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The soju (Korean traditional distilled liquor) market is increasing worldwide. However, in contrast to well-explored distilled liquors, including baijiu (China) and shochu (Japan), soju is less investigated, with limited research on its aroma characteristics. To facilitate better understanding of the aroma characteristics of soju, this study aims to overview recent research on the flavor characteristics of soju and compare data with those of baijiu and shochu, well-established products in the market. Soju is generally made using rice and nuruk (a traditional Korean fermentation starter). Previous studies have reflected that the aroma characteristics vary with raw materials’ nutrition percentages, microbial taxa influenced in fermentation starters, and/or pressure reduction during distillation. The research on the aroma characteristics of baijiu, characterized by solid-state fermentation involving qu (a traditional Chinese fermentation starter), is focused on differences in regional characteristics of the flavor type. Research on the aroma characteristics of shochu has primarily demonstrated that the microbial community could contribute significantly to the development of specific aromatic compounds and/or attributes. Moreover, the association of the aroma characteristics of baijiu and shochu with their volatile compound development by the determination of selective ingredients has been examined. Understanding the current research progress can potentially facilitate the improvement in the aroma characteristics of soju.

Abstract A digital healthcare system based on augmented reality (AR) has promising uses for postoperative rehabilitation. We compare effectiveness of AR-based and conventional rehabilitation in patients after rotator cuff repair (RCR). This study randomly allocates 115 participants who underwent RCR to digital healthcare rehabilitation group (DR group) and conventional rehabilitation group (CR group). The DR group performs AR-based home exercises using UINCARE Home+, whereas the CR group performs brochure-based home exercises. The primary outcome is a change in the Simple Shoulder Test (SST) score between baseline and 12 weeks postoperatively. The secondary outcomes are the Disabilities of the Arm, Shoulder and Hand (DASH) score; Shoulder Pain And Disability Index (SPADI) score; EuroQoL 5-Dimension 5-Level (EQ5D5L) questionnaire score; pain; range of motion (ROM); muscle strength; and handgrip strength. The outcomes are measured at baseline, and at 6, 12, and 24 weeks postoperatively. The change in SST score between baseline and 12 weeks postoperatively is significantly greater in the DR group than in the CR group (p = 0.025). The SPADI, DASH, and EQ5D5L scores demonstrate group×time interactions (p = 0.001, = 0.04, and = 0.016, respectively). However, no significant differences over time are observed between the groups in terms of pain, ROM, muscle strength, and handgrip strength. The outcomes show significant improvement in both groups (all p

Out-of-hospital cardiac arrest in pregnancy is extremely rare. In this case report, a 43-year-old female patient at 24.0 weeks of gestation collapsed outside her home after cardiac arrest. The paramedics performed cardiopulmonary resuscitation with defibrillation for ventricular fibrillation. Spontaneous circulation was achieved after 19 minutes. The fetus was stable during postarrest care. The patient exhibited high blood pressure with seizure-like symptoms for 2 days afterwards, which resolved with magnesium sulfate. She gradually recovered and returned to her daily activities while on treatment with beta blockers for cardiomyopathy and premature ventricular contractions until delivery. At 37.2 weeks of gestation, she underwent elective Cesarean section under spinal anesthesia. The baby weighed 2.55 kg and did not present with any complications. Here, we report a case of successful full-term delivery in a patient who underwent cardiopulmonary resuscitation for sudden cardiac arrest during the second trimester of pregnancy.

Extramedullary relapse in acute lymphoblastic leukemia (ALL) usually occurs in the central nervous system and testes those are known as sanctuary sites. Only a few cases of isolated breast relapse after allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in pediatric ALL, with little known about the optimal treatment and prognosis of such cases. Herein, we report a pediatric case of isolated breast relapse with early T-cell precursor ALL after HSCT. We also describe a literature review of six pediatric cases, including our case.

Neuroimaging studies using electroencephalography (EEG) have been crucial in uncovering brain activity in sensory perception, emotion regulation, and decision-making. Despite tea’s global popularity, its temperature-related neural basis remains underexplored. This study investigated the effect of hot and cold germinated wheat beverages (HB and CB) in changes of brain waves using EEG. Four distinct approaches and topographical assessments were performed to gain deeper insights into the impact of EEG signals in the human brain. The four approaches showed different impacts of HB and CB intake, as all EEG spectral powers increased after drinking HB and decreased after consumption of CB. Significant increases in delta and theta waves were observed as a result of drinking HB, but significant decreases in alpha and beta waves were observed after drinking CB. The topographic maps illustrate the significant effects of HB more prominently than those of CB, displaying greater changes in delta, theta, and beta. These findings suggest the intake of HB is probably related to relaxation, calmness, mindfulness and concentration, while the intake of CB is related to alertness, attention, and working memory. Ultimately, the neuroscientific approaches provided in this study could advance consumer-based research on beverage consumption.

Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3R mutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis. Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.

Abstract Background There is paucity of studies applying fat suppressed (FS) technique to T2 mapping to overcome chemical shift artifacts. The purpose of the study is to difference between FS T2 and conventional T2 mapping and reproducibility of FS T2 mapping in the femoral articular cartilage. Methods Eighteen patients who had normal-looking femoral cartilage and underwent knee MRI with conventional T2 and FS T2 mapping were included. T2 values of each mapping were measured by two readers independently from nine regions in the medial femoral condyle (MFC) and lateral femoral condyle (LFC). Each anatomical region was divided by lines at ± 10°, 30°, 50°, 70°, 90°, and 110°. Comparisons of T2 values between conventional and FS T2 mapping were statistically analyzed. The T2 values between FS and conventional T2 mapping in the anterior, central and posterior femoral condyles were compared. Results The overall femoral condyle T2 values from the FS T2 map were significantly lower than those from the conventional T2 map (48.5ms vs. 51.0ms, p

Background and purposeSpinal cord infarction (SCI) is difficult to diagnosis using MRI findings. We aimed to suggest the optimal timing of MRI studies for diagnosing SCI.Materials and methodsThis retrospective study was approved by our institutional review board. The requirement for informed consent was waived. MRI scans of SCI patients diagnosed between January 2015 and August 2019 were enrolled in the SCI group and subdivided according to the interval between symptom onset and time of MRI scan (A, within 6 h; B, 6-12 hours; C, 12-24 hours; D, 24-72 hours; E, 3-7 days). Three radiologists analyzed the T2WI scans and evaluated the confidence level of diagnosing SCI using a five-point Likert scale: 1, certainly not; 2, probably not; 3, equivocal; 4, probably yes; 5, certainly yes. Scores of 4 and 5 were defined as "T2WI-positive SCI" and scores of 1-3 were defined as "T2WI-negative SCI".ResultsThe SCI group included 58 MRI scans of 34 patients (mean age, 60.6 ± 14.0 years; 18 women). The T2WI positivity rate was 72.4% (42/58). In contrast to the other subgroups, subgroup A included fewer cases of T2WI-positive SCI (1/4, 25%) than T2WI-negative SCI. A confidence score of 5 was the most common in subgroup D (4/27, 14.8%). Among the 12 patients who underwent MRI studies more than twice, confidence scores increased with time.ConclusionIn patients with suspected SCI showing equivocal initial MRI findings, follow-up MRI studies are helpful, especially when performed between 24 and 72 hours after symptom onset.

In order to fulfill the objective of the comparative flavor profiling of hot and cold serving, different concentrations of hot (hot infusion) and cold (boiled and cold serving) roasted-steamed-germinated wheat beverages were prepared in order to explore the comparative profile of the amino acids, volatiles, taste, total flavonoid content (TFC), total phenolic content (TPC), and antioxidant capacities, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) and the Trolox equivalent antioxidant activity (TEAC). The instrumental analysis was performed using electronic sensors (an electric nose and an electric tongue), high-performance liquid chromatography, and spectrophotometry, and the statistical assessment was conducted using univariate (correlation pattern and heatmap) and multivariate (clustering and principal component analysis) analyses. The cold beverages at the highest concentration showed the highest values of TFC, TPC, DPPH, and TEAC, showing 32.31 ± 1.13 μg CE/100 mL, 202.37 ± 20.94 μg GAE/100 mL, 68.43 ± 3.41 μM TE/100 mL, and 126.66 ± 4.00 mM TE/100 mL, respectively. The correlation analysis revealed a remarkable correlation between the taste and the flavor compounds. The clustering analysis and the PCA clearly divided the key metabolites, which were attributed to the different tastes in the hot and cold beverages. This study clearly demonstrates the impact of different temperatures on the aroma metabolites, the taste, and the characteristics of wheat beverages.

Abstract Background Genipin is a compound derived from gardenia fruit extract. Although Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. Here, we investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers. Methods MTT assays were performed to determine the cell viability of gastric cancer and gastric epithelial cell lines (AGS, MKN45, SNU638, MKN74, HFE-145). A TUNEL assay and Western blotting were carried out to investigate apoptosis. Stat3 activity was measured by proteome profiler phospho kinase array, immunofluorescence and immunoblotting. Mitochondria function was monitored with an XF24 analyzer and by flow cytometry, confocal microscopy using fluorescent probes for general mitochondrial membrane potential (MMP). Results Genipin induced apoptosis in gastric cancer cells, including AGS and MKN45 cells. Genipin also reduced Mcl-1 mRNA and protein levels. Furthermore, we found that phosphorylation of Stat3 is regulated by Genipin. Additionally, the protein level of phospho Janus kinase 2 (JAK2) was decreased by Genipin treatment, indicating that the Stat3/JAK2/Mcl-1 pathway is suppressed by Genipin treatment in gastric cancer cells. Mcl-1 is closely related to mitochondrial function. These findings suggest that Genipin contributes to the collapse of mitochondrial functions like MMP. Conclusions Genipin induced apoptosis by suppressing the Stat3/Mcl-1 pathway and led to mitochondrial dysfunction. Our results reveal a novel mechanism for the anti-cancer effect of Genipin in gastric cancer.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Some mountainous regions without water service facilities are among the areas most vulnerable to drought. In these locations, it is particularly essential to establish practical alternatives to cope with the increase in the intensity and duration of droughts caused by climate change. This study proposes a methodology for the conjunctive use of a sand dam and groundwater well under various drought conditions. The method has been applied to a small mountainous area in South Korea. Owing to the scarcity of observational data, it is crucial to properly estimate the hydrological components necessary for judging the feasibility and reliability of conjunctive operations. The step-by-step procedures for performing the tasks are presented in this study. For the inflow of the sand dam, which is a portion of the basin runoff, two different approaches were employed and compared: the Kajiyama formula and a simple two-parameter monthly water balance model (TPM). Water budget analysis allowed for the determination of whether the current and increased water demand could be met under various drought conditions. Preliminary analysis revealed that a sand dam alone could not reliably meet the demand for 10-year or more severe drought conditions. Various water allocation scenarios between surface water (i.e., sand dam) and groundwater were tested. Conjunctive use of a sand dam and groundwater well turned out to increase the reliability of the water supply. As water demand increases and droughts become more severe, the role of groundwater increases. With appropriate resource allocation, 100% water supply reliability could be achieved, even for one year-lasting 50-year drought. We demonstrated how a system could be flexibly operated to meet the target demands monthly, given the system reliability level.

Background/Purpose: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity. Methods: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine. Moreover, comparative assessment was made by performing the same evaluations with a commercially available tri-component DTaP vaccine as the positive control. Results: Both groups showed significantly increased levels of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin, and the levels of interferon-γ and interleukin-10 were significantly increased after two doses of vaccination. Furthermore, since cross cell-mediated immune reactivity between the two vaccines was detected, the possibility of interchangeability was indirectly suggested. Although the positive control group showed significantly higher titers in antibody responses for filamentous hemagglutinin and pertactin compared to the experimental group, anti-pertussis toxin antibody titers of the two groups were not significantly different and the protective efficacy against the clinical and reference strains was maintained in both groups for 18 weeks. Conclusion: The results showed inferior immunogenicity of the new DTaP vaccine compared to a commercial vaccine despite comparable cellular immunity and protective efficacy. Some efforts are necessary for improving immunogenicity against filamentous hemagglutinin and pertactin before conducting human clinical trials. Keywords: Diphtheria-tetanus-acellular pertussis vaccine, Immunogenicity, Efficacy, Mice

The objective of this study was to investigate the possibility of using germinated wheat as a nutritionally improved novel cereal beverage. To enhance the health-related functionality of a germinated wheat beverage (GWB), the roasting time and temperature of germinated wheat were optimized using a central composite design and response surface methodology. The optimum roasting conditions were determined as roasting temperature of 180 °C and roasting time of 44.56 min, resulting in maximum total flavonoid content (0.74 mg CE/g), total phenolic content (1.95 mg GE/g), 2,2-diphnyl-1-picrylhydrazyl (DPPH) radical scavenging activity (5.10 μM TE/g), Trolox equivalent antioxidant capacity (9.45 mM TE/g), and γ-aminobutyric acid content (2.25 mg/g). The germinated wheat roasted with optimum conditions was prepared in two types of GWB (hot and cold), and the sensory characteristics were tested by consumers (n = 102). The cold GWB showed relatively high preferences compared to hot GWB in appearance, odor, taste, and overall acceptabilities. In the intensity results of the sensory properties of GWB, the cold GWB tended to have stronger browning, grain odor, and nutty taste than the hot GWB. Conclusively, this study showed that optimizing the roasting conditions of germinated wheat could achieve desirable sensory properties and consumer acceptance while improving the health-related functionality of GWB.

Abstract Background An HIV cure has not yet been achieved because latent viral reservoirs persist, particularly in resting CD4+ T lymphocytes. In vitro, it is difficult to infect resting CD4+ T cells with HIV-1, but infections readily occur in vivo. Endothelial cells (EC) line the lymphatic vessels in the lymphoid tissues and regularly interact with resting CD4+ T cells in vivo. Others and we have shown that EC promoted productive and latent HIV infection of resting CD4+ T cells. However, the EC used in previous studies were from human umbilical cords (HUVEC), which are macrovascular; whereas EC residing in the lymphoid tissues are microvascular. Methods In this study, we investigated the effects of microvascular EC stimulation of resting CD4+ T cells in establishing viral infection and latency. Human resting and activated CD4+ T cells were cultured alone or with endothelial cells and infected with a pseudotyped virus. Infection levels, indicated by green fluorescent protein expression, were measured with flow cytometry and data was analyzed using Flowing Software and Excel. Results We confirmed that EC from lymphatic tissue (LEC) were able to promote HIV infection and latency formation in resting CD4+ T cells while keeping them in resting phenotype, and that IL-6 was involved in LEC stimulation of CD4+ T cells. However, there are some differences between stimulation by LEC and HUVEC. Unlike HUVEC stimulation, we demonstrated that LEC stimulation of resting memory T cells does not depend on major histocompatibility complex class II (MHC II) interactions with T cell receptors (TCR) and that CD2-CD58 interactions were not involved in LEC stimulation of resting T cells. LEC also secreted lower levels of IL-6 than HUVEC. We also found that LEC stimulation increases HIV infection rates in activated CD4+ T cells. Conclusions While differences in T cell stimulation between lymphatic EC and HUVEC were observed, we confirmed that similar to macrovascular EC stimulation, microvascular EC stimulation promotes direct HIV infection and latency formation in resting CD4+ T cells without T cell activation. LEC stimulation also increased infection rates in activated CD4+ T cells. Additionally, the present study established a physiologically more relevant model of EC interactions with resting CD4+ T cells and further highlighted the importance of investigating the roles of EC in HIV infection and latency in both resting and activated CD4+ T cells.

Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50 = 0.2 ± 0.1 µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections.

Abstract Background Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model. Methods Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice. Results Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range. Conclusions A murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine.

As an effective water management method to respond to the increasing severity of drought, this study proposed a conjunctive operation using a surface reservoir and subsurface dams. The proposed methodology predicts the probable rainfall according to the drought severity and the water demand, and uses these as the basis for water allocation. Sokcho City, located in South Korea, was used as the study case. Sokcho is a tourist city that has suffered from water shortages for many years due to its excessive dependence on a single groundwater dam. Considering conjunctive operation, drought frequency, and drought duration, a total of 80 cases under four scenarios were generated and simulated to determine the water supply capability over the entire year. The results indicate that domestic water can be supplied throughout the year with appropriate water allocation, even when a once-in-50-year drought lasts for 120 days. Furthermore, the water supply potential, which is the additionally available capacity in a reservoir, was used to assess the effects of conjunctive operation. It was estimated that, for a once-in-10-year drought, up to 318% of the annual water demand was available in the reservoir. As the proposed methodology is relatively simple, it offers a useful water resource management tool for sites with similar social and environmental conditions.

The purpose of this study was to develop a formulation of Sunsik with improved health benefits by adding germinated wheat (GW) and herbal plant extract (HPE) using a response surface methodology (RSM). The central composite experimental design (CCD) was used to evaluate the effects of Sunsik with added HPE (2–4%) and GW (10–20%) on total phenolic content (TPC), total flavonoid content (TFC), Trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, gamma butyric acid (GABA) content, total color changes (△E), browning index (BI), water absorption index (WAI), and water solubility index (WSI). As a result of the CCD, the independent and dependent variables were fitted by the second-order polynomial equation, and the lack of fit for response surface models was not significant except in relation to WSI. The GABA content, TPC, and TEAC were more adequate for a linear model than for a quadratic model, and they might be affected by GW rather than HPE. Alternatively, the TFC, DPPH radical scavenging capacity, WAI, WSI, △E, and BI were fitted with quadratic models. The optimum formulation that could improve antioxidant and physicochemical properties was Sunsik with 3.5% and 20% added HPE and GW, respectively.

Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin-treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

To evaluate the in vivo technical feasibility, efficiency, and safety of switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation (RFA) as a no-touch ablation technique in the porcine liver.The animal care and use committee approved this animal study and 16 pigs were used in two independent experiments. In the first experiment, RFA was performed on 2-cm tumor mimickers in the liver using a no-touch technique in the SM mode (2 groups, SM1: 10 minutes, n = 10; SM2: 15 minutes, n = 10) and SB-mode (1 group, SB: 10 minutes, n = 10). The technical success with sufficient safety margins, creation of confluent necrosis, ablation size, and distance between the electrode and ablation zone margin (DEM), were compared between groups. In the second experiment, thermal injury to the adjacent anatomic organs was compared between SM-RFA (15 minutes, n = 13) and SB-RFA modes (10 minutes, n = 13).The rates of the technical success and the creation of confluent necrosis were higher in the SB group than in the SM1 groups (100% vs. 60% and 90% vs. 40%, both p < 0.05). The ablation volume in the SM2 group was significantly larger than that in the SB group (59.2±18.7 cm3 vs. 39.8±9.7 cm3, p < 0.05), and the DEM in the SM2 group was also larger than that in the SB group (1.39±0.21 cm vs. 1.07±0.10 cm, p < 0.05). In the second experiment, the incidence of thermal injury to the adjacent organs and tissues in the SB group (23.1%, 3/13) was significantly lower than that in the SM group (69.2%, 8/13) (p = 0.021).SB-RFA was more advantageous for a no-touch technique for liver tumors, showing the potential of a better safety profile than SM-RFA.

Reactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of colorectal cancer patients.We examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n = 190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in colorectal cancer cells.We observed significantly longer mean disease-free survival in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p = 0.035), and the median overall survival of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p = 0.036). Cell invasiveness decreased in the Romo1 knockdown colorectal cancer cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p = 0.025).Romo1 overexpression in tumor tissue was significantly associated with survival in curatively resected colorectal cancer patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high lymph node ratio. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1.

Background: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. Methods: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. Results: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. Conclusion: Our results show that KRG can be used as a possible anticancer drug for patients with CRC

Natural products have shown great promise in sensitizing cells to TNF-related apoptosis-inducing ligand (TRAIL) therapy. Sea cucumber (SC) extracts possess antitumor activity, and hence their potential to sensitize colorectal cancer (CRC) cells to TRAIL therapy was evaluated. This study used Western blotting to evaluate the combination effects of SC and TRAIL in CRC, and determined the molecular mechanism underlying these effects. SC fractions and TRAIL alone did not affect apoptosis; however, combined treatment dramatically induced the apoptosis of CRC cells, but not of normal colon cells. Combined treatment induced the expression of apoptotic proteins (poly (ADP-ribose) polymerase (PARP), caspase 3, and 8), and this effect was markedly inhibited by the ubiquitination of X-linked inhibitor of apoptosis protein (XIAP). SC did not affect the mRNA levels, but it increased proteasomal degradation and ubiquitination of the XIAP protein. Furthermore, SC induced reactive oxygen species (ROS) production, thereby activating c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress-related apoptotic pathways in CRC. Altogether, our results demonstrate that the SC F2 fraction may sensitize CRC cells to TRAIL-induced apoptosis through XIAP ubiquitination and ER stress.

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages.

To analyze the enhancement patterns and apparent diffusion coefficient (ADC) values of non-measurable surgical cavity wall enhancement pattern, newly appearing after completion of standard concurrent chemoradiotherapy (CCRT) with temozolomide in glioblastoma patients for the prognosis prediction.From January 2010 to April 2014, among 190 patients with histopathologically confirmed glioblastoma, a total of 33 patients with non-measurable wall enhancement on post-CCRT MR imaging were enrolled and divided into two subgroups: non-progression (n = 18) and progression groups (n = 15). We analyzed the wall enhancement patterns, which were categorized into three patterns: thin, thick and nodular enhancement. ADC values were measured in the enhancing portions of the walls. The progression-free survival (PFS) related to the wall enhancement was analyzed by Kaplan-Meier analysis, and survival curves were compared using the log-rank test.Statistically significant differences in the surgical cavity wall enhancement patterns was shown between the progression and non-progression groups (P = 0.0032). Thin wall enhancement was more frequently observed in the non-progression group, and thick or nodular wall enhancement were observed in the progression group (P = 0.0016). There was no statistically significant difference in the mean ADC values between the progression and non-progression groups. The mean PFS was longer in patients with thin wall enhancement than in those with nodular or thick wall enhancement (35.5 months vs. 15.8 months, P = 0.008).Pattern analysis of non-measurable surgical cavity wall enhancement on post-CCRT MR imaging might be useful tool for predicting prognosis of GBM patient before clear progression of non-measurable disease.

As soy-derived glyceollins are known to induce antioxidant enzymes in various types of cells and tissues, we hypothesized that the compounds could protect neurons from damage due to reactive oxygen species (ROS). In order to examine the neuroprotective effect of glyceollins, primary cortical neurons collected from mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated from mice carrying wild-type nuclear factor (erythroid-derived 2)-like 2 (Nrf2), but the compounds were ineffective in those isolated from Nrf2 knockout mice, suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated neuroprotection. Furthermore, the inhibition of heme oxygenase-1 (HO-1), a major downstream enzyme of Nrf2, abolished the suppressive effect of glyceollins against glutamate-induced ROS production and cytotoxicity, confirming that activation of HO-1 by glyceollins is responsible for the neuroprotection. To examine whether glyceollins also improve cognitive ability, mice pretreated with glyceollins were challenged with scopolamine and subjected to behavioral tests. Glyceollins attenuated scopolamine-induced cognitive impairment of mice, but failed to enhance memory in Nrf2 knockout mice, suggesting that the memory-enhancing effect is also mediated by the Nrf2 signaling pathway. Overall, glyceollins showed neuroprotection against glutamate-induced damage, and attenuated scopolamine-induced memory deficits in an Nrf2-dependent manner.

Novel ruthenium bipyridyl sensitizer incorporating conjugated benzo[1,9]quinolizino-(acridin-2-yl)vinyl-2,2′-bipyridine ligand [JJ-12] has been synthesized and demonstrated as efficient sensitizer in dye-sensitized solar cells. A mesoporous titania film stained with JJ-12 exhibits a remarkable incident monochromatic photon-to-current conversion efficiency of 82%. Under standard AM 1.5 sunlight, the solar cell using a liquid-based electrolyte consisting of 0.6 M 1,2-dimethyl-3-propylimidazolium iodide (DMPII), 0.05 M I2, 0.1 M LiI, and 0.5 M tert-butylpyridine in acetonitrile exhibits a short-circuit photocurrent density of 16.47 mA/cm2, an open-circuit voltage of 0.71 V, and a fill factor of 0.71, corresponding to an overall conversion efficiency of 8.34 %.

β-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modifed to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modifed β-glucan. Alkali-treated β-glucan had a distinct shape and smaller particle size than untreated β-glucan. The reduced particle size was conducive to the stability of the suspension because the β-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of β-glucan, whereas exposure of macrophages to heat-treated β-glucan decreased their immune activity. β-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of β-glucan is a key factor in β-glucan-induced immune responses of macrophages. Thus, the modifcation of the β-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future. [ABSTRACT FROM AUTHOR]

Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia beating by densely grouping mitochondria just beneath the apical membrane. However, this efficient localization comes at a cost because electrons leaked during oxidative phosphorylation react with molecular oxygen to form superoxide, and thus, the cluster of mitochondria creates a hotspot for oxidant production. The relatively high oxygen concentration overlying airway epithelia further intensifies the risk of generating superoxide. Thus, airway ciliated cells face a unique challenge of producing harmful levels of oxidants. However, surprisingly, highly ciliated epithelia produce less reactive oxygen species (ROS) than epithelia with few ciliated cells. Compared to other airway cell types, ciliated cells express high levels of mitochondrial uncoupling proteins, UCP2 and UCP5. These proteins decrease mitochondrial protonmotive force and thereby reduce production of ROS. As a result, lipid peroxidation, a marker of oxidant injury, decreases. However, mitochondrial uncoupling proteins exact a price for decreasing oxidant production; they decrease the fraction of mitochondrial respiration that generates ATP. These findings indicate that ciliated cells sacrifice mitochondrial efficiency in exchange for safety from damaging oxidation. Employing uncoupling proteins to prevent oxidant production, instead of relying solely on antioxidants to decrease postproduction oxidant levels, may offer an advantage for targeting a local area of intense ROS generation. [ABSTRACT FROM AUTHOR]