AIFM2 promotes hepatocellular carcinoma metastasis by enhancing mitochondrial biogenesis through activation of SIRT1/PGC-1α signaling.

AIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD+. However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC.

RNA-Sequencing Analysis and Expression of Lymphocyte-Specific Protein Tyrosine Kinase, Linker for Activation of T Cells, and 70-kDa T-Cell Receptor Zeta-Chain Associated Protein Kinase in Rat Liver Transplant Rejection.

OBJECTIVES: The prevention and treatment of liver transplant rejection remain challenging. We investigated the pathophysiological mechanisms of liver transplant rejection in rats and screened candidate genes to determine their degree of rejection response for possible development of potential therapeutic targets. MATERIALS AND METHODS: Brown Norway-Brown Norway transplant tolerant models and Lewis-Brown Norway transplant rejection models were established. We collected liver tissue and venous blood at 7 days posttransplant for hematoxylin and eosin staining and RNA sequencing analysis, respectively. We conducted differential expression gene analysis, KEGG and GO enrichment analysis. We performed immunohistochemistry to detect highly expressed immunerelated proteins, including lymphocyte-specific protein tyrosine kinase, linker for activation of T cells, and 70-kDa T-cell receptor zeta-chain-associated protein kinase. RESULTS: Significant differences were found in liver function and Banff scores between rejection and tolerant groups, indicating the successful establishment of liver transplant models. RNA-sequencing screened 7521 differentially expressed genes, with 3355 upregulated and 3058 downregulated. KEGG analysis of upregulated genes showed that 8 of the top 20 enrichment pathways were associated with immune system processes and 5 were related to immune system diseases. Among these immune pathways, 289 genes were upregulated; of these, 147 genes were removed after comparison with the IMMPORT database, of which 97 genes were significantly changed. Our GO analysis showed upregulated genes mainly participating in immune response processes, with downregulated genes mainly participating in metabolic processes. Real-time polymerase chain reaction and immunohistochemistry verified expression of the immune-related proteins, consistent with RNAsequencing results, which were mainly expressed in inflammatory cells in sinus and portal vein. CONCLUSIONS: Immune-related genes were found to be associated with liver transplant rejection. The 3 immune-related genes that we analyzed may play a role in liver transplant rejection and can possibly serve as candidate markers for monitoring the degree of liver transplant rejection.

Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling.

Hepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro. Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.

Deciphering the molecular mechanism of tetrandrine in inhibiting hepatocellular carcinoma and increasing sorafenib sensitivity by combining network pharmacology and experimental evaluation.

CONTEXT: The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. OBJECTIVE: Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. MATERIALS AND METHODS: CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. RESULTS: For SMMC7721 (IC50 = 22.5 µM) and PLC8024 (IC50 = 18.4 µM), TET (10, 20 µM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 µM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). DISCUSSION AND CONCLUSIONS: TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

Revisiting Orthotopic Rat Liver Transplant.

OBJECTIVES: Orthotopic liver transplant remains technically challenging. MATERIALS AND METHODS: We performed whole graft orthotopic liver transplants with different anhepatic times (≤20 min, n = 19; vs 30 min, n = 9) and partial orthotopic liver transplants in rats including a male-to-male Sprague-Dawley group (n = 15), a male-to-male Lewis-to-Brown Norway group (n = 20), and a male-to-male Sprague-Dawley-to-Lewis group (n = 20); there was also a female-to-male SpragueDawley group (n = 19). RESULTS: For the groups with ≤20-minute or 30-minute anhepatic time, 14-day and 30-day survival rates were 94.7%, 89.5%, 88.9%, and 88.9%, respectively, and there was no difference in survival (P = .716). For 50% orthotopic liver transplants from the male-tomale Sprague-Dawley group, 14-day and 30-day survival rates were 93.3% and 86.7%, respectively, with no difference between whole and 50% graft orthotopic liver transplant. The 14-day and 30-day survival rates were, respectively, 30% and 10% for the Lewis-to-Brown Norway group and 30% and 6.6% for the Sprague-Dawley-to-Lewis group, with no differences between the 2 groups (P = .564). Most of the recipient rats died within 72 hours. Acute rejections and wound dehiscence were the causes of death. Recipients from the female-to-male SpragueDawley orthotopic liver transplant group died shortly after surgery. CONCLUSIONS: Orthotopic liver transplants can be performed to achieve high success rates in the extended anhepatic time; however, orthotopic liver transplants from female Sprague-Dawley donor rats have a high risk of failure.

LncRNA ST8SIA6-AS1 Promotes Cholangiocarcinoma Progression by Suppressing the miR-145-5p/MAL2 Axis.

BACKGROUND: The tumor-promoting roles of ST8SIA6-AS1 and miR-145-5p have been found in several cancers, but their function in cholangiocarcinoma (CHOL) remains speculative. The purpose of this study was to examine the regulatory functions of the ST8SIA6-AS1/MAL2/miR-145-5p pathway in CHOL progression. METHODS: RT-qPCR assay was used to detect ST8SIA6-AS1 expression in CHOL tissues and cell lines. Cell migration, apoptosis, invasion, and proliferation abilities were assessed by RIP, RNA pull-down, and luciferase assays. CCK-8, BrdU, transwell, and FITC assays to investigate the regulatory functions of ST8SIA6-AS1, miR-145-5p, and MAL2 function in CHOL cells. RESULTS: Findings revealed the enrichment of ST8SIA6-AS1 in CHOL tissues and cell lines. It was also found that ST8SIA6-AS1 facilitated cell growth and migration, but it reduced the apoptosis level of the CHOL cells. The results of experiments showed that ST8SIA6-AS1 sponged miR-145-5p, thereby allowing MAL2 to exert its biological function on CHOL cells. CONCLUSION: This research suggested that the ST8SIA6-AS1/miR-145-5p/MAL2 axis could enhance CHOL progression, which might be useful to improve the clinical outcomes of CHOL patients.

The Role of Tacrolimus Nanomicelles in Acute Rejection After Liver Transplantation in Rats.

Although there is some progress in immunosuppressive therapy of acute rejection, there is still a lack of standardized diagnosis and treatment. For the acute rejection after liver transplantation, there is still a lack of an exact treatment at this stage. Tacrolimus (TAC) side effects will also affect the survival rate and quality of life of recipients after transplantation to a large extent. Rat orthotopic liver transplantation model was established and divided into three groups. In the tolerance group, Brown Norway (BN) to Lewis liver transplantation was used; in the rejection group, Lewis to BN liver transplantation was used; in the TAC group, TAC was injected after operation on the basis of establishing rejection model. The expression of GITRL in Kupffer cells and the change of cytokines were detected 7 days after operation. In this study, the animal model of acute rejection of rat liver transplantation was established to simulate the clinical allogeneic liver transplantation, and the important role of TAC in the acute rejection of rat liver transplantation was evaluated.

High glypican-1 expression is a prognostic factor for predicting a poor clinical prognosis in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate, which imposes a huge burden on patients and society. Glypican-1 (GPC1) is considered to be an ideal diagnostic marker. The present study aimed to investigate GPC1 expression in HCC, its association with clinicopathological factors and its prognostic significance in HCC progression. Reverse transcription-quantitative PCR, western blotting and immunohistochemical staining were used to investigate GPC1 expression in 175 HCC and paired normal tissues, and in HCC and normal cells. Serolo2gical levels of GPC1 were examined via enzyme-linked immunosorbent assay in patients with HCC. Kaplan-Meier survival analysis and Cox regression analysis were used to assess the prognostic significance of GPC1. The present results suggested that GPC1 expression was upregulated in HCC tissues, especially in metastatic HCC. Similar results were observed in HCC cell lines. Serum GPC1 was higher in patients with HCC than in healthy controls (HCs). Patients with high GPC1 expression had shorter recurrence-free survival (RFS) and disease-specific survival (DSS) times compared with those with low GPC1 expression. In addition, high GPC1 expression was significantly associated with tumor size and Tumor-Node-Metastasis (TNM) stage (P<0.05). Furthermore, tumor size, TNM stage and GPC1 expression were independent predictive factors for RFS and DSS in patients with HCC. In conclusion, the present results revealed that high GPC1 expression was closely associated with a poor prognosis in patients with HCC and that it may therefore be used as a potential target for accurate diagnosis and treatment of HCC.

Drainage procedure for pancreatolithiasis: re-examination of the pancreatic duct diameter standard.

PURPOSE: Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown. METHODS: The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008-2012 with 3+ years of follow-up were assessed. RESULTS: At postsurgical follow-up (median, 4.5 years; range, 3-7 years; procedure: Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the <8 mm group than in the >8 mm group (P < 0.05), and 80% of the pancreatic fistula cases occurred in the <8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P < 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively. CONCLUSION: Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery.

Knockdown of terminal differentiation induced ncRNA (TINCR) suppresses proliferation and invasion in hepatocellular carcinoma by targeting the miR-218-5p/DEAD-box helicase 5 (DDX5) axis.

Terminal differentiation induced ncRNA (TINCR), a newly identified lncRNA, has been found to be associated with different human cancers including hepatocellular carcinoma (HCC). However, little is known regarding the pathological mechanisms of TINCR in HCC progression. In this study, we confirmed that TINCR expression was upregulated in HCC tumors and cell lines, and high TINCR expression was associated with larger tumor size, advanced tumor node metastasis stage, and poor prognosis. Functionally, knockdown of TINCR facilitated apoptosis and suppressed viability, colony formation and invasion in Huh7 and Hep3B cells. Mechanically, TINCR functioned as competing endogenous RNA (ceRNA) to regulate DEAD-box helicase 5 (DDX5) expression through sponging miR-218-5p. Moreover, the miR-218-5p expression was downregulated and DDX5 expression was upregulated in HCC tumors. The silencing of miR-218-5p or ectopic expression of DDX5 abated the tumor-suppressive effect of TINCR knockdown in vitro. Furthermore, si-TINCR-induced inactivation of AKT signaling was rescued by suppression of miR-218-5p or overexpression of DDX5. Also, the silencing of TINCR resulted in tumor growth inhibition in vivo. In summary, knockdown of TINCR suppressed HCC progression presumably by inactivation of AKT signaling through targeting the miR-218-5p/DDX5 axis, suggesting a novel TINCR/miR-218-5p/DDX5 pathway and therapy target for HCC.

Revisiting Partial Hepatectomy of Large Hepatocellular Carcinoma in Older Patients.

Hepatectomy of large hepatocellular carcinomas (>10 cm) in over 70 year-old patients is presumed futile. We retrospectively reviewed 5970 patients with liver tumors Jan 2010 through Dec 2016 in our institute, of them, 37 older patients with large hepatocellular carcinomas staged I-III and Child-Pugh A liver functions receiving conservative treatments (conservative group, n = 37) and 16 older patients with large hepatocellular carcinomas staged I- III who underwent partial hepatectomy (resection group, n = 16) were included, the risk factors for poor survival were analyzed by univariate and multivariate analyses. Compared with the conservative treatments, Partial hepatectomy achieved better median survival time (25.5 months versus 11 months, log-rank = 0.0001) and better median performance status (1 versus 3, p = 0.023), there was different in Charlson comorbidity index (p = 0.019). For the conservative group, the 3-month, 1, 2, 3-year survival rate was 78.4%, 43.2%, 5.4%, 0%; for the resection group, The 3-month, 1, 2, 3-year survival rate was 100%, 93.7.2%, 56.3%, 12.5%; Multivariate Cox regression analysis showed the Charlson comorbidity index and the performance status associated with poor outcomes of those patients (p = 0.001, 0.018, respectively). Resections of large hepatocellular carcinomas in older patients can be performed safely to prolong life expectancy and improve life quality with or without cancer recurrence.

Tauroursodeoxycholic acid alleviates hepatic ischemia reperfusion injury by suppressing the function of Kupffer cells in mice.

The aim of this study is to investigate the protective effect and the mechanism of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion (IR) injury. Male Balb/c mice were intraperitoneally injected with tauroursodeoxycholic acid (400 mg/kg) or saline solution, once per day for 3 days before surgery, and then the model of hepatic I/R injury was established. Blood and liver samples were collected from each group at 3, 6, and 24 h after surgery. Liver pathological changes, liver function, hepatocyte apoptosis and proinflammatory factors were detected. KCs were extracted, cultured and treated with TUDCA or phosphate-buffered saline (PBS) for 24 h, and then viability and phagocytosis were examined. Additionally, IRE1α/TRAF2/NF-κB pathway activity and AML cell apoptosis were detected. The results showed that TUDCA alleviated hepatic I/R injury, the level of liver function markers, and hepatocyte apoptosis in vivo. Furthermore, the proinflammatory effects of KCs were suppressed by down-regulating IRE1α/TRAF2/NF-κB pathway activity in vivo. TUDCA dose-dependently suppressed the expression of inflammatory factors and IRE1α/TRAF2/NF-κB pathway activity in vitro, consistent with the in vivo results. Therefore, TUDCA can effectively alleviate hepatic IR injury by down-regulating the activity of the IRE1α/TRAF2/NF-κB pathway to suppress the function of KCs.

Investigation of the expressions of MMPs and TIMPs between isogeneic and allogeneic rat aortic transplantation.

The present study investigated the effects of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in transplantation-associated arteriosclerosis by observing their expression in transplanted aortas in rats. Allogenic and isogenic abdominal aortic transplantations were performed and grafts were removed from the recipients at the designated time points (day 7, 14, 28 and 56 post transplantation). Hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and western blot analysis were used to evaluate the grafts. Significant proliferation of the intima was observed in the allogenic transplantation groups (P<0.05). The expressions of MMPs and TIMPs in the allografts were significantly increased compared with the isografts, and the suppression of MMP2 in allografts reduced injury after transplantation. The present study concluded that the imbalance of MMPs and TIMPs led to the disturbance of synthesis and the degradation of the extracellular matrix and it may represent a key cause of chronic rejection.

Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function.

Regulatory T cells in rejected allograft patients display an inability to control responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding CD7. We investigated whether the dysfunctional immunoregulation in liver allograft rejection patients results from reduced regulatory T-cell Gal1 expression and/or responder T-cell CD7 expression. Circulating regulatory T cells and responder T cells were profiled from 31 acute rejection transplant patients, 85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7- responder T cells were co-cultured with regulatory T cells to assess regulatory T-cell suppressor function. Gal1-small interfering RNA was used to silence regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+ regulatory T cells were higher in healthy controls than in transplant patients in remission and lowest in acute rejection transplant patients. Notably, CD7+ responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in the same manner. Silencing Gal1 expression in regulatory T cells reduced their ability to suppress CD7+ (but not CD7-) responder T cells. Additionally, the proportions of CD43+ and CD45+ responder T cells were higher in healthy controls than in acute rejection transplant patients. CD43 co-expression (but not CD45 co-expression) on CD7+ responder T cells promoted their apoptosis in a Gal1-dependent manner. In sum, dysfunctional immunoregulation in liver allograft rejection patients can be partly attributed to reduced regulatory T-cell Gal1 expression and reduced responder T-cell CD7 expression. Responder T-cell CD43 downregulation in acute rejection patients may further contribute to reduced responder T-cell responsiveness to regulatory T-cell control.

Primary mucinous adenocarcinoma of the lung: A case report and review of the literature.

Mucinous adenocarcinoma is an unusual histological type of lung cancer, and its clinicopathological feature is distinctive from that of other histopathological types of lung adenocarcinoma. Mucinous adenocarcinoma has a mucus-producing function, which explains its name. The present study reports a rare case of a mucus-producing adenocarcinoma of the lung. A 60-year-old Chinese female patient was diagnosed with mucinous adenocarcinoma of the lung, which manifested as respiratory symptoms, including fever, cough and expectoration. The patient received thoracic exploratory operation and right pneumonectomy, since the above respiratory symptoms seriously affected her daily life, and other inspections could not establish the diagnosis. Histopathology revealed no mutations in epidermal growth factor receptor. The patient received adjuvant chemotherapy using taxol and cisplatin. However, metastases in the left lung were detected 7 months after the operation. Pemetrexed and cisplatin were used as the second-line treatment. The patient survived 3 years after the initial diagnosis. The present study reports a rare mucus-producing adenocarcinoma of the lung, which is of bad prognosis. Therefore, further studies on this type of cancer are urgently required.

Simultaneous ABO-incompatible living-donor liver transplantation and splenectomy without plasma exchange in China: Two case reports.

ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients. The patients had good graft function without signs of antibody-mediated rejection throughout the 12-month follow-up. Thus, ABO-i LDLT with splenectomy is undoubtedly life-saving when an ABO-compatible graft cannot be obtained for patients in critical condition.

Exogenous vascular endothelial growth factor delivery prior to endothelial precursor cell transplantation in orthotopic liver transplantation-induced hepatic ischemia/reperfusion injury.

Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow-derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)-induced hepatic ischemia/reperfusion injury (HIRI). OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in 6 experimental groups to comparatively assess the effects of the VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome-encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome-encapsulated VEGF plasmid followed by EPCs. VEGF plasmid delivery to liver tissue, endogenous VEGF, and vascular endothelial growth factor receptor (VEGFR) expression, liver transaminase levels, hepatocellular injury levels, apoptosis, apoptotic biomarkers, hepatotrophic mitogens, angiogenesis, and nitric oxide synthase (NOS) activity were assayed after OLT. Exogenous VEGF gene delivery prior to EPC transplantation significantly increased endogenous VEGF and VEGFR expression, significantly reduced liver transaminase levels, significantly reduced hepatocellular injury levels, significantly reduced hepatic apoptosis levels, and significantly reduced several apoptotic biomarkers (ie, B cell lymphoma 2-associated X protein/B cell lymphoma 2 ratio, caspase 3 activity, and heat shock protein 70 expression) in post-OLT-induced HIRI. Moreover, VEGF gene delivery prior to EPC transplantation significantly increased hepatotrophic mitogen expression (ie, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, hepatocyte growth factor, and transforming growth factor α), angiogenesis, and NOS activity in post-OLT-induced HIRI. In conclusion, exogenous liposomal delivery of the VEGF gene prior to bone marrow-derived EPC transplantation may be an effective strategy in decreasing OLT-induced HIRI. Liver Transplantation 23 804-812 2017 AASLD.

A case report of simultaneous orthotopic liver transplantation and jejunectomy.

BACKGROUND: Liver transplantation (LT) accompanied by jejunectomy to treat patients with acute or chronic hepatic cirrhosis with thrombosis in the portal system is extremely rare. CASE PRESENTATION: A 47-year-old man presented with hematemesis and melena, and a diagnosis of decompensated cirrhosis, chronic portal vein thrombosis (PVT) and secondary gastro-esophageal variceal hemorrhage was made. Coagulants were administered, but portal vein thrombi occurred rapidly, and gastrointestinal bleeding recurred shortly thereafter. The patient underwent LT, phlebothrombectomy and a partial jejunectomy. His recovery from a fistula was uneventful, and follow-up visits over 70 months were unremarkable. CONCLUSION: Liver transplantation and partial jejunectomy is a feasible and effective surgical option for select patients with end-stage liver disease accompanied by acute portal venous thrombosis.

Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice.

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity.