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Extracellular vesicles (EVs), nanovesicles released by cells to effectively exchange biological information, are gaining interest as drug delivery system. Yet, analogously to liposomes, they show short blood circulation times and accumulation in the liver and the spleen. For tissue specific delivery, EV surfaces will thus have to be functionalized. We present a novel platform for flexible modification of EVs with target-specific ligands based on the avidin-biotin system. Genetic engineering of donor cells with a glycosylphosphatidylinositol-anchored avidin (GPI-Av) construct allows the isolation of EVs displaying avidin on their surface, functionalized with any biotinylated ligand. For proof of concept, GPI-Av EVs were modified with i) a biotinylated antibody or ii) de novo designed and synthesized biotinylated ligands binding carbonic anhydrase IX (CAIX), a membrane associated enzyme overexpressed in cancer. Functionalized EVs showed specific binding and uptake by CAIX-expressing cells, demonstrating the power of the system to prepare EVs for cell-specific drug delivery., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: The purpose of the study was to evaluate the relationship of implant-related injuries to the adjacent anatomical structures in a newer generation straight proximal humeral nail (PHN) regarding different entry points. The proximity of the proximal lateral locking-screws of the MultiLoc proximal humeral nail (ML PHN) may cause iatrogenic tendon injuries to the lateral edge of the bicipital humeral groove (BG) as reference point for the tendon of the long head of biceps brachii (LBT) as well as the lateral insertion of the infraspinatus tendon (IST)., Materials and Methods: The study comprised n = 40 upper extremities. Nail application was performed through a deltoid approach and supraspinatus tendon (SSP) split with a ML PHN. All tests were performed in three different entry points. First nail (N1) - standard position in line with the humeral shaft axis; second nail (N2) - a more lateral entry point; third alternative (N3) - medial position, centre of the humeral head. After nail placement, each specimen was screened for potential implant-related injuries or worded differently hit rates (HR) to the BG and the IST. The distances to the anatomical structures were measured and statistically interpreted., Results: The observed iatrogenic IST injury rate was 17.5% (n = 7/40) for N1, 5% (n = 2/40) for N2 and 62.5% (n = 25/40) for N3, which was statistically significantly higher (p < 0.001). Regarding the BG, the evaluated HR was 7.5% (n = 3/40) for both N1 and N2. Only the nail placed in the head centre (N3) showed an iatrogenic injury rate of 20% (n = 8/40) (p < 0.062). No statistically significant association between humeral head size and the HR could be observed (head diameter: IST: p = 0.323, BG: p = 0.621; head circumference: IST: p = 0.167; BG: p = 0.940). For the IST and BG, all distances in nail positions N1 and N2 as well as N2 and N3 differ statistically significant (p < 0.001)., Conclusions: An entry point for nail placement in line or slightly laterally to the humeral shaft axis - but still at the cartilage - should be advocated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Epidermolysis bullosa, a group of heritable blistering disorders, shows extensive phenotypic variability due to mutations in as many as 20 distinct genes. There is no cure for this devastating group of disorders; however, a number of preclinical developments show promise, and some approaches have already reached the stage of early clinical trials. Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International, a global coalition of national patient organizations advocating on behalf of the patients and families with epidermolysis bullosa, supports research and organizes periodic scientific and clinical meetings on this disease. The most recent meeting, EB2017, was held in Salzburg in September 2017. This report summarizes some of the recent research and clinical developments that have identified promising avenues toward treatment and perhaps eventual cure, with improved quality of life for patients with epidermolysis bullosa., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Opinions vary concerning the position of forearm rotation during detachment of the supinator in radial nerve palsy Henry's and Thompson's approaches., Purpose: To define the optimal forearm position for a safe detachment of the supinator during these approaches and to clarify their close relationship to the posterior interosseous nerve (PIN)., Methods: The study sample comprised 90 upper extremities of 45 human adult cadavers, embalmed using Thiel's method. After detection of the radial nerve in the interval between the brachialis and brachioradialis, its pathway was traced to the Arcade of Frohse (AF). Measurements involved the distance between the AFand the radial border of the distal biceps tendon (DBT) in pronation and supination, the interval between the AF and the radiocapitellar joint space (RCJS) in supination and the radial length (RL)., Results: Distances between the DBT and the AF were significantly shorter during pronation (right side: 14.1 ± 3.4mm; left side: 13.5 ± 3.2mm) compared with supination (right side: 20.5 ± 3.6mm; left side: 19.8 ± 3.5mm) for both right and left extremities. The mean interval between the AF and the centre of the RCJS was 25.2 ± 5.9mm for the right side and 24.7 ± 5.6mm for the left side, which correlated positively with the RL., Conclusion: These results indicate a safe detachment of the supinator from the radius with the forearm placed in supination during both Henry's and Thompson's approaches., (© 2017 Elsevier Ltd. All rights reserved.)

Ten new sesquiterpene alcohols of which seven germacranes, a eudesmane, a guaiane and an oplopane were isolated from the aerial parts of Artemisia alba Turra. Their structures and relative stereochemistry were elucidated by spectral methods ((1)H and (13)C NMR, COSY, HSQC, HMBC, NOESY, and MS). In addition, the known 7-hydroxycadin-4-en-3-one, centaureidin and axillarin were found for the first time in the studied species., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Here we characterize the biological activity of a hairpin polyamide 1 that inhibits binding of the minor-groove transcription factor LEF-1, constitutively expressed in colon cancers. Genome-wide analysis of mRNA expression in DLD1 colon cancer cells treated with 1 reveals that a limited number of genes are affected; the most significant changes correspond to genes related to cell cycle, signaling, and proteolysis rather than the anticipated WNT signaling pathway. Treated cells display increased doubling time and hypersensitivity to DNA damage that most likely results from downregulation of DNA-damage checkpoint genes, including YWAE (14-3-3epsilon protein) and DDIT3. Promoter analyses on a genomic level revealed numerous potential polyamide binding sites and multiple possible mechanisms for transcriptional antagonism, underscoring the utility of gene expression profiling in understanding the effects of polyamides on transcription at the cellular level.