Osteosarcoma (OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-489-3p in OS cells. MiR-489-3p inhibited OS metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in OS tissues than in adjacent non-cancerous tissues. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of OS cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET tyrosine kinase receptor. In conclusion, our results reveal that miR-489-3p-PAX3-MET signaling is critical to OS metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of OS. © 2016 Wiley Periodicals, Inc.

ObjectiveTo explore the association between quality of life and social support in elderly osteoporosis patients in a Chinese population.MethodsA total of 214 elderly patients who underwent bone mineral density screening were divided into two groups: elderly patients with primary osteoporosis (case group, n = 112) and normal elderly patients (control group, n = 102). Quality of life and social support were compared between the two groups.ResultsQuality of life and social support were significantly different between the case and control groups. The physical function, role-physical, bodily pain, general health, vitality, social-functioning, role-emotional and mental health scores in case group were significantly lower than those in the control group (P < 0.01). The objective support, subjective support, utilization of support, and total scores in case group were significantly lower than those in the control group (P < 0.01). Quality of life and social support were positively correlated in the case group (r = 0.672, P < 0.01).ConclusionQuality of life and social support in elderly patients with osteoporosis in China were poorer than in elderly patients without osteoporosis and were positively correlated. Our findings indicate that increased efforts to improve the social support and quality of life in elderly osteoporosis patients are urgently needed in China. Further longitudinal studies should be conducted to provide more clinical evidence to determine causative factors for the observed association between risk factors and outcomes.

PurposeInsulin resistance plays a role in the development of dementia and hypertension. We investigated a possible relationship between cognitive impairment and insulin resistance in elderly Chinese patients with primary hypertension.Materials and MethodsOne hundred and thirty-two hypertensive elderly patients (>60 years) were enrolled in this study, and assigned into either the cognitive impairment group (n=61) or the normal cognitive group (n=71). Gender, age, education, body mass index (BMI), waist hip ratio (WHR), total cholesterol (TC), triglyceride (TG), C-reactive protein (CRP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), creatinine (Cr), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR), systolic blood pressure, diastolic blood pressure, smoking history, atherosclerosis and the proportion of uncontrolled hypertension were compared between the two groups. Multi-factorial logistic regression analysis was performed.ResultsNo significant differences were found in gender, age, TC, CRP, HDL-C, LDL-C, Cr, BP, smoking history, atherosclerosis and the proportion of uncontrolled hypertension between the two groups. The cognitive impairment group had lower education levels, and higher BMI, WHR, TG, FPG, FINS, and HOMA-IR levels than the control group. Logistic regression analysis revealed the levels of education, BMI, WHR, and HOMA-IR as independent factors that predict cognitive impairment in patients.ConclusionOur study demonstrates that poor education and increased BMI, WHR, and HOMA-IR are independent risk factors for cognitive impairment in elderly patients with hypertension. Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients.

Hyperosmotic stress may be initiated during a diverse range pathological circumstances, which in turn results in tissue damage. In this process, the activation of survival signaling, which has the capacity to restore cell homeostasis, determines cell fate. Autophagy is responsible for cell survival and is activated by various pathological stimuli. However, its interplay with hyperosmotic stress and its effect on terminally differentiated cardiac myocytes is unknown. Nuclear factor of activated T‑cells 5 (NFAT5), an osmo‑sensitive transcription factor, mediates the expression of cell survival associated‑genes under hyperosmotic conditions. The present study investigated whether NFAT5 signaling is required in hyperosmotic stress‑induced autophagy. It was demonstrated that the presence of a hyperosmotic stress induced an increase in NFAT5 expression, which in turn triggered autophagy through autophagy‑related protein 5 (Atg5) activation. By contrast, NFAT5 silencing inhibited DNA damage response 1 protein expression, which then initiated the activation of mammalian target of rapamycin signaling. Therefore, the balance between NFAT5‑induced apoptosis and autophagy may serve a critical role in the determination of the fate of cardiomyocytes under hyperosmotic stress. These data suggest that autophagy activation is a beneficial adaptive response to attenuate hyperosmotic stress‑induced cell death. Therefore, increasing autophagy through activation of NFAT5 may provide a novel cardioprotective strategy against hyperosmotic stress‑induced damage.

ObjectiveThis study aimed to assess the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C for renal dysfunction in older patients with coronary disease.MethodsA total of 84 older patients with coronary artery disease were included in this study. Serum NGAL and cystatin C levels were analysed using commercially available kits. Medical data of all patients were recorded and analysed.ResultsNGAL and cystatin C levels were significantly positively correlated with N-terminal prohormone of brain natriuretic peptide levels and negatively correlated with the estimated glomerular filtration rate. The areas under the receiver operating characteristic curves of serum NGAL and cystatin C levels for diagnosing early renal dysfunction were 0.884 and 0.744, respectively.ConclusionSerum NGAL and cystatin C are potential early and sensitive markers of renal dysfunction in older patients with coronary artery disease.