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Essential hypertension involves complex cardiovascular regulation. The autonomic nervous system function fluctuates throughout the sleep-wake cycle and changes with advancing age. However, the precise role of the autonomic nervous system in the development of hypertension during aging remains unclear. In this study, we characterized autonomic function during the sleep-wake cycle in different age groups with essential hypertension. This study included 97 men (53 with and 44 without hypertension) aged 30-79 years. They were stratified by age into young (< 40 years), middle-aged (40-59 years), and older (60-79 years) groups. Polysomnography and blood pressure data were recorded for 2 min before and during an hour-long nap. Autonomic function was assessed by measuring heart rate variability and blood pressure variability. Data were analyzed using t tests, correlation analyses, and two-way analysis of variance. During nonrapid eye movement (nREM), a main effect of age was observed on cardiac parasympathetic measures and baroreflex sensitivity (BRS), with the highest and lowest levels noted in the younger and older groups, respectively. The coefficients of the correlations between these measures and age were lower in patients with hypertension than in normotensive controls. The BRS of young patients with hypertension was similar to that of their middle-aged and older counterparts. However, cardiac sympathetic activity was significantly higher (p = 0.023) and BRS was significantly lower (p = 0.022) in the hypertension group than in the control group. During wakefulness, the results were similar although some of the above findings were absent. Autonomic imbalance, particularly impaired baroreflex, plays a more significant role in younger patients with hypertension. The nREM stage may be suitable for gaining insights into the relevant mechanisms., (© 2023. The Author(s).)

Cardiovascular function is related to age, sex, and state of consciousness. We hypothesized that cardiovagal baroreflex sensitivity (BRS) demonstrates different patterns in both sexes before and after 50 years of age and that these patterns are associated with patterned changes during the sleep-wake cycle. We recruited 67 healthy participants (aged 20-79 years; 41 women) and divided them into four age groups: 20-29, 30-49, 50-69, and 70-79 years. All the participants underwent polysomnography and blood pressure measurements. For each participant, we used the average of the arterial pressure variability, heart rate variability (HRV), and BRS parameters during the sleep-wake stages. BRS and HRV parameters were significantly negatively correlated with age. The BRS indexes were significantly lower in the participants aged ≥ 50 years than in those aged < 50 years, and these age-related declines were more apparent during non-rapid eye movement sleep than during wakefulness. Only BRS demonstrated a significantly negative correlation with age in participants ≥ 50 years old. Women exhibited a stronger association than men between BRS and age and an earlier decline in BRS. Changes in BRS varied with age, sex, and consciousness state, each demonstrating a specific pattern. The age of 50 years appeared to be a crucial turning point for sexual dimorphism in BRS. Baroreflex modulation of the cardiovascular system during sleep sensitively delineated the age- and sex-dependent BRS patterns, highlighting the clinical importance of our results. Our findings may aid in screening for neurocardiac abnormalities in apparently healthy individuals., (© 2022. The Author(s).)

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study., (© 2022. The Author(s).)

Chondrosarcoma is a malignant primary bone tumor. Sirtuin-1 (SIRT1), which is a member of sirtuin family, plays a dual role either in cancer promotion or suppression. There is no report about the role of SIRT1 in the human chondrosarcoma cells. Resveratrol is a potent activator of SIRT1. However, its effects on chondrosarcoma have not been extensively studied. Here, we investigated the role of SIRT1 induction by resveratrol in human chondrosarcoma cell growth and tumor progression. Resveratrol significantly decreased cell viability and induced cell apoptosis in human chondrosarcoma cells in a dose-dependent manner. The protein expression and activity of SIRT1 were activated after treatment with resveratrol. Resveratrol significantly inhibited NF-κB signaling by deacetylating the p65 subunit of NF-κB complex, which could be reversed by siRNA-SIRT1 transfection or deacetylation inhibitor MS-275. Resveratrol induced-apoptosis involved a caspase-3-mediated mechanism. Both siRNA-SIRT1 transfection and MS-275 significantly inhibited the resveratrol-induced caspase-3 cleavage and activity in human chondrosarcoma cells. Moreover, in vivo chondrosarcoma xenograft study revealed a dramatic reduction in tumor volume and the increased SIRT1 and cleaved caspase-3 expressions in tumors by resveratrol treatment. These results suggest that resveratrol induces chondrosarcoma cell apoptosis via a SIRT1-activated NF-κB deacetylation and exhibits anti-chondrosarcoma activity in vivo.

A combination therapy of pentoxifylline with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) decreased proteinuria or glomerular filtration rate decline in early chronic kidney disease (CKD). Whether adding pentoxifylline to ACEI/ARB provides additional benefits on outcome is unclear in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND). A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 14,117 CKD 5 ND with serum creatinine levels >6 mg/dL and hematocrit levels <28% and who have been treated with ACEI/ARB. All patients were divided into pentoxifylline users and nonusers. Patient follow-up took place until dialysis, death before initiation of dialysis or December 31, 2009. Finally, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before dialysis. After propensity score-matching, use of pentoxifylline was associated with a lower risk for long-term dialysis or death in ACEI/ARB users (HR, 0.94; 95% CI, 0.90-0.99) or ARB users (HR, 0.91; 95% CI, 0.85-0.97). In conclusion, pentoxifylline exhibited a protective effect in reducing the risk for the composite outcome of long-term dialysis or death in ACEI/ARB treated CKD 5 ND.

Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma. However, the response rate is only 40-65%. This study investigated the anti-tumor effect and underlying mechanisms of the combination of cisplatin and the NEDD8-activating enzyme inhibitor MLN4924 in human bladder urothelial carcinoma. The combination of cisplatin and MLN4924 exerted synergistic cytotoxicity on two high-grade bladder urothelial carcinoma cell lines, NTUB1 and T24 (combination index <1). MLN4924 also potentiated the cisplatin-induced apoptosis and activation of caspase-3 and -7, phospho-histone H2A.X and PARP. c-Jun N-terminal kinase (JNK) activation and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) were also observed during cisplatin and MLN4924 treatment. Inhibition of JNK activation partially restored cell viability and Bcl-xL expression. Bcl-xL overexpression also rescued cell viability. MLN4924 significantly potentiated cisplatin-induced tumor suppression in urothelial carcinoma xenograft mice. In summary, MLN4924 synergistically enhanced the anti-tumor effect of cisplatin via an increase in DNA damage, JNK activation and down-regulation of Bcl-xL in urothelial carcinoma cells. These findings provide a new therapeutic strategy for the treatment of bladder cancer.