The F0F1 ATP synthase regulates human neutrophil migration through cytoplasmic proton extrusion coupled with ATP generation

Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect. Further analysis revealed that cell surface F-ATPase can translocate to the leading edge of directional fMLP-stimulated neutrophils toward ADP hydrolyzed from pannexin 1 channel-released ATP, followed by F-ATPase-catalyzed ATP regeneration using ADP and protons transferred from the cytoplasm. Therefore, the membrane-expressed F-ATPase regulates human neutrophil migration via cytoplasm proton extrusion and extracellular ATP generation.     

Indole 3-acetic acid-photodynamic therapy in the treatment of multiple actinic keratoses: A proof of concept pilot study

BackgroundActinic Keratoses (AK) are considered a form of in situ Squamous Cell Carcinoma (SCC) arising on chronically photoexposed skin. PDT with ALA or MAL is an effective treatment for multiple AK due its high Overall Response Ratio (ORR) but is burdened by important drawbacks: time-consumption, pain and high costs. Indole-3 acetic acid (IAA) is a newly described photosensitizer with proven clinical efficacy on seborrheic dermatitis and acne vulgaris. The aim of the study was to assess efficacy, safety and tolerability of a cycle of IAA-PDT at 0.015% in liposomal gel in the treatment of multiple AK of face or scalp.MethodsWe treated 12 patients affected by multiple AK on face/scalp with 4 weekly applications. The product was applied for 15 min under occlusion; medicated area was then irradiated for 15 min with a LED light at 520 nm wavelength for a total fluency of 9 J/cm2.ResultsNo grade 3/4 SAE have been reported; all 12 patients successfully completed the cycle. CR at 3 months follow-up was 25%, with an ORR of 50%. Patients reported almost no pain during irradiations, with mean overall Visual Analogic Scale (VAS) score of 0.3 ± 0.7. IAA-PDT led to a significant improve on Disease Life Quality Index (DLQI) mean score, but no variations on Actinic Keratosis Quality of Life (AKQoL) mean score.ConclusionsAlthough larger studies are needed, this is a first “proof of concept” of IAA- PDT as a possible treatment for multiple AK on face/scalp.     

Two new sesquiterpenoids from cultures of the basidiomycete Tremella foliacea

Two new sesquiterpenoids, trefoliol B (1) and trefoliol C (2), together with known echinocidin A (3), were isolated from cultures of the basidiomycetes Tremella foliacea. The new structures were elucidated on the basis of extensive spectroscopic methods. At the same time, trefoliol B (1) and echinocidin A (3) were tested for their cytotoxicities against five human cancer cell lines and for their inhibitory activities against isozymes of 11β-hydroxysteroid dehydrogenases (11β-HSD). No compound showed significant activity (IC₅₀ > 40 μM). Compound 1 showed moderate inhibitory activities against 11β-HSD1 (human IC₅₀ = 13.1 μM; mouse IC₅₀ = 91.8 μM).     

The changing gender differences in hepatitis a incidence in South Korea

We examined the trend in gender difference for hepatitis A incidence in South Korea after introducing universal vaccination in toddlers and in military recruits. We found that the male-female incidence rate ratio has decreased significantly especially among persons aged 20–29 years, suggesting additional impact from vaccinating military recruits.     

射干内生真菌Fusarium proliferatum的ISSR和SRAP位点遗传多样性分析

目的为了解射干内生真菌Fusarium proliferatum的遗传多样性。方法选用了52条ISSR引物和90条SRAP引物对17株射干内生真菌F. proliferatum进行了遗传多样性分析。筛选出了27条ISSR引物和38条SRAP引物可用于遗传多样性分析。结果结果,27条ISSR引物共扩增出了178个条带,其中131条(63%)具有多态性;38条SRAP引物能够扩增出357条稳定性较好的条带,其中323条(91%)具有稳定性差异。27条ISSR引物PCR扩增产物的多态性信息量(PIC)介于0.19～0.91,平均为0.70;38条SRAP引物PCR扩增产物的多态性信息量PIC介于0～0.93,平均为0.73。聚类分析结果表明,根据27个ISSR、38个SRAP及ISSR+SRAP遗传位点分析得出遗传相似系数变化范围分别为0.73～0.99、0.72～0.95和0.73～0.95,平均分别为0.84、0.85和0.85。根据材料间的遗传相似系数聚类,三者之间的聚类有较小的差异,但总体上,17株内生真菌被聚为3大类,分离自根的内生真菌F. proliferatum聚为一类,分离自茎和叶的F. proliferatum聚集于另外两类。研究表明,内生真菌F. proliferatum遗传相似性较大,其亲缘关系较近,与传统方法鉴定出的结果一致。结论采用分子标记技术比传统的方法鉴定更为有效,同时,ISSR和SRAP标记可更真实地反映射干内生真菌F. proliferatum的遗传多样性,为该内生真菌在分子生物技术方面的研究等提供一定参考。     

Surgery for lumbar disc herniation: Analysis of 500 consecutive patients treated in an interdisciplinary spine centre

Surgical removal of a symptomatic herniated lumbar disc is performed either with or without the support of a microscope. Up to the time of writing, the literature has reported similar clinical outcomes for the two procedures. Five hundred consecutive patients, operated upon for primary single-level lumbar disc herniation in our University Spine Center between 2003–2011, with (n = 275), or without (n = 225), the aid of a microscope were included. Data were retrospectively analyzed, comparing the primary endpoint of clinical outcome and the secondary endpoints of complications, surgical time and length of hospitalization. Clinical outcomes and reoperation rates were comparable in both groups. Surgical time was significantly shorter with a mean time of 47 minutes without use of the microscope compared to the mean time of 87 minutes (p < 0.001) with the use of the microscope. Mean length of hospitalization was shorter in those operated with the microscope (5.3 days) compared to those without (6.1 days, p = 0.004). There was no difference in rates of complications. Microdiscectomy versus open sequestrectomy and discectomy for surgical treatment of lumbar disc herniation is associated with similar clinical outcomes and reoperation rates. Open sequestrectomy is associated with shorter operation times. Microdiscectomy is associated with shorter hospitalization stays.