ObjectiveTo summarize the current research status of the relationship between DNA methylation and liver regeneration.MethodThe related literatures at home and abroad were searched to review the studies on relationships between the methylation level of liver cells, regulation of gene expression, and methylation related proteins and liver regeneration.ResultsThe DNA methylation was an important epigenetic regulation method in vivo and its role in the liver regeneration had been paid more and more attentions in recent years. The existing studies had found the epigenetic phenomena during the liver regeneration such as the genomic hypomethylation, methylation changes of related proliferating genes and DNA methyltransferase and UHRF1 regulation of the liver regeneration.ConclusionsThere are many relationships between DNA methylation and liver regeneration. Regulation of liver regeneration from DNA methylation level is expected to become a reality in the near future.
Objective To establish a stable model of orthotopic liver transplantation (OLT) using donation after cardiac death (DCD) in rat, and to analyze death causes within 24 h after OLT, then explore appropriate treatment strategies for it. Methods The heart arrested 10 min before liver graft harvesting. The rat OLT model using DCD was performed by Kamada two-cuff technique. The operative time and death were recorded. Results One hundred OLT models using DCD were performed successfully within 40 d, the donor operative time was (20±5) min, the recepient operative time was (55±5) min, the anhepatic phase was (20±3) min. Nine rats were died during the operation, including 4 cases of massive haemorrhage, 1 case of anesthesia accident, 1 case of longer anhepatic phase, 1 case of sleeve implant failure, and 2 cases of aeroembolism. Twenty-two rats died within 12 h after the operation, including 6 cases of intestinal necrosis, 6 cases of anastomotic bleeding, 3 cases of pulmonary edema, 4 cases of intraoperative massive haemorrhage, 2 cases of vascular embolism, and 1 case of unexplained death. Nineteen rats died 12–24 h after the operation, including 9 cases of intestinal necrosis, 3 cases of anastomotic bleeding, 2 cases of pulmonary edema, 1 case of intraoperative massive haemorrhage, 1 case of vascular embolism, and 3 cases of unexplained death. Conclusions There are many reasons resulting in early death of rat OLT using DCD, postoperative intestinal necrosis, intraoperative and postoperative bleeding, and postoperative pulmonary edema are main causes. For these reasons, prevention and improvement measures are helpful to establish a stable model and improve a successful rate of rat OLT using DCD.
ObjectiveTo summarize the role of ionized free calcium/calmodulin/calmodulin-dependent protein kinase Ⅱ (Ca2+/CaM/CaMKⅡ) signaling pathway in liver fibrosis so as to provide a theoretical basis for the treatment of liver fibrosis. MethodThe recent literature relevant research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis both domestically and internationally was reviewed. ResultsThe Ca2+/CaM/CaMKⅡ signaling pathway played a bidirectional regulatory role in the process of liver fibrosis, potentially facilitating the activation of hepatic stellate cells and triggering hepatocyte apoptosis through synergistic transforming growth factor-β1 and platelet-derived growth factor pathways. ConclusionsAt present, there is very little research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis, and there is still insufficient understanding. Future research should focus on the mechanism of this signaling pathway in liver fibrosis, especially its upstream genes or downstream target proteins, which will aid to develop targeted and effective treatment strategies, achieve the reversal of liver fibrosis and even liver cirrhosis, and provide more effective treatment options for patients with liver fibrosis.
【Abstract】Objective To explore the changes of expression of AFP mRNA in human hepatocellular carcinoma （HCC） tissues after oral Xeloda therapy.Methods Total RNA was extracted from HCC tissue samples collect after operation and nested reverse transcription polymerase chain reaction （RT-nested PCR） assay was performed to determine the expression of AFP mRNA in this study.Results The final product of AFP mRNA amplified by RT-PCR was 174 bp and by RT-nested PCR was 101 bp. The AFP mRNA is positive in 12 of 21 patients (positive rate 57.14%) amplified by RT-nested PCR assay in Xeloda treatment group which is much lower than control group: 18 of 20 patients (positive rate 90.00%),P＜0.05.The serum AFP value of Xeloda treatment group 〔(23.2±12.8) μg/L〕 is much lower than that of control group 〔(39.6±24.3) μg/L〕 four weeks after operation (P＜0.05). However, There was no difference between two groups in serum AFP value before operation.Conclusion Xeloda can effectively suppress the expression of AFP mRNA in human HCC tissues and lower it’s product serum AFP value.The clinical application of Xeloda in HCC patients deserve further study.
ObjectiveObjective To summarize the latest research progress on the copper death mechanism in metabolic associated fatty liver disease (MAFLD) and to provide new avenues for the treatment of MAFLD. MethodsWe reviewed recent domestic and international research on copper and copper death in MAFLD, and summarized the role of copper death mechanisms in the pathogenesis of MAFLD and related treatments. ResultsCopper death is primarily caused by abnormal intracellular copper accumulation binding to acylated proteins in the tricarboxylic acid cycle, leading to protein oligomerization, downregulation of iron-sulfur cluster protein expression, triggering a toxic stress response, and ultimately cell death. The occurrence and progression of MAFLD are closely associated with genes associated with the copper death pathway. Imbalanced copper metabolism can lead to insulin resistance, causing abnormalities in blood glucose and lipid metabolism, promoting fat accumulation in the liver, and ultimately contributing to the development of MAFLD. Targeting genes involved in the copper death pathway can delay the progression of MAFLD. ConclusionThe occurrence and progression of MAFLD are closely linked to the copper death signaling pathway, with copper metabolism imbalance as a core component. This pathway not only directly leads to hepatocyte death but also triggers insulin resistance and abnormal lipid metabolism, jointly driving the progression of MAFLD. Therefore, targeted regulation of the copper death pathway is a novel therapeutic strategy to slow the progression of MAFLD.
ObjectiveTo understand the current research status of calorie restriction and calorie restriction mimetics in inflammatory diseases. MethodThe literatures about the effect of caloric restriction and caloric restriction mimetics on immune cells, inflammatory responses, and clinical applications were reviewed and analyzed. ResultsAs a dietary therapy, the caloric restriction affected the immune system and function by limiting daily energy intake, regulating cellular metabolic pathways and energy patterns, reducing the inflammatory reaction and improving body symptoms. A growing numbers of attention had been paid in aging, type 2 diabetes, cardiovascular disease, osteoarthritis, neurodegenerative diseases, etc. And it was found that some caloric restriction mimetics such as resveratrol, rapamycin, metformin, etc. could not only achieve similar effects with caloric restriction, but also did not need to strictly restrict diet. ConclisionsAlthough calorie restriction has been studied extensively, there is still no widely accepted and uniform calorie restriction protocol, which is challenging in clinical practice. The development of calorie restriction mimetics, which has similar effects to calorie restriction without requiring strict dietary restriction, is more in line with human physiology and is advantageous to patients. There is a certain understanding how these drugs can prevent inflammation by regulating metabolic pathways, and the relation between them is complex. In future, the knowledge proposed in new field of immunometabolism is preferred to prevent inflammation in age-related diseases, and anti-inflammatory drugs should be reused as a therapeutic option for treatment of age-related diseases.
Objective To summarize the diagnosis and treatment progress of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) in recent years. Methods Through the retrieval of relevant literatures, the progress in the diagnosis and treatment of BR-PDAC in recent years were reviewed, to summarize the current status of definition, management, and outcome of BR-PDAC. Results Pancreatic surgery had significantly changed during the past years and resection approaches had been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, BR-PDAC, which had recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), had become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. The key point was preoperative diagnostic accuracy to define the resectability of BR-PDAC and radical tumor resection followed by neoadjuvant treatment. Conclusion Surgery followed by neoadjuvant treatment is the only treatment option for BR-PDAC with the chance of long-term survival.
Objective To investigate the effect on expression regulation of calmodulin-dependent kinases casades (CaMK) Ⅱ on liver function after liver transplantation in rats. Methods Allogeneic orthotopic liver transplantation model was established by using the classic two-cuff method. The lentiviral expression systems of CaMKⅡγ protein and CaMKⅡγ shRNA were constructed. The lentiviral vector expressing CaMKⅡγ shRNA and the lentiviral vector expressing CaMKⅡγ protein were perfused into the rat after liver transplantation respectively, and the corresponding blank vector and normal saline were perfused into the control group at the same time. The serum levels of ALT and AST were measured at different time points of inferior vena cava blood in rats. Results The serum ALT and AST levels were debased in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ shRNA (P<0.05). The serum ALT and AST levels were raised in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ protein (P<0.05). There were no significant difference of serum ALT and AST levels between the blank control group and the saline group (P>0.05). Conclusion Specific blocking of CaMK Ⅱ signaling pathway can effectively reduce the serum ALT and AST levels after liver transplantation in rats, and enhanced CaMK Ⅱ signaling pathway increases the serum ALT and AST levels after liver transplantation in rats.
Objective To explore the methods of hepatic artery reconst ruction with iliac arterial interpositiongraf t in orthotopic liver t ransplantation (OL T) and influential factor of relevant complications postoperatively.Methods Analyzed ret rospectively 8 OL T , the hepatic artery reconst ruction with arterial inflow based on recipientinf rarenal aorta using donor iliac artery graf t tunneled through the t ransverse mesocolon and pancreas. Results Thetime required for hepatic artery reconst ruction with iliac arterial interposition graf t was 52 - 126 minutes. Amongthe 8 patient s , 2 patient s developed postoperative bililary t ract complications , 1 with biliary fistula , 1 with int rahepatic biloma , the others were recovered smoothly and liver function returned to normal about one week af ter livert ransplantation. No complications of hepatic artery were observed. Conclusion Iliac arterial interpositional graft is aneffective and reliable method of revascularization in liver transplantation when the use of hepatic artery is not possible.
ObjectiveTo clone full-length cDNA of rat galectin-9 and construct recombinant adenovirus granule containing rat galectin-9 gene. MethodsThe galectin-9 gene was amplified by RT-PCR from rat liver tissue and inserted orientationally into plasmid pDC316-GFP digested by restriction endonucleases NotⅠ and HindⅢ. The recombinant pDC316-GFP-galectin-9 shuttle plasmid was identified by PCR, restriction endonuclease digestion and sequencing, and then co-transfected with rescue plasmid pBHGlox△E1.3Cre into HEK-293 cells by liposome reagent. Recombinant adenovirus vector containing rat galectin-9 gene (Ad5-galectin-9) was generated by sitespecific recombination and confirmed by PCR, and then Ad5-galectin-9 was propagated in HEK-293 cells and purified. The infectious titer of viral stock was determined by TCID50 assay. ResultsConstruction of pDC316-GFP-galectin-9 shuttle plasmid was confirmed to be correct by PCR, restriction endonuclease digestion and sequencing. Construction of recombinant adenovirus Ad5-galectin-9 was confirmed to be correct by PCR. The infective titer of Ad5-galectin-9 was 1.4×109 U/ml. ConclusionRecombinant adenovirus vector containing rat galectin-9 gene (Ad5-galectin-9) is successfully constructed, which provides the foundation of further research on the function of galectin-9 gene.