Pulmonary Foreign Body Granulomatosis after Cosmetic Injection.

INTRODUCTION: We occasionally encounter irregular marginated masses discovered incidentally in young individuals. In most cases, further investigations are conducted to assess the presence of a primary malignancy, as these masses often raise suspicions of malignancy. However, rare exceptional cases leave us perplexed. Granulomas arising from common lung infections and those induced by foreign substances can often pose challenge in distinguishing them from lung cancer. Therefore, we aimed to present a case of multiple pulmonary granulomatosis following cosmetic procedure. CASE PRESENTATION: A 55-year-old woman visited the hospital after an incidental discovery of an abnormal chest radiograph during a routine health check-up. Subsequent computed tomography (CT) scans showed worrisome lung nodules, leading to biopsies and positron emission tomography CT scans. Histological examination of the biopsied specimens revealed a chronic inflammatory reaction surrounded by multinucleated foreign body giant cells. Upon sharing the biopsy results with the patient and conducting additional history-taking, she had undergone various cosmetic procedures (botox injection, dermal filler treatments, and thread lifts) around the face and neck, approximately 5-6 months ago. It was hypothesized that these cosmetic materials might have led to the observed pulmonary granulomatosis. After 3 months of conservative care, a follow-up CT showed no change in the lesions. CONCLUSION: We present this case to underscore the importance of considering pulmonary foreign body granulomatosis as a potential differential diagnosis, especially when it closely resembles lung cancer, particularly following cosmetic injections.

Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease.

OBJECTIVE: To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. MATERIALS AND METHODS: This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1-7 according to acquisition conditions. CT images in groups 2-7 were converted into the target CT style (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. RESULTS: Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2-7 improved after CT conversion (original vs. converted: 0.63 vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists' scores were significantly higher (P < 0.001) and less variable on converted CT. CONCLUSION: CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

Comparison of Corneal Epithelial Wound Healing between Topical RCI001, Solcoseryl, and Polydeoxyribonucleotide in the Murine Ocular Alkali Burn Model.

PURPOSE: To compare the corneal epithelial wound healing effects of RCI001, Solcoseryl, and polydeoxyribonucleotide (PDRN) in a rat alkali burn model. METHODS: In 40 male Sprague-Dawley rats, we induced alkali burn using filter paper soaked in 0.2N sodium hydroxide. The rats were then treated with topical 0.5% RCI001, 1.0% RCI001, Solcoseryl, or PDRN twice a day for 2 weeks. Corneal epithelial integrity and epithelial healing rate were measured at day 0, 3, 5, 7, 10, and 14. Histologic and immunohistochemistry findings were also assessed. RESULTS: Both the 0.5% and 1.0% RCI001 groups showed significantly more epithelial healing compared to the control group at day 5, 7, 10, and 14 (each p < 0.05). No statistical difference was found between the 0.5% and 1.0% RCI001 groups. Neither the Solcoseryl nor the PDRN groups showed a significant difference from the control. RCI001 treatment resulted in significantly reduced stromal edema, and a trend towards less inflammatory cell infiltration. CONCLUSIONS: Topical application of RCI001 showed enhanced corneal epithelial wound healing in the murine corneal alkali burn model, presumably by suppressing inflammation. Meanwhile, Solcoseryl and PDRN did not show sufficient therapeutic effects compared to RCI001.

Exogenous 8-Hydroxydeoxyguanosine Attenuates PM2.5-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation.

Particulate matter 2.5 (PM2.5) induces lung injury by increasing the generation of reactive oxygen species (ROS) and inflammation. ROS aggravates NLRP3 inflammasome activation, which activates caspase-1, IL-1ß, and IL-18 and induces pyroptosis; these factors propagate inflammation. In contrast, treatment with exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases RAC1 activity and eventually decreases dinucleotide phosphate oxidase (NOX) and ROS generation. To establish modalities that would mitigate PM2.5-induced lung injury, we evaluated whether 8-OHdG decreased PM2.5-induced ROS generation and NLRP3 inflammasome activation in BEAS-2B cells. CCK-8 and lactate dehydrogenase assays were used to determine the treatment concentration. Fluorescence intensity, Western blotting, enzyme-linked immunosorbent assay, and immunoblotting assays were also performed. Treatment with 80 µg/mL PM2.5 increased ROS generation, RAC1 activity, NOX1 expression, NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activity, and IL-1ß and IL-18 levels in cells; treatment with 10 µg/mL 8-OHdG significantly attenuated these effects. Furthermore, similar results, such as reduced expression of NOX1, NLRP3, ASC, and caspase-1, were observed in PM2.5-treated BEAS-2B cells when treated with an RAC1 inhibitor. These results show that 8-OHdG mitigates ROS generation and NLRP3 inflammation by inhibiting RAC1 activity and NOX1 expression in respiratory cells exposed to PM2.5.

Comparison of Coronary Computed Tomography Angiography Image Quality With High-concentration and Low-concentration Contrast Agents: The Randomized CONCENTRATE Trial.

PURPOSE: To confirm that the image quality of coronary computed tomography (CT) angiography with a low tube voltage (80 to 100 kVp), iterative reconstruction, and low-concentration contrast agents (iodixanol 270 to 320 mgI/mL) was not inferior to that with conventional high tube voltage (120 kVp) and high-concentration contrast agent (iopamidol 370 mgI/mL). MATERIALS AND METHODS: This prospective, multicenter, noninferiority, randomized trial enrolled a total of 318 patients from 8 clinical sites. All patients were randomly assigned 1: 1: 1 for each contrast medium of 270, 320, and 370 mgI/mL. CT scans were taken with a standard protocol in the high-concentration group (370 mgI/mL) and with 20 kVp lower protocol in the low-concentration group (270 or 320 mgI/mL). Image quality and radiation dose were compared between the groups. Image quality was evaluated with a score of 1 to 4 as subject image quality. RESULTS: The mean HU, signal-to-noise ratio, and contrast-to-noise ratio of the 3 groups were significantly different (all P<0.0001). The signal-to-noise ratio and contrast-to-noise ratio of the low-concentration groups were significantly lower than those of the high-concentration group (P<0.05). However, the image quality scores were not significantly different among the 3 groups (P=0.745). The dose length product and effective dose of the high-concentration group were significantly higher than those of the low-concentration group (P<0.0001 and 0.003, respectively). CONCLUSIONS: The CT protocol with iterative reconstruction and lower tube voltage for low-concentration contrast agents significantly reduced the effective radiation dose (mean: 3.7±2.7 to 4.1±3.1 mSv) while keeping the subjective image quality as good as the standard protocol (mean: 5.7±3.4 mSv).

Exogenous 8-hydroxydeoxyguanosine attenuates doxorubicin-induced cardiotoxicity by decreasing pyroptosis in H9c2 cardiomyocytes.

Doxorubicin (DOX), which is widely used in cancer treatment, can induce cardiomyopathy. One of the main mechanisms whereby DOX induces cardiotoxicity involves pyroptosis through the NLR family pyrin domain containing 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Increased NAPDH oxidase (NOX) and oxidative stress trigger pyroptosis. Exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases reactive oxygen species (ROS) production by inactivating NOX. Here, we examined whether 8-OHdG treatment can attenuate DOX-induced pyroptosis in H9c2 cardiomyocytes. Exposure to DOX increased the peroxidative glutathione redox status and NOX1/2/4, toll-like receptor (TLR)2/4, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while an additional 8-OHdG treatment attenuated these effects. Furthermore, DOX induced higher expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a c-terminal caspase recruitment domain (ASC), and pro-caspase-1. Moreover, it increased caspase-1 activity, a marker of pyroptosis, and interleukin (IL)-1ß expression. All these effects were attenuated by 8-OHdG treatment. In addition, the expression of the cardiotoxicity markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased by DOX, whereas the increase of ANP and BNP induced by DOX treatment was reversed by 8-OHdG. In conclusion, exogenous 8-OHdG attenuated DOX-induced pyroptosis by decreasing the expression of NOX1/2/3, TLR2/4, and NF-κB. Thus, 8-OHdG may attenuate DOX-induced cardiotoxicity through the inhibition of pyroptosis.

Value of shear wave elastography during second-look breast ultrasonography for suspicious lesions on magnetic resonance imaging.

PURPOSE: This study aimed to determine whether the addition of shear wave elastography (SWE) helps to improve diagnostic performance of second-look ultrasonography (SLUS) for suspicious lesions on magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed 76 breast lesions in 62 patients who underwent SLUS and SWE for suspicious lesions on MRI from August 2017 to November 2019. The six-point color scale (Ecol) and four-type color pattern (Epattern) were used for qualitative evaluation, and the mean (Emean) and maximum elasticity (Emax) and standard deviation of elasticity (ESD) were recorded as quantitative parameters. Clinical and imaging findings between benign and malignant lesions were compared, and the diagnostic performance was assessed using receiver-operating characteristic (ROC) analysis. RESULTS: The biopsies revealed 52 benign and 24 malignant lesions. Of all SWE parameters, only ESD was significantly higher in malignant lesions than in benign lesions (p = 0.012). The sensitivity of B-mode US was 100%, but the specificity was low (19.2%). Using SWE parameters to classify lesions improved specificity at the expense of sensitivity. When lesions assigned to Breast Imaging Reporting and Data System (BI-RADS) category 3 or 4a were reclassified considering each SWE parameter, the area under the ROC curve (AUC) and sensitivity increased. The AUC of the US BI-RADS category adjusted by ESD was higher than that of B-mode US BI-RADS (0.770 vs. 0.746). CONCLUSION: SWE parameters, and especially ESD, may play a complimentary role in improving the specificity of SLUS. However, the decision to omit biopsies for suspicious lesions with soft features should be made with caution.

Investigating the Anti-Inflammatory Effects of RCI001 for Treating Ocular Surface Diseases: Insight Into the Mechanism of Action.

The ocular surface is continuously exposed to various environmental factors, and innate and adaptive immunity play crucial roles in ocular surface diseases (OSDs). Previously, we have reported that the topical application of RCI001 affords excellent anti-inflammatory and antioxidant effects in dry eye disease and ocular chemical burn models. In this study, we examined the inhibitory effects of RCI001 on the Rac1 and NLRP3 inflammasomes in vitro and in vivo. Following RCI001 application to RAW264.7 and Swiss 3T3 cells, we measured Rac1 activity using a glutathione-S-transferase (GST) pull-down assay and G-protein activation assay kit. In addition, we quantified the expression of inflammatory cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells using ELISA and real-time PCR. In the mouse ocular alkali burn model, RCI001 was administered via eye drops (10 mg/mL, twice daily) for 5 days, and 1% prednisolone acetate (PDE) ophthalmic suspension was used as a positive control. Corneal epithelial integrity (on days 0-5) and histological examinations were performed, and transcript and protein levels of Rac1, NLRP3, caspase-1, and IL-1ß were quantified using real-time PCR and western blotting in corneal tissues collected on days 3 and 5. We observed that RCI001 dose-dependently inhibited Rac1 activity and various inflammatory cytokines in LPS-stimulated murine macrophages. Furthermore, RCI001 restored corneal epithelial integrity more rapidly than corticosteroid treatment in chemically injured corneas. Compared to the saline group, activation of Rac1 and the NLRP3 inflammasome/IL-1ß axis was suppressed in the RCI001 group, especially during the early phase of the ocular alkali burn model. Topical RCI001 suppressed the expression of activated Rac1 and inflammatory cytokines in vitro and rapidly restored the injured cornea by inhibiting activation of Rac1 and the NLRP inflammasome/IL-1ß axis in vivo. Accordingly, RCI001 could be a promising therapeutic agent for treating OSDs.

YES-10 Improves Stress, Tension, and Fatigue by Reducing Cortisol and IL-6 Levels.

The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.

Multidetector CT findings of primary pleural angiosarcoma : a systematic review, an additional cases report.

BACKGROUND: To demonstrate and analyze the relatively common imaging findings in this rare primary pleural angiosarcoma (PPA). CASE PRESENTATION: Three cases of PPA, proven by video-assisted thoracic surgery biopsies are retrospectively reviewed. Patients were all male. Age ranges from 65 to 75 years old age (mean; 69). Major chief complaints were dyspnea and chest pain. One has a history of colon cancer, the other has a tuberculosis history and the other has no known history. Multidetector chest CT and PET CT were all done. Immunohistochemical studies were performed including CD31, CD34, or factor VIII-related antigen, vimentin, and cytokeratin. We also review the literatures on recently published PPA. All masses were from 1 to 10 cm. All three patients had multiple pleural based masses, which were ovoid in shape with relatively sharp margin in unilateral hemithorax. Multiple small circumscribed pleural masses are limited in the pleural space in two patients, whereas two, huge lobulated masses about up to 10 cm were present with pleural and extrapleural involvement in one patient. In two patients with pleural mass only, multiple pleural masses were only seen in parietal pleura in one patient and were in both visceral and parietal pleura in one patient. Pleural effusion were found in one side in one patient and in both sides in one patient. One angiosarcoma was arised from chronic tuberculotic pleurisy sequelae. All pleural masses are heterogenous with irregular internal low densities in all patients. Hematogenous metastases were found in liver, vertebra, rib in one patient, and were in lungs with mediastinal lymph node metastases in the other patient. Three patients survived for longer than 3months after diagnosis, but continued to deteriorate rapidly. Two patients underwent chemotherapy after surgical excision, and the other one with multiple metastases treated chemotherapy after CT-guided biopsy, but eventually all died. As a result of comparative analysis of a total of 13 patients' images including 10 cases previously published, there was pleural effusion in all except 2 cases. CONCLUSIONS: PPA were all necrotic without any vascularized enhancing nature, and manifested as unilateral circumscribed or localized pleural-based masses.

Comparison of therapeutic effects between topical 8-oxo-2'-deoxyguanosine and corticosteroid in ocular alkali burn model.

We compared the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.

Exogenous 8-hydroxydeoxyguanosine ameliorates liver fibrosis through the inhibition of Rac1-NADPH oxidase signaling.

BACKGROUND AND AIM: Exogenous 8-hydroxydeoxyguanosine (8-OHdG) was suggested as an inhibitor of Rac1 and NADPH oxidase (NOX). The aim of this study was to evaluate the effects of the exogenous 8-OHdG on hepatic fibrogenesis in vitro and in vivo model of liver fibrosis. METHODS: Adult Sprague-Dawley rats were allocated to sham-operated rats (n = 7), rats that underwent bile duct ligation (BDL) (n = 6), and BDL rats treated with 8-OHdG (60 mg/kg/day by gavage, n = 6). All rats were sacrificed on day 21. Double immunofluorescence staining between either NOX1 or NOX2 and α-smooth muscle actin (SMA) in liver was performed. Hepatic fibrotic contents were assessed by hydroxyproline assay and quantified by Sirius red staining. In vitro, hepatic stellate cell (HSC) line LX-2 and HHSteC cells were stimulated by angiotensin II (10 µM). The reactive oxygen species (ROS) production was measured by confocal microscopy. The expressions of NOX1, NOX2, α-SMA, transforming growth factor (TGF)-ß1, and collagen Iα were analyzed by quantitative real-time polymerase chain reaction or immunoblotting. RESULTS: The 8-OHdG treatment in BDL rats reduced the NOX1 and NOX2 protein expression, which overlapped with α-SMA compared with BDL rats. The 8-OHdG treatment in BDL rats significantly decreased the mRNA expression of NOX1, NOX2, α-SMA, TGF-ß1, and collagen Iα, and fibrotic contents. Increases of ROS production, Rac1 activation, NOX1, NOX2, and fibronectin expression induced by angiotensin II in HSCs were attenuated by 8-OHdG. CONCLUSIONS: Rac1 activation and NOX-derived ROS are implicated to liver fibrosis. The 8-OHdG ameliorates liver fibrosis through the inhibition of Rac1 activation and NOX-derived ROS.

Comparing attenuations of malignant and benign solitary pulmonary nodule using semi-automated region of interest selection on contrast-enhanced CT.

BACKGROUND: The purpose of this study was to determine whether semi-automated region of interest (ROI) measurement of CT attenuations of solitary pulmonary nodule (SPN) is an accurate approach in differentiating malignant from benign SPN. METHODS: Ninety cases of pathologically proven SPN were retrospectively reviewed. CT attenuations of SPN before and after contrast injection were measured using semi-automated ROI selection method. Attenuations within a range of -100 to 200 Hounsfield units (HU) as soft tissue density range were set. The ROI included the entire SPN regardless of its internal soft tissue contents after automatic elimination of airs, calcific, or bony densities. RESULTS: There were 42 (46.7%) malignant SPN and 48 (53.3%) benign SPN, which were grouped into A (18 tuberculoma, 13 fungus), B (5 focal organizing pneumonia, 5 abscess), and C (7 other benign tumors). The malignant SPN showed significantly higher mean attenuations of enhancement and net-enhancement than all benign SPN (P<0.001). Using the area under the receiver operating characteristic curve (AUC), the cut-off net-enhancement of 15 HU gave 83% sensitivity, 65% specificity and 73% accuracy for predicting malignancy. Malignant SPN (mean 67.9 HU) had significantly higher enhancement than group A (mean 52.6 HU, P<0.001, 95% CI: 8.73, 21.81) and group B (mean 57.0 HU, P=0.025, 95% CI: -1.43, 20.34) while group C showed no significant difference (mean 68.1 HU, P=0.97). Net enhancements were higher in group B (mean 18.8 HU) than in group A (mean 8.8 HU) (P<0.001, 95% CI: 11.8, 23.18). CONCLUSIONS: The semi-automated ROI measurement of SPN's attenuations on CT is an accurate approach in distinguishing indeterminate SPN.

Aggressive mycobacterium abscessus on repeated exogenous lipoid pneumonia in the right middle lobe.

A 65-year-old woman with no underlying disease had been repeated the development and improvement of lipoid pneumonia in the Rt. lower lobe. On a continuous follow up scan, this lesion showed a very aggressive tendency so that the CT-guided lung biopsy was performed to exclude lung cancer. However, as there was no consistent clinical course with the result, she performed the video-assisted thoracic surgery (VATS), wedge resection of Rt. lower lobe. Finally, nontuberculous mycobacterium (NTM) infection was confirmed, not lung cancer, and improved by proper treatment. We report this case for the following reasons: unlike previously reported cases, NTM infection occurred in an unusual situation and uncommon imaging findings similar to lung cancer confused the early diagnosis.

Inhibitory Effects of Roseoside and Icariside E4 Isolated from a Natural Product Mixture (No-ap) on the Expression of Angiotensin II Receptor 1 and Oxidative Stress in Angiotensin II-Stimulated H9C2 Cells.

Hypertension is a major risk factor for the development of cardiovascular diseases. This study aimed to elucidate whether the natural product mixture No-ap (NA) containing Pine densiflora, Annona muricate, and Monordica charantia, or its single components have inhibitory effects on hypertension-related molecules in Angiotensin II (Ang II)-stimulated H9C2 cells. Individual functional components were isolated and purified from NA using various columns and solvents, and then their structures were analyzed using ESI⁻MS, ¹H-NMR, and 13H-NMR spectra. H9C2 cells were stimulated with 300 nM Ang II for 7 h. NA, telmisartan, ginsenoside, roseoside (Roseo), icariside E4 (IE4), or a combination of two components (Roseo and IE4) were administered to the cells 1 h before Ang II stimulation. The expression and activity of hypertension-related molecules or oxidative molecules were determined using RT-PCR, western blot, and ELISA. Ang II stimulation increased the expression of Ang II receptor 1 (AT1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), tumor growth factor-ß (TGF-ß) mRNA, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and the levels of hydrogen peroxide (H2O2) and superoxide anion (•O2-) and reduced anti-oxidant enzyme activity. NA significantly improved the expression or activities of all hypertension-related molecules altered in Ang II-stimulated cells. Roseo or IE4 pretreatment either decreased or increased the expression or activities of all hypertension-related molecules similar to NA, but to a lesser extent. The pretreatment with a combination of Roseo and IE4 (1:1) either decreased or increased the expression of all hypertension-related molecules, compared to each single component, revealing a synergistic action of the two compounds. Thus, the combination of single components could exert promising anti-hypertensive effects similar to NA, which should be examined in future animal and clinical studies.

Therapeutic Effects of Topical 8-Oxo-2'-deoxyguanosine on Ethanol-Induced Ocular Chemical Injury Models.

PURPOSE: To evaluate the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) on experimental ocular chemical injury models. METHODS: We created ocular chemical injury models with 8-week-old BALB/c mice (n = 70) by applying 100% ethanol; the mice were then treated with 8-oxo-dG eye drops 10 and 5 mg/mL and phosphate-buffered saline (PBS) twice daily. After 7 days, clinical findings such as corneal integrity, clarity, and neovascularization were assessed. Histology, immunohistochemistry findings, and inflammatory cytokine levels using real-time polymerase chain reactions in the corneas of the mice were also analyzed. RESULTS: Topical application of 8-oxo-dG eye drops resulted in a significant improvement of epithelial defects and clarity, dose dependently (each P < 0.001). Inflammatory cell infiltration and corneal stromal edema were also decreased in the 8-oxo-dG-treated mice compared with PBS-treated controls, based on hematoxylin and eosin staining. The expressions of F4/80 and neutrophil elastase-positive inflammatory cells and IL-1 and TNF-α cytokine levels were significantly reduced in the 8-oxo-dG group compared with the PBS group (each P < 0.01). CONCLUSIONS: Topical 8-oxo-dG application showed an excellent therapeutic effect in ocular chemical injury models by suppressing inflammation.

Computed tomographic thoracic morphologic indices in normal subjects and patients with chronic obstructive pulmonary disease: Comparison with spiral CT densitometry and pulmonary function tests.

OBJECTIVES: To determine what computed tomographic (CT) dimensions can predict obstructive lung disease on routine chest CT scans by comparing morphological and densitometric CT findings with pulmonary function test (PFT) in normal subjects and patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Consecutive patients (n = 646; 260 females and 386 males; mean age 54.9 years, ranged 20-90 years) who received chest CT scans with densitometry during a 3-month period were retrospectively analyzed in single center. PFT was undertaken in 235 patients (152 males, 83 females) at same times of CT scanning. The patients were grouped by age (<30 years, 31-45 years, 46-60 years, and >61 years). CT parameters including tracheal, azygoesophageal, thoracic vertical, anterior-posterior (AP), transverse diameters, transverse cardiac diameter, diameters of main, right, and left pulmonary arteries, and CT densitometric values including lung volume and density (-900 to -1000 Hounsfield Units, HU), low attenuation value cluster (default threshold: -950 HU) were compared with PFT values. Spearman correlation coefficients was used to evaluate the relationship between the CT indices and PFT. RESULTS: Ninety of 235 patients with PFT were smokers (76 males, 14 females). Obstructive PFT was detected in 65 patients (27.7%: 46 males, 19 females). Male smokers with obstructive PFT displayed significantly larger thoracic anterior-posterior (mean: normal, 172.3 cm versus COPD, 185.9 cm, p = 0.0001) and smaller transverse diameters (mean: normal, 247.0 cm vs. COPD, 235.8 cm, p = 0.01), and increased right pulmonary artery diameter (mean: normal, 20.3 cm v s. COPD, 22.1 cm, p < 0.001), and increased left pulmonary artery diameter (mean: normal, 19.7 cm vs. COPD, 20.6 cm, p < 0.025). The lung parenchyma density (-1000 to -900 HU) and greater concentration of largest cluster on densitometry were significantly different between normal and obstructive PFT pattern in male smoker. Residual volume and total lung capacity are positively correlated with lung volume and lung density (-1000 to -800) of densitometry. CONCLUSIONS: CT findings of the overexpansion of the lungs, such as increases in the vertical diameter of the lung and decreases in the transverse diameter of the heart, can be significant as indirect findings of early chronic obstructive diseases. However, despite the significant CT findings in male smokers, particularly those in their 40s, most lung function parameters were not decidedly abnormal.

8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice.

8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been recently shown to exert anti-inflammatory effects through inhibition of Rac1. Inflammation in adipose tissue is a hallmark of obesity-induced insulin resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic diseases has not been fully elucidated. The aim of this study was to examine the effect of exogenously administered 8-OHdG on adipose tissue and whole body metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8-OHdG administration blunted the rise in body weight and fat mass. The decrease in adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through induction of adipose triglyceride lipase and inhibition of fatty acid synthase expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in amelioration of adipose tissue inflammation and adipokine dysregulation. Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK activation and reduces JNK activation in adipocytes. In conclusion, our results show that orally administered 8-OHdG protects against HFD-induced metabolic disorders by regulating adipocyte metabolism.

Synthetic 8-hydroxydeoxyguanosine inhibited metastasis of pancreatic cancer through concerted inhibitions of ERM and Rho-GTPase.

8-hydroxydeoxyguanosine (8-OHdG) is generated consequent to oxidative stress, but its paradoxical anti-oxidative, anti-inflammatory, and anti-mutagenic effects via Rho-GTPase inhibition were noted in various models of inflammation and cancer. Metastasis occurs through cell detachment, epithelial-mesenchymal transition (EMT), and cell migration; during these processes, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. In this study, we explored the anti-metastatic mechanisms of 8-OHdG in Panc-1 pancreatic cancer cells. 8-OHdG inhibits cell migration by inactivating ERM and Rho-GTPase proteins, and inhibiting focal adhesion kinase (FAK) and matrix metalloproteinases (MMPs). At 15min, 8-OHdG significantly inactivated ERM (p < 0.05) and led to a significant retardation of wound healing; siERM and H1152 (ROCK inhibitor) had similar effects (p < 0.05). However, FAK inhibitor 14, DPI (NOX inhibitor), and NAC (antioxidant) significantly delayed wound healing without inhibiting ERM or CD44 (p < 0.05). In the experiments on cell migration, siERM, siCD44, DPI, and 8-OHdG significantly inhibited MMPs. 8-OHdG significantly decreased DCF-DA activation in Panc-1 pancreatic cancer cells and down-regulated NOXs (nox-1, nox-2, and nox-3). Finally, all of these anti-migration actions of 8-OHdG resulted in significant inhibition of EMT, as evidenced by the up-regulation of ZO-1 and claudin-1 and down-regulation of vimentin. We found significant inhibition of lung metastasis of Panc-1 cells by 8-OHdG. In conclusion, exogenous 8-OHdG had potent anti-metastasis effects mediated by either ERM or Rho GTPase inhibition in metastasis-prone pancreatic cancer cells.

Age-Related Changes in Nuclear Factor Erythroid 2-Related Factor 2 and Reactive Oxygen Species and Mitochondrial Structure in the Tongues of Fischer 344 Rats.

OBJECTIVES: Previously the authors reported age-related changes in the activities of anti-oxidative enzyme activities and protein expressions in the tongues of rats. Because more information is required about relations between aging and oxidative stress and anti-oxidative enzyme efficiency, the authors investigated differences between the expression of master regulator of anti-oxidative enzymes (nuclear factor erythroid 2-related factor 2 [Nrf2]), levels of reactive oxygen species (ROS), and mitochondrial structures in the tongues of young and aged Fischer 344 rats. METHODS: Age-dependent changes in Nrf2 protein and ROS were determined by Western blotting and using chemical kits, respectively. Tongue specimens were examined by electron microscopy. The study was conducted using rats aged 7 months (young, n=8) or 22 months (old, n=8). RESULTS: Nrf2 protein levels in the tongues of aged rats were lower than in young rats. ROS levels were higher in older rats and mitochondrial structural deficits were observed their tongues. Three young rats showed moderate mitochondrial degeneration, whereas profound degeneration with mitochondrial cristae disruption, swelling, rupture, or intramitochondrial vacuole formation was observed in all 8 old rats. Notably, mitochondrial rupture was observed in 5 old rats. CONCLUSION: Antioxidant defense systems of old rats were compromised by Nrf2 deficiency, which could lead to the deleterious accumulation and release of ROS and probably mitochondrial structural deficits in aged tongue tissues.