[Analysis of the efficacy and safety of low-dose aspirin in preventing renal artery stenosis in kidney transplantation].

Objective: To evaluate the clinical value of aspirin as a prophylactic for transplant renal artery stenosis (TRAS). Methods: From January 2017 to November 2019, clinical data of 307 patients who had undergone renal transplant in Zhengzhou University People's Hospital were collected. Patients were divided into two groups: the treatment group (124 recipients who had taken oral aspirin 100 mg/d after transplant) and the control group (183 recipients who had not taken aspirin after transplant). The general data, incidence of initially diagnosed and confirmed TRAS, type of renal artery anastomosis vessels, duration of stenosis, location of stenosis, and complications were compared between the two groups. The treatment group was further divided into two subgroups, the early group (92 recipients) and the delayed group (32 recipients), according to the time of starting aspirin after operation. Subgroup analysis was performed. Results: Among all 307 patients included, there were 241 males and 66 females, aged 19-64 years. There were no statistical difference between the treatment and control groups in terms of gender, age, comorbidities, number of arterial vessels, type of graft, and acute rejection all P>0.05. Among 46 initially diagnosed TRAS patients, 13 (10.5%) and 33 (18.0%) cases were in the treatment and control group respectively, with no statistically significant difference in stenosis rate (P>0.05). The number of confirmed TRAS patients was 1 (0.8%) and 24 (13.1%) in the treatment and control group respectively, with statistically significant difference in stenosis rate (P<0.001). The proportion of patients with bleeding disorders in the treatment group was slightly higher than that in the control group (13.7% vs 8.7%), and the proportion of infarct diseases was slightly lower than that in the control group (1.6% vs 4.9%). But there was no significant difference in aspirin-related complications between the two groups (P>0.05). Subgroup analysis showed that there was no significant difference in initially diagnosed and confirmed TRAS and aspirin-related complications between the early group and the delayed group (all P>0.05). Conclusions: Oral low-dose aspirin after kidney transplantation can effectively reduce the incidence of TRAS, without increasing the risk of aspirin-related complications.

MicroRNA-448 inhibits the regeneration of spinal cord injury through PI3K/AKT/Bcl-2 axis.

OBJECTIVE: This study aims to elucidate the potential role of microRNA-448 in the recovery of spinal cord injury (SCI), and to explore the underlying mechanism. MATERIALS AND METHODS: MicroRNA-448 expression was determined by microarray and the established SCI model in mice. The target gene of microRNA-448 was predicted using bioinformatics. The functional binding of the target gene to microRNA-448 was verified by Dual-Luciferase reporter gene assay. The regulatory effects of microRNA-448 and Bcl-2 on apoptosis, motor neuron number and grip strength were evaluated. After injection of microRNA-448 mimics, microRNA-448 inhibitor or Bcl-2 siRNA in mice, expression levels of PI3K/AKT and Caspase3 were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. RESULTS: Grip strength of SCI mice significantly decreased compared with mice in the sham group. The microRNA-448 expression gradually increased with the progression of SCI, whereas the Bcl-2 expression decreased. Dual-Luciferase reporter gene assay showed the binding condition between microRNA-448 and Bcl-2. Furthermore, the Bcl-2 expression was negatively regulated by microRNA-448 at both mRNA and protein levels. The injection of microRNA-448 inhibitor into the injured spinal cord of SCI mice significantly upregulated the expressions of p-PI3K, p-AKT and Caspase3, as well as motor neuron regeneration and grip strength. However, the promotive effects of microRNA-448 inhibitor were blocked by Bcl-2 siRNA transfection. CONCLUSIONS: MicroRNA-448 is upregulated after SCI, which may be involved in the regenerative process of spinal motor nerves by regulating PI3K/AKT/Bcl-2 axis.

Effect of PGE in multiple experimental models. IX: In vivo effects of PGE on immune response of leucocytes to wounds.

There have been conflicting results obtained when comparing the in vitro with in vivo effects of prostaglandin E (PGE) on immune function. The in vitro studies have demonstrated immune suppression with PGE administration while the in vivo studies demonstrated improved survival when utilizing infected models. To attempt to resolve this discrepancy, we evaluated the in vivo effect of PGE on host immune function utilizing multiple rat models. PGE was found to have no effect on the ability of leucocytes to infiltrate a sponge matrix wound over a 2-week period of study. PGE also failed to alter the percentage of T-lymphocyte subset populations infiltrating the sponge matrix model. There was noted to be no effect of PGE on the ability of neutrophils to chemiluminescence, or on metabolic function of lymphocytes. In conclusion, PGE does not appear to have immunosuppressive properties when studied using certain in vivo models.

Effect of ibuprofen on the inflammatory response to surgical wounds.

Patients suffering severe trauma frequently become immunosuppressed following injury. This can predispose patients to infectious sequelae. Biochemically, these patients synthesize excessive quantities of cyclooxygenase products (prostaglandins). It has been hypothesized that the prostaglandins cause the immunosuppression and that inhibition of the cyclooxygenase enzyme could thus prevent the immunosuppression. We investigated the effect of the cyclooxygenase inhibitor ibuprofen on the inflammatory response. Rats were subjected to a 30% total body surface area burn and were administered either ibuprofen for a period of 7 days or 14 days, or were administered the carrier for 14 days. The rats were then killed and multiple immunologic variables were measured. Ibuprofen was found to decrease neutrophil chemiluminescence, lymphocyte blastogenesis, and helper/inducer T-lymphocyte infiltration of a sponge matrix model. The same ibuprofen protocol decreased survival in a cecal ligation and puncture model. In conclusion, the cyclooxygenase enzyme system appears to produce metabolites essential for optimal survival following traumatic injury.

Effect of insulin-like growth factor 1 on host response to tumor.

Oncology patients suffer multiple detrimental metabolic alterations. Among these are catabolism of tumor free body mass to supply nutrients to feed the tumor. This results not only in enhanced tumor growth but also poor wound healing and immunosuppression of the tumor host. Efforts are therefore being directed at finding methods for improving the nutritional status of the tumor host without enhancing tumor growth. We investigated the ability of two hormones, insulin-like growth factor-1 (IGF-1) and insulin, to improve physiologic function in tumor-bearing animals. Tumor-bearing animals received a continuous infusion of IGF-1 (2.20 mg/kg/day), insulin (820 microns/kg/day) or placebo via an osmotic minipump for 7 days. All animals were pair fed to eliminate nutritional intake as a variable. The placebo group lost 31.37 +/- 4.3 g of tumor free body mass during the study period. The insulin treated group lost 26.34 +/- 7.42 g and the IGF-1 group lost 5.07 +/- 3.25 g (P < 0.001, ANOVA). IGF-1 treatment failed to alter plasma glucose, lactate, or total amino acid concentration and failed to alter hepatic ketone body concentrations, but did improve hepatic mitochondria redox potential. Finally, IGF-1 improved splenic weight by 110% and splenic lymphocyte count by 300%. In conclusion IGF-1 appears to offer potential in supporting tumor free host body mass without stimulating tumor growth.

Impact of exogenous insulinlike growth factor 1 on hepatic energy metabolism in burn injury.

BACKGROUND: Insulinlike growth factor 1 (IGF-1) has previously been demonstrated to improve the nutritional status of burned animals. The method by which it achieves this result has not yet been fully elucidated, but may be the result of alterations in hepatic metabolism. OBJECTIVE: To determine if IGF-1 is able to correct the burn-induced impairments in hepatic metabolic function. DESIGN: Seventy-two Sprague-Dawley rats were subjected to a sham burn (n = 24), or a 50% total body surface area scald burn (n = 48). Half the scald burn group received 3 micrograms/kg per day of IGF-1. The remainder received a placebo. The rats were sequentially assayed for multiple components of hepatic function. RESULTS: Insulinlike growth factor 1 corrected the burn-induced decrease in hepatic adenosine triphosphate concentration and prevented the burn-induced increase in hepatic ketone body levels. Insulinlike growth factor 1 was also able to prevent the burn-induced decrease in the hepatic acetoacetate-beta-hydroxybutyrate ratio. Since this ratio is directly proportional to mitochondrial redox potential this indicates that IGF-1 is also able to prevent the burn-induced impairment in hepatic redox potential. CONCLUSIONS: These data indicate that part of the previously demonstrated beneficial effect of IGF-1 in burn injury may be due to its ability to improve multiple components of hepatic metabolism.

Blockade of prostaglandin products augments macrophage and neutrophil tumor necrosis factor synthesis in burn injury.

Cyclooxygenase products are believed to be a major regulator of host tumor necrosis factor-alpha (TNF-alpha) production in response to trauma and sepsis. To study this relationship, Lewis rats underwent a 30% burn or sham burn. Dimethyl-prostaglandin E (dPGE, 50 micrograms/kg), ibuprofen (IFU, 2 mg/kg), or saline was administered twice daily. Rats were sacrificed at Day 7 to obtain Kupffer cells, peritoneal macrophages, splenic macrophages, and neutrophils. For in vivo studies, 10(6) cells from each group were cultured with 10 micrograms of lipopolysaccharide (LPS). For in vitro studies, cells from the burn and sham groups were cultured with LPS and dPGE (10 micrograms/ml), IBU (10 micrograms/ml), or saline. The supernatants were harvested after 2, 6, and 24 hr of culture and assayed for TNF-alpha (mu/ml) by L929 cytolysis. Burn injury resulted in a significant increase in Kupffer cell and neutrophil TNF-alpha production compared to the sham group (P < 0.001, ANOVA). The administration of IBU to burned animals led to a pronounced elevation of TNF-alpha production by Kupffer cells, peritoneal macrophages, and neutrophils compared to vehicle-treated burned animals (P < 0.001, ANOVA). With in vitro studies, IBU increased Kupffer cell, peritoneal macrophage, and neutrophil TNF-alpha release by 213, 327, and 198%, respectively (P < 0.05, ANOVA). dPGE caused a marked decrease in Kupffer cell and peritoneal macrophage TNF-alpha synthesis by 50 and 43%, respectively (P < 0.01, ANOVA). In conclusion, prostaglandins are critical for down regulating TNF-alpha production. Clinical use of cyclooxygenase inhibitors may result in adverse outcomes due to the excessive TNF-alpha production.

Effect of thermal injury and sepsis on neutrophil function.

Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils. As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound. We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats. Despite having a higher concentration of neutrophils in the blood, both the burned and burned-infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively). Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001). This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group. The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned-infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively).