Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.     

WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

From glass to life: a commentary on the assessment of the reproductive potential of cryopreserved human oocytes

Journal of Assisted Reproduction and Genetics -     

Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH) and severe PH(SPH). As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero, dretro, d RMS) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain μ and standard deviation σ of strain were assessed in the regions of interest(ROI)(1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only dretro showed significant results in SPH analysis. According to ROC analysis area under the curve(AUC) of the σROI[0…10 Hz, 2 cm × 2 cm] parameter reached 0.71(P = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for μROI[0…10 Hz, 1 cm × 1 cm] was 0.78(P = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. Dretro parameter had an AUC of 0.86(P = 0.0001) for the diagnosis of CSPH and 0.84(P = 0.0001) for the diagnosis of SPH. A cut-off value of-132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.     

软组织损伤引起慢性疼痛的治疗

目的：综述运动系统软组织损伤引起慢性疼痛的各种治疗方法的研究进展。资料来源：应用计算机检索Medline1980—01／2006—04与运动系统软组织损伤引起慢性疼痛的治疗相关文章，检索词“Soft tissue injury，pain．chronic，comprehensive therapy”，并限定文章语言种类为“English”；同时计算机检索中国期刊全文数据库1994—01／2006-04期间的相关文章，检索词“软组织损伤、慢性疼痛、治疗方法”，并限定语言种类为中文。同时手工查阅相关书籍。资料选择：对资料进行初审，所选文献内容符合：①软组织损伤引起的慢性疼痛药物治疗的研究。②软组织损伤引起的慢性疼痛微创治疗的研究。③软组织损伤引起的慢性疼痛运动疗法的研究。④软组织损伤引起的慢性疼痛心理治疗的研究。⑤软组织损伤引起的慢性疼痛其他疗法的研究。排除重复性研究的文献。资料提炼：共收集到40篇关于软组织损伤引起的慢性疼痛治疗方法的文献，均为全文，23篇符合纳入标准，排除17篇重复性研究。同时录入书籍3本。资料综合：软组织损伤引起的慢性疼痛的产生是生理、心理及社会因素复杂结合的结果，个体表现差异较大，目前尚无特效治疗方法，常用的治疗方法有：药物治疗、微创治疗、运动疗法、心理治疗、物理疗法及其他疗法。结论：对于软组织损伤引起的慢性疼痛的治疗必须以整体的观点对其进行合理的评估和个体化治疗，才能收到良好的效果。