-
Sunesen Lohse ha publicado una actualización hace 11 horas, 29 minutos
There is a need for more evidence showing the benefit of immune check inhibitors in non-small cell lung cancer patients ≥75 years.Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) protein is expressed in all virus-associated malignancies, where it performs an essential role in the maintenance, replication and transcription of the EBV genome. In recent years, it has become apparent that EBNA1 can also influence cellular gene transcription. Here, we demonstrate that EBNA1 is able to stimulate the expression of the Transforming growth factor-beta (TGFβ) superfamily member, bone morphogenic protein 2 (BMP2), with consequential activation of the BMP signalling pathway in carcinoma cell lines. We show that BMP pathway activation is associated with an increase in the migratory capacity of carcinoma cells, an effect that can be ablated by the BMP antagonist, Noggin. Gene expression profiling of authentic EBV-positive nasopharyngeal carcinoma (NPC) tumours revealed the consistent presence of BMP ligands, established BMP pathway effectors and putative target genes, constituting a prominent BMP «signature» in this virus-associated cancer. Our findings show that EBNA1 is the major viral-encoded protein responsible for activating the BMP signalling pathway in carcinoma cells and supports a role for this pathway in promoting cell migration and possibly, metastatic spread.A thermally activated shape memory polymer based on the mixture of polycaprolactone (PCL) and polydimethylsiloxane (PDMS) was fabricated into the nanofibre mesh using the electrospinning process. The added percentages of the PDMS segment in the PCL-based polymer influenced the mechanical properties. Polycaprolactone serves as a switching segment to adjust the melting temperature of the shape memory electro-spun PCL-PDMS scaffolds to our body temperature at around 37 °C. LDN-193189 Three electro-spun PCL-PDMS copolymer nanofibre samples, including PCL6-PDMS4, PCL7-PDMS3 and PCL8-PDMS2, were characterised to study the thermal and mechanical properties along with the shape memory responses. The results from the experiment showed that the PCL switching segment ratio determines the crystallinity of the copolymer nanofibres, where a higher PCL ratio results in a higher degree of crystallinity. In contrast, the results showed that the mechanical properties of the copolymer samples decreased with the PCL composition ratio. After five thermomechanical cycles, the fabricated copolymer nanofibres exhibited excellent shape memory properties with 98% shape fixity and above 100% recovery ratio. Moreover, biological experiments were applied to evaluate the biocompatibility of the fabricated PCL-PDMS nanofibre mesh. Owing to the thermally activated shape memory performance, the electro-spun PCL-PDMS fibrous mesh has a high potential for biomedical applications such as medical shrinkable tubing and wire.The efficacy of analgesics such as meloxicam and ketoprofen to control pain in piglets when mixed with iron dextran (ID) before injection is unknown. The purpose of this study was to compare perceived pain in castrated piglets treated 1 h before castration with either of these drugs alone, or when mixed with ID, by observing the time it takes for piglets to navigate a chute. Piglets were divided into seven treatment groups (n = 25 piglets per treatment group) including castration with analgesia (meloxicam or ketoprofen), castration with analgesic plus ID, castration without analgesic or ID, sham handled and given ID, and sham handled alone. Piglets were placed in a short chute and their time to navigate the chute was recorded at four timepoints following castration. Piglets given meloxicam or ketoprofen, with or without ID did not differ from each other in their chute navigation times. Additionally, these piglets did not differ from treatment groups that were not castrated. Piglets castrated without analgesia had significantly longer navigation times. These results indicate that meloxicam or ketoprofen, whether mixed with ID prior to injection or not, provide similar analgesic efficacy.Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, non-invasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest.