Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies]

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.     

Inhibition of Leishmania (Leishmania) amazonensis and Rat Arginases by Green Tea EGCG, (+)-Catechin and (?)-Epicatechin: A Comparative Structural Analysis of Enzyme-Inhibitor Interactions

Epigallocatechin-3-gallate (EGCG), a dietary polyphenol (flavanol) from green tea, possesses leishmanicidal and antitrypanosomal activity. Mitochondrial damage was observed in Leishmania treated with EGCG, and it contributed to the lethal effect. However, the molecular target has not been defined. In this study, EGCG, (+)-catechin and (−)-epicatechin were tested against recombinant arginase from Leishmania amazonensis (ARG-L) and rat liver arginase (ARG-1). The compounds inhibit ARG-L and ARG-1 but are more active against the parasite enzyme. Enzyme kinetics reveal that EGCG is a mixed inhibitor of the ARG-L while (+)-catechin and (−)-epicatechin are competitive inhibitors. The most potent arginase inhibitor is (+)-catechin (IC₅₀ = 0.8 µM) followed by (−)-epicatechin (IC₅₀ = 1.8 µM), gallic acid (IC₅₀ = 2.2 µM) and EGCG (IC₅₀ = 3.8 µM). Docking analyses showed different modes of interaction of the compounds with the active sites of ARG-L and ARG-1. Due to the low IC₅₀ values obtained for ARG-L, flavanols can be used as a supplement for leishmaniasis treatment.     

Proteomic studies highlight outer‐membrane proteins related to biofilm development in the marine bacterium Pseudoalteromonas sp. D41

Bacterial biofilm development is conditioned by complex processes involving bacterial attachment to surfaces, growth, mobility, and exoproduct production. The marine bacterium Pseudoalteromonas sp. strain D41 is able to attach strongly onto a wide variety of substrates, which promotes subsequent biofilm development. Study of the outer‐membrane and total soluble proteomes showed ten spots with significant intensity variations when this bacterium was grown in biofilm compared to planktonic cultures. MS/MS de novo sequencing analysis allowed the identification of four outer‐membrane proteins of particular interest since they were strongly induced in biofilms. These proteins are homologous to a TonB‐dependent receptor (TBDR), to the OmpW and OmpA porins, and to a type IV pilus biogenesis protein (PilF). Gene expression assays by quantitative RT‐PCR showed that the four corresponding genes were upregulated during biofilm development on hydrophobic and hydrophilic surfaces. The Pseudomonas aeruginosa mutants unable to produce any of the OmpW, OmpA, and PilF homologues yielded biofilms with lower biovolumes and altered architectures, confirming the involvement of these proteins in the biofilm formation process. Our results indicate that Pseudoalteromonas sp. D41 shares biofilm formation mechanisms with human pathogenic bacteria, but also relies on TBDR, which might be more specific to the marine environment.     

Obese adolescents exhibit a constant ratio of GH isoforms after whole body vibration and maximal voluntary contractions

Background

Growth hormone (GH) is a heterogeneous protein composed of several molecular isoforms, the most abundant ones being the 22?kDa- and 20?kDa-GH. Exercise-induced secretion of GH isoforms has been extensively investigated in normal-weight individuals due to antidoping purposes, particularly recombinant human GH (rhGH) abuse. On the other hand, the evaluation of exercise-induced responses in GH isoforms has never been performed in obese subjects.

Methods

The acute effects of whole body vibration (WBV) or maximal voluntary contraction (MVC) alone and the combination of MVC with WBV (MVC?+?WBV) on circulating levels of 22?kDa- and 20?kDa-GH were evaluated in 8 obese male adolescents [mean age?±?SD: 17.1?±?3.3?yrs.; weight: 107.4?±?17.8?kg; body mass index (BMI): 36.5?±?6.6?kg/m²; BMI standard deviation score (SDS): 3.1?±?0.6].

Results

MVC (alone or combined with WBV) significantly stimulated 22?kDa- and 20?kDa-GH secretion, while WBV alone was ineffective. In particular, 22?kDa- and 20?kDa-GH peaks were significantly higher after MVC?+?WBV and MVC than WBV. In addition, 22?kDa-GH (but not 20?kDa-GH) peak was significantly higher after MVC?+?WBV than MVC. Importantly, the ratio of circulating levels of 22?kDa- to 20?kDa-GH was constant throughout the time window of evaluation after exercise and similar among the three different protocols of exercise.

Conclusions

The results of the present study confirm the ability of MVC, alone and in combination with WBV, to stimulate both 22?kDa- and 20?kDa-GH secretion in obese patients, these responses being related to the exercise workload. Since the ratio of 22?kDa- to 20?kDa-GH is constant after exercise and independent from the protocols of exercise as in normal-weight subjects, hyposomatotropism in obesity does not seem to depend on an unbalance of circulating GH isoforms. Since the present study was carried out in a small cohort of obese sedentary adolescents, these preliminary results should be confirmed in further future studies enrolling overweight/obese subjects with a wider age range.

     

Phylogeography of Y-chromosome haplogroup I reveals distinct domains of prehistoric gene flow in europe

To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia ~9,000 years ago.     

Effects of chronic physical activity and of ultrasound treatment on bone consolidation

The objective of this study was to investigate the effects of ultrasound treatment and physical exercise on the velocity of bone consolidation and resistance to deformation. We performed osteotomy in the upper third of the right tibia of rats. Physical training consisted of swimming 1 h per day with a load of 5% b.w. for 30 days. Therapy with medium-intensity ultrasound was applied daily on the damaged area. Wistar rats were divided into the following groups: osteotomized sedentary animals with no ultrasound treatment (1.OSnUS), osteotomized trained animals with no ultrasound treatment (2.OTnUS), osteotomized sedentary animals with ultrasound treatment (3.OSwUS), and osteotomized trained animals with ultrasound treatment (4.OTwUS). The animals were sacrificed for the following analyses: muscle glycogen, serum alkaline phosphatase at the 5th, 10th, 20th, and 30th days, test of maximum resistance to flexion, rupture flexion and mean tibial rigidity at the 30th day. Muscle glycogen was increased at the 20th day; alkaline phosphatase was elevated at the 5th and 20th days in groups 3.OSwUS and 4.OTwUS, and decreased at the 10th day. Groups 1.OSnUS and 2.OTnUS did not show significant variations. In the mechanical resistance tests, we noted that ultrasound therapy and the association of physical activity used in the present study showed significant differences in bone resistance and bone rigidity after 30 days of treatment. These facts suggest that ultrasound or physical activity, or their combination may accelerate the process of bone tissue repair.