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Objective: This study was conducted to evaluate the effectiveness of the combination therapy of Yukmijihwang-tang and Western medicine on primary glomerulonephritis.Methods: We conducted a search using keywords, such as Yukmijihwang-tang and Liuwei Dihuang, in eight databases (CNKI, CiNii, Pubmed, Embase, Cochrane, Science On, OASIS, RISS). There was no limit to the publication period of the papers. A meta-analysis was conducted and classified according to the outcome measurements, such as the total effective rate (TER), serum creatinine (SCr), and blood urea nitrogen (BUN). Data analysis was performed using the RevMan 5.4.1 software, and Cochrane’s risk of bias (ROB) was used to assess the quality of the papers.Results: A total of 12 randomized control trials were selected. The meta-analysis showed that the treatment group combining Yumijihwang-tang and Western medicine was more efficient than the control group using Western medicine alone (RR: 1.29, CI: 1.20 to 1.39 p=Yukmijihwang-tang with Western medicine is effective in treating primary glomerulonephritis. However, these findings should be interpreted cautiously due to the unknown or high risk of bias in the included trials.

This study was to analyze the awareness of the public, reality of use and satisfaction of nail treatments with natural ingredients to develop various products of nail treatments with natural ingredients that can minimize or recover nail damages with 294 Korean women in their 20s to 30s. It was found that they had higher interests in nail treatments with natural ingredients than general nail treatments and they felt that nail treatment with natural ingredients were safer than general nail treatments. Respondents with nail damages showed high expected effect of nail treatments with natural ingredients and the expected effect of nail treatments with natural ingredients was higher as the degree of nail damages was high. In terms of general characteristics of nail care and satisfaction of nail treatments with natural ingredients, the results of investigating mediating effect of the awareness of nail treatments with natural ingredients showed its complete mediation. The expected effects of nail treatments with natural ingredients were high as the degree of nail damages was high, and satisfaction after using nail treatments with natural ingredients was high as the expected effects were high. It is expected that the market competitiveness of nail treatments with natural ingredients will be further increased if awareness of nail treatments with natural ingredients increases.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species are rare in nature due to reproductive barriers but how such hurdles can be overcome is largely unknown. Here we report the hybrid genome structure of xBrassicoraphanus, a synthetic allotetraploid of Brassica rapa and Raphanus sativus. We performed cytogenetic analysis and de novo genome assembly to examine chromosome behaviors and genome integrity in the hybrid. Transcriptome analysis was conducted to investigate expression of duplicated genes in conjunction with epigenome analysis to address whether genome admixture entails epigenetic reconfiguration. Allotetraploid xBrassicoraphanus retains both parental chromosomes without genome rearrangement. Meiotic synapsis formation and chromosome exchange are avoided between nonhomologous progenitor chromosomes. Reconfiguration of transcription network occurs, and less divergent cis-elements of duplicated genes are associated with convergent expression. Genome-wide DNA methylation asymmetry between progenitors is largely maintained but, notably, B. rapa-originated transposable elements are transcriptionally silenced in xBrassicoraphanus through gain of DNA methylation. Our results demonstrate that hybrid genome stabilization and transcription compatibility necessitate epigenome landscape adjustment and rewiring of cis-trans interactions. Overall, this study suggests that a certain extent of genome divergence facilitates hybridization across species, which may explain the great diversification and expansion of angiosperms during evolution.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.

This study aimed to investigate the risk of all-cause mortality and incidence of CVD according to metabolic health and body mass index (BMI) in Korean adults. This study was retrospectively designed using the National Health Insurance Service-National Health Screening Cohort data. Participants were divided into six groups according to two category of metabolic syndrome and three categories of BMI. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome (all-cause mortality and incidence of CVDs) were estimated using multivariable Cox proportional hazards regression models. 151,706 participants aged ≥ 40 years were enrolled; median follow-up period was 9.7 years in the study. Compared to metabolically healthy normal weight, the fully adjusted HRs (95% CIs) of metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese for composite outcome were 1.07 (1.03–1.12), 1.12 (1.07–1.17), 1.33 (1.25–1.41), 1.28 (1.22–1.34), and 1.31 (1.26–1.37), respectively, in men, and 1.10 (1.05–1.16), 1.22 (1.16–1.29), 1.34 (1.26–1.43), 1.27 (1.19–1.34), and, 1.40 (1.34–1.47), respectively, in women. High BMI and metabolic unhealthiness were associated with an increased risk on the composite of all-cause mortality and incidence of CVD in both sexes.

This study investigated the case of a nineteen-year-old female patient with chronic nausea, vomiting, and abdominal distension, who was diagnosed with CNVS and Spleen-Qi deficiency. Subjective symptoms were recorded with the Numerical Rating Scale (NRS) every morning, and the Gastrointestinal Symptom Rating Scale (GSRS) was used on the days of admission and discharge. For eleven days following admission, she took Bojungikki-tang-gagam and received acupuncture and moxibustion therapy. After three days of treatment, her nausea and vomiting ceased, and abdominal distension improved from NRS 3 to 0 after seven days of treatment. The GSRS score for the specific symptoms improved from 3 to 2; however, the total score remained largely unchanged (from 20 to 21). This case suggests that Korean medical treatment may improve CNVS.

Objectives: Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs. Methods: Participants were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared. Results: The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4,728/38,590 (12.25%) in females and 3,158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01–1.39) and 1.39 (1.28–1.50), respectively, in males, and 1.22 (1.09–1.37) and 1.53 (1.42–1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73–1.00) in males and 0.80 (0.72–0.88) in females. Conclusions: Migraine increased the risk of ischemic CCVDs in both sexes, but female migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than female migraineurs who did not take those medications.

Summary Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+) Tfh (cTfh) and CXCR5+PD-1+forkhead box protein 3 (FoxP3+) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing–remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.

Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis. Induced pluripotent stem cells (iPSCs) are regarded as useful stem cells due to their pluripotent differentiation potential. In this study, we explored the therapeutic efficacy of human iPSC‐derived EC and iPSC‐derived SMC in peripheral artery disease model. After the induction of mesodermal differentiation of iPSC, CD34+ progenitor cells were isolated by magnetic‐activated cell sorting. Cultivation of the CD34+ progenitor cells in endothelial culture medium induced the expression of endothelial markers and phenotypes. Moreover, the CD34+ cells could be differentiated into SMC by cultivation in SMC culture medium. In a murine hindlimb ischemia model, cotransplantation of EC with SMC improved blood perfusion and increased the limb salvage rate in ischemic limbs compared to transplantation of either EC or SMC alone. Moreover, cotransplantation of EC and SMC stimulated angiogenesis and led to the formation of capillaries and arteries/arterioles in vivo. Conditioned medium derived from SMC stimulated the migration, proliferation, and tubulation of EC in vitro, and these effects were recapitulated by exosomes isolated from the SMC‐conditioned medium. Together, these results suggest that iPSC‐derived SMC enhance the therapeutic efficacy of iPSC‐derived EC in peripheral artery disease via an exosome‐mediated paracrine mechanism., Co‐transplantation of the induced pluripotent stem cell (iPSC)‐derived endothelial cells and smooth muscle cells enhanced the therapeutic efficacies of endothelial cells and smooth muscle cells in a murine hindlimb ischemia model. Smooth muscle cells promoted angiogenesis and therapy of peripheral artery disease through exosome‐mediated paracrin mechanism.

To prepare a photocurable ceramic suspension for use in commercialized additive manufacturing equipment, the effects of the rheological properties of zirconia particles added to a binder, and the presence or absence of a silane coupling agent on the particles was evaluated. To this end, three experimental groups (ZSs, ZMs, ZLs) and three control groups (ZS, ZM, ZL) were designed depending on the size of the underlying zirconia particles. The test-group zirconia suspensions were prepared through silanization, which was not applied to the control-group suspensions. Depending on the particle size, viscosity differences between the test and control groups were 16,842, 18,623, and 12,303 mPa·s, respectively. Compared to the other groups, the viscosity of the ZLs group suspension decreased by 70.98–88.04%. This confirmed that the viscosity of the suspensions was affected by the particle size and the presence of silane coating. The dispersion stability of the zirconia suspensions was evaluated over 20 days. A sedimentation test confirmed that the sedimentation rate of the ZLs group was slower than those of the other groups. This study aimed to optimize the suspension manufacturing method to effectively be utilized in further commercializing zirconia three-dimensional (3D) printing and could also help to develop various medical applications.

Ovarian cancer is a common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic role remains unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on the regulation of autophagic and apoptotic pathways in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using MTT and colony formation assays in SK-OV-3 cells. PKM2 expression was positively correlated with the severity of the tumor, and expression of pro-apoptotic proteins increased in SK-OV-3 cells following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by mTOR inhibition. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation of SK-OV-3 cells. Compound 3K treatment suppressed tumor progression in an in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected the Warburg effect and induced autophagic cell death. Therefore, use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].

BACKGROUND Few studies have reported on the trends in influenza vaccination rates among cancer survivors in Korea. We investigated these trends over a recent 11-year period (2005-2015). METHODS Data were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) III- VI (2005-2015). After excluding individuals younger than 40 years of age, the participants included 2,210 cancer survivors (861 men and 1,349 women). We categorized these study participants into four groups according to age and sex. RESULTS The influenza vaccination rate decreased significantly among male cancer survivors, with rates of 74.8, 64.7, 56.2, and 55.2% (β coefficient=-0.257, P for trend

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015.METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC).RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids.CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species rarely occur in nature mainly due to reproductive barriers but how such hurdles can be overcome is largely unknown. xBrassicoraphanus is a fertile intergeneric allopolyploid synthesized between Brassica rapa and Raphanus sativus in the Brassicaceae family. Genomes of B. rapa and R. sativus are diverged enough to suppress synapsis formation between non-homologous progenitor chromosomes during meiosis, and we found that both genomes reside in the single nucleus of xBrassicoraphanus without genome loss or rearrangement. Expressions of syntenic orthologs identified in B. rapa and R. sativus were adjusted to a hybrid nuclear environment of xBrassicoraphanus, which necessitates reconfiguration of transcription network by rewiring cis-trans interactions. B. rapa coding sequences have a higher level of gene-body methylation than R. sativus, and such methylation asymmetry is maintained in xBrassicoraphanus. B. rapa-originated transposable elements were transcriptionally silenced in xBrassicoraphanus, rendered by gain of CHG methylation in trans via small RNAs derived from the same sequences of R. sativus subgenome. Our work proposes that not only transcription compatibility but also a certain extent of genome divergence supports hybrid genome stabilization, which may explain great diversification and expansion of angiosperms during evolution.

Background Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults. Methods This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses. Results A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06–1.30) and 1.47 (1.34–1.62), respectively, in men and 1.20 (1.02–1.42) and 1.52 (1.30–1.78), respectively, in women. Conclusions Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and “healthy aging” become more and more important, these guidelines are also expected to increase in clinical usefulness.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride–glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p &lt, 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Background: The International Agency for Research on Cancer classifies 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as a known carcinogen. This study aimed to investigate the association between exposure to secondhand smoke (SHS) and NNAL concentrations in non-smokers.Methods: This was a cross-sectional study based on data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey. Urine NNAL concentrations were categorized into tertiles of 3,615 study participants who were non-smokers. All sampling and weight variables were stratified, and analyses to account for the complex sampling design were conducted.Results: The overall, male, and female percentages of SHS exposure among non-smokers were 22.4%, 29.2%, and 20.4%, respectively. The geometric means of urine NNAL concentrations were 1.896±0.098 pg/mL and 1.094±0.028 pg/mL in the SHS exposure and non-exposure groups, respectively. After adjusting for confounding variables, in the total group, the geometric mean of urine NNAL concentrations was significantly higher in the SHS exposure group than in the SHS non-exposure group (adjusted P-value

Single-incision cholecystectomy is a surgical method that offers comparable results to conventional laparoscopic cholecystectomy. However, a high risk of postoperative incisional hernia is an issue in single-incision cholecystectomy. This study evaluated the risk factors and incidences of incisional hernia after single-incision cholecystectomy and the advantage issue of using barbed suture material during wound closures.A total of 1,111 patients underwent laparoscopic or robotic single-incision cholecystectomy between March 2014 and February 2020 at our institution at CHA Bundang Medical Center. During this period, there were 693 patients who underwent wound closure with monofilament suture material (Monosyn 2-0; B. Braun) and the other 418 patients used barbed suture material (Stratafix 2-0; Ethicon).The two patient groups were comparable in age, body mass index, and diagnosis. The total incidence of incisional hernia after single-incision cholecystectomy was 0.5% (five cases). All patients who developed incisional hernia were in the monofilament suture material group (0.7% vs. 0%,Our study showed a low incidence of incisional hernia, all of which occurred in the monofilament suture material group. If technically appropriate, single-incision cholecystectomy does not appear to present a high incidence of hernia. Barbed suture material can be safely applied in wound closure showing comparable incisional hernia incidence to monofilament suture material.

We evaluated the potential serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) roles in diagnosing and monitoring brain metastases (BMs). We included 70 patients with newly diagnosed BMs, 71 age- and cancer type-matched patients without BMs, and 67 healthy controls (HCs). We compared sNfL and sGFAP levels among the groups using a single-molecule array immunoassay. We prospectively followed 26 patients with BMs every 2–3 months by measuring sNfL and sGFAP levels and performing magnetic resonance imaging (MRI) scans. The sNfL and the sGFAP levels were higher in patients with BMs (medians: sNfL, 63.7 µL, sGFAP, 819.5 pg/µL) than in those without BMs (sNfL, 13.3 µL, sGFAP, 154 pg/µL, p &lt, 0.001) and HCs (sNfL, 12.5 µL, sGFAP, 135 pg/µL, 0.001). The sNfL and the sGFAP cutoff levels had a sensitivity and a specificity of 91%. The sGFAP cutoff level had a sensitivity of 91% and a specificity of 97%. The sNfL and the sGFAP levels were related to the BM size but not to the primary cancer type. After BM treatment, sNfL and sGFAP levels decreased with reduced BM lesions on MRI, however, they increased when BMs progressed. sNfL and sGFAP are potential biomarkers for BM screening in cancer patients.

The detection efficiency on dry rehydratable films and identification of false positive and false negative colonies to improve the detection accuracy of coliform dry rehydratable films were evaluated in this study. A total of 173 commercial spices and jeotgal were used in this study. The detection accuracy for coliform on 3M Petrifilm coliform count film was 97.9%, and false negative was 2.1% (nine strains). For Sanita-kun coliform count film, the detection accuracy was 97.3%, and false positive was 2.7% (six strains). The 3M Petrifilm coliform count film and Sanita-kun coliform count film showed similar detection accuracies. The biochemical identification of the false negative colonies on 3M Petrifilm coliform count film revealed the presence of Escherichia hermannii and Pantoea spp., which were included in the coliform group. The false positive colonies on Sanita-kun coliform count film were identified as Bacillus licheniformis, Bacillus rhizosphaerae, Bacillus clausi, Bacillus pumilus, and Bacillus safensis, which were gram positive and oxidase positive. In order to improve the detection accuracy for coliform, it is necessary to further incubate over 48 h to confirm the gas generation in 3M Petrifilm coliform count film. In Sanita-kun coliform count film, additional biochemical tests such as the gram stain and oxidase tests are necessary.

(1) Background: Subclinical inflammation as a risk factor of cardiovascular diseases was clinically measured using C-reactive protein (CRP) level. (2) Methods: This study was cross-sectionally designed based the 2015&ndash, 2018 Korean National Health and Nutrition Examination Survey (KNHANES). The ratio of daily omega-3 fatty acids to energy intake (&omega, 3FA ratio) was classified into four quartile groups (Q1, &lt, 0.3%, Q2, 0.3%&ndash, &lt, 0.6%, Q3, 0.6%&ndash, 1.0%, and Q4, &ge, 1.0% in both sexes). Logistic regression analysis was conducted to investigate the association between the &omega, 3FA ratio and subclinical inflammation defined as CRP levels &ge, 3 mg/dL. (3) Results: The &omega, 3FA ratio in subjects without and with subclinical inflammation was 0.8% and 0.7% in men (p-value = 0.001), and 0.8% and 0.8% in women (p-value = 0.491), respectively. The prevalence of subclinical inflammation in males decreased with increasing quartile of &omega, 3FA ratio (12.9%, 9.6%, 7.4%, and 7.7%, p-value = 0.033), while female prevalence was not significant among quartile groups. Compared to Q1, odds ratios (95% confidence intervals) for subclinical inflammation of Q2, Q3, and Q4 were 0.740 (0.465&ndash, 1.177), 0.564 (0.341&ndash, 0.930), and 0.549 (0.317&ndash, 0.953) in males, and 1.066 (0.653&ndash, 1.741), 1.105 (0.600&ndash, 1.718), and 0.934 (0.556&ndash, 1.571) in females after full adjustment. (4) Conclusion: The &omega, 3FA ratio is associated with subclinical inflammation in men.

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, the usage of a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types of cancer. Especially, vascular abnormal structures of which deter delivery route by leakage and cause the poor perfusion were considered to be environment unfavorable to T cells and immune checkpoint blockade (ICB) delivery within the tumor microenvironment (TME). Herein, we report stabilization of tumor blood vessels by endothelial dysfunctional blocker CU06-1004, which modified the TME and showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged the survival of tumor-bearing mice by decreasing tumor growth. T-cell infiltration increased in the tumors of the combination group, with cytotoxic CD8+ T cell activity within the tumor parenchyma upregulated compared with anti-PD-1 monotherapy. Tumor inhibition was associated with reduced hypoxia and reduced vessel density in the central region of the tumor. These effects correlated significantly with enhanced expression of IFN gamma and PD-L1 in tumors. Taken together, our findings suggest that CU06-1004 is a potential candidate drug capable of improving therapeutic efficacy of anti-PD-1 through beneficial changes in the TME.

Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan–Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models. The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683–0.850) and 1.055 (0.966–1.152) in men and 0.805 (0.649–0.999), and 1.049 (0.873–1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839–1.071) and 0.530 (0.452–0.621) in men and 1.163 (0.921–1.469) and 0.439 (0.323–0.596) in women, respectively. Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality. Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Background The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. Methods This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. Results The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58–4.53), 31.02 (9.46–101.74), and 1.89 (1.12–3.17) in boys; and 6.50 (3.22–13.11), 20.09 (7.08–57.04), and 3.94 (1.98–7.77) in girls, respectively. Conclusion SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS., Graphical Abstract

Ovarian cancer is the common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, the frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic roles remain unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on autophagic and apoptotic pathway regulation in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using the MTT and colony formation assay in SK-OV-3. The results of tissue microarray showed that PKM2 expression positively correlated with the severity of the tumor. Moreover, the expression of pro-apoptotic proteins increased in SK-OV-3 following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by the inhibition of mTOR. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation in SK-OV-3. Compound 3K treatment suppressed tumor progression in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected Warburg effects and induced autophagic cell death. Therefore, the use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

Inflammatory bowel disease is an autoimmune disease that causes chronic inflammation of the gastrointestinal tract. Endothelial dysfunction, defined by a reduced endothelial barrier and an increase in the expression of adhesion molecules, is part of the pathology of inflammatory bowel disease. In this study, we assessed the therapeutic effect of CU06-1004, an endothelial dysfunction blocker that reduces vascular hyperpermeability and inflammation in a mouse model of colitis. Acute colitis was induced in mice using 3% (w/v) dextran sodium sulfate added to their drinking water for 7 days. Twenty-four hours after the addition of dextran sodium sulfate, either mesalazine or CU06-1004 was administered orally each day. Administration of CU06-1004 significantly reduced the clinical manifestations (weight loss, diarrhea, and bloody stool) and histological changes (epithelium loss, inflammatory cell infiltration, and crypt destruction) induced by dextran sodium sulfate. Proinflammatory cytokines were also reduced, indicating that inflammation was ameliorated. From a vascular perspective, CU06-1004 reduced interrupted and tortuous vessels, enhanced junction protein expression, and reduced inflammatory adhesion molecules, indicating a broad improvement of endothelial dysfunction. Endothelial protection induced epithelial barrier restoration and decreased epithelial inflammation. Blocking endothelial dysfunction with CU06-1004 significantly ameliorated the progression of inflammatory bowel disease. Therefore, CU06-1004 may represent a potential therapeutic agent for the treatment of inflammatory bowel disease as well as other inflammatory diseases.