1 µM) and yangonin (IC50 of 15.0 µM). The synthesized analogues did not exhibit toxicity on HepG2 human hepatoma cells in vitro at concentrations of up to 40 µM. These findings confirm the previously-identified kavalactone scaffold as a promising chemotype for new anthelmintics and provide a basis for a detailed SAR investigation focused on developing a novel anthelmintic agent.Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter 5 mm per year) in patients with small/medium size AAA. Moreover, no correlation was found between MCE capacity and the aneurysm growth rate. A multivariate Cox regression analysis revealed a significant association between lower MCE capacity with the need for surgery in all AAA patients. Nevertheless, the significance was lost when only small/medium size AAA patients were included. Our results suggest that MCE, a major HDL functional activity, is not involved in AAA progression.Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.Nocturnal (night) eating syndrome and sleep-related eating disorder have common characteristics, but are considered to differ in their level of consciousness during eating behavior and recallability. To date, there have been no large population-based studies determining their similarities and differences. We conducted a cross-sectional web-based survey for Japanese young adults aged 19-25 years to identify factors associated with nocturnal eating behavior and sleep-related eating disorder-like behavior using Munich Parasomnia Screening and logistic regression. Of the 3347 participants, 160 (4.8%) reported experiencing nocturnal eating behavior and 73 (2.2%) reported experiencing sleep-related eating disorder-like behavior. Smoking (p less then 0.05), use of hypnotic medications (p less then 0.01), and previous and/or current sleepwalking (p less then 0.001) were associated with both nocturnal eating behavior and sleep-related eating disorder-like behavior. A delayed sleep-wake schedule (p less then 0.05) and sleep disturbance (p less then 0.01) were associated with nocturnal eating behavior but not with sleep-related eating disorder-like behavior. Both nocturnal eating behavior and sleep-related eating disorder-like behavior had features consistent with eating disorders or parasomnias. Nocturnal eating behavior but not sleep-related eating disorder-like behavior was characterized by a sleep-awake phase delay, perhaps representing an underlying pathophysiology of nocturnal eating syndrome.Improved implant osteointegration offers meaningful potential for orthopedic, spinal, and dental implants. In this study, a laser treatment was used for the structuring of a titanium alloy (Ti6Al4V) surface combined with a titanium dioxide coating, whereby a porous surface was created. The objective was to characterize the pore structure shape, treatment-related metallographic changes, cytocompatibility, and attachment of osteoblast-like cells (MG-63). The treatment generated specific bottleneck pore shapes, offering the potential for the interlocking of osteoblasts within undercuts in the implant surface. The pore dimensions were a bottleneck diameter of 27 µm (SD 4 µm), an inner pore width of 78 µm (SD 6 µm), and a pore depth of 129 µm (SD 8 µm). The introduced energy of the laser changed the metallic structure of the alloy within the heat-affected region (approximately 66 µm) without any indication of a micro cracking formation. The phase of the alloy (microcrystalline alpha + beta) was changed to a martensite alpha phase in the surface region and an alpha + beta phase in the transition region between the pores. The MG-63 cells adhered to the structured titanium surface within 30 min and grew with numerous filopodia over and into the pores over the following days. Cell viability was improved on the structured surface compared to pure titanium, indicating good cytocompatibility.  https://www.selleckchem.com/products/ipi-549.html  In particular, the demonstrated affinity of MG-63 cells to grow into the pores offers the potential to provide significantly improved implant fixation in further in vivo studies.Pancreatic cancer is one of the deadliest cancer types urgently requiring effective therapeutic strategies. Autophagy occurs in several compartments of pancreatic cancer tissue including cancer cells, cancer associated fibroblasts, and immune cells where it can be subjected to a multitude of stimulatory and inhibitory signals fine-tuning its activity. Therefore, the effects of autophagy on pancreatic carcinogenesis and progression differ in a stage and context dependent manner. In the initiation stage autophagy hinders development of preneoplastic lesions; in the progression stage however, autophagy promotes tumor growth. This double-edged action of autophagy makes it a hard therapeutic target. Indeed, autophagy inhibitors have not yet shown survival improvements in clinical trials, indicating a need for better evaluation of existing results and smarter targeting techniques. Clearly, the role of autophagy in pancreatic cancer is complex and many aspects have to be considered when moving from the bench to the bedside.