Separation of charge carriers and generation of reactive oxygen species by TiO2 nanoparticles mixed with differently-coated gold nanorods under light irradiation

Combinations of semiconductor nanoparticles (NPs) with noble metal NPs enable an increase in the photoactivity of semiconductor NPs into the visible and near-infrared regions. The design rationale of the semiconductor-metal hybrid nanostructures for the optimization of charge carrier separation and reactive oxygen species (ROS) generation remains unclear. In this study, the interactions of Au nanorods (AuNRs) with TiO₂ NPs were modulated by controlling their surface charges. Positively charged AuNRs formed aggregates with the negatively charged TiO₂ NPs (AuNR@CTAB/TiO₂) upon mixing, suggesting that Schottky junctions may exist between Au and TiO₂. In contrast, negatively charged AuNRs (AuNR@PSS) remained spatially separated from the TiO₂ NPs in the mixed suspension (AuNR@PSS/TiO₂), owing to electrostatic repulsion. We used electron spin resonance (ESR) spectroscopy to detect the separation of charged carriers and ROS generation in these two mixtures under simulated sunlight irradiation. We also explored the role of dissolved oxygen in charge carrier separation and ROS generation by continuously introducing oxygen into the AuNR@CTAB/TiO₂ suspension under simulated sunlight irradiation. Moreover, the generation of ROS by the AuNR@CTAB/TiO₂ and AuNR@PSS/TiO₂ mixtures were also examined under 808?nm laser irradiation. Our results show that the photogenerated electrons of excited semiconductor NPs are readily transferred to noble metal NPs simply by collisions, but the transfer of photogenerated hot electrons from excited AuNRs to TiO₂ NPs is more stringent and requires the formation of Schottky junctions. In addition, the introduction of oxygen is an efficient way to enhance the photocatalytic activity of semiconductor NPs/noble metal NPs system combinations.     

Ferroxidase-like and antibacterial activity of PtCu alloy nanoparticles

Many metal nanoparticles are reported to have intrinsic enzyme-like activities and offer great potential in chemical and biomedical applications. In this study, PtCu alloy nanoparticles (NPs), synthesized through hydrothermal treatment of Cu²⁺ and Pt²⁺ in an aqueous solution, were evaluated for ferroxidase-like and antibacterial activity. Electron spin resonance (ESR) spectroscopy and colorimetric methods were used to demonstrate that PtCu NPs exhibited strong ferroxidase-like activity in a weakly acidic environment and that this activity was not affected by the presence of most other ions, except silver. Based on the color reaction of salicylic acid in the presence of Fe³⁺, we tested the ferroxidase-like activity of PtCu NPs to specifically detect Fe²⁺ in a solution of an oral iron supplement and compared these results with data acquired from atomic absorption spectroscopy and the phenanthroline colorimetric method. The results showed that the newly developed PtCu NPs detection method was equivalent to or better than the other two methods used for Fe²⁺ detection. The antibacterial experiments showed that PtCu NPs have strong antibacterial activity against Staphylococcus aureus and Escherichia coli. Herein, we demonstrate that the peroxidase-like activity of PtCu NPs can catalyze H₂O₂ and generate hydroxyl radicals, which may elucidate the antibacterial activity of the PtCu NPs against S. aureus and E. coli. These results showed that PtCu NPs exhibited both ferroxidase- and peroxidase-like activity and that they may serve as convenient and efficient NPs for the detection of Fe²⁺ and for antibacterial applications.     

Exploring the activities of ruthenium nanomaterials as reactive oxygen species scavengers

Research on noble metal nanoparticles (NPs) able to scavenge reactive oxygen species (ROS) has undergone a tremendous growth recently. However, the interactions between ruthenium nanoparticles (Ru NPs) and ROS have never been systematically explored thus far. This research focused on the decomposition of hydrogen peroxide (H₂O₂), scavenging of hydroxyl radicals (^?OH), superoxide radical (O₂^??), singlet oxygen (¹O₂), 2,2′-azino-bis(3-ethylbenzenothiazoline- 6-sulfonic acid ion (ABTS^?+), and 1,1-diphenyl-2-picrylhydrazyl radical (^?DPPH) in the presence of commercial Ru NPs using the electron spin resonance technique. In vitro cell studies demonstrated that Ru NPs have excellent biocompatibility and exert a cytoprotective effect against oxidative stress. These findings may spark fresh enthusiasm for the applications of Ru NPs under relevant physiologically conditions.     

Intrinsic catalytic activity of rhodium nanoparticles with respect to reactive oxygen species scavenging: implication for diminishing cytotoxicity

Noble metal nanoparticles (NPs) and their hybrids have demonstrated a strong potential to mimic the catalytic activity of natural enzymes and diminish oxidative stress. There is a large space to explore the intrinsic catalytic activity of Rh NPs with respect to reactive oxygen species (ROS) scavenging. We found that Rh NPs can quench H₂O₂, ^?OH, O₂^??, ¹O₂ and inhibit lipid peroxidation under physiological conditions. In vitro cell experiments proved that Rh NPs have great biocompatibility and protect cells from oxidative damage caused by H₂O₂. This study can provide important insights that could inform future biological applications.     

The measurement of bioreductive capacity of tumor cells using methylene blue

Purpose: Methylene blue (MB) can be used as an intracellular electron acceptor. The purpose of this study was to demonstrate the usefulness of MB for the determination of total bioreductive capacity of cell suspensions.Methods and Materials: We measured oxygen consumption by Clark electrode and pentose cycle activity by release of ¹⁴CO₂ from 1-¹⁴C-glucose.Results: Methylene blue catalyzes the reaction of intracellular reductants NADPH, NADH, and reduced glutathione (GSH) with oxygen, causing the production of hydrogen peroxide. The reaction rate correlates with the negative charge of molecule (NADPH⁻⁴ > NADH⁻² > GSH⁻¹), suggesting that reaction with positively charged oxidized MB is the limiting step of the reaction. In a cellular system MB causes the electron flow from cellular endogenous substrates to oxygen. It is activated by the disruption of the NADP⁺/NADPH ratio due to several processes. These are direct oxidation of NADPH and GSH, the GSH peroxidase catalyzed reaction of GSH with H₂O₂, followed by NADPH oxidation by oxidized glutathione (GSSG). This results in increased cellular oxygen consumption and stimulation of the oxidative limb of pentose cycle (PC) in the presence of MB. The cellular effect of MB differs from other electron accepting drugs. Diamide and tert-butylhydroperoxide act as direct oxidants, while MB is an electron carrier to oxygen. Accordingly, MB shows the highest effect on PC activation and oxygen consumption.Conclusions: Our results indicate that MB may be used for the determination of the total bioreductive capacity of the cells, measured by oxygen consumption and PC activation.     

Comparative neurotoxicity of oxaliplatin, ormaplatin, and their biotransformation products utilizing a rat dorsal root ganglia in vitro explant culture model

Purpose: Neurotoxicity is one of the major toxicities of platinum-based anticancer drugs, especially oxaliplatin and ormaplatin. It has been postulated that biotransformation products are likely to be responsible for the toxicity of platinum drugs. In our preceding pharmacokinetic study, both oxaliplatin and ormaplatin were observed to produce the same types of major plasma biotransformation products. However, while the plasma concentration of ormaplatin was much lower than that of oxaliplatin at an equimolar dose, one of their common biotransformation products, Pt(dach)Cl₂, was present at 29-fold higher concentrations in the plasma following the i.v. injection of ormaplatin than of oxaliplatin. Because ormaplatin has severe neurotoxicity and Pt(dach)Cl₂ is very cytotoxic, we have postulated that Pt(dach)Cl₂ is likely to be responsible for the differences in neurotoxicity between ormaplatin and oxaliplatin. In order to test this hypothesis, we compared the neurotoxicity of oxaliplatin, ormaplatin, and their biotransformation products. Since the dorsal root ganglia (DRGs) have been suggested to be the likely targtet for platinum drugs and in vitro DRG explant cultures have been suggested to be a valid model for studying cisplatin-associated neurotoxicity, our comparative neurotoxicity study was conducted with DRG explant cultures in vitro. Methods: Based on the previous studies of cisplatin neurotoxicity, we established our in vitro DRG explant culture utilizing DRGs dissected from E-19 embryonic rats. Rat DRGs were incubated for 30 min with different platinum compounds to mimic in vivo exposure conditions; this was by followed by a 48-h incubation in culture medium at 37 °C. At the end of the incubation, the neurites were fixed and stained with toluidine blue, and neurite outgrowth was quantitated by phase-contrast microscopy. The inhibition of neurite outgrowth by platinum compounds was used as an indicator of in vitro neurotoxicity. Since an in vivo study has indicated that the order of neurotoxicity is ormaplatin > cisplatin ≥ oxaliplatin > carboplatin as measured by morphometric changes to rat DRGs, we initially validated our DRG explant culture model by comparing the in vitro neurotoxicity of ormaplatin, cisplatin, oxaliplatin, and carboplatin. After observing the same neurotoxicity rank between this study and a previous in vivo study, we further compared the neurotoxicity of oxaliplatin, ormaplatin, and their biotransformation products including Pt(dach)Cl₂, Pt(dach)(H₂O)Cl, Pt(dach)(H₂O)₂, Pt(dach)(Met), and Pt(dach)(GSH) utilizing the DRG explant culture model. Results: Our study indicated that Pt(dach)Cl₂ and its hydrolysis products were more potent at inhibiting neurite outgrowth than the parent drugs oxaliplatin and ormaplatin. In contrast, no detectable inhibition of neurite outgrowth was observed for DRGs dosed with Pt(dach)(Met) and Pt(dach)(GSH). Conclusion: This study suggests that biotransformation products such as Pt(dach)Cl₂ and its hydrolysis products are more neurotoxic than the parent drugs oxaliplatin and ormaplatin. The different neurotoxicity profiles of oxaliplatin and ormaplatin are more likely due to the different plasma concentrations of their common biotransformation product Pt(dach)Cl₂ than to differences in their intrinsic neurotoxicity. Received: 12 June 1998 / Accepted: 22 October 1998     

Effects of noble metal nanoparticles on the hydroxyl radical scavenging ability of dietary antioxidants

Noble metal nanoparticles (NPs) have been widely used in many consumer products. Their effects on the antioxidant activity of commercial dietary supplements have not been well evaluated. In this study, we examined the effects of gold (Au NPs), silver (Ag NPs), platinum (Pt NPs), and palladium (Pd NPs) on the hydroxyl radical (·OH) scavenging ability of three dietary supplements vitamin C (L-ascorbic acid, AA), (?)-epigallocatechin gallate (EGCG), and gallic acid (GA). By electron spin resonance (ESR) spin-trapping measurement, the results show that these noble metal NPs can inhibit the hydroxyl radical scavenging ability of these dietary supplements.     

Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

Activity of Plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae,Escherichia coli,and Enterobacter spp. from Athens,Greece

Abstract

The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC₅₀/MIC₉₀ to tobramycin, amikacin and gentamicin being 32/>32, 32/>32 and 4/>8 μg/ml, respectively. ACHN-490 retained activity (MICs?4 μg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC₅₀ and MIC₉₀ of 1 and 2 μg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens.     

In vitro activity of the ketolide cethromycin in multidrug-resistant clinical Neisseria gonorrhoeae isolates and international reference strains

Antimicrobial resistance in Neisseria gonorrhoeae is a major public health problem, which compromises the treatment of gonorrhoea globally. We evaluated the in vitro activity of the ketolide cethromycin against a large panel of clinical gonococcal isolates and international reference strains (n?=?254), including numerous multidrug-resistant and extensively drug-resistant isolates. Cethromycin showed potent in vitro activity against most of the gonococcal isolates with the following modal MIC, MIC₅₀ and MIC₉₀: 0.064?mg/L, 0.125?mg/L and 0.5?mg/L, respectively. However, cross-resistance between azithromycin and cethromycin was identified (Spearman’s rank correlation coefficient 0.917) and isolates displaying high-level resistance to azithromycin (MIC >256?mg/L; n?=?9) also showed high MICs of cethromycin (32–256?mg/L). In conclusion, the cross-resistance with azithromycin indicates that cethromycin may not be considered for empirical first-line monotherapy of gonorrhoea. However, cethromycin might be valuable in combination antimicrobial therapy and for second-line therapy e.g. for cases with ceftriaxone resistance or allergy.     

Sulforaphane induces G2–M arrest and apoptosis in high metastasis cell line of salivary gland adenoid cystic carcinoma

New chemotherapeutic strategy should be investigated to enhance clinical management in salivary gland adenoid cystic carcinoma (ACC). Recently, sulforaphane (SFN), as a natural compound from cruciferous vegetables exhibits a potent anti-cancer activity in various tumor cells, but remains uncertain in ACC cells. The present study examined whether SFN suppresses proliferation and in ACC cells, if so, the possible molecular targets would be further investigated. Cell survives, apoptosis, cell cycle progression and molecular targets were identified by multiple detecting techniques, including trypan blue dye exclusion assay, electron microscopy, AO/EB staining, flow cytometry and immunoblotting in human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M). The results showed that 5–20 μM SFN suppressed proliferation and induced apoptosis of ACC-M cells in dose- and time-dependent manners. Cell cycle analysis demonstrated treatment of ACC-M cells with 20 μM SFN resulted in G₂/M cell cycle arrest, which was associated with a marked decline in protein levels of G₂/M regulatory proteins including cyclin B1 and cyclin-dependent kinase 1 (Cdk1). In terms of apoptosis, SFN increased the expression of Bax and decreased the level of Bcl-2 and subsequently triggered release of cytochrome c from mitochondria and activation of caspase-3, but Fas level and caspase-8 activity remained unchanged at all time points. Furthermore, levels of nuclear factor-κB (NF-κB) p65 in both of the cytoplasm and the nucleus have also been markedly suppressed by SFN in a time-dependent manner. Taken together, these results suggest SFN inhibits cell growth via inducing G₂/M cell arrest and apoptosis in ACC-M cells. These events have been associated with SFN-regulated multiple targets involved in ACC-M cell proliferation. The present study provides an evidence for testing SFN efficacy in vivo and warranting future investigations to exam the clinical potential of SFN in ACC chemotherapy.     

Solar-excited graphene quantum dots for bacterial inactivation via generation of reactive oxygen species

Nanoscale photocatalysts have attracted abundant research attention in the solar-activated disinfection. In this work, we find that solar irradiation significantly improves the antimicrobial activity of graphene quantum dots (GQDs), accompanied by severe oxidative stress and membrane damage. By using electron spin resonance (ESR) technique, we confirm that different reactive oxygen species (ROS), including singlet oxygen (¹O₂), hydroxyl radical (?OH), and superoxide anion (O₂^??) were generated by GQDs upon irradiation with simulated sunlight. Additionally, these generated ROS will further facilitate lipid peroxidation of cell membrane and suppress bacterial antioxidant systems, enhancing the phototoxicity of GQDs. These findings will bring major advancements of GQDs in applications of solar-driven bacterial disinfection.     

Application of Biosynthesized Silver Nanoparticles Against a Cancer Promoter Cyanobacterium,Microcystis aeruginosa

Background: Nanotechnology opens new applications in many fields including medicine. Among all metallic nanoparticles, silver nanoparticles (silver NPS) have proved to be the most effective against a large variety of organisms including toxic cyanobacteria. Materials and Methods: Silver NPs were biosynthesized in vivo with different alga species namely, Spirulina platensis, Chlorella vulgaris and Scenedesmus obliquus following two scenarios. First: by suspending a thoroughly washed algae biomass in 1 mM aqueous AgNO3 solution. Second:by culturing them individually in culture media containing the same concentration of AgNO3. Silver NPs were characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM), energy dispersive analysis (EDX) and Fourier transform infra-red (FTIR) spectroscopy. The biosynthesized silver NPs were tested for cytotoxic activity against a cancer promoter cyanobacteruim Microcystis aeruginosa, considering effects on cell viability and chlorophyll content. Results: The surface plasmon band indicated the biosynthesis of silver NPs at ~400 nm. Transmission electron microscopy (TEM) revealed that the silver NPs had a mean average size below 100 nm. Energy-dispersive analysis X-ray (EDX) spectra confirmed the presence of silver element. FTIR spectralanalyses suggested that proteins and or polysaccharides may be responsible for the biosynthesis of silver NPs and (-COO-) of carboxylate ions is responsible for stabilizing them. The toxic potentialities of the biosynthesized silver NPs against the cancer promoter cyanobacterium, Microcystis aeruginosa showed high reduction in viable cells count and the total chlorophyll content. Conclusions: The potential activity of the biosynthesized silver NPs from the studied algae species against Microcystis aeruginosa cells is expected to be mainly mediated by therelease of silver ions (Ag+) from the particle surface and bioactive compounds as indicated by FTIR analysis.     

Cisplatin’s tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng

Purpose We previously observed that American ginseng berry and ginsenoside Re attenuated cisplatin-induced emesis in a rat model, suggesting that the herb may have a value in treating chemotherapy-induced nausea/vomiting. However, it is not clear whether consuming ginseng concurrently with chemotherapy affects the efficacy of chemotherapeutic agents. In this study, we explored if the ginseng extract and its constituents, ginsenosides Rb₁, Rb₃, and Re, alter tumoricidal activity of cisplatin in human cancer cells. Methods Tumoricidal effects of cisplatin, and/or American ginseng berry extract (AGBE) and ginsenosides Rb₁, Rb₃, and Re, on human breast carcinoma MCF-7 cells were measured as cell proliferation in vitro. Cell counts were performed in MCF-7 cells pretreated with test agents for 72 h. Results Cisplatin decreased MCF-7 cell proliferation significantly in a concentration-dependent manner. Compared to control group, cisplatin reduced the cell proliferations to 56.5±3.3% at 1 μg/ml, to 36.6±2.4% at 5 μg/ml, and to 26.9±2.4% at 15 μg/ml (P<0.01). AGBE also inhibited the cell proliferation significantly, although in a less extended manner. When the berry extract at 0.5 mg/ml was used with cisplatin at 1 μg/ml, a significant enhancement of cisplatin’s activity was observed (35.8±2.5%; P<0.05). We also observed that Rb₁ did not change cisplatin’s activity; Rb₃, at a higher concentration, increased cisplatin’s anti-proliferation activity (48.0±1.2%; P<0.05); Re increased cisplatin’s activity (Re 0.1 mg/ml, 48.0±2.8%; Re 0.3 mg/ml, 31.9±2.2%, P<0.01). Conclusion Our data suggest that AGBE and the tested ginsenosides do not attenuate cisplatin’s tumoricidal activity in MCF-7 cells, but in fact may actually enhance it. Additionally, the ginseng extract and ginsenoside Re by themselves exerted anti-proliferative activity against MCF-7 cells. The herb might potentially serve a complementary role with the chemotherapeutic agents in treating cancer, in addition to decreasing chemotherapy-induced nausea/vomiting.     

The polymorphism of EGFR 142285G > A exerts no risk effect on breast cancer

The association between the epidermal growth factor receptor (EGFR) 142285G?>?A polymorphism and the susceptibility to breast cancer is unclear. We conducted a meta-analysis of all published studies to estimate the association of EGFR 142285G?>?A polymorphism and breast cancer risk. Systematic computerized searching of the PubMed, Web of Science, and Wanfang databases was performed for relevant publications. Overall, there were three eligible case–control studies with 1,360 cases and 1,522 controls included into our study. The pooled ORs showed that the EGFR 142285G?>?A variant genotypes did not increase or decrease the risk of breast cancer under the following gene models: A vs. G, OR?=?1.07, 95 % CI 0.96–1.19, P _OR?=?0.240; AA vs. GG, OR?=?1.14, 95 % CI 0.91–1.42, P _OR?=?0.239; GA vs. GG, OR?=?0.99, 95 % CI 0.83–1.17, P _OR?=?0.892; GA?+?AA vs. GG, OR?=?1.03, 95 % CI 0.87–1.21, P _OR?=?0.727; AA vs. GG?+?GA, OR?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.096. The between-study heterogeneity was not significant among all studies. The current meta-analysis showed no evidence for significant association between EGFR 142285G?>?A polymorphism and breast cancer risk. Subsequent studies with large sample size are needed for further elucidation.     

Planning the breast boost: How accurately do surgical clips represent the CT seroma?

Background and purpose

To measure the distance between surgical clips and edge of CT-defined seroma in a coronal plane in women who have undergone wide local excision of breast cancer and to evaluate dosimetric coverage of CT-defined boost volumes by conventional clip-based electron fields.

Materials and methods

Planning CT images of 30 lumpectomy cavities from 30 patients were reviewed. All seroma cavities had at least 4 clips and Cavity Visualization Score ?3. Distances between clips and seroma edge (D_c-s) were measured at the radial margins for each patient. Clips-based electron fields were generated by including all the clips with 2 cm margin in the coronal plane and three-dimensional conformal radiotherapy plans (3D-CRT) were devised based on CT tumor beds (CT-TBs). The parameters of dose-volume histogram between the two boost treatment plans were analyzed.

Results

The mean seroma edge extended beyond the clips by 0.3-0.5 cm. In all 120 D_c-ss, 76.7% were ?0.5 cm, 8.3% were >1 cm and 15% were between 0.5 and 1 cm. Twenty patients (20/30) had D_c-smax (The maximal D_c-s of each patient) > 0.5 cm and 7 patients had D_c-smax > 1 cm. With the electron fields, only 46.7% (14/30) had D₉₀ (The minimal dose received by 90% of the planning target volume (PTV)) > 90% and geographical miss (any portion of the PTV receiving <50% of the prescribed dose) was found in 36.7% (11/30). D_c-smax > 0.5 cm was associated with D₉₀ < 90% (P < 0.001) and >1 cm was associated with geographic miss (P = 0.001).

Conclusions

Surgical clips are not always consistent with the edge of seroma. Electron boost field based on clips leads to insufficient dose coverage to the CT-TB. 3D-CRT planning should be considered to ameliorate the dose coverage to the tumor bed.     

Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes,the role of ROS-mediated signaling pathways

Radiotherapy plays an important role in treatment of cancers with low toxicity to the surrounding normal tissues. However, it still fails to eradicate hypoxic tumors due to the occurrence of radioresistance. Therefore, the search for new radiation sensitizers is of great significance. Platinum (Pt) complexes have been identified as potential radiation sensitizers to increase the sensitivity of cancer cells to radiotherapy. In the present study, we have synthesized four Pt complexes containing (2 – benzimidazole [4, 5-f] – [1, 10] phenanthroline) ligand and found that they could effectively enhance the X-ray-induced growth inhibition against A375 human melanoma cells through induction of G2/M cell cycle arrest. In contrast, they showed much lower cytotoxicity toward human normal cells. The complexes also dramatically inhibited the TrxR activity and caused intracellular ROS overproduction, due to the Auger electron effect of heavy metal element under X-ray radiation. Excessive ROS triggered DNA damage and activated downstream signaling pathways, including the phosphorylation of p53 and p38MAPK, and down-regulation of phosphorylated AKT and ERK, finally resulted in increase of radiosensitivity and inhibition of tumor reproduction. Taken together, our results suggest that the synthetic Pt complexes could be further developed as sensitizers of X-ray radiotherapy.     

Relationships of FOXE1 and ATM genetic polymorphisms with papillary thyroid carcinoma risk: a meta-analysis

We conducted the meta-analysis of all relevant case–control studies aiming to evaluate the relationships of common polymorphisms in forkhead box E1 (FOXE1) and ataxia telangiectasia mutated (ATM) genes to the risk of papillary thyroid carcinoma (PTC). A range of electronic databases were searched without language restrictions: Web of Science (1945?~?2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966?~?2013), EMBASE (1980?~?2013), CINAHL (1982?~?2013), and the Chinese Biomedical Database (CBM) (1982?~?2013). This meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Eight case–control studies with 2,085 PTC patients and 10,341 healthy controls were included. Fourteen common polymorphisms were evaluated, including rs3758249 A?>?G, rs907577 G?>?A, rs1867277 G?>?A, rs3021526 C?>?T, rs1443434 G?>?T, rs907580 G?>?A, rs965513 A?>?G, rs944289 C?>?T, and rs189037 G?>?A polymorphisms in the FOXE1 gene and rs373759 G?>?A, rs4988099 A?>?G, rs1801516 G?>?A, rs664677 T?>?C, and rs609429 G?>?C polymorphisms in the ATM gene. Our results demonstrated that the FOXE genetic polymorphisms might be closely related to an increased risk of developing PTC under five genetic models (all P?<?0.005), especially for rs3758249, rs907577, rs1867277, rs3021526, rs1443434, rs907580, rs704839, rs894673, and rs10119760 polymorphisms. Nevertheless, no positive associations were found between the ATM genetic polymorphisms and the development of PTC (all P?>?0.05). The current meta-analysis provided evidence that FOXE1 genetic polymorphisms may contribute to increased PTC risk, especially for rs3758249, rs907577, rs1867277, rs3021526, rs1443434, rs907580, rs704839, rs894673, and rs10119760 polymorphisms. However, the ATM genetic polymorphisms may not be important dominants of susceptibility to PTC.     

Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms

The immunomodulatory effects of physiological temperature change remain poorly understood and inter-relationships between changes in core temperature, stress hormones and cytokines during exertional hyperthermia are not well established. This experimental study was designed to examine how cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and IL-1ra (receptor antagonist)) and hormone (epinephrine (Epi), norepinephrine (NE), growth hormone (GH) and cortisol (CORT)) responses are modified when the exercise-induced rise in core temperature is attenuated or exacerbated by immersion in a water bath. Ten men ((mean?±?SD) age: 26.9?±?5.7 years; height 1.75?±?0.07?m; body mass 76.0?±?10.9?kg; O_2?peak: 48.0?±?12.4?mL?kg^?1?min^?1) completed two 40-min cycle ergometer exercise trials at 65%?O_2?peak while immersed to mid-chest. Rectal temperature (T_re) peaked at 39.1?±?0.03 and 37.5?±?0.13°C during the hot (39°C) and cold (18°C) conditions, respectively. Blood samples were collected before, during (20- and 40-min) and after (30- and 120-min) exercise. Increases in circulating NE (>350%), Epi (>500%), GH (>900%), IL-12 (>150%) and TNF-α?(>90%) were greatest after 40-min exercise in the heat. Substantial elevations of CORT (80%), IL-1ra (150%) and IL-6 (>400%) did not occur until after exercise was complete. Core temperature clamping decreased the rise in circulating stress hormone concentrations and abolished increases in plasma cytokine concentrations. These findings suggest that exercise-associated elevations of T_re mediate increases of circulating stress hormones, which subsequently contribute to induction of circulating cytokine release.     

Structure activity relationship of plumbagin in BRCA1 related cancer cells

It has been shown earlier that plumbagin, a naturally occurring naphthaquinone has specific anticancer activity in BRCA1 blocked ovarian cancer cells. Plumbagin can induce estrogen dependent cell signaling and apoptosis in BRCA1 blocked ovarian cancer cells. Being a reactive oxygen species (ROS) generator and apoptosis inducing agent, plumbagin has immense potential as a promising anticancer agent. In this study we analyzed whether there would be increased anticancer activity if the positions of the functional groups on plumbagin were altered and further to analyze the detailed molecular mechanism of action of the lead molecule. Methods like MTT assay, apoptosis analysis by flow cytometry, assessment of mitochondrial membrane potential‐Δψ_m, suppression subtractive hybridization, microarray, molecular docking and estrogen receptor–DNA binding activity by electrophoresis mobility shift assay (EMSA) were adopted for assessing the anticancer activity. Consequently we found that, plumbagin was the most potent anticancer agent when compared to structurally related compounds. The anti‐cancer activities were in the order plumbagin > 1,4‐naphthaquinone > juglone > lawsone > menadione. Molecular docking studies showed that plumbagin could be well docked in the receptor ligand complex of TRAIL–DR5 complexes to activate the extrinsic pathway of apoptosis. Since the antiproliferative activity of plumbagin could be reduced by inhibiting ERα, we speculated that plumbagin interferes with the binding of ERα to ERE and we confirmed this by EMSA. This study clearly indicates that plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells. © 2012 Wiley Periodicals, Inc.