Energy Level Engineering in Gold Nanoclusters for Exceptionally Bright NIR Electrochemiluminescence at a Low Trigger Potential.

Electrochemiluminescence (ECL) is a widely used light output mechanism from electrochemical excitation. Understanding the intrinsic essence for ideal ECL generation remains a fundamental challenge. Here, based on the molecular orbital theory, we reported an energy level engineering strategy to regulate the ECL performance by using ligand-protected gold nanoclusters (AuNCs) as luminophores and N,N-diisopropylethylamine (DIPEA) as a coreactant. The energy level matching between the AuNCs and DIPEA effectively promoted their electron transfer reactions, thus improving the excitation efficiency and reducing the trigger potential. Simultaneously, the narrow band gap of the AuNCs further enabled enhanced emission efficiency. Using the energy level engineering theory developed here, a dual-enhanced strategy was proposed, and ß-CD-AuNCs were designed to further verify this mechanism. The ß-CD-AuNCs/DIPEA system resulted in highly stable near-infrared ECL with an unprecedented ECL efficiency (145-fold higher than that of the classic Ru(bpy)32+/tetra-n-butylammonium perchlorate system) and a low trigger potential of 0.48 V. A visual NIR-ECL based on this ECL system was successfully realized by an infrared camera. This work provides an original mechanistic understanding for designing efficient ECL systems, which promises to be a harbinger for broad applicability of this strategy for other ECL systems and ECL sensing platforms.

Co-Reactant-Mediated Low-Potential Anodic Electrochemiluminescence Platform and Its Immunosensing Application.

Screening high-performance anodic electrochemiluminescence (ECL) systems with low triggering potential is a promising way to broaden their applications. In addition to electrochemiluminophore, co-reactant also plays an important role in the ECL process, since the oxidation of co-reactants is one of the most important steps in the anodic ECL process. Herein, a novel co-reactant-mediated high-performance low-potential Au nanocluster (AuNC)-based ECL system has been successfully developed. Benefiting from the isopropyl substitution and hydroxyl addition to the triethylamine (TEA), the BSA-AuNC/2-(diisopropylamino)ethanol (DIPEA-OH) ECL system achieved higher energy efficiency at a lower potential of 0.75 V. In addition, compared with the BSA-AuNC/TEA system, the ECL intensity and quantum yield (ΦECL) with DIPEA-OH as a co-reactant increased 22.34-fold and 13-fold (as high as 68.17%), respectively. Based on the low potential, high ΦECL of the AuNC/DIPEA-OH ECL system, a sandwich-type immunosensor has been constructed for a highly selective SARS-CoV-2 N protein assay. In the absence of any complex signal amplification strategies, the ECL immunosensor for the SARS-CoV-2 N protein detection showed a linear range of 0.001-100 ng/mL and a detection limit of 0.35 pg/mL. Moreover, the ECL platform had good reproducibility and stability and exhibited acceptable detection performance in the detection of actual serum samples. This work established a framework for in-depth design and study of anode ECL co-reactants for AuNCs and other luminophores, and expanded the potential application of ECL sensors in the clinical diagnosis of COVID-19.

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival.

BACKGROUND: ATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC. METHODS: One hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence. RESULTS: Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (Highnucleus/Lowcytosol), moderate risk (Highnucleus/Highcytosol or Lownucleus/Lowcytosol), and low risk (Lownucleus/Highcytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015). CONCLUSIONS: High nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increased ubiquitination of thioredoxin-interacting protein.

Numerous studies have revealed that hyperglycemia is a pivotal driver of diabetic vascular complications. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). In this study, a downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanistically, SNHG15 reduced thioredoxin-interacting protein (TXNIP) expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of lncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. In conclusion, SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.

Laparoscopic ultrasound-guided superselective portal vein injection combined with real-time indocyanine green fluorescence imaging and navigation for accurate resection of localized intrahepatic bile duct dilatation: a case report.

BACKGROUND: Primary intrahepatic bile duct dilatation can be very harmful to patients although it belongs to benign biliary disease. It can occur in any part of the liver, intraoperative laparoscopic ultrasound (LUS) guidance combine with real-time indocyanine green (ICG) fluorescence navigation are the means of choice for accurate surgical resection. CASE PRESENTATION: Herein we reported a 43-year-old female patient presented with repeated right upper abdominal pain and distension for 3 years and aggravated for half a year, without fever and jaundice. A diagnosis of localized bile duct dilatation with lithiasis in segment 4 (S4) was made on the basis of preoperative imaging. Correspondingly, we selected to perform a laparoscopic surgery with LUS guided real time ICG fluorescence imaging (ICG-FI) and navigation to make the operation more simply and accurately, as well as to retain normal tissues in a certain extent. Laparoscopic resection of S4b and partial S4a was successfully performed, without any complications. CONCLUSION: Laparoscopic anatomical surgery for intrahepatic bile duct dilatation is a technically challenging operation. The combined use of preoperative three-dimensional computerized tomography (CT) planning, intraoperative LUS guided super-selection, ICG hepatic segment staining and real-time fluorescence navigation could help surgeons accurately complete the segmentectomy or subsegmentectomy with minimized trauma and maximized liver tissue preservation.

Biliary diseases as main causes of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

BACKGROUND & AIMS: Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. METHODS: An analysis between pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates and those caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae was performed. RESULTS: Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae were biliary disorders including extra- and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus. CONCLUSIONS: Pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates mainly occurs in patients with biliary disorders or with a treatment history of malignancy. The mainstay of treatment remains carbapenems in combination with adequate aspiration or drainage.

CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma.

BACKGROUND: Increasing evidence indicates that downregulation of cell adhesion molecule 1 (CADM1) contributes to tumorigenesis in various cancers. The present study was undertaken to investigate the CADM1 expression pattern in human hepatocellular carcinoma (HCC), and to elucidate the mechanism underlying CADM1-mediated tumor suppression. METHODS: CADM1 expression in HCC cell lines was measured by quantitative real-time PCR. The function of CADM1 in the context of tumor suppression in HCC cells was determined using proliferation assays, cell cycle analysis, EdU incorporation assays, in vitro colony formation analysis, and in vivo tumorigenicity assays. The mechanism by which CADM1 acts as a tumor suppressor gene in HCC was investigated using Western blotting analysis. RESULTS: Downregulation of CADM1 expression is frequently detected in both HCC cells and clinical samples. Restoration of CADM1 expression in HCC cell lines significantly inhibits cell growth and negatively regulates the G1/S transition. CADM1 overexpression can inhibit the tumorigenicity of HCC cells both in vitro and in vivo. Western blotting analysis revealed that ectopic expression of CADM1 in HCC cells is associated with increased expression of Retinoblastoma (Rb) protein. CONCLUSIONS: Our results showed that suppression of tumorigenesis by CADM1 may be mediated by the Rb-E2F pathway, involving upregulation of Rb protein levels. This pathway could therefore represent an attractive target for HCC therapy.

Endovascular treatment of isolated abdominal aortic dissection and postoperative aortic remodeling.

OBJECTIVE: We report our experience of endovascular management and postoperative aortic remodeling of all types of isolated abdominal aortic dissection (IAAD). METHODS: This was retrospective study of 28 IAAD patients treated by endovascular means in our department between January 2007 and July 2013. We reviewed the risk factors, clinical features, computed tomography images, follow-up results, and aortic remodeling of these IAAD patients and propose a new morphologic classification into three types-supraceliac, paravisceral, and infrarenal-according to the location of the primary entry site. RESULTS: There were four supraceliac IAADs, one paravisceral IAAD, and 23 infrarenal IAADs in our case series. Suprarenal (supraceliac + paravisceral) IAAD patients were relatively younger than infrarenal patients (45.2 ± 8.6 years vs 60.6 ± 15.5 years; P < .05). No difference was observed between suprarenal and infrarenal IAADs with respect to true lumen, false lumen, and dissection length on imaging (P > .05). All patients received endovascular treatment. The primary technical success rate was 100%. During a follow-up of 35.7 ± 19.9 months, only one infrarenal patient needed an endovascular reintervention. All patients with supraceliac or infrarenal IAADs were alive at the time of follow-up; however, a paravisceral patient died of a dissecting abdominal aortic aneurysm rupture 21 months after endovascular treatment. In the suprarenal and infrarenal groups, endovascular treatment was associated with a significant decrease in the false lumen size and increase in the true lumen size (P < .05). The maximum abdominal aorta diameter decreased after endovascular treatment in both groups but was statistically significant only in the infrarenal group (P < .05). CONCLUSIONS: IAAD is a rare vascular disease. We propose it should be categorized as supraceliac, paravisceral, and infrarenal IAAD according to the location of the primary entry site. Endovascular treatment for supraceliac and infrarenal IAADs is a safe method with a high technical success rate and promising aortic remodeling, whereas endovascular treatment for paravisceral IAADs remains difficult.

Evaluating the effectiveness of illness script teaching on clinical reasoning skills in post-baccalaureate nursing students.

BACKGROUND: Typically, nurse education curricula are separated into the teaching of theoretical knowledge and practical skills. This separation may hinder nursing students' development of clinical reasoning skills, making it difficult for them to prioritize tasks and make decisions about interventions. Illness scripts have been shown to help medical students improve their clinical reasoning skills; however, they are rarely used in nurse education. OBJECTIVES: To evaluate the influence of illness script teaching method on post-baccalaureate nursing students' clinical reasoning skills. DESIGN: The study adopted a single-arm quantitative pre-experimental research design and incorporated qualitative focus group discussions. SETTINGS/PARTICIPANTS: This study was conducted at a university in northern Taiwan. Participants included 35 post-baccalaureate nursing students who were enrolled in an elective course focused on clinical skills. METHODS: To enhance nursing students' clinical reasoning skills, illness scripts for five clinical scenarios were developed and implemented as part of their curriculum. The Nurses Clinical Reasoning Scale was utilized to assess self-rated clinical reasoning abilities, while dual-teacher scoring was used to evaluate clinical reasoning objectively. The VARK learning preference questionnaire was used to examine how learning preferences affect learning outcomes. After the course, semi-structured focus groups were held to collect student feedback on the effectiveness of the teaching methods and the learning outcomes. RESULTS: This study's quantitative and qualitative results show that illness script-based teaching improves nursing students' clinical reasoning. Quantitative results showed significant objective reasoning score improvements. However, minimal changes in self-rated scores suggest a learning style-influenced gap between perceived and actual abilities. Qualitative findings showed that students valued linking clinical issues to practical applications but struggled with knowledge gaps and engagement. CONCLUSIONS: The illness script teaching method improved students' understanding of clinical scenarios and enhanced their clinical reasoning abilities. Incorporating illness scripts into nurse education was beneficial for nursing students.

MicroRNA-561-5p Inhibits Cell Proliferation and Invasion by Targeting RAC1 in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study aims to investigate how miR-561-5p regulated the expression of RAC1 and whether its effects on RAC1 was associated with the proliferation, migration, invasion, and apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. MATERIALS AND METHODS: RT-qPCR was performed to assess miR-561-5p expression in human PDAC tissues. A series of in vitro experiments including cell counting Kit-8, colony formation, cell migration and invasion, and apoptosis assays were used to assess the PDAC cell biological behaviors. TargetScan v7.2 was used to identify the miR-561-5p target genes, dual-luciferase reporter assay was performed to confirm the targeted relationship between miR-561-5p and Rac family small GTPase 1 (RAC1). Also, RAC1 was upregulated in miR561-5p overexpressed PDAC cells to evaluate the functional involvement of RAC1 in miR-561-5p mediated PDAC cell proliferation and invasion. RESULTS: The results demonstrated that miR-561-5p expression was lower in PDAC tissues compared with in normal tissues. Overexpression of miR-561-5p inhibited PDAC cell proliferation, migration, and invasion, and promoted apoptosis in vitro, while miR-561-5p-knockdown had the opposite effects in the PDAC cell line BxPC3. Using bioinformatics analysis and dual-luciferase reporter assays, the present study revealed that RAC1 was a direct target of miR-561-5p and that RAC1 overexpression could partly rescue the suppressive effects of miR-561-5p mimics on PDAC cells. CONCLUSION: The overexpression of miR-561-5p may suppress carcinogenesis in PDAC cells by targeting RAC1 and inhibit PDAC cell proliferation and invasion.

Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation.

BACKGROUND: The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression. MATERIALS AND METHODS: We examined the expression of HOTAIR in 110 HCC samples using real-time reverse transcription-polymerase chain reaction and analyzed its correlation with clinical parameters and prognosis in 60 HCC patients that have undergone liver transplantation (LT). Suppression of HOTAIR using siRNA was performed to explore its roles in tumor progression. RESULTS: The expression level of HOTAIR in cancer tissues was higher than in adjacent noncancerous tissues. High expression level of HOTAIR was an independent prognostic factor for predicting HCC recurrence in LT patients (P = .001, hazard ratio, 3.564). Furthermore, in patients exceeding the Milan criteria, those with a high expression level of HOTAIR revealed a significantly shorter recurrence-free survival. Moreover, siRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-α induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin. CONCLUSIONS: The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.

Experimental and clinical evidence suggests that GRPEL2 plays an oncogenic role in HCC development.

Hepatocellular carcinoma (HCC) continues to cause severe burden worldwide. The limited options especially toward HCC with metastasis prompts us to identify novel molecules for either diagnostic/prognostic or therapeutic purposes. GRPEL2 is well defined in maintaining mitochondrial homeostasis, which is critical to multiple biological processes for cancer survival. However, its role in HCC progression was not investigated before. In our analysis using data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) dataset and tissue microarray, higher expression levels of GRPEL2 were obseved in HCC tissues compared to in normal liver tissues, and indicated higher tumor grade, higher tumor stage, and shorter overall survival (OS). Consistent with the results of above analyses, the functional experiments validated that GRPEL2 acted as a tumor-promoting factor in HCC progression. GRPEL2 knockdown suppressed cell growth, migration, and invasion in vitro, as well as inhibited tumor growth in vivo. Moreover, GRPEL2 deficiency also accelerated reactive oxygen species (ROS) production and increased mitochondrial membrane potential (MMP), leading to cell apoptosis. In addition, we found that the cell cycle and NF-κB signaling pathways were responsible for GRPEL2-induced HCC progression, based on the results of Gene Set Enrichment Analysis (GSEA) and subsequent experimental validation. Our study, for the first time, identified the role of GRPEL2 in HCC development and provided a compelling biomarker for targted therapy in HCC treatment.

Size-focusing results in highly photoluminescent sulfur quantum dots with a stable emission wavelength.

Sulfur quantum dots (SQDs) are a new kind of functional nanomaterial, but several challenges still exist in relation to their synthesis and application, such as low-yield and time-consuming synthetic methods, low photoluminescence quantum yields (PLQYs), and the non-selectivity of their detection mechanisms. Herein, we report the drastic enhancement of the fluorescence performance of water-soluble SQDs via the one-pot synthesis of size-focusing QDs using ultrasound microwave radiation. The synthetic period has been greatly shortened to 2 h via the present process. Notably, the proposed SQDs exhibit a highly stable emission wavelength with a record high PLQY of 58.6%. The mechanistic study indicates that size-focusing is a key factor relating to the proposed high-performance SQDs. As they also have robust stability, the proposed SQDs show a wide range of potential applications. Inspired by the characteristic properties of the SQDs and specific analytes, a simple SQD-based fluorescence sensing platform, via a redox-reaction-mediated mechanism, has been successfully developed for the rapid and selective detection of Ce(iv). In addition, this system has been effectively applied to some Ce(iv)-related biological assays, such as ascorbic acid (AA) analysis. This work is an important breakthrough in the SQD field, opening up avenues for solving the challenging problems relating to SQD-based probes, enriching the fundamental understanding of them, and greatly extending their applications, especially in biomedicine.

LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increasing ubiquitination of thioredoxin-interacting protein.

OBJECTIVE: Numerous evidence indicates that hyperglycemia is a pivotal driver of the vascular complications of diabetes. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). MATERIALS AND METHODS: Cell proliferation, migration, apoptosis, and tube formation were measured by cell counting kit-8 assay, transwell assay, flow cytometry, and tube formation assay, respectively. RNA pull-down and RNA-binding protein immunoprecipitation were used to detect the interaction between lncRNA SNHG15 and thioredoxin-interacting protein (TXNIP). Co-immunoprecipitation was used to detect the ubiquitination level of TXNIP and the interaction between TXNIP and E3 ubiquitin ligase ITCH. RESULTS: A downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanically, SNHG15 reduced TXNIP expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of LncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. CONCLUSION: SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.

Compare with safety and efficacy of entecavir and adefovir dipivoxil combination therapy and tenofovir disoproxil fumarate monotherapy for chronic hepatitis B patient with adefovir-resistant.

Objective: To compare the 2-year efficacy and safety of combination therapy with entecavir (ETV) and adefovir dipivoxil (ADV) to that of tenofovir disoproxil fumarate (TDF) monotherapy in treatment of patients with adefovir drug-resistant chronic hepatitis B. Methods: HBeAg-positive CHB patients (n = 100) with adefovir-resistance (rtA181T/V and/or rtN236T) were enrolled. Patients were treated with either ETV 0.5 mg plus ADV 10 mg per day (n = 52) or TDF 300 mg per day (n = 48) for 48 weeks. Tests for liver and kidney function, Serum Phosphorus, HBV serum markers, HBV DNA load and ultrasonography of liver were performed every 3 months. Student's t-test and χ2 test were used to compare the efficacy, side effects in the two groups. Results: Fifty-two patients in ETV + ADV group and forty-eight patients in TDF group were followed-up for 96 weeks. HBV DNA undetectable rate were 76.9% versus 81.3% (P = 0.631) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV + ADV combination therapy and TDF monotherapy group respectively. Serum ALT normalized rate were 84.6% versus 87.5% (P = 0.777) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV+ADV combination therapy and TDF monotherapy group respectively. But the level of serum Phosphorus was significantly lower in ETV + ADV combination therapy group compare with TDF monotherapy group (1.13 ±0.15 versus 1.22 ±0.16, P = 0.004) at week 96. Conclusion: Both ETV + ADV combination therapy and TDF monotherapy provided effective treatments in chronic hepatitis B with adefovir-resistant. However, it was associated with poor serological responses up to week 96. The long term treatment of hepatitis B with ETV (0.5 mg/day) combination of ADV (10 mg/day) can potentially cause hypophosphatemia and renal impairment, so regular monitoring of serum phosphate, serum creatinine and evaluation of eGFR is needed.

Galectin-1 attenuates hepatic ischemia reperfusion injury in mice.

BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a primary cause of organ dysfunction occurring during liver resection surgery and transplantation. Galectin-1, an endogenous lectin expressed on lymphoid organs, plays an important role in governing innate and adaptive immunity. This study was designed to determine the therapeutic role of galectin-1 and underlying mechanism in hepatic IRI. METHODS: Male C57BL/6 mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion with or without treatment with recombinant galectin-1 (rGal-1) or neutralizing anti-IL-10 antibody. Mice were sacrificed at 6 and 24 h following reperfusion. Liver damage related enzymes were determined and cytokines/chemokines were measured by qPCR and ELISA. RESULTS: Administration of rGal-1 significantly attenuated hepatic IRI, including a remarkable reduction in serum ALT/AST levels and an improved liver histology score compared to controls. rGal-1 treatment reduced TUNEL positive apoptotic hepatocytes, attenuated proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-12, IFN-γ, IL-17) and chemokines (CXCL-1, CXCL-10) levels, but upregulated IL-10 expression, compared with controls. In addition, rGal-1 increased the production of IL-10 in hepatic macrophages in vivo and in vitro. Blockade of IL-10 using neutralizing anti-IL-10 antibody reversed the protection of galectin-1 in hepatic IRI in mice. CONCLUSION: These data suggest that galectin-1 may attenuate hepatic IRI via an IL-10-dependent mechanism, which is a promising therapeutic target.

Prognostic value of Rho GDP dissociation inhibitors in patients with hepatocellular carcinoma following liver transplantation.

Rho GDP dissociation inhibitors (GDIs) are pivotal regulators of Rho GTPases, which are essential for tumor progression, yet their role in hepatocellular carcinoma (HCC) remains poorly understood. The purpose of the present study was to assess the role of RhoGDIs in the invasiveness and migration of liver cancer, and to determine their clinical prognostic significances in HCC following liver transplantation (LT). In the present study, the expression of RhoGDIs was assessed using reverse transcription-quantitative polymerase chain reaction and confirmed by western-blot analysis and immunohistochemistry. Their prognostic values were also analyzed, and determined in patients treated with LT. In addition, the functions of RhoGDIs in liver cancer cell line were studied in vitro. As a result, the downregulation of RhoGDI1 and RhoGDI2 at mRNA and protein levels were detected in HCC when compared with that of adjacent noncancerous tissues (P<0.05). However, the level of RhoGDI3 was identified to be similar in tumor and para-carcinoma tissues. Additionally, Kaplan-Meier curves demonstrated that patients with lower expression of RhoGDI1 or RhoGDI2 exhibited significantly increased risk of tumor recurrence following LT (P=0.007 and P=0.006, respectively). Cox proportional hazards model analysis revealed that the decreased expression level of RhoGDI2 was an unfavorable independent prognostic factor (hazard ratio, 3.306; P=0.001). In vitro studies involving the silencing of RhoGDI1 or RhoGDI2 demonstrated a significant increase in the migratory and invasive ability of tumor cells upon the silencing of these genes. Results from the present study indicate that RhoGDI dysregulation is a frequent event in human HCC, and that it promotes cancer progression by stimulating cell migration and invasion. RhoGDI2 may be a prognostic biomarker for patients with HCC following LT, and act as a potential therapeutic target.

First case report of isolated penile mucormycosis in a liver transplantation recipient.

Mucormycosis is a rare but potentially lethal complication of liver transplantation. Most reported cases have involved rhinocerebral, pulmonary, gastrointestinal, or disseminated forms. We present herein the case of a 61-year-old male patient with hepatocellular carcinoma who developed isolated penile mucormycosis after orthotopic liver transplantation. Such a case has not been reported in the literature to date. Early diagnosis and timely surgical intervention combined with comprehensive treatment are the key factors for improving the survival rate in patients with mucormycosis.

O-GlcNAcylation plays a role in tumor recurrence of hepatocellular carcinoma following liver transplantation.

O-linked-ß-N-acetylglucosamine (O-GlcNAc) modification is a crucial post-translational modification. The enzymes responsible for the addition and removal of O-GlcNAc have been identified as O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In this study, O-GlcNAcylation level was examined in forty hepatocellular carcinoma (HCC) tissues of patients who underwent liver transplantation (LT) and ten healthy liver tissues by immunohistochemistry analysis. We also examined the expression of OGT and OGA in sixty HCC samples using real-time reverse-transcription polymerase chain reaction and analyzed their correlations with clinical parameters and prognosis in sixty HCC patients treated with LT. Additionally, the global O-GlcNAcylation level was altered through OGT and OGA silencing in the HCC cell line, and the effects of O-GlcNAcylation on cancer malignancy were investigated. We found that the global O-GlcNAcylation levels were significantly elevated in HCC tissues than that in healthy liver tissues (P = 0.031); moreover, O-GlcNAcylation was significantly enhanced in the tumor tissues of patients who had suffered from HCC recurrence after LT compared with those who had not (P = 0.046). Importantly, low expression of OGA was an independent prognostic factor for predicting tumor recurrence of HCC following LT (P = 0.041, hazard ratio, 0.438), especially in AFP low patients. In vitro assays demonstrated that O-GlcNAcylation play important roles in migration, invasion, and viability of HCC cells, partly through regulating E-cadherin, MMP1, MMP2, and MMP3 expression. Altogether, these results suggest that O-GlcNAcylation might play important roles in HCC formation and progression and may be a potential marker to predict patient risk of recurrence after LT and a valuable target for therapy.

Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation.

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we evaluated the expression of MALAT1 by quantitative real-time PCR in 9 liver cancer cell lines and 112 HCC cases including 60 cases who received liver transplantation (LT) with complete follow-up data. Moreover, small interfering RNA (siRNA) was used to inhibit MALAT1 expression to investigate its biological role in tumor progression. We found that MALAT1 was up-regulated in both cell lines and clinical tissue samples. Patients with high expression level of MALAT1 had a significantly increased risk of tumor recurrence after LT, particularly in patients who exceeded the Milan criteria. On multivariate analysis, MALAT1 was an independent prognostic factor for predicting HCC recurrence (hazard ratio, 3.280, P = 0.003).In addition, inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. Our data suggest that lncRNA MALAT1 play an important role in tumor progression and could be a novel biomarker for predicting tumor recurrence after LT and serve as a promising therapeutic target.