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Monocyte-derived cells were shown to promote cartilage repair in osteoarthritis. The role of the long non-coding RNA (lncRNA) MM2P in this function of monocyte-derived cells remained unexplored. Treatment of RAW264.7 murine macrophages and mouse bone marrow-derived macrophages with IL-4 or IL-13 upregulated MM2P expression, upstream of STAT3 and STAT6 phosphorylation. Specifically, MM2P blocked SHP2-mediated dephosphorylation of STAT3 at Try705 and interacted with the RNA-binding protein FUS. In turn, p-STAT3 increased the Sox9 gene expression. These cells released Sox9 mRNA and protein-containing exosomes, as demonstrated by a transmission electron microscope, nanoparticle tracking analysis, and detection of typical surface markers. Their culture supernatant promoted the differentiation of mouse primary chondrocytes, i.e., upregulated the expression of Col1a2 and Acan genes and promoted the secretion of extracellular matrix components proteoglycan and type II collagen. These effects were mediated by Sox9 mRNA and protein delivered to chondrocytes by exosomes. Together, ex vivo treatment of monocyte-derived cells with IL-4 or IL-13 promoted chondrocyte differentiation and functions through exosome-mediated delivery of Sox9 mRNA and protein.

Poor platelet graft function (PPGF) is a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no optimal treatment has been recommended. This study investigated aspects of platelet recovery after allo-HSCT, including prognostic value and the effect of recombinant human thrombopoietin (rhTPO). We retrospectively analyzed 275 patients who received allo-HSCT in our center. Of them, 135 (49.1%) patients had good platelet graft function (GPGF) and 140 (50.9%) had PPGF. The latter included 59 (21.5%) patients with primary PPGF and 81 (29.4%) with secondary PPGF. Multivariate analysis showed that male gender (P = .024), lower CD34 cell count (P = .04), and no use of rhTPO (P <.001) were associated with PPGF. The 3-year overall survival rate of patients with PPGF (58%) was significantly less than that of patients with GPGF (82%; P <.001). We further analyzed the effect of rhTPO on prognosis of patients after allo-HSCT. Although no advantage was apparent when analyzing the entire cohort, for patients with myelodysplastic syndromes and aplastic anemia, rhTPO was associated with a significant survival advantage (P = .014).

Osteosarcoma (OS) is a common malignant primary bone tumor and patients with OS are known to have a poor response to chemotherapy. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules (approximately 22 nucleotides in length) and they have recently become a topic for research as regards their role in cancer therapeutics. Previous studies have reported miR‑18a expression in patients with OS is significantly decreased compared with that in normal adjacent tissue. miR‑18a belongs to the miR‑17‑92 cluster encoded by the host gene MIR17HG. However, the detailed role of miR‑18a in OS remains to be determined. In this study, we demonstrated that miR‑18a mimics inhibited MG63 and Saos‑2 cell viability and migration. In addition, flow cytometry assay revealed that miR‑18a induced OS cell apoptosis. Western blot analysis indicated that the expression levels of Bcl‑2 and p‑Akt were downregulated, while the levels of cleaved caspase‑3 and Bax proteins were upregulated by miR‑18a. Moreover, we demonstrated that mediator complex subunit 27 (MED27) was the target of miR‑18a through dual luciferase assay. Finally, data from in vivo experiments indicated that tumor growth in mice was significantly suppressed by miR‑18a mimics, accompanied by a decrease in the percentage of Ki67-positive cells, and by the downregulation in MED27 and p‑Akt protein expression levels. The findings of the present study may aid in the clarification of the function of miR‑18a, particularly as regards its role in the regulation of OS cell apoptosis, and indicate that MED27 may be a potential novel therapeutic target in the treatment of OS.

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The role of autologous stem cell transplantation (ASCT) as a frontline treatment in patients with diffuse large B cell lymphoma (DLBCL) who are in their first remission has not been fully elucidated in the rituximab era. We analyzed 272 DLBCL patients who received 4–6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or R-CHOP followed by ASCT, from January 2005 to June 2013 in our institution. Multivariate analysis showed the none germinal center B cell (non-GCB) subtype (P=0.014, P=0.012) and International Prognostic Index (IPI) (3–5) (P=0.004, P=0.016) were independent unfavorable predictors of overall survival (OS) and progression-free survival (PFS), respectively. To investigate the treatment effect of upfront ASCT, we selected 94 high-intermediate and high-risk DLBCL patients who achieved complete remission after R-CHOP, with 41 in the ASCT and 53 in the non-ASCT groups. Survival analysis revealed patients who received upfront ASCT compared with those who did not had better OS (3-year OS: 74.5% vs. 50.4%, P=0.029) or PFS (3-year PFS: 59.6% vs. 32.1%, P=0.004), suggesting up-front ASCT following R-CHOP could improve the outcome of high-intermediate and high-risk DLBCL patients.

Background: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring. Methods: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF. Results: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67–2.66], P <0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction. Conclusions: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.