BackgroundIn our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo.MethodsWe selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed.Results and conclusionForced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.

Introduction: Ribosomal protein SA pseudogene 52 (RPSAP52) has been characterized as an oncogenic lncRNA in pituitary tumors. Analysis of TCGA dataset revealed the upregulation of RPSAP52 in glioblastoma (GBM). We, therefore, investigated the roles of RPSAP52 in GBM. Methods: A total of 50 GBM patients (33 males and 20 females; 54-75 years; mean age: 61.8±5.8 years) were selected from the 89 cases of GBM patients. Under the guidance of MRI, brain biopsy was performed to collect GBM tissues from each patient for the diagnosis of GBM. U-373 MG cells were employed and had transient transfections. qRNA, Western blot, and a series of experiments were performed to characterize their associations. Results: The results showed that RPSAP52 was upregulated in GBM patients, and its high expression levels predicted poor survival. In GBM tissues, expression levels of RPSAP52 were significantly and positively correlated with that of TGF-β1. In GBM tissues, RPSAP52 positively regulated the expression of TGF-β1. Cell stemness assay showed that, compared to C and NC groups, overexpression of RPSAP52 and TGF-β1 led to increased, while silencing of RPSAP52 led to decreased CD133+ cells. Overexpression of TGF-β1 attenuated the effects of RPSAP52 siRNA silencing. Conclusion: Therefore, RPSAP52 upregulates TGF-β1 to increase cancer cell stemness and predict postoperative survival in GBM.

Our study aimed to explore the intercorrelations of brachial‐ankle pulse wave velocity (baPWV), ankle‐brachial index (ABI), ambulatory arterial stiffness index (AASI), 24‐hour mean pulse pressure (24‐h   PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49‐65) years and 50.5 (35.5‐84.1) ml/min/1.73 m2, respectively. In Pearson correlation analysis, baPWV was significantly associated with 24‐h  PP (r = .531, p < .001), AIx@75 (r = .306, p < .001). Additionally, 24‐h  PP was associated with AASI (r = .507, p < .001) and AIx@75 (r = .217, p = .019). During follow‐up for a median of 25 months, 26.5% (n = 31) of patients had a composite outcome; of these, 10 initiated dialysis, 17 had 40% eGFR loss, and 4 died. Increased AASI, 24‐h  PP, and baPWV were associated with poor renal outcomes in a univariate Cox analysis. After adjusting for age, sex, MAP, eGFR, and 24 hours proteinuria, 1‐SD increase in AASI and 24‐h  PP was associated with renal outcomes. The ROC analysis yielded the largest area under the curve (AUC) of 0.727 (95% CI: 0.624 to 0.831; p < .001) for 24  ‐h PP. When the Youden's index was at its maximum, the 24‐h PP value was 52 mmHg. In conclusion, 24‐h  PP, baPWV, and AIx@75 were linked well to one another. Arterial stiffness is a target for delaying the decline in kidney function. The use of 24‐h  PP as an arterial stiffness marker should be valued in CKD clinical practice.

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m2. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10–1.39; P < 0.001; per 10 mmHg) was associated with heavy proteinuria. During the median follow-up of 23 months, 70 patients (19.7%) had a composite outcome; of these, 25 initiated dialysis, 25 had 40% eGFR loss, and 20 died. Cox analysis showed that the renal risk of LNSBP for CKD outcomes remained significant even after adjusting for background factors, including age, sex, medical history of hypertension and diabetes, smoking status, eGFR, 24-h proteinuria, and etiology of CKD (HR 1.18; 95% CI 1.06–1.32; P = 0.002; per 10 mmHg). Concentrating on LNSBP could be valuable in guiding antihypertensive treatment to control heavy proteinuria and improve renal prognosis in elderly CKD patients.

Osteocalcin (OCN) is a bone-derived and vitamin K dependent hormone that affects energy metabolism and vascular calcification. The relationship between serum OCN and vascular function in patients with chronic kidney disease (CKD) is uncertain. This study investigated the association between serum OCN and vascular function as expressed with reactive hyperemia index (RHI) and augmentation index (AIx) measured by Endo-PAT 2000 device. This cross-sectional analysis was based on 256 pre-dialysis CKD patients who had completed the Endo-PAT 2000 test and serum OCN at the First Center of Chinese PLA Hospital from November 2017 to December 2019. Based on whether the RHI was less than 1.67, the patients were divided into endothelial dysfunction and normal endothelial function groups. Multiple logistic and linear regression were used to analyze the association between OCN and vascular function. Subgroup analyses were performed to examine the effects of OCN on vascular function in different CKD populations. After mul-tivariate adjustment, CKD with low OCN were more likely to have endothelial dysfunction (OR: 0.794; 95%CI: 0.674-0.934; P = .006); on the contrary, patients with high OCN had a higher degree of arterial stiffness (standardized β: 0.174; P = .003). Subgroup analyses showed that higher OCN was associated with severe arterial stiffness but a better endothelial function in young (age < 65 years, P RHI /P AIx@75 = .027/.011), male (P RHI /P AIx@75 = .040/.016), patients with a history of hypertension (P RHI /P AIx@75 = .004/.009) or diabetes (P RHI /P AIx@75 = .005/.005), and in early CKD (P RHI /P AIx@75 = .014/.015). In conclusion, serum OCN correlates with vascular function in CKD patients: beneficial for endothelial function but detrimental to arterial stiffness.

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Background Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non‐dialysis patients. Therefore, this study aimed to determine frailty‐associated factors in elderly CKD stage I–IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. Methods A total of 774 elderly CKD I–IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. Results Seven hundred seventy‐four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2. The prevalence of sarcopenia was 30.6%. The FI exhibited a right‐skewed distribution. The age‐related slope of FI was 1.4% per year on a logarithmic scale (r2 = 0.706, 95% CI 0.9, 1.8, P < 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, P = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II–IV, low level of serum albumin and increased waist–hip ratio were significantly associated with high FI status, while advanced age and CKD stage III–IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results. Conclusions Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I‐IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist–hip ratio and low serum albumin level should be assessed for frailty.