Nerves within bone and their application in tissue engineering of bone regeneration.

Nerves within bone play an irreplaceable role in promoting bone regeneration. Crosstalk between the nerve system and bone has arisen to the attention of researchers in the field of basic medicine, clinical medicine, and biomaterials science. Successful bone regeneration relies on the appropriate participation of neural system components including nerve fibers, signaling molecules, and neural-related cells. Furthermore, more about the mechanisms through which nerves took part in bone regeneration and how these mechanisms could be integrated into tissue engineering scaffolds were under exploration. In the present review, we aimed to systematically elaborate on the structural and functional interrelationship between the nerve system and bone. In particular, peripheral nerves interact with the bone through innervated axons, multiple neurotrophins, and bone resident cells. Also, we aimed to summarize research that took advantage of the neuro-osteogenic network to design tissue engineering scaffolds for bone repair.

Vitamins for Prevention of Contrast-induced Acute Kidney Injury: A Systematic Review and Trial Sequential Analysis.

BACKGROUND: To date, universally accepted preventive measures for contrast-induced acute kidney injury (CI-AKI) do not exist, and they warrant further research. OBJECTIVE: The purpose of this study was to evaluate the efficacy of vitamins, including vitamin C and E, for prevention of CI-AKI. METHODS: We electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome of interest was the incidence of CI-AKI. RESULTS: A total of 19 studies were included in this meta-analysis. Pooled analysis showed that vitamin C plus saline [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49-0.82, p = 0.0005] and vitamin E plus saline (RR = 0.39, 95% CI 0.24-0.62, p < 0.0001) significantly reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C plus saline was further confirmed by trial sequential analysis (TSA). However, TSA indicated that more trials are required to confirm the efficacy of vitamin E plus saline. There was no significant difference in preventing CI-AKI between vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47-1.71, p = 0.75), between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30-1.30, p =  0.20), as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49-1.92, p = 0.93). CONCLUSIONS: Vitamin C plus saline administration is effective at reducing the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context is encouraging, but more trials are required. Furthermore, this meta-analysis and TSA indicated insufficient power to draw a definitive conclusion on the effect of vitamin C plus NAC, versus saline or NAC alone, which needs to be explored further.

Association of triiodothyronine levels with left ventricular function, cardiovascular events, and mortality in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have altered free triiodothyronine (fT3) levels. A low fT3 level is a strong and inverse mortality predictor in HD patients. However, little is known about the relationship between fT3 and left ventricular function in HD patients. METHODS: A total of 128 maintenance HD patients were enrolled in this study. A thyroid function test with blood sampling and echocardiography was conducted. Low-T3 syndrome was defined as fT3 level <3.62 pmol/L and normal thyroid stimulating hormone (TSH). Overall mortality and rate of cardiovascular (CV) events were assessed during 48 months of follow-up. RESULTS: Low-T3 syndrome was detected in 57 (44.5%) of the 128 patients. Patients with low-T3 syndrome had a shorter duration of HD (49.1 vs. 73.3, p = 0.01), and lower serum albumin (35.1 vs. 40.4 g/L, p<0.001), left ventricular ejection fraction (LVEF; 54.7% vs. 63.9%, p<0.001), and fractional shortening at endocardial levels (endoFS; 29.3% vs. 34.8%, p = 0.001) compared to those with normal fT3 levels. In multivariate linear regression, LVEF, albumin, and duration of HD were independently correlated with fT3 levels. In addition, fT3 was also correlated with LVEF. During the study period, 13 (10.1%) patients died, CV events occurred in 15 (11.7%) patients. In Cox regression analysis, low fT3 level and elevated high-sensitivity C-reactive protein (hs-CRP) were associated with mortality and CV events. CONCLUSIONS: In HD patients, fT3 level is positively correlated with LVEF. Low fT3 level and elevated hs-CRP predicted all-cause mortality and CV events.

L-Carnitine Ameliorates the Decrease of Aquaporin 2 Levels in Rats with Cisplatin-Induced Kidney Injury.

BACKGROUND: It has been found that L-carnitine ameliorated cisplatin-induced acute kidney injury (AKI) in rats. However, the detailed role of L-carnitine in improving the renal urinary concentration function in cisplatin-induced AKI is not fully understood. METHODS: In this study, 30 Sprague-Dawley rats were divided randomly into 5 groups: control, cisplatin (CIS), L-carnitine (CAR), L-carnitine plus cisplatin (CAR + CIS), and cisplatin plus L-carnitine (CIS + CAR) groups. Cisplatin (7 mg/kg) and L-carnitine (300 mg/kg) were injected intraperitoneally. Urine (24 h) and blood samples were collected to analyze renal urinary concentrating function. Immunoblotting, confocal laser microscopy, and enzyme-linked immunosorbent assays were used to assess the level and localization of the water channel aquaporin (AQP) 2, and levels of stimulatory G protein α subunit (GSα protein), arginine vasopressin (AVP) receptor 2, adenylyl cyclase and serum AVP. RESULTS: Renal urinary concentrating function was improved by L-carnitine in rats with cisplatin-induced AKI. AQP2 expression, which decreased after cisplatin treatment, was improved by L-carnitine in different regions of the kidney. Moreover, our data indicated that L-carnitine could increase AQP2 accumulation at the apical plasma membranes of the renal-collecting ducts. Finally, intervention with L-carnitine effectively improved the expression of AQP2 upstream signaling proteins, such as GSα protein, adenylyl cyclase, and serum AVP levels in rats with cisplatin-induced AKI. CONCLUSION: L-carnitine resolves the cisplatin-induced urinary concentration defect, which may occur by increasing AVP/cyclic adenosine monophosphate/AQP2 levels, indicating the potential use of L-carnitine to ameliorate the renal urinary concentration effect in cancer patients treated with cisplatin.

Loss of PP2A and PTEN immunoexpression coexists with survivin overexpression in adenomyosis.

Phosphatase and tensin homolog (PTEN) and protein phosphatase type 2A (PP2A) are negative modulators of PI3K/AKT/survivin signaling. To evaluate immunoexpression of PTEN, PP2A and survivin in adenomyosis, ectopic lesions from 28 patients with adenomyosis and endometria from 30 controls without adenomyosis were employed in the study. The expression of PTEN, PP2A and survivin was examined with the use of immunohistochemistry. We found a decreased expression of PP2A and PTEN in adenomyosis. The expression of PTEN showed great individual differences in adenomyosis, although expression of both PP2A and PTEN was lower in adenomyosis than in normal endometria. In contrast, the expression of survivin was higher in adenomyosis. Our results suggest the important role of the PI3K cascade in the pathogenesis and development of adenomyosis.