TXL protects endothelial cells from PA-induced injury. This protection is likely mediated by boosting intracellular antioxidant capacity through AMPK pathway, which may account for the therapeutic efficacy in TXL-mediated cardiovascular protection.</p

Initial Coin Offering (ICO) in Perspective Law of Sharia Business

Tixl (TXL) is a crypto money project that uses Initial Coin Offering (ICO) to fund its development phase. Various problems underlying the existence of Tixl (TXL) and the proposed solutions are closely related to the condition of society in the information technology era. This study aims to determine the various factors underlying the use of ICO as a way to raise funds, examine Tixl (TXL) as a crypto money project and its position in public life which is reviewed in the perspective of the maṣlaḥa mursala, and token sales transactions in ICO organized by Tixl gmmbH in the perspective of Islamic treaty law. This research is a library research using a conceptual approach and qualitative analysis techniques. This paper shows that there are three factors underlying the use of ICOs as a way to raise funds, namely a change in orientation in the business model, tokenization, and characteristics of business activities. As a crypto money project, Tixl (TXL) cannot provide benefits that are comprehensive or kully, even the harm caused is greater than the benefits. Transaction of token sales in ICO held by Tixl (TXL) is a transaction that is damaged because it is contrary to maqāṣid al-sharī'ah

Effects of Chinese Medicine Tong xinluo on Diabetic Nephropathy via Inhibiting TGF- β

Diabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by interstitial and glomeruli fibrosis. Epithelial-to-mesenchymal transition (EMT) plays an important role in the pathogenesis of DN. Tong xinluo (TXL), a Chinese herbal compound, has been used in China with established therapeutic efficacy in patients with DN. To investigate the molecular mechanism of TXL improving DN, KK-Ay mice were selected as models for the evaluation of pathogenesis and treatment in DN. In vitro, TGF-β1 was used to induce EMT. Western blot (WB), immunofluorescence staining, and real-time polymerase chain reaction (RT-PCR) were applied to detect the changes of EMT markers in vivo and in vitro, respectively. Results showed the expressions of TGF-β1 and its downstream proteins smad3/p-smad3 were greatly reduced in TXL group; meantime, TXL restored the expression of smad7. As a result, the expressions of collagen IV (Col IV) and fibronectin (FN) were significantly decreased in TXL group. In vivo, 24 h-UAER (24-hour urine albumin excretion ratio) and BUN (blood urea nitrogen) were decreased and Ccr (creatinine clearance ratio) was increased in TXL group compared with DN group. In summary, the present study demonstrates that TXL successfully inhibits TGF-β1-induced epithelial-to-mesenchymal transition in DN, which may account for the therapeutic efficacy in TXL-mediated renoprotection

PGC-1 α

Aim. To investigate the effect of Tongxinluo (Txl), a Chinese herbal compound, on diabetic peripheral neuropathy (DPN). Methods and Results. Diabetic rat model was established by peritoneal injection of streptozotocin (STZ). Txl ultrafine powder treatment for 16 weeks from the baseline significantly reversed the impairment of motor nerve conductive velocity (MNCV), mechanical hyperalgesia, and nerve structure. We further proved that Tongxinluo upregulates PGC-1α and its downstream factors including COX IV and SOD, which were involved in mitochondrial biogenesis. Conclusion. Our study indicates that the protective effect of Txl in diabetic neuropathy may be attributed to the induction of PGC-1α and its downstream targets. This finding may further illustrate the pleiotropic effect of the medicine

Why closing an Airport May not Matter – The Impact of the Relocation of TXL Airport on the Bus Network of Berlin

This paper investigates the closure of TXL airport and its impact on the bus network of Berlin. The results of the scenario are based on a co-evolutionary algorithm for public transit network design. The algorithm is integrated in a multi-modal multi-agent simulation. In the simulation, competing minibus operators start exploring the public transport market offering their services. With more successful operators expanding and less successful operators going bankrupt, a sustainable network of minibus services evolves. In the TXL scenario, the impact of the massive change in demand is found to be locally confined. Only transit lines serving TXL airport directly are affected. Furthermore, transit lines are found to have a higher probability of surviving if connecting two different activity centers, e.g. transit hubs. Following a hub-and-spoke approach by letting the line end in low-demand areas renders a line less attractive because of a reduced connectivity, e.g. to one train station only

Maîtrise des risques dans le processus de réponse à appel d’offres

Un appel d'offres (AO) permet à un client d’émettre une demande de travaux ou de services envers des prestataires potentiels et de faire ensuite, par analyse des réponses reçues, le choix de celui qui sera retenu. Du point de vue du soumissionnaire, il existe plusieurs risques au moment de répondre car il doit élaborer une réponse sur un développement futur. De nature différente, ces risques peuvent être regroupés en catégories. Nous proposons une typologie des risques sur laquelle nous nous appuyons afin d'assister le prestataire lors du processus de réponse à appel d’offre (PRAO) via une méthodologie d'aide à la décision fondée sur l’expérience acquise dans le déroulement des projets passés pour détecter, rendre compte et minimiser les risques du PRAO en cours