RESUMEN
Whole-body vibration therapy is an intentional biomechanical stimulation of the body using various frequencies of vibrations with the motive of health improvement. Ever since its discovery, this therapy has been extensively used in physiotherapeutic measures and the sports industry. For its property of increasing bone mass and density, space agencies use this therapy on astronauts who return to Earth after long-term space missions to regain lost bone and muscle mass. The potential of this therapy to restore bone mass encouraged researchers to look for its scope in the treatment of age-related bone degenerative diseases such as osteoporosis and sarcopenia, as well as in the correction of posture control and gait in geriatrics and post-menopausal women. Osteoporosis and osteopenia account for roughly half of all fractures worldwide. These degenerative diseases also cause gait and posture changes. Bisphosphonates, monoclonal antibodies, parathyroid hormone fragments, hormone replacement therapies, and calcium and vitamin D supplementation are among the medical treatments available. Lifestyle changes and physical exercise are advised. However, vibration therapy's scope as a treatment option is yet to be explored. The safe range of frequency, amplitude, duration, and intensity of the therapy is still to be determined. This article is a review of the results of various clinical trials done in the last 10 years that target the effect of vibration therapy in both osteoporotic women and the elderly for the treatment of such ailments and deformities. We collected data from PubMed using advanced search and applied the exclusion criteria. In total, we analyzed nine clinical trials.
RESUMEN
Cyclic nucleotides (cAMP & cGMP) are critical intracellular second messengers involved in the transduction of a diverse array of stimuli and their catabolism is mediated by phosphodiesterases (PDEs). We previously detected focal genomic amplification of PDE1C in >90 glioblastoma multiforme (GBM) cells suggesting a potential as a novel therapeutic target in these cells. In this report, we show that genomic gain of PDE1C was associated with increased expression in low passage GBM-derived cell cultures. We demonstrate that PDE1C is essential in driving cell proliferation, migration and invasion in GBM cultures since silencing of this gene significantly mitigates these functions. We also define the mechanistic basis of this functional effect through whole genome expression analysis by identifying down-stream gene effectors of PDE1C which are involved in cell cycle and cell adhesion regulation. In addition, we also demonstrate that Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no effect on invasion/migration. Up-regulation of at least one of this gene set (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is associated with worse outcome and PDE1C silencing down-regulated their expression, thus also indicating potential to influence patient survival. Therefore we conclude that proliferation, migration, and invasion of GBM cells could also be regulated downstream of PDE1C.
