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Harbour porpoises (Phocoena phocoena) are the only cetacean residents found year-round in Swedish waters and they are exposed to numerous natural and anthropogenic threats. Since the in situ monitoring of cetaceans can be difficult, invasive and often expensive, investigation of stranding patterns and examination of stranded animals can be used as a cost-effective source of data to study these elusive animals. The aim of this study was to investigate the spatiotemporal patterns of harbour porpoise stranding reports and the possible underlying causes in Swedish waters over a ten-year period (2014–2023). Additionally, the Swedish stranding network plays a key role in the collection of stranded carcasses for health and disease surveillance, and geographic coverage of the network also was analysed. When making spatial comparisons, the ten-year period was divided into two five-year blocks. Data on 854 stranded harbour porpoises were analysed from the coasts of the Skagerrak, Kattegat, and Baltic Seas. Both significant spatial and temporal patterns could be identified. Strandings peaked in July through September and hotspots occurred along most of the Swedish west coast, with the most frequent hotspots located around Öresund and especially the area around the Kullen peninsula. The spatial patterns of strandings found in this study are consistent with data on porpoise abundance, prey abundance, and gillnet fisheries’ efforts. The latter is known to be one of the primary causes of porpoise mortality. Furthermore, the coverage of the Swedish stranding network increased between the two periods, likely reflecting an increased awareness of the carcass-based surveillance program, and gaps requiring network expansion efforts were identified. These results also provide baseline data to enable the continued monitoring of stranding trends, as changes may indicate changes in population distribution, size or mortality rates.

Abstract The conventional differentiation of affective disorders into major depressive disorder (MDD) and bipolar disorder (BD) has insufficient biological evidence. Utilizing multiple proteins quantified in plasma may provide critical insight into these limitations. In this study, the plasma proteomes of 299 patients with MDD or BD (aged 19–65 years old) were quantified using multiple reaction monitoring. Based on 420 protein expression levels, a weighted correlation network analysis was performed. Significant clinical traits with protein modules were determined using correlation analysis. Top hub proteins were determined using intermodular connectivity, and significant functional pathways were identified. Weighted correlation network analysis revealed six protein modules. The eigenprotein of a protein module with 68 proteins, including complement components as hub proteins, was associated with the total Childhood Trauma Questionnaire score (r = −0.15, p = 0.009). Another eigenprotein of a protein module of 100 proteins, including apolipoproteins as hub proteins, was associated with the overeating item of the Symptom Checklist-90-Revised (r = 0.16, p = 0.006). Functional analysis revealed immune responses and lipid metabolism as significant pathways for each module, respectively. No significant protein module was associated with the differentiation between MDD and BD. In conclusion, childhood trauma and overeating symptoms were significantly associated with plasma protein networks and should be considered important endophenotypes in affective disorders.

Abstract Data-driven approaches to subtype transdiagnostic samples are important for understanding heterogeneity within disorders and overlap between disorders. Thus, this study was conducted to determine whether plasma proteomics-based clustering could subtype patients with transdiagnostic psychotic-affective disorder diagnoses. The study population included 504 patients with schizophrenia, bipolar disorder, and major depressive disorder and 160 healthy controls, aged 19 to 65 years. Multiple reaction monitoring was performed using plasma samples from each individual. Pathologic peptides were determined by linear regression between patients and healthy controls. Latent class analysis was conducted in patients after peptide values were stratified by sex and divided into tertile values. Significant demographic and clinical characteristics were determined for the latent clusters. The latent class analysis was repeated when healthy controls were included. Twelve peptides were significantly different between the patients and healthy controls after controlling for significant covariates. Latent class analysis based on these peptides after stratification by sex revealed two distinct classes of patients. The negative symptom factor of the Brief Psychiatric Rating Scale was significantly different between the classes (t = −2.070, p = 0.039). When healthy controls were included, two latent classes were identified, and the negative symptom factor of the Brief Psychiatric Rating Scale was still significant (t = −2.372, p = 0.018). In conclusion, negative symptoms should be considered a significant biological aspect for understanding the heterogeneity and overlap of psychotic-affective disorders.

The Swedish National Veterinary Institute (SVA) is working on implementing reusable and adaptable workflows for epidemiological analysis and dynamic report generation to improve disease surveillance. Important components of this work include: data access, development environment, computational resources and cloud-based management. The development environment relies on Git for code collaboration and version control and the R language for statistical computing and data visualization. The computational resources include both local and cloud-based systems, with automatic workflows managed in the cloud. The workflows are designed to be flexible and adaptable to changing data sources and stakeholder demands, with the ultimate goal to create a robust infrastructure for the delivery of actionable epidemiological information.

Abstract There is increasing evidence supporting the association between gut microbiome composition and mood disorders; however, studies on the circulating microbiome are scarce. This study aimed to analyze the association of the serum microbial DNA composition with depressive and anxiety symptoms in patients with mood disorders. The sera of 69 patients with mood disorders, aged from 19 to 60, were analyzed. Bacterial DNA was isolated from extracellular membrane vesicles and, subsequently, amplified and quantified with specific primers for the V3–V4 hypervariable region of the 16S rDNA gene. Sequence reads were clustered into Operational Taxonomic Units and classified using the SILVA database. There were no significant associations between alpha diversity measures and the total Hamilton depression rating scale (HAM-D) or Beck anxiety inventory (BAI) scores. Only the weighted UniFrac distance was associated with the total HAM-D score (F = 1.57, p = 0.045). The Bacteroidaceae family and Bacteroides genus were negatively associated with the total HAM-D score (β = − 0.016, p

Since autism diagnosis is directly linked to the availability of supportive services, identifying best practices for early diagnosis of autism has long been a concern of professionals and families. Meanwhile, studies show persistent racial disparities in autism diagnosis. Although numerous clinical diagnostic guidelines have been published, there is not enough discussion of diagnostic procedures through the lens of culturally diverse families. Purpose: This study focuses on the autism diagnostic experiences that Korean immigrant mothers had with their children. Methods: Eleven first-generation Korean-American mothers of children with autism were included in the study. The data was collected using semi-structured interviews in Korean. Results: The main five factors (i.e., cultural beliefs and values, language barriers, complex emotions, immigration and navigating systems, and facilitators and assets) that mainly influence the diagnosis process were identified through thematic analysis. Conclusion: Dynamics are interactive within and between the factors, influencing the entire diagnostic process by either delaying or facilitating the identification of a child's autism and the provision of treatment.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

Signal transducer and activator of transcription 3 (STAT3) regulates cell growth, cell survival, angiogenesis, metastasis of cancer cells, and cancer immune evasion by regulating gene expression as a transcription factor. However, the effect of STAT3 on translation is almost unknown. We demonstrated that STAT3 acts as a trans‐acting factor for MLST8 gene expression and the protein level of mLST8, a core component of mechanistic target of rapamycin complex 1 and 2 (mTORC1/2), positively regulates the mTORC1/2 downstream pathways. Suppression of STAT3 by siRNA attenuated 4E‐BP1 phosphorylation, cap‐dependent translation, and cell proliferation in a variety of cancer cells. In HCT116 cells, STAT3 knockdown‐induced decreases in 4E‐BP1 and AKT phosphorylation levels were further attenuated by MLST8 knockdown or recovered by mLST8 overexpression. STAT3 knockdown‐induced G2/M phase arrest was partially restored by co‐knockdown of 4EBP1, and the attenuation of cell proliferation was enhanced by the expression of an mTORC1‐mediated phosphorylation‐defective mutant of 4E‐BP1. ChIP and promoter mapping using a luciferase reporter assay showed that the −951 to −894 bp of MLST8 promoter seems to include STAT3‐binding site. Overall, these results suggest that STAT3‐driven MLST8 gene expression regulates cap‐dependent translation through 4E‐BP1 phosphorylation in cancer cells.

Abstract Background The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care. Methods This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA. Results Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists. Conclusions TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients.

Abstract Background Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Methods Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. Results Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. Conclusions Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori–induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori–infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori–infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori–infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori–infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori–infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection. Keywords: Apoptosis, Gastric epithelial cells, Helicobacter pylori, Panax ginseng

Disruption of apoptosis leads to cancer cell progression; thus, anticancer agents target apoptosis of cancer cells. Reactive oxygen species (ROS) induce apoptosis by activating caspases and caspase-dependent DNase, leading to DNA fragmentation. ROS increase the expression of apoptotic protein Bax, which is mediated by activation of nuclear factor-κB (NF--κB). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of endogenous ROS, and its activation is involved in apoptosis. Lutein, an oxygenated carotenoid and known antioxidant, is abundant in leafy dark green vegetables, such as spinach and kale, and in yellow-colored foods, such as corn and egg yolk. High amounts of lutein increase ROS levels and exhibit anticancer activity. However, its anticancer mechanism remains unclear. This study aimed to determine whether lutein activates NADPH oxidase to produce ROS and induce apoptosis in gastric cancer AGS cells. Lutein increased ROS levels and promoted the activation of NADPH oxidase by increasing the translocation of NADPH oxidase subunit p47 phox to the cell membrane. It increased NF-κB activation and apoptotic indices, such as Bax, caspase-3 cleavage, and DNA fragmentation, and decreased Bcl-2, cell viability, and colony formation in AGS cells. The specific NADPH oxidase inhibitor ML171, and the known antioxidant N-acetyl cysteine reversed lutein-induced cell death, DNA fragmentation, and NF-κB DNA-binding activity in AGS cells. These results suggest that lutein-induced ROS production is dependent on NADPH oxidase, which mediates NF-κB activation and apoptosis in gastric cancer AGS cells. Therefore, lutein supplementation may be beneficial for increasing ROS-mediated apoptosis in gastric cancer cells.

The proteomics data included in this article supplement the research article titled “Predictive protein markers for the severity of depression in mood disorders: A preliminary trans-diagnostic approach study (manuscript ID: JPSYCHIATRES-D-20-00437).” Plasma protein was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This data article included 370 plasma protein profiles expressed in patients with bipolar II disorder (BD-II) and major depressive disorder (MDD). The tables present the comparison of protein expressions between BD-II and MDD, and the relationship between the severity of the depressive symptoms and protein expression. In addition, details of results adjusting the use of each psychotropic medication (antipsychotics, mood stabilizers, and antidepressants) for 20 proteins that showed a significant relationship with the severity of the depressive symptom were presented in the table. Results of the bioinformatics analysis of proteins, which were significantly related to the severity of depressive symptom, are presented. The blood protein profiles and the results of the analyses presented in this data article provide detailed information on the proteins associated with mood disorders, and could be used as the basis for further mass spectrometry studies in psychiatric disorders.

Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1–3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Iba1) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1–3 region 2 days later and granule cell death in hippocampal dentate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5-minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.

Leptin is a pluripotent peptide hormone produced mainly by adipocytes, as well as by other tissues such as the stomach. Leptin primarily acts on the central nervous system, particularly the hypothalamus, where this hormone regulates energy homeostasis and neuroendocrine function. Owing to this, disruption of leptin signaling has been linked with numerous pathological conditions. Recent studies have also highlighted the diverse roles of leptin in the digestive system including immune regulation, cell proliferation, tissue healing, and glucose metabolism. Of note, leptin acts differently under physiological and pathological conditions. Here, we review the current knowledge on the functions of leptin and its downstream signaling in the gastrointestinal tract and accessory digestive organs, with an emphasis on its physiological and pathological implications. We also discuss the current therapeutic uses of recombinant leptin, as well as its limitations.

Acute pancreatitis is a common clinical condition with increasing the proinflammatory mediators, including interleukin-6 (IL-6). Obesity is a negative prognostic factor in acute pancreatitis. Obese patients with acute pancreatitis have a higher systemic inflammatory response rate. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Cerulein, a cholecystokinin analog, induces calcium (Ca2+) overload, oxidative stress, and IL-6 expression in pancreatic acinar cells, which are hallmarks of acute pancreatitis. A recent study showed that resistin aggravates the expression of inflammatory cytokines in cerulein-stimulated pancreatic acinar cells. We aimed to investigate whether resistin amplifies cerulein-induced IL-6 expression and whether astaxanthin (ASX), an antioxidant carotenoid with anti-inflammatory properties, inhibits ceruelin/resistin-induced IL-6 expression in pancreatic acinar AR42J cells. We found that resistin enhanced intracellular Ca2+ levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF-κB activity, and IL-6 expression in cerulein-stimulated AR42J cells, which were inhibited by ASX in a dose-dependent manner. The calcium chelator BAPTA-AM inhibited cerulein/resistin-induced NADPH oxidase activation and ROS production. Antioxidant N-acetyl cysteine (NAC) and ML171, a specific NADPH oxidase 1 inhibitor, suppressed cerulein/resistin-induced ROS production, NF-κB activation, and IL-6 expression. In conclusion, ASX inhibits IL-6 expression, by reducing Ca2+ overload, NADPH oxidase-mediated ROS production, and NF-κB activity in cerulein/resistin-stimulated pancreatic acinar cells. Consumption of ASX-rich foods could be beneficial for preventing or delaying the incidence of obesity-associated acute pancreatitis.

In alcoholic pancreatitis, alcohol increases gut permeability, which increases the penetration of endotoxins, such as lipopolysaccharides (LPS). LPS act as clinically significant triggers to increase pancreatic damage in alcoholic pancreatitis. Ethanol or LPS treatment increases reactive oxygen species (ROS) production in pancreatic acinar cells. ROS induce inflammatory cytokine production in pancreatic acinar cells, leading to pancreatic inflammation. The nuclear erythroid-2-related factor 2 (Nrf2) pathway is activated as a cytoprotective response to oxidative stress, and induces the expression of NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Lycopene exerts anti-inflammatory and antioxidant effects in various cells. We previously showed that lycopene inhibits NADPH oxidase to reduce ROS and IL-6 levels, and zymogene activation in ethanol or palmitoleic acid-treated pancreatic acinar cells. In this study, we examined whether lycopene inhibits IL-6 expression by activating the Nrf2/NQO1-HO-1 pathway, and reducing intracellular and mitochondrial ROS levels, in ethanol and LPS-treated pancreatic AR42J cells. Lycopene increased the phosphorylated and nuclear-translocated Nrf2 levels by decreasing the amount of Nrf2 sequestered in the cytoplasm via a complex formation with Kelch-like ECH1-associated protein 1 (Keap1). Using exogenous inhibitors targeting Nrf2 and HO-1, we showed that the upregulation of activated Nrf2 and HO-1 results in lycopene-induced suppression of IL-6 expression and ROS production. The consumption of lycopene-rich foods may prevent the development of ethanol and LPS-associated pancreatic inflammation by activating Nrf2-mediated expression of NQO1 and HO-1, thereby decreasing ROS-mediated IL-6 expression in pancreatic acinar cells.

PURPOSE: To identify factors influencing psychosocial adjustment in patients with surgical removal of benign breast tumor. METHODS: With a survey design, data were collected using the Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), Body Image Scale, Physical Discomfort Scale, and Family Support Scale with patients who had had surgical removal of a benign breast tumor from September to November 2017. Data were analysed with descriptive statistics, t-test, ANOVA, Pearson's correlation coefficients, and stepwise multiple regression. RESULTS: The mean scores for physical discomfort, body image, family support, and psychosocial adjustment were 1.57±0.51, 0.37±0.64, 3.62±0.67, and 4.00±0.45, respectively. Family support, body image, physical discomfort, number of surgical removal of benign breast tumor (twice), and cancer insurance status (yes) were verified as factors influencing psychosocial adjustment. These factors accounted for 57.4% of psychosocial adjustment. CONCLUSION: In this study, family support, body image, and physical discomfort were identified as significant predictors of psychosocial adjustment. Therefore, this study can be used as fundamental data to develop nursing intervention strategies in order to increase psychosocial adjustment in patients with surgical removal of a benign breast tumor.

Lutein is a xanthophyll carotenoid obtained from various foods, such as dark green leafy vegetables and egg yolk. Lutein has antioxidant activity and scavenges reactive oxygen species such as singlet oxygen and lipid peroxy radicals. Oxidative stress activates inflammatory mediators, leading to the development of metabolic and inflammatory diseases. Thus, recent basic and clinical studies have investigated the anti-inflammatory effects of lutein based on its antioxidant activity and modulation of oxidant-sensitive inflammatory signaling pathways. Lutein suppresses activation of nuclear factor-kB and signal transducer and activator of transcription 3, and induction of inflammatory cytokines (interleukin-1β, interleukin-6, monocyte chemoattratant protein-1, tumor necrosis factor-α) and inflammatory enzymes (cyclooxygenase-2, inducible nitric oxide synthase). It also maintains the content of endogenous antioxidant (glutathione) and activates nuclear factor erythroid 2–related factor 2 (Nrf2) and Nrf2 signaling-related antioxidant enzymes (hemeoxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase). In this review, we have discussed the current knowledge regarding the anti-inflammatory function of lutein against inflammatory diseases in various organs, including neurodegenerative disorders, eye diseases, diabetic retinopathy, osteoporosis, cardiovascular diseases, skin diseases, liver injury, obesity, and colon diseases.

The dynamics of infectious diseases are greatly influenced by the movement of both susceptible and infected hosts. To accurately represent disease dynamics among a mobile host population, detailed movement models have been coupled with disease transmission models. However, a number of different host movement models have been proposed, each with their own set of assumptions and results that differ from the other models. Here, we compare two movement models coupled to the same disease transmission model using network analyses. This application of network analysis allows us to evaluate the fit and accuracy of the movement model in a multilevel modeling framework with more detail than established statistical modeling fitting methods. We used data that detailed mobile pastoralists' movements as input for 100 stochastic simulations of a Spatio-Temporal Movement (STM) model and 100 stochastic simulations of an Individual Movement Model (IMM). Both models represent dynamic movement and subsequent contacts. We generated networks in which nodes represent camps and edges represent the distance between camps. We simulated pathogen transmission over these networks and tested five network metrics-strength, betweenness centrality, three-step reach, density, and transitivity-to determine which could predict disease simulation outcomes and thereby be used to correlate model simulation results with disease transmission simulations. We found that strength, network density, and three-step reach of movement model results correlated with the final epidemic size of outbreak simulations. Betweenness centrality only weakly correlated for the IMM model. Transitivity only weakly correlated for the STM model and time-varying IMM model metrics. We conclude that movement models coupled with disease transmission models can affect disease transmission results and should be carefully considered and vetted when modeling pathogen spread in mobile host populations. Strength, network density, and three-step reach can be used to evaluate movement models before disease simulations to predict final outbreak sizes. These findings can contribute to the analysis of multilevel models across systems.

BACKGROUND:The duration of antidepressant use affects the treatment of depression. Using the National Health Insurance database, which covers almost the entire national population, we verified the factors associated with the inadequate short-term use of initially prescribed antidepressants and their effects on the relapse and recurrence of depressive episodes. METHODS:There were 752,190 patients included who had been newly prescribed antidepressants in 2012 with the diagnosis of depressive disorder. They were followed-up until December 31, 2015. They were classified as short-term and long-term antidepressant users depending on whether they used a specific initial antidepressant for at least four weeks. Sociodemographic, clinical, and medical utilization factors affecting the duration of antidepressant use were investigated. We also identified whether the duration of antidepressant use affected the risk of relapse and recurrence, which was defined by the restarting of antidepressants. RESULTS:Initial antidepressants were taken for less than 28 days by 458,057 (60.84%) patients. Tricyclic antidepressants were used as the initial antidepressant more frequently than selective serotonin reuptake inhibitors (64.5% versus 19.3%). The type of initial antidepressant, polypharmacy, psychiatric and medical comorbidities, type of insurance coverage, and type of medical institution visited were associated with short-term use. Short-term use marginally increased the risk of relapse and recurrence of depressive episodes (Hazard ratio: 1.06, 95% confidence intervals 1.048-1.075). CONCLUSIONS:Short-term antidepressant use is widespread in Korea, and assessment in various aspects are necessary to set proper treatment plans.

BackgroundThe epidemiology of pharmaceutically treated depression (PTD) and treatment resistant depression (TRD) is largely unknown in South Korea. The aim of this study was to develop a greater understanding of the characteristics of PTD and TRD in nearly the entire adult population in South Korea using the Health Insurance Review and Assessment Service (HIRA).MethodDiagnostic codes and prescription data for South Korean adults were extracted from the HIRA. Subjects were included in the PTD cohort if they received at least one prescription for antidepressants and were diagnosed with depression. TRD was defined as PTD having two or more regimen failures of antidepressants or antipsychotics.ResultsIn 2012, there were 41,256,396 adults in South Korea with 834,694 meeting the criteria for PTD (2.0%). Among subjects with PTD, 57% stopped treatment in less than 28 days of antidepressant supply. Tricyclic and tetracyclic antidepressants were the most frequently used antidepressants as a first-line regimen for PTD (44.3% of PTD) followed by selective serotonin reuptake inhibitors (32.1% of PTD). Results also indicated that 34,812 subjects developed TRD (4.2% of PTD). Median PTD and TRD durations were 28 and 623 days respectively. Proportions of psychiatric and non-psychiatric comorbidities were higher in TRD cases than in PTD cases that were not treatment resistant.ConclusionsDespite a small proportion of patients with TRD, the prolonged duration of illness and higher comorbidity implies the need for better treatment.

House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant nutrient with anti-inflammatory activity. The present study aimed to investigate whether HDM induce intracellular and mitochondrial ROS production, TLR4 activation, and pro-inflammatory cytokine expression (IL-6 and IL-8) in respiratory epithelial A549 cells. Additionally, we examined whether lycopene inhibits HDM-induced alterations in A549 cells. The treatment of A549 cells with HDM activated TLR4, induced the expression of IL-6 and IL-8, and increased intracellular and mitochondrial ROS levels. TAK242, a TLR4 inhibitor, suppressed both HDM-induced ROS production and cytokine expression. Furthermore, lycopene inhibited the HDM-induced TLR4 activation and cytokine expression, along with reducing the intracellular and mitochondrial ROS levels in HDM-treated cells. These results collectively indicated that the HDM induced TLR4 activation and increased intracellular and mitochondrial ROS levels, thus resulting in the induction of cytokine expression in respiratory epithelial cells. The antioxidant lycopene could inhibit HDM-induced cytokine expression, possibly by suppressing TLR4 activation and reducing the intracellular and mitochondrial ROS levels in respiratory epithelial cells.

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells.

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.

Oxidative stress is a major risk factor for acute pancreatitis. Reactive oxygen species (ROS) mediate expression of inflammatory cytokines such as interleukin-6 (IL-6) which reflects the severity of acute pancreatitis. The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway is activated to induce the expression of antioxidant enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) as a cytoprotective response to oxidative stress. In addition, binding of Kelch-like ECH-associated protein 1 (Keap1) to Nrf2 promotes degradation of Nrf2. Docosahexaenoic acid (DHA)—an omega-3 fatty acid—exerts anti-inflammatory and antioxidant effects. Oxidized omega-3 fatty acids react with Keap1 to induce Nrf2-regulated gene expression. In this study, we investigated whether DHA reduces ROS levels and inhibits IL-6 expression via Nrf2 signaling in pancreatic acinar (AR42J) cells stimulated with cerulein, as an in vitro model of acute pancreatitis. The cells were pretreated with or without DHA for 1 h and treated with cerulein (10−8 M) for 1 (ROS levels, protein levels of NQO1, HO-1, pNrf2, Nrf2, and Keap1), 6 (IL-6 mRNA expression), and 24 h (IL-6 protein level in the medium). Our results showed that DHA upregulates the expression of NQO1 and HO-1 in cerulein-stimulated AR42J cells by promoting phosphorylation and nuclear translocation of Nrf2. DHA increased interaction between Keap1 and Nrf2 in AR42J cells, which may increase Nrf2 activity by inhibiting Keap1-mediated sequestration of Nrf2. In addition, DHA-induced expression of NQO1 and HO-1 is related to reduction of ROS and IL-6 levels in cerulein-stimulated AR42J cells. In conclusion, DHA inhibits ROS-mediated IL-6 expression by upregulating Nrf2-mediated expression of NQO1 and HO-1 in cerulein-stimulated pancreatic acinar cells. DHA may exert positive modulatory effects on acute pancreatitis by inhibiting oxidative stress and inflammatory cytokine production by activating Nrf2 signaling in pancreatic acinar cells.

Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are differently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified differentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLCγ1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the effects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLCγ. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLCγ1, Cdc42, and ROCK1.

Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling through modulation of several intracellular targets of interleukins in immune cells. In the present study, we report that LRRK2 phosphorylates RCAN1 (RCAN1-1S) and is markedly up-regulated during interleukin-1β (IL-1β) treatment. During IL-1β treatment, LRRK2-mediated phosphorylation of RCAN1 promoted the formation of protein complexes, including that between Tollip and RCAN1. LRRK2 decreased binding between Tollip and IRAK1, which was accompanied by increased formation of the IRAK1-TRAF6 complex. TAK1 activity was significantly enhanced by LRRK2. Furthermore, LRRK2 enhanced transcriptional activity of NF-κB and cytokine IL-8 production. These findings suggest that LRRK2 might be important in positively modulating IL-1β-mediated signaling through selective phosphorylation of RCAN1.

According to the Foreign Agricultural Service of the United States Department of Agriculture, worldwide consumption of fresh grapefruit in 2014/15 increased from 4.2 million to 5.2 million metric tons. China, which is the largest producer of grapefruit, was largely responsible for the increase. In South Korea, however, the state of Florida in the United States has traditionally dominated the grapefruit market. The South Korean grapefruit market has been increasing in recent years and is expected to keep growing. The industry in Florida now faces fierce competition from other suppliers with lower import prices and different harvest seasons. This 5-page fact sheet written by Yan Heng, Hyeyoung Kim, and Lisa House and published by the Food and Resource Economics Department aims to provide an overview of the grapefruit market in South Korea and evaluate the potential of this market for Florida fresh grapefruit producers.­http://edis.ifas.ufl.edu/fe1003

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Background/AimsThe most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.MethodsNinety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).ResultsThe 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P

ObjectivesThe purpose of this study was to design a prediction model that explains the characteristics of elderly adults at risk of malnutrition.MethodsData were obtained from a large data set, 2008 Korean Elderly Survey, in which the data of 15,146 subjects were entered. With nutritional status a target variable, the input variables included the demographic and socioeconomic status of participants. The data were analyzed by using the SPSS Clementine 12.0 program's feature selection node to select meaningful variables.ResultsAmong the C5.0, C&R Tree, QUEST, and CHAID models, the highest predictability was reported by C&R Tree with the accuracy rate of 77.1%. The presence of more than two comorbidities, living alone status, having severe difficulty in daily activities, and lower perceived economic status were identified as risk factors of malnutrition in elderly.ConclusionsA reliable decision support model was designed to provide accurate information regarding the characteristics of elderly individuals with malnutrition. The findings demonstrated the good feasibility of data mining when used for a large community data set and its value in assisting health professionals and local decision makers to come up with effective strategies for achieving public health goals.

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

Oxcarbazepine, an antiepileptic drug, has been reported to modulate voltage-dependent sodium channels, and it is commonly used in epilepsy treatment. In this study, we investigated the neuroprotective effect of oxcarbazepine in the hippocampus after transient ischemia in gerbils. Gerbils randomly received oxcarbazepine 100 or 200 mg/kg before and after transient ischemia. We examined its neuroprotective effect in the cornu ammonis 1 subfield of the gerbil hippocampus at 5 days after transient ischemia by using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-Jade B histofluorescence staining for neuroprotection, and by using glial fibrillary protein and ionized calcium-binding adapter molecule 1 immunohistochemistry for reaction of astrocytes and microglia, respectively. Pre- and post-treatment with 200 mg/kg of oxcarbazepine, but not 100 mg/kg of oxcarbazepine, protected pyramidal neurons of the cornu ammonis 1 subfield from transient ischemic damage. In addition, pre- and post-treatment with oxcarbazepine (200 mg/kg) significantly ameliorated astrocytes and microglia activation in the ischemic cornu ammonis 1 subfield. In brief, our current results indicate that post-treatment as well as pre-treatment with 200 mg/kg of oxcarbazepine can protect neurons from ischemic insults via attenuation of the glia reaction.

Autophagy is a lysosomal pathway that degrades and recycles unused or dysfunctional cell components as well as toxic cytosolic materials. Basal autophagy favors cell survival. However, the aberrant regulation of autophagy can promote pathological conditions. The autophagy pathway is regulated by several cell-stress and cell-survival signaling pathways that can be targeted for the purpose of disease control. In experimental models of disease, the carotenoid astaxanthin has been shown to modulate autophagy by regulating signaling pathways, including the AMP-activated protein kinase (AMPK), cellular homolog of murine thymoma virus akt8 oncogene (Akt), and mitogen-activated protein kinase (MAPK), such as c-Jun N-terminal kinase (JNK) and p38. Astaxanthin is a promising therapeutic agent for the treatment of a wide variety of diseases by regulating autophagy.

Information on production methods (genetic modification (GM) or organic production) and locations (country of origin) are commonly found on food package labels. Both pieces of information may be used as a proxy for food safety and (perceived) quality by consumers. Our study investigates the interactive effects between information on production method and country-of-origin labeling (COOL) by conducting choice experiments in the European Union, United States and Japan. This study also investigates the effect of information about potential benefits of biotechnology on consumer acceptance of GM foods. Results indicate that consumers preferred GM foods produced domestically to GM foods imported from foreign countries, and individuals with information on consumer benefits, producer benefits, and environmental benefits were willing to pay more than individuals without information in some cases, but the effect of information varied by type of information, location, and the country of origin of the products.

Eosinophil cationic protein (ECP), a cytotoxic protein contained in eosinophils granules, can contribute to various inflammatory responses. Although Helicobacter pylori infection increases infiltration of eosinophils, the mechanisms of eosinophil degranulation by H. pylori infection are largely unknown. The goal of this study was to investigate the role of H. pylori outer membrane vesicles (OMVs) in modulating eosinophil degranulation. We found that eosinophils treated with H. pylori OMVs released significantly more ECP compared with untreated controls. In addition, eosinophils cocultured with OMV-preexposed primary gastric epithelial cells exhibited significantly increased ECP release. Similarly, eosinophils cocultured with culture supernatant (CM) from primary gastric epithelial cells exposed to OMVs (OMV-CM) released significantly higher amounts of ECP compared with eosinophils cocultured with CM from unexposed control cells. Furthermore, OMVs and OMV-CM both induced the upregulation of ICAM-1 on gastric epithelial cells and β2 integrin CD11b on eosinophils. In addition, both transduction of ICAM-1 shRNA into gastric epithelial cells and treatment with neutralizing mAbs to CD18 significantly decreased OMV-mediated or OMV-CM-mediated release of ECP. These results suggest that the eosinophil degranulation response to H. pylori OMVs occurs via a mechanism that is dependent on both β2 integrin CD11/CD18 and ICAM-1.

Foot-and-mouth disease virus (FMDV) causes morbidity and mortality in a range of animals and threatens local economies by acting as a barrier to international trade. The outbreak in the United Kingdom in 2001 that cost billions to control highlighted the risk that the pathogen poses to agriculture. In response, several mathematical models have been developed to parameterize and predict both transmission dynamics and optimal disease control. However, a lack of understanding of the multi-strain etiology prevents characterization of multi-strain dynamics. Here, we use data from FMDV serology in an endemic setting to probe strain-specific transmission and immunodynamics. Five serotypes of FMDV affect cattle in the Far North Region of Cameroon. We fit both catalytic and reverse catalytic models to serological data to estimate the force of infection and the rate of waning immunity, and to detect periods of sustained transmission. For serotypes SAT2, SAT3, and type A, a model assuming life-long immunity fit better. For serotypes SAT1 and type O, the better-fit model suggests that immunity may wane over time. Our analysis further indicates that type O has the greatest force of infection and the longest duration of immunity. Estimates for the force of infection were time-varying and indicated that serotypes SAT1 and O displayed endemic dynamics, serotype A displayed epidemic dynamics, and SAT2 and SAT3 did not sustain local chains of transmission. Since these results were obtained from the same population at the same time, they highlight important differences in transmission specific to each serotype. They also show that immunity wanes at rates specific to each serotype, which influences patterns of local persistence. Overall, this work shows that viral serotypes can differ significantly in their epidemiological and immunological characteristics. Patterns and processes that drive transmission in endemic settings must consider complex viral dynamics for accurate representation and interpretation.

Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori-) infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA), a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation), levels of reactive oxygen species (ROS), NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits), activation of redox-sensitive transcription factors (NF-κB, AP-1), expression of oncogenes (β-catenin, c-myc), and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.

Background: Korean Panax Red Ginseng (KPRG) is known to enhance endothelium-dependent vasorelaxation by activating eNOS. Activation of Rho-associated kinase (ROCK) is implicated in endothelial dysfunction in part through destabilization of eNOS mRNA. This study, a randomized, double-blind, placebo-controlled, crossover trial, is aimed to analyze the effect of KPRG on endothelial function, arterial stiffness, and ROCK activity of peripheral blood mononuclear cells (PBMC) in patients with coronary artery disease (CAD). Methods: Patients (n=20, 12 males, 62.5 yrs) with stable angina (multi-vessel disease: n=10) were treated alternatively with either KPRG (3g/d) or placebo (starch, 3g/d) for 10 weeks (washout period for 4 wks). Measurements of flow mediated dilation (FMD) and nitroglycerine mediated dilation (NMD) on the brachial artery and collection of peripheral venous blood for the biochemical study were performed at day 0 (baseline) and after completion (endpoint) of each treatment. Activity of ROCK of PBMC was assessed by analyzing phospho-Thr853 in the myosin binding subunit (MBS) of myosine light chain phosphatase with use of Western blot, and was expressed as the % ratio of phospho-Thr853-MBS/total MBS at endpoint versus baseline. Patients were classified into low (5%) FMD group (n=9). Results: Treatment with KPRG significantly increased FMD in low FMD group (3.49±0.35% vs 5.50±0.72%, p=0.013), but not in high FMD group. Brachial ankle pulse wave velocity (ba-PWV), measured by VP2000, tends to be decreased by KPRG (1770±185 vs. 1499±95, p=0.05. There was no significant changes in nitroglycerine mediated dilation after each drug treatment in both patient groups. Treatment with KPRG significantly decreased ROCK activity in PBMC of CAD patients (n=6) by 23.9±3.01 as compared with the baseline (p