Biological constraints in algal biotechnology

In the past decade, considerable progress has been made in developing the appropriate biotechnology for microalgal mass cultivation aimed at establishing a new agro-industry. This review points out the main biological constraints affecting algal biotechnology outdoors and the requirements for making this biotechnology economically viable. One of them is the availability of a wide variety of algal species and improved strains that favorably respond to varying environmental conditions existing outdoors. It is thus just a matter of time and effort before a new methodology like genetic engineering can and will be applied in this field as well. The study of stress physiology and adaptation of microalgae has also an important application in further development of the biotechnology for mass culturing of microalgae. In outdoor cultures, cells are exposed to severe changes in light and temperature much faster than the time scale required for the cells to acclimate. A better understanding of those parameters and the ability to rapidly monitor those conditions will provide the growers with a better knowledge on how to optimize growth and productivity. Induction of accumulation of high value products is associated with stress conditions. Understanding the physiological response may help in providing a better production system for the desired product and, at a later stage, give an insight of the potential for genetic modification of desired strains. The potential use of microalgae as part of a biological system for bioremediation/detoxification and wastewater treatment is also associated with growing the cells under stress conditions. Important developments in monitoring and feedback control of the culture behavior through application of on-line chlorophyll fluorescence technique are in progress. Understanding the process associated with those unique environmental conditions may help in choosing the right culture conditions as well as selecting strains in order to improve the efficiency of the biological process.     

The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task

Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.     

Oncomirs: the potential role of non-coding microRNAs in understanding cancer

MicroRNAs (miRNAs) are members of a family of non-coding RNAs of 8-24 nucleotide RNA molecules that regulate target mRNAs. The first miRNAs, lin-4 and let-7, were first discovered in the year 1993 by Ambros, Ruvkun, and co-workers while studying development in Caenorhabditis elegans. miRNAs can play vital functions form C. elegans to higher vertebrates by typical Watson-Crick base pairing to specific mRNAs to regulate the expression of a specific gene. It has been well established that multicellular eukaryotes utilize miRNAs to regulate many biological processes such as embryonic development, proliferation, differentiation, and cell death. Recent studies have shown that miRNAs may provide new insight in cancer research. A recent study demonstrated that more than 50% of miRNA genes are located in fragile sites and cancer-associated genomic regions, suggesting that miRNAs may play a more important role in the pathogenesis of human cancers. Exploiting the emerging knowledge of miRNAs for the development of new human therapeutic applications will be important. Recent studies suggest that miRNA expression profiling can be correlated with disease pathogenesis and prognosis, and may ultimately be useful in the management of human cancer. In this review, we focus on how miRNAs regulate tumorigenesis by acting as oncogenes and anti-oncogenes in higher eukaryotes.     

Composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore

Purpose

To investigate the independent relationship of individual- and area-level socio-economic status (SES) with the presence and severity of visual impairment (VI) in an Asian population.

Methods

Cross-sectional data from 9993 Chinese, Malay and Indian adults aged 40–80 years who participated in the Singapore Epidemiology of eye Diseases (2004–2011) in Singapore. Based on the presenting visual acuity (PVA) in the better-seeing eye, VI was categorized into normal vision (logMAR≤0.30), low vision (logMAR>0.30<1.00), and blindness (logMAR≥1.00). Any VI was defined as low vision/blindness in the PVA of better-seeing eye. Individual-level low-SES was defined as a composite of primary-level education, monthly income<2000 SGD and residing in 1 or 2-room public apartment. An area-level SES was assessed using a socio-economic disadvantage index (SEDI), created using 12 variables from the 2010 Singapore census. A high SEDI score indicates a relatively poor SES. Associations between SES measures and presence and severity of VI were examined using multi-level, mixed-effects logistic and multinomial regression models.

Results

The age-adjusted prevalence of any VI was 19.62% (low vision = 19%, blindness = 0.62%). Both individual- and area-level SES were positively associated with any VI and low vision after adjusting for confounders. The odds ratio (95% confidence interval) of any VI was 2.11(1.88–2.37) for low-SES and 1.07(1.02–1.13) per 1 standard deviation increase in SEDI. When stratified by unilateral/bilateral categories, while low SES showed significant associations with all categories, SEDI showed a significant association with bilateral low vision only. The association between low SES and any VI remained significant among all age, gender and ethnic sub-groups. Although a consistent positive association was observed between area-level SEDI and any VI, the associations were significant among participants aged 40–65 years and male.

Conclusion

In this community-based sample of Asian adults, both individual- and area-level SES were independently associated with the presence and severity of VI.     

Development of Duloxetine Hydrochloride Loaded Mesoporous Silica Nanoparticles: Characterizations and In Vitro Evaluation

This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol–gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The “n” value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r²) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-014-0273-x) contains supplementary material, which is available to authorized users.KEY WORDS: controlled release, duloxetine hydrochloride, meso silica nanoparticles, sol–gel synthesis     

The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.