Effect of chemisorbed thiophenols with an electron donating group on surface-enhanced Raman scattering of gold nanorods.

Surface-enhanced Raman scattering (SERS) is a powerful technique to amplify the weak Raman scattering intensity by molecules chemisorbed on a metallic surface. Herein, we present the interfacial electronic effect of para-substituted aromatic thiophenols (TPs) with an electron donating group (EDG) on SERS of anisotropic gold nanorods (AuNRs) under resonant conditions. Probe molecules with an EDG showed great SERS enhancement in AuNRs at the resonant excitation wavelength. We found that the SERS enhancement with an EDG is caused by the formation of aggregates through intermolecular interactions among probe molecules, such as dimerization with hydrogen bonding via an amino group (-NH2) of p-aminothiophenol (p-ATP) and hydroxyl group (-OH) of p-mercaptophenol (p-MP), resulting in hot-spots between AuNRs. Furthermore, SERS having a stronger EDG (-NH2, p-ATP) with the Hammett constant of -0.66 exhibited greater enhancement than p-MP having hydroxyl (-OH) groups with the Hammett constant of -0.37. We found that the greater enhancement is ascribed to the temporary formation of a positively charged electron withdrawing group (-NH3+) in p-ATP, unlike p-MP, via the interaction of the lone pair of the amino group (-NH2) with ethanol. Therefore, this investigation provides new insightful experimental observations on SERS enhancement of probe molecules with an EDG.

Tuning Chemical Interface Damping: Interfacial Electronic Effects of Adsorbate Molecules and Sharp Tips of Single Gold Bipyramids.

The optimization of the localized surface plasmon resonance (LSPR)-decaying channels of hot-electrons is essential for efficient optical and photochemical processes. Understanding and having the ability to control chemical interface damping (CID) channel contributions will bring about new possibilities for tuning the efficiency of plasmonic hot-electron energy transfer in artificial devices. In this scanning electron microscopy-correlated dark-field scattering study, the CID was controlled by focusing on the electronic nature of disubstituted benzene rings acting as adsorbates, as well as the effects of sharp tips on gold bipyramids (AuBPs) with similar aspect ratios to those of gold nanorods. The results showed that the sharp tips on single AuBPs, as well as the electronic effects of the adsorbate molecules, increase the interfacial contact between the nanoparticles and adsorbate molecules. Electron withdrawing groups (EWGs) on the adsorbates induce larger homogeneous LSPR line widths compared to those of electron donating groups (EDGs). Depending on the location (ortho, meta, and para) of the EDG, the effect of benzene rings with an EDG, which was considered to be induced by sulfur atoms bound to the nanoparticle surface, is weakened by the back transfer of electrons facilitated by the difference in the availability of the electrons of the EDG. Therefore, this study reports that the CID in the LSPR total decay channels can be tuned by controlling the electron withdrawing and electron donating features of adsorbate molecules with the surface topology of metal.

6-Gingerol Suppresses Adipocyte-Derived Mediators of Inflammation In Vitro and in High-Fat Diet-Induced Obese Zebra Fish.

The present study was performed to investigate the molecular mechanism of 6-gingerol on adipocyte-mediated systemic inflammation in vitro and in high-fat diet-induced obese zebra fish. 6-Gingerol decreased adipogenesis due to the suppression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor gamma, CCAATT enhancer binding protein α, and adipocyte protein 2, and triglyceride synthesis enzymes, including sterol regulatory element-binding protein-1, fatty acid synthase, lysophosphatidic acid acyltransferase, and acyl-coA : diacylglycerol acyltransferase 1, in 3T3-L1. A coculture insert system using 3T3-L1 with RAW 264.7 (coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages) revealed that 6-gingerol increased anti-inflammatory cytokine interleukin-10. The expression of TNFα, monocyte chemotactic protein-1, interleukin-1ß, and interleukin-6 were decreased in the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages treated with 6-gingerol. Moreover, the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages treated with 6-gingerol inhibited the protein expression of TNFα and monocyte chemotactic protein-1 in RAW 264.7. 6-Gingerol decreased c-JUN N-terminal kinase and I kappa B kinase beta and its downstream target AP-1 expression in the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages. Furthermore, 6-gingerol decreased the expression of inducible nitric oxide synthase stimulated by the coculture insert system using fully differentiated 3T3-L1 cells with RAW 264.7 macrophages in RAW 264.7 and attenuated nitric oxide production in diet-induced obese zebra fish. Our results suggest that 6-gingerol suppresses inflammation through the regulation of the c-JUN N-terminal kinase-I kappa B kinase beta and its downstream targets.

Fucoxanthin Suppresses Lipid Accumulation and ROS Production During Differentiation in 3T3-L1 Adipocytes.

Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor-γ and of their target protein, fatty acid binding protein 4. Lipogenesis-related enzymes, such as diglyceride acyltransferase 1 and lysophosphatidic acid acyltransferase-θ, were downregulated by fucoxanthin. The ROS-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and the NADPH-generating enzyme glucose-6-phosphate dehydrogenase also decreased following fucoxanthin treatment. The adipokine adiponectin and the ROS-scavenging enzymes superoxide dismutase 2, glutathione reductase and catalase were dose-dependently increased by fucoxanthin. Furthermore, lipolysis-related enzymes and superoxide dismutase 1 were slightly decreased, because of the suppression of lipid-generating factors and the cytosolic enzyme NOX4. To confirm these results, we investigated lipid accumulation and ROS production in zebrafish, where fucoxanthin suppressed lipid and triglyceride accumulation, as well as ROS production. Our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic and lipogenic factors and ROS-regulating enzymes. Copyright © 2016 John Wiley & Sons, Ltd.

Ellagic acid suppresses lipid accumulation by suppressing early adipogenic events and cell cycle arrest.

Ellagic acid (EA) is a natural polyphenol found in various fruits and vegetables. In this study, we examined the inhibitory effect of EA on fat accumulation in 3T3-L1 cells during adipogenesis. Our data showed that EA reduced fat accumulation by down-regulating adipogenic markers such as peroxisome proliferator activated receptor γ (PPARγ) and the CCAAT/enhancer binding protein α (C/EBPα) at the mRNA and protein levels in a dose-dependent manner. We found that the decrease in adipogenic markers resulted from reduced expression of some early adipogenic transcription factors such as KLF4, KLF5, Krox20, and C/EBPß within 24 h. Also, these inhibitions were correlated with down-regulation of TG synthetic enzymes, causing inhibition of triglyceride (TG) levels in 3T3-L1 cells investigated by ORO staining and in zebrafish investigated by TG assay. Additionally, the cell cycle analysis showed that EA inhibited cell cycle progression by arresting cells at the G0/G1 phase.

Seapolynol Extracted from Ecklonia cava Inhibits Adipocyte Differentiation in Vitro and Decreases Fat Accumulation in Vivo.

Seapolynol (SN) is a polyphenol mixture derived from Ecklonia cava. We evaluated the effects of SN on lipid accumulation in adipocytes, zebrafish, and mice. SN effectively inhibited lipid accumulation in three experimental models by suppressing adipogenic factors. Triglyceride synthetic enzymes such as diacylglycerol acyltransferase 1 (DGAT1) and GPAT3 were also downregulated by SN. This SN-induced inhibition of adipogenic factors was shown to be due to the regulatory effect of SN on early adipogenic factors; SN downregulated the expression of Krueppel-like factor 4 (KLF4), KLF5, CCAAT-enhancer-binding protein ß (C/EBPß), C/EBPδ, and Protein C-ets-2 (ETS2), while KLF2, an anti-early adipogenic factor, was upregulated by SN. SN-mediated inhibition in early adipogenesis was closely correlated with the inhibition of mitotic clonal expansion via cell cycle arrest. SN inhibited cell cycle progression by suppressing cell cycle regulators, such as cyclin A, cyclinD, and pRb but increased p27, a cell cycle inhibitor. In a mouse study, SN effectively reduced body weight and plasma lipid increases induced by a high-fat diet; triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels were markedly reduced by SN. Moreover, SN remarkably improved high-fat-diet-induced hepatic lipid accumulation. Furthermore, SN activated AMP-activated protein kinase-α (AMPKα), an energy sensor, to suppress acetyl-coA carboxylase (ACC), inhibiting lipid synthesis. Our study suggests that SN may be an edible agent that can play a positive role in prevention of metabolic disorders.

A correlation between tocopherol content and antioxidant activity in seeds and germinating seeds of soybean cultivars.

BACKGROUND: Tocopherols are crucial lipid-soluble antioxidants and essential nutrients. There is increasing interest in the biofortification of crops with vitamin E for reducing micronutrient malnutrition. However, relatively little is known about the development of soybean cultivars with high levels of tocopherol through combined breeding. RESULT: Tocopherol contents of seeds and germinating seeds of 28 Korean soybean cultivars were analyzed and evaluated for health-promoting activities. Total tocopherol concentrations ranged from 203.9 to 503.1 µg g⁻¹ in seeds and from 20.1 to 230.1 µg g⁻¹ in germinating seeds. The traditional landraces of HaNagari (HN, 503.1 µg g⁻¹), Orialtae (OL, 486.6 µg g⁻¹), SuMoktae (SM, 476.5 µg g⁻¹) and SoRitae (SR, 475.5 µg g⁻¹) showed high levels of tocopherol content. The contents of the four isomers of tocopherol in seeds and germinating seeds were correlated with lipid peroxidation. The γ- and δ-tocopherol contents in seeds were related to 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity (0.434; P < 0.01 and 0.373; P < 0.05). CONCLUSION: Total tocopherol content was higher in soybean landraces as compared with modern cultivars developed by cross-breeding. These results suggest that soybean breeding is necessary to increase tocopherol levels.

Variation block-based genomics method for crop plants.

BACKGROUND: In contrast with wild species, cultivated crop genomes consist of reshuffled recombination blocks, which occurred by crossing and selection processes. Accordingly, recombination block-based genomics analysis can be an effective approach for the screening of target loci for agricultural traits. RESULTS: We propose the variation block method, which is a three-step process for recombination block detection and comparison. The first step is to detect variations by comparing the short-read DNA sequences of the cultivar to the reference genome of the target crop. Next, sequence blocks with variation patterns are examined and defined. The boundaries between the variation-containing sequence blocks are regarded as recombination sites. All the assumed recombination sites in the cultivar set are used to split the genomes, and the resulting sequence regions are termed variation blocks. Finally, the genomes are compared using the variation blocks. The variation block method identified recurring recombination blocks accurately and successfully represented block-level diversities in the publicly available genomes of 31 soybean and 23 rice accessions. The practicality of this approach was demonstrated by the identification of a putative locus determining soybean hilum color. CONCLUSIONS: We suggest that the variation block method is an efficient genomics method for the recombination block-level comparison of crop genomes. We expect that this method will facilitate the development of crop genomics by bringing genomics technologies to the field of crop breeding.

Detection of internal mammary lymph node metastasis with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with stage III breast cancer.

PURPOSE: The present study assessed the positive predictive value (PPV) of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of internal mammary node (IMN) metastasis in patients with clinical stage III breast cancer. METHODS: Patients who were diagnosed with clinical stage III breast cancer and underwent pretreatment (18)F-FDG PET/CT were retrospectively analyzed. The (18)F-FDG PET/CT scans were prospectively reviewed by two board-certified nuclear medicine physicians in a blinded manner. The intensities of IMNs were graded into four categories (no activity and lower, similar, and higher activities than that of the mediastinal blood pool). IMNs were measured from the combined CT (largest diameter of the short axis). Histologic data of the IMNs were obtained by ultrasonography-guided fine-needle aspiration biopsy or surgical excision. The PPV was calculated for pathologically confirmed IMNs. Visual grade, maximum standardized uptake values (SUVmax), and sizes were analyzed according to the pathology results. RESULTS: There were 249 clinical stage III breast cancer patients (age 48.0 ± 10.1 years, range 26-79 years) who had undergone initial (18)F-FDG PET/CT prior to treatment. Excluding 33 cases of stage IV breast cancer, 62 of 216 patients had visible IMNs on (18)F-FDG PET/CT, and histologic confirmation was obtained in 31 patients. There were 27 metastatic and four nonmetastatic nodes (PPV 87.1%). Metastatic nodes mostly presented with visual grade 3 (83.9%), and SUVmax and size were 3.5 ± 4.3 and 5.6 ± 2.0 mm, respectively. CONCLUSION: (18)F-FDG PET/CT has a high PPV for IMN metastasis in clinical stage III breast cancer, indicating the possibility of metastasis in IMNs with FDG uptake similar to/lower than that of the blood pool or small-sized nodes.

Gelidium elegans, an edible red seaweed, and hesperidin inhibit lipid accumulation and production of reactive oxygen species and reactive nitrogen species in 3T3-L1 and RAW264.7 cells.

Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose-dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide-induced nitric oxide production was significantly reduced in G. elegans extract-treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents.

Preoperative fluorine 18 fluorodeoxyglucose tumoral uptake ratio between upper and lower abdomen in primary advanced-stage ovarian cancer.

OBJECTIVE: The objective of this study was to assess whether the ratio of upper abdomen (UA) to lower abdomen (LA) (relative to the umbilicus) standardized fluorine 18 fluorodeoxyglucose uptake, as measured by preoperative positron emission tomography and computed tomography, is predictive of recurrence, survival, and suboptimal cytoreduction (residual tumor >1.0 cm) in advanced-stage ovarian cancer (AOC). METHODS: Positron emission tomography/computed tomography before surgical staging was performed in 159 AOC patients. The ratio between the highest maximum standardized uptake value (SUV(max)) in the UA and the LA was expressed as UA/LA SUV(max). Clinicopathological characteristics and follow-up information were collected retrospectively. Cox proportional hazards analysis was used to identify prognostic factors for recurrence and survival. Logistic regression analysis was used to identify predictors of suboptimal cytoreduction. RESULTS: The median age and follow-up period were 55 years (range, 27-80 years) and 32 months (range, 1-92 months), respectively; 133 and 26 patients had stage III and IV disease, respectively. There were 120 and 54 cases of recurrence and disease-specific death, respectively. Multivariate analysis showed that recurrence was associated significantly with high UA/LA SUV(max) (P < 0.05; hazard ratio [HR], 4.902; 95% confidence interval [CI], 2.521-9.531) and suboptimal cytoreduction (P < 0.05; HR, 2.431; 95% CI, 1.561-3.788), and that disease-specific death was significantly associated with high UA/LA SUV(max) (P < 0.05; HR, 2.777; 95% CI, 1.270-6.075), suboptimal cytoreduction (P < 0.05; HR, 1.951; 95% CI, 1.080-3.524), and histology (P < 0.05; HR, 4.134; 95% CI, 1.676-10.196). Upper abdomen/lower abdomen SUV(max) was the only independent predictor of suboptimal cytoreduction (P < 0.05; odds ratio, 4.644; 95% CI, 1.676-12.862). CONCLUSIONS: High preoperative UA/LA SUV(max) was significantly associated with poor prognosis and may be predictive of suboptimal cytoreduction in AOC. This parameter may be considered in the treatment of AOC patients.

Grateloupia lanceolata (Okamura) Kawaguchi, the edible red seaweed, inhibits lipid accumulation and reactive oxygen species production during differentiation in 3T3-L1 cells.

Grateloupia lanceolata (Okamura) Kawaguchi is a red alga native to coastal areas of East Asia. The effect of a G. lanceolata extract on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells was assessed by examining adipogenic transcription factors and ROS-regulating genes at the molecular level. An ethanol extract of G. lanceolata inhibited lipid accumulation and ROS production during adipogenesis. Treatment with the G. lanceolata extract lead to a reduction in the mRNA levels of the transcription factors, peroxisome proliferator-activated receptor-γ and CCAAT/ enhancer binding protein-α, and at the protein level for the target protein, adipocyte protein 2. ROS-producing nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 and NADPH-producing glucose-6-phosphate dehydrogenase mRNAs decreased following G. lanceolata extract treatment. In contrast, the mRNA level of ROS scavenging enzymes, including superoxide dismutase (SOD), glutathione peroxidase, and catalase increased in the extract-treated group. The increase in SOD1 (Cu/Zn-SOD) and 2 (Mn-SOD) proteins was correlated with their mRNA levels. Additionally, the G. lanceolata extract significantly enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes. Our results show that G. lanceolata extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes.

Pycnogenol® inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses.

Pycnogenol® is a group of flavonoids with antioxidant effects. Adipogenesis is the process of adipocyte differentiation. It causes the increase of lipids as well as ROS (reactive oxygen species). Lipid accumulation and ROS production were determined in 3 T3-L1 adipocyte, and the effect of Pycnogenol® was evaluated. Lipid accumulation was elevated in adipocyte treated with hydrogen peroxide, one of the ROS. Pycnogenol® showed an inhibitory effect on the lipid accumulation and ROS production during the adipogenesis. We also investigated the molecular events associated with ROS production and lipid accumulation. Our results showed that Pycnogenol® inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol® suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol® increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). Our results suggest that Pycnogenol® inhibits lipid accumulation and ROS production by regulating adipogenic gene expression and pro-/antioxidant enzyme responses in adipocytes.

Smad4 and p53 synergize in suppressing autochthonous intestinal cancer.

BACKGROUND: Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models. METHOD: To recapitulate human CRCs, we generated Villin-Cre;Smad4F / F ;Trp53F / F mice. We then compared the intestinal phenotype of Villin-Cre;Smad4F / F ;Trp53F / F mice (n = 40) with Villin-Cre;Smad4F / F (n = 30) and Villin-Cre;Trp53F / F mice (n = 45). RESULTS: Twenty-week-old Villin-Cre;Smad4F / F ;Trp53F / F mice displayed spontaneous highly proliferative intestinal tumors, and 85% of mice developed adenocarcinomas. p21 was downregulated in the intestinal mucosa in Villin-Cre;Smad4F / F ;Trp53F / F mice than in Villin-Cre;Smad4F / F and Villin-Cre;Trp53F / F mice. Villin-Cre;Smad4F / F ;Trp53F / F mice displayed multistep intestinal tumorigenesis and Wnt activation. Long-term CWP232291 (small-molecule Wnt inhibitor) treatment of Villin-Cre;Smad4F / F ;Trp53F / F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr-5, and Sca-1. CWP232291 treatment reduced the CSC frequency. Small-molecule Wnt inhibitors reduced intestinal CSC populations and inhibited their growth, along with Bcl-XL downregulation. Furthermore, BH3I-1, a Bcl-XL antagonist, increasingly inhibited intestinal CSCs than bulk tumor cells. CONCLUSION: Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/ß-catenin pathway.

High content screening identifies decaprenyl-phosphoribose 2' epimerase as a target for intracellular antimycobacterial inhibitors.

A critical feature of Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of M. tuberculosis within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against M. tuberculosis, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of M. tuberculosis with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2' epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials.

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

Small Animal PET Imaging of hTERT RNA-Targeted HSV1-tk Gene Expression with Trans-Splicing Ribozyme.

Background: Trans-splicing ribozymes (TSR) are useful anticancer agents targeting cancer-specific transcripts and replacing the RNA to induce anticancer gene expression specifically and selectively in cancer cells. Similar to other gene therapy methods, it is also important to evaluate the transgene expression for target specificity and ribozyme activity. Materials and Methods: In this study, the authors performed in vivo small animal positron emission tomography (PET) imaging and biodistribution assay to evaluate human telomerase reverse transcriptase (hTERT) RNA-targeting-specific TSR, which directs the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene selectively in hTERT-positive tumors through targeted RNA replacement of the hTERT transcript. Results: The hTERT RNA-targeted HSV1-tk expression with TSR was monitored by PET imaging with 124I labeled 2'-fluoro-2'-deoxy-1-ß-D-arabinofuranosyl-5-iodouracil, which is one of the thymidine derivatives acting as substrates for HSV1-tk, in hTERT-positive tumor-bearing mice. Conclusions: Imaging of hTERT RNA-targeted HSV1-tk expression by TSR could be used in the development of advanced gene therapy using tumor-specific TSR.

Indirect Interactions between Raman Probes Encapsulated within Cucurbit[7]urils and Gold Nanorods to Enhance Long-term Stability and Signal.

Surface-enhanced Raman scattering (SERS) is a powerful technique that enhances Raman signals by adsorbing probe molecules on rough metal surfaces. However, SERS is limited because target molecules must strongly interact with metal to enhance a stable Raman signal. In this study, to improve long-term SERS stability, we use cucurbit[7]urils (CB[7]) as bridge molecules and sample containers to probe Rhodamine 6G (R6G) molecules. We observed interactions between gold nanorods (AuNRs) and CB[7] via aggregate formation, which enhanced the Raman signal and improved long-term R6G probe stability by up to 20 days when encapsulated within CB[7] during SERS analysis.

Development of 64Cu-NOTA-Trastuzumab for HER2 Targeting: A Radiopharmaceutical with Improved Pharmacokinetics for Human Studies.

The purpose of this study was to develop 64Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2 (HER2). Methods: Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64Cu. Serum stability and immunoreactivity of 64Cu-NOTA-trastuzumab were tested. Small-animal PET imaging and biodistribution studies were performed in a HER2-positive breast cancer xenograft model (BT-474). The internal dosimetry for experimental animals was determined using the image-based approach with the Monte Carlo N-particle code. Results:64Cu-NOTA-trastuzumab was prepared with high radiolabeling yield and radiochemical purity (>98%) and showed high stability in serum and good immunoreactivity. Uptake of 64Cu-NOTA-trastuzumab was highest at 48 h after injection as determined by PET imaging and biodistribution results in BT-474 tumors. The blood radioactivity concentrations of 64Cu-NOTA-trastuzumab decreased biexponentially with time in both mice with and mice without BT-474 tumor xenografts. The calculated absorbed dose of 64Cu-NOTA-trastuzumab was 0.048 mGy/MBq for the heart, 0.079 mGy/MBq for the liver, and 0.047 mGy/MBq for the spleen. Conclusion:64Cu-NOTA-trastuzumab was effectively targeted to the HER2-expressing tumor in vitro and in vivo, and it exhibited a relatively low absorbed dose due to a short residence time. Therefore, 64Cu-NOTA-trastuzumab could be applied to select the right patients and right timing for HER2 therapy, to monitor the treatment response after HER2-targeted therapy, and to detect distal or metastatic spread.

Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish.

BACKGROUND: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. METHODS: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. RESULTS: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the C/EBPß transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase 3ß, which are also essential for stimulating the expression of CEBPß. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. CONCLUSION: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.