Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression.

This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT. The median progression-free survival (PFS) and overall survival (OS) were 2.4 months and 11.6 months, respectively. Fluorescence-activated cell sorting revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8+T-cells in the responders. Proteomic analysis identified a consistent upregulation of extracellular matrix-receptor interactions and phagosome pathways in the responders. Among the differentially expressed proteins, the transferrin receptor protein (TFRC) was higher in the responders before treatment (fold change > 1.2). TFRC validation with an independent cohort showed the prognostic significance of either OS or PFS in patients with low PD-L1 expression. In summary, CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression; however, it induced decreasing MDSC, resulting in a durable response. Higher baseline TFRC levels predicted a favorable response to nivolumab in NSCLC with low PD-L1 expression.

Evaluation of the Effects of Euglena gracilis on Enhancing Immune Responses in RAW264.7 Cells and a Cyclophosphamide-Induced Mouse Model.

In this study we evaluated the immune-enhancing effects of ß-glucan, the main component of Euglena gracilis (Euglena), and Euglena on inflammatory factor expression in RAW264.7 macrophages and ICR mice with cyclophosphamide-induced immunosuppression. Macrophages were treated with ß-glucan or Euglena for 48 h. The ß-glucan and Euglena groups exhibited higher levels of inducible nitric oxide synthase, nitric oxide, and tumor necrosis factor (TNF)-α than the control (vehicle alone) group. Animals were fed saline and ß-glucan (400 mg/kg body weight (B.W.)) or Euglena (400 or 800 mg/kg B.W.) for 19 days, and on days 17-19, cyclophosphamide (CCP, 80 mg/kg B.W.) was administered to induce immunosuppression in the ICR mouse model. CCP reduced the body weight, spleen index, and cytokine expression of the mice. To measure cytokine and receptor expression, splenocytes were treated with concanavalin A (ConA) or lipopolysaccharide (LPS) as a mitogen for 24 h. In vivo, ConA stimulation significantly upregulated the expression of interferon (IFN)-γ, interleukin (IL)-10, IL-12 receptor ß1, IL-1ß, and IL-2 in splenocytes from the ß-glucan- or Euglena-treated groups compared with those in the splenocytes from the CCP-treated group; LPS stimulation increased the levels of the cytokines TNF-α, IL-1ß, and IL-6 in splenocytes from the ß-glucan- or Euglena-treated groups compared with those from the CCP-treated group, but most of these differences were not significant. These results demonstrate the effect of Euglena in ameliorating macrophages and immunosuppression in CCP-treated mice. Thus, Euglena has the potential to enhance macrophage- and splenocyte-mediated immune-stimulating responses.

Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia.

Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli, 5.0 * 10^9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E. coli, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum ß-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2~4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics.

Systematic review of changed smoking behaviour, smoking cessation and psychological states of smokers according to cigarette type during the COVID-19 pandemic.

OBJECTIVES: Although the global COVID-19 pandemic has increased interest in research involving high-risk smokers, studies examining changed smoking behaviours, cessation intentions and associated psychological states among smokers are still scarce. This study aimed to systematically review the literature related to this subject. DESIGN: A systematic review of published articles on cigarettes and COVID-19-related topics DATA SOURCES: Our search was conducted in January 2021. We used the keywords COVID-19, cigarettes, electronic cigarettes (e-cigarettes) and psychological factors in PubMed and ScienceDirect and found papers published between January and December 2020. DATA SELECTION: We included articles in full text, written in English, and that surveyed adults. The topics included smoking behaviour, smoking cessation, psychological state of smokers and COVID-19-related topics. DATA EXTRACTION AND SYNTHESIS: Papers of low quality, based on quality assessment, were excluded. Thirteen papers were related to smoking behaviour, nine papers were related to smoking cessation and four papers were related to psychological states of smokers. RESULTS: Owing to the COVID-19 lockdown, cigarette users were habituated to purchasing large quantities of cigarettes in advance. Additionally, cigarette-only users increased their attempts and willingness to quit smoking, compared with e-cigarette-only users. CONCLUSIONS: Owing to the COVID-19 outbreak, the intention to quit smoking was different among smokers, according to cigarette type (cigarette-only users, e-cigarette-only users and dual users). With the ongoing COVID-19 pandemic, policies and campaigns to increase smoking cessation intentions and attempts to quit smoking among smokers at high risk of COVID-19 should be implemented. Additionally, e-cigarette-only users with poor health-seeking behaviour require interventions to increase the intention to quit smoking.

Setting the policy agenda for graphic health warning labels: An analysis of online news media coverage in South Korea, 2016.

INTRODUCTION: In South Korea, a bill requesting the implementation of graphic health warning labels (GHWLs) on tobacco products was adopted at the Assembly Plenary Session on 29 May 2015, and the law was implemented on 23 December 2016. During the period, a plan of the technical details of GHWLs, such as the making of graphic warnings, was examined by the Regulatory Reform Committee (RRC). This study aims to investigate what the media reported over that period and whether the RRC's policy decisions changed. METHODS: We conducted a content analysis of online media reports from the first legislative examination (22 April 2016) to the re-examination (13 May 2016). We coded 150 news reports according to two types (news and opinions) and three slants in terms of being in favor of or opposed to the initially government's implementation plan of GHWLs: positive, negative, and neutral. RESULTS: At the first legislative examination, some committee members recommended placing pictorial warnings at the bottom of a cigarette pack as opposed to the plan. Initially, the media reported the results of the committee decisions neutrally. However, over time, positive news and opinions on tobacco control policy and support for positioning the GHWLs at the top of packages increased before the committee carried out the re-examination. Only 15 (10.0%) news reports adopted a negative slant, while the reports with positive (n=101; 67.3%) and neutral slants (n=34; 22.7%) comprised the majority. At the re-examination, the committee withdrew their earlier recommendation to position the GHWLs at the bottom of cigarette packs, finally deciding that the pictorial warnings should be located at the top of the packs, as per the original government's plan. CONCLUSIONS: The friendly media coverage of the tobacco control policy suggests that the media would be a major factor in the policymakers' decision. Because the media play an important role in defining social issues in the policy-decision process, garnering support from the media is important in the tobacco control legislative process.

Implementing Structured Clinical Templates at a Single Tertiary Hospital: Survey Study.

BACKGROUND: Electronic health record (EHR) systems have been widely adopted in hospitals. However, since current EHRs mainly focus on lowering the number of paper documents used, they have suffered from poor search function and reusability capabilities. To overcome these drawbacks, structured clinical templates have been proposed; however, they are not widely used owing to the inconvenience of data entry. OBJECTIVE: This study aims to verify the usability of structured templates by comparing data entry times. METHODS: A Korean tertiary hospital has implemented structured clinical templates with the modeling of clinical contents for the last 6 years. As a result, 1238 clinical content models (ie, body measurements, vital signs, and allergies) have been developed and 492 models for 13 clinical templates, including pathology reports, were applied to EHRs for clinical practice. Then, to verify the usability of the structured templates, data entry times from free-texts and four structured pathology report templates were compared using 4391 entries from structured data entry (SDE) log data and 4265 entries from free-text log data. In addition, a paper-based survey and a focus group interview were conducted with 23 participants from three different groups, including EHR developers, pathology transcriptionists, and clinical data extraction team members. RESULTS: Based on the analysis of time required for data entry, in most cases, beginner users of the structured clinical templates required at most 70.18% more time for data entry. However, as users became accustomed to the templates, they were able to enter data more quickly than via free-text entry: at least 1 minute and 23 seconds (16.8%) up to 5 minutes and 42 seconds (27.6%). Interestingly, well-designed thyroid cancer pathology reports required 14.54% less data entry time from the beginning of the SDE implementation. In the interviews and survey, we confirmed that most of the interviewees agreed on the need for structured templates. However, they were skeptical about structuring all the items included in the templates. CONCLUSIONS: The increase in initial elapsed time led users to hold a negative opinion of SDE, despite its benefits. To overcome these obstacles, it is necessary to structure the clinical templates for optimum use. In addition, user experience in terms of ease of data entry must be considered as an essential aspect in the development of structured clinical templates.

The association between new graphic health warning labels on tobacco products and attitudes toward smoking among south Korean adolescents: a national cross-sectional study.

BACKGROUND: Graphic health warning labels (GHWLs) on tobacco products are more effective than text warnings for communicating the risk of smoking. The implementation of GHWLs can prevent adolescents from initiating smoking. Therefore, this study examined the association between GHWLs newly implemented on December 23, 2016, in South Korea and attitudes toward smoking among adolescents. METHODS: This post-implementation cross-sectional analysis examined the responses of 62,276 students (31,624 boys and 30,652 girls) who participated in the 2017 Web-based Korean Youth Risk Behavior Survey, which was completed anonymously as a self-administered questionnaire by middle and high school students. Multinomial logistic regression was applied to explore the attitudes toward smoking among the youth (13-18 years old) who have been exposed to GHWLs in order to identify relationship of exposure to the GHWLs with smoking initiation and awareness of the danger of smoking. RESULTS: Six months after implementation, 69.4% of adolescents reported having been exposed to GHWLs in the previous 30 days. Among those exposed to GHWLs both boys and girls in grade 7 were significantly more likely than grade 12 high school students to decide not to start smoking (boys: AOR = 3.96, 95% CI 3.31-4.75, p < 0.001; girls: AOR = 2.76, 95% CI 2.32-3.30, p < 0.001) and to think that smoking was dangerous to their health (boys: AOR = 3.01, 95% CI 2.52-3.58, p < 0.001; girls: AOR = 2.42, 95% CI 2.03-3.88, p < 0.001) after seeing GHWLs. These associations were greater for adolescents who had experienced smoking-prevention education or had been exposed to anti-tobacco advertisements. However, those who smoked, used e-cigarettes, or experienced secondhand smoking were significantly less likely to decide not to smoke and to view smoking as dangerous. CONCLUSIONS: To maintain the perception of the harm of tobacco from childhood through adolescence, the government should implement both comprehensive tobacco controls, including smoking-prevention education in schools, and measures to encourage a smoke-free environment in homes.

Analysis of the legislative process related to the implementation of graphic health warning labels on tobacco products in South Korea.

INTRODUCTION: Well-designed health warnings on tobacco packaging enhance cost-effectively public awareness of the risks of using tobacco products. However, many countries have experienced difficulties in implementing pictorial warnings. The purpose of this study is to present the topics that arose during the legislative process that preceded implementation of graphic health warning labels (GHWLs) on tobacco products in South Korea, and discuss the outcomes. METHODS: We used qualitative content analysis to analyze lawmakers' statements, and those of committee members in meetings that preceded the drafting of the legislative document pertaining to GHWLs in South Korea. RESULTS: In discussions surrounding the adoption of the GHWLs, the main point of contention was the level of disgust induced by pictorial warnings. When discussing how warnings should be inscribed on packaging after adoption of GHWLs, lawmakers disagreed regarding the physical position of the warnings. Because of continuous objections raised by some lawmakers, implementation of GHWLs was delayed, and, when actually introduced, the warnings were toned down. Some lawmakers communicated with tobacco companies; thus the companies participated in the legislative process in South Korea. CONCLUSIONS: To prevent tobacco companies from negatively influencing tobacco control efforts, it is essential that all communications with such companies be publicly disclosed and that the tobacco industry be prohibited from contacting lawmakers involved in the legislative process of tobacco control.

Improved Antioxidant, Anti-inflammatory, and Anti-adipogenic Properties of Hydroponic Ginseng Fermented by Leuconostoc mesenteroides KCCM 12010P.

Hydroponic ginseng (HPG) has been known to have various bio-functionalities, including an antioxidant effect. Recently, fermentation by lactic acid bacteria has been studied to enhance bio-functional activities in plants by biologically converting their chemical compounds. HPG roots and shoots were fermented with Leuconostoc mesenteroides KCCM 12010P isolated from kimchi. The total phenolic compounds, antioxidant, anti-inflammatory, and anti-adipogenic effects of these fermented samples were evaluated in comparison with non-fermented samples (control). During 24 h fermentation of HPG roots and shoots, the viable number of cells increased to 7.50 Log colony forming unit (CFU)/mL. Total phenolic and flavonoid contents of the fermented HPG roots increased by 107.19% and 645.59%, respectively, compared to non-fermented HPG roots. The antioxidant activity of fermented HPG, as assessed by 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ß-carotene-linoleic, and ferric reducing antioxidant power (FRAP) assay, was also significantly enhanced. In an anti-inflammatory effect of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, the nitric oxide content and the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) decreased when treated with fermented samples. Simultaneously, lipid accumulation in 3T3-L1 adipocyte was reduced when treated with fermented HPG. Fermentation by L. mesenteroides showed improved antioxidant, anti-inflammatory and anti-adipogenic HPG effects. These results show that fermented HPG has potential for applications in the functional food industry.

Physiochemical Analysis, Antioxidant Effects, and Sensory Characteristics of Quark Cheese Supplemented with Ginseng Extract.

The objective of this study was to evaluate physicochemical and sensory properties, the texture profile, and antioxidant activity of ginseng extract-supplemented quark cheese as a new cheese product intended to improve public health. After addition of less than 1.0% ginseng extract, the moisture content of quark significantly decreased, while fat and protein levels increased, although microbial counts and lactose and ash contents were not affected significantly (p<0.05). In terms of color, L* values decreased significantly with increasing concentration of ginseng extract, while a* values increased significantly (p<0.05). The results of texture profiling showed that cohesiveness and springiness were unaffected, whereas hardness, gumminess, and chewiness increased significantly. The 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical-scavenging activities of the cheese fortified with 0%, 0.5%, or 1.0% of the ginseng extract were 4.22%±0.12%, 20.14%±1.34%, and 56.32%±1.54%, respectively. The results of sensory analysis indicated that bitterness, ginseng odor, and aftertaste significantly improved with increasing concentration of ginseng extract (p<0.05). However, there was no significant difference in the overall quality attributes of quark cheese between the no-supplement control and samples with less than 0.5% of the ginseng extract (p>0.05), suggesting that these products could help to promote public health as functional foods.

Comparative study on anti-oxidative and anti-inflammatory properties of hydroponic ginseng and soil-cultured ginseng.

Hydroponic ginseng (HPG) and soil-cultured ginseng (SCG) were extracted in 70% methanol to quantify relative content of 8 ginsenosides and polyphenolic compounds, and flavonoids to compare their antioxidative effects. Level of nitric oxide and inflammatory targets produced in LPS-stimulated RAW 264.7 cells were measured. 2-year-old HPG shoots contained highest levels of ginsenoside Rb2, Rb3, Rd, Re, and F1. Total polyphenol content was highest in shoots of HPG, followed by roots of HPG and SCG. HPG shoots had high radical scavenging activity and an elevated ability to inhibit linoleic acid oxidation. 2-year-old HPG shoots reduced nitric oxide production in RAW 264.7 cells by 47%, whereas 6-year-old SCG roots reduced it by only 21%. HPG also significantly lowered mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6, as determined by RT-PCR, compared to SCGs. Therefore, HPG may have potential for utilization as an alternative to SCG, because of superior antioxidant and anti-inflammatory properties.

Convenience store visitors recall cigarette advertisements even if they do not purchase cigarettes.

BACKGROUND: This study examined the extent to which visitors to convenience stores remember the cigarette advertisements they encounter in these stores and investigated the relationships between how advertisements are recalled and attitudes toward them. METHODS: Exit surveys of 1007 visitors to three convenience stores located in Seoul, Korea, were conducted between 25 November 2015 and 7 December 2015. RESULTS: Of the respondents, 23.4% (n = 236) freely recalled the cigarette advertisement in the store just visited. However, the percentage of participants who correctly recalled the advertisement increased to 55.2% (n = 556) after we presented them with a card showing options for the advertisement (i.e. a cued recall task). Regardless of sex or purchasing cigarettes, free recall performance was significantly associated with age, number of weekly visits to the convenience store and current smoking status. In addition, free recall increased with having a positive attitude toward cigarette advertisements. CONCLUSIONS: Repeated visits to convenience stores may continue to expose individuals to cigarettes and their advertisements; such exposure may subconsciously affect recall of the advertisements and maintenance of a positive attitude toward cigarette advertisements. Therefore, to denormalize smoking in society, cigarette advertising and displays at points of sale including convenience stores, should be banned.

Increased antioxidative and nitric oxide scavenging activity of ginseng marc fermented by Pediococcus acidilactici KCCM11614P.

This study aimed to improve the antioxidant and nitric oxide scavenging activities of ginseng marc fermented by Pediococcus acidilactici, thereby creating a biofunctional resource with improved anti-inflammatory capability. P. acidilactici was inoculated in 1% ginseng marc extract; cell viability, pH, and total titratable acidity were measured. Total phenolic and flavonoid contents were measured using Folin-Ciocalteu reagent and colorimetric method. Ferric reducing antioxidant power (FRAP), ß-carotene, and sodium nitroprusside (SNP) assays were used to evaluate functionality. Polyphenols and flavonoids totaled 33.7 ± 0.4 and 10.0 ± 0.4 mg/g of solid, respectively, at 24 h fermentation. P. acidilactici had 40 nM ß-galactosidase and 20 nM ß-glucosidase activities. Antioxidative activities increased up to 34.5 and 10.2%, respectively, as measured via FRAP and ß-carotene assays. Anti-inflammatory activity of the fermented extract-as measured via SNP assay-increased 342%, suggesting that ginseng marc fermented by P. acidilactici could be used in food or pharmaceutical industries.

Differences in visual fixation duration according to the position of graphic health warning labels: An eye-tracking approach.

INTRODUCTION: The Framework Convention on Tobacco Control (FCTC) recommends that graphic health warning labels (GHWLs) be positioned at the top of the principal area of cigarette packs, rather than at the bottom, to increase visibility. However, during the legislative process of introducing GHWLs in South Korea, the position of GHWLs has become a contested issue. The pro-tobacco industry group argued that the warnings should be placed at the bottom of cigarette packs because evidence for the effectiveness of the upper position was insufficient. Therefore, this study investigated whether the position of the GHWL affects eye movement. METHODS: Participants (30 daily smokers and 24 non-smokers) were shown six cigarette packs in random order with different position combinations (top, middle, bottom) and image concepts (skin aging, toxic constituents). Participants' eye movements were recorded using eye-tracking equipment to measure visual fixation duration in milliseconds (ms). RESULTS: Participants visually fixated longer on the health warning area than on the tobacco branding area (p<0.05). Mean fixation duration on the health warning area was significantly longer at the top or middle positions compared to the bottom, by 28% (mean difference=340 ms, p=0.006) and by 30% (mean difference=368 ms, p=0.002), respectively. By contrast, mean fixation duration on the branding area was longer with the warning at the bottom compared to top or middle positions by 25% and 33%, with mean differences of 157 ms (p=0.100) and 212 ms (p=0.026), respectively. No significant difference in fixation time was observed between the top and middle positions (p>0.05). CONCLUSIONS: The duration of visual fixation on GHWLs was longer when they were displayed at the top and middle, rather than at the bottom. Therefore, GHWLs should be positioned from the top to the middle of the tobacco package.

Tobacco company strategies for maintaining cigarette advertisements and displays in retail chain stores: In-depth interviews with Korean convenience store owners.

INTRODUCTION: This study gathered data from store owners regarding the advertising and display of, and the contractual arrangements and promotional activities related to, the sale of tobacco products in convenience stores. METHODS: In-depth interviews were conducted with three owners of convenience stores in South Korea: to examine the procedures for managing the sale of tobacco products; for allocating the advertising allowance for such products; and for coordinating the promotional activities of tobacco companies. RESULTS: All tobacco advertisements and displays in convenience stores are installed and managed in accordance with the contract between the tobacco companies and the convenience store headquarters. The headquarters receives an allowance from the tobacco company in return for maintaining and displaying their product and promotional materials. The headquarters then pays a monthly advertising allowance to each franchisee as an operating subsidy. However, the owners also stated that tobacco companies provide financial incentives directly to them to engage in illegal promotional activities. CONCLUSIONS: Because tobacco advertisements and displays at convenience stores are related to the profitability of these products, the participants in these relationships have become increasingly entangled. Illegal promotional activities must be monitored to limit tobacco sales and advertising. Furthermore, efforts to ban the advertising and display of tobacco products at the point of sale must be based on the development of policies emerging from an understanding of the roles of the major stakeholders.

Ninjurin1 Is Up-regulated in Circulating Prostate Tumor Cells and Plays a Critical Role in Prostate Cancer Cell Motility.

BACKGROUND/AIM: Ninjurin1 is a 17-kDa membrane protein that is highly expressed in circulating tumor cells (CTCs) obtained from locally-advanced prostate cancer patients. As CTCs are implicated in the initiation of distant metastasis, we examined the potential contribution of Ninjurin1 to the motility of prostate cancer cells. MATERIALS AND METHODS: Ninjurin1 expression was evaluated in CTCs harvested from seven locally advanced patients with no metastatic hallmarks using real-time polymerase chain reaction (PCR). The role of Ninjurin1 in cell motility was investigated using small interfering RNA (siRNA), neutralizing antibodies against Ninjurin1 and Ninjurin1-overexpressing adenoviruses. RESULTS: Ninjurin1 was ranked as the most significantly up-regulated adhesion protein identified by RNA-Seq analysis. Both Ninjurin1 down-regulation by siRNA and neutralizing antibodies blocking Ninjurin1 homophilic interactions effectively inhibited cell motility. In contrast, cell motility was enhanced in prostate cancer cells infected with adenovirus enabling Ninjurin1 overexpression. CONCLUSION: Ninjurin1-neutralizing antibodies or Ninjurin1-targeting siRNA merit further development for patients with metastatic potential.

Dose-dependent mortality and organ injury in a cecal slurry peritonitis model.

BACKGROUND: The cecal slurry model was introduced as an alternative method for creating an animal sepsis model. This study was performed to evaluate dose-dependent mortality and organ injury in a sepsis model of cecal slurry peritonitis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 5.0, 7.5, 10, or 15 mL/kg groups, according to the volume of cecal slurry administered into the peritoneal cavity. In the survival study, rats were observed for 14 d after sepsis induction. In the second experiment, blood and tissue were harvested to measure organ injury and the 2', 7'-dichlorofluorescein diacetate concentrations. RESULTS: All rats in the 5.0 mL/kg group survived for 14 d, whereas all rats in the 15 mL/kg group died within 24 h. The survival rates in the 7.5 mL/kg and 10 mL/kg groups were 60% and 30%, respectively. In the arterial blood gas analysis, lactate concentrations increased and HCO3- decreased in a dose-dependent manner across the groups. Alanine aminotransferase and blood urea nitrogen concentrations increased as the dose of cecal slurry increased. 2', 7'-Dichlorofluorescein diacetate concentrations also increased in a dose-dependent manner. CONCLUSIONS: The cecal slurry model of sepsis evaluated in this study demonstrates dose-dependent mortality, metabolic acidosis, liver and kidney injuries, and reactive oxygen species production, and it could be used for subsequent sepsis experiments, considering the severity of sepsis induced.

Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements.

Circulating tumor cells serve as useful biomarkers with which to identify disease status associated with survival, metastasis and drug sensitivity. Here, we established a novel application for detecting PSA/PSMA-positive prostate cancer cells circulating in peripheral blood employing an adenovirus called Ad5/35E1aPSESE4. Ad5/35E1aPSESE4 utilized PSES, a chimeric enhancer derived from PSA/PSMA promoters that is highly active with and without androgen. A fluorescence signal mediated by GFP expression upon Ad5/35E1aPSESE4 infection was selectively amplified in PSA/PSMA-positive prostate cancer cells in vitro and ex vivo. Furthermore, for the in vivo model, blood drawn from TRAMP was tested for CTCs with Ad5/35E1aPSESE4 infection and was positive for CTCs at week 16. Validation was performed on patient blood at various clinical stages and found out 1-100 CTCs expressing GFP upon Ad5/35E1aPSESE4 infection. Interestingly, CTC from one patient was confirmed to be sensitive to docetaxel chemotherapeutic reagent and to abundantly express metastasis-related genes like MMP9, Cofilin1, and FCER1G through RNA-seq. Our study established that the usage of Ad5/35E1aPSESE4 is effective in marking PSA/PSMA-positive prostate cancer cells in patient blood to improve the efficacy of utilizing CTCs as a biomarker.

Proinflammatory and anti-inflammatory cytokine balance in patients with cirrhotic hepatitis during live-donor liver transplant.

OBJECTIVES: The immune system releases cytokines during the stress response, and the balance between proinflammatory and anti-inflammatory cytokines is important. This prospective study was done to determine which cytokines are responsible for maintaining cytokine balance during live-donor liver transplant surgery. MATERIALS AND METHODS: Recipients undergoing live-donor liver transplant surgery due to cirrhotic hepatitis were allocated to a recipient group (n=44), and healthy donors were placed in the donor group (n=45). In donors, blood sampling for cytokine level analysis was performed after anesthetic induction (before the start of surgery, time point 1). In recipients, blood samples were collected before the start of surgery (time point 1), 60 minutes after the start of the anhepatic period (time point 2), and 60 minutes after reperfusion (time point 3). The proinflammatory cytokines measured were interleukin-1 ß, interleukin-6, and tumor necrosis factor-α; the anti-inflammatory cytokines were interleukin-10 and interleukin-4. Cytokines were quantified using sandwich enzyme-linked immunoassays. The time course of proinflammatory and anti-inflammatory cytokine concentrations during surgery in the recipient group was evaluated. RESULTS: Interleukin-6, interleukin-10 and tumor necrosis factor-α showed significant changes in concentration during surgery, with interleukin-6 reaching levels 40 times higher than the preoperative value at the anhepatic stage. Interleukin-10 reached a peak at the neohepatic phase, with values 60 times higher than the preoperative value. The preoperative concentrations of interleukin-6 and interleukin-10 in the recipient group were higher than those in the donor group with a median of 4.48 vs 1.98 pg/mL (P < .001) and 2.98 vs 1.22 (P = .026). CONCLUSIONS: Interleukin-6 and interleukin-10 play a major role in cytokine balance before and during live-donor liver transplant surgery.