Exploration of the Binding Mechanism of Cyclic Dinucleotide Analogs to Stimulating Factor Proteins and the Implications for Subsequent Analog Drug Design.

Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

The complete mitochondrial genome of Xanthomantis bimaculata (Mantodea: Iridopterygidae) and its phylogeny.

The mitochondrial genome sequence of Xanthomantis bimaculata (Mantodea: Iridopterygidae) from Yunnan, China is a circular molecule with the typical insect mitochondrial gene arrangement, which is 15,941 bp in length and contains 22 tRNAs, two rRNAs, 13 protein-coding genes, and one control region. The overall AT content of the mitogenome is 73.12% (A = 37.58%, T = 35.54%, C = 16.54%, G = 10.34%). In BI and ML phylogenetic analyses, X. bimaculata was a sister clade to Sceptuchus simplex. The monophyly of the families Iridopterygidae, Thespidae and Liturgusidae were supported.

The mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) from Fujian and the phylogeny of Caenidae within Ephemeroptera.

The phylogenetic relationship of Caenidae remains hotly debated within the Ephemeroptera. We sequenced the complete mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) to discuss the phylogenetic relationships among the Caenidae. The mitochondrial genome of Caenis sp. collected from Jian'ou, Fujian province, China is a circular molecule of 15,392 bp in length containing 37 genes (13 protein-coding genes, 22 tRNAs, and two rRNAs), which showed the typical insect mitochondrial gene arrangement. In BI and ML phylogenetic trees using 23 species from 13 families, the monophyly of the families Caenidae, Heptageniidae, Isonychiidae, and Vietnamellidae was strongly supported. The clade of Caenidae is a sister clade to the clade of Teloganodidae and Baetidae.

Expression of LAMP3 and its correlation with clinicopathologic characteristics and prognosis in hepatocellular carcinoma.

Lysosome-associated membrane protein (LAMP) 3 is one of members of lysosome-associated membrane protein family, which has been reported to play an important role in multiple malignant tumors. However, there is less research about the expression of LAMP3 in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of LAMP3 and explore its roles in HCC.The expression of LAMP3 in 99 cases of HCC tissues was performed by immunohistochemistry. In addition, the expression of LAMP3 in 20 pairs of HCC tissues and pericarcinomatous tissues was determined by quantitative real-time polymerase chain reaction and Western blotting. Immunohistochemical staining showed that LAMP3 was mainly expressed in the cytoplasm. And the expression of LAMP3 in HCC tissues (64/99, 64.6%) was significantly lower than that in pericarcinomatous tissues (23/99, 23.2%). In addition, the expression of LAMP3 mRNA and protein in HCC tissues was also significantly lower than that in pericarcinomatous tissues for 20 pairs of HCC samples. Low expression of LAMP3 was correlated with age, tumor-node-metastasis (TNM) staging, Edmondson grade, alpha-fetoprotein (AFP). Kaplan-Meier analysis showed that patients with low expression of LAMP3 had worse overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that low expression of LAMP3 was an independent prognostic factor of OS and DFS for HCC patients.The results suggested that LAMP3 may play an important role in the development and progression of hepatocellular carcinoma, and serve as an independent prognostic predictor for HCC patients after surgical resection.

Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance.

GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the synthesis of 60S subunit and maturation, is closely related to cell proliferation and growth. Till now, a small number of existing studies have found a contradictory dual role of GTPBP4 in cancer. Whether the expression level of GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients' prognosis or its function and underlying molecular mechanisms still remains unclear. In the present study, the above issues were explored for the first time. Our results showed that GTPBP4 was overexpressed in HCC and knockdown of GTPBP4 delayed cell proliferation, impaired colony formation ability, induced cell cycle arrest in G2/M period and promoted apoptosis in HCC cell lines. Besides, in vivo xenograft nude mice model revealed that GTPBP4 knockdown could significantly suppress HCC tumorigenesis. Gene microarray and further pathway enrichment analyses indicated that ERBB signaling pathway was the most significantly changed one. More importantly, high GTPBP4 expression level significantly correlated to the poor prognosis of HCC patients. Taken together, all these findings suggest that GTPBP4 serves as an oncogene and plays a pivotal role in HCC development, which will be a potential therapeutic target or a biomarker for HCC.

Nicotinamide adenine dinucleotide detection based on silver nanoclusters stabilized by a dumbbell-shaped probe.

We have developed a novel method for detecting nicotinamide adenine dinucleotide (NAD+) based on fluorescent silver nanoclusters (AgNCs) stabilized by a dumbbell-shaped DNA template containing two cytosine-loops joined in a dsDNA stem. The design involves two types of components: a dumbbell-shaped DNA template and three enzymes. In the presence of NAD+ as a cofactor, Escherichia coli DNA ligase (E.coli DNA ligase) catalyzes template ligation to generate a sealed (no terminal nucleotides) dumbbell-shaped structure, preventing digestion by exonuclease III (Exo III) and exonuclease I (Exo I). The loop regions of the intact template serve as sites for the deposition of highly fluorescent AgNCs. In the absence of NAD+, the ligation reaction does not occur, and the unsealed dumbbell-shaped template is digested into mononucleotides via cooperation of Exo III and Exo I. The destruction of the DNA template results in the agglomeration of AgNCs into silver nanoparticles with low fluorescence. The fluorescence enhancement depends on the ligation and digestion of the DNA template, allowing quantitative detection of NAD+ in the range of 0.5 nM-5000 nM with a detection limit of ∼0.25 nM.

Simple and Cost-Effective Glucose Detection Based on Carbon Nanodots Supported on Silver Nanoparticles.

We present a new glucose oxidase (GOx)-mediated strategy for detecting glucose based on carbon nanodots supported on silver nanoparticles (C-dots/AgNPs) as nanocomplexes. The strategy involves three processes: quenching of C-dots' fluorescence by AgNPs, production of H2O2 from GOx-catalyzed oxidation of glucose, and H2O2-induced etching of AgNPs. In the C-dots/AgNPs complex, AgNPs act as a "nanoquencher" to decrease C-dots fluorescence by surface plasmon-enhanced energy transfer (SPEET) from C-dots (donor) to AgNPs (acceptor). The H2O2 formed by GOx-catalyzed oxidation of glucose etches the AgNPs to silver ions, thus freeing the C-dots from the AgNPs surfaces and restoring the C-dots' fluorescence. Therefore, the increase in fluorescence depends directly on the concentration of H2O2, which, in turn, depends on the concentration of glucose. The strategy allows the quantitative analysis of glucose with a detection limit of 1.39 µM. The method based on C-dots/AgNPs offers the following advantages: simplicity of design and facile preparation of nanomaterials, as well as low experimental cost, because chemical modification and separation procedures are not needed.

Copper-Mediated DNA-Scaffolded Silver Nanocluster On-Off Switch for Detection of Pyrophosphate and Alkaline Phosphatase.

We present a new copper-mediated on-off switch for detecting either pyrophosphate (PPi) or alkaline phosphatase (ALP) based on DNA-scaffolded silver nanoclusters (DNA/AgNCs) templated by a single-stranded sequence containing a 15-nt polythymine spacer between two different emitters. The switch is based on three favorable properties: the quenching ability of Cu(2+) for DNA/AgNCs with excitation at 550 nm; the strong binding capacity of Cu(2+) and PPi; and the ability of ALP to transform PPi into orthophosphate (Pi). The change in fluorescence of DNA/AgNCs depends on the concentrations of Cu(2+), PPi, and ALP. Copper(II) acts as a mediator to interact specifically with the Probe, while PPi and ALP convert the signal of the Probe by removing and recovering Cu(2+), operating as an on-off switch. In the presence of Cu(2+) only, DNA/AgNCs exhibit low fluorescence because the combination of Cu(2+) and DNA template disturbs the precise formation of DNA/AgNCs. When PPi is added to the system containing Cu(2+), free DNA template is obtained due to the stronger interaction of PPi and Cu(2+), leading to a significant fluorescence increase (ON state) which depends on the concentration of PPi. Further addition of ALP results in the release of free Cu(2+) via ALP-catalysis of hydrolysis of PPi into Pi, thereby returning the system to the low fluorescence OFF state. The switch allows the analysis of either PPi or ALP by observation of the fluorescence status, with the detection limit of 112.69 nM and 0.005 U/mL for PPi and ALP, respectively. The AgNCs on-off switch provides the advantages of simple design, convenient operation, and low experimental cost without need of chemical modification, organic dyes, or separation procedures.

Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection.

As the most predominant tumour-infiltrating immune cells, tumour-associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68-positive TAMs display dissimilarly polarized programmes comprising CD11c-positive pro-inflammatory macrophages (M1) and CD206-positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c-positive TAM density (P = 0.005) and low versus high CD206-positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.

A versatile proximity-dependent probe based on light-up DNA-scaffolded silver nanoclusters.

It is well-known that proximity-dependent probes containing an analyte recognization site and a signal formation domain could be assembled specifically into a sandwich-like structure (probe-analyte-probe) via introducing an analyte. In this work, using the design for zirconium ion (Zr(4+)) detection as the model, we develop a novel and reliable proximity-dependent DNA-scaffolded silver nanocluster (DNA/AgNC) probe for Zr(4+) detection via target-induced emitter proximity. The proposed strategy undergoes the two following processes: target-mediated emitter pair proximity as target recognition implement and the synthesis of DNA/AgNCs with fluorescence as a signal reporter. Upon combination of the rationally designed probe with Zr(4+), the intact templates were obtained according to the -PO3(2-)-Zr(4+)-PO3(2-)- pattern. The resultant structure with an emitter pair serves as a potent template to achieve highly fluorescent DNA/AgNCs. To verify the universality of the proposed proximity-dependent DNA/AgNC probe, we extend the application of the proximity-dependent probe to DNA and adenosine triphosphate (ATP) detection by virtue of a specific DNA complementary sequence and ATP aptamer as a recognition unit, respectively. The produced fluorescence enhancement of the DNA/AgNCs in response to the analyte concentration allows a quantitative evaluation of the target, including Zr(4+), DNA, and ATP with detection limits of ∼3.00 µM, ∼9.83 nM, and ∼0.81 mM, respectively. The proposed probe possesses good performance with simple operation, cost-effectiveness, good selectivity, and without separation procedures.

Label-Free Detection of Sequence-Specific DNA Based on Fluorescent Silver Nanoclusters-Assisted Surface Plasmon-Enhanced Energy Transfer.

We have developed a label-free method for sequence-specific DNA detection based on surface plasmon enhanced energy transfer (SPEET) process between fluorescent DNA/AgNC string and gold nanoparticles (AuNPs). DNA/AgNC string, prepared by a single-stranded DNA template encoded two emitter-nucleation sequences at its termini and an oligo spacer in the middle, was rationally designed to produce bright fluorescence emission. The proposed method takes advantage of two strategies. The first one is the difference in binding properties of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) toward AuNPs. The second one is SPEET process between fluorescent DNA/AgNC string and AuNPs, in which fluorescent DNA/AgNC string can be spontaneously adsorbed onto the surface of AuNPs and correspondingly AuNPs serve as "nanoquencher" to quench the fluorescence of DNA/AgNC string. In the presence of target DNA, the sensing probe hybridized with target DNA to form duplex DNA, leading to a salt-induced AuNP aggregation and subsequently weakened SPEET process between fluorescent DNA/AgNC string and AuNPs. A red-to-blue color change of AuNPs and a concomitant fluorescence increase were clearly observed in the sensing system, which had a concentration dependent manner with specific DNA. The proposed method achieved a detection limit of ∼2.5 nM, offering the following merits of simple design, convenient operation, and low experimental cost because of no chemical modification, organic dye, enzymatic reaction, or separation procedure involved.

Expression of Kindlin-1 in human hepatocellular carcinoma and its prognostic significance.

Kindlin-1 is a member of the Kindlin family of focal adhesion proteins and is implicated in cell adhesion, proliferation, polarity, and motility. Although expression of Kindlin-1 has recently been reported in a variety of human cancers, studies on its expression in human hepatocellular carcinoma (HCC) are currently lacking. This study aimed to determine the clinicopathological parameters and prognostic value of Kindlin-1 in HCC patients after surgical resection. The messenger RNA (mRNA) and protein levels of Kindlin-1 in 22 matched HCC specimens were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting assays. The clinical and prognostic significance of Kindlin-1 in 68 cases of HCC was determined by immunohistochemistry. Kindlin-1 expression was higher in HCC tumor tissues relative to that in adjacent normal tissue at the both mRNA and protein levels (p < 0.05). Immunohistochemical results revealed that overexpression of Kindlin-1 was detected in 37 of 68 (54.4 %) tumor tissues and in seven of 68 (10.3 %) adjacent non-tumor tissues (p < 0.05). Positive Kindlin-1 expression was significantly correlated with tumor size, tumor capsula, status of metastasis, and tumor-node-metastasis (TNM) stage. Additionally, Kaplan-Meier survival analysis showed that positive Kindlin-1 expression was associated with unfavorable overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified Kindlin-1 as an independent prognostic predictor for OS and DFS in HCC patients (p = 0.041 and 0.027, respectively). Taken together, our data suggest that Kindlin-1 could play an important role in HCC and might serve as a promising prognostic marker and potential target for HCC therapy.

Kindlin-2: a novel prognostic biomarker for patients with hepatocellular carcinoma.

The association of aberrant expression of Kindlin-2 with tumor progression has been reported in recent years. The purpose of this study was to investigate the expression of Kindlin-2 in hepatocellular carcinoma (HCC), and to evaluate its clinical and prognostic significance. The mRNA and protein levels of Kindlin-2 in HCC and adjacent non-cancerous tissues were examined by real-time PCR and western blotting. The relationships between Kindlin-2 expression, clinicopathological features and postoperative survival of HCC patients were also evaluated. Kindlin-2 expression was higher in HCC tissues as compared to adjacent non-cancerous tissues at both mRNA and protein levels (P<0.05, respectively). Positive expression of Kindlin-2 was significantly correlated with larger tumor size (P=0.034), capsular invasion (P=0.009), microvascular invasion (P=0.028) and poor prognosis of HCC patients (P<0.001). Moreover, multivariate survival analysis identified Kindlin-2 as an independent prognostic factor for overall and disease-free survival of HCC patients (P=0.018 and 0.001, respectively). Taken together, our findings suggested that Kindlin-2 was highly expressed in HCC tissues and was closely related to clinical progression. Therefore, Kindlin-2 protein could be a potential biomarker for predicting poor prognosis of HCC patients after surgery.

A novel molecular beacon-based method for isothermal detection of sequence-specific DNA via T7 RNA polymerase-aided target regeneration.

Developing molecular beacon (MB)-based method for DNA detection has been of great interest to many researchers because of its intrinsic advantages of simplicity, rapidity, and specificity. In this work, we have developed a novel MB-based method for isothermal detection of sequence-specific DNA via T7 RNA polymerase-aided target regeneration strategy. The proposed method involves three primary processes of target-mediated ligation by T4 DNA ligase, transcription reaction by T7 RNA polymerase, and MB switch for signal output. Upon the hybridization with DNA target, a rationally designed MB and a pair of primers encoded with T7 promoter sequence were ligated via the formation of a phosphodiester bond by T4 DNA ligase. The resultant joint fragment acted as template to initiate T7 RNA polymerase-mediated transcription reaction. Correspondingly, a great amount of RNA strands complementary to MB and partial primers were transcribed to initiate new cyclic reactions of MB switch, ligation, and transcription. With such signal amplification strategy of the regeneration of target-like RNA fragments, our proposed assay achieved a detection limit as low as ∼10 pM, which was ∼3 orders of magnitude lower than the traditional MB-based method with a recognition mechanism in 1:1 stoichiometric ratio between MB and target molecule.

A new mode to light up an adjacent DNA-scaffolded silver probe pair and its application for specific DNA detection.

By fluorescence enhancement of a proximity-dependent DNA-scaffolded silver nanocluster probe pair and exonuclease III-mediated signal amplification, we present a new fluorescence turn-on mode and its application for specific DNA detection.

Overexpression of HOXA13 as a potential marker for diagnosis and poor prognosis of hepatocellular carcinoma.

HOXA13 is a member of homeobox genes that encode transcription factors regulating embryonic development and cell fate. Abnormal HOXA13 expression was reported in hepatocellular carcinoma (HCC), but its correlation with tumor angiogenesis and prognosis still remain unclear. This study was aimed to uncover the expression, diagnostic and prognostic significance of HOXA13 in HCC. Immunohistochemistry was performed to detect HOXA13 expression in HCC and corresponding paracarcinomatous tissues from 90 patients. Enzyme-linked immunosorbent assay was used to detect serum HOXA13 in 90 HCC patients and 20 healthy volunteers. Receiver operating characteristics was analyzed to calculate diagnostic accuracy of serum HOXA13, alpha-fetoprotein (AFP) and their combination. Immunoreactivity of HOXA13 was detected in 72.2% of HCC, and 12.2% of adjacent non-cancerous samples. HOXA13 expression was significantly associated with tumor size, microvascular invasion, pathological grade, tumor capsula status, AFP level, tumor-node-metastasis stage and positively correlated with VEGF (p < 0.001) and microvessel density (p < 0.001). The combination of serum HOXA13 and AFP had a markedly higher area under the curve than HOXA13 alone. HOXA13 expression was associated with unfavorable overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001). Multivariate analysis indicated that patients with HOXA13-expressing tumors had a significantly shorter OS (p = 0.030) and DFS (p = 0.005) than those with HOXA13-negative tumors. Thus, HOXA13 expression possibly plays an important role in tumor angiogenesis, progression and prognosis of HCC. Moreover, we demonstrate that serum HOXA13 may serve as a biomarker for early HCC diagnosing and predicting outcome.

Misdiagnosed gastrinoma: A case report.

Gastrinoma is most commonly located in the gastrinoma triangle (comprising of the duodenum, pancreas and bile ducts) or in the adjacent lymph nodes. Due to the low mortality rate, it is often misdiagnosed as other diseases with similar clinical characteristics, such as a solid pseudopapillary tumor of the pancreas (SPTP). Therefore, the current study reports a rare case of gastrinoma located in the tail of the pancreas of a female patient under medical examination, who exhibited no clinical symptoms. The tumor, which was located in the body and tail of the pancreas, was successfully resected and the spleen was preserved. The outcome of surgery combined with the postoperative pathological examination resulted in the patient being misdiagnosed with a SPTP. During the consequent six-year follow-up period, low-density liver lesions and an intractable peptic ulcer gradually appeared. Finally, the patient diagnosis was confirmed as a malignant pancreatic neuroendocrine carcinoma with liver metastases. On June 1, 2011, a liver transplant was successfully performed and the patient has maintained a good overall condition. The underlying clinical and pathological factors that may have resulted in misdiagnosis are investigated in the present study. Through providing our preliminary clinical experiences and lessons, the aim of the present study was to focus the attention of clinicians on this type of cancer in order to improve its diagnosis and treatment.

Protective effect of S-adenosylmethionine on hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic HBV infection.

BACKGROUND: Although hepatectomy is often performed with the Pringle maneuver, the problem of hepatic ischemia-reperfusion injury (HIRI) can also be serious. Thus, the present study was designed to investigate the protective effect of S-adenosylmethionine (SAMe) on HIRI, especially for patients with hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection and cirrhosis. METHODS: Eighty-one HCC patients with chronic HBV infection, undergoing partial hepatectomy with inflow occlusion, were divided into three groups. In the pretreatment group (PR group, n = 26), patients were given SAMe two hours before surgery. In the post-treatment group (PO group, n = 25), patients were given SAMe six hours after surgery. And in the control group (control group, n = 30), patients received partial hepatectomy without any SAMe. All pre-, intra- and postoperative blood samples were collected to measure the plasma levels of transaminases, bilirubin and cytokines. The results were compared among the three groups. RESULTS: There were no statistically significant intergroup differences observed in age, gender, hepatic inflow occlusion time and the results of liver function tests. Preoperative administration of SAMe (PR group) significantly reduced the plasma levels of alanine transaminase (ALT), aspartate transferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) as compared to the other two groups. In the PO group, TBIL and DBIL were significantly lower than in the control group. Significant differences were also seen in IL-6 and TNF-α between the PR group and the other groups. In all groups, postoperative liver reserve function in the PR group as revealed by ICGR15 (Post ICGR15) was at its best before abdominal closure. Compared to the control group, the risk of complications and the hospital stay after surgery were significantly meliorated in the PR group. Additionally, patients with cirrhosis had a more acute rate of change in ALT and AST than non-cirrhotic patients. CONCLUSIONS: Taken together, our preliminary findings suggest that preoperative administration of SAMe is useful and safe for reducing the HIRI in partial hepatectomy, especially for HCC patients whose disease is associated with chronic HBV infection and cirrhosis.

Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma.

BACKGROUND: Nodal, a TGF-ß-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. METHODS: We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters. RESULTS: Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC. CONCLUSIONS: Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery.