Diagnostic Performance of Artificial Intelligence-Based Computer-Aided Detection Software for Automated Breast Ultrasound.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the diagnostic performance of radiologists following the utilization of artificial intelligence (AI)-based computer-aided detection software (CAD) in detecting suspicious lesions in automated breast ultrasounds (ABUS). MATERIALS AND METHODS: ABUS-detected 262 breast lesions (histopathological verification; January 2020 to December 2022) were included. Two radiologists reviewed the images and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. ABUS images were classified as positive or negative using AI-CAD. The BI-RADS category was readjusted in four ways: the radiologists modified the BI-RADS category using the AI results (AI-aided 1), upgraded or downgraded based on AI results (AI-aided 2), only upgraded for positive results (AI-aided 3), or only downgraded for negative results (AI-aided 4). The AI-aided diagnostic performances were compared to radiologists. The AI-CAD-positive and AI-CAD-negative cancer characteristics were compared. RESULTS: For 262 lesions (145 malignant and 117 benign) in 231 women (mean age, 52.2 years), the area under the receiver operator characteristic curve (AUC) of radiologists was 0.870 (95% confidence interval [CI], 0.832-0.908). The AUC significantly improved to 0.919 (95% CI, 0.890-0.947; P = 0.001) using AI-aided 1, whereas it improved without significance to 0.884 (95% CI, 0.844-0.923), 0.890 (95% CI, 0.852-0.929), and 0.890 (95% CI, 0.853-0.928) using AI-aided 2, 3, and 4, respectively. AI-CAD-negative cancers were smaller, less frequently exhibited retraction phenomenon, and had lower BI-RADS category. Among nonmass lesions, AI-CAD-negative cancers showed no posterior shadowing. CONCLUSION: AI-CAD implementation significantly improved the radiologists' diagnostic performance and may serve as a valuable diagnostic tool.

Nucleotide-binding leucine-rich repeat network underlies nonhost resistance of pepper against the Irish potato famine pathogen Phytophthora infestans.

Nonhost resistance (NHR) is a robust plant immune response against non-adapted pathogens. A number of nucleotide-binding leucine-rich repeat (NLR) proteins that recognize non-adapted pathogens have been identified, although the underlying molecular mechanisms driving robustness of NHR are still unknown. Here, we screened 57 effectors of the potato late blight pathogen Phytophthora infestans in nonhost pepper (Capsicum annuum) to identify avirulence effector candidates. Selected effectors were tested against 436 genome-wide cloned pepper NLRs, and we identified multiple functional NLRs that recognize P. infestans effectors and confer disease resistance in the Nicotiana benthamiana as a surrogate system. The identified NLRs were homologous to known NLRs derived from wild potatoes that recognize P. infestans effectors such as Avr2, Avrblb1, Avrblb2, and Avrvnt1. The identified CaRpi-blb2 is a homologue of Rpi-blb2, recognizes Avrblb2 family effectors, exhibits feature of lineage-specifically evolved gene in microsynteny and phylogenetic analyses, and requires pepper-specific NRC (NLR required for cell death)-type helper NLR for proper function. Moreover, CaRpi-blb2-mediated hypersensitive response and blight resistance were more tolerant to suppression by the PITG_15 278 than those mediated by Rpi-blb2. Combined results indicate that pepper has stacked multiple NLRs recognizing effectors of non-adapted P. infestans, and these NLRs could be more tolerant to pathogen-mediated immune suppression than NLRs derived from the host plants. Our study suggests that NLRs derived from nonhost plants have potential as untapped resources to develop crops with durable resistance against fast-evolving pathogens by stacking the network of nonhost NLRs into susceptible host plants.

Long-term effects of defoliant exposure on brain atrophy progression in humans.

As the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin is classified as a group 1 human carcinogen. We investigated the long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on the progression of brain atrophy in humans. We retrospectively selected 546 patients exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (exposed group) and 1353 patients not exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (control group). The patients in both groups underwent brain T1-weighted magnetic resonance imaging (MRI) twice. We divided the patients into two propensity score-matched groups, analyzed voxel-wise whole brain atrophy in the MRI images of each patient, and compared the progression of brain atrophy between the two groups. The exposed group showed significant brain atrophy progression in the bilateral frontal and temporal lobes, compared with the control group. The ventrolateral prefrontal area in the frontal lobe and whole temporal lobe were the main atrophic regions in the exposed group, compared with the control group. The neurotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin can damage the brain, even in patients exposed to it over 40 years ago. Humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin should thus be evaluated for progression of brain atrophy.

Iron-Palladium magnetic nanoparticles for decolorizing rhodamine B and scavenging reactive oxygen species.

HYPOTHESIS: Here, FePd magnetic nanoparticles (MNPs) are developed as artificial enzymes with high biocompatibility and reusability. EXPERIMENT: The nanoparticles (NPs) are synthesized in an aqueous solvent by one-pot synthesis utilizing glutathione (GSH) and cysteine (Cys) as surfactants. FINDINGS: The prepared hydrophilic FePd NPs are redispersible in water. Further, they exhibit catalytic activity for the degradation of rhodamine B (RhB), as well as for the inhibition of reactive oxygen species (ROS) production induced by H2O2, which are two- and seven-fold enhancements of their catalytic performances, respectively, compared with that of horseradish peroxidase. The computational simulation and electrochemical analysis indicate that the enhancement of the catalytic effect is due to the protection of the MNP surface by GSH and Cys. In vitro experiments reveal that FePd MNPs behave like a peroxidase and decrease the ROS in mammalian cells. The cytotoxicity assessment of FePd MNPs via exposures to different cell lines for over seven days indicates that they can maintain the cell viability of >90% for up to 20 µgmL-1 concentration. FePd MNPs with high saturation magnetization and biocompatibility can be utilized as recyclable peroxidase-mimicking nanozymes and biosensors in a variety of catalytic and biological applications.

Risk of Cancer in Middle-aged Patients With Gout: A Nationwide Population-based Study in Korea.

OBJECTIVE: Gout is reportedly associated with a higher incidence of cancer. However, patients with gout tend to have several cancer-related factors including obesity, smoking, and alcohol consumption; thus, the precise association between gout and cancer risk remains unclear. We aimed to investigate the risk of cancer in Korean patients with gout. METHODS: Based on the Korea Health Insurance Service database, the subjects comprised patients aged 41-55 years with gout newly diagnosed between 2003 and 2007. We used a multivariable-adjusted Cox proportional hazards model in gout patients and a 1:2 ratio for the matched controls by age, sex, and index year. RESULTS: We compared 4176 patients with gout with 8352 controls. The mean age and follow-up duration were 48.8 years and 10.1 years in both groups. Overall cancer risk was significantly different between gout patients and controls (HR 1.224, 95% CI 1.073-1.398). The all-cause mortality (HR 1.457, 95% CI 1.149-1.847) and cancer mortality (HR 1.470, 95% CI 1.020-2.136) were higher in patients with gout. In the subgroup analysis, the cancer risks of the stomach (HR 1.710, 95% CI 1.221-2.395), head and neck (HR 1.850, 95% CI 1.071-3.196), and hematologic or lymphoid organ (HR 2.849, 95% CI 1.035-7.844) were higher in patients with gout. CONCLUSION: Patients aged 41-55 years with gout have a higher risk of cancer and all-cause and cancer mortality compared with the general population. Therefore, special attention should be paid to higher cancer risk and mortality in these patients who are diagnosed in middle age.

Role of Aggregatibacter actinomycetemcomitans-induced autophagy in inflammatory response.

BACKGROUND: Aggressive periodontitis is characterized by the early-onset and rapid progression of periodontal destruction and is closely associated with Aggregatibacter actinomycetemcomitans. Autophagy is a conserved process that is critical for removing damaged proteins, organelles, and even intracellular pathogens. Therefore, this study examined whether A. actinomycetemcomitans induces autophagy. In addition, the relationship among autophagy, bacterial internalization, and inflammatory molecules in periodontal aggressive inflammation was analyzed. METHODS: The expression of autophagy-related proteins in human gingival tissue and THP-1 cells was assessed by Western blot analysis. The formation of light chain 3 (LC3) puncta was examined by confocal microscopy. The degree of bacterial internalization into the cells was determined by the viable cell count. Phagocytosis and reactive oxygen species (ROS) production were measured using confocal microscopy and flow cytometry. RESULTS: When macrophages were infected with live A. actinomycetemcomitans, the autophagy influx was activated by the increase in LC3-II, autophagy-related gene 5/12, and Beclin-1 expression through the Toll-like receptors and extracellular signal-regulated kinase signaling pathways. The inhibition of A. actinomycetemcomitans-induced autophagy suppressed bacterial internalization via phagocytosis into the macrophages and increased interleukin (IL)-1ß production. Moreover, treatment with an ROS inhibitor inhibited these enhanced inflammatory responses. CONCLUSIONS: A. actinomycetemcomitans-induced autophagy promotes bacterial internalization by phagocytosis, which restricts the excessive inflammatory response by downregulating IL-1ß and ROS production in macrophages. Thus, A. actinomycetemcomitans-induced autophagy and its role in regulating the inflammatory response may play an important role in the aggressive periodontal inflammatory process, and be a target for the development of new periodontal therapies.

Catechin ameliorates Porphyromonas gingivalis-induced inflammation via the regulation of TLR2/4 and inflammasome signaling.

BACKGROUND: Porphyromonas gingivalis is a major periodontopathogen found in patients with chronic periodontitis that can lead to alveolar bone or tooth loss. Interleukin-1ß (IL-1ß), a proinflammatory cytokine, is most relevant to the pathogenesis of periodontitis. Catechin is one of the main polyphenol compounds found in green tea and possesses a range of health benefits. This study examined the anti-inflammatory effects of catechin in THP-1-derived macrophages infected with P. gingivalis as well as its effects on P. gingivalis-induced periodontitis in a mouse model. METHODS: The cytokine levels and relevant protein expression in THP-1 cells were measured using an enzyme-linked immunosorbent assay and Western blot analysis, respectively. An apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosome formation was measured by confocal laser scanning microscopy. Micro-computed tomography was used to determine the level of bone loss induced by a P. gingivalis oral infection. RESULTS: Catechin attenuated the production of IL-1ß by inhibiting pro-IL-1ß expression via the downregulation of nuclear factor-κB, p38 mitogen-activated protein kinase, and Toll-like receptor signaling. In addition, catechin inhibited the activation of inflammasomes induced by P. gingivalis, but did not affect the growth of P. gingivalis. Catechin reduced the level of alveolar bone loss in a P. gingivalis-induced periodontitis mouse model. CONCLUSION: Catechin possesses anti-inflammatory properties by reducing the level of IL-1ß production, suggesting that it can potentially be used for the prevention and treatment of periodontal inflammation caused by P. gingivalis.

Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages.

Streptococcus mutans (S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin (IL)-1ß, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1ß secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1ß secretion via caspase-1 activation, and S. mutans-induced IL-1ß secretion required absent in melanoma (AIM2), NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate (ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.

Global gene expression profiling for fruit organs and pathogen infections in the pepper, Capsicum annuum L.

Hot pepper (Capsicum annuum) is one of the most consumed vegetable crops in the world and useful to human as it has many nutritional and medicinal values. Genomic resources of pepper are publically available since the pepper genomes have been completed and massive data such as transcriptomes have been deposited. Nevertheless, global transcriptome profiling is needed to identify molecular mechanisms related to agronomic traits in pepper, but limited analyses are published. Here, we report the comprehensive analysis of pepper transcriptomes during fruit ripening and pathogen infection. For the ripening, transcriptome data were obtained from placenta and pericarp at seven developmental stages. To reveal global transcriptomic landscapes during infection, leaves at six time points post-infection by one of three pathogens (Phytophthora infestans, Pepper mottle virus, and Tobacco mosaic virus P0 strain) were profiled. The massive parallel transcriptome profiling in this study will serve as a valuable resource for detection of molecular networks of fruit development and disease resistance in Capsicum annuum.

Trans-cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans-induced inflammation in THP-1-derived macrophages via autophagy activation.

BACKGROUND: Inflammation is an essential response against bacterial infection as a host defense mechanism, which can lead to tissue damage. Aggregatibacter actinomycetemcomitans (Aa) is major pathogen for aggressive periodontitis characterized by rapid destruction of periodontal tissue surrounding teeth. Trans-cinnamic aldehyde is a key bioactive compound of the cinnamon extracts, which has anti-inflammatory, antioxidant, antipyretic, antimicrobial, and anti-cancer properties. The objective of the present study was to investigate the anti-inflammatory effect of trans-cinnamic aldehyde against Aa infection in human THP-1 derived macrophages and on Aa-induced periodontitis in mice. METHODS: THP-1 cells were differentiated with phorbol 12-mystristate 13-acetate and were infected with live Aa. Trans-cinnamic aldehyde was pretreated 30 minutes before the bacterial infection. Cytokine production was determined by enzyme-linked immunosorbent assay (ELISA) and protein expressions were detected by Western blot analysis. Autophagosome formation was detected by Cyto-ID. Viable cell count was carried out to determine bacterial adhesion, internalization, and intracellular survival. Experimental periodontitis was induced by inoculating Aa orally to mice, and microcomputed tomography was used to evaluate bone loss. RESULTS: Pretreatment of trans-cinnamic aldehyde significantly inhibited Aa-stimulated release of tumor necrosis factor-α and interleukin (IL)-1ß. Pretreatment of trans-cinnamic aldehyde inhibited Aa-induced expression of TLR signaling pathway as well as the phosphorylation of JNK, p38, and nuclear factor (NF)-κB. Also, trans-cinnamic aldehyde treatment downregulated the expression of pro-IL-1ß, caspase-1, and inflammasome components. Trans-cinnamic aldehyde treatment significantly decreased intracellular survival of Aa. Moreover, the autophagosome formation and the expressions of autophagy markers including Beclin-1, ATG5, and LC3 were increased. Finally, trans-cinnamic aldehyde significantly inhibited bone loss in Aa-induced mouse periodontitis. CONCLUSIONS: Trans-cinnamic aldehyde inhibited Aa-stimulated expression of inflammatory responses and inhibited intracellular bacterial survival via autophagy activation. These results suggest that trans-cinnamic aldehyde may serve as an anti-inflammatory agent for aggressive periodontitis.

Asparagus cochinchinensis stimulates release of nerve growth factor and abrogates oxidative stress in the Tg2576 model for Alzheimer's disease.

BACKGROUD: Use of multifunctional drugs with neurotrophic supporting and oxidative stress suppressing activity may be considered a therapeutic strategy to protect or repair cellular damage caused during the progression of Alzheimer's disease (AD). In this study, we investigated the therapeutic effects of aqueous extract of A. cochinchinesis root (AEAC), particularly its role as a nerve growth factor (NGF) stimulator and anti-oxidant in Tg2576 mice showing AD phenotypes of human. METHODS: Tg2576 mice were received 100 mg/kg/day AEAC via oral administration, while mice in the Vehicle treated group received dH2O for 4 weeks. Non-Tg littermates were used as a control group. Following AEAC treatment for 4 weeks, NGF function, anti-oxidantive status, Aß-42 peptide level, γ-secretase expression and neuronal cell functions were analyzed in the brain of Tg2576 mice. RESULTS: AEAC containing flavonoids, phenols, saponins and protodioscin induced enhancement of NGF secretion and decreased intracellular ROS in the neuronal and microglial cell line. These effects as well as enhanced SOD levels were also detected in AEAC treated Tg2576 mice. The expression of p-Akt among downstream effectors of the high affinity NGF receptor was dramatically recovered in AEAC treated Tg2576 mice, while the expression of p75NTR was slightly recovered in the same group. Significant recovery on the level of Aß-42 peptides and the expression of γ-secretase members including PS-2, APH-1 and NCT were detected in AEAC treated Tg2576 mice. Furthermore, AEAC treated Tg2576 mice showed decreased numbers of dead cells and suppressed acetyl choline esterase (AChE) activity. CONCLUSIONS: These results suggest that AEAC contribute to improving the deposition of Aß-42 peptides and neuronal cell injuries during the pathological progression stage of AD in the brain of Tg2576 mice through increased NGF secretion and suppressed oxidative stress.

Modality switching between therapy and imaging based on the excitation wavelength dependence of dual-function agents in folic acid-conjugated graphene oxides.

Owing to its near infrared (NIR) absorption, graphene oxide (GO) is promising for both photothermal (PT) therapy and multiphoton (MP) imaging. Novel therapy/imaging modality switching is proposed here based on the selected excitation wavelength of femtosecond (FS) laser. GO-based destruction of cancer cells is demonstrated when the laser power of 800-nm-wavelength FS laser is increased above 7 mW. However, GO-based imaging is mainly monitored without damaging the sample when using 1200-nm wavelength FS laser in the same laser power range. Folic acid (FA) conjugated graphene oxide (FA-GO) was synthesized for selective cancer cell targeting. Dual-function FA-GO-based cancer cell targeting agents were experimentally optimized to enable therapy/imaging modality switching.

Portulaca oleracea L. Extract Enhances Glucose Uptake by Stimulating GLUT4 Translocation to the Plasma Membrane in 3T3-L1 Adipocytes.

This study investigated the effects of Portulaca oleracea L. extract on glucose uptake in 3T3-L1 adipocytes. P. oleracea extract (POE) markedly enhanced glucose uptake, which was caused by increased GLUT4 expression at the plasma membrane (PM) in 3T3-L1 adipocytes. This increase in PM-GLUT4 expression was associated with insulin receptor substrate-1 (IRS-1) phosphorylation, phosphatidylinositol 3-kinase (PI3K) activation, and Akt phosphorylation, and finally, enhanced intracellular glucose uptake. POE was not associated with protein kinase C (PKC)λ/ζ phosphorylation in the insulin signaling pathway, but did promote 5'-AMP-activated kinase (AMPK) phosphorylation. Increased glucose uptake through POE was inhibited through treating with the PI3K inhibitor or AMPK inhibitor in 3T3-L1 adipocytes. This result suggested that POE may enhance glucose uptake by stimulating GLUT4 translocation to the PM through activating the PI3K and AMPK pathway in 3T3-L1 adipocytes.

Butanol extracts of Asparagus cochinchinensis fermented with Weissella cibaria inhibit iNOS-mediated COX-2 induction pathway and inflammatory cytokines in LPS-stimulated RAW264.7 macrophage cells.

Roots of Asparagus cochinchinesis have been widely used to treat fever, cough, kidney disease, breast cancer, inflammatory and brain disease, although the effects of their fermented products have not been assessed until now. To investigate the anti-inflammatory effects on macrophages of a butanol extract from A. cochinchinensis roots fermented with Weissella cibaria (BAW), alterations in the inducible nitric oxide synthase (iNOS)-mediated cyclooxygenase-2 (COX-2) induction pathway and inflammatory cytokine expression were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following pretreatment with BAW. Briefly, W. cibaria was selected from two bacterial strains for the fermentation of A. cochinchinensis roots based on its hyaluronidase inhibition and NO suppression rates. Following fermentation with W. cibaria, the level of various key components including total phenols and protodioscin were significantly enhanced in BAW. In addition, BAW exhibited high free radical scavenging activity (IC50=31.62 µg/ml) and induced a decrease of intracellular ROS production in RAW264.7 cells following DCFH-DA staining. Significant suppressions in the expression level of important members of the iNOS-mediated COX-2 induction pathway and the phosphorylation of mitogen-activated protein kinase members were detected. The expressions of pro-inflammatory and anti-inflammatory cytokines were recovered in BAW pretreated RAW264.7 cells. Overall, these results suggest that BAW may suppress inflammatory responses through differential regulation of the iNOS-mediated COX-2 induction pathway and inflammatory cytokine expressions in LPS-activated RAW264.7 cells.

Comparison of therapeutic responses to an anticancer drug in three stocks of ICR mice derived from three different sources.

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.

Cyanidin-3-rutinoside increases glucose uptake by activating the PI3K/Akt pathway in 3T3-L1 adipocytes.

In this study, the effect of cyanidin-3-rutinoside (C3R) on glucose uptake by 3T3-L1 adipocytes was studied. C3R significantly increased glucose uptake, which was associated with enhanced plasma membrane glucose transporter type 4 (PM-GLUT4) expression in 3T3-L1 adipocytes. The potentiating effect of C3R on glucose uptake and PM-GLUT4 expression was related to enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) and Akt, as well as augmented activation of phosphatidylinositol-3-kinase (PI3K) in the insulin signaling pathway. C3R induced glucose uptake was inhibited only by the PI3K inhibitor, but not by an AMPK inhibitor in 3T3-L1 adipocytes. Therefore, C3R likely up-regulates glucose uptake and PM-GLUT4 expression in 3T3-L1 adipocytes by activating the PI3K/Akt pathways.

Ethyl acetate extract from Asparagus cochinchinensis exerts anti­inflammatory effects in LPS­stimulated RAW264.7 macrophage cells by regulating COX­2/iNOS, inflammatory cytokine expression, MAP kinase pathways, the cell cycle and anti-oxidant activity.

Asparagus cochinchinesis (A. cochinchinesis) is a medicine traditionally used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although numerous studies of the anti­inflammatory effects of A. cochinchinesis have been conducted, the underlying mechanisms of such effects in macrophages remain to be demonstrated. To investigate the mechanism of suppressive effects on the inflammatory response in macrophages, alterations of the nitric oxide (NO) level, the cell viability, inducible nitric oxide synthase (iNOS) and cyclooxygenase­2 (COX­2) expression levels, inflammatory cytokine expression, the mitogen-activated protein kinase (MAPK) signaling pathway, cell cycle arrest and reactive oxygen species (ROS) levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following treatment with ethyl acetate extract from A. cochinchinesis root (EaEAC). RAW264.7 cells pretreated two different concentrations of EaEAC prior to LPS treatment exhibited no significant toxicity. The concentration of NO was significantly decreased in the EaEAC + LPS treated group compared with the vehicle + LPS treated group. A similar decrease in mRNA transcript level of COX­2, iNOS, pro-inflammatory cytokines [tumor necrosis factor­α and interleukin (IL)­1ß] and anti­inflammatory cytokines (IL­6 and IL­10) was detected in the EaEAC + LPS treated group compared with the vehicle + LPS treated group, although the decrease rate varied. Enhancement of the phosphorylation of MAPK family members following LPS treatment was partially rescued in the EaEAC pretreated group, and the cell cycle was arrested at the G2/M phase. Furthermore, the EaEAC pretreated group exhibited a reduced level of ROS generation compared with the vehicle + LPS treated group. Taken together, these results suggest that EaEAC suppresses inflammatory responses through inhibition of NO production, COX­2 expression and ROS production, as well as differential regulation of inflammatory cytokines and cell cycle in RAW264.7 cells. In addition, these results provide strong evidence to suggest that EaEAC may be considered as an important candidate for the treatment of particular inflammatory diseases.

In vivo feasibility test using transparent carbon nanotube-coated polydimethylsiloxane sheet at brain tissue and sciatic nerve.

Carbon nanotubes, with their unique and outstanding properties, such as strong mechanical strength and high electrical conductivity, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Polydimethylsiloxane (PDMS)-based elastomers have been used in a wide range of biomedical applications because of their optical transparency, physiological inertness, blood compatibility, non-toxicity, and gas permeability. In present study, most of artificial nerve guidance conduits (ANGCs) are not transparent. It is hard to confirm the position of two stumps of damaged nerve during nerve surgery and the conduits must be cut open again to observe regenerative nerves after surgery. Thus, a novel preparation method was utilized to produce a transparent sheet using PDMS and multiwalled carbon nanotubes (MWNTs) via printing transfer method. Characterization of the PDMS/MWNT (PM) sheets revealed their unique physicochemical properties, such as superior mechanical strength, a certain degree of electrical conductivity, and high transparency. Characterization of the in vitro and in vivo usability was evaluated. PM sheets showed high biocompatibility and adhesive ability. In vivo feasibility tests of rat brain tissue and sciatic nerve revealed the high transparency of PM sheets, suggesting that it can be used in the further development of ANGCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1736-1745, 2017.

Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon.

The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)­induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5­HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)­18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidate­treated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5­HMF and AD treatment groups. In IEC­18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5­HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5­HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC­18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5­HT receptor signaling pathway.

Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.