Scalable Printing of Metal Nanostructures through Superluminescent Light Projection.

Direct printing of metallic nanostructures is highly desirable but current techniques cannot achieve nanoscale resolutions or are too expensive and slow. Photoreduction of solvated metal ions into metallic nanoparticles is an attractive strategy because it is faster than deposition-based techniques. However, it is still limited by the resolution versus cost tradeoff because sub-diffraction printing of nanostructures requires high-intensity light from expensive femtosecond lasers. Here, this tradeoff is overcome by leveraging the spatial and temporal coherence properties of low-intensity diode-based superluminescent light. The superluminescent light projection (SLP) technique is presented to rapidly print sub-diffraction nanostructures, as small as 210 nm and at periods as small as 300 nm, with light that is a billion times less intense than femtosecond lasers. Printing of arbitrarily complex 2D nanostructured silver patterns over 30 µm × 80 µm areas in 500 ms time scales is demonstrated. The post-annealed nanostructures exhibit an electrical conductivity up to 1/12th that of bulk silver. SLP is up to 480 times faster and 35 times less expensive than printing with femtosecond lasers. Therefore, it transforms nanoscale metal printing into a scalable format, thereby significantly enhancing the transition of nano-enabled devices from research laboratories into real-world applications.

Best cutoff score of cervical-pedicle thickness as a morphological parameter for predicting cervical central stenosis.

There are various factors for the cause of cervical central stenosis (CCS), such as osteophyte, cervical-disc degeneration, and cervical ligamentum flavum hypertrophy. However, the pedicle of the cervical vertebra has not yet been analyzed for its relationship with CCS. We created a new morphologic parameter called the cervical-pedicle thickness (CPT) to assess the association between CCS and the cervical pedicle. We obtained morphological cases involving the CPT from 82 patients with CCS. There were also 84 in the normal group who underwent cervical spine magnetic resonance imaging (CS-MR) as part of routine health screening. We obtained the T2-weighted CS-MR axial images from group members, and assessed the CPT at the level of the C6 vertebra on CS-MR. The mean CPT was 3.46 ± 0.57 mm in the normal group, 4.97 ± 0.75 mm in the CCS group, which thus had a significantly higher CPT (P < .01) than did the normal group. For the prognostic value of the CPT as a predictor of CCS, ROC analysis indicated that the best cutoff score for the CPT was 4.18 mm, with 93.9% sensitivity, 92.9% specificity, and AUC 0.97. Greater CPT was highly associated with a possibility of CCS. This conclusion will be helpful for assessing the CCS patients.

Optimal Duration for Dual Antiplatelet Therapy After Left Main Coronary Artery Stenting.

BACKGROUND: Coronary interventions using drug-eluting stents (DESs) of left main coronary artery (LMCA) lesions have shown favorable clinical outcomes. However, duration of dual antiplatelet therapy (DAPT) after LMCA interventions has not yet been investigated.Methods and Results:From a multicenter Korean Multicenter Angioplasty Team (KOMATE) registry, 1,004 patients who received DES implantations for LMCA lesions and did not experience major adverse cardiovascular events (including major bleeding) for 1 year after coronary intervention were analyzed. Patients were divided into 2 groups; DAPT ≤12 (n=503) and >12 months (n=501). The primary endpoint was number of net clinical adverse events (NACEs), composite of cardiac deaths, myocardial infarctions, stent thrombosis and major bleeding events. During a 4.5-year follow-up period after LMCA interventions, the DAPT >12 months group showed a lower NACE rate than the DAPT ≤12 months group (adjusted-HR 0.53 [0.29-0.99], P=0.045). For patients who maintained DAPT >12 months, rate of cardiac deaths, myocardial infarctions, and stent thrombosis events were lower than in patients who had DAPT ≤12 months (adjusted-HR 0.35 [0.17-0.73], P=0.005) without increased major bleeding (P=0.402). CONCLUSIONS: For patients who can continue DAPT without major bleeding events, prolonged DAPT (>12 months) after LMCA stenting demonstrated better long-term efficacy outcomes than DAPT ≤12 months with comparable safety.

Engulfment and cell motility 1 promotes tumor progression via the modulation of tumor cell survival in gastric cancer.

BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) protein has been implicated in phagocytosis of apoptotic cells, cell migration, neurite outgrowth, cancer cell invasion and metastasis, and poor prognosis in various cancers. We investigated the role of ELMO1 in mediating the oncogenic behavior of gastric cancer (GC) cells. We also investigated the correlation between expression of ELMO1 in GC tissues and various clinicopathological parameters. METHODS: We studied the impact of ELMO1 on tumor cell behavior using the pcDNA-myc vector and small interfering RNA in AGS and SNU1750 GC cell lines. We performed western blotting and immunohistochemistry to investigate the expression of ELMO1 in GC cells and tissues. RESULTS: ELMO1 overexpression inhibited apoptosis via the modulation of PARP, caspase-3 and caspase-7 in GC cells. ELMO1 overexpression led to significant increase in the number of migrating and invading GC cells. The expression of E-cadherin decreased and that of Snail increased in GC cells upon ELMO1 overexpression. Phosphorylation of PI3K/Akt and GSK-3ß was increased and that of ß-catenin was decreased upon ELMO1 overexpression in GC cells. These results were reversed after ELMO1 knockdown. ELMO1 expression was significantly associated with tumor size, cancer stage, lymph node metastasis and survival. ELMO1-positive tumors had significantly higher mean of Ki-67 labeling index than ELMO1-negative tumors. There was no significant relationship between ELMO1 expression and the mean value of the apoptotic index. CONCLUSIONS: Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.

Consecutive Jailed- and Kissing-Corsair Technique: Side Branch Protection and Dilation during Stent Implantation.

The primary concern in percutaneous coronary intervention for bifurcation lesions is occlusion of a side branch after stenting of a main branch, especially in high-risk patients. We describe a novel technique, consecutive jailed- and kissing-Corsair technique, using a Corsair microcatheter for protection of side branches in bifurcation lesions.

Forkhead­box A1 regulates tumor cell growth and predicts prognosis in colorectal cancer.

Forkhead box A1 (FOXA1) functions as a tumor suppressor gene or an oncogene in various types of cancer; however, the distinct function of FOXA1 in colorectal cancer is unclear. The present study aimed to evaluate whether FOXA1 affects the oncogenic behavior of colorectal cancer cells, and to investigate its prognostic value in colorectal cancer. The impact of FOXA1 on tumor cell behavior was investigated using small interfering RNA and the pcDNA6­myc vector in human colorectal cancer cell lines. To investigate the role of FOXA1 in the progression of human colorectal cancer, an immunohistochemical technique was used to localize FOXA1 protein in paraffin­embedded tissue blocks obtained from 403 patients with colorectal cancer. Tumor cell apoptosis and proliferation were evaluated using a terminal deoxynucleotidyl transferase­mediated dUTP nick­end labeling assay and Ki­67 immunohistochemical staining, respectively. FOXA1 knockdown inhibited tumor cell invasion in colorectal cancer cells, and induced apoptosis and cell cycle arrest. FOXA1 knockdown activated cleaved caspase­poly (ADP­ribose) polymerase, upregulated the expression of p53 upregulated modulator of apoptosis, and downregulated BH3 interacting domain death agonist and myeloid cell leukemia­1, leading to the induction of apoptosis. FOXA1 knockdown increased the phosphorylation level of signal transducer and activator of tran-scription­3. By contrast, these results were reversed following the overexpression of FOXA1. The overexpression of FOXA1 was associated with differentiation, lymphovascular invasion, advanced tumor stage, depth of invasion, lymph node metastasis and poor survival rate. The mean Ki­67 labeling index value of FOXA1­positive tumors was significantly higher than that of FOXA1­negative tumors. However, no significant association was observed between the expression of FOXA1 and the mean apoptotic index value. These results indicate that FOXA1 is associated with tumor progression via the modulation of tumor cell survival in human colorectal cancer.

Reversine induces cell cycle arrest and apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells.

Reversine, a 2,6­diamino­substituted purine analogue, has been reported to be effective in tumor suppression via induction of cell growth arrest and apoptosis of cancer cells. However, it remains unclear whether reversine exerts anticancer effects on human colorectal cancer cells. In the present study, in vitro experiments were conducted to investigate the anticancer properties of reversine in human colorectal cancer cells. The effect of reversine on human colorectal cancer cell lines, SW480 and HCT­116, was examined using a WST­1 cell viability assay, fluorescence microscopy, flow cytometry, DNA fragmentation, small interfering RNA (siRNA) and western blotting. Reversine treatment demonstrated cytotoxic activity in human colorectal cancer cells. It also induced apoptosis by activating poly(ADP­ribose) polymerase, caspase­3, ­7 and ­8, and increasing the levels of the pro­apoptotic protein second mitochondria­derived activator of caspase/direct inhibitor of apoptosis­binding protein with low pI. The pan­caspase inhibitor Z­VAD­FMK attenuated these reversine­induced apoptotic effects on human colorectal cancer cells. Additionally, reversine treatment induced cell cycle arrest in the subG1 and G2/M phases via increase in levels of p21, p27 and p57, and decrease in cyclin D1 levels. The expression of Fas and death receptor 5 (DR5) signaling proteins in SW480 and HCT116 cells was upregulated by reversine treatment. Reversine­induced apoptosis and cell cycle arrest were suppressed by inhibition of Fas and DR5 expression via siRNA. In conclusion, Reversine treatment suppressed tumor progression by the inhibition of cell proliferation, induction of cell cycle arrest and induction of apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells. The present study indicated that reversine may be used as a novel anticancer agent in human colorectal cancer.

Cardiac tamponade after radiofrequency ablation for hepatocellular carcinoma: Case report and literature review.

RATIONALE: Radiofrequency ablation (RFA) is a safe and effective local treatment modality with a low complication rate and is commonly used to treat hepatocellular carcinoma (HCC). The clinical outcome of RFA may be closely related to the location, size, and shape of index tumors, and major complications, including hemorrhage, liver abscess, infarction, visceral organ perforation, hemothorax, pneumothorax, tumoral seeding, and hepatic failure. Cardiac tamponade is a rare and serious life-threatening complication associated with RFA. To date, a review of the medical literature reported 5 cases of cardiac tamponade after RFA for HCC. Herein, we report another case of cardiac tamponade after RFA for HCC in a 56-year-old man. PATIENT CONCERNS: He had suffered from liver cirrhosis due to alcohol abuse. He had chronic obstructive pulmonary disease. Magnetic resonance imaging showed a 3.0-cm exophytic subcapsular HCC in segment IVa of left hepatic lobe. As the patient was at high risk for surgery because of poor lung function, RFA was selected as the treatment of choice. The index tumor was located in the vicinity of the diaphragm and colon. During RFA procedure, thermal injury to the adjacent diaphragm and colon was minimized by introducing artificial ascites. Bleeding or tumoral seeding was prevented by ablating the electrode track during electrode retraction. DIAGNOSIS: Two hours after RFA, the patient presented with dyspnea, chest discomfort, and low blood pressure (80/60 mm Hg), suggesting cardiac tamponade. Immediate follow-up contrast-enhanced computed tomography image depicted the slightly high attenuated hemopericardium. Transthoracic echocardiography (TTE) showed a moderate amount of pericardial effusion with tamponade and a large hematoma. INTERVENTIONS: Under fluoroscopy and portable echocardiography guidance, a cardiologist immediately inserted a 7-French pigtail catheter into the pericardial space and collected more than 200 cc of bloody pericardial fluid. OUTCOMES: After pericardiocentesis, the patient's symptoms and hemodynamic status were dramatically improved. Follow-up TTE showed scanty amount of pericardial effusion and the drainage catheter was removed. The patient was discharged. LESSONS: When treating HCC in the left lobe (especially segments II and IVa), attention should be paid to cardiac tamponade. The early diagnosis and immediate treatment of cardiac tamponade may increase the chance of cure.

Fermented Ganjangs (Soy Sauce and Sesame Sauce) Attenuates Colonic Carcinogenesis in Azoxymethane/Dextran Sodium Sulfate-Treated C57BL/6J Mice.

The effects of different ganjangs (also designated as kanjang), including acid-hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame sauce (FSeS), on azoxymethane (AOM, 10 mg/kg)/dextran sulfate sodium (DSS, 2%)-induced colorectal carcinogenesis in C57BL/6J mice were studied. Low doses (4 mL/kg) of both FSeS and FSS significantly increased colon length, suppressed AOM/DSS-induced increases in colon weight/length ratios, and induced colorectal neoplasia compared with AHSS-treated and control mice. Fermented sauces, particularly low doses of FSeS and FSS, showed activity against AOM/DSS-induced colorectal carcinogenesis by abrogating serum and mRNA levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and IL-17α as well as by reducing mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2 in colon mucosa. FSeS significantly increased colonic p53 expression compared with other sauces. However, AHSS showed weak activity against AOM/DSS-induced colonic carcinogenesis. Overall, FSeS showed the strongest anticancer effect, followed by FSS and AHSS. Thus, fermentation with microorganisms rather than chemical processes is important, and raw materials are another factor influencing anticancer activity.

Bacteremia Prediction Model for Community-acquired Pneumonia: External Validation in a Multicenter Retrospective Cohort.

OBJECTIVE: Many studies have described constructing a prediction model for bacteremia in community-acquired pneumonia (CAP), but these studies were not validated in external heterogeneous groups. The objective of this study was to test the generalizability of a previous bacteremia prediction model for CAP by external validation. METHODS: This multicenter retrospective cohort analysis was performed in eight tertiary urban hospital emergency departments (EDs). We reviewed adult patients who were hospitalized after presentation to the ED with CAP. We categorized the enrolled patients into three groups according to the bacteremia prediction model score and calculated the number of patients with or without a blood culture-positive result. We performed a multivariable analysis to identify significant predictors for bacteremia. RESULTS: Among the enrolled 2,001 patients, 1,592 (79.6%), 371 (18.5%), and 38 (1.9%) were stratified to a low-, moderate-, and high-risk group, respectively, and this proportion was similar with previous study. Each group had a bacteremia-positive rate as follows: 1.2% for the low-risk group, 7.2% for the moderate-risk group, and 31.5% for the high-risk group. The area under the receiver operating characteristic curve for the bacteremia model in the external validation cohort was 0.81, and there was no significant difference with that of the previous internal validation cohort (p = 0.246). Assuming that blood cultures were not performed in the low-risk patients, the sensitivity and specificity of this model were 0.68 and 0.81, respectively. Additionally, the positive predictive value and negative predictive value were 9.54 and 98.87%, respectively. A platelet count less than 130 × 109 cells/L, albumin less than 3.3 mg/dL, and C-reactive protein greater than 17 mg/dL were identified as significant predictors with a sensitivity and specificity of 0.70 and 0.83, respectively. CONCLUSION: The bacteremia prediction model was well validated in the general population and could help physicians make the decision to reduce the number of blood cultures in patients with CAP.

Dynamic prediction of patient outcomes during ongoing cardiopulmonary resuscitation.

PURPOSE: The probability of the return of spontaneous circulation (ROSC) and subsequent favourable outcomes changes dynamically during advanced cardiac life support (ACLS). We sought to model these changes using time-to-event analysis in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Adult (≥18 years old), non-traumatic OHCA patients without prehospital ROSC were included. Utstein variables and initial arterial blood gas measurements were used as predictors. The incidence rate of ROSC during the first 30min of ACLS in the emergency department (ED) was modelled using spline-based parametric survival analysis. Conditional probabilities of subsequent outcomes after ROSC (1-week and 1-month survival and 6-month neurologic recovery) were modelled using multivariable logistic regression. The ROSC and conditional probability models were then combined to estimate the likelihood of achieving ROSC and subsequent outcomes by providing k additional minutes of effort. RESULTS: A total of 727 patients were analyzed. The incidence rate of ROSC increased rapidly until the 10th minute of ED ACLS, and it subsequently decreased. The conditional probabilities of subsequent outcomes after ROSC were also dependent on the duration of resuscitation with odds ratios for 1-week and 1-month survival and neurologic recovery of 0.93 (95% CI: 0.90-0.96, p<0.001), 0.93 (0.88-0.97, p=0.001) and 0.93 (0.87-0.99, p=0.031) per 1-min increase, respectively. Calibration testing of the combined models showed good correlation between mean predicted probability and actual prevalence. CONCLUSIONS: The probability of ROSC and favourable subsequent outcomes changed according to a multiphasic pattern over the first 30min of ACLS, and modelling of the dynamic changes was feasible.

Biomarkers for discrimination between latent tuberculosis infection and active tuberculosis disease.

OBJECTIVE: We aimed to determine whether combinations of multiplex cytokine responses could differentiate Mycobacterium tuberculosis (Mtb) infection states. METHODS: Mtb-specific antigen-induced and unstimulated cytokines were measured by Luminex assay in supernatants of QuantiFERON® Gold In-Tube assay (QFT) in 48 active pulmonary TB patients (TB), 15 latent TB infection subjects (LTBI), and 13 healthy controls (HCs). RESULTS: Among the 29 cytokines, eight Mtb antigen-specific biomarkers (GM-CSF, IFN-γ, IL-1RA, IL-2, IL-3, IL-13, IP-10, and MIP-1ß) in the Mtb-infected group were significantly different from those of the HCs. Five Mtb-specific biomarkers (EGF, GM-CSF, IL-5, IL-10, and VEGF), two unstimulated biomarkers (TNF-α[Nil] and VEGF[Nil]), and one Mtb-specific biomarker ratio (IL-2/IFN-γ) showed significant differences between active TB and LTBI. Three unstimulated biomarkers (IL-8[Nil], IL-13[Nil], and VEGF[Nil]) and 5 Mtb-specific biomarkers (IFN-γ, IL-2, IL-3, IP-10, and VEGF) were significantly different between active TB and non-active TB groups. Combinations of three cytokine biomarkers resulted in the accurate prediction of 92.1-93.7% of Mtb-infected cases and 92.3-100% of HCs, respectively. Moreover, combinations of five biomarkers accurately predicted 90.9-100% of active TB cases and 80-100% of LTBI subjects, respectively. In discriminating between active TB and non-active TB regardless of QFT results, combinations of six biomarkers predicted 79.2-95.8% of active TB cases and 67.9-89.3% of non-active TB subjects. CONCLUSIONS: Taken together, our data suggest that combinations of whole blood Mtb antigen-dependent cytokines could serve as biomarkers to determine TB disease states. Especially, VEGF is highlighted as a key biomarker for reflecting active TB, irrespective of stimulation.

Clinical Risk Factors for Upper Gastrointestinal Bleeding after Percutaneous Coronary Intervention: A Single-Center Study.

BACKGROUND/AIMS: Percutaneous coronary intervention (PCI) is often performed therapeutically, and antithrombotic treatment is required for at least 12 months after stent implantation. However, the development of post-PCI upper gastrointestinal bleeding (UGIB) increases morbidity and mortality. We investigated the incidence and risk factors for UGIB in Korean patients within 1 year after PCI. METHODS: The medical records of 3,541 patients who had undergone PCI between January 2006 and June 2012 were retrospectively reviewed. We identified 40 cases of UGIB. We analyzed the incidence and clinical risk factors associated with UGIB occurring within 1 year after PCI by comparing the results for each case to matched controls. The propensity score matching method using age and sex was utilized. RESULTS: UGIB occurred in 40 patients (1.1%). Two independent risk factors for UGIB were a history of peptic ulcer disease (odds ratio [OR], 12.68; 95% confidence interval [CI], 2.70 to 59.66; p=0.001) and the use of anticoagulants (OR, 7.76; 95% CI, 2.10 to 28.66; p=0.002). CONCLUSIONS: UGIB after PCI occurred at a rate of 1.1% in the study population. Clinicians must remain vigilant for the possibility of UGIB after PCI and should consider performing timely endoscopy in patients who have undergone PCI and are suspected of having an UGIB.

Constrictive Pericarditis Long after a Gunshot Wound.

Constrictive pericarditis is an uncommon post-inflammatory disorder characterized by a variably thickened, fibrotic, and frequently calcified, pericardium. Etiology of the constriction can occur for many reasons. Although foreign bodies are not the common cause of constrictive pericarditis, the long-term presence of foreign bodies, like bullets, is presumed to cause chronic constrictive pericarditis even after a very long asymptomatic period. A 69-year-old patient with atrial flutter was admitted to the hospital. A cardiac computed tomography showed a bullet located adjacent to the right atrium. The transthoracic echocardiography showed a thickened pericardium and septal bouncing motion, which were compatible with constrictive pericarditis. The history of the patient revealed an injury by gunshot during the Korean War in 1950. Radiofrequency ablation of the atrial flutter was performed, and after ablation, the bullet was removed surgically. The patient was discharged home after surgery without complications.

Totally occluded grafted right internal mammary artery to anomalously originated right coronary artery.

An anomalous aortic origin of a coronary artery is rare and surgical intervention is recommended when the patient is symptomatic. We performed coronary artery bypass graft surgery in a 21-year-old male patient with a right coronary artery anomalously originating from the left coronary sinus. The artery was significantly stenosed by external compression between the aorta and the pulmonary artery. However, the graft became occluded 1 year after the operation. In such cases, the dynamic nature of the stenosis can cause relatively intact antegrade competitive flow from the native coronary artery and lead to an occlusion of the grafted artery. Methods for evaluating flow rates or intraluminal pressures of native arteries could be helpful in decision-making in similar cases.

Metallic foreign body in heart mimicking moderator band.

A foreign body in heart is rare, but it is more frequently encountered than the past as iatrogenic causes are increasing. Clinicians should be aware that foreign body could be mistaken for normal structure of heart. In order for accurate diagnosis, multi-imaging modalities should be used for information of exact location, mobility and hemodynamic effects. A decision to intervene should be made based on potential harms harbored by foreign bodies. Endovascular retrieval should be considered as an option. However, when fatal complications occur or when foreign bodies are embedded deeply, a surgical removal should be attempted.

Late gadolinium enhancement in cardiac MRI in patients with severe aortic stenosis and preserved left ventricular systolic function is related to attenuated improvement of left ventricular geometry and filling pressure after aortic valve replacement.

BACKGROUND AND OBJECTIVES: WE INVESTIGATED ECHOCARDIOGRAPHIC PREDICTORS: left ventricular (LV) geometric changes following aortic valve replacement (AVR) according to the late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with severe aortic stenosis (AS) and preserved LV systolic function. SUBJECTS AND METHODS: We analyzed 41 patients (24 males, 63.1±8.7 years) with preserved LV systolic function who were scheduled to undergo AVR for severe AS. All patients were examined with transthoracic echocardiography (TTE), CMR before and after AVR (in the hospital) and serial TTEs (at 6 and 12 months) were repeated. RESULTS: The group with LGE (LGE+) showed greater wall thickness (septum, 14.3±2.6 mm vs. 11.5±2.0 mm, p=0.001, posterior; 14.3±2.5 mm vs. 11.4±1.6 mm, p<0.001), lower tissue Doppler image (TDIS', 4.4±1.4 cm/s vs. 5.5±1.2 cm/s, p=0.021; TDI E', 3.2±0.9 cm/s vs. 4.8±1.4 cm/s, p=0.002), and greater E/e' (21.8±10.3 vs. 15.4±6.3, p=0.066) than those without LGE (LGE-). Multivariate analysis show that TDI e' (odds ratio=0.078, 95% confidence interval=0.007-0.888, p=0.040) was an independent determinant of LGE+. In an analysis of the 6- and 12-month follow-up compared with pre-AVR, LGE- showed decreased LV end-diastolic diameter (48.3±5.0 mm vs. 45.8±3.6 mm, p=0.027; 48.3±5.0 mm vs. 46.5±3.4 mm, p=0.019). Moreover, E/e' (at 12 months) showed further improved LV filling pressure (16.0±6.6 vs. 12.3±4.3, p=0.001) compared with pre-AVR. However, LGE+ showed no significant improvement. CONCLUSION: The absence of LGE is associated with favorable improvements in LV geometry and filling pressure. TDI E' is an independent determinant of LGE in patients with severe AS and preserved LV systolic function.

Anti-colitic effects of kanjangs (fermented soy sauce and sesame sauce) in dextran sulfate sodium-induced colitis in mice.

This study was conducted to investigate the preventive effects of different kanjangs (Korean soy sauces), including acid-hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame sauce (FSeS), on 2% dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice. The fermented sauces, particularly FSeS, significantly suppressed DSS-induced body weight loss, increased colon length, and decreased colon weight/length ratios. Histological observations suggested that the fermented sauces prevented edema, mucosal damage, and the loss of crypts induced by DSS compared to the control mice and animals fed AHSS. FSeS and FSS decreased the serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, and IL-17α. mRNA expression of these cytokines as well as that of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon mucosa was also inhibited by the two sauces. Our results suggest that fermented sauces, especially FSeS, exert an anticolitic effect partially by reducing the serum levels of proinflammatory cytokines and inhibiting the mRNA expression of these factors in the colon tissue of mice treated with DSS. However, AHSS did not protect against DSS-induced colitis. In addition, low-dose treatment (4 mL/kg) with the fermented sauces resulted in greater anticolitic effects than consumption of a high quantity (8 mL/kg) of the sauces.

Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells.

BACKGROUND/OBJECTIVES: This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS: 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical ((•)OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS: The ability of FSeS to scavenge DPPH, (•)OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 µM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P < 0.05). Following treatment with 100 µg/mL of FSeS and FSS to prevent H2O2-induced oxidation, cell viability increased from 56.7% (control) to 83.7% and 75.6%, respectively. However, AHSS was not able to reduce H2O2-induced cell damage (viability of the AHSS-treated cells was 54.6%). FSeS more effectively suppressed H2O2-induced ROS generation and lipid peroxidation compared to FSS and AHSS (P < 0.05). Compared to the other sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS: These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity.

MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis.

INTRODUCTION: Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis. METHODS: Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti-SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines. RESULTS: The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1ß. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice. CONCLUSIONS: Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.