RNA m5C methylation: a potential modulator of innate immune pathways in hepatocellular carcinoma.

RNA 5-methylcytosine (m5C) methylation plays a crucial role in hepatocellular carcinoma (HCC). As reported, aberrant m5C methylation is closely associated with the progression, therapeutic efficacy, and prognosis of HCC. The innate immune system functions as the primary defense mechanism in the body against pathogenic infections and tumors since it can activate innate immune pathways through pattern recognition receptors to exert anti-infection and anti-tumor effects. Recently, m5C methylation has been demonstrated to affect the activation of innate immune pathways including TLR, cGAS-STING, and RIG-I pathways by modulating RNA function, unveiling new mechanisms underlying the regulation of innate immune responses by tumor cells. However, research on m5C methylation and its interplay with innate immune pathways is still in its infancy. Therefore, this review details the biological significance of RNA m5C methylation in HCC and discusses its potential regulatory relationship with TLR, cGAS-STING, and RIG-I pathways, thereby providing fresh insights into the role of RNA methylation in the innate immune mechanisms and treatment of HCC.

Risk factors of pancreatitis after percutaneous transhepatic biliary drainage in patients with pancreatic cancer and obstructive jaundice / 中华内科杂志

Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.

Anesthetics inhibit extracellular signal-regulated Kinase1/2 phosphorylation via NMDA receptor, phospholipase C and protein kinase C in mouse hippocampal slices.

BACKGROUND: Extracellular signal-regulated kinase 1/2 (ERK1/2) has been implicated in learning and memory; however, whether intravenous anesthetics modulate ERK1/2 remains unknown. The aim of this study was to examine the effect of several intravenous anesthetics on the phosphorylation of ERK1/2 in the hippocampus of adult mice. METHODS: Western blotting was used to examine cellular levels of phosphorylated and unphosphorylated ERK1/2 in mouse hippocampus slices, which were incubated with or without anesthetics including propofol, etomidate, ketamine and midazolam, a protein kinase C (PKC) activator or inhibitor, or phospholipase C (PLC) activator or inhibitor. RESULTS: Propofol, etomidate, ketamine and midazolam reduced phosphorylation of ERK1/2 in a time-dependent manner. Washing out propofol after 5 min increased ERK1/2 phosphorylation. The anesthetic-induced depression of ERK1/2 phosphorylation was blocked by 0.1 µM phorbol-12-myristate 13-acetate (an activator of PKC), 50 µM U73122 (an inhibitor of PLC). The anesthetic-induced depression of ERK1 phosphorylation was blocked by 1 mMN-methyl-d-aspartate (NMDA). Whereas 100 µM chelerythrine (an inhibitor of PKC) and 100 µM carbachol (an activator of PLC) and 20 µM PD-98059 (an inhibitor of MEK) had additive effects on propofol-induced inhibition of ERK1/2 phosphorylation. In contrast, 10 µM MK801 (a NMDA receptor antagonist) did not block anesthetic-induced inhibition of ERK1/2 phosphorylation. CONCLUSION: Intravenous anesthetics markedly decreased phosphorylation of ERK1/2 in mouse hippocampal slices, most likely via the NMDA receptor, and PLC- and PKC-dependent pathways. Thus, ERK1/2 represents a target for anesthetics in the brain.

Effect of electro-acupuncture at Zusanli acupoint on blood coagulation during intestinal ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effect of electro-acupuncture (EA) at Zusanli (ST36) acupoint on blood coagulation during intestinal ischemia-reperfusion (I/R) in rats.Methods Forty healthy male Sprague-Dawley rats,aged 6-8 months,weighing 250-300 g,were divided into 5 groups (n =8 each) using a random number table:sham operation group (group S),intestinal I/R group (group I/R),EA at Zusanli acupoint group (group EA),EA at non-acupoint group (group NE) and α7 nicotinic acetylcholine receptor antagonist α-bungarotoxin (α-BGT) group (group α-BGT).Intestinal I/R was induced by clamping the superior mesenteric artery for 4-5 min followed by 120 min of reperfusion.Bilateral Zusanli acupoints were stimulated with an electric stimulator (frequency 3 Hz,voltage 2-4 V,wave length 2 ms) for 30 min starting from the time point immediately after beginning of ischemia in group EA,while EA was performed at the points 5 mm lateral to the bilateral Zusanli instead in group NE.In group α-BGT,α-BGT 1 μg/kg was intraperitoneally injected at 45 min before ischemia,and the other treatments were similar to those previously described in group EA.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of the concentrations of tumor necrosis factor alpha (TNFα),tissue factor (TF),antithrombin (AT),tissue plasminogen activator (tPA),fiber plasminogen activator inhibitor-1 (PAl-l) and D-dimer in plasma (by enzyme-linked immunosorbent assay) and platelet count (PLT).The animals were sacrificed after blood sampling,the distal ileum specimens were removed for examination of the pathological changes with a light microscope,and the damage to the intestinal mucous membrane was assessed and scored according to Chin.Results Compared with group S,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly increased,and the plasma AT concentration and PLT were decreased in I/R,NE and α-BGT groups,the concentrations of plasma TNFα and TF were significantly increased,and the plasma AT concentration was decreased in group EA,and Chiu's scores were significantly increased in I/R,EA,NE and α-BGT groups (P＜ 0.05).Compared with group I/R,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly decreased,the plasma AT concentration and PLT were increased,and Chiu's scores were decreased in group EA (P＜0.05),and no significant change was found in the variables mentioned above in NE and α-BGT groups (P＞0.05).Compared with group EA,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly increased,the plasma AT concentration and PLT were decreased,and Chiu's scores were increased in group NE (P＜0.05).Conclusion EA at Zusanli acupoint can improve blood coagulation during intestinal I/R in rats,and the mechanism is related to activating the cholinergic anti-inflammatory pathway.

Effect of hydroxyapatite nanoparticles on MII-stage porcine oocytes vitrification and the study of its mechanism / 生物医学工程学杂志

Nano-cryopreservation may become a new way in the next generation of cryopreservation technology. However, research using nanoparticles in oocytes vitrification has not been reported in the literature. In this study, HA nanoparticles with different diameters were added into cryoprotectant and M II-stage porcine oocytes were vitrified by Cryotop. The results showed that nanoparticles improved the survival rate of cryopreserved M II-stage porcine oocytes, but the difference between nanoparticles with different diameters of was not significant. In order to study the mechanism of nano-cryopreservation, the cooling rate of cryoprotectant was measured by ultra-fast temperature measurement system and the melting enthalpy of cryoprotectant was measured by differential scanning calorimeter (DSC). The results showed that the adding of nanoparitcles could not increase the cooling rate of cryoprotectant, but could decreases the amount of ice crystals during freezing and warming. Therefore, the mechanical injury within and outside cells might be effectively reduced.

Effect of vagus nerve stimulation on blood coagulation and fibrinolysis in endotoxemic rats / 中华麻醉学杂志

Objective To evaluate the effect of vagus nerve stimulation on the blood coagulation and fibrinolysis in endotoxemic rats.Methods Ninety-six male Sprague-Dawley rats,weighing 250-280 g,were equally and randomly divided into 4 groups using a random number table:normal saline group (S group) ; lipopolysaccharide (LPS) group; vagus nerve cutting group (VNC group) and vagus nerve stimulation group (VNS group).Endotoxemia was induced by LPS 10 mg/kg injected via the left femoral vein.In group S,normal saline 5 ml/kg was injected via the left femoral vein.In S and LPS groups,the bilateral vagus nerves were only isolated.The bilateral vagus nerves were isolated,ligated and cut immediately after LPS injection in VNC group.The distal end of the vagus nerve was stimulated with direct current (5 V,2 ms,1 Hz) continuously for 20 min starting from the end of LPS injection in group VNS.Six rats were sacrificed before LPS injection (T0) and at 2,4 and 6 h after LPS injection (T1-3) and arterial blood samples were taken for determination of the levels of plasma tumor necrosis factorα (TNF-α),antithrombin (AT),tissue-type plasminogen activator (tPA),plasminogen activator inhibitor type 1 (PAI-1) and D-Dimer.Results Compared with group S,the plasma TNF-α,tPA,PAI-1 and D-Dimer levels were significantly increased,and AT level was decreased after LPS injection in LPS and VNC groups (P ＜ 0.05).Compared with group LPS group,the plasma AT level was significantly decreased,and the plasma PAI-1 level was increased in group VNC,and the plasma TNFα,tPA,PAI-1 and D-Dimer levels were decreased,and the plasma AT level was increased in VNS group (P ＜ 0.05).Conclusion Electrical stimulation of the vagus nerve can improve the blood coagulation and fibinonlysis in endotoxemic rats,and activation of cholinergic anti-inflammatory pathway,inhibition of inflammatory responses and reduction of damage to vascular endothelial cells may be involved in the mechanism.