International journal of molecular sciences
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Lysosomal-associated membrane protein 3 (LAMP3), identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC) is still unknown. ⋯ LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037). Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17-3.09, p = 0.010) and disease-free survival (HR = 1.80, 95% CI = 1.18-2.74, p = 0.006). In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.
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Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. ⋯ This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL).
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Based on own translational research of the biochemical and hormonal effects of cow's milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. ⋯ In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases.
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Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. ⋯ Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia's therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.
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Review
Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis.
Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. ⋯ To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients.