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

Synthesis of high-refractive index sulfur containing polymers for 193-nm immersion lithography: A progress report

To be able to extend the 193 nm immersion lithography technology platform, the development of high refractive index immersion fluids and resists is required. This paper reports our investigations into generating high refractive index polymers for use in photoresist formulations for 193 nm immersion lithograph. In this study a series of model compounds have been screened for refractive index and transparency at 589 nm and 193 nm. For the compounds studied this series of experiments demonstrated that sulfur-containing compounds have a positive effect on the refractive index of a molecule at 589 nm. However, the situation is complicated by the presence of absorption bands for some small molecules in the low waveleingth region. To demonstrate this, we examined the refractive index dispersion of a series of molecules based on ethyl acetate with varying degrees of sulfur substitution. These results indicated that an anomalous increase in refractive index could be expected 20 - 30 nm above the absorption maximum. The implications for design of high refractive index resists for 193 nm immersion lithography are discussed

Proprioception and flexibility profiles of elite synchronized swimmers

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LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers

Strong quantum memory at resonant Fermi edges revealed by shot noise

Studies of non-equilibrium current fluctuations enable assessing correlations involved in quantum transport through nanoscale conductors. They provide additional information to the mean current on charge statistics and the presence of coherence, dissipation, disorder, or entanglement. Shot noise, being a temporal integral of the current autocorrelation function, reveals dynamical information. In particular, it detects presence of non-Markovian dynamics, i.e., memory, within open systems, which has been subject of many current theoretical studies. We report on low-temperature shot noise measurements of electronic transport through InAs quantum dots in the Fermi-edge singularity regime and show that it exhibits strong memory effects caused by quantum correlations between the dot and fermionic reservoirs. Our work, apart from addressing noise in archetypical strongly correlated system of prime interest, discloses generic quantum dynamical mechanism occurring at interacting resonant Fermi edges.Comment: 6 pages, 3 figure

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy

Macroscopic transport by synthetic molecular machines

Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential.

Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.published_or_final_versio

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model.

Background Modified Erxian decoction (MEXD), i.e., Erxian decoction (EXD) with Fructus Schisandrae chinensis (Wu Wei Zi) added, has been used to alleviate menopausal symptoms. This study aimed to investigate the effects of MEXD on menopausal sweating and serum hormone levels in a rat model of menopause after oral administration of MEXD. Methods Quality control of MEXD was conducted by employing a reversed-phase high performance liquid chromatography column. The three treatment groups received oral administration of MEXD in 0.5% sodium carboxylmethyl cellulose (CMC-Na) at three different doses (5.5, 11, and 22 g/kg body weight) once-daily for 6 consecutive weeks, with 10 animals per group. Huangqijing oral liquor (5 mL/kg) prepared from the roots of Huang qi (Astragalus membranaceus) with an antiperspirant effect was used as a positive control. The negative control group received the same volume of vehicle (0.5% CMC-Na). Ten 3-month-old Sprague–Dawley rats were used as a young group for comparison with the treatment groups (12–14 months old rats). Blood was collected from all animals after 3–6 weeks of treatment. At the end of the treatment, the uterine weight, ovarian weight, and body weight were recorded. Serum malondialdehyde contents and superoxide dismutase activities were determined by thiobarbituric acid colorimetric assays and chemoluminescence assays, respectively. Serum levels of estradiol, follicle-stimulating hormone, and luteinizing hormone were measured by radioimmunoassays. Rat foot pad assays were used to determine the antiperspirant activity of MEXD and histological examinations were conducted on plantar sweat glands. Results Treatment with MEXD (11 g/kg) significantly inhibited sweat excretion in the menopause model rats after treatment for 3 (P = 0.0026) and 6 (P < 0.0001) weeks. The decoction markedly decreased the number of secretory cells in plantar sweat glands. In addition, MEXD (11 g/kg) significantly increased the serum estradiol levels (P < 0.001) and superoxide dismutase activities (P = 0.0405). Furthermore, MEXD (11 g/kg) markedly decreased the serum levels of follicle-stimulating hormone (P = 0.001), luteinizing hormone (P = 0.0213), and malondialdehyde (P = 0.01). Conclusion Modified Erxian decoction significantly inhibited sweat excretion, regulated serum levels of pituitary gonadotropins and estradiol, and exhibited antioxidative effects in a rat model of menopause.published_or_final_versio