Approaches for discovering novel bioactive small molecules targeting autophagy

Introduction: In recent years, development of novel bioactive small molecules targeting autophagy has been implicated for autophagy-related disease treatment. Screening new small molecules regulating autophagy allows for the discovery of novel autophagy machinery and therapeutic agents.

Areas covered: Two major screening methods for novel autophagy modulators are introduced in this review, namely target based screening and phenotype based screening. With increasing attention focused on chemical compound libraries, coupled with the development of new assay systems, this review attempts to provide an efficient strategy to explore autophagy biology and discover small molecules for the treatment of autophagy-related diseases.

Expert opinion: Adopting an appropriate autophagy screening strategy is important for developing small molecules capable of treating neurodegenerative diseases and cancers. Phenotype based screening and target based screening were both used for developing effective small molecules. However, each of these methods has many pros and cons. An efficient approach is suggested to screen for novel lead compounds targeting autophagy, which could provide new hits with better efficiency and rapidity.     

Differences in lethal response between male and female calanoid copepods and life cycle traits to cadmium toxicity

This study determined the effect of cadmium (Cd) toxicity comparatively on two copepods, Eurytemora affinis (Poppe 1880) from a temperate region (Seine Estuary, France) and Pseudodiaptomus annandalei (Sewell 1919) from a subtropical region (Danshuei Estuary, Taiwan), according to their sex and reproductive stages. In addition, the effect of Cd to their life cycle traits was quantified. In the first experiment, both copepod sexes were exposed to 40, 80, 150, 220, and 360?µg/L of Cd and a control cultured in salinity 15, except that the temperature was 18?°C for E. affinis and 26?°C for P. annandalei. This allowed calculating median lethal concentration (LC50) of Cd after 96?h. This was 120.6?µg/L Cd for P. annandalei males which were almost twice as sensitive as P. annandalei females (LC50?=?239.5?µg/L Cd). For E. affinis females, the LC50 was 90.04?µg/L Cd, reflecting a 1.4 times higher sensitivity of females than of males (LC50?=?127.75?µg/L Cd). The males of both species were similarly sensitive; however, the E. affinis females were 2.7 times more sensitive than the P. annandalei females. We also compared the sensitivity of ovigerous females (OVF) and non-ovigerous females (NOF) of both species to Cd. Mortality was higher in NOF than in OVF of both copepod species in both the control and the 40?µg/L Cd treatment. Finally, the total population, fecundity and female morphology of both copepod species were estimated after exposing one generation cycle (nauplius to adult) to 40?μg/L Cd (for E. affinis) and 160?μg/L Cd (for P. annandalei). A significant decrease in cohort production, survival and clutch size but no significant difference in the prosome length of both copepod species exposed to Cd were detected. The ratio of OVF:NOF was high in both copepod species exposed to Cd. Cd toxicity did not significantly affect the M:F sex ratio and % OVF of E. affinis. However, the effect of Cd toxicity in P. annandalei was significant in the M:F sex ratio and was in favor of females and their reproductive activities due to an increase in % OVF. Moreover, there was a significant decrease in total production of P. annandalei due to high mortality in their nauplii and copepodid developmental stages. Toxicity to Cd appears to be affected by multiple factors including sex, reproductive life stage and species. The ecological implication of Cd toxicity on E. affinis and P. annandalei copepod ecology is more related to a skewed sex ratio, low egg production, reduced hatchability and reduced survival that affects the recruitment potential of the copepod nauplii resulting in a decreasing copepod population. Mortality, reproduction and population growth of model species may provide important bio-indicators for environmental risk assessment.     

Constituents from the leaves of <Emphasis Type="Italic">Clausena lansium</Emphasis> and their anti-inflammatory activity

Five new acyclic amides, clausenalansamides C-G (1–5), clausenaline G (6) and (±)-5-(4-methylphenyl)-γ-valerolactone (7) reported from the natural source for the first time, were characterized from the leaves of Clausena lansium. Their structures were established by spectroscopic and spectrometric methods, and the absolute configurations of new compounds 1–5 were determined by electronic circular dichroism and single-crystal X-ray diffraction analyses. Eighteen compounds were evaluated for their anti-inflammatory activity and only imperatorin (11) and wampetin (12) displayed significant inhibition of fMLP/CB-induced superoxide anion generation with IC₅₀ values of 1.7 ± 0.3 and 6.8 ± 1.1 μM, respectively.     

Transdermal iontophoresis patch with reverse electrodialysis

Reverse electrodialysis (RED) technology generates energy from the salinity gradient by contacting waters with different salinity. Herein, we develop the disposable skin patch using this eco-friendly energy. The current density, which can be controlled easily without special circuit, is enough to iontophoretic drug delivery. In vitro study, this iontophoretic system enhanced the transdermal delivery of peptide, which is difficult to penetrate the skin barrier by simple diffusion. We design the disposable iontophoretic skin patch using RED system and suggest this patch can be apply on new cosmetic patch or disposable drug patch.     

A comparison of food portion size estimation by older adults,young adults and nutritionists

Objectives

To investigate the ability of older adults, younger adults and nutritionists to assess portion size using traditional methods versus a computer-based method. This was to inform the development of a novel dietary assessment method for older adults “The NANA system”.

Design

Older and younger adults assessed the portion size of self-served portions of foods from a buffet style set up using traditional and computerised portion size assessment aids. Nutritionists assessed the portion size of foods from digital photographs using computerised portion size aids. These estimates were compared to known weights of foods using univariate analyses of covariance (ANCOVA).

Setting

The University of Sheffield, United Kingdom.

Subjects

Forty older adults (aged 65 years and over), 41 younger adults (aged between 18 and 40 years) and 25 nutritionists.

Results

There was little difference in the abilities of older and younger adults to assess portion size using both assessment aids with the exception of small pieces morphology. Even though the methods were not directly comparable among the test groups, there was less variability in portion size estimates made by the nutritionists.

Conclusion

Older adults and younger adults are similar in their ability to assess food portion size and demonstrate wide variability of estimation compared to the ability of nutritionists to estimate portion size from photographs. The results suggest that the use of photographs of meals consumed for portion size assessment by a nutritionist may improve the accuracy of dietary assessment. Improved portion size assessment aids are required for all age groups.

     

Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens

Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS. Antibacterial activity of kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method. MIC of kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml. The bactericidal test showed that kuwanon G completely inactivated S. mutans at the concentration 20 microg/ml in 1 min. Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis. Transmission electron microscopy (TEM) of kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm.