MOON, HYUN-SEUK, CHUNG-SOO CHUNG, HONG-GU LEE, TAE-GYU KIM, YUN-JAIE CHOI, AND CHONG-SUCHO. Inhibitory effect of (Ϫ)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity. 2007;15:2571-2582. Objective: The objective of this study was to investigate the molecular mechanisms underlying the attenuating effect of (Ϫ)-epigallocatechin-3-gallate (EGCG) on proliferation and lipid accumulation of 3T3-L1 cells, with a focus on the duration of EGCG treatment. Research Methods and Procedures: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and diamidino-2-phenylindole staining. The anti-adipogenic effect of EGCG on 3T3-L1 cells was analyzed by glycerol-3-phosphate dehydrogenase activity and Oil red O staining. Western blot analysis was used to detect adenosine monophosphate-activated protein kinase (AMPK) activation and phosphorylation of its substrate, acetyl-CoA carboxylase (ACC), and expression of insulin (INS) receptor, INS receptor substrate-1 (IRS-1), and adipocyte marker proteins. Results: Exposure to EGCG during the early period of adipogenesis (7 days) was sufficient to prevent lipid accumulation. During this period, EGCG greatly decreased expression of the adipocyte marker proteins peroxisome proliferator-activated receptor ␥2 (PPAR␥2) and liver X receptor (LXR)-␣. Furthermore, EGCG significantly induced generation of reactive oxygen species (ROS), which led to AMPK activation, and these effects were eliminated by N-acetylcysteine (NAC) treatment. Also, EGCG increased the tyrosine phosphorylation of INS receptor and INS-1 with increasing incubation time. In contrast, EGCG treatment did not alter glycerol release in the presence or absence of 2Ј,5Ј-dideoxyadenosine (DDA), indicating that EGCG had no effect on lipolysis. Discussion: Our data demonstrate that EGCG decreased cell viability and inhibited differentiation of 3T3-L1 cells in a manner dependent on the duration of treatment. Also, we showed that inhibition of adipocyte differentiation by EGCG was associated with decreased glycerol-3-phosphate dehydrogenase (GPDH) activity accompanied by a strong inhibition of PPAR␥2-induced transcriptional activity. Furthermore, the inhibition of adipocyte differentiation by EGCG involved generation of ROS and activation of AMPK.

Variovorax paradoxus is a microorganism of special interest due to its diverse metabolic capabilities, including the biodegradation of both biogenic compounds and anthropogenic contaminants. V. paradoxus also engages in mutually beneficial interactions with both bacteria and plants. The complete genome sequence of V. paradoxus S110 is composed of 6,754,997 bp with 6,279 predicted protein-coding sequences within two circular chromosomes. Genomic analysis has revealed multiple metabolic features for autotrophic and heterotrophic lifestyles. These metabolic diversities enable independent survival, as well as a symbiotic lifestyle. Consequently, S110 appears to have evolved into a superbly adaptable microorganism that is able to survive in ever-changing environmental conditions. Based on our findings, we suggest V. paradoxus S110 as a potential candidate for agrobiotechnological applications, such as biofertilizer and biopesticide. Because it has many associations with other biota, it is also suited to serve as an additional model system for studies of microbeplant and microbe-microbe interactions.Variovorax paradoxus is a metabolically diverse, aerobic bacterium that engages in mutually beneficial interactions with a variety of bacteria and plants. V. paradoxus belongs to the subclass of Proteobacteria and can metabolically utilize natural compounds produced by other biota, such as acyl homoserine lactones (AHLs) (25) and alkyl/aryl-sulfonates (38). This metabolic capacity suggests that Variovorax plays an essential role in the natural cycling of biogenic chemicals. Variovorax species are also able to degrade a variety of contaminants, including pesticides and crude oil-associated S-metabolites (5,19,37,41,42,46,50,51,52), often in synergistic and mutually beneficial interactions with other bacteria. In addition, a close relative of Variovorax was found to be the central, nonphotosynthetic partner within the phototrophic consortium "Chlorochromatium aggregatum" (22). Moreover, V. paradoxus is resistant to various heavy metals, including cadmium and mercury (2).V. paradoxus belongs to a group referred to as plant growthpromoting rhizobacteria (PGPR), which exert beneficial effects on plant growth. As a common plant symbiont found in the rhizosphere (2, 3), the metabolic diversity of V. paradoxus appears to be related to its role as a PGPR. By degrading toxic contaminants, this bacterium can prevent harm otherwise experienced by the plant and thus can promote plant growth. Strains of Variovorax can enhance the host plant's stress tolerance and disease resistance (2, 3) and aid in nutrient availability and uptake (38). The effectiveness of Variovorax as a PGPR is likely to be more potent because it also appears to be a good endophytic symbiont (34,36,39,43,44,45,47) and thus interacts more closely with the host plant. Conversely, endospheric habitats are known to offer microbes the advantage of a more uniform and protective niche compared to the competitive, high-stress environment of the soil (36).The diverse metabol...

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Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung lymph nodes. The results of this 28-day graphene inhalation study suggest low toxicity and a NOAEL of no less than 1.88 mg/m(3).

LPLN ≥ 2 and a ratio of the number of positive LN/number of dissected LN > 0.3 were prognostic of poor LPFS. The prediction curve of LPR according to the number and size of LPLN could be useful for determining the benefit of additional lateral pelvic treatment.

4001 Background: Adjuvant chemotherapy and/or chemoradiotherapy have been the standard of care in GC for years, supported by randomized trials. We compared the efficacy of different chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II/III, node-positive GC. Methods: From Feb 2013 through Nov 2018, we randomly assigned, in a 1:1:1 ratio, patients with pathologically-staged II or III, node-positive, D2-resected GC, to receive adjuvant S-1 (40-60 mg twice daily 4-weeks-on/2-weeks-off) for one year, S-1 (2-weeks-on/1-week-off) plus oxaliplatin 130 mg/m2 (SOX) for six months, or SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to the type of surgery (total or subtotal gastrectomy), stage (II or III), and Lauren histologic classification (diffuse or intestinal). The primary endpoint was disease-free survival (DFS). A total of 900 patients had to be enrolled to demonstrate superiority of SOX or SOXRT to S-1 (hazard ratio [HR] 0.667), with 90% power at a two-sided significance level of 5%. Results: A total of 538 patients were included for this interim efficacy analysis. Median age was 58 years, men constituted 65%, and stage II and III were 31% and 69%, respectively. Baseline tumor and patient characteristics were balanced between treatment arms. Adverse events were as anticipated in each arm, generally well-tolerated and manageable. DFS in the control arm (S-1) were significantly shorter than in SOX and SOXRT arms (stratified HR for recurrence): S-1 vs. SOX, 0.617 (P = 0.016) and S-1 vs. SOXRT, 0.686 (P = 0.057). The DFS at 3-years was found to be 65%, 78% and 73% in S-1, SOX and SOXRT arms, respectively. No difference in DFS between SOX and SOXRT was found (HR 0.910, P = 0.667). Based on the results after the observation of 145 recurrence events at the cutoff date of Dec 27, 2018, the independent data monitoring committee considered the results sufficient to meet the endpoint of the trial and recommended early stopping of the trial. Conclusions: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared to S-1 monotherapy. Clinical trial information: NCT0176146.

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To better understand the potential ecotoxicological impact of silver nanoparticles (AgNPs) and silver nanowires (AgNWs) released into freshwater environments, the toxicities of these nanomaterials were assessed and compared using Organization for Economic Cooperation and Development (OECD) test guidelines, including a “Daphnia sp., acute immobilization test,” “Fish, acute toxicity test,” and “freshwater alga and cyanobacteria, growth inhibition test.” Based on the estimated median lethal/effective concentrations of AgNPs and AgNWs, the susceptibility to the nanomaterials was different among test organisms (daphnia > algae > fish), suggesting that the AgNPs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 1” for Raphidocelis subcapitata, while the AgNWs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 2” for Raphidocelis subcapitata, according to the GHS (Globally Harmonized System of Classification and Labelling of Chemicals). In conclusion, the present results suggest that more attention should be paid to prevent the accidental or intentional release of silver nanomaterials into freshwater aquatic environments.