MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-ß-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H2O2-stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H2O2-stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline.

[Non-invasive assessment of portal hypertension in patients with liver cirrhosis using FibroScan transient elastography].

OBJECTIVE: To investigate the clinical value of FibroScan transient elastography for assessing portal hypertension in liver cirrhosis patients by determining the relationship between the liver or spleen stiffness measurement with the imaging parameters of esophageal varices, portal vein width, spleen volume, and splenic vein width. METHODS: A total of 259 patients with liver cirrhosis underwent FibroScan measurement, ultrasound, computed tomography and routine blood analyses. One-hundred-and-one of those patients also underwent endoscopy to diagnose esophageal varices. Receiver operating characteristic (ROC) curves were generated and the areas under the curves (AUCs) were calculated to assess the accuracy of the FibroScan liver and spleen stiffness measurements to predict esophageal varices. Pearson's correlation analysis was used to assess the relationship between clinical features. RESULTS: The median liver and spleen stiffness of the cirrhotic patients were 24.27 kPa and 44.64 kPa, respectively. Liver and spleen stiffness increased in conjunction with increases in Child-Pugh score. Liver stiffness was positively correlated with spleen stiffness (P less than 0.05). Liver and spleen stiffness were positively correlated with esophageal varices, portal vein width, spleen thickness, spleen volume, and splenic vein width. The correlation of spleen stiffness was higher than that of liver stiffness. Spleen stiffness was also negatively correlated with white blood cell count and platelet count. Liver and spleen stiffness also increased in conjunction with increased severity of esophageal varices. The AUC of spleen stiffness was higher than that of liver stiffness for predicting esophageal varices (0.804 vs. 0.737). The optimal cut-off level of spleen stiffness was 44.5 kPa (sensitivity: 88%; specificity: 68%). The estimated prevalence of esophageal varices was 97.87% and the optimized cut-off level of liver stiffness was 18.0 kPa. CONCLUSION: FibroScan appears to be a clinically valuable non-invasive method to assess portal hypertension in cirrhotic patients. Both liver and spleen stiffness measurements correlated with portal hypertension but the spleen stiffness measurement may be of higher clinical value.

[Analysis of prognostic factors of severe jaundice patients using HB-H-6 resin plasma perfusion].

OBJECTIVE: To investigate the influencing factors of efficacy of plasma perfusion in patients with severe jaundice. METHODS: The clinical data of 78 patients with severe jaundice due to different causes receiving HB-H-6 resin plasma perfusion therapy admitted to Tianjin Third Central Hospital from October 2006 to July 2010 were retrospectively analyzed. Patients were divided into improved group (n = 51) and ineffective group (n = 27) according to outcomes. The effecting factors of prognosis, including age, sex, hospital stay days, number of perfusion therapy received, Child-Pugh scores before perfusion, total bilirubin (TBil) levels before perfusion, and mean TBil rebound rate were studied by univariate and multivariate logistic regression analysis. RESULTS: All 78 patients received (3.31 ± 1.36) times of HB-H-6 resin plasma perfusion treatment. Child-Pugh score before perfusion, TBil (µmol/L) before perfusion and mean TBil rebound rate in improved group were significantly lower than those in ineffective group [Child-Pugh score before perfusion: 8.06 ± 1.01 vs. 9.44 ± 1.19; TBil before perfusion: 384.29 ± 170.41 vs. 504.93 ± 206.88; mean TBil rebound rate: -(7.35 ± 20.76)% vs. (37.32 ± 23.22)%]. They were also significantly different in gender between two groups (improved group: 30 males, 21 females; ineffective group: 24 males, 3 females, P < 0.05 or P < 0.01). Gender and mean TBil bounce rate were defined as independent significant factors influencing the clinical results by multivariate logistic regression analysis. Regression coefficient ß were 5.35 and -2.82 for gender and mean TBil bounce rate respectively [χ (2) = 64.42, P = 0.000]. Receive operating characteristic curve (ROC curve) analysis showed that the area under the curve (AUC) was 0.90 (0.82, 0.97), and mean TBil bounce rate higher than 29.5% indicated poor prognosis. No obvious side effects were observed after plasma perfusion. CONCLUSIONS: Gender and mean TBil bounce rate were independent risk factors in treatment of severe jaundice with HB-H-6 resin plasma perfusion. Mean TBil bounce rate higher than 29.5% indicated a poor prognosis.