Effect of Microstructures of Carbon Nanoproducts Grown on Carbon Fibers on the Interfacial Properties of Epoxy Composites.

Two kinds of carbon nanoproducts with different microstructures, namely, carbon nanotubes (CNTs) and carbon nanofibers (CNFs), were grown on the surface of carbon fibers (CFs) by chemical vapor deposition (CVD) at low temperatures to improve the interface bonding between fibers and resins. The short-beam method and the micro-debonding method were used to test the interlaminar shear strength (ILSS) and interfacial shear strength (IFSS) of the composites. The results showed that the contribution of CNTs to the improvement of interfacial properties was better than that of CNFs. Specifically, the ILSS and IFSS of the CF-CNFs/epoxy composites increased by 18.59 and 24.39%, respectively, while the ILSS and IFSS of the CF-CNTs/epoxy composites increased by 26.97 and 47.79%, respectively. Compared with CNFs, the high degree of graphitization of CNTs and the π-interactions with the resin can better induce the formation of an interphase between the fiber and the resin, which suppressed the initiation of cracks and extended the propagation path of the cracks in the composites.

Influencing factors and growth kinetics analysis of carbon nanotube growth on the surface of continuous fibers.

Carbon nanotubes (CNTs) were continuously grown on the surface of the moving carbon fiber by chemical vapor deposition method using a custom-designed production line to prepare composite reinforcements on a large-scale. The systematic study of different parameters affecting the CNT growth revealed simple growth kinetics, which helps to control the surface morphology and structural quality of CNTs. Since hydrogen maintains the activity of the catalyst, it promotes the growth of CNTs in a continuous process. The increase of acetylene partial pressure promotes the accumulation of amorphous or graphite carbon on the catalyst surface, resulting in the decrease of CNT growth rate when acetylene concentration reaches 40%. The growth temperature significantly affects the CNT diameter and structural quality. As the temperature increases, the crystallinity of the tube wall increases obviously, and the CNT diameter increases due to the aggregate growth of the catalyst particles. According to the Arrhenius formula, the apparent activation energy is observed to be 0.67 eV, which proves that both bulk diffusion and surface diffusion exist when activated carbon passes through the catalyst to form CNTs.

5-Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT-Dependent and Independent Manners.

Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5-HT1D expression level was significantly up-regulated in HCC tissues and cell lines. The 5-HT1D expression level was closely correlated with unfavorable clinicopathological characteristics. Survival analyses show that elevated 5-HT1D expression level predicts poor overall survival and high recurrence probability in HCC patients. Functional studies revealed that 5-HT1D significantly promoted HCC proliferation, epithelial-mesenchymal transition, and metastasis in vitro and in vivo. Mechanistically, 5-HT1D could stabilize PIK3R1 by inhibiting its ubiquitin-mediated degradation. The interaction between 5-HT1D and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) enhanced the expression of FoxO6 through the PI3K/Akt signaling pathway; FoxO6 could also be directly transcriptionally activated by 5-HT1D in an Akt-independent manner. MicroRNA-599 was found to be an upstream suppressive modulator of 5-HT1D. Additionally, 5-HT1D could attenuate tryptophan hydroxylase 1 expression through the PI3K/Akt/cut-like homeobox 1 axis in HCC. Conclusion: Herein, we uncovered the potent oncogenic effect of 5-HT1D on HCC by interacting with PIK3R1 to activate the PI3K/Akt/FoxO6 pathway, and provided a potential therapeutic target for HCC.

miR-214 Down-Regulation Promoted Hypoxia/Reoxygenation-Induced Hepatocyte Apoptosis Through TRAF1/ASK1/JNK Pathway.

OBJECTIVE: This study investigated the role of miR-214 in the hepatocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury. MATERIALS AND METHODS: In vivo hepatic ischemia/reperfusion (HIR) injury, mice model and in vitro HR model were established. miR-214, TRAF1, ASK1, and JNK expression levels were detected by qRT-PCR and western blot. The apoptosis of mouse hepatocyte AML12 was detected by flow cytometry analysis. The interaction between miR-214 and TRAF1 was confirmed by dual-luciferase reporter gene assay. RESULTS: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated in HIR injury mice compared with sham mice. miR-214 expression was down-regulated in liver tissues of HIR and H/R-induced hepatocytes, whereas TRAF1, ASK1, and JNK expressions were up-regulated in HIR and H/R groups. H/R stimulation promoted the apoptosis of hepatocytes, and miR-214 overexpression inhibited the apoptosis of hepatocytes. Besides, TRAF1 was a target of miR-214 and negatively regulated by miR-214. miR-214/TRAF1 pathway involved in the modulation of H/R-induced apoptosis of hepatocytes. In vivo study proved miR-214 reduced hepatic injury of HIR mice. CONCLUSION: miR-214 overexpression reduces hepatocyte apoptosis after HIR injury through negatively regulating TRAF1/ASK1/JNK pathway.

The mechanism of long non-coding RNA MEG3 for hepatic ischemia-reperfusion: Mediated by miR-34a/Nrf2 signaling pathway.

To investigate the function of MEG3 in hepatic ischemia-reperfusion (HIR) progress, involving its association with the level of miR-34a during hypoxia-induced hypoxia re-oxygenation (H/R) in vitro. HIR mice model in vivo was established. MEG3, miR-34a expression, along with Nrf2 mRNA and protein level were detected in tissues and cells. Serum biochemical parameters (ALT and AST) were assessed in vivo. A potential binding region between MEG3 and miR34a was confirmed by luciferase assays. Hepatic cells HL7702 were subjected to hypoxia treatment in vitro for functional studies, including TUNEL-positive cells detection and ROS analysis. MEG3, Nrf2 expression was significantly down-regulated in infarction lesion from HIR mice, as opposed to increased miR-34a production, while similar results were also observed in H/R HL7702 cells, while the above effects were reversed by MEG3 over-expression. By using bioinformatics study and RNA pull down combined with luciferase assays, we demonstrated that MEG3 functioned as a competing endogenous RNA (ceRNA) for miR-34a, and there was reciprocal repression between MEG3 and miR-34a in an Argonaute 2-dependent manner. Functional studies demonstrated that MEG3 showed positive regulation on TUNEL-positive cells and ROS level. Further in vivo study confirmed that MEG3 over-expression could improve hepatic function of HIR mice, and markedly decreased the expression of serum ALT and AST. MEG3 protected hepatocytes from HIR injury through down-regulating miR-34a expression, which could add our understanding of the molecular mechanisms in HIR injury.

lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214.

The aberrant expression of long noncoding RNAs (lncRNAs) has been involved in various human tumors including hepatocellular carcinoma (HCC). Our study aimed to investigate the potential molecular mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in HCC. The expression of MIAT and micro-RNA (miR)-214 in HCC tissues and cells was examined by quantitative real-time PCR, and the levels of enhancer of zeste homolog 2 (EZH2) and ß-catenin were detected by Western blot assay. Immunoprecipitation analysis was used to detect the level of H3/H4 histone acetylation. RNA pull-down assay was performed to confirm the targeting regulatory relationship between miR-214 and MIAT. Cell viability, proliferation, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), [3H]thymidine incorporation, and Transwell assays, respectively. BALB/c nude mice were used to establish a hepatocellular carcinoma animal model with subcutaneous injection of SK-HEP-1 cells. Upregulation of MIAT is related to the proliferation and invasion of HCC, and downregulating MIAT expression inhibited HCC cell proliferation and invasion. The H3/H4 histone acetylation level of MIAT promoter in HCC tissues was higher than that in normal tissues. MIAT negatively regulated miR-214 in HCC cells. Inhibition of miR-214 reversed the influence of MIAT downregulation on HCC cell proliferation and invasion. In nude mouse xenograft models, downregulation of MIAT markedly suppressed the tumor growth of HCC via releasing miR-214. In conclusion, lncRNA MIAT promotes the proliferation and invasion of HCC cells through sponging miR-214, which brings a novel target for the therapy and prognosis of hepatocellular carcinoma. NEW & NOTEWORTHY This is the first research showing long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) to have a regulatory effect on hepatocellular carcinoma. Micro-RNA (miR)-214 could be sponged by MIAT to promote the proliferation and invasion of hepatocellular carcinoma cells. The lncRNA MIAT/miR-214 axis brings a novel insight for the therapy and prognosis of hepatocellular carcinoma.

Synthesis and growth mechanism of carbon nanotubes growing on carbon fiber surfaces with improved tensile strength.

An effective approach has been developed for the catalytic decomposition of acetylene (C2H2) by chemical vapor deposition (CVD), to achieve homogeneous growth of carbon nanotubes (CNTs) on the surfaces of carbon fibers. The morphology of CNTs grown on carbon fiber surfaces was observed by a scanning electron microscope and high-resolution transmission electron microscope, which revealed the uniform coverage of CNTs on the carbon fiber surfaces. The single fiber tensile test demonstrated that the tensile strength of carbon fibers could be increased by more than 12% with the catalytic growth of CNTs on their surface. The reparation of the damage caused during the formation of catalyst nanoparticles, and the cross-link of neighboring graphite crystallites induced by CNTs all occurred during the CVD process, which were considered to be the main reasons for improvement. The growth mechanism model of CNTs formation was established based on the thermodynamics principle and the interface microstructure of CNT-grown carbon fiber, illuminating the detailed mechanism for the growth of CNTs and the change of the shape of catalyst particles.

C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion of ERO1α signalling in acute liver failure.

CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) has been shown to be a key molecule in endoplasmic reticulum (ER) stress-mediated apoptosis. ER oxidoreductin 1-α (ERO1α), a target of CHOP, is an important oxidizing enzyme that regulates reactive oxygen species (ROS), which play a prominent role in hepatocellular death during acute liver failure (ALF). However, little is known about how CHOP facilitates ROS-induced hepatocellular injury. The present study was designed to investigate the roles and molecular mechanisms of CHOP in ALF. In the liver tissues from ALF patients, the expression of CHOP was significantly increased, which was accompanied by increased expression of dsRNA-dependent protein kinase (PKR)-like ER kinase (PERK) signalling, activating transcription factor 4 (ATF6) signalling, inositol-requiring enzyme-1 (IRE1) signalling and ERO1α, as compared with healthy controls. In the mouse model of galactosamine (GaIN)/lipopolysaccharide (LPS)-induced ALF, the hepatocellular injury was accompanied by up-regulated PERK signalling, ATF6 signalling, IRE1 signalling, CHOP and ERO1α. In contrast, CHOP deficiency decreased hepatocellular apoptosis/necrosis and increased animal survival. Furthermore, disruption of CHOP decreased ERO1α expression leading to reducing ROS-induced cell death in vivo and in vitro. Interestingly, ERO1α overexpression restored GaIN/LPS-induced hepatocellular injury in CHOP-deficient mice. Our studies demonstrate for the first time that CHOP promotes liver damage during ALF through activation of ERO1α, a key mediator to link ER stress and ROS. Therefore, targeting CHOP/ERO1α signalling could be a novel therapeutic approach during ALF.

De novo phyllodes tumor in an adolescent female after liver transplantation.

Phyllodes tumor of the breast is a rare disease constituting 0.3-0.9% of all breast neoplasms. Occurring mainly in females aged 35 to 55 yr, the disease is especially rare among adolescent females. There is no published literature about de novo phyllodes tumor after liver transplantation. Here we describe a case of de novo phyllodes tumors in an adolescent female after liver transplantation from a living donor for Wilson disease.

Visualization of microfibrillar elements in cross-section of polyacrylonitrile fiber along the fiber spinning line.

The microfibrils served as the structural elements in polyacrylonitrile (PAN) fiber, which played an important role in the quality of the PAN precursor fibers. Their morphologies were examined by the scanning electron microscopy (SEM), atomic force microscopy (AFM) and high-resolution transmission electron microscope (HRTEM). The microfibrils existed in all of PAN fibers and arranged evenly in the cross-sections. Furthermore, the pores existed between the microfibrils. The unoriented microfibrillar network was already formed in nascent fiber during coagulated process. Although the microfibrillar network was elongated and the microfibrils oriented along the fiber longitudinal direction during the spinning process, the interconnected microfibrillar network was still existed in the fiber transverse section. Furthermore, the transverse connection of the microfibrils was reinforced and the small microfibrils were tended to aggregate into the large fibrils. For mechanical performance of PAN fibers, their tensile strength increased to 708 MPa and the elongation at break decreased to 15.5%. PAN fibers exhibited ductile rupture during the mechanical test and the microfibrils served as reinforcing elements.

Paradoxical approach towards coexistence of hepatic cyst and liver sarcoma: A case report.

INTRODUCTION: Liver sarcoma is exceedingly rare and is a clinical challenge. CASE REPORT: A 69-year-old female presented with right upper quadrant pain after a fall. Her CT scan showed multiple cysts. She was initially diagnosed as hepatic cysts with hemorrhage and underwent puncture and drainage of liver cysts. But the cysts relapsed quickly. Then she underwent fenestration of the hepatic cysts. The liver cysts reoccurred again accompanied by massive bleeding and obstructive jaundice. She underwent right trihepatectomy and her final pathological report showed liver sarcoma. However, the hepatic sarcoma reoccurred again. Its' diagnosis and treatment process are extremely complex. In the end, she had a bad ending. CONCLUSION: We believe that timely diagnosis and complete excision of liver sarcoma are very important.

Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling.

OBJECTIVES: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen reactivated in several human malignancies. So far, the major focus of studies on KK-LC-1 has been on its potential as diagnostic biomarker and immunotherapy target. However, its biological functions and molecular mechanisms in cancer progression remain unknown. MATERIALS AND METHODS: Expression of KK-LC-1 in HCC was analysed using RT-qPCR, Western blot and immunohistochemistry. The roles of KK-LC-1 on HCC progression were examined by loss-of-function and gain-of-function approaches. Pathway inhibitor DAPT was employed to confirm the regulatory effect of KK-LC-1 on the downstream Notch signalling. The interaction of KK-LC-1 with presenilin-1 was determined by co-immunoprecipitation. The association of CpG island methylation status with KK-LC-1 reactivation was evaluated by methylation-specific PCR, bisulphite sequencing PCR and 5-Aza-dC treatment. RESULTS: We identified that HCC tissues exhibited increased levels of KK-LC-1. High KK-LC-1 level independently predicted poor survival outcome. KK-LC-1 promoted cell growth, migration, invasion and epithelial-mesenchymal transition in vitro and in vivo. KK-LC-1 modulated the Notch1/Hes1 pathway to exacerbate HCC progression through physically interacting with presenilin-1. Upregulation of KK-LC-1 in HCC was attributed to hypomethylated CpG islands. CONCLUSIONS: This study identified that hypomethylation-induced KK-LC-1 overexpression played an important role in HCC progression and independently predicted poor survival. We defined the KK-LC-1/presenilin-1/Notch1/Hes1 as a novel signalling pathway that was involved in the growth and metastasis of HCC.

A Pharmacogenomic Landscape in Human Liver Cancers.

Liver cancers are highly heterogeneous with poor prognosis and drug response. A better understanding between genetic alterations and drug responses would facilitate precision treatment for liver cancers. To characterize the landscape of pharmacogenomic interactions in liver cancers, we developed a protocol to establish human liver cancer cell models at a success rate of around 50% and generated the Liver Cancer Model Repository (LIMORE) with 81 cell models. LIMORE represented genomic and transcriptomic heterogeneity of primary cancers. Interrogation of the pharmacogenomic landscape of LIMORE discovered unexplored gene-drug associations, including synthetic lethalities to prevalent alterations in liver cancers. Moreover, predictive biomarker candidates were suggested for the selection of sorafenib-responding patients. LIMORE provides a rich resource facilitating drug discovery in liver cancers.

Liver transplantation using the otherwise-discarded partial liver resection graft with hepatic benign tumor: Analysis of a preliminary experience on 15 consecutive cases.

RATIONALE: The shortage of available donor organs limits the development of liver transplantation. This case-serial study presents a novel way to expand the donor pool by using the other-wise discarded partial liver resection graft with hepatic benign tumor. PATIENT CONCERNS: From 2012 to 2016, 15 patients with hepatic lesions were admitted to our hospital. 12 patients suffered from right epigastric discomfort and 3 patients worried about uncertain diagnosis. INTERVENTIONS: Regular hepatic lobectomy was performed for all patients and after back-table management the resected partial liver grafts were used for patients with end-stage liver disease for liver transplantation. OUTCOMES: All patients had improved liver function within 1 week of transplantation. Patients had no serious small-for-size syndrome despite graft-to-recipient weight ratio less than 0.8%. Back-table hepatic venous reconstruction with prosthetic vascular grafts was performed without serious early complications, and late thrombosis in vessel graft did not affect liver function. Postoperative computed tomography scans demonstrated a remarkable growth in graft volume and a continuous decrease in hemangioma in recipients using the grafts with hemangioma. One patient died from pulmonary embolism on day 7 after transplant, and the rest of 14 recipients had been surviving well, especially recipient 1 for more than 4 years, although 3 recipients had tumor recurrence and had been treated with sorafenib. DIAGNOSES: The postoperative pathological diagnosis reported cavernous hemangioma (n = 11), perivascular epithelioid cell tumor (n = 2), inflammatory pseudotumor for (n = 1), and focal nodular hyperplasia (n = 1). LESSONS: The partial liver grafts with hepatic benign tumors are safe for liver transplantation. In addition, prosthetic vascular grafts can be used for hepatic venous outflow reconstruction, especially in right lobe liver transplantation.

Short-term starvation attenuates liver ischemia-reperfusion injury (IRI) by Sirt1-autophagy signaling in mice.

Calorie restriction or starvation (fasting) has some beneficial effects in terms of prolonging life and increasing resistance to stress. It has also been shown that calorie restriction has a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying mechanism has not been elucidated. In this study we investigated the effects and molecular mechanisms of short-term starvation (STS) on liver IRI in a mouse liver IRI model. We found that STS significantly attenuated liver IRI in this model, as evidenced by inhibition of serum aminotransferase levels, and decreased pathological damage and hepatocellular apoptosis, especially after 2- or 3-day starvation. Furthermore, we found that 2- or 3-day starvation induced expression of hepatocellular autophagy in vivo and in vitro. Further experiments provided support for the notion that STS-induced autophagy played a key role during starvation-regulated protection against liver IRI via autophagy inhibition with 3-methyladenine. Interestingly, the longevity gene Sirt1 was also significantly up-regulated in liver after STS. Importantly, inhibition of Sirt1 by sirtinol abolished STS-induced autophagy and further abrogated STS-mediated protection against liver IRI. In conclusion, our results indicate that STS attenuates liver IRI via the Sirt1-autophagy pathway. Our findings provide a rationale for a novel therapeutic strategy for managing liver IRI.

Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers.

Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.

Up-regulation of miR-877 induced by paclitaxel inhibits hepatocellular carcinoma cell proliferation though targeting FOXM1.

Paclitaxel is an effective chemotherapeutic agent for treatment of cancer patients, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miR-877 associated with HCC cell lines response to paclitaxel and to evaluate these miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the expression of miR-877 in paclitaxel-treated HCC cell lines. We verified that miR-877 was up-regulated in paclitaxel-induced HCC cells by real-time PCR. We further investigated the role and mechanisms of miR-877. Over-expression of miR-877 in HCC cells partially restores paclitaxel sensitivity. The proliferation activity and the colony formation activity of HCC cells were both inhibited after transfected with miR-877. MiRNA targets prediction algorithms imply FOXM1 serves as a target gene for miR-877. A fluorescent reporter assay confirmed that miR-877 binds specifically to the predicted site of the FOXM1 mRNA 3'-untranslated region (3'UTR). When miR-877 was overexpressed in HCC cells, the protein levels of FOXM1 was downregulated. These results indicate that miR-877 could influence the sensitivity of paclitaxel treatment in hepatocellular carcinoma cell lines by targeting FOXM1.

Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell transplantation­induced tumor growth.

Previous studies revealed that Kanglaite (KLT) exhibits antitumor and immunomodulatory activities. In the present study, we show that KLT treatment stimulated the immune response by increasing the number of T cells and natural killer (NK) cells in the blood of hepatocellular carcinoma (HCC) patients. Experiments in tumor-bearing mice were further designed in order to explore the effects of KLT on the immune system and the underlying molecular mechanisms. The results showed that KLT improves the tumor cell transplantation-induced reduction in the serum level of the cytokines IFN­Î³ and IL­2, and rescues the levels of CD4+ T cells in host mice. These events enhanced the cytotoxic activities of natural killer and CD8+ T cells against the hepatic HepG2 cancer cells. KLT administration further increased the mRNA level of certain nuclear factor κB (NF­κB)­responsive genes in CD4+ cells. The chromatin immunoprecipitation assay showed that KLT increases the association of the NF-κB p65 subunit to the promoter regions of interleukin (IL)-2- and B-cell lymphoma (Bcl)-2-encoding genes in CD4+ T cells. Our study demonstrated that KLT is the main active ingredient of coix seed exhibiting anticancer and immunomodulatory properties. Induction of NF-κB­mediated gene transcription in CD4+ T cells is involved in the immunomodulatory activity of KLT.

Magnesium isoglycyrrhizinate protects hepatic L02 cells from ischemia/reperfusion induced injury.

Human liver ischemia/reperfusion injury (IRI) is a common and major clinical problem complicating liver surgery and transplantation. The pathogenesis underlying IRI is complex, involving a series of signaling mediators and mechanisms. This study aimed to investigate the effects of Magnesium Isoglycyrrhizinate (MgIG) on the changes of oxidant stress and apoptosis induced by IRI in human hepatic L02 cells. L02 cells with IRI were treated with or without MgIG and mitoKATP (Mitochondrial adenosine triphosphate-dependent potassium) channel modulators. Cell viability was assessed using CCK-8 assay. Cell apoptosis was quantified by flow cytometry. The activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. Effects of MgIG on the expression of Bax, Bcl-2, Caspase 3, PARP (poly ADP-ribose polymerase), Akt, and ERK in L02 cells with IRI were examined. Our results showed that MgIG treatment significantly reduced the population of apoptotic cells and the expression of apoptosis-related proteins in hepatic L02 cells with IRI. MgIG also counteract ischemia reperfusion induced oxidative challenge as it effectively reduced malondialdehyde (MDA) and increased the activities of SOD and GSH-Px. L02 cells treated with MgIG showed increased expression of p-Akt and p-ERK, indicating that the protective effect of MgIG might be associated with the activation of Akt and ERK pathways. Moreover, the addition of Diazoxide (DE), a mitoKATP channel opener, enhanced the cytoprotective activity of MgIG, while the mitoKATP blocker 5-hydroxydecanoate (5-HD) reduced the cytoprotective activity of MgIG.

The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats.

Hydrogen sulfide (H2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H2S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpression of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H2S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H2S on hepatic I/R injury in the old rats. This study reveals the different effects of H2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H2S in miR-34a modulation of the Nrf-2 pathway.