c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

Presence of an ultra-small microbiome in fermented cabbages.

Background: Ultramicrobacteria (UMB), also known as ultra-small bacteria, are tiny bacteria with a size less than 0.1 µm3. They have a high surface-to-volume ratio and are found in various ecosystems, including the human body. UMB can be classified into two types: one formed through cell contraction and the other that maintains a small size. The ultra-small microbiome (USM), which may contain UMB, includes all bacteria less than 0.2 µm in size and is difficult to detect with current methods. However, it poses a potential threat to food hygiene, as it can pass through sterilization filters and exist in a viable but non-culturable (VBNC) state. The data on the USM of foods is limited. Some bacteria, including pathogenic species, are capable of forming UMB under harsh conditions, making it difficult to detect them through conventional culture techniques. Methods: The study described above focused on exploring the diversity of USM in fermented cabbage samples from three different countries (South Korea, China, and Germany). The samples of fermented cabbage (kimchi, suancai, and sauerkraut) were purchased and stored in chilled conditions at approximately 4 °C until filtration. The filtration process involved two steps of tangential flow filtration (TFF) using TFF cartridges with different pore sizes (0.2 µm and 100 kDa) to separate normal size bacteria (NM) and USM. The USM and NM isolated via TFF were stored in a refrigerator at 4 °C until DNA extraction. The extracted DNA was then amplified using PCR and the full-length 16S rRNA gene was sequenced using single-molecule-real-time (SMRT) sequencing. The transmission electron microscope (TEM) was used to confirm the presence of microorganisms in the USM of fermented cabbage samples. Results: To the best of our knowledge, this is the first study to identify the differences between USM and NM in fermented cabbages. Although the size of the USM (average 2,171,621 bp) was smaller than that of the NM (average 15,727,282 bp), diversity in USM (average H' = 1.32) was not lower than that in NM (average H' = 1.22). In addition, some members in USM probably underwent cell shrinkage due to unfavorable environments, while others maintained their size. Major pathogens were not detected in the USM in fermented cabbages. Nevertheless, several potentially suspicious strains (genera Cellulomonas and Ralstonia) were detected. Our method can be used to screen food materials for the presence of USM undetectable via conventional methods. USM and NM were efficiently separated using tangential flow filtration and analyzed via single-molecule real-time sequencing. The USM of fermented vegetables exhibited differences in size, diversity, and composition compared with the conventional microbiome. This study could provide new insights into the ultra-small ecosystem in fermented foods, including fermented cabbages.

Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice.

Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.

IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation.

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Serum high-mobility group box 1 protein level correlates with the lowest SaO2 in patients with sleep apnea: a preliminary study / Nível sérico da proteína de alta mobilidade do grupo Box-1 está associado à SaO2 mais baixa em pacientes com apneia do sono: um estudo preliminar

Abstract Introduction: Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea. Objective: We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients. Methods: We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay. Results: Serum high-mobility group box 1 protein level was 56.16 ± 30.33 ng/mL in chronic intermittent hypoxia and 18.63 ± 6.20 ng/mL in control mice (p<0.05). The mean apnea-hypopnea index and respiratory disturbance index values of enrolled obstructive sleep apnea patients were 50.35 ± 27.96 and 51.56 ± 28.53, respectively, and the mean serum high-mobility group box 1 protein level was 30.13 ± 19.97 ng/mL. The apnea-hypopnea index and respiratory disturbance index were not significantly correlated with the serum high-mobility group box 1 protein level (p>0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaO2) (p<0.05). Conclusion: High-mobility group box 1 protein may be involved in the pathogenesis of obstructive sleep apnea, and the possibility of this protein being a useful biologic marker in obstructive sleep apnea should be further evaluated.

Resumo Introdução: O nível sérico da proteína de alta mobilidade do grupo Box-1 está relacionado com a gravidade da apneia obstrutiva do sono. Objetivo: Avaliar o uso do nível sérico da proteína de alta mobilidade do grupo Box-1 como um marcador biológico em pacientes com apneia obstrutiva do sono. Método: Geramos um modelo murino de hipóxia intermitente crônica que imita a apneia obstrutiva do sono em humanos. Pacientes com apneia obstrutiva do sono que fizeram polissonografia foram incluídos prospectivamente. Amostras de soro foram obtidas de camundongos e pacientes com apneia obstrutiva do sono e o nível sérico da proteína de alta mobilidade do grupo Box-1 foi medido por enzyme-linked immunosorbent assay. Resultados: O nível sérico da proteína de alta mobilidade do grupo Box-1 foi 56,16 ± 30,33 ng/mL em hipóxia intermitente crônica e 18,63 ± 6,20 ng/mL em camundongos controle (p < 0,05). Os valores médios do índice de apneia-hipopneia e do índice de distúrbio respiratório nos pacientes com apneia obstrutiva do sono foram 50,35 ± 27,96 e 51,56 ± 28,53, respectivamente, e o nível médio da proteína de alta mobilidade do grupo Box-1 foi 30,13 ± 19,97 ng/mL. O índice de apneia-hipopneia e o índice de distúrbio respiratório não foram significantemente associados com o nível da proteína de alta mobilidade do grupo Box-1 p> 0,05). Em vez disso, esse nível de proteína foi significantemente associado com o valor mais baixo da concentração arterial de oxigênio (SaO2) (p <0,05). Conclusão: A proteína de alta mobilidade do grupo Box-1 pode estar envolvida na patogênese da apneia obstrutiva do sono e a possibilidade de que essa proteína possa ser um marcador biológico útil na apneia obstrutiva do sono deve ser avaliada mais detalhadamente.

No evidence of delay in colorectal cancer diagnosis during the COVID-19 pandemic in Gwangju and Jeonnam, Korea

Objectives: We evaluated whether the coronavirus disease 2019 (COVID-19) pandemic caused delays in the diagnosis and treatment of colorectal cancer (CRC) in Korea, where there have been no regional or hospital lockdowns during the pandemic period. Methods: Data on CRC patients (n=1,445) diagnosed in Gwangju Metropolitan City and Jeonnam Province between January 2019 and December 2021 were assessed. The stage at the time of CRC diagnosis, route to diagnosis, time to initial cancer treatment, and length of hospital admission were compared before and during the COVID-19 pandemic. Logistic regression was also performed to identify factors associated with the risk for diagnosis in an advanced stage. Results: No negative effects indicating a higher CRC stage at diagnosis or delayed treatment during the pandemic were observed. Instead, the risk for an advanced stage at diagnosis (TNM stage III/IV) decreased in CRC patients diagnosed during the pandemic (odds ratio, 0.768; 95% confidence interval, 0.647 to 0.911). No significant differences in the interval from diagnosis to operation or chemotherapy were observed. Conclusion: No negative effects on CRC diagnosis and treatment were found until the end of 2021, which may be related to the small magnitude of the COVID-19 epidemic, the absence of a lockdown policy in Korea, and the rebound in the number of diagnostic colonoscopy procedures in 2021.

Serum high-mobility group box 1 protein level correlates with the lowest SaO2 in patients with sleep apnea: a preliminary study.

INTRODUCTION: Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea. OBJECTIVE: We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients. METHODS: We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay. RESULTS: Serum high-mobility group box 1 protein level was 56.16 ±â€¯30.33 ng/mL in chronic intermittent hypoxia and 18.63 ±â€¯6.20 ng/mL in control mice (p < 0.05). The mean apnea-hypopnea index and respiratory disturbance index values of enrolled obstructive sleep apnea patients were 50.35 ±â€¯27.96 and 51.56 ±â€¯28.53, respectively, and the mean serum high-mobility group box 1 protein level was 30.13 ±â€¯19.97 ng/mL. The apnea-hypopnea index and respiratory disturbance index were not significantly correlated with the serum high-mobility group box 1 protein level (p > 0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaO2) (p < 0.05). CONCLUSION: High-mobility group box 1 protein may be involved in the pathogenesis of obstructive sleep apnea, and the possibility of this protein being a useful biologic marker in obstructive sleep apnea should be further evaluated.

Kinetic Modeling of Slightly Acidic Electrolyzed Water Decay Characteristics in Fresh Cabbage Disinfection Against Human Norovirus.

To consistently disinfect fresh vegetables efficiently, the decay of disinfectants such as chlorine, electrolyzed oxidizing water (EOW), ozonated water, and plasma-activated water during the disinfection maintenance stage needs to be understood. The aim of our study was to evaluate the changes in the inactivation kinetics of slightly acidic electrolyzed water (SAEW) against human norovirus (HuNoV), based on the cabbage-to-SAEW ratio. After disinfection of fresh cabbage with disinfected SAEW solution, SAEW samples were collected and analyzed for physicochemical properties such as pH, available chlorine concentrations (ACCs), and oxidation-reduction potential (ORP). SAEW virucidal effects were evaluated. We confirmed the decay of post-disinfection SAEW solution and demonstrated the different patterns of the decay kinetic model for HuNoV GI.6 and GII.4. In addition, the goodness of fit of the tested models based on a lower Akaike information criterion, root-mean-square error (RMSE), and residual sum of squares (RSS) was close to zero. In particular, the change in both the HuNoV GI.6 and GII.4 inactivation exhibited a strong correlation with the changes in the ACC of post-disinfection SAEW. These findings demonstrate that physicochemical parameters of SAEW play a key role in influencing the kinetic behavior of changes in the disinfection efficiency of SAEW during the disinfection process. Therefore, to optimize the efficiency of SAEW, it is necessary to optimize the produce-to-SAEW ratio in future studies.

Validation of the Korean Version of the COVID-19 Phobia Scale (K-C19PS).

The purpose of this study was to evaluate the reliability and validity of a Korean version of the 20-item COVID-19 phobia tool, which was developed through a translation-reverse translation process. These data were collected from 226 persons using a self-reported questionnaire. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, for 19 out of 20 items, the item-level convergence and differential validity were confirmed. In addition, the reliability and validity of the tool as a whole has been verified. For the subscales, Cronbach's α was 0.90 for psychological, 0.87 for psychosomatic, 0.86 for economic, and 0.87 for social. Appropriate reliability was confirmed. Correlations between the COVID-19 phobia tool and fear of COVID-19 confirmed validity. The Korean version of the COVID-19 phobia tool is an appropriate scale for measuring the fear of COVID-19 and relevant psychological characteristics. Therefore, future studies in areas such as health and nursing could use this tool as required.

Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis.

The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid-Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.

Determination of Transfer Patterns of Pectobacterium carotovorum subsp. carotovorum Planktonic Cells and Biofilms During Mechanical Cutting of Kimchi Cabbage.

Cross-contamination of Pectobacterium carotovorum subsp. carotovorum (PCC) from a stainless-steel surface to cabbage (Brassica rapa L. subsp. pekinensis) was evaluated. To investigate the PCC transfer pattern from mechanical knife surfaces to cabbage during 100 cuts, two mathematical models (power and logarithmic model) were fitted to the mean log10 detection data from cabbage. Overall, regression analysis determined that the best-fitting regression curves of planktonic cells and detached cells from biofilms transferred onto fresh cabbage were Y = 3.7X-0.41 , RMSE = 0.371 and Y = 4.6X-0.35 , RMSE = 0.254, respectively. For salted cabbage, the best-fit regression curves of planktonic cells and biofilm were Y = 5.8X-0.38 , RMSE = 0.209 and Y = 5.4X-0.23 , RMSE = 0.195, respectively. Our data provide a meaningful indication of the level of PCC cross-contamination.

Effect of clove powder on quality characteristics and shelf life of kimchi paste.

Clove has been shown to extend the shelf life of various foods. This study investigated whether it can prolong the shelf life of kimchi paste. Clove powder at concentrations of 0%, 0.5%, 1%, 1.5%, and 2% was added to kimchi paste, which was then sealed and stored at 10°C for 20 days. Changes in microbial counts, gas composition, sugar and organic acid contents, pH, titratable acidity, and reducing sugar content were evaluated. Adding clove powder inhibited the growth of total aerobic and lactic acid bacteria and delayed changes in O2 and CO 2 concentration and sugar and organic acid contents. It also slowed the decrease in pH, increase in titratable acidity, and changes in reducing sugar content. These results indicate that clove powder effectively prolongs the quality attributes and thus extends the shelf life of kimchi paste.

Difference of stage at cancer diagnosis by socioeconomic status for four target cancers of the National Cancer Screening Program in Korea: Results from the Gwangju and Jeonnam cancer registries.

BACKGROUND: The aim of this study was to evaluate whether stage at cancer diagnosis differed according to patient economic status. METHODS: A total of 10,528 patients with cancer of the stomach, colorectum, breast, or cervix, which are target organs of the Korean National Cancer Screening Program (NCSP; fully implemented in 2005) were extracted from population-based cancer registries. The patients were classified into four groups based on socioeconomic status (SES), as determined using their National Health Insurance (NHI) monthly premium at the time of cancer diagnosis. Cancer stage at diagnosis was defined as early (in situ/local) or late stage (regional/distant) based on the Surveillance, Epidemiology, and End Results (SEER) summary stage. Multivariable logistic regression analysis was performed to estimate the risk of non-local stage using age, residential area, and community deprivation index as covariates. RESULTS: The lowest SES subjects showed significantly higher risks of being diagnosed at a later stage for stomach, colorectal, and female breast cancer, but not for cervical cancer, compared with the highest SES subjects. The estimated ORs were 1.28 (95% CI, 1.10-1.49), 1.29 (95% CI, 1.03-1.61), and 1.35 (95% CI, 1.02-1.81) in the lowest SES subjects with stomach, colorectal, and breast cancer, respectively. CONCLUSIONS: In conclusion, later stage diagnoses of stomach, colon, and female breast cancer are still associated with SES in Korea in the era of the NCSP for the lower SES population.

Integrated micro-optofluidic platform for real-time detection of airborne microorganisms.

We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration.

Draft Genome Sequence of Lactobacillus plantarum wikim18, Isolated from Korean Kimchi.

This report describes the draft genome sequence of Lactobacillus plantarum strain wikim18, isolated from the traditional Korean food kimchi. The reads generated by Ion Torrent PGM were assembled into 327 contigs. RAST annotation of the genome revealed 12 tRNAs and 3,316 protein-coding gene sequences.

Effects of Brown Rice Extract Treated with Lactobacillus sakei Wikim001 on Osteoblast Differentiation and Osteoclast Formation.

Phytic acid (myo-inositol hexakisphosphate) or phytate is considered an anti-nutrient due to the formation of precipitated complexes that strongly reduces the absorption of essential dietary minerals. In this study, brown rice with reduced phytate was made by inoculation with Lactobacillus sakei Wikim001 having high phytase activity. The effects of brown rice extract treated with L. sakei Wikim001 (BR-WK) on osteoblast differentiation and osteoclast formation were investigated. The proliferation of SaOS-2 cells was measured by the MTT assay. Treatment with BR-WK increased cell proliferation by 136% at a concentration of 100 µg/mL. The Alkaline phosphate activity in SaOS-2 cells was 129% higher when BR-WK was processed at a concentration of 100 µg/mL. The proliferation of bone marrow macrophages decreased by nearly 60% in response to treatment with BR-WK. In addition, BR-WK reduced the number of tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells from bone marrow macrophages. These results indicate that BR-WK stimulates bone formation through its positive action on osteoblast differentiation and function and furthermore, decreases osteoclast differentiation.

Lycopene inhibits IL-6 expression in cerulein-stimulated pancreatic acinar cells.

Reactive oxygen species (ROS) are known to be involved in the pathogenesis of acute and chronic pancreatitis. The cholecystokinin (CCK) analog cerulein causes pathophysiological, morphological, and biochemical events similar to those observed in human acute pancreatitis. The oxidant-sensitive transcription factor NF-κB plays a critical role in the development of cerulein pancreatitis by regulating the expression of pro-inflammatory cytokines in the pancreas. Lycopene has an anti-oxidant effect in various cells. In the present study, we investigated whether cerulein induces NF-κB activation and IL-6 expression in pancreatic acinar cells and whether lycopene inhibits these events. NF-κB-DNA-binding activity was determined by electrophoretic mobility shift assay, and mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR analyses. The IL-6 concentration in the medium was determined by enzyme-linked immunosorbent assay. Our results showed that cerulein induced IL-6 expression in a time-dependent manner. NF-κB-DNA-binding activity and intracellular levels of ROS in pancreatic acinar cells were increased by cerulein. Lycopene inhibited the cerulein-induced increase in intracellular ROS, NF-κB activation, and IL-6 expression in pancreatic acinar cells in a dose-dependent manner. In conclusion, lycopene may be beneficial in the prevention and/or treatment of acute pancreatitis by inhibiting the activation of NF-κB and the expression of inflammatory cytokines through reduction in intracellular levels of ROS in pancreatic acinar cells.

Levels of intra- and extracellular heat shock protein 60 in Kawasaki disease patients treated with intravenous immunoglobulin.

Immune reactivity to autologous heat shock protein 60 (HSP60) has been reported to be associated with a favorable prognosis in autoimmune diseases. To provide a clue for the possible role of HSP60 in Kawasaki disease (KD), we investigated the levels of intra- and extracellular HSP60 in the course of KD. In KD patients, autologous HSP60 was abundantly expressed in CD11c(+) cells during the acute phase and subsequently decreased during the subacute phase. Most of HSP60-expressing CD11c(+) cells observed in the acute phase was composed of CD11c(low) cells instead of CD11c(high) cells, which were dominant in the subacute phase. In contrast, circulating HSP60 levels were higher in the subacute phase than those in the acute phase, reflecting higher level of HSP60 exposure to the immune system of patients during recovery. These changes in the levels of intra- and extracellular HSP60 were not observed in patients with other febrile diseases. The observed features of HSP60 expression in patients with KD are in favor of a role for autologous HSP60 as a regulator for control of inflammation, rather than a proinflammatory mediator in KD.