RESUMEN
BACKGROUND: Rosmarinic acid (RA) has a wide range of beneficial effects on human health. On the other hand, RA has been reported to induce metal-mediated reactive oxygen species (ROS) generation and DNA damage. However, its mechanism remains unknown. In this study, to clarify the underlying mechanism, we analyzed metal-mediated DNA damage in isolated DNA treated with RA and its analog isorinic acid. RESULTS: RA plus Cu(II), but not Fe(III), significantly increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage, in calf thymus DNA. Furthermore, a comparison of the 8-oxodG formation induced by RA and its analog isorinic acid suggested that the catechol groups in RA could be associated with their abilities to form 8-oxodG. Interestingly, the 8-oxodG formation induced by RA and isorinic acid plus Cu(II) was markedly enhanced by the addition of NADH, an endogenous reductant. To elucidate the mechanism of RA plus Cu(II)-induced oxidative DNA damage, we examined DNA damage in 32P-labeled DNA treated with RA in the presence of Cu(II). RA plus Cu(II) caused DNA cleavage, which was enhanced by piperidine treatment, suggesting that RA causes not only DNA strand breakage but also base modification. RA plus Cu(II)-induced DNA damage was inhibited by catalase (H2O2 scavenger), bathocuproine (Cu(I) chelator), and methional (scavenger of a variety of ROS other than â¢OH) but not by typical â¢OH scavengers and SOD, indicating the involvement of H2O2, Cu(I), and ROS other than â¢OH. DNA cleavage site analysis showing RA-induced site-specific DNA damage (frequently at thymine and some cytosine residues) supports the involvement of ROS other than â¢OH, because â¢OH causes DNA cleavage without site specificity. Based on these results, Cu(I) and H2O2 generation with concomitant RA autoxidation could lead to the production of Cu(I)-hydroperoxide, which induces oxidative DNA damage. o-Quinone and o-semiquinone radicals are likely to be again reduced to RA by NADH, which dramatically increases oxidative DNA damage, particularly at low concentrations of RA. CONCLUSIONS: In this study, physiologically relevant concentrations of RA effectively induced oxidative DNA damage in isolated DNA through redox cycle reactions with copper and NADH.
RESUMEN
Inorganic metal halide solar cells made from perovskite stand out for having outstanding efficiency, cheap cost, and simple production processes and recently have generated attention as a potential rival in photovoltaic technology. Particularly, lead-free Ca3AsBr3 inorganic materials have a lot of potential in the renewable industry due to their excellent qualities, including thermal, electric, optoelectronic, and elastic features. In this work, we thoroughly analyzed the stress-driven structural, mechanical, electrical, and optical properties of Ca3AsBr3 utilizing first-principles theory. The unstressed planar Ca3AsBr3 compound's bandgap results in 1.63 eV, confirming a direct bandgap. The bandgap within this compound could have changed by applying hydrostatic stress; consequently, a semiconductor-to-metallic transition transpired at 50 GPa. Simulated X-ray diffraction further demonstrated that it maintained its initial cubic form, even after external disruption. Additionally, it has been shown that an increase in compressive stress causes a change of the absorption spectra and the dielectric function with a red shift of photon energy at the lower energy region. Because of the material's mechanical durability and increased degree of ductility, demonstrated by its stress-triggered mechanical characteristics, the Ca3AsBr3 material may be suitable for solar energy applications. The mechanical and optoelectronic properties of Ca3AsBr3, which are pressure sensitive, could potentially be advantageous for future applications in optical devices and photovoltaic cell architecture.
RESUMEN
Sucrose and high-fructose corn syrup comprise nearly equal amounts of glucose and fructose. With the use of high-fructose corn syrup in the food industry, consumption of fructose, which may be a tumor promoter, has increased dramatically. We examined fructose-induced oxidative DNA damage in the presence of Cu(II), with or without the addition of H2O2. With isolated DNA, fructose induced Cu(II)-mediated DNA damage, including formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), to a greater extent than did glucose, and H2O2 enhanced the damage. In cultured human cells, 8-oxodG formation increased significantly following treatment with fructose and the H2O2-generating enzyme glucose oxidase. Fructose may play an important role in oxidative DNA damage, suggesting a possible mechanism for involvement of fructose in carcinogenesis.
Asunto(s)
Desoxiguanosina , Peróxido de Hidrógeno , Humanos , 8-Hidroxi-2'-Desoxicoguanosina , Peróxido de Hidrógeno/toxicidad , Estrés Oxidativo , Daño del ADN , Glucosa , Cobre/farmacología , Oxidación-ReducciónRESUMEN
Conventional triboelectric nanogenerators (TENGs) face challenges pertaining to low output current density at low working frequencies and high internal impedance. While strategies, such as surface modification to enhance surface charge density, permittivity regulation of materials, and circuit management, have partially mitigated these issues. However, they have also resulted in increased complexity in the fabrication process. Therefore, there is an urgent demand for a universal and simplified approach to address these challenges. To fulfill this need, this work presents a free-standing electrode and fixed surface tiny electrode implemented triboelectric nanogenerator (FFI-TENG). It is fabricated by a straightforward yet effective method: introducing a tiny electrode onto the surface of the tribo-negative material. This approach yields substantial enhancements in performance, notably a more than tenfold increase in output current density, a reduction in effective working frequencies, and a decrease in matching resistance as compared to vertical contact-separation TENGs (CS-TENGs) or single-electrode TENGs (SE-TENGs). Simultaneously, a comprehensive examination and proposition regarding the operational mechanism of FFI-TENG, highlighting its extensive applicability are also offered. Significantly, FFI-TENG excels in mechanical energy harvesting even under ultra-low working frequencies (0.1 Hz), outperforming similar contact-separation models. This innovation positions it as a practical and efficient solution for the development of low-entropy energy harvesters.
RESUMEN
In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.
RESUMEN
Background/Aim: Recently, robotic surgery for rectal cancer has become a common minimally invasive surgery. In addition, the technology of augmented and mixed reality is applied in various living environments, including medicine. We successfully performed robotic surgery for rectal cancer with three-dimensional (3D) images as mixed reality (MR) using HoloLens2. Case Report: The patient was diagnosed with rectal cancer by colonoscopy and a positron-emission computed-tomography scan, and we performed robot-assisted anterior resection. The operator used HoloLens2 and performed the surgery while visualizing 3D images of pelvic anatomy with the location of the rectal cancer as hologram. The operation was performed completely and safely, and she was discharged 11 days after surgery with no postoperative complications. Conclusion: This case presents the usefulness of a MR system offering organ visualization as hologram during surgery.
RESUMEN
Myricetin (MYR), found in tea and berries, may have preventive effects on diseases, including Alzheimer's disease and cancer. However, MYR is also a mutagen, inducing DNA damage in the presence of metal ions. We have studied the molecular mechanisms of DNA damage by MYR in the presence of Cu(II) (MYR+Cu). Using 32P-5'-end-labeled DNA fragments, we analyzed site-specific DNA damage caused by MYR+Cu. MYR+Cu caused concentration-dependent DNA strand breaks and base alterations, leading to cleavage of DNA at thymine, cytosine, and guanine nucleotides. Formation of the oxidative DNA damage indicator, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in calf thymus DNA was increased by MYR+Cu. The production of 8-oxodG in MYR-treated HL-60 cells was significantly higher than in HP100 cells, which are more resistant to H2O2 than are HL-60 cells. Reactive oxygen species (ROS) scavengers were used to elucidate the mechanism of DNA damage. DNA damage was not inhibited by typical free hydroxyl radical (â¢OH) scavengers such as ethanol, mannitol, or sodium formate. However, methional, catalase, and bathocuproine inhibited DNA damage induced by MYR+Cu. These results suggest that H2O2, Cu(I), and ROS other than â¢OH are involved in MYR+Cu-induced DNA damage. We conclude that the Cu(I)/Cu(II) redox cycle and concomitant H2O2 production via autoxidation of MYR generate a complex of H2O2 and Cu(I), probably Cu(I)-hydroperoxide, which induces oxidative DNA damage.
RESUMEN
Neuroblastoma is a typical solid tumor common in childhood. The present study investigated the inhibitory effects of lactoferrin on the proliferation of IMR-32 neuroblastoma cells, including under X-ray irradiation. In controlled in vitro assays, it was found that lactoferrin inhibited cell proliferation, accompanied by cell membrane disruption. Furthermore, intracellular reactive oxygen species generation increased in IMR-32 cells treated with lactoferrin, causing membrane lipid peroxidation and the leakage of lactate dehydrogenase. The IC50 values for cell proliferation were ~2.0 nM for doxorubicin, 2.7 mM for dibutyryl-cAMP and 45.9 µM for lactoferrin. X-ray irradiation at 1 Gy decreased cell proliferation to ~30%, which was not restored by lactoferrin. In the Fenton reaction system with iron chloride, lactoferrin increased hydroxyl radical (OH·) formation via H2O2, as confirmed by electron spin resonance spectra. On the whole, the findings of the present study indicate that lactoferrin, found abundantly in milk, may help prevent or treat neuroblastoma in infants with modest efficacy, and does not exert a protective effect against X-rays.
RESUMEN
The structural, optical, electrical, thermodynamic, superconducting, and mechanical characteristics of LiGa2Ir full-Heusler alloys with the MnCu2Al configuration were comprehensively examined in this work using the first-principles computation approach premised upon density functional analysis. This theoretical approach is the first to investigate the influence of pressure on the mechanical and optical characteristics of LiGa2Ir. The structural and chemical bonding analysis shows that hydrostatic pressure caused a decrease in the lattice constant, volume, and bond length of each cell. According to the mechanical property calculations, the LiGa2Ir cubic Heusler alloy exhibits mechanical stability. It also has ductility and anisotropic behavior. This metallic substance shows no band gap throughout the applied pressure range. The physical characteristics of the LiGa2Ir full-Heusler alloy are analyzed in the operating pressure range of 0-10 GPa. The quasi-harmonic Debye model is employed to analyze thermodynamic properties. The Debye temperature (291.31 K at 0 Pa) increases with hydrostatic pressure. A newly invented structure attracted a lot of attention around the globe for its superior superconductivity (Tc â¼ 2.95 K). Optical functions have also been improved after applying stress to utilize it in optoelectronic/nanoelectric devices. The optical function analysis is supported strongly by the electronic properties. Due to these reasons, LiGa2Ir imposed an essential guiding principle for relevant future research and could be a credible candidate substance for industrial settings.
RESUMEN
Silicon quantum dot multilayer (Si-QDML) is a promising material for a light absorber of all silicon tandem solar cells due to tunable bandgap energy in a wide range depending on the silicon quantum dot (Si-QD) size, which is possible to overcome the Shockley-Queisser limit. Since solar cell performance is degenerated by carrier recombination through dangling bonds (DBs) in Si-QDML, hydrogen termination of DBs is crucial. Hydrogen plasma treatment (HPT) is one of the methods to introduce hydrogen into Si-QDML. However, HPT has a large number of process parameters. In this study, we employed Bayesian optimization (BO) for the efficient survey of HPT process parameters. Photosensitivity (PS) was adopted as the indicator to be maximized in BO. PS (σp/σd) was calculated as the ratio of photoconductivity (σp) and dark conductivity (σd) of Si-QDML, which allowed the evaluation of important electrical characteristics in solar cells easily without fabricating process-intensive devices. 40-period layers for Si-QDML were prepared by plasma-enhanced chemical vapor deposition method and post-annealing onto quartz substrates. Ten samples were prepared by HPT under random conditions as initial data for BO. By repeating calculations and experiments, the PS was successfully improved from 22.7 to 347.2 with a small number of experiments. In addition, Si-QD solar cells were fabricated with optimized HPT process parameters; open-circuit voltage (VOC) and fill factor (FF) values of 689 mV and 0.67, respectively, were achieved. These values are the highest for this type of device, which were achieved through an unprecedented attempt to combine HPT and BO. These results prove that BO is effective in accelerating the optimization of practical process parameters in a multidimensional parameter space, even for novel indicators such as PS.
RESUMEN
Vehicle-integrated photovoltaics (VIPV) are gaining attention to realize a decarbonized society in the future, and the specifications for solar cells used in VIPV are predicated on a low cost, high efficiency, and the ability to be applied to curved surfaces. One way to meet these requirements is to make the silicon substrate thinner. However, thinner substrates result in lower near-infrared light absorption and lower efficiency. To increase light absorption, light trapping structures (LTSs) can be implemented. However, conventional alkali etched pyramid textures are not specialized for near-infrared light and are insufficient to improve near-infrared light absorption. Therefore, in this study, as an alternative to alkaline etching, we employed a nanoimprinting method that can easily fabricate submicron-sized LTSs on solar cells over a large area. In addition, as a master mold fabrication method with submicron-sized patterns, silica colloidal lithography was adopted. As a result, by controlling silica coverage, diameter of silica particles (D), and etching time (tet), the density, height, and size of LTSs could be controlled. At the silica coverage of 40%, D = 800 nm, and tet = 5 min, the reduction of reflectance below 65% at 1100 nm and the theoretical short-circuit current gain of 1.55 mA/cm2 was achieved.
RESUMEN
PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.
Asunto(s)
Aneurisma de la Aorta Abdominal , Aneurisma de la Aorta Torácica , Humanos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Abdominal/cirugía , Estudios Prospectivos , Pérdida de Líquido Cefalorraquídeo , Drenaje , Líquido Cefalorraquídeo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases, including COVID-19.
Asunto(s)
Antivirales , COVID-19 , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , SARS-CoV-2 , Peróxido de Hidrógeno , Hidroxilaminas/farmacología , Estrés Oxidativo , Daño del ADNRESUMEN
BACKGROUND/AIM: Fibroblast activation protein (FAP) is known to have prognostic significance in colorectal cancer (CRC). However, FAP and tertiary lymphoid structures (TLSs) have not been associated with each other in predicting the prognosis of CRC recurrence. PATIENTS AND METHODS: FAP expression was evaluated by real-time reverse transcription polymerase chain reaction in 195 CRC patients at Osaka International Cancer Institute (first data set). Immunohistochemistry (IHC) was then performed to stain FAP at the invasive margin (IM) and in the central tumour (CT) in 159 CRC patients at Osaka University Hospital (second data set). Consecutive slides were used to evaluate the presence of TLSs in 159 CRC patients from Osaka University Hospital. RESULTS: The high FAP mRNA expression group (n=82) was associated with poor recurrence-free survival (RFS) compared with the low FAP expression group (n=83) (p=0.004). In the second data set, patients with high FAP expression in CT and TLS absence (n=49) showed significantly poorer RFS compared with those with low expression of FAP in CT and presence of TLSs (n=101) (p=0.002). CONCLUSION: FAP in the CT combined with TLSs was shown to have significant prognostic value in predicting CRC recurrence after curative resection.
Asunto(s)
Neoplasias Colorrectales , Estructuras Linfoides Terciarias , Humanos , Colorantes , Hospitales Universitarios , Neoplasias Colorrectales/genética , FibroblastosRESUMEN
The submucosal invasion depth predicts prognosis in early colorectal cancer. Although colorectal cancer with shallow submucosal invasion can be treated via endoscopic resection, colorectal cancer with deep submucosal invasion requires surgical colectomy. However, accurately diagnosing the depth of submucosal invasion via endoscopy is difficult. We developed a tool to diagnose the depth of submucosal invasion in early colorectal cancer using artificial intelligence. We reviewed data from 196 patients who had undergone a preoperative colonoscopy at the Osaka University Hospital and Osaka International Cancer Institute between 2011 and 2018 and were diagnosed pathologically as having shallow submucosal invasion or deep submucosal invasion colorectal cancer. A convolutional neural network for predicting invasion depth was constructed using 706 images from 91 patients between 2011 and 2015 as the training dataset. The diagnostic accuracy of the constructed convolutional neural network was evaluated using 394 images from 49 patients between 2016 and 2017 as the validation dataset. We also prospectively tested the tool from 56 patients in 2018 with suspected early-stage colorectal cancer. The sensitivity, specificity, accuracy, and area under the curve of the convolutional neural network for diagnosing deep submucosal invasion colorectal cancer were 87.2% (258/296), 35.7% (35/98), 74.4% (293/394), and 0.758, respectively. The positive predictive value was 84.4% (356/422) and the sensitivity was 75.7% (356/470) in the test set. The diagnostic accuracy of the constructed convolutional neural network seemed to be as high as that of a skilled endoscopist. Thus, endoscopic image recognition by deep learning may be able to predict the submucosal invasion depth in early-stage colorectal cancer in clinical practice.
RESUMEN
BACKGROUND/AIM: Previous studies have shown that postoperative adjuvant chemotherapy improves overall survival in patients with stage III colorectal cancer (CRC). However, adjuvant chemotherapy may not be necessary for some patients. This study aimed to develop a new nutritional-inflammation score, which would be useful in identifying a favorable prognosis group among stage III CRC patients. PATIENTS AND METHODS: This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and a new prognostic model was developed. RESULTS: Multivariate analyses in TS revealed that lymph node metastasis (N2) (p=0.002), low albumin (p=0.017), high monocyte counts (p=0.008), and low platelet counts (p=0.018) were independent risk factors for disease free survival (DFS). The Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dl albumin level, >450 monocyte counts, and <1.65×105 platelet counts. Using KPS, DFS and overall survival (OS) were validated in VS. The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. CONCLUSION: KPS serves as a new model for the prognosis of patients with stage III CRC.
Asunto(s)
Neoplasias Colorrectales , Albúminas/uso terapéutico , Neoplasias Colorrectales/patología , Humanos , Inflamación/patología , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
We demonstrate single-frequency stimulated Brillouin lasing in short fiber Fabry-Perot resonators. A sub-milliwatt threshold for lasing is observed in resonators with high quality factors of â¼1.5 × 108 and effective resonator lengths as short as â¼5 mm. The strong dispersion of fiber Bragg gratings results in unequal frequency separations for neighboring pairs of longitudinal modes with separation differences larger than the Brillouin gain bandwidth, thereby avoiding cascaded lasing. Our achievement will enable compact, robust, efficient narrow-linewidth light sources.
RESUMEN
BACKGROUND/AIM: There are few reports on the clinical significance of the geriatric nutritional risk index (GNRI) in patients with locally advanced rectal cancer who undergo preoperative chemotherapy (NAC, neoadjuvant chemotherapy) followed by radical resection; this study examined the relationship between preoperative GNRI, postoperative complications, and prognosis in these patients. PATIENTS AND METHODS: Fifty-seven patients with rectal cancer who underwent radical resection after NAC at Osaka University Hospital between November 2011 and May 2018 were included. The GNRI was calculated as follows: GNRI= [1.489×serum albumin level (g/l)]+[41.7×present/ideal body weight (kg)]. Patients were classified into high (GNRI ≥96.74; n=36) and low GNRI (GNRI <96.74; n=21) groups, based on the results of the receiver operating characteristic curve analysis. RESULTS: The Kaplan-Meier analysis showed that the low GNRI group had a significantly poorer cancer-specific survival (CSS) and a poorer overall survival tendency than the high GNRI group. In the univariate analysis, venous invasion, lymphatic vessel invasion, and low GNRI were significantly correlated with CSS; depth of tumor invasion, lymph node metastasis, and lymphatic vessel invasion were significantly correlated with disease-free survival (DFS). In the multivariate analysis, there were no significantly poor prognostic factors for CSS and DFS. CONCLUSION: Preoperative GNRI may be a useful predictor for recurrence and poor prognosis in elderly patients with rectal cancer who undergo radical resection after NAC. Further studies and accumulation of cases should investigate the relationship between preoperative GNRI and prognosis after NAC in elderly patients.
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Anciano , Humanos , Estado Nutricional , Pronóstico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Purpurin (1,2,4-trihydroxy-9,10-anthraquinone), a natural red anthraquinone pigment, has historically been used as a textile dye. However, purpurin induced urinary bladder tumors in rats, and displayed a mutagenic activity in assay using bacteria and mammalian cells. Many carcinogenic dyes are known to induce bladder cancers via DNA adduct formation, but carcinogenic mechanisms of purpurin remain unknown. In this study, to clarify the mechanism underlying carcinogenicity of purpurin, copper-mediated DNA damage induced by purpurin was examined using 32P-labeled DNA fragments of human genes relevant to cancer. Furthermore, we also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in calf thymus DNA. RESULTS: Purpurin plus Cu(II) cleaved 32P-labeled DNA fragments only under piperidine treatment, indicating that purpurin caused base modification, but not breakage of the DNA backbone. In the absence of Cu(II), purpurin did not induce DNA cleavage even with piperidine treatment. Purpurin plus Cu(II) caused piperidine-labile sites predominantly at G and some T residues. Bathocuproine, a Cu(I) chelator, completely prevented the occurrence of piperidine-labile sites, indicating a critical role of Cu(I) in piperidine-labile sites induced by purpurin plus Cu(II). On the other hand, methional, a scavenger of a variety of reactive oxygen species (ROS) and catalase showed limited inhibitory effects on the induction of piperidine-labile sites, suggesting that ROS could not be major mediators of the purpurin-induced DNA damage. Considering reported DNA adduct formation by quinone metabolites of several carcinogenic agents, quinone form of purpurin, which is possibly generated via purpurin autoxidation accompanied by Cu(I)/Cu(II) redox cycle, might lead to DNA adducts and piperidine-labile sites. In addition, we measured contents of 8-oxodG. Purpurin moderately but significantly increased 8-oxodG in calf thymus DNA in the presence of Cu(II). The 8-oxodG formation was inhibited by catalase, methional and bathocuproine, suggesting that Cu(I)-hydroperoxide, which was generated via Cu(I) and H2O2, caused oxidative DNA base damage. CONCLUSIONS: We demonstrated that purpurin induces DNA base damage possibly mediated by Cu(I)/Cu(II) redox cycle both with and without ROS generation, which are likely to play an important role in its carcinogenicity.
RESUMEN
We investigate photonic transport through fiber optical cavities under tunable fast modulation, which is induced by modulating atom-cavity coupling in a cavity quantum electrodynamics (CQED) system. The modulation bandwidth exceeds the timescales of all other system processes, such as cavity decay and atom-cavity coupling, and allows control of the dynamics of photonic transport through the cavity array. The transmission as a function of the modulation frequency clearly shows enhancement peaks in single cavity and two coupled-cavity cases. In particular, in the coupled-cavity case, the position of the enhancement peak is shifted due to the delocalized cavity field in the coupled system.