• Woodruff Gravgaard posted an update 5 months, 4 weeks ago

    nal autophagy.Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), are driven by neuroinflammation triggered by activated microglial cells; hence, the phenotypic regulation of these cells is an appealing target for intervention. Human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) may be a potential therapeutic candidate to treat NDs given their immunomodulatory properties. Evidence suggests that the mechanism of action of hAD-MSCs is through their secretome, which includes secreted factors such as cytokines, chemokines, or growth factors as well as extracellular vesicles (EVs). Recently, EVs have emerged as important mediators in cell communication given, they can transfer proteins, lipids, and RNA species (i.e., miRNA, mRNA, and tRNAs) to modulate recipient cells. However, the therapeutic potential of hAD-MSCs and their secreted EVs has not been fully elucidated with respect to human microglia. In this study, we determined the therapeutic potential of different hAD-MSCs doses (200,000, 100,000, and 50,000 cells) or their secreted EVs (50, 20, or 10 µg/ml), on human microglial cells (HMC3) that were activated by lipopolysaccharides (LPS). Upregulation of inducible nitric oxide synthase (iNOS), an activation marker of HMC3 cells, was prevented when they were cocultured with hAD-MSCs and EVs. Moreover, hAD-MSCs inhibited the secretion of proinflammatory factors, such as IL-6, IL-8, and MCP-1, while their secreted EVs promoted the expression of anti-inflammatory mediators such as IL-10 or TIMP-1 in activated microglia. The present data therefore support a role for hAD-MSCs and their secreted EVs, as potential therapeutic candidates for the treatment of NDs.Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human diseases. We aimed to identify the effect of the lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1)/miR-296/notch homolog protein 2 (NOTCH2) axis on the progression and radioresistance of lung cancer. Expression of AGAP2-AS1, miR-296, and NOTCH2 in lung cancer cells and tissues from radiosensitive and radioresistant patients was determined, and the predictive role of AGAP2-AS1 in the prognosis of patients was identified. THP-1 cells were induced and exosomes were extracted, and the lung cancer cells were respectively treated with silenced AGAP2-AS1, exosomes, and exosomes upregulating AGAP2-AS1 or downregulating miR-296. The cells were radiated under different doses, and the biological processes of cells were assessed. Moreover, the natural killing cell-mediated cytotoxicity on lung cancer cells was determined. The relationships between AGAP2-AS1 and miR-296, and between miR-296 and NOTCH2 were verified. AGAP2-AS1 and NOTCH2 increased while miR-296 decreased in radioresistant patients and lung cancer cells. The malignant behaviors of radioresistant cells were promoted compared with the parent cells. Inhibited AGAP2-AS1, macrophage-derived exosomes, and exosomes overexpressing AGAP2-AS1 or inhibiting miR-296 facilitated the malignant phenotypes of radioresistant lung cancer cells. Furthermore, AGAP2-AS1 negatively regulated miR-296, and NOTCH2 was targeted by miR-296. M2 macrophage-derived exosomal AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing miR-296 and elevating NOTCH2. Selleck DC661 This study may be helpful for the investigation of radiotherapy of lung cancer.Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%, P  less then  0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%, P  less then  0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%, P  less then  0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%, P  less then  0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median , 0.107 vs. 0.233 , P = 0.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.

    Accuracy of internal fit and microleakage for CAD-CAM systems used in metal coping fabrication and veneered with layering or pressing porcelain in ceramometallic restoration is unclear.

    A master metal die was milled to resemble the right mandibular first molar preparation for coverage with ceramometallic restoration. Master die was duplicated to twenty-four resin specimen dies.They were divided into two groups according to metal coping construction technique using either conventional (C) or CAD (D) wax. Each group was subdivided into two subgroups (n = 6) according to the technique of porcelain veneering (layered or pressed) to fabricate ceramometallic restorations, where subgroup (CL, DL) were conventionally layered by porcelain and (CP, DP) were press veneered. A standardized thickness of metal and porcelain was performed in all specimens as per manufacturer’s instructions for techniques ceramometallic restoration construction. Evaluation of internal fit was done with silicone replica technique using stchniques of ceramometallic restoration were considered reliable in restoration production within a clinically acceptable range regarding internal fit and microleakage. There is a strong positive correlation between internal fit and microleakage of ceramometallic restoration constructed.

    Both construction techniques of ceramometallic restoration were considered reliable in restoration production within a clinically acceptable range regarding internal fit and microleakage. There is a strong positive correlation between internal fit and microleakage of ceramometallic restoration constructed.

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