TRIM32/USP11 Balances ARID1A Stability and the Oncogenic/Tumor-Suppressive Status of Squamous Cell Carcinoma

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Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

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Highlights

• •Flow cytometry analysis is used to isolate ASC speck⁽⁺⁾ NPC cells.
• •Proteome analysis of ASC speck⁽⁺⁾ NPC cells reveals enriched mitochondrial OxPhos proteins.
• •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
• •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.

     

A bivariate radioimmunoassay for arginine vasopressin and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin)

Pairs of radioimmunoassays, each of which include a two-dimensional matrix of standards, have been previously employed to resolve specificity problems in steroid immunoassay. In this study the bivariate radioimmunoassay principle has been applied to simultaneous measurement of plasma antidiuretic hormone, arginine vasopressin, and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin), by utilizing two arginine vasopressin antisera which show significantly different cross-reactivities with the synthetic analog. Data processing consists of mathematical representation of two curved dose-response surfaces followed by solution of this pair of nonlinear simultaneous equations for the unknown arginine vasopressin and desmopressin concentrations. Details of numerical procedures are given in the Appendix. The assay appears entirely adequate in terms of sensitivity, accuracy, and precision for measurement of these antidiuretic agents in clinical samples. No evidence of significant covariance in estimated concentrations could be detected but precision of estimation is (not unexpectedly) a function of the concentration of both agents. The plasma disappearance half-time of desmopressin (probably the second of a biphasic disappearance) was estimated as 37 min in one normal subject, which is in good agreement with a previously reported value of 30 min.     

Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

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Fluid shear stress regulates HepG2 cell migration though time-dependent integrin signaling cascade

Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear. In this study, hepatocellular carcinoma HepG2 cells were exposed to 1.4 dyn/cm² FSS for transient duration (15s and 30s), short duration (5 min, 15 min and 30 min) and long duration (1h, 2h and 4h), respectively. The expression and translocation of Integrins induced FAK-Rho GTPases signaling events were examined. Our results showed that FSS endowed HepG2 cells with higher migration ability via reorganizing cellular F-actin and disrupting intercellular tight junctions. We further demonstrated that FSS regulated the expression and translocation of Integrins and their downstream signaling cascade in time-dependent patterns. The FSS downregulated focal adhesion components (Paxillin, Vinculin and Talin) while upregulated the expression of Rho GTPases (Cdc42, Rac1 and RhoA) in long durations. These results indicated that FSS enhanced tumor cell migration through Integrins-FAK-Rho GTPases signaling pathway in time-dependent manners. Our in vitro findings shed new light on the role of FSS acting in physiologic and pathological processes during tumor progression, which has emerged as a promising clinical strategy for liver carcinoma.     

Hepatic DNAJB9 Drives Anabolic Biasing to Reduce Steatosis and Obesity

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Development of PEGylated serum albumin with multiple reduced thiols as a long-circulating scavenger of reactive oxygen species for the treatment of fulminant hepatic failure in mice

Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.     

Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 10⁹/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 10⁹/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.     

Bayesian Nonparametric Modeling for Comparison of Single-Neuron Firing Intensities

Summary .  We propose a fully inferential model-based approach to the problem of comparing the firing patterns of a neuron recorded under two distinct experimental conditions. The methodology is based on nonhomogeneous Poisson process models for the firing times of each condition with flexible nonparametric mixture prior models for the corresponding intensity functions. We demonstrate posterior inferences from a global analysis, which may be used to compare the two conditions over the entire experimental time window, as well as from a pointwise analysis at selected time points to detect local deviations of firing patterns from one condition to another. We apply our method on two neurons recorded from the primary motor cortex area of a monkey's brain while performing a sequence of reaching tasks.     

Development and characterization of a human cell line from an ovarian mixed mullerian tumor (carcinosarcoma)

Summary A cell line derived from a human ovarian carcinosarcoma was established in tissue culture and in nude mice. Two sublines, LDF and HDF, separated by discontinuous density centrifugation were also established from the parent line JoN. The cloning efficiency of the JoN line was 21%. Morphologic features of adenocarcinoma cells characteristic of the parent JoN cells were retained in the sublines and clones; all lines showed the same karyotype and DNA content (pseudodiploid and pseudotetraploid). Keratin, as demonstrated immunohistochemically, was strongly expressed in the parent line JoN and the xenograft tumor, but not at all in the LDF sublines and only moderately in the HDF sublines. Vimentin, however, was expressed in neither the parent line JoN nor the xenograft tumor, but was present in both sublines. Transglutaminase and plasminogen activator activity was high in the parent line JoN. Neither, sublines nor clones showed the same high enzyme activity as the parent line. It is concluded that this human tumor line JoN is comprised of epithelial cells, capable of multidirectional differentiation.