Anti-tumorigenic and Pro-apoptotic effects of CKBM on gastric cancer growth in nude mice

Natural botanical products can be integrated with western medicine to optimize the treatment outcome, increase immune function and minimize the side effects from western drug treatment. CKBM is a combination of herbs and yeasts formulated based on traditional Chinese medicinal principles. Previous study has demonstrated that CKBM is capable of improving immune responsiveness through the induction of cytokine mediators, such as TNF-α and IL-6. In this study, we aimed to investigate the effect of this immunomodulatory drug on gastric cancer growth using a human xenograft model. Gastric cancer tissues were implanted subcutaneously into athymic nude mice followed by a 14-day or 28-day of CKBM treatment. Results showed that higher doses of CKBM (0.4 or 0.8 ml/mouse/day) produced a dose-dependent inhibitory effect on gastric tumor growth after 28-day drug treatment. This was associated with a decrease of cellular proliferation by 30% with concomitant increase in apoptosis by 97% in gastric tumor cells when compared with the control group. In contrast, CKBM showed no effect on angiogenesis in gastric tumors. This study demonstrates the anti-tumorigenic action of CKBM on gastric cancer probably via inhibition of cell proliferation and induction of apoptosis, and provides future potential targets of this drug candidate on cancer therapy.published_or_final_versio

Bottom-up Design of Three-Dimensional Carbon-Honeycomb with Superb Specific Strength and High Thermal Conductivity

Low-dimensional carbon allotropes, from fullerenes, carbon nanotubes, to graphene, have been broadly explored due to their outstanding and special properties. However, there exist significant challenges in retaining such properties of basic building blocks when scaling them up to three-dimensional materials and structures for many technological applications. Here we show theoretically the atomistic structure of a stable three-dimensional carbon honeycomb (C-honeycomb) structure with superb mechanical and thermal properties. A combination of sp(2) bonding in the wall and sp(3) bonding in the triple junction of C-honeycomb is the key to retain stability of C-honeycomb. The specific strength could be the best in structural carbon materials, and this strength remains at,a high level but tunable with different cell sizes. C-honeycomb is also found to have a very high thermal conductivity, for example, &gt;100 W/mK along the axis of the hexagonal cell with a density only similar to 0.4 g/cm(3). Because of the low density and high thermal conductivity, the specific thermal conductivity of C-honeycoMbs is larger than most engineering materials, including metals and high thermal conductivity semiconductors, as well as lightweight CNT arrays and graphene-based nanocomposites. Such high specific strength, high thermal conductivity, and anomalous Poisson&#39;s effect in C-honeycomb render it appealing for the use in various engineering practices.</p

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

Women's preference for cesarean delivery and differences between Taiwanese women undergoing different modes of delivery

<p>Abstract</p> <p>Background</p> <p>The rate of cesarean delivery was 35% in 2007 in Taiwan. It is unclear how many of the cesarean deliveries were without medical indications. Women's preference for cesarean delivery during their course of pregnancy has rarely been studied and therefore our objectives were to examine rate of cesarean deliveries without medical indications, to explore women's preference for cesarean delivery as their gestation advances, and to compare background and perinatal factors among women who underwent different modes of delivery in Taiwan.</p> <p>Methods</p> <p>This prospective study applied a longitudinal design. The study participants were 473 women who received prenatal care at four hospitals in Taipei and answered structured questionnaires at 20 to 24 weeks of pregnancy, 34 to 36 weeks of pregnancy, and 5 to 7 weeks after delivery.</p> <p>Results</p> <p>Of the 151 women (31.9%) who had cesarean deliveries, 19.9% were without medical indication. Three indications: malpresentation, prior cesarean section, and dysfunctional labor together accounted for 82.6% of cesarean section with medical indications. The prevalence of maternal preference for cesarean delivery was found to be 12.5% and 17.5% during the second and third trimester, respectively. Of the women who preferred cesarean delivery during the second trimester, 93.2% eventually had a cesarean delivery. Women who were older, with older spouses, and who had health problems before or during pregnancy were more likely to have cesarean deliveries.</p> <p>Conclusions</p> <p>About 20% of cesarean deliveries were without medical indications. Women's preference for cesarean delivery during the second trimester predicts subsequent cesarean delivery. Counseling regarding mode of delivery should be offered early in pregnancy, especially for women who are older or with older spouses, have health problems, or had a prior cesarean section.</p

Changes in Plasma Membrane Surface Potential of PC12 Cells as Measured by Kelvin Probe Force Microscopy

The plasma membrane of a cell not only works as a physical barrier but also mediates the signal relay between the extracellular milieu and the cell interior. Various stimulants may cause the redistribution of molecules, like lipids, proteins, and polysaccharides, on the plasma membrane and change the surface potential (Φs). In this study, the Φss of PC12 cell plasma membranes were measured by atomic force microscopy in Kelvin probe mode (KPFM). The skewness values of the Φss distribution histogram were found to be mostly negative, and the incorporation of negatively charged phosphatidylserine shifted the average skewness values to positive. After being treated with H2O2, dopamine, or Zn2+, phosphatidylserine was found to be translocated to the membrane outer leaflet and the averaged skewness values were changed to positive values. These results demonstrated that KPFM can be used to monitor cell physiology status in response to various stimulants with high spatial resolution

Hyperphosphorylation as a Defense Mechanism to Reduce TDP-43 Aggregation

Several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are characterized by inclusion bodies formed by TDP-43 (TDP). We established cell and transgenic Drosophila models expressing TDP carboxyl terminal fragment (ND251 and ND207), which developed aggregates recapitulating important features of TDP inclusions in ALS/FTLD-U, including hyperphosphorylation at previously reported serine403,404,409,410 residues, polyubiquitination and colocalization with optineurin. These models were used to address the pathogenic role of hyperphosphorylation in ALS/FTLD-U. We demonstrated that hyperphosphorylation and ubiquitination occurred temporally later than aggregation in cells. Expression of CK2α which phosphorylated TDP decreased the aggregation propensity of ND251 or ND207; this effect could be blocked by CK2 inhibitor DMAT. Mutation of serines379,403,404,409,410 to alanines (S5A) to eliminate phosphorylation increased the aggregation propensity and number of aggregates of TDP, but mutation to aspartic acids (S5D) or glutamic acids (S5E) to simulate hyperphosphorylation had the opposite effect. Functionally, ND251 or ND207 aggregates decreased the number of neurites of Neuro2a cells induced by retinoic acid or number of cells by MTT assay. S5A mutation aggravated, but S5E mutation alleviated these cytotoxic effects of aggregates. Finally, ND251 or ND251S5A developed aggregates in neurons, and salivary gland of transgenic Drosophila, but ND251S5E did not. Taken together, our data indicate that hyperphosphorylation may represent a compensatory defense mechanism to stop or prevent pathogenic TDP from aggregation. Therefore, enhancement of phosphorylation may serve as an effective therapeutic strategy against ALS/FTLD-U

Comparison of intravascular ultrasound guided versus angiography guided drug eluting stent implantation: a systematic review and meta-analysis

BACKGROUND: Intravascular ultrasound (IVUS) can be a useful tool during drug-eluting stents (DES) implantation as it allows accurate assessment of lesion severity and optimal treatment planning. However, numerous reports have shown that IVUS guided percutaneous coronary intervention is not associated with improved clinical outcomes, especially in non-complex patients and lesions. METHODS: We searched the literature in Medline, the Cochrane Library, and other internet sources to identify studies that compare clinical outcomes between IVUS-guided and angiography-guided DES implantation. Random-effects model was used to assess treatment effect. RESULTS: Twenty eligible studies with a total of 29,068 patients were included in this meta-analysis. The use of IVUS was associated with significant reductions in major adverse cardiovascular events (MACE, odds ratios [OR] 0.77, 95 % confidence intervals [CI] 0.71-0.83, P < 0.001), death (OR 0.62, 95 % CI 0.54-0.71, p < 0.001), and stent thrombosis (OR 0.59, 95 % CI: 0.47-0.73, P < 0.001). The benefit was also seen in the repeated analysis of matched and randomized studies. In stratified analysis, IVUS guidance appeared to be beneficial not only in patients with complex lesions or acute coronary syndromes (ACS) but also patients with mixed lesions or presentations (MACE: OR 0.69, 95 % CI: 0.60-0.79, p < 0.001, OR 0.81, 95 % CI 0.74-0.90, p < 0.001, respectively). By employing meta-regression analysis, the benefit of IVUS is significantly pronounced in patients with complex lesions or ACS with respect to death (p = 0.048). CONCLUSIONS: IVUS guidance was associated with improved clinical outcomes, especially in patients with complex lesions admitted with ACS. Large, randomized clinical trials are warranted to identify populations and lesion characteristics where IVUS guidance would be associated with better outcomes