Oncotarget
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Physical exercise, a potent functional intervention in protecting against cardiovascular diseases, is a hot topic in recent years. Exercise has been shown to reduce cardiac risk factors, protect against myocardial damage, and increase cardiac function. This improves quality of life and decreases mortality and morbidity in a variety of cardiovascular diseases, including myocardial infarction, cardiac ischemia/reperfusion injury, diabetic cardiomyopathy, cardiac aging, and pulmonary hypertension. ⋯ The cellular adaptations associated with exercise are due to the activation of several signaling pathways, in particular, the growth factor neuregulin1 (NRG1)-ErbB4-C/EBPβ and insulin-like growth factor (IGF)-1-PI3k-Akt signaling pathways. Of interest, microRNAs (miRNAs, miRs) such as miR-222 also play a major role in the beneficial effects of exercise. Thus, exploring the mechanisms mediating exercise-induced benefits will be instrumental for devising new effective therapies against cardiovascular diseases.
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Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. ⋯ Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.
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The histiocytoses are rare tumors characterized by the primary accumulation and tissue infiltration of histiocytes and dendritic cells. Identification of the activating BRAFV600E mutation in Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) cases provided the basis for the treatment with BRAF and/or MEK inhibitors, but additional treatment options are needed. Twenty-four cases of neoplastic histiocytic diseases [11 extrapulmonary LCH, 4 ECD, 4 extranodal Rosai-Dorfman disease (RDD), 3 follicular dendritic cell sarcoma (FDCS), 1 histiocytic sarcoma (HS) and 1 blastic plasmacytoid dendritic cell neoplasm (BPDCN)] were analyzed using immunohistochemical and mutational analysis in search of biomarkers for targeted therapy. ⋯ Increased expression of PD-L1 (≥2+/≥5%) was seen in 3/4 ECD, 7/8 LCH, 3/3 FDCS and 1/1 HS, with overall 81% concordance between 2 antibodies used in the study (SP142 vs. MAB1561 clone). These results show for the first time significant expression of the PD-L1 immune checkpoint protein in these disorders, which may provide rationale for addition of immune check-point inhibitors in treatment of disseminated and/or refractory histiocytoses.