Musculoskeletal diseases are extremely widespread and a significant burden on the health systems of the industrialized countries. The use of mesenchymal stromal cells is a promising approach to cure cartilage and tendon injuries, which often also occur in younger people as consequences of sport accidents. Although particular interest is on the collagen and the glycosaminoglycan composition of the tendon and potential alterations compared to healthy tissue, there is nowadays also increasing evidence that some selected phospholipids (PL) are potential mediators of tissue regeneration. Therefore, PL (and potential changes thereof) attract increasing interest in this field. We have used positive and negative ion matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to elucidate the lipid compositions of human mesenchymal stromal cells in dependence on the composition of the cell culture medium and the cultivation time. The de novo biosynthesis of PL was monitored by adding biosynthesis pathway. This pathway does not make use of glucose but relies on the use of other molecules as energy sources. Potential pathways to explain the experimental observations are discussed.Unbiased, all-atom simulations of mixtures representative of the inner and outer leaflets of a mammalian red blood cell and a synaptic vesicle reveal many cholesterol flip-flop events over the 5 μsec duration of the simulations. Enough events are observed for a direct estimate of the flip-flop rate. Slower rates are found in more ordered membranes, and faster rates in more disordered membranes, consistent with earlier reports in the literature. However, the rates found here are neither as fast as the fastest nor as slow as the slowest rates obtained by previous simulations. The difference likely stems from the compositions studied here, which unlike previous work include exclusively lipids with differing acyl chains, as observed in mammalian lipidomes.While liposomes have proven to be effective drug delivery nanocarriers, their therapeutic attributes could be improved through the development of clinically viable triggered release strategies in which encapsulated drug contents could be selectively released at the sites of diseased cells. As such, a significant amount of research has been reported involving the development of stimuli-responsive liposomes and a broad range of strategies have been explored for driving content release. These have included the introduction of trigger groups at either the lipid headgroup or within the acyl chains that alter lipid self-assembly properties of known lipids as well as the rational design of lipid analogs programed to undergo conformational changes induced by events such as binding interactions. This review article describes advances in the design of stimuli-responsive liposome strategies with an eye towards emerging trends in the field.

Neuropathic pain (NPP) is the common symptom of most clinical diseases, and its treatment has always been a difficult problem at present. Therefore, the purpose of this study is to explore a new method for the treatment of NPP by transplanting olfactory ensheathing cells combined with chitosan (OECs-CS).

Animal model of chronic compression sciatic nerve injury (CCI) was made, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) biomaterials were prepared, and biocompatibility of OECs and CS were detected by MTT method, OECs and OECs-CS were transplanted into the site of the injured sciatic nerve respectively, behavioral method was used to measured the mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. On days 7 and 14 after surgery, the expression level of P2X7 receptor (P2X7R) in the L4-5 spinal cord was measured by using in situ hybridization, western-blotting and qRT-PCR. To explore the therapeutic effect of OECs-CS transplantation on pain suppression.

Aftn inhibit P2X7R overexpression mediated NPP, while OECs-CS transplantation has better therapeutic effect than OECs transplantation alone. Our results provide a novel method and theoretical basis for the treatment of NPP.Extracellular vesicle (EV) biology involves understanding the cellular and molecular mechanisms of cell communication. Studies conducted so far with various bacterial infection models demonstrate the release of various types of EVs that include exosomes and microvesicles. Depending upon the infection and cell type, EV cargo composition changes and ultimately might impact the host immune response and bacterial growth. The mechanisms behind the EVs release, cargo composition, and impact on the immune system have not been fully investigated. Future research needs to include in vivo models to understand the relevance of EVs in host immune function during bacterial infection, and to determine aspects that are shared or species-specific in the host. This would aid in the development of EVs as therapeutics or as markers of disease.Cisplatin induces acute renal failure in humans and mice.Tubular apoptosis, necrosis and inflammation are the primary pathogenesis of cisplatin-induced acute kidney injury(AKI). We previously reported that the depletion of Numb from proximal tubules exacerbates tubular cells apoptosis in cisplatin-induced AKI, however, the role of Numb in tubular necrosis and renal inflammation in cisplatin-induced AKI remains unclear. A mouse model of AKI was produced by cisplatin intraperitoneally injection in mice from proximal tubule-specific depletion of Numb (PT-Nb-KO) and their wild-type littermates (PT-Nb-WT) respectively. Renal Numb expression was determined by Western blotting. Renal morphological damage was examined by hematoxylin and eosin staining (H&E staining). Tubular necrosis was evaluated by histological study and the protein level of renal Mixed lineage kinase domain-like protein (MLKL) which is a molecular marker of necrosis. Leukocyte infiltration and pro-inflammatory cytokines was determined by immunostaining and quantitative real-time PCR (qRT-PCR) respectively.The protein level of Numb was dramatically decreased in kidneys of PT-Nb-KO mice compared with PT-Nb-WT mice. After cisplatin injection, a significant increase of tubular injury score and the protein level of renal MLKL were detected in PT-Nb-KO mice compared with those in PT-Nb-WT. In addition, the number of F4/80-positve and CD3-positive cells, markers for macrophages and neutraphils respectively, showed significantly increased in kidneys from PT-Nb-KO mice compared with those in PT-Nb-WT mice. Consistently, the gene expression of pro-inflammatory cytokines including TNF-α and MCP-1 in the kidneys was higher in PT-Nb-KO mice than those in PT-Nb-WT mice. Numb play additional protective role in cisplatin-induced AKI through ameliorating tubular necrosis and renal inflammation besides attenuating cisplatin-induced tubular apoptosis.Cytochrome c (cytc) is a heme protein of 12 kDa that transfers electrons in the mitochondrial respiratory chain. Increased cytc peroxidase activity leads to cardiolipin (CL) oxidation, a hallmark of early apoptosis stage. Here, we aimed to investigate the interaction between cytc with cardiolipin hydroperoxide (CLOOH) in a mimetic mitochondrial membrane. Cytc-CL peroxidase reaction occurred at faster rates with CLOOH than with H2O2. Moreover, liposomes containing CLOOH promoted increased protein aggregation with minor or no release of cytc from the membrane. Dimeric and trimeric cytc species were observed in the first 15 min, followed by increased formation of high-molecular-weight aggregates afterwards. nLC-MS/MS analysis identified several Lys and His residues covalently modified by lipid aldehydes that showed mass increments corresponding to 4-hydroxynonenal (HNE), 4-oxononenal (ONE), hexanoyl, heptenal and octenal addition. Noteworthy, most modifications were observed at Lys and His residues located at A-site (K73, K87, K88), L-site (H26, H33, and K27) membrane binding sites. Further, dityrosine cross-linked peptides were also characterized at residues Y48-Y74, Y48-Y97 and Y74-Y97. Collectively, our findings show that CLOOH causes irreversible protein damage and crosslinking of cytc in the membrane.The hydrolysis of β-lactam antibiotics by class C β-lactamases proceeds through the acylation and the rate-determining deacylation steps mediated by the nucleophilic serine and the deacylation water, respectively. The pose of poor substrates such as carbapenems in the acylated enzyme is responsible for the low efficient deacylation reaction. Here we present the crystal structures of the Y150F variant of the ACC-1 class C β-lactamase in the apo and acylated states. In the acylated enzyme complexed with two carbapenems, imipenem and meropenem, the lactam carbonyl oxygen is located in the oxyanion hole. However, the five-membered pyrroline ring displays a novel orientation that has not been reported so far. The ring is rotated such that its C3 carboxylate makes salt bridges with Lys67 and Ly315, which is accompanied by the side-chain rotamer change of Phe150. The C3 carboxylate is placed where the deacylation water occupies in the apo-enzyme, which, together with the displacement of the catalytic base residue at position 150, explains why carbapenems are poor substrates of ACC-1.Opportunities to share or sell images are common in radiology. But because these images typically originate as protected health information, their use admits a host of ethical and regulatory considerations. This article discusses four scenarios that reflect data sharing or selling arrangements in radiology, especially as they might occur in „big data” systems or applications. The objective of this article is to acquaint radiologists with a variety of regulatory standards and ethical perspectives that pertain to certain data use agreements, such that the attitudes and practices of data holders and their sharers or purchasers can withstand ethical or regulatory scrutiny and not invite undesirable outcomes.

To determine the effect of dual tasking on trunk muscle endurance in patients after lumbar diskectomy.

Cross-sectional study.

Rehabilitation hospital setting.

Individuals (N=14) undergoing primary lumbar diskectomy.

Using a randomized design on 2 separate days, muscle endurance was evaluated during prone bridging and Biering-Sorensen tests. Each test was randomly performed under 2 cognitive conditions single task without cognitive condition and self-regulated dual task (ie, mathematical task).

The primary outcomes were time to failure and pain assessed by the visual analog scale from 0 to 100 mm. The secondary outcomes were kinesiophobia assessed by the Tampa Scale and disability assessed by the Oswestry Disability Index. Associations were tested using a repeated measures analysis of variance with relevant interaction test.

A significant interaction between condition, endurance tests, and kinesiophobia (P=.005) was found. The post hoc comparison showed positive effects between cognitive conditiol task is associated with fear avoidance, especially during back extension. This strategy seems especially relevant for patients with high levels of fear avoidance and may be used to improve trunk muscle endurance.