The CCAAT/enhancer binding protein delta (CEBPD, C/EBPδ, NF-IL6β) is induced in many inflammation-related diseases, suggesting that CEBPD and its downstream targets may play central roles in these conditions. Neuropathological studies show that a neuroinflammatory response parallels the early stages of Alzheimer's disease (AD). However, the precise mechanistic correlation between inflammation and AD pathogenesis remains unclear. CEBPD is upregulated in the astrocytes of AD patients. Therefore, we asked if activation of astrocytic CEBPD could contribute to AD pathogenesis. In this report, a novel role of CEBPD in attenuating macrophage-mediated phagocytosis of damaged neuron cells was found. By global gene expression profiling, we identified the inflammatory marker pentraxin-3 (PTX3, TNFAIP5, TSG-14) as a CEBPD target in astrocytes. Furthermore, we demonstrate that PTX3 participates in the attenuation of macrophage-mediated phagocytosis of damaged neuron cells. This study provides the first demonstration of a role for astrocytic CEBPD and the CEBPD-regulated molecule PTX3 in the accumulation of damaged neurons, which is a hallmark of AD pathogenesis.

BackgroundThe up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear.Methodology and Principal FindingsWe found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd−/− mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd−/− mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd−/− mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd−/− mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena.Conclusions and SignificanceCollectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.

The authors have fabricated the pentacene thin films on polymethylmethacrylate ͑PMMA͒ and on silicon dioxide dielectric surfaces featuring similar surface energy and surface roughness. On both surfaces the pentacene films displayed high crystal quality from x-ray diffraction scans, although the film on PMMA had significantly smaller grain size. The pentacene transistors with PMMA exhibited excellent electrical characteristics, including high mobility of above 1.1 cm 2 / V s, on/off ratio above 10 6 , and sharp subthreshold slope below 1 V / decade. The analysis of molecular microstructure of the pentacene films provided a reasonable explanation for the high performance using resonance micro-Raman spectroscopy.The performance of organic thin-film transistors ͑OT-FTs͒ has greatly improved lately. In particular, we can see performance improvements in conjugated oligoacenes, i.e., pentacene. 1-3 Pentacene, deposited on dielectric surfaces with surface-induced structure, forms a polycrystalline thin film with grain morphology. 1 General assumptions suggest that mobility properties appear to be dominated by grain boundary effects that occur due to the large amount of charged trapping states at the boundary. 1,2,4 Most researchers utilize crystal structure and grain size to interpret the performance of OTFTs. However, some reported data are not consistent with the observations presented above. 3,5,6 Whether in the intragrain or in grain boundary of organic film, the structures still have weak van der Waals forces, unlike the inorganic polycrystalline media. However, little is known about the importance of molecular structure and microstructure within a polycrystalline organic film on OTFT performance.Surface properties of a dielectric layer, i.e., surface energy ͑␥ s ͒ and surface roughness ͑R rms ͒, are the distinctive factors that determine potential improvements in electric characteristics of OTFT. 7 Polymeric insulators have been considered as a preferable surface modification layer and/or gate dielectric materials due to their numerous advantages over inorganic materials. Therefore, in addition to studying the ␥ s and R rms , it is also interesting to explore the influence of polar groups of polymer insulators on the structure of organic semiconductors and the corresponding performance of OTFTs.In this letter, we have investigated the crystal structure, thin-film morphology, and molecular structure and microstructure of pentacene films grown on the polymeric and inorganic dielectric surfaces with similar ␥ s and R rms values. Hence, the impact of different ␥ s and R rms values could be distinguished. The study includes silicon dioxide ͑SiO 2 , ␥ s = 49.8 mJ/ m 2 , R rms = 4.8 Å͒ and polymethylmethacrylate ͑PMMA͒ ͑␥ s = 49.1 mJ/ m 2 , R rms = 5.0 Å͒ surfaces. We should note that the pentacene film, grown on PMMA surface with a very small grain size, allows the production of OTFTs with very good performance characteristics. Here, we used x-ray diffraction ͑XRD͒, atomic force microscope ͑AFM͒, and resonance micro-Rama...

Aims Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Methods Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies. Results PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. Conclusion Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514–525.

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Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.

Background Cyclooxygenase-2 (COX-2) inhibitors are prescribed for the management of osteoarthritis (OA)-associated pain and inflammation. However, the role of COX-2 in normal and osteoarthritic articular chondrocytes has not been well investigated. We hypothesize that COX-2 plays a role in articular chondrocytes under normal conditions and during OA progression. Methods In vivo COX-2 levels in articular cartilage of normal and papain-induced osteoarthritic rats were compared. The role of COX-2 in human articular chondrocytes (HACs) was tested in vitro by COX-2 overexpression or activity inhibition. The levels of COX-2 and marker gene for normal function or articular cartilage degeneration were evaluated: mRNA by qRT-PCR; proteins by western blotting or immunohistochemistry; and glycosaminoglycan (GAG) by Safranin O–fast green staining. Parathyroid hormone-related protein (PTHrP) promoter activity was detected with luciferase reporter assays. Results In the OA rat study, COX-2 and PTHrP were simultaneously increased in osteoarthritic rat chondrocytes, while increased PTHrP levels were reduced by celecoxib, a COX-2 selective inhibitor. The levels of normal cartilage matrices, GAG and type II collagen decreased, while markers of degeneration, collagen type X and MMP13 were elevated in osteoarthritic articular chondrocytes. Celecoxib rescued the loss of GAG and the increased collagen type X and MMP13 levels. In vitro, COX-2 overexpression in HACs significantly increased Col2a1, Col10a1, PTHrP and MMP13 mRNA expression, which was decreased when COX-2 activity was suppressed. More importantly, COX-2 overexpression upregulated the PTHrP transcription, mRNA expression and protein levels. Conclusion COX-2 plays a pathophysiological role by preventing terminal differentiation of articular chondrocytes by upregulating PTHrP expression at the early stage of OA progression. The Translational potential of this article COX2 up-regulates PTHrP expression in normal and OA articular chondrocytes.

Neurofibromas may arise anywhere along a nerve from the dorsal root ganglion to the terminal nerve branches; however, peroneal nerve involvement is not common. Surgical resection of neurofibroma with total preservation of nerve function had been thought to be difficult. Here, we report a case of an intermuscular intraneural neurofibroma derived from the deep peroneal nerve in a patient with neurofibromatosis type 1. The diagnostic criteria, characteristics of imaging studies, and operative approach are described. The function of the deep peroneal nerve was preserved, with satisfactory results.