E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH AND RESULTS: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSIONS: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

[Effect of salmon calcitonin on postoperative humeral head replacement in elderly patients].

OBJECTIVE: To observe the effect of anti-osteoporosis drugs on the curative effect of femoral head replacement in the elderly patients with proximal humerus fracture. METHODS: From November 2012 to June 2016, 38 patients with proximal humeral fractures received humeral head replacement were divided into the treatment group and the control group according to whether the anti-osteoporosis drugs were used after the operation. The treatment group included 19 cases, of which 11 cases were three part fractures, 18 cases were four part fractures, and bone density was(0.58±0.14) g/cm²; the control group involved 19 cases, of which 10 cases were the three part fractures, 9 cases were four part fractures, and bone density was(0.58±0.11) g/cm². Periprosthetic bone mineral density(BMD) was measured at 4, 8, 12, 24 and 48 weeks after operation, and visual analogue scale(VAS) was used to evaluate the pain and Neer score was used to evaluate the function of the shoulder joint. RESULTS: The incisions of all patients were healed with grade A and no complications occurred. Thirty-five patients were followed up for 1 year. The bone density around the prosthesis of treatment group was higher than that of control group, the difference was statistically significant(P<0.05);VAS in two groups had no statistical significance(P>0.05). The total score and functional score of Neer in the treatment group were better than those in the control group, the difference was statistically significant(P<0.05), and there was no significant difference in pain and activity score between the two groups(P>0.05). According to the Neer score, the results of treatment group was excellent in 10 cases, good in 5 cases, fair in 3 cases;in the control group, 3 cases were excellent, 9 cases were good, and 5 cases were fair;the difference between the two groups was statistically significant(P<0.05). CONCLUSIONS: Artificial humeral head replacement combined with anti-osteoporosis drugs in the treatment of proximal humeral fractures in elderly patients can effectively improve the bone density around the prosthesis and restore shoulder function. The early clinical effect is satisfactory.