A randomized,double-blind,placebo-controlled,clinical trial on probiotic soy milk and soy milk: effects on epigenetics and oxidative stress in patients with type II diabetes

This clinical trial aimed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation, and oxidative stress among type II diabetic patients. Forty patients with type II diabetes mellitus aged 35–68 years were assigned to two groups in this randomized, double-blind, controlled clinical trial. Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7, while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks. Fasting blood samples, anthropometric measurements, and 24-h dietary recalls were collected at the baseline and at the end of the study, respectively. Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region (P < 0.01 and P < 0.0001, respectively) compared with the baseline values, while plasma concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG) decreased significantly compared with soy milk (P < 0.05). In addition, a significant increase in superoxide dismutase (SOD) activity was observed in probiotic soy milk group compared with baseline value (P < 0.01). There were no significant changes from baseline in the promoter methylation of MSH2 within either group (P > 0.05). The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients, indicating that probiotic soy milk is a promising agent for diabetes management.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0503-1) contains supplementary material, which is available to authorized users.     

Production and Characterization of Monoclonal Antibodies to Barley Yellow Mosaic Virus and Their Use in Detection of Four Bymoviruses

Six monoclonal antibodies (MAbs) against a French isolate of barley yellow mosaic virus (BaYMV) pathotype 2 were produced and their isotypes determined. These MAbs were compared in ELISA for their reactivity with different isolates of BaYMV, wheat yellow mosaic virus (WYMV), wheat spindle streak mosaic virus (WSSMV) and oat mosaic virus (OMV).The six MAbs detected BaYMV in TAS ELISA and western blot, whereas in ACP ELISA no reaction was observed with isolates of BaYMV and WYMV. These MAbs could recognize the sequential motifs situated at the surface of viral particles. The six MAbs detected all the European isolates of BaYMV pathotype 1 and 2 and the Japanese isolate of this viral pathotype 1–1. In contrast to other MAbs, MAb IV did not react with the Japanese isolate of BaYMV pathotype II-l. In TAS ELISA. MAbs I, II, III, and IV detected the Japanese isolate of WYMV and American isolates of WSSMV only when they were captured by anti-WYMV polyclonal antibodies, A French isolate of OMV was detected only by the MAbs I and II in TAS ELISA with Polyclonal anti-BaYMV.     

A weakened interface in the P182L variant of HSP27 associated with severe Charcot‐Marie‐Tooth neuropathy causes aberrant binding to interacting proteins

HSP27 is a human molecular chaperone that forms large, dynamic oligomers and functions in many aspects of cellular homeostasis. Mutations in HSP27 cause Charcot‐Marie‐Tooth (CMT) disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of CMT disease is triggered by the P182L mutation in the highly conserved IxI/V motif of the disordered C‐terminal region, which interacts weakly with the structured core domain of HSP27. Here, we observed that the P182L mutation disrupts the chaperone activity and significantly increases the size of HSP27 oligomers formed in vivo, including in motor neurons differentiated from CMT patient‐derived stem cells. Using NMR spectroscopy, we determined that the P182L mutation decreases the affinity of the HSP27 IxI/V motif for its own core domain, leaving this binding site more accessible for other IxI/V‐containing proteins. We identified multiple IxI/V‐bearing proteins that bind with higher affinity to the P182L variant due to the increased availability of the IxI/V‐binding site. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27 and suggest that the IxI/V motif plays an important, regulatory role in modulating protein–protein interactions.     

Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti‐Alzheimer's Agents

Alzheimer's disease (AD) is a well‐known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal‐chelating properties. Among the synthesized compounds, 14‐amino‐13‐(3‐nitrophenyl)‐2,3,4,13‐tetrahydro‐1H‐benzo[6,7]chromeno[2,3‐b]quinoline‐7,12‐dione ( 6m ) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀s of 0.86 and 6.03 μm , respectively. Also, the compound could inhibit β‐secretase 1 (BACE1) with IC₅₀=19.60 μm and showed metal chelating ability toward Cu²⁺, Fe²⁺, and Zn²⁺. In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.     

Current distribution and potential expansion of the harmful benthic dinoflagellate Ostreopsis cf. siamensis towards the warming waters of the Bay of Biscay,North-East Atlantic

In a future scenario of increasing temperatures in North-Atlantic waters, the risk associated with the expansion of the harmful, benthic dinoflagellate Ostreopsis cf. siamensis has to be evaluated and monitored. Microscopy observations and spatio-temporal surveys of environmental DNA (eDNA) were associated with Lagrangian particle dispersal simulations to: (i) establish the current colonization of the species in the Bay of Biscay, (ii) assess the spatial connectivity among sampling zones that explain this distribution, and (iii) identify the sentinel zones to monitor future expansion. Throughout a sampling campaign carried out in August to September 2018, microscope analysis showed that the species develops in the south-east of the bay where optimal temperatures foster blooms. Quantitative PCR analyses revealed its presence across almost the whole bay to the western English Channel. An eDNA time-series collected on plastic samplers showed that the species occurs in the bay from April to September. Due to the water circulation, colonization of the whole bay from the southern blooming zones is explained by inter-site connectivity. Key areas in the middle of the bay permit continuous dispersal connectivity towards the north. These key areas are proposed as sentinel zones to monitor O. cf. siamensis invasions towards the presumably warming water of the North-East Atlantic.