SIRT1-mediated downregulation of p27(Kip1) is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27(Kip1)). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1 knockdown or knockout on cell proliferation and colony formation. Furthermore, treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM), had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited cell proliferation in culture and colony formation in soft agar, and induced cell cycle arrest. Significantly, NAM inhibited the progression of tumors and extended the survival of mice in a KSHV-induced tumor model. Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.

Exploration of change in persistence patterns of opioid use among patients with non-cancer and cancer pain over a three-year follow-up period

Background: Little is known about the different patterns of persistent opioid use and whether the patterns of clinical opioid use remain the same throughout the long-term opioid therapy. Aim: This study explores the different patterns of persistent opioid use and the change in these patterns over time in patients with non-cancer and cancer pain. Method: This retrospective cross-sectional study included patients with non-cancer and cancer pain receiving opioid prescriptions during 2013-2015 at outpatient tertiary hospital settings in Malaysia. A three-dimensional persistence measure consisting of treatment intensity, frequency and distribution were used to define persistent opioid users as wide (use opioids most of the days in a year), intermediate (use opioids daily) or strict (use opioids continuously to achieve a therapeutic concentration) users. The number of patients in each persistence definition and the change in persistence patterns over time was recorded. Results: Majority of persistent opioid users in the non-cancer and cancer groups were in the wide (9.3% vs.4.8%), followed by intermediate (3.1% vs.0.5%), and strict (1.8% vs.0.9%) definitions. Over a three-year study duration, change to a less stringent persistence definition was observed in the non-cancer group whereas no discernible pattern of change was observed in the cancer group. Conclusion: Change in the patterns of clinical opioid use over time was detected among persistent opioid users in both non-cancer and cancer groups using a three-dimensional persistence measure. This measure which is sensitive to the changes in clinical use of opioids over time can greatly impact future research and practices for better pain management involving opioids

Increasing Incidence of Nontuberculous Mycobacteria, Taiwan, 2000–2008

To assess the species distribution and epidemiologic trends of nontuberculous mycobacteria, we examined isolates from patients in Taiwan. During 2000–2008, the proportion increased significantly from 32.3% to 49.8%. Associated disease incidence increased from 2.7 to 10.2 cases per 100,000 patients. Mycobacterium avium complex and M. abscessus were most frequently isolated

Effects of natural and synthetic antioxidants on changes in refined, bleached, and deodorized palm olein during deep-fat frying of potato chips

The effects of antioxidants on the changes in quality characteristics of refined, bleached, and deodorized (RBD) palm olein during deep-fat frying (at 180°C) of potato chips for 3.5 h/d for seven consecutive days in five systems were compared in this study. The systems were RBD palm olein without antioxidant (control), with 200 ppm butylated hydroxytoluene (BHT), 200 ppm butylated hydroxyanisole (BHA), 200 ppm oleoresin rosemary, and 200 ppm sage extract. Fried oil samples were analyzed for peroxide value (PV), thiobarbituric acid (TBA) value, iodine value (IV), free fatty acid (FFA) content, polymer content, viscosity, E1% 1 cm at 232 and 268 nm, color, fatty acid composition, and C18:2/C16:0 ratio. Sensory quality of the potato chips fried in these systems prior to storage was also evaluated. The storage stability of fried potato chips for 14 wk at ambient temperature was also determined by means of the TBA values and sensory evaluation for rancid odor. Generally, in the oil, oleoresin rosemary gave the lowest rate of increase of TBA value, polymer content, viscosity, E1% 1 cm at 232 and 268 nm compared to control and three other antioxidants. The order of effectiveness (P BHA > sage extract > BHT > control. Prior to storage, the sensory evaluation of fried potato chips for each system showed that there was no significant (P>0.05) difference in terms of flavor, odor, texture, and overall acceptability. The same order of effectiveness (P 0.05) difference in sensory evaluation for rancid odor during storage periods

The use of nanocrystal quantum dot as fluorophore reporters in molecular beacon-based assays

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More sustainable electricity generation in hot and dry fuel cells with a novel hybrid membrane of Nafion/nano-silica/hydroxyl ionic liquid

A new hybrid proton exchange membrane (PEM) has been prepared from hydroxyl functionalized imidazolium ionic liquid (IL-OH), Nafion and nano-SiO2. The IL-OH, with a hydroxyl group that acts as both a proton acceptor and donor, forms strong hydrogen bonds with both Nafion and nano-SiO2, resulting in an effective hydrogen bond network in the ternary membrane. Such an anhydrous hydrogen-bond network, which is unknown previously, endows the PEMs with higher proton conductivity, greater thermal stability and surprisingly a more robust mechanical performance than PEMs consisting of conventional ionic liquids. The resulting PEMs have a tensile strength that is more than twice as strong as recast Nafion and an anhydrous ionic conductivity of ∼55 mS cm−1 at temperatures above 160 °C, with a proton transfer number of ∼0.9. A laboratory assembled H2–O2 fuel cell employing this new PEM delivered a power density of 340 and 420 mW cm−2 at 160 and 180 °C, respectively

Applications of multi-walled carbon nanotube in electronic packaging

Thermal management of integrated circuit chip is an increasing important challenge faced today. Heat dissipation of the chip is generally achieved through the die attach material and solders. With the temperature gradients in these materials, high thermo-mechanical stress will be developed in them, and thus they must also be mechanically strong so as to provide a good mechanical support to the chip. The use of multi-walled carbon nanotube to enhance the thermal conductivity, and the mechanical strength of die attach epoxy and Pb-free solder is demonstrated in this work

Immense Essence of Excellence: Marine Microbial Bioactive Compounds

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery