Notes

The function regarding lncRNAs within Rare Tumors having a Focus on HOX Transcript Antisense RNA (HOTAIR).
Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.As an indispensable structure protein, the herpes simplex virus 1 (HSV-1) UL6 has been described to exert numerous roles in viral proliferation. However, its exact subcellular localization and subcellular transport mechanism is not well known. In the present study, by utilizing confocal fluorescent microscopy, UL6 was shown to mainly locate in the nucleus in enhanced yellow fluorescent protein or Flag tag fused expression plasmid-transfected cells or HSV-1-infected cells, whereas its predicted nuclear localization signal was nonfunctional. In addition, by exploiting dominant negative mutant and inhibitor of different nuclear import receptors, as well as co-immunoprecipitation and RNA interference assays, UL6 was established to interact with importin α1, importin α7 and transportin-1 to mediate its nuclear translocation under the help of Ran-mediated GTP hydrolysis. Accordingly, these results will advance the knowledge of UL6-mediated biological significances in HSV-1 infection cycle.BACKGROUND Colorectal cancer (CRC) accounts for the highest fatality rate among all malignant tumors. Immunotherapy has shown great promise in management of many malignant tumors, necessitating the need to explore its role in CRC. RESULTS Our analysis revealed a total of 71 differentially expressed IRGs, that were associated with prognosis of CRC patients. Ten IRGs (FABP4, IGKV1-33, IGKV2D-40, IGLV6-57, NGF, RETNLB, UCN, VIP, NGFR, and OXTR) showed high prognostic performance in predicting CRC outcomes, and were further associated with tumor burden, metastasis, tumor TNM stage, gender, age, and pathological stage. Interestingly, the IRG-based prognostic index (IRGPI) reflected infiltration of multiple immune cell types. CONCLUSIONS This model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor prognosis of CRC. METHODS We performed a comprehensive analysis of expression profiles for immune-related genes (IRGs) and overall survival time in 437 CRC patients from the TCGA database. We employed computational algorithms and Cox regression analysis to estimate the relationship between differentially expressed IRGs and survival rates in CRC patients. Furthermore, we investigated the mechanisms of action of the IRGs involved in CRC, and established a novel prognostic index based on multivariate Cox models.Recently, Mahalanobis distance (DM) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed DM variants using sets of biomarkers collected at the two visits of the Long Life Family Study (LLFS) and performed joint analyses of longitudinal observations of DM and follow-up mortality in LLFS using joint models. We found that DM is significantly associated with mortality (hazard ratio per standard deviation 1.31 [1.16, 1.48] to 2.22 [1.84, 2.67]) after controlling for age and other covariates. GWAS of random intercepts and slopes of DM estimated from joint models found a genome-wide significant SNP (rs12652543, p=7.2×10-9) in the TRIO gene associated with the slope of DM constructed from biomarkers declining in late life. Review of biological effects of genes corresponding to top SNPs from GWAS of DM slopes revealed that these genes are broadly involved in cancer prognosis and axon guidance/synapse function. Although axon growth is mainly observed during early development, the axon guidance genes can function in adults and contribute to maintenance of neural circuits and synaptic plasticity. Our results indicate that decline in axons' ability to maintain complex regulatory networks may potentially play an important role in the increase in physiological dysregulation during aging.BACKGROUND Regular physical activity is of paramount importance to reduce chronic disease risk. Classical ballet training requires balance, strength, and range of motion. Participation in social ballet classes is increasing. Ballet training interventions may be an alternative method of regular, enjoyable activity. This review aimed to determine the effectiveness of classical ballet training interventions on physical and psychological health. METHODS Ten databases were searched until April 2019. The included studies investigated classical ballet training interventions of a ≥4-week duration, on any population (no restrictions on experience and clinical condition), measuring physical health or psychological outcomes. RESULTS Twenty-three studies (25 intervention groups) were included, comprising experienced (19 groups) and novice dancers (6 groups). In experienced populations, muscular strength was the most commonly reported outcome. However, only 25% of these studies reported improvements. With novice dancers, including clinical populations, balance showed the most positive change, improving in 75% of studies that reported this measure. CONCLUSIONS Classical ballet training may improve balance in novices and maintain physical activity across the life span. Experienced dancers showed no further improvement, perhaps due to an already greater ability. There was large heterogeneity between the included studies. A greater focus on classical ballet interventions for inexperienced populations is required.CONTEXT Contemporary synthetic playing surfaces have been associated with an increased risk of ankle injury in the various types of football. Triaxial accelerometers facilitate in vivo assessment of planar mechanical loading on the player. OBJECTIVE To quantify the influence of playing surface on the PlayerLoad elicited during footwork and plyometric drills focused on the mechanism of ankle injury. DESIGN Repeated-measures, field-based design. SETTING Regulation soccer pitches. PARTICIPANTS A total of 15 amateur soccer players (22.1 [2.4] y), injury free with ≥6 years competitive experience. INTERVENTIONS Each player completed a test battery comprising 3 footwork drills (anterior, lateral, and diagonal) and 4 plyometric drills (anterior hop, inversion hop, eversion hop, and diagonal hop) on natural turf (NT), third-generation artificial turf (3G), and AstroTurf. Global positioning system sensors were located at C7 and the mid-tibia of each leg to measure triaxial acceleration (100 Hz). MAIN OUTCOME MEASURES PlayerLoad in each axial plane was calculated for each drill on each surface and at each global positioning system location. RESULTS Analysis of variance revealed a significant main effect for sensor location in all drills, with PlayerLoad higher at mid-tibia than at C7 in all movement planes. AstroTurf elicited significantly higher PlayerLoad in the mediolateral and anteroposterior planes, with typically no difference between NT and 3G. In isolated inversion and eversion hopping trials, the 3G surface also elicited lower PlayerLoad than NT. CONCLUSIONS PlayerLoad magnitude was sensitive to unit placement, advocating measurement with greater anatomical relevance when using microelectromechanical systems technology to monitor training or rehabilitation load. AstroTurf elicited higher PlayerLoad across all planes and drills and should be avoided for rehabilitative purposes, whereas 3G elicited a similar mechanical response to NT.CONTEXT Clinically, it has been suggested that increased activation of intrinsic foot muscles may alter the demand of extrinsic muscle activity surrounding the ankle joint in patients with stage II posterior tibial tendon dysfunction. However, there is limited empirical evidence supporting this notion. OBJECTIVE The purpose of this study was to investigate the effects of a 4-week short-foot exercise (SFE) on biomechanical factors in patients with stage II posterior tibial tendon dysfunction. DESIGN Single-group pretest-posttest. SETTING University laboratory. PARTICIPANTS Fifteen subjects (8 males and 7 females) with stage II posterior tibial tendon dysfunction who had pain in posterior tibial tendon, pronated foot deformity (foot posture index ≥+6), and flexible foot deformity (navicular drop ≥10 mm) were voluntarily recruited. INTERVENTION All subjects completed a 4-week SFE program (15 repetitions × 5 sets/d and 3 d/wk) of 4 stages (standing with feedback, sitting, double-leg, and one-leg standing positionerior and fibularis longus muscles, although it could not influence their structural deformity and ankle joint moment. It could produce a potential benefit of decreased tibialis posterior activation.CONTEXT Despite significant emphasis on anterior cruciate ligament injury prevention, injury rates continue to rise and reinjury is common. Interventions to reduce injury have included resistance, balance, and jump training elements. The use of sand-based jump training has been postulated as an effective treatment. However, evidence on landing mechanics is limited. OBJECTIVE To determine potential differences in landing strategies and subsequent landing knee valgus when performing single-leg landing (SLL) and drop jump (DJ) tasks onto sand and land, and to compare between both male and female populations. DESIGN A randomized repeated-measures crossover design. SETTING University laboratory. PARTICIPANTS Thirty-one participants (20 males and 11 females) from a university population. INTERVENTIONS All participants completed DJ and SLL tasks on both sand and land surfaces. MAIN OUTCOME MEASURES Two-dimensional frontal plane projection angle (FPPA) of knee valgus was measured in both the DJ and SLL tasks (right and left) for both sand and land conditions. RESULTS FPPA was lower (moderate to large effect) for SLL in sand compared with land in both legs (left 4.3° [2.8°]; right 4.1° [3.8°]) for females. However, effects were unclear (left -0.7° [2.2°]) and trivial for males (right -1.1° [1.9°]). FPPA differences for males and females performing DJ were unclear; thus, more data is required. Differences in FPPA (land vs sand) with respect to grouping (sex) for both SLL left (4.9° [3.0°]) and right (5.1° [4.0°]) were very likely higher (small)/possibly moderate for females compared with males. buy LDC203974 CONCLUSIONS The effects of sand on FPPA during DJ tasks in males and females are unclear, and further data is required. However, the moderate to large reductions in FPPA in females during SLL tasks suggest that sand may provide a safer alternative to firm ground for female athletes in anterior cruciate ligament injury prevention and rehabilitation programs, which involve a SLL component.
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