Risk profiles of personality traits for suicidality among mood disorder patients and community controls.

OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.

Efficient spin-light emitting diodes based on InGaN/GaN quantum disks at room temperature: a new self-polarized paradigm.

A well-behaved spin-light emitting diode (LED) composed of InGaN/GaN multiple quantum disks (MQDs), ferromagnetic contact, and Fe3O4 nanoparticles has been designed, fabricated, and characterized. The degree of circular polarization of electroluminescence (EL) can reach up to a high value of 10.9% at room temperature in a low magnetic field of 0.35 T, which overcomes a very low degree of spin polarization in nitride semiconductors due to the weak spin-orbit interaction. Several underlying mechanisms play significant roles simultaneously in this newly designed device for the achievement of such a high performance. Most of all, the vacancy between nanodisks can be filled by half-metal nanoparticles with suitable energy band alignment, which enables selective transfer of spin polarized electrons and holes and leads to the enhanced output spin polarization of LED. Unlike previously reported mechanisms, this new process leads to a weak dependence of spin relaxation on temperature. Additionally, the internal strain in planar InGaN/GaN multiple quantum wells can be relaxed in the nanodisk formation process, which leads to the disappearance of Rashba Hamiltonian and enhances the spin relaxation time. Our approach therefore opens up a new route for the further research and development of semiconductor spintronics.

Presence of an SH2 domain in the actin-binding protein tensin.

The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

Prevalence of metabolic syndrome among patients with schizophrenia or schizoaffective disorder in Taiwan.

OBJECTIVE: Because of ethnic differences in metabolic syndrome (MS) criteria, this study aimed to investigate the MS prevalence among patients with schizophrenia or schizoaffective disorder in Taiwan. METHOD: We recruited 650 patients with schizophrenia or schizoaffective disorder from 36 psychiatric institutions. The MS prevalence was assessed based on the modified Adult Treatment Panel (ATP) III criteria for Asians. RESULTS: The overall MS prevalence was 34.9%, with 38.9% in female and 31.5% in male patients respectively. The difference of MS prevalence between our sample and the general population was marked in male patients under 40 years of age and in female patients under 50 years old. Body mass index > or =24 and age over 40 years old are two important risk factors of MS. Female and polypharmacy had marginal significance with the presence of MS. CONCLUSION: Patients with schizophrenia or schizoaffective disorder in Taiwan had a high prevalence of MS, which appeared early in their lives.

MicroRNA-124 inhibits colorectal cancer cell proliferation and suppresses tumor growth by interacting with PLCB1 and regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) is the most common malignancy for cancer-associated death. This study aimed to investigate the effects of microRNA-124 (miR-124) on tumor proliferation of CRC in vivo and in vitro. MATERIALS AND METHODS: MiR-124 mimics were synthesized and transfected into SW620 cells, which were divided into SW620, microRNA-normal control (miR-NC) and miR-124 mimics group. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine miR-124, chemokine (C-C motif) ligand-20 (CCL20), tankyrase-2 (TNKS2), phospholipase Cbeta1 (PLCB1) and Wnt4. Cell counting kit-8 (CCK-8) was employed to evaluate cell proliferation. The interaction between miR-124 and PLCB1 was tested with the Dual-Luciferase assay. Cell cycle, apoptosis and invasion were also evaluated. CRC xenograft mouse model was established and tumor size was measured. Hematoxylin and eosin (HE) was used to examine inflammation. Western blot was utilized to detect Wnt4. RESULTS: MiR-124 was over-expressed in SW620 cells, significantly reduced CCL20 and enhanced TNKS2 compared to that of the miR-NC group (p<0.05). MiR-124 might play roles by initiating PLCB1 expression. MiR-124 significantly decreased cell viability compared to the miR-NC group (p<0.05). MiR-124 regulated cell cycle and markedly induced apoptosis and inhibited cell invasion compared to the miR-NC group (p<0.05). MiR-124 significantly decreased tumor size of CRC models compared to miR-NC mice (p<0.05). MiR-124 remarkably alleviated inflammation of tumor tissues. MiR-124 markedly enhanced Wnt4 expression compared to the miR-NC group (p<0.05). CONCLUSIONS: MiR-124 inhibited tumor cell proliferation in vitro and suppressed tumor growth in vivo by interacting with PLCB1 and regulating the Wnt/ß-catenin signaling pathway.

Inhibition of the integrin/FAK signaling axis and c-Myc synergistically disrupts ovarian cancer malignancy.

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin-FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer.

Deficiency of the cysteine protease cathepsin S impairs microvessel growth.

During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.

Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization.

BACKGROUND: We sought to identify and characterize potential alterations in E2F-1, a transcription factor that binds to the retinoblastoma protein (pRB), in bladder neoplasms and to elucidate a possible role for E2F-1 as an oncogene or a tumor suppressor gene. METHODS: Tumor samples from 133 evaluable patients with bladder cancer were analyzed for E2F-1 gene mutations by use of polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. In addition, tumors were studied for E2F-1 and pRB protein expression by use of immunohistochemistry. Results from the above analyses were correlated with clinicopathologic parameters and outcome. All P values are two-sided. RESULTS: A polymorphism, consisting of a nucleotide change at amino acid codon 393 in exon 7 (GGC-->AGC [Gly-->Ser]), was identified in seven of 133 case patients, being present in both tumor and corresponding normal tissues. No bandshifts were identified in the nuclear-localization or DNA-binding domains on PCR-SSCP analysis. On immunohistochemical analysis, E2F-1 nuclear reactivity was observed in less than 5% of the cells from 53 tumors and in 5%-75% of the cells from the remaining 80 tumors. The pattern of E2F-1 protein expression was not altered in relation to the identified polymorphism. pRB nuclear reactivity greater than 20% (of tumor cells stained) was present in 66% of the samples. E2F-1 nuclear reactivity correlated inversely with the percentage of cells showing pRB reactivity (Kendall tau(b) = -0.18; P = .019). On multivariate analysis, patients with lower E2F-1 reactivity had statistically significantly increased risks of progression to metastases (P = .001) and death (P = .02). CONCLUSIONS: E2F-1 alterations occur at the phenotypic level, rather than at the genotypic level, in bladder cancer. The adverse outcome for patients whose tumors exhibit low E2F-1 nuclear expression suggests a possible tumor suppressor role for E2F-1 in bladder cancer.

Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation.

Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway.

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.

Cigarette smoking and chromosome 9 alterations in bladder cancer.

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan.

Previous studies examining the putative association between DRD2 TaqI A1 and alcoholism have produced conflicting results. Major critiques of such studies include potential confounding arising from population admixture by inappropriate selection of controls, failure to screen out substance abusers from controls, and the failure to assess the severity of alcoholics. To address these issues, we compared the allelic frequency of two polymorphisms of DRD2, TaqI A and NcoI, among severe alcoholics and their ethnically matched nonalcoholic controls within four major aboriginal groups and Han (Chinese) in Taiwan. The sample of alcoholics and controls examined for the five groups included 36 and 31 (Atayal), 24 and 23 (Ami), 58 and 58 (Bunun), 35 and 35 (Paiwan), and 50 and 66 (Han). A borderline association between TaqI A1 and alcoholism among the Ami (P = 0.08) and an association between NcoI N1 and alcoholism among Han (P = 0.01) were found. Results of haplotype analysis further confirm that the frequency of haplotype A1N1 was higher in alcoholics than in controls for the Ami (P = 0.01) and Han (P = 0.03). If controls with tobacco abuse were excluded from the analysis, the results remained unchanged. Severity in medical complications of alcohol dependence with withdrawal symptoms was not associated with higher prevalence of DRD2 TaqI A1 or NcoI N1 alleles. The absence of an association between DRD2 and alcoholism among the three aboriginal groups suggests either a higher rate of phenocopies among aboriginal alcoholics or genetic heterogeneity in the susceptibility to alcoholism.

Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients.

BACKGROUND: Concomitant fluvoxamine use can potentially reduce the dosage of clozapine needed in treatment-refractory patients with schizophrenia. Previous reports have shown that fluvoxamine can increase plasma clozapine concentrations by inhibition of cytochrome P450 (CYP) 1A2. We evaluated the safety and efficacy of fluvoxamine, 50 mg/day, coadministration with clozapine, 100 mg/day, in refractory schizophrenic patients. METHOD: In this prospective study, 18 treatment-refractory patients with DSM-IV schizophrenia (10 nonsmokers and 8 smokers) were treated with clozapine at a target dose of 100 mg h.s. After steady-state conditions of clozapine had been reached, 50 mg/day of fluvoxamine was then added. Plasma levels of clozapine, norclozapine, and clozapine N-oxide were measured prior to fluvoxamine addition and on days 14 and 28 during combined treatment. Side effects and efficacy were monitored with standardized rating instruments. RESULTS: After 14 days of combined treatment, the mean +/- SD plasma clozapine level increased 2.3-fold to 432.4+/-190.9 ng/mL without further elevation on day 28. All patients completed the study without significant adverse side effects. Twelve of the 18 patients achieved plasma clozapine concentrations of at least 350 ng/mL. While plasma norclozapine levels also rose (but to a smaller extent), plasma clozapine N-oxide levels remained unchanged after the add-on therapy. Patients who smoked had 34% lower plasma clozapine concentrations than nonsmokers (NS). Three of the 4 patients who did not reach clozapine plasma levels of at least 300 ng/mL were smokers. Plasma norclozapine/clozapine ratios, especially in smokers, declined significantly with fluvoxamine addition. CONCLUSION: The addition of fluvoxamine, 50 mg/day, to low-dose clozapine, 100 mg/day, can raise plasma clozapine levels to at least 300 ng/mL in most patients. Only slight dosage adjustments with clozapine may be needed after fluvoxamine coadministration in some patients who smoke. Plasma clozapine levels remained stable after 14 days of fluvoxamine addition. The combined treatment was well tolerated, and clinical improvement was observed in our patients. Further long-term studies with this drug combination are needed to determine its economic impact.

Ubiquitin hybrid protein gene expression during human colon cancer progression.

Ubiquitin is involved in cell-cycle control and DNA replication through a specific proteolytic pathway. Our previous studies demonstrated selected higher expression of a gene encoding ubiquitin-ribosomal protein S27a in poorly differentiated colon carcinoma cell lines. In this study, we evaluated this ubiquitin hybrid protein gene expression in surgical specimens of colon cancers. Northern blot analysis showed that ubiquitin hybrid protein messenger RNA was overexpressed in primary colon cancers compared with adjacent normal colon mucosae in 17 of 20 patients. Dot blot analysis of RNA of 27 tumor samples revealed significantly greater expression in higher Dukes' stage primary colon tumors and liver metastases. These data imply that protein translation machinery is highly activated during progression and metastasis of colon tumors, and that ubiquitin hybrid protein may be useful as a marker of biological aggressiveness.

Inhibition of peritoneal tumor-cell implantation: model for laparoscopic cancer surgery.

A serious concern in applying laparoscopic surgery to malignancies is the possibility of tumor spillage and seeding. We developed a model of peritoneal tumor implantation using a murine bladder tumor cell line, MBT-2. Anesthetized C3H male mice underwent mock laparoscopy with or without peritoneal disruption and instillation of tumor cells via a 16-gauge angiocatheter, and the effect of heparin and the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) on tumor cell adherence and growth was evaluated. Animals were divided into six groups: Group 1 = tumor cells only; Group 2 = peritoneal disruption + tumor cells; Group 3 = heparin + tumor cells; Group 4 = peritoneal disruption + heparin + tumor cells; Group 5 = GRGDS + tumor cells; and Group 6 = peritoneal disruption + GRGDS + tumor cells. In all animals, a greater tumor burden was noted at the sites of peritoneal disruption. Moreover, 50% and 63% of animals in Groups 1 and 2 developed tumors compared with 17% and 31% of those in Groups 3 and 4, respectively. There was significantly more tumor at the sites of peritoneal disruption in the "tumor only" groups than in those that received heparin (mean tumor volume 32.32 mm3 in Group 2 v 2.77 mm3 in Group 4; p < 0.05). The GRGDS-treated groups showed a trend toward decreased number and size of tumors compared with the tumor only groups, although the differences were not statistically significant. These findings imply that prophylactic irrigation with substances that decrease cell adherence may prevent tumor implantation after accidental intraoperative tumor spillage.

[Determination of D-catechin plasma concentration and pharmacokinetic parameters using HPLC method].

d-Catechin (alpha-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol) is an important hepatotropic drug. It has been extensively used in 1980's. A few methods for quantitative analysis of d-catechin in biological fluids have been reported, but they are not so sensitive or specific for pharmacokinetic interest. In this study, a specific, sensitive and reproducible RPHPLC-DAD method for quantifying d-catechin in plasma is established. Sep-Pak C18 cartridge is used for sample preparation. HPLC separation is performed on Waters HPLC system consisting of a Model 990 diode array detector. A 150 x 5 mm ID column containing YWG C18, held at 25 +/- 0.5 degrees C, and a mobile phase of methanol-0.03 mol/L citric buffer solution containing 0.04% TEMED,pH 4.7 (16:84, v/v) at a flow rate of 2 ml/min is used. Under the studied conditions, the tR for d-catechin is 7.74 min, that of the internal standard (cefetaxime, CTX) is 9.32 min. The peak of d-catechin is identified with the DAD and MS techniques. The limit of detection of the method is 9 ng, and the minimal detectable concentration in plasma is 17.4 ng/ml. There is a linear relationship between the peak area ratio over the range of 69.6-1160 ng/ml with r = 0.9993. The method has been applied to determine the d-catechin concentration in rabbit plasma. The pharmacokinetic characteristics and parameters are studied.

Anomalous quantum efficiency for photoconduction and its power dependence in metal oxide semiconductor nanowires.

The quantum efficiency and carrier lifetime that decide the photoconduction (PC) efficiencies in the metal oxide semiconductor nanowires (NWs) have been investigated. The experimental result surprisingly shows that the SnO2, TiO2, WO3, and ZnO NWs reveal extraordinary quantum efficiencies in common, which are over one to three orders of magnitude lower than the theoretical expectation. The surface depletion region (SDR)-controlled photoconductivity is proposed to explain the anomalous quantum efficiency and its power dependence. The inherent difference between the metal oxide nanostructures such as carrier lifetime, carrier concentration, and dielectric constant leading to the distinct PC performance and behavior are also discussed.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.