Pharmacokinetic Comparison Between a Fixed-Dose Combination of Atorvastatin/Omega-3-Acid Ethyl Esters and the Corresponding Loose Combination in Healthy Korean Male Subjects.

Purpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects. Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters. Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054-1.1883) and 0.9885 (0.9588-1.0192) for atorvastatin, 0.9607 (0.9068-1.0178) and 0.9770 (0.9239-1.0331) for EPA, and 0.9961 (0.9127-1.0871) and 0.9634 (0.8830-1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated. Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia.

AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma.

Introduction: AVEN, an apoptosis and caspase activation inhibitor, has been associated with adverse clinical outcomes and poor prognosis in Acute myeloid leukemia (AML). Targeting AVEN in AML improves apoptosis sensitivity and chemotherapy efficacy, making it a promising therapeutic target. However, AVEN's role has not been studied in solid tumors. Therefore, our study investigated AVEN as a prognostic biomarker in a more comprehensive manner and developed an AVEN-derived prognostic model in Lung adenocarcinoma (LUAD). Method: Pan-cancer analysis was performed to examine AVEN expression in 33 cancer types obtained from the TCGA database. GEPIA analysis was used to determine the predictive value of AVEN in each cancer type with cancer-specific AVEN expression. Lung Adenocarcinomas (LUAD) patients were grouped into AVENhigh and AVENlow based on AVEN expression level. Differentially expressed genes (DEGs) and pathway enrichment analysis were performed to gain insight into the biological function of AVEN in LUAD. In addition, several deconvolution tools, including Timer, CIBERSORT, EPIC, xCell, Quanti-seq and MCP-counter were used to explore immune infiltration. AVEN-relevant prognostic genes were identified by Random Survival Forest analysis via univariate Cox regression. The AVEN-derived genomic model was established using a multivariate-Cox regression model and GEO datasets (GSE31210, GSE50081) were used to validate its prognostic effect. Results: AVEN expression was increased in several cancer types compared to normal tissue, but its impact on survival was only significant in LUAD in the TCGA cohort. High AVEN expression was significantly correlated with tumor progression and shorter life span in LUAD patients. Pathway analysis was performed with 838 genes associated with AVEN expression and several oncogenic pathways were altered such as the Cell cycle, VEGFA-VEGFR2 pathway, and epithelial-mesenchymal-transition pathway. Immune infiltration was also analyzed, and less infiltrated B cells was observed in AVENhigh patients. Furthermore, an AVEN-derived genomic model was established, demonstrating a reliable and improved prognostic value in TCGA and GEO databases. Conclusion: This study provided evidence that AVEN is accumulated in LUAD compared to adjacent tissue and is associated with poor survival, high tumor progression, and immune infiltration alteration. Moreover, the study introduced the AVEN-derived prognostic model as a promising prognosis tool for LUAD.

Safety and pharmacokinetic comparison between fenofibric acid 135 mg capsule and 110 mg enteric-coated tablet in healthy volunteers.

This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a non-compartmental method with Phoenix WinNonlin®. A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (Cmax) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795-0.9614) and 0.8630 (0.8472-0.8791) in the fasting study and 1.0926 (1.0102-1.1818) and 0.9998 (0.9675-1.0332) in the fed study, respectively. The time to reach Cmax of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. Trial Registration: Clinical Research Information Service Identifier: KCT0007177, KCT0003304.

Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer.

ETS-related gene (ERG) fusion affects prostate cancer depending on the degree of expression of ERG. Solute Carrier Family 45 Member 3 (SLC45A3) is the second-most common 5' partner gene of ERG rearrangement. However, the molecular pathological features of SLC45A3:ERG (S:E) fusion and therapeutic methods have not been studied at all. S:E fusion-positive cancers (n = 10) were selected from the Tumor Fusion Gene Data Portal website. Fusion-negative cancers (n = 50) were selected by sorting ERG expression level in descending order and selecting the bottom to 50th sample. Totally, 1325 ERG correlated genes were identified by a Pearson correlation test using over 0.3 of absolute correlation coefficiency (|R| > 0.3). Pathway analysis was performed using over-representation analysis of correlated genes, and seven cancer-related pathways (focal adhesion kinase (FAK)/PI3K-Akt, JAK-STAT, Notch, receptor tyrosine kinase/PDGF, TGF-ß, VEGFA, and Wnt signaling) were identified. In particular, focal adhesion kinase (FAK)/PI3K-Akt signaling and JAK-STAT signaling were significantly enriched in S:E fusion-positive prostate cancer. We further identified therapeutic targets and candidate drugs for S:E fusion-positive prostate cancer using gene−drug network analysis. Interestingly, PDGFRA and PDGFRB were the most frequently predicted therapeutic targets, and imatinib targeted both genes. In this study, we provide extensive information on cellular signaling pathways involved in S:E fusion-positive prostate cancer and also suggest therapeutic methods.

Pharmacokinetic Interaction between Atorvastatin and Omega-3 Fatty Acid in Healthy Volunteers.

The interaction between statins and omega-3 fatty acids remains controversial. The aim of this phase 1 trial was to evaluate the pharmacokinetics of drug-drug interaction between atorvastatin and omega-3 fatty acids. Treatments were once-daily oral administrations of omega-3 (4 g), atorvastatin (40 mg), and both for 14 days, 7 days, and 14 days, respectively, with washout periods. The concentrations of atorvastatin, 2-OH-atorvastatin, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were determined with LC-MS/MS. Parameters of DHA and EPA were analyzed after baseline correction. A total of 37 subjects completed the study without any major violations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the co-administration of a single drug for the area under the concentration-time curve during the dosing interval at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.042 (0.971-1.118), 1.185 (1.113-1.262), 0.157 (0.091-0.271), and 0.557 (0.396-0.784), respectively. The GMRs (90% Cis) for the co-administration at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.150 (0.990-1.335), 1.301 (1.2707-1.1401), 0.320 (0.243-0.422), and 0.589 (0.487-0.712), respectively. The 90% CIs for most primary endpoints were outside the range of typical bioequivalence, indicating a pharmacokinetic interaction between atorvastatin and omega-3.

Weight Gain and Lipid Profile Changes in Koreans with Human Immunodeficiency Virus undergoing Integrase Strand Transfer Inhibitor-Based Regimens.

BACKGROUND: This study explored the relationship between integrase strand transfer inhibitor (INSTI)-based anti-retroviral agents and weight gain over time, and the risk factors for weight gain in Korean people living with human immunodeficiency virus (PLWH). MATERIALS AND METHODS: The study was conducted retrospectively in PLWHs 18 years of age or older who took one of three INSTI-based single-tablet regimens (STRs) (tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat [TDF/F/EVG/c], tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat [TAF/F/EVG/c], and abacavir/lamivudine/dolutegravir [ABC/3TC/DTG]) for more than 2 years at three university-affiliated hospitals in South Korea from May 2014 to December 2020. Analysis was performed in the treatment-naïve and treatment-experienced groups, respectively. RESULTS: Individual INSTI-based STRs were associated with weight gain at the 24-month follow up in both treatment-naïve (n = 179) and treatment-experienced (n = 290) groups. Body mass index (BMI) categories changed over time for TAF/F/EVG/c and ABC/3TC/DTG, with significant increases in the rates of overweight and obesity in treatment-naïve patients, whereas there was no change for TDF/F/EVG/c. TAF/F/EVG/c significantly increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) compared to other regimens over 24 months. In the treatment-naïve group, a baseline CD4+ T cell count <100 cells/mm3, human immunodeficiency virus (HIV) viral load (VL) ≥100,000 copies/mL, no physical exercise, and TAF/F/EVG/c (vs. TDF/F/EVF/c) were risk factors for ≥10% weight gain. In the treatment-experienced group, age <45 years, BMI <25 kg/m², and no physical exercise were risk factors for ≥5% weight gain. CONCLUSION: INSTI-based STR continued to increase body weight at the 24-month follow up in treated and untreated Korean PLWH. Exercise, together with demographic-, HIV-, and anti-retroviral therapy-related factors, influenced weight gain. Therefore, when prescribing an INSTI-based STR, weight gain and metabolic changes should be closely monitored in PLWH with these risk factors.

Allergenic characterization of Bomb m 4, a 30-kDa Bombyx mori lipoprotein 6 from silkworm pupa.

BACKGROUND: Silkworm pupa (SWP) food anaphylaxis has been described frequently in Asian countries. However, false-positive reactions by skin pricks and serum IgE (sIgE) tests to the extract complicate diagnosis, requiring identification of clinically relevant major allergens. OBJECTIVES: In this study, we characterized a novel SWP allergen, Bomb m 4, a 30-kDa lipoprotein, and evaluated its diagnostic sensitivity. METHODS: Bomb m 4 was identified by a proteomic analysis. This recombinant (r)Bomb m 4 was overexpressed in Escherichia coli, and the IgE reactivity by ELISA was compared with other reported allergenic proteins: Bomb m 1 (arginine kinase), 27-kDa glycoprotein, Bomb m 3 (tropomyosin) using the serum samples from 17 SWP allergic patients and 11 asymptomatic sensitized subjects. RESULTS: rBomb m 4-specific IgE was recognized by all 17 SWP allergic patients. The 27-kDa glycoprotein and Bomb m 1 sIgE were found in 35.3% and 0%, respectively, in the SWP allergic patients. ELISA sIgE reactivity increased significantly, when 4 M urea was added in serum samples. However, only 16% inhibition of sIgE reactivity to the whole SWP extract was exhibited by rBomb m 4, whereas more than 93% of self-inhibition of rBomb m 4 sIgE was obtained, possibly due to the low abundance of Bomb m 4 in the extract. Three linear epitopes (81-95, 191-205 and 224-238 residues) of rBomb m 4 were identified. These epitopes are shown to be released by pepsin digestion. Receiver operator characteristic (ROC) analysis showed the highest diagnostic value of Bomb m 4 followed by Bomb m 1, 27-kDa glycoprotein and Bomb m 3. CONCLUSION: Bomb m 4 is the major allergen of SWP allergic patients. It has cryptic epitopes which are exposed to IgE antibodies with digestive enzymes. This recombinant Bomb m 4 allergen permits exact diagnosis of SWP allergy.

Controlling Graphene Wrinkles through the Phase Transition of a Polymer with a Low Critical Solution Temperature.

A novel method for controlling reduced graphene oxide (rGO) wrinkles through a phase transition in a solution using a low critical solution temperature (LCST) polymer dispersant has been developed. The polymer dispersant is designed by control of architecture and composition using reversible addition-fragmentation chain transfer polymerization. Synthesized poly(2-(dimethylaminoethyl) methacrylate-block-styrene) (PDbS) can be successfully functionalized on the rGO surface via noncovalent functionalization. PDbS-functionalized rGO (PDbS-rGO) exhibits good dispersibility in an aqueous phase at room temperature and forms wrinkles on the PDbS-rGO surface because of phase transition at the LCST of the polymer dispersant. The formation of PDbS-rGO wrinkles is controlled by varying the aggregation number of the polymer dispersant on the PDbS-rGO surface that strongly depends on temperature. This is confirmed by transmission electron microscopy, scanning electron microscopy, and Raman spectroscopy (ID' /IG ratios are 0.560, 0.579, and 0.684, which correspond to 45, 70, and 95 °C, respectively). In addition, the mechanism of wrinkle control is proved by gold nanoparticles that are grown in polymer dispersant on the PDbS-rGO surface.

Comparison of Prospective and Retrospective Methods of a Tigecycline Post-Marketing Surveillance Study in the Safety Outcomes of Patients with Complicated Skin Structure Infection, Complicated Intraabdominal Infection and Community-Acquired Pneumonia.

INTRODUCTION: Safety data can be collected through prospective and retrospective methods during post-marketing surveillance (PMS). This study aimed to compare prospective and retrospective methods in terms of examining safety data from PMS of tigecycline. METHODS: This PMS study was an open-label, noncomparative, observational, noninterventional and multicenter study of patients who received tigecycline for infections. From July 2007 to April 2015, 3172 patients were included in this study, of which 738 were enrolled prospectively and 2434 retrospectively. To reduce selection bias, demographic and baseline characteristics were adjusted using 1:2 propensity score matching. RESULTS: After propensity score matching, data from 1446 patients were analyzed. The incidences of adverse events (AEs) and serious AEs (SAEs) were determined to be significantly higher in the prospective method compared with those of the retrospective method (P < 0.001 and P = 0.004, respectively). However, no significant differences in the incidences of adverse drug reactions (ADRs) and serious ADRs (SADRs) were detected between the two groups (P = 0.09 and P = 0.33, respectively). In a subgroup analysis of 360 patients from 14 hospitals involved in both prospective and retrospective methods, the incidence of AEs was found to be significantly higher using the prospective method compared with when the retrospective method was used (P < 0.001), but there were no significant differences in ADRs (P = 0.14), SAEs (P = 0.24) and SADRs. CONCLUSION: In general, the prospective method can detect safety data effectively in a PMS study, whereas retrospective data collection may be an alternative option in collecting ADR data when a prospective PMS study is not deemed feasible.

Does a nurse-led postpartum self-care program for first-time mothers in Bangladesh improve postpartum fatigue, depressive mood, and maternal functioning?: a non-synchronized quasi-experimental study.

Purpose: This study aimed to test the efficacy of a nurse-led postpartum self-care (NLPPSC) intervention at reducing postpartum fatigue (PPF) and depressive mood and promoting maternal functioning among first-time mothers in Bangladesh. Methods: A non-synchronized quasi-experimental design was used. First-time mothers were recruited during postpartum and assigned to the experimental or control group (34 each). The experimental group received the NLPPSC in the hospital, a 1-day intervention that focused on increasing self-efficacy. The control group received usual care. Data on PPF, depressive mood, maternal functioning, self-care behaviors, postpartum self-efficacy, and self-care knowledge were collected at postpartum 2 weeks (attrition 23.5%) and 6 weeks (attrition 16.1%). Data were analyzed using descriptive statistics, bivariate statistics, and linear mixed model analysis. Results: One-third (33.3%) of new mothers experienced depressive mood (Edinburgh Postnatal Depression Scale scores of ≥13 points). The NLPPSC intervention was statistically significant in decreasing PPF (ß=-6.17, SE=1.81, t=-3.39, p<.01) and increased maternal functioning at postpartum 6 weeks in the experimental group (ß=13.72, t=3.73, p<.01) compared to the control. Knowledge was also statistically significant for increased maternal functioning over time (ß=.37, SE=.18, t=2.03, p<.05). However, there were no statistically significant differences in depressive mood over time. Conclusion: The NLPPSC intervention was feasible and effective in improving fatigue and maternal functioning in Bangladeshi mothers by postpartum 6 weeks. Postpartum care knowledge was effective in improved maternal functioning and thus supports implementing the NLPPSC intervention for new mothers after childbirth.

Recurrence of clinical events at the same anatomical location in patients with MOG antibody-associated disease.

OBJECTIVES: Likelihood of clinical events occurring within the same anatomical location in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) was retrospectively investigated. METHODS: A total of 236 clinical events in 90 patients with MOGAD from nine referral hospitals were analyzed via logistic regression, and odds ratios (ORs) were calculated. Anatomical lesion location was divided into four groups; optic nerve, spinal cord, cerebral hemisphere, and brainstem/cerebellum. RESULTS: At all locations, there was an increased likelihood of a second attack occurring at the same location as the initial event (cerebral hemisphere OR = 22.14, brainstem/cerebellum OR = 18.4, spinal cord OR = 9.1, and optic nerve OR = 7.8). There was an increased likelihood of a third attack occurring at the same location as the initial event in the optic nerve (OR = 14.9), cerebral hemisphere (OR = 11.7), and spinal cord (OR = 6.7). There were positive trends toward a third clinical event occurring at the same location as the first and/or second events if the event was in the optic nerve (OR = 13.5), cerebral hemisphere (OR = 6.9), or spinal cord (OR = 5.7). CONCLUSIONS: The current study suggests that clinical relapses of MOGAD during early stage tend to recur at the same anatomical locations in the central nervous system.

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

Cyclic Peptide Mimotopes for the Detection of Serum Anti-ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma.

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.

Value of Area Postrema Syndrome in Differentiating Adults With AQP4 vs. MOG Antibodies.

Objectives: To compare the frequency of area postrema syndrome (APS) in adults with anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: APS is defined as acute or subacute, single or combined, episodic or constant nausea, vomiting, or hiccups, persisting for at least 48 h, which cannot be attributed to any other etiology. The presence of APS was investigated in 274 adults with AQP4 antibodies and 107 adults with MOG antibodies from 10 hospitals. Results: The study population comprised Korean adults (≥18 years). At the time of disease onset, 14.9% (41/274) adults with AQP4 antibodies had APS, while none of the participants with MOG antibodies developed APS (p < 0.001). During the course of the disease, 17.2% (47/274) adults with AQP4 antibodies had APS in contrast to 1.9% (2/107) adults with MOG antibodies with APS (p < 0.001). Conclusions: APS, one of the core clinical characteristics of individuals with AQP4 antibodies, is an extremely rare manifestation in Korean adults with MOG antibodies.

Highly Exfoliated and Functionalized Single-Walled Carbon Nanotubes as Fast-Charging, High-Capacity Cathodes for Rechargeable Lithium-Ion Batteries.

Compared with traditional metal-oxide lithium-ion battery (LIB) cathodes, nanocarbon-based cathode materials have received much attention for potential application in LIBs because of their superior power density and long-term cyclability. However, their lithium-ion storage capacity needs further improvement for practical applications, and the trade-off between capacity and conductivity, when oxygen functional groups as lithium-ion storage sites are introduced to the nanocarbon materials, needs to be addressed. Here, we report a sequential oxidation-reduction process for the synthesis of single-walled carbon nanotubes (SWCNTs) for LIB cathodes with fast charging, long-term cyclability, and high gravimetric capacity. A LIB cathode based on highly exfoliated (dbundle < 10 nm) and oxygen-functionalized single-walled carbon nanotubes is obtained via the modified Brodie's method using fuming nitric acid and a mild oxidant (B-SWCNTs). Post treatment including horn sonication and hydrogen thermal reduction developed surface defects and removed the unnecessary C-O groups, resulting in an increase in the Li-ion storage capacity. The B-SWCNTs exhibit a high reversible gravimetric capacity of 344 mA h g-1 at 0.1 A g-1 without noticeable capacity fading after 1000 cycles. Furthermore, it delivers a high gravimetric energy density of 797 W h kgelectrode-1 at a low gravimetric power density of 300 W kgelectrode-1 and retains its high gravimetric energy density of ∼100 W h kgelectrode-1 at a high gravimetric power of 105 W kgelectrode-1. These results suggest that the highly exfoliated, oxygen-functionalized single-walled carbon nanotubes can be applied to LIBs designed for high-rate operations and long cycling.

Lignin-based barrier restricts pathogens to the infection site and confers resistance in plants.

Pathogenic bacteria invade plant tissues and proliferate in the extracellular space. Plants have evolved the immune system to recognize and limit the growth of pathogens. Despite substantial progress in the study of plant immunity, the mechanism by which plants limit pathogen growth remains unclear. Here, we show that lignin accumulates in Arabidopsis leaves in response to incompatible interactions with bacterial pathogens in a manner dependent on Casparian strip membrane domain protein (CASP)-like proteins (CASPLs). CASPs are known to be the organizers of the lignin-based Casparian strip, which functions as a diffusion barrier in roots. The spread of invading avirulent pathogens is prevented by spatial restriction, which is disturbed by defects in lignin deposition. Moreover, the motility of pathogenic bacteria is negatively affected by lignin accumulation. These results suggest that the lignin-deposited structure functions as a physical barrier similar to the Casparian strip, trapping pathogens and thereby terminating their growth.

Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma.

Tumor-associated autoantibodies are promising diagnostic biomarkers for early detection of tumors. We have screened a novel tumor-associated autoantibody in hepatocellular carcinoma (HCC) model mice. Its target antigen was identified as eukaryotic translation initiation factor 3 subunit A (EIF3A) by proteomic analysis, and the elevated expression of EIF3A in HCC tissues of tumor model mice as well as human patients was shown. Also, its existence in tumor-derived exosomes was revealed, which seem to be the cause of tumor-associated autoantibody production. To use serum anti-EIF3A autoantibody as biomarker, ELISA detecting anti-EIF3A autoantibody in human serum was performed using autoantibody-specific epitope. For the sensitive detection of serum autoantibodies its specific conformational epitopes were screened from the random cyclic peptide library, and a streptavidin antigen displaying anti-EIF3A autoantibody-specific epitope, XC90p2(-CPVRSGFPC-), was used as capture antigen. It distinguished patients with HCC (n = 102) from healthy controls (n = 0285) with a sensitivity of 79.4% and specificity of 83.5% (AUC = 0.87). Also, by simultaneously detecting with other HCC biomarkers, including alpha-fetoprotein, HCC diagnostic sensitivity improved from 79.4% to 85%. Collectively, we suggest that serum anti-EIF3A autoantibody is a useful biomarker for the diagnosis of HCC and the combinational detection of related biomarkers can enhance the accuracy of the cancer diagnosis.

Efficacy and safety of combination antifungal therapy in Korean haematological patients with invasive aspergillosis.

This randomised, double-blind, placebo-controlled trial assessed the efficacy, safety and tolerability of voriconazole+anidulafungin (combination) or voriconazole+placebo (monotherapy) for invasive aspergillosis (IA; NCT00531479). We present a post hoc analysis of Korean and non-Korean patients with IA (including baseline positive serum galactomannan [GM]). Immunocompromised patients ≥ 16 years with IA were randomised 1:1, combination or monotherapy, for ≥ 2 weeks' treatment. The primary endpoint was 6- and 12-week all-cause mortality (Korean modified intent-to-treat [mITT] population). Overall, 454 patients enrolled (Koreans: 56 [combination: 28, monotherapy: 28], non-Koreans: 398 [combination: 200, monotherapy: 198]). The mITT population comprised 40 Koreans (combination: 23; monotherapy: 17) and 237 non-Koreans (combination: 112; monotherapy: 125). Week 6 treatment difference in mortality rate between combination and monotherapy was -6.4% in non-Koreans. This reduction was more marked in Koreans (-22.4%). Week 12 difference in all-cause mortality between combination and monotherapy was -17.7% (Koreans) and -20.2% at Week 6 (Koreans; positive baseline GM). Week 6 mortality (Koreans [mITT]; baseline GM >0.5-2.0) was 0/13 (combination) and 2/6 (monotherapy). Serious adverse events were numerically higher for combination than monotherapy (Koreans: 57.1%, 46.4%; non-Koreans: 49.5%, 46.0%). In Koreans, combination therapy was associated with marginally better outcomes than monotherapy and more so than in non-Koreans.

Lipases associated with plant defense against pathogens.

When facing microbe invaders, plants activate genetic and metabolic defense mechanisms and undergo extracellular and intracellular changes to obtain a certain level of host resistance. Dynamic adjustment and adaptation occur in structures containing lipophilic compounds and cellular metabolites. Lipids encompassing fatty acids, fatty acid-based polymers, and fatty acid derivatives are part of the fundamental architecture of cells and tissues and are essential compounds in numerous biological processes. Lipid-associated plant defense responses are mostly facilitated by the activation of lipases (lipid hydrolyzing proteins), which cleave or transform lipid substrates in various subcellular compartments. In this review, several types of plant defense-associated lipases are described, including their molecular aspects, enzymatic actions, cellular functions, and possible functional relevance in plant defense. Defensive roles are discussed considering enzyme properties, lipid metabolism, downstream regulation, and phenotypic traits in loss-of-function mutants.

Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma.

BACKGROUND: Tumor-associated (TA) autoantibodies, which are generated by the immune system upon the recognition of abnormal TA antigens, are promising biomarkers for the early detection of tumors. In order to detect autoantibody biomarkers effectively, antibody-specific epitopes in the diagnostic test should maintain the specific conformations that are as close as possible to those presenting in the body. However, when using patients' serum as a source of TA autoantibodies the characterization of the autoantibody-specific epitope is not easy due to the limited amount of patient-derived serum. METHODS: To overcome these limits, we constructed a B cell hybridoma pool derived from a hepatocellular carcinoma (HCC) model HBx-transgenic mouse and characterized autoantibodies derived from them as tumor biomarkers. Their target antigens were identified by mass spectrometry and the correlations with HCC were examined. With the assumption that TA autoantibodies generated in the tumor mouse model are induced in human cancer patients, the enzyme-linked immunosorbent assays (ELISA) based on the characteristics of mouse TA autoantibodies were developed for the detection of autoantibody biomarkers in human serum. To mimic natural antigenic structures, the specific epitopes against autoantibodies were screened from the phage display cyclic random heptapeptide library, and the streptavidin antigens fused with the specific epitopes were used as coating antigens. RESULTS: In this study, one of HCC-associated autoantibodies derived from HBx-transgenic mouse, XC24, was characterized. Its target antigen was identified as splicing factor 3b subunit 1 (SF3B1) and the high expression of SF3B1 was confirmed in HCC tissues. The specific peptide epitopes against XC24 were selected and, among them, XC24p11 cyclic peptide (-CDATPPRLC-) was used as an epitope of anti-SF3B1 autoantibody ELISA. With this epitope, we could effectively distinguish between serum samples from HCC patients (n = 102) and healthy subjects (n = 85) with 73.53% sensitivity and 91.76% specificity (AUC = 0.8731). Moreover, the simultaneous detection of anti-XC24p11 epitope autoantibody and AFP enhanced the efficiency of HCC diagnosis with 87.25% sensitivity and 90.59% specificity (AUC = 0.9081). CONCLUSIONS: ELISA using XC24p11 peptide epitope that reacts against anti-SF3B1 autoantibody can be used as a novel test to enhance the diagnostic efficiency of HCC.