Particle size effect on surface/interfacial tension and Tolman length of nanomaterials: A simple experimental method combining with theoretical.

Surface tension and interfacial tension are crucial to the study of nanomaterials. Herein, we report a solubility method using magnesium oxide nanoparticles of different radii (1.8-105.0 nm, MgO NPs) dissolved in pure water as a targeted model; the surface tension and interfacial tension (and their temperature coefficients) were determined by measuring electrical conductivity and combined with the principle of the electrochemical equilibrium method, and the problem of particle size dependence is discussed. Encouragingly, this method can also be used to determine the ionic (atomic or molecular) radius and Tolman length of nanomaterials. This research results disclose that surface/interfacial tension and their temperature coefficients have a significant relationship with particle size. Surface/interfacial tension decreases rapidly with a radius <10 nm (while the temperature coefficients are opposite), while for a radius >10 nm, the effect is minimal. Especially, it is proven that the value of Tolman length is positive, the effect of particle size on Tolman length is consistent with the surface/interfacial tension, and the Tolman length of the bulk does not change much in the temperature range. This work initiates a new era for reliable determination of surface/interfacial tension, their temperature coefficients, ionic radius, and Tolman length of nanomaterials and provides an important theoretical basis for the development and application of various nanomaterials.

Apigenin regulates the migration, invasion, and autophagy of hepatocellular carcinoma cells by downregulating YAP.

Apigenin is an edible flavonoid with anticancer properties; however, the underlying mechanisms in hepatocellular carcinoma (HCC) remain to be clarified. In the present study, we demonstrated that apigenin decreased the viability of both SMMC-7721 and SK-Hep1 cells in a dose-dependent manner, and inhibited the migration and invasion of HCC cells with different metastatic potential by regulating actin cytoskeletal rearrangements. Moreover, we showed that apigenin decreased the expression of YAP, and subsequently reduced migration and invasion by modulating the expression of the epithelial-mesenchymal transition (EMT) markers, and promoted the autophagy of HCC cells by regulating the expression of autophagy-related genes. Collectively, the present findings might provide a novel mechanism for the therapeutic application of apigenin in HCC.

Emerin knockdown induces the migration and invasion of hepatocellular carcinoma cells by up-regulating the cytoplasmic p21.

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.

Lateral percutaneous nephrolithotomy: A safe and effective surgical approach.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is traditionally performed with the patient in the prone position for large renal calculi. However, anesthetic limitations exist with the prone position. Similarly, the supine position is associated with poorer ergonomics due to the awkward downward position of the renal tract, a smaller window for percutaneous puncture, and a higher risk of anterior calyx puncture. This study aimed to demonstrate the feasibility and safety of lateral-PCNL in managing large renal calculi without the disadvantages of prone and supine positions. METHODS: Retrospectively, 347 lateral-PCNL cases performed from July 2001 to July 2015 were examined. the patient's thorax, abdomen, and pelvis were positioned over a bridge perpendicular to a "broken" table, creating an extended lumbodorsal space. The procedure was evaluated in terms of stone clearance at 3 months' postprocedure, operative time, and complications. RESULTS: Primary stone clearance was achieved in 82.7% of patients. The mean operating time was 97 min. The average time taken to establish the tract and mean radiation time were 4.5 min and 6.93 min, respectively. In total, 2.3% of patients required postoperative transfusion, and 13.5% of patients had postoperative fever. There was one case of hydrothorax, but no bowel perforation. CONCLUSIONS: Our lateral-PCNL technique allows for effective stone clearance due to good stone ergonomics and it should be considered as a safe alternative even in the most routine procedures.

Association of longevity with TNF-α G308A and IL-6 G174C polymorphic inflammatory biomarkers in Caucasians: a meta-analysis.

BACKGROUND: Mutations in genes encoding tumor necrosis factor (TNF)-α and interleukin (IL)-6 were previously shown to affect mortality. Single nucleotide polymorphisms (SNPs) in the functional promoter regions of TNF-α (G308A) and IL-6 (G174C) are among the most widely studied. OBJECTIVES: To determine whether TNF-α G308A and IL-6 G174C SNPs confer susceptibility to longevity, we performed a meta-analysis to comprehensively estimate the association between these SNPs and longevity in long-lived individuals (LLI, aged ≥ 80 years). MATERIALS AND METHODS: Studies addressing the role of TNF-α and IL-6 SNPs in longevity were identified from the PubMed database. Pooled ORs with 95 % confidence intervals (CIs) were used to assess the association between SNPs and longevity. RESULTS: The meta-analysis was based on four studies of TNF-α G308A and nine of IL-6 G174C, covering a total of 2945 LLI individuals and 2992 controls. Overall, no significantly increased risks were observed for G308A [A vs. G (additive model): OR = 0.98, 95 % CI = 0.79-1.22, p = 0.852; AA + AG vs. GG (dominant model): OR = 0.97, 95 % CI = 0.75-1.24, p = 0.791] or for G174C [C vs. G (additive model): OR = 1.07, 95 % CI = 0.94-1.22, p = 0.293; CC + CG vs. GG (dominant model): OR = 1.09, 95 % CI = 0.93-1.28, p = 0.299]. There was no change in the significance when a cutoff age of ≥ 90 years was introduced. CONCLUSIONS: We found no evidence that the TNF-α G308A and IL-6 G174C SNPs affected the probability of reaching an advanced age in Caucasians, and that they have little effect on delaying the onset and progression of age-related diseases, but this does not rule out the possibility of population-specific effects caused by different genes and/or environmental factors and their interactions.

Paraoxonase (PON1) polymorphisms Q192R and L55M are not associated with human longevity: A meta-analysis.

BACKGROUND: Genetic mutations in the paraoxonase 1 (PON1) encoding gene have been considered to affect mortality and of these the functional promoter region polymorphisms Q192R and L55M are among the most widely studied. OBJECTIVE: The aim of this study was to determine whether the Q192R and L55M polymorphisms of PON1 can increase susceptibility to longevity. A meta-analysis was performed to obtain a comprehensive estimation of the association between Q192R and L55M and longevity in long-lived individuals (LLIs) aged 80 years or more. MATERIAL AND METHODS: A search was carried out in the PubMed database (from January 2001 to May 2014) to obtain data on the role of PON1 polymorphisms in longevity and a pooled odds ratio (OR) with a 95% confidence interval (CI) was used to assess the associations. RESULTS: The meta-analysis was based on 9 studies of PON1 Q192R and 5 studies of PON1 L55M that covered a total of 5086 LLIs and 4494 controls. Overall, significantly increased risks were not observed for either Q192R or L55M. The results of the statistical calculations were as follows: R vs. Q (additive model): OR = 1.080, 95% CI = 0.989-1.179, p = 0.088 and RR + RQ vs. QQ (dominant model): OR = 1.099, 95% CI = 0.975-1.240, p = 0.124; M vs. L (additive model): OR = 0.946, 95% CI = 0.862-1.039, p = 0.245 and MM + ML vs. LL (dominant model): OR = 0.951, 95% CI = 0.836-1.081, p = 0.442 for Q192R and L55M, respectively. The results did not change with an age cut-off among the LLIs of ≥ 93 years. CONCLUSION: No evidence that the Q192R and L55M polymorphisms of PON1 impacted on the probability of reaching extreme ages was found although this cannot be completely ruled out; however, the possibility of population-specific effects due to the influence of and interaction between different genes or environmental factors could not be ruled out.

QUALITY OR SACRIFICE? THE INFLUENCE OF DECISION TASK AND PRODUCT CHARACTERISTICS ON THE DUAL ROLE OF PRICE.

People perceive price as a cue of monetary sacrifice, a quality signal, or both. However, this research proposed that the relative salience of these two roles varies with different decision tasks (i.e., selection and rejection). Furthermore, the effect of decision task type on price perception differs by product type (i.e., tangible goods or services). Two experiments show that (1) the price-quality perception under the selection task is higher than that of a rejection task for tangible goods but not for services; and (2) for goods and services, the sacrifice perception is greater in the rejection task than that in a selection task. These findings have important implications for formulating product assortment and marketing communications strategies.

The METTL3-m6A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma.

The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m6A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.

Calmodulin activation of polo-like kinase 1 is required during mitotic entry.

Polo-like kinase 1 (Plk1) is a conserved key regulator of the G2/M transition, but its upstream spatiotemporal regulators remain unknown. With the help of immunofluorescence, co-immunoprecipitation, and glutathione S-transferase (GST) pull-down assay, we found that calmodulin (CaM) is one such regulatory molecule that associates with Plk1 from G2 to metaphase. More importantly, this interaction results in considerable stimulation of Plk1 kinase activity leading to hyperphosphorylation of Cdc25C. Our results provide new insight into the role of CaM as an upstream regulator of Plk1 activation during mitotic entry.

Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy.

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit­8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

Downregulation of zinc finger protein 71 expression in oral squamous cell carcinoma tissues and its underlying molecular mechanism.

BACKGROUND: Patients with oral squamous cell carcinoma (OSCC) have poor prognoses due to a limited understanding of the pathogenesis of OSCC. Zinc finger protein (ZNF) is the largest transcription factor family in the human genome and exert diverse and important functions. Nevertheless, the exact expression status and molecular mechanism of ZNF71 have not been described in OSCC. Therefore, this study aimed to identify the specific expression level of ZNF71 in OSCC tissues and to further interpret the potential molecular mechanism of ZNF71 in the pathogenesis of OSCC. METHODS: In-house immunohistochemical staining of 116 OSCC samples and 29 non-OSCC samples was employed to detect the expression status of ZNF71 at the protein level of OSCC tissues. Single-cell RNA sequencing data from 7 OSCC samples was used to explore the expression landscape of ZNF71 in different cell types from OSCC tissues. High-throughput RNA sequencing data and gene chips data from 893 OSCC samples and 301 non-OSCC samples were utilized to identify the specific expression level of ZNF71 at the bulk mRNA level of OSCC tissues. Here, standardized mean difference (SMD) value was applied to calculate the expression differences between OSCC group and non-OSCC group. Multiple datasets were included; hence, the results were considered to be more reliable. Sensitivity analysis was conducted to evaluate the stability of the results. Enrichment analysis and immune infiltration analysis were used to explore the underlying molecular mechanism of ZNF71 in OSCC. RESULTS: ZNF71 was significantly downregulated in OSCC tissues at the protein level (SMD = -1.96, 95 % confidence interval [95 % CI]: -2.43 to -1.50). ZNF71 was absent in various cell types from OSCC tissues including cancerous epithelial cells and tumor-infiltrating immune cells. ZNF71 was downregulated in OSCC tissues at the bulk mRNA level (SMD = -0.38, 95 % CI: -0.75 to -0.02). Enrichment analysis showed that positively and differentially co-expressed genes mainly concentrated on "herpes simplex virus 1 infection" and "regulation of plasma membrane bounded cell projection organization", and negatively and differentially co-expressed genes mainly participated in "cell cycle" and "DNA metabolic process". Moreover, the putative target genes of ZNF71 mainly participated in "cellular respiration" and "protein catabolic process". Finally, immune infiltration analysis revealed that ZNF71 expression was positively correlated with multiple immune cells including activated B cells, memory B cells, and natural killer (NK) cells, and negatively correlated with various immune cells, including CD56 bright NK cells, neutrophil, and immature dendritic cells. CONCLUSION: The downregulation of ZNF71 may influence the initiation and promotion of OSCC by reducing immune infiltration, accelerating cell cycle progression, and affecting metabolic process, and this requires further research.

[Effect of genistein on MAPK signal pathway in the collagen-induced arthritis fibroblast-like synoviocytes].

OBJECTIVE: To study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibroblast-like synoviocytes (FLS). METHODS: The rat model of collagen-induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 micromol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50, 100, and 200 pmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected. RESULTS: Gen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10+/-0.04, significantly lower than that in the model group (2.12+/-0.03, P<0.01). Besides, after Gen's action on FLS, the expression of p-ERK was down-regulated. It was only 0.34+/-0.02 in the high dose Gen group, significantly lower than that in the model group (2.68+/-0.14, P<0.01). There was no change in the expression of ERK (P>0.05). CONCLUSIONS: Gen could inhibit the proliferation of FLS in CIA rats. Its mechanism of action was mainly correlated to down-regulating the tyrosine kinase of MAPK signal transduction pathway and inhibiting phosphorylation of ERK.

Expression level and prospective mechanism of miRNA-99a-3p in head and neck squamous cell carcinoma based on miRNA-chip and miRNA-sequencing data in 1, 167 cases.

BACKGROUND: The role of miR-99a-3p in Head and neck squamous cell carcinoma (HNSCC) has not been reported. Therefore, in this study, we examined the expression level and its molecular mechanisms of miR-99a-3p in HNSCC. MATERIALS AND METHODS: MiR-99a-3p-related miRNA-chip and miRNA-sequencing data were collected. We then carried out meta-analyses to pool the standard mean difference (SMD) value and generate a summarized receiver operating characteristic (sROC) curve. MiR-99a-3p mimic was transfected into FaDu cells and those genes influenced by miR-99a-3p were gathered. The target genes were also predicted from 12 tools through miRwalk2.0, and combined with differentially expressed genes in HNSCC from the The Cancer Genome Atlas and Genotype-Tissue Expression sequencing databases. FunRich and DAVID were used for the pathway signaling analyses for the potential targets of miR-99a-3p in HNSCC. RESULTS: The SMD was -0.30 (95% CI: -0.51, -0.08) in the fixed-effect model and -0.28 (95% CI: -0.67, 0.10) in the random-effect model (I2 = 60%), indicating a reduced expression level of miR-99a-3p in HNSCC tissues based on 1167 cases. In the sROC curve, the area under the curve (AUC) was 0.77 (95% CI: 0.73, 0.81). The 251 potential targets of miR-99a-3p were enriched in several pathways related to cancer, with the "Pathways in cancer" standing at the top. vascular endothelial growth factor A was selected as an example with up-regulated trend in HNSCC tissues. CONCLUSION: MiR-99a-3p exhibits a significant lower expression status in HNSCC, and this reduced or deletion status promotes the malignant progression of HNSCC. However, its molecular mechanism is still unclear and requires further investigation.

Drug repositioning in head and neck squamous cell carcinoma: An integrated pathway analysis based on connectivity map and differential gene expression.

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Melanoma-associated antigen family protein-D1 regulation of tumor cell migration, adhesion to endothelium, and actin structures reorganization in response to hypoxic stress.

Melanoma-associated antigen family protein-D1 (MAGE-D1) is a recently identified p75 neurotrophin receptor intracellular binding protein and functions as an adaptor that mediates multiple signaling pathways, including Dlx/Msx-mediated transcription. Here, a new regulatory function for MAGE-D1 in tumor cell motility and adhesion to endothelium is described. MAGE-D1 over-expression suppressed HeLa cell and BEL7402 cell migration, invasion, and adhesion to the monolayer of ECV304 cells. We also report that MAGE-D1 over-expression disrupted actin cytoskeleton rearrangement induced by hypoxia and down-regulated hypoxia inducible factor 1-dependent luciferase gene expression. These findings provide new insight into the ability of MAGE-D1 to suppress the motility and adhesion response of tumor cells by interfering with actin cytoskeleton reorganization and hypoxia inducible factor 1-dependent gene expression.

[Effects of arsenic trioxide on expressions of vascular endothelial growth factor and P-glycoprotein in multidrug resistant leukemia cell line K562/A02].

OBJECTIVE: To investigate the effects of arsenic trioxide (ATO) on the expressions of vascular endothelial growth factor (VEGF) and P-glycoprotein (P-gp) in K562/A02 cells and to explore the correlation between VEGF and P-gp. METHODS: The inhibition rate of K562/A02 cell proliferation was detected by using methyl thiazolyl tetrazolium assay (MTT); the level of VEGF was detected by enzyme-linked immunosorbent assay (ELISA) and the expression rate of P-gp was determined by flow cytometry (FCM). RESULTS: 0.05 micromol/L ATO had no influences on the cell proliferation and the expression of VEGF in K562/A02 cells; 0.4 and 3.2 micromol/L ATO could significantly inhibit the K562/A02 cell proliferation and down-regulate the expression of VEGF in K562/A02 cells (P<0.05). The expression of P-gp did not changed after being exposed to 0.05 and 0.4 micromol/L ATO for 24, 48 and 72 hours (P>0.05). 3.2 micromol/L ATO could remarkably reduce the expression of P-gp in K562/A02 cells after 48- and 72-hour incubation with ATO (P<0.05). CONCLUSIONS: The down-regulation of P-gp and VEGF after being exposed to ATO probably contributes to the reversion of multidrug resistance in K562/A02 cells. The level of VEGF may be related to the expression rate of P-gp in K562/A02 cells.

Knockdown of c-Met by adenovirus-delivered small interfering RNA inhibits hepatocellular carcinoma growth in vitro and in vivo.

c-Met is highly expressed and constitutively activated in various human tumors. We employed adenovirus-mediated RNA interference technique to knock down c-Met expression in hepatocellular carcinoma cells and observed its effects on hepatocellular carcinoma cell growth in vitro and in vivo. Among the five hepatocellular carcinoma and one normal human liver cell lines we analyzed, c-Met was highly expressed and constitutively tyrosine phosphorylated in only MHCC97-L and HCCLM3 hepatocellular carcinoma cells. Knockdown of c-Met could inhibit MHCC97-L cells proliferation by arresting cells at G0-G1 phase. Soft agar colony formation assay indicated that the colony forming ability of MHCC97-L cells decreased by approximately 70% after adenovirus AdH1-small interfering RNA (siRNA)/met infection. In vivo experiments showed that adenovirus AdH1-siRNA/met inhibited the tumorigenicity of MHCC97-L cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knockdown of c-Met by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of hepatocellular carcinoma in which c-Met is overexpressed.

Prognostic nutritional index predicts prognosis in patients with metastatic nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to investigate the prognostic value of Onodera's prognostic nutritional index (PNI) in patients with metastatic nasopharyngeal carcinoma (NPC). METHODS: A total of 187 patients with metastatic NPC treated with cisplatin-based chemotherapy were retrospectively reviewed. The PNI was calculated using the following formula: serum albumin level (gram per liter) +0.005× peripheral lymphocyte count (per cubic millimeter). A receiver operating characteristics curve for overall survival (OS) with the highest Youden index was determined to calculate the best cutoff value of PNI. The relationship between PNI and clinicopathological parameters was compared with the χ2 test. Survival analysis was applied to evaluate the predictive value of PNI. RESULTS: The median PNI in this study was 49.0 (ranging from 32.2 to 78.4). The best cutoff value of PNI for OS was 51.0 according to the receiver operating characteristics analysis. The median OS time was 13.0 months. The multivariate analysis indicated that the complete response (hazard ratio 0.681, 95% confidence interval 0.574-0.902; P=0.013) and PNI (hazard ratio 1.732, 95% confidence interval 1.216-2.892; P=0.005) were independent prognostic factors for OS in patients with metastatic NPC. CONCLUSION: This study revealed that PNI is a simple and effective predictor for overall survival in patients with metastatic NPC.

Simultaneous determination of 2',3'-dideoxyinosine and the active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS and the application to cell pharmacokinetics.

A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 2',3'-dideoxyinosine (ddI) and the active metabolites, 2',3'-dideoxyadenosine-5'-triphosphate (ddA-TP) in human peripheral-blood mononuclear cell for the first time. The analytes were separated on a HILIC column (100mm×2.1mm, 1.7µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The cell homogenates sample was prepared by the solid phase extraction. The calibration curves were linear over a concentration range of 0.5-200.0ng/mL for ddI and 0.25-100.0ng/mL for ddA-TP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ddI and support cell pharmacokinetics after the patients with AIDS were orally administrated with ddI and tenofovir disoproxyl fumarate (TDF).