K-ras mutation detected by peptide nucleic acid-clamping polymerase chain reaction, Ki-67, S100P, and SMAD4 expression can improve the diagnostic accuracy of inconclusive pancreatic EUS-FNB specimens.

OBJECTIVES: We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and K-ras mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases. METHODS: Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for K-ras mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed. RESULTS: K-ras mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases. CONCLUSIONS: K-ras mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose.

Ultrastrong and ductile steel welds achieved by fine interlocking microstructures with film-like retained austenite.

The degradation of mechanical properties caused by grain coarsening or the formation of brittle phases during welding reduces the longevity of products. Here, we report advances in the weld quality of ultra-high strength steels by utilizing Nb and Cr instead of Ni. Sole addition of Cr, as an alternative to Ni, has limitations in developing fine weld microstructure, while it is revealed that the coupling effects of Nb and Cr additions make a finer interlocking weld microstructures with a higher fraction of retained austenite due to the decrease in austenite to acicular ferrite and bainite transformation temperature and carbon activity. As a result, an alloying design with Nb and Cr creates ultrastrong and ductile steel welds with enhanced tensile properties, impact toughness, and fatigue strength, at 45% lower material costs and lower environmental impact by removing Ni.

Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.

Irregularities in insulin signaling have significantly increased the risk of various cancers, yet the precise underlying mechanisms remain unclear. Within our study, we observed that inhibiting neddylation enhances cancer cell migration across different cancer types by activating both insulin receptor substrates 1 and 2 (IRS1 and IRS2), along with the PI3K/AKT signaling pathway. Notably, in the context of high-grade serous carcinoma (HGSC) patients, whether they had type 2 diabetes mellitus or not, IRS1 and IRS2 displayed a parallel relationship with each other while exhibiting an inverse relationship with NEDD8. We also identified C-CBL as an E3 ligase responsible for neddylating IRS1 and IRS2, with clinical evidence further confirming a reciprocal relationship between C-CBL and pAKT, thereby reinforcing the tumor suppressive role of C-CBL. Altogether, these findings suggest that neddylation genuinely participates in IRS1 and IRS2-dependent insulin signaling, effectively suppressing cancer cell migration. Thus, caution is advised when considering neddylation inhibitors as a treatment option for cancer patients, particularly those presenting with insulin signaling dysregulations linked to conditions like obesity-related type 2 diabetes or hyperinsulinemia.

The Effectiveness and Safety of Chuna Manual Therapy Adjuvant to Western Medicine in Patients with Chronic Obstructive Pulmonary Disease: A Randomized, Single-Blind, Investigator-Initiated, Pilot Trial.

Recently, non-pharmacological treatments are gaining increasing importance for improving the quality of life in patients with chronic obstructive pulmonary disease (COPD). This pilot study aimed to evaluate the feasibility of conducting extensive research on Chuna manual therapy (CMT). This study investigated the effectiveness and safety of CMT adjuvant to Western medicine (WM) in patients with COPD. Forty patients with COPD were randomized into two groups in a 1:1 ratio: experimental (CMT plus WM) and control (WM only) groups. The CMT intervention was administered once a week for eight weeks. The primary outcome measured was the 6-min walk distance (6MWD). Secondary outcomes measured were: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), assessments using the modified Medical Research Council (mMRC) scale and Visual Analog Scale (VAS) for dyspnea, the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and the EuroQoL five-dimensional questionnaire (EQ-5D). The mean differences in FEV1 (L) between Weeks 1 and 8 were statistically significant between the groups (p = 0.039). Additionally, the experimental group showed improved 6MWD, mMRC, VAS for dyspnea, CAT, SGRQ (total), and EQ-VAS scores than the control group. However, the differences between the two groups were not statistically significant. No adverse events were observed during this trial. CMT has the potential to alleviate symptoms, improve quality of life, and delay the decline in lung function in patients with COPD. The results of this pilot study could lead to large-scale clinical trials in the future.

The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis.

BACKGROUND: Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet. METHODS: Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression. RESULTS: Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2. CONCLUSIONS: Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.

Pathological Characteristics of Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

BACKGROUND: This study aimed to identify pain-related behavior and pathological characteristics of the knee joint in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA). METHODS: Knee joint inflammation was induced by intra-articular injection of MIA (4 mg/50 µL, n = 14) in 6-week-old male rats. Knee joint diameter, weight-bearing percentage on the hind limb during walking, the knee bending score, and paw withdrawal to mechanical stimuli were measured to evaluate edema and pain-related behavior for 28 d after MIA injection. Histological changes in the knee joints were evaluated using safranin O fast green staining on days 1, 3, 5, 7, 14, and 28 after OA induction (n = 3, respectively). Changes in bone structure and bone mineral density (BMD) were examined 14 and 28 d after OA (n = 3, respectively) using micro-computed tomography (CT). RESULTS: The knee joint diameter and knee bending scores of the ipsilateral joint significantly increased 1 d after MIA injection, and the increased knee joint diameter and knee bending score persisted for 28 d. Weight-bearing during walking and paw withdrawal threshold (PWT) decreased from 1 and 5 d, respectively, and were maintained up to 28 d after MIA. Cartilage destruction started on day 1, and Mankin scores for bone destruction significantly increased for 14 d, as shown by micro-CT imaging. CONCLUSION: The present study demonstrated that histopathological structural changes in the knee joint due to inflammation started soon after MIA injection, which induced OA pain from inflammation-related acute pain to spontaneous and evoked associated chronic pain.

Diesel exhaust particle exposure accelerates oxidative DNA damage and cytotoxicity in normal human bronchial epithelial cells through PD-L1.

Diesel exhaust particles (DEPs) are a major cause of cancer progression as well as a variety of acute and chronic diseases. It is well-known that programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can induce immune escape in tumor cells. However, the function of PD-L1 in bronchial epithelial cells or how PD-L1 relates to cellular oxidation under DEPs-mediated oxidative stress is not well known. In this study, we investigated how PD-L1 affected DEPs-induced oxidative stress and cytotoxicity in human bronchial epithelial (HBE) cells, Beas-2B. DEPs not only induced intracellular reactive oxygen species (ROS) production, but also increased PD-L1 expression in HBE cells. Beas-2B cells overexpressing PD-L1 showed higher levels of ROS production, DNA damage, and apoptosis after DEPs treatment compared to control cells. In particular, the expression of an antioxidant enzyme heme-oxygenase-1 (HO-1) and nuclear translocation and transcriptional activity of Nrf2, a major regulator of HO-1, were lower in Beas-2B overexpressing PD-L1 cells than in control cells. DEPs-induced ROS generation, DNA damage and apoptosis in Beas-2B cells overexpressing PD-L1 were significantly restored by overexpressing HO-1. Collectively, our results suggest that DEPs can increase the expression of PD-L1 in HBE cells and that overexpressing PD-L1 might eventually promote DEPs-induced oxidative DNA damage and apoptosis.

Surface ECG-based complexity parameters for predicting outcomes of catheter ablation for nonparoxysmal atrial fibrillation: efficacy of fibrillatory wave amplitude.

Catheter ablation (CA) is a well-established therapy for rhythm control in atrial fibrillation (AF). However, CA outcomes for persistent AF remain unsatisfactory because of the high recurrence rate despite time-consuming efforts and the latest ablation technology. Therefore, the selection of good responders to CA is necessary. Surface electrocardiography (sECG)-based complexity parameters were tested for the predictive ability of procedural termination failure during CA and late recurrence of atrial arrhythmias (AA) after CA. A total of 130 patients with nonparoxysmal AF who underwent CA for the first time were investigated. A 10-second sECG of 4 leads (leads I, II, V1, and V6) was analyzed to compute the fibrillatory wave amplitude (FWA), dominant frequency (DF), spectral entropy (SE), organization index (OI), and sample entropy (SampEn). The study endpoints were procedural termination failure during CA and late (≥1 year) AA recurrence after CA. In the multivariate analysis, FWA in lead V1 and DF in lead I were independent predictors of successful AF termination during CA (P <.05). The optimal cut-off values for FWA in lead V1 and DF in lead I were 60.38 µV (area under the curve [AUC], 0.672; P = .001) and 5.7 Hz (AUC, 0.630; P = .016), respectively. The combination of FWA of lead V1 and DF of lead I had a more powerful odds ratio for predicting procedural termination failure (OR, 8.542; 95% CI, 2.938-28.834; P < .001). FWA in lead V1 was the only independent predictor of late recurrence after CA. The cut-off value is 65.73 µV which was 0.634 of the AUC (P = .009). These sECG parameters, FWA in lead V1 and DF in lead I, predicted AF termination by CA in patients with nonparoxysmal AF. In particular, FWA in lead V1 was an independent predictor of late recurrence of AA after CA.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of ß-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.

Suppression of the TRIF-dependent signaling pathway of TLRs by epoxomicin.

Toll-like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88- and the TRIF-dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide α',ß'-epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF-kB and IRF3 induced by TLR agonists, decreased the expression of interferon-inducible protein-10, and inhibited the activation of NF-kB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88- and TRIF-dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.

Evaluation of the Radial Procurvatum Using the Center of Rotation of Angulation Methodology in Chondrodystrophic Dogs.

The radial joint orientation angles were calculated using the center of rotation of angulation (CORA) methodology within the frontal and sagittal planes in chondrodystrophic dog breeds, including Welsh Corgi, Dachshund, Pekinese, Poodle, Beagle and Maltese, and it was compared whether there is a statistically significant difference between the breeds. Radial joint orientation angles were obtained in eighty-eight dogs, including 23 Welsh Corgis, 16 Dachshunds, 14 Pekinese, 13 Maltese, 12 Poodles and 10 Beagles. Using the CORA methodology, the cranial proximal radial angle (CrPRA) and caudal distal radial angle (CdDRA) in the sagittal plane and medial proximal radial angle (MPRA) and lateral distal radial angle (LDRA) in the frontal plane were measured for the six breeds studied. The mean values of joint angles for each breed were compared statistically were observed. The CrPRA, CdDRA, and LDRA mean values of Dachshund and Welsh Corgi breeds were significantly smaller than other breeds, and in MPRA, Pekingese showed significantly smaller values than other breeds. This study confirms that the mean values of radial joint orientation angles can be significantly different among chondrodystrophic breeds. To accurately evaluate the degree of angular deformity of the radius, it may be helpful to refer to the average value for each breed with chondrodystrophy.

Case Report: Imaging Features and Successful Management of Ureteral Stenosis in a Kitten With Bilateral Atypical Papillary Transitional Mucosal Hyperplasia.

A 3-month-old cat weighing 2.62 kg was brought to the VIP Animal Medical Center with vomiting, diarrhea, anorexia, and depression. Laboratory findings confirmed azotemia with elevated blood urea nitrogen (BUN) (168.9 mg/dl) and creatinine (5.9 mg/dl) and symmetric dimethylarginine (SDMA) (86 µg/dl). Abdominal radiography revealed bilateral renomegaly. Ultrasonography revealed bilateral hydronephrosis and left partial and right complete ureteral obstructions with bilateral focal irregular and circumferential thickenings at ureters. Reduction of bilateral renal function was confirmed through excretory urography on computed tomography. The cat underwent subcutaneous ureteral bypass surgery on the left kidney, right nephrectomy, and bilateral ureterectomy. Histopathology of bilateral ureteral irregular and circumferential thickening revealed bilateral atypical papillary transitional mucosal hyperplasia. Three days after surgery, the left hydronephrosis resolved, and azotemia was almost resolved. This is the first report of successful management of ureteral stenosis with congenital papillary transitional mucosal hyperplasia in a kitten using multimodality imaging.

Comparable Plasma Lipid Changes in Patients with High-Grade Cervical Intraepithelial Neoplasia and Patients with Cervical Cancer.

Cervical cancer is the fourth most prevalent cancer among women worldwide and usually develops from cervical intraepithelial neoplasia (CIN). In the present study, we compared alterations in lipids associated with high-grade CIN and cervical cancer with those associated with a normal status and low-grade CIN by performing global lipid profiling on plasma (66 healthy controls and 55 patients with CIN1, 44 with CIN2/3, and 60 with cervical cancer) using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. We identified 246 lipids and found 31 lipids with similar alterations in both high-grade CIN and cervical cancer. Among these 31 lipids, four lipid classes (phosphatidylcholine, phosphatidylethanolamine, diglyceride, and free fatty acids) were identified as the major lipid classes with significant differences in the patients with CIN2/3 and cervical cancer compared to the healthy controls and the patients with CIN1. Lipid metabolites belonging to the same classes were positively correlated with each other. High-grade CIN and cervical cancer induce comparable changes in lipid levels, which are closely related to the development of cervical tumors. These results suggest that lipid profiling is a useful method for monitoring progression to cervical cancer.

Taxonomic and Functional Differences in Cervical Microbiome Associated with Cervical Cancer Development.

The cervical microbiome is associated with cervical cancer risk, but how microbial diversity and functional profiles change in cervical cancer remains unclear. Herein, we investigated microbial-compositional and functional differences between a control group and a high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2/3-CC) group. After retrospective collection of 92 cervical swab samples, we carried out 16S rRNA amplicon sequencing on 50 and 42 samples from the control and CIN2/3-CC groups, respectively. The EzBioCloud pipeline was applied to identify the genomic features associated with the groups using 16S rRNA data. A linear discriminant analysis effect size (LEfSe) was performed to assess the enrichment in the assigned taxonomic and functional profiles. We found a lower richness in the control group relative to the CIN2/3-CC group; however, the ß-diversity tended to be similar between the groups. The LEfSe analysis showed that a phylum Sacchaaribacteria_TM7, 11 genera, and 21 species were more abundant in the CIN2/3-CC group and that one uncharacterized Gardnerella species was more abundant only in the control group. Further characterization of the functional pathways using EzBioCloud showed that the 4 KEGG orthologs (Phosphotransferase system [PTS] sucrose-specific IIA, IIB, IIC components and PTS cellubiose-specific IIC component) were involved in the KEGG pathway of starch and sucrose metabolism. The two pathways of folate biosynthesis and oxidative phosphorylation were more abundant in the CIN2/3-CC group. Further confirmation of these results in larger samples can help to elucidate the potential association between the cervical microbiome and cervical cancer.

Proinflammatory Dietary Intake is Associated with Increased Risk of Metabolic Syndrome and Its Components: Results from the Population-Based Prospective Study.

Metabolic syndrome (MetS) is a major public health challenge throughout the world, although studies on its association with the inflammatory potential of diet are inconsistent. The aim of this prospective study was to assess the association between the Dietary Inflammatory Index (DII®) and the risk of MetS and its components in a Korean population. Data from 157,812 Korean adults (mean age 52.8 years; 53,304 men and 104,508 women with mean follow-up of 7.4 years) collected by members of the Korean Genome and Epidemiology Study form the basis for this report. DII scores were calculated based on Semi-Quantitative Food-Frequency Questionnaire data. Multivariable-adjusted Cox proportional hazard models were used to estimate the association between DII scores and MetS. In women, higher DII scores (pro-inflammatory diet) increased the risk of MetS (hazard ratio [HR]quintile5 v. 1 1.43; 95% confidence interval (CI) 1.21-1.69; p for trend ≤ 0.0001) and its five components. A positive association was observed for postmenopausal women, with a 50% higher risk of developing MetS (HRquintile5 v. 1 1.50; 95% CI 1.23-1.83; p for trend = 0.0008) after fully adjusting for potential confounders. Irrespective of the menopausal status of women, higher DII (=Q5) scores were positively associated with all 5 components of MetS (p < 0.05). In men, higher DII scores significantly increased the risk of low HDL cholesterol [HR]quintile5 v. 1 1.59 (1.27-1.99); p for trend = 0.0001], elevated waist circumferences [HR]quintile5 v. 1 1.28 (1.08-1.52); p for trend = 0.01], and high blood pressure [HR]quintile5 v. 1 1.17 (1.03-1.32); p for trend = 0.05]. These results indicate that diet with pro-inflammatory potential, as represented by higher DII scores, is prospectively associated with increased risk of MetS, and the relationship is stronger in women than in men.

Positive Association of Dietary Inflammatory Index with Incidence of Cardiovascular Disease: Findings from a Korean Population-Based Prospective Study.

Recently, diets with higher inflammatory potentials based on the dietary inflammatory index (DII®) have been shown to be associated with increased cardiovascular disease (CVD) risk in the general population. We aimed to prospectively investigate the association between the DII and CVD risk in the large Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort comprised of 162,773 participants (men 55,070; women 107,703). A validated semi-quantitative food frequency questionnaire (SQ-FFQ) was used to calculate the DII score. Statistical analyses were performed by using a multivariable Cox proportional hazard model. During the mean follow-up of 7.4 years, 1111 cases of CVD were diagnosed. Higher DII score was associated with increased risk of CVD in men (hazard ratio [HR]Quintile 5 vs. 1 1.43; 95% CI 1.04-1.96) and in women (HRQuintile 5 vs. 1 1.19; 95% CI 0.85-1.67), although not significant for women. The risk of CVD was significantly higher in physically inactive men (HRQuintile 5 vs. 1 1.80; 95% CI 1.03-3.12), obese men (HRQuintile 5 vs. 1 1.77; 95% CI 1.13-2.76) and men who smoked (HRQuintile 5 vs. 1 1.60; 95% CI 1.10-2.33), respectively. The risk of developing stroke was significantly higher for men (HRQuintile 5 vs. 1 2.06; 95% CI 1.07-3.98; p = 0.003), but not for women. A pro-inflammatory diet, as indicated by higher DII scores, was associated with increased risk of CVD and stroke among men.

Association of Blood Mercury Level with the Risk of Depression According to Fish Intake Level in the General Korean Population: Findings from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2013.

Mercury is a cumulative neurotoxic agent, exposure to high levels of which may increase the risk of psychiatric symptoms. The purpose of this study was to examine the associations between blood mercury and depression risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) with 11,754 participants (male: 5834 female: 5920) aged ≥19 years from 2008 to 2013. The associations of blood mercury with risk of depression were estimated using multivariate logistic regression after adjustment for potential confounders. We found a significantly increased risk of depression in the highest quintile for blood mercury (multivariate OR = 2.05; 95% CI = 1.20-3.48; P trend = 0.03) among female, but not male. A stratification analysis by fish intake showed that the association between depression and blood mercury was strengthened (OR = 4.00; 95% CI = 1.51-10.6; P trend = 0.015) among females with the lowest tertile of fish intake. The results of this study suggest that higher levels of blood mercury, especially in cases of lower fish intake, are positively associated with the risk of depression in Korean women.

Suppressive effects of dehydrocostus lactone on the toll-like receptor signaling pathways.

Toll-like receptors (TLRs) are a group of pattern-recognition receptors (PRRs) that are at the core of innate and adaptive immune responses. TLRs activation triggers the activation of two downstream signaling pathways, the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-ß (TRIF)-dependent pathways. To evaluate the therapeutic potential of DHL, a natural sesquiterpene lactone derived from Inulahelenium L. and Saussurea lappa, we examined its effect on signal transduction via the TLR signaling pathways. DHL inhibited the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), the representative transcription factors involved in the inflammatory response, induced by TLR agonists, as well as the expression of cyclooxygenase-2 and interferon inducible protein-10. DHL also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the TLRs signaling pathways. All results suggest that DHL might become a new therapeutic drug for a variety of inflammatory diseases.

The Association between Dietary Inflammatory Index (DII) and Cancer Risk in Korea: A Prospective Cohort Study within the KoGES-HEXA Study.

Several epidemiological studies have shown that there are consistent positive associations between dietary inflammatory index (DII®) and cancer incidence in Western populations. However, few DII-cancer studies have been conducted in East Asian populations. In a large cohort representative of the general Korean population, we investigated whether the DII is associated with overall cancer risk. A total of 163,660 participants (56,781 males and 106,879 females) had evaluable data for analyses. This follow-up study was carried out over the course of 7.9 years. DII was calculated based on Semi-Quantitative Food-Frequency Questionnaire (SQ-FFQ) data for 106 food items. Cancers were self-reported based on notification by the participants' medical doctors. Multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). After the follow-up, 1,643 cases of cancer (520 males and 1123 females) had developed. In a fully adjusted model, women in the highest DII quintile showed a 44% increased risk of getting cancer (HRQ5vsQ1 = 1.44; 95% CI = 1.14-1.82; p-trend = 0.0006), while men showed no apparent association (HRQ5vsQ1 = 0.80; 95% CI = 0.58-1.10). These results indicate that in Korean women, a more pro-inflammatory diet is associated with a higher risk of cancer incidence.

Higher Pro-Inflammatory Dietary Score is Associated with Higher Hyperuricemia Risk: Results from the Case-Controlled Korean Genome and Epidemiology Study_Cardiovascular Disease Association Study.

In previous studies, the elevated dietary inflammatory index (DII®) scores have been consistently associated with several chronic diseases. However, the relationship with hyperuricemia remains unknown. The aim of this study was to determine if the DII is associated with hyperuricemia risk. The study included 13,701 participants (men 5102; women 8599) in a large-scale cross-sectional study in South Korea. A validated semi-quantitative food frequency questionnaire (SQFFQ) was used to measure dietary intake, and blood samples were obtained to determine hyperuricemia. As the DII score increased, the hyperuricemia risk increased among women (OR 1.35, 95% CI 1.03-1.77, p trend = 0.02). However, no significant results were found for men. Women with lower BMI scores had higher risks of hyperuricemia with higher DII scores (OR 1.62, 95% CI 1.05-2.52, p trend = 0.03). As the DII increased, however, only women who consumed alcohol ("past or current drinkers") had higher risks of hyperuricemia (OR 1.92, 1.22-3.02, p trend = 0.004). Among the DII components, intake of flavonoids showed a significant association with the hyperuricemia risk in women (OR 0.75, 0.59-0.96, p trend = 0.03). Our results suggest that higher intake of pro-inflammatory diet is significantly associated with higher risk of hyperuricemia among women. These results reinforce the importance of less pro-inflammatory habitual dietary patterns in lowering the risk of hyperuricemia and secondary afflictions such as cardiovascular diseases.