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Aquaculture is notably vulnerable to diseases, with Edwardsiella tarda causing significant mortality across various commercially important fish species in both freshwater and marine environments. In the aquaculture industry, sustainable disease control hinges on the effective development of vaccines. Oral vaccines present an appealing approach to immunization in fish due to their ease of antigen administration, reduced stress compared to non-oral delivery methods, and their potential applicability to both small and large finfish species. In mammals, the exposure of mucosal surfaces to antigens results in the secretion of antigen-specific IgA at these locations. Mammals have a common mucosal immune system, in which stimulation of one epithelium can also give rise to specific IgA or IgM responses in other mucosal organs. Mucosal immunoglobulins are particularly important in developing vaccines that provide mucosal immunity. However, it remains unclear whether fish share a common mucosal system. Moreover, neither Peyer's patches nor intestinal lymph nodes were identified. Nevertheless, oral vaccination remains an attractive method for inducing immunity. We investigated whether the activation of the mucosal immune response was induced by direct injection of the antigen. After oral antigen administration, antigen-specific antibody titers increased in the experimental group (E. tarda FKC vaccine). In the challenge experiment, the cumulative survival rate was 72% (E. tarda). This suggests that oral administration of antigens can activate intestinal mucosal immunity in flounders. Additionally, these results help understand the intestinal mucosal immune system of teleost fish. In the future, research on the signaling mechanisms of these genes is expected to provide helpful information for developing vaccine adjuvants., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history., Design: Retrospective matched cohort and crossover case series study., Methods: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis., Results: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively., Conclusions: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group., Design: Retrospective population-based cohort study., Methods: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group. The study observed for 180 days from their index date. Cumulative incidence and risk of NIU following COVID-19 vaccination, and attributable risk factors were assessed., Results: Multivariable analysis showed elevated risk of nonanterior NIU within 60 days (hazard ratio [HR] 1.27 [95% confidence interval {CI} 1.03-1.55] and 61-180 days (HR 1.39 [95% CI 1.20-1.62]). Subgroup analysis highlighted an increased risk in females for early and delayed nonanterior uveitis (HR 1.44 [95% CI 1.08-1.92]; HR 1.78 [95% CI 1.43-2.20], respectively). Regardless of the location and onset timing of uveitis, a history of NIU was identified as the most significant risk factor, with a high hazard ratio ranging from 100 to 200., Conclusions: COVID-19 vaccination may modestly increase the risk of nonanterior uveitis especially in females. Despite adjustments, bias may persist in the exposed group, owing to significant differences between unexposed and exposed groups and low incidence of nonanterior uveitis in the unexposed group. Future research should aim to refine these findings by assessing uveitis risk in prior NIU patients and by enlarging the sample size or cohort matching., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nanoplastics (NPs) exposure to humans can occur through various routes, including the food chain, drinking water, skin contact, and respiration. NPs are plastics with a diameter of less than 100 nm and have the potential to accumulate in tissues, leading to toxic effects. This study aimed to investigate the neurotoxicity of polystyrene NPs on neural progenitor cells (NPCs) and hippocampal neurogenesis in a rodent model. Toxicity screening of polystyrene NPs based on their charge revealed that cationic amine-modified polystyrene (PS-NH 3 + ) exhibited cytotoxicity, while anionic carboxylate-modified polystyrene (PS-COO - ) and neutral NPs (PS) did not. NPCs treated with PS-NH 3 + showed a significant reduction in growth rate due to G1 cell cycle arrest. PS-NH 3 + increased the expression of cell cycle arrest markers p21 and p27, while decreasing cyclin D expression in NPCs. Interestingly, PS-NH 3 + accumulated in mitochondria, leading to mitochondrial dysfunction and energy depletion, which caused G1 cell cycle arrest. Prolonged exposure to PS-NH 3 + in C17.2 NPCs increased the expression of p16 and senescence-associated secretory phenotype factors, indicating cellular senescence. In vivo studies using C57BL/6 mice demonstrated impaired hippocampal neurogenesis and memory retention after 10 days of PS-NH 3 + administration. This study suggests that NPs could deplete neural stem cell pools in the brain by mitochondrial dysfunction, thereby adversely affecting hippocampal neurogenesis and neurocognitive functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Solid organ transplant recipients (SOTRs) are susceptible to severe coronavirus disease 2019 (COVID-19); however, immunogenicity studies of the Omicron variants per vaccination schedules are still lacking. We examined humoral immunogenicity following third-dose mRNA vaccine administration in Korean SOTRs who received primary COVID-19 vaccine series on homologous or heterologous schedules., Methods: We recruited SOTRs at Severance Hospital from October 27, 2021, to March 31, 2022. Blood samples were collected between 14 days and 5 months after the second and third mRNA vaccine (BNT162b2 or mRNA-1273) doses. SARS-CoV-2 anti-spike IgG titer was analyzed. The neutralization inhibition rate was analyzed using the surrogate neutralization assay for the wild-type, Delta, and Omicron variants., Results: No significant differences existed in the SARS-CoV-2 anti-spike IgG positivity rate between the homologous BNT162b2/BNT162b2/BNT162b2 (85%) and other heterologous groups (83% of ChAdOx1/ChAdOx1/BNT162b2, 90% of ChAdOx1/ChAdOx1/mRNA-1273, and 78% of ChAdOx1/BNT162b2/BNT162b2). No significant difference existed in the neutralization inhibition rates between the four groups for wild-type, Delta, and Omicron variants. Median neutralization inhibition rates against the Omicron variant (2-5%) were significantly lower than those against the wild-type (87-97%) and Delta (55-89%) variants (P < 0.001)., Conclusions: Regardless of the schedule, the neutralization inhibition rate against the Omicron variant was poor; therefore, additional preventive measures are required in such high-risk populations., Competing Interests: Declaration Competing of Interest The authors of this manuscript have no conflicts of interest to disclose, as described by the American Journal of Transplantation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS-FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Wechsler Adult intelligence scale-Revised (WAIS-R) Block design test (BDT) is a neuropsychological test widely used to assess cognitive declines in aging population. Previous studies suggest parietal lobe is the key region to influence the performance on the BDT; yet, it has not been clearly identified. The aim of the current study, therefore, is to identify the functional neural correlates of the BDT in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia patients. The current study includes 213 cognitively impaired mid to old-aged community dwelling Korean. All participants underwent comprehensive clinical and neuropsychological assessments and 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans. Performance on the BDT was assessed using the WAIS-IV Korean version. Voxel-wise analyses were used to investigate the correlation between regional cerebral glucose metabolism and BDT performance. The same analyses were conducted on the subgroups categorized by clinical severity based on the Clinical Dementia Rating (CDR). Significant positive correlations between performance on the BDT and regional cerebral glucose metabolism were found bilaterally in the inferior parietal lobules, right thalamus and right middle frontal gyrus. Our results suggest that performance on the BDT in MCI and AD patients functionally relies on the brain regions known to be associated with motor and executive functions in addition to visuospatial function., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Liver tissue engineering offers a promising strategy for liver failure patients. Since transplantation rejection resulting in vessel thrombosis is regarded as a major hurdle, vascular reconstruction is one of indispensable requirements of whole organ engineering. Here we demonstrated a novel strategy for reconstruction of a vascularized bioengineered human liver (VBHL) using decellularized liver scaffolds in an efficient manner. First we achieved fully functional endothelial coverage of scaffolds by adopting the anti-CD31 aptamer as a potent coating agent for re-endothelialization. Through an ex vivo human blood perfusion that recapitulates the blood coagulation response in humans, we demonstrated significantly reduced platelet aggregation in anti-CD31 aptamer coated scaffolds. We then produced VBHL constructs using liver parenchymal cells and nonparenchymal cells, properly organized into liver-like structures with an aligned vasculature. Interestingly, VBHL constructs displayed prominently enhanced long-term liver-specific functions that are affected by vascular functionality. The VBHL constructs formed perfusable vessel networks in vivo as evidenced by the direct vascular connection between the VBHL constructs and the renal circulation. Furthermore, heterotopic transplantation of VBHL constructs supported liver functions in a rat model of liver fibrosis. Overall, we proposed a new strategy to generate transplantable bioengineered livers characterized by highly functional vascular reconstruction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Women have an increased likelihood of sustaining a fall-related injury compared to men; however, little is known about fall prevention strategies between genders. The purpose of this study was to compare the gender differences in lower limb reactions and three-dimensional recovery patterns following a treadmill-induced trip perturbation., Methods: Seventy-six participants who are right limb dominant enrolled in the study, which included 41 females (26.15 [9.92] years old) and 35 males (27.11 [9.15] years old). The outcome measures included a three-dimensional (3D) range of motion (ROM) analysis on the bilateral hip, knee, and ankle joints following the trip perturbation at a 0.89 m/s velocity for 0.12 m. This induced trip caused subjects to walk forward for a 0.26 s duration., Findings: The female group demonstrated significantly increased frontal plane ROM in the right hip (t = 2.71, p = 0.01) and left ankle (t = 2.16, p = 0.03) as well as increased sagittal plane ROM in the right (t = 2.07, p = 0.04) and left (t = 2.36, p = 0.02) ankles. There was a significant gender interaction on 3D body region (F = 6.84, p = 0.01) following the perturbation., Interpretation: There was a 3D gender difference on the lower limbs for balance control. The female group demonstrated increased sagittal motion in both ankles following a trip perturbation. In addition, their ROM increased on the dominant hip and non-dominant ankle in the frontal plane, which was compensated by step width for standing stability. Clinicians might want to consider the implications of gender differences on lower limb reaction patterns to help patients avoid potential injuries/falls., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Antimicrobial peptides (AMPs) are molecular factors in innate immunity and are believed to play a key role in invertebrate host defence. We identified theromacin (TM) from an Asian polychaeta, Perinereis linea, using de novo RNA-seq analysis. TM, a typical AMP of invertebrates, is a cysteine-rich AMP with five disulfide bonds consisting of ten cysteine residues. In gene expression analysis, TM genes were constantly upregulated after lipopolysaccharide (LPS) stimulation. In contrast, after peptidoglycan (PGN) stimulation, it was upregulated initially and downregulated after 12 h. We synthesized a peptide based on the macin AMP in the TM amino acid sequence. The synthetic peptide showed antibacterial activity against some Gram-positive and Gram-negative bacteria. Therefore, the AMPs of P. linea might have broad roles in host defence and exhibit different degrees of activity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Eremochloa ophiuroides, a perennial warm-season lawn grass, has a characteristic phenotype of red pigmentation in tissues during maturation. The putative gene families associated with the red coloration were previously identified in E. ophiuroides. These genes encode chalcone synthases, flavonol 3-hydroxylases, and flavonol 3'-hydroxylases, acting on the early flavonoid-biosynthesis pathway. Here, a type-I chalcone isomerase (CHI) gene was isolated from E. ophiuroides based on leaf-transcriptome data, and the corresponding enzyme was functionally characterized in vitro and in planta. Complementation of Arabidopsis tt5 mutants by overexpressing EoCHI recapitulated the wild-type seed coat color. Wounding and methyl jasmonate treatments significantly elevated the transcript level of EoCHI and total anthocyanin content in shoots. Confocal microscopy indicated the localization of EoCHI to the endoplasmic reticulum. The genomic EoCHI sequence contained two introns with a novel pattern of exon‒intron organization. Further examinations on genomic structures of CHI family from ancient to advanced plant lineages should be of interests to decipher evolutionary pathways of extant plant CHI genes., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Sulfate metabolism and glucose (Glc) signaling are important processes required for plant growth, development, and environmental responses. However, whether sulfate metabolism is involved in Arabidopsis response to Glc stress remains largely unclear. Recently, we have found that proline content alterative 17 (pca17) is a double-mutant line in which both AtRZF1 (for Arabidopsis thaliana Ring Zinc Finger 1) and AHL (for Arabidopsis Halotolerance 2-like) genes are mutated. It was found that insensitive response of atrzf1 mutant to abiotic stresses was suppressed in pca17 mutant by regulating proline metabolism. Here, pca17 appeared to have sensitive response to Glc treatment by reducing cysteine (Cys) and adenosine monophosphate (AMP) contents in sulfate metabolism. Under Glc treatment, transcript levels of sulfate metabolism-related genes were significantly lower in pca17 than those in wild-type (WT) and atrzf1. Furthermore, AHL-overexpressing transgenic lines displayed more insensitive phenotypes than WT during Glc condition while ahl RNAi lines exhibited sensitive responses based on several parameters, including seed germination rate, cotyledon greening percentage, root elongation, and fresh weight. Interestingly, the pca17 phenotype in applied AMP with Glc treatment was similar to atrzf1 phenotype. Taken together, our results indicate that AHL is involved in Glc response by modulating sulfate metabolism in Arabidopsis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) is a warm-season turfgrass, widely planted in residential lawns and recreational fields. Here, we uncovered three major terpenes released from the shoots of Eo: (E)-β-ocimene (6%), α-muurolene (87.8%), and eremophilene (6.2%). Methyl jasmonate (MeJA) treatment increased the emission of monoterpenes, including (E)- and (Z)-β-ocimene, limonene, and myrcene, as well as sesquiterpene blends of (E)-caryophyllene, α-copaene, (+)-cyclosativene, and α-farnesene. RNA sequencing analysis predicted 14 putative Eo terpene synthase (EoTPS) genes, and two full-length EoTPS were successfully amplified: Eo7816 (1722 bp) and Eo6039 (1701 bp). Phylogenetic analysis revealed that Eo7816 and Eo6039 belonged to the clades of TPS-b and TPS-a, respectively. The Arabidopsis transgenic plants overexpressing Eo7816 exclusively released (E)-β-ocimene (96%) with (Z)-β-ocimene and myrcene. In contrast, Eo6039-overexpressing Arabidopsis plants emitted significant amounts of α-muurolene (69.4%) and eremophilene (21.8%). Together, we demonstrated that the two TPSs play roles in producing major volatile terpenes in Eo., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Apurinic/apyrimidinic endonuclease/redox factor-1 (Ref-1), a multifunctional protein secreted from stimulated cells, has been identified as a new serological biomarker. Despite recent reports on the role of Ref-1 in inflammation, the biological function of secreted Ref-1 remains unknown, especially in vivo. This study aimed to evaluate the possible roles of secreted Ref-1 in lipopolysaccharide-induced systemic inflammation in vivo. We generated a secretory Ref-1 adenoviral vector system, AdPPT-LS-Ref-1, by conjugation of preprotrypsin leading sequence (PPT-LS) with full-length Ref-1 sequences. Expression of tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells and lipopolysaccharide (LPS)-induced cyclooxygenase-2 in Raw264.7 cells was inhibited by secretory Ref-1, and this inhibitory effect was abrogated following neutralization of Ref-1 with anti-Ref-1 antibody. Plasma Ref-1 levels following administration of AdPPT-LS-Ref-1 (2 × 10 9 ifu, i.p.) for 24 h were substantially higher than those recorded following administration of Adβgal (84.6 ± 7.2 ng/ml vs. 4.4 ± 1.5 ng/ml). Treatment with LPS (10 mg/kg, i.v. for 6 h) markedly increased VCAM-1 expression, cathepsin or myeloperoxidase activity, which were significantly suppressed by treatment with AdPPT-LS-Ref-1. Furthermore, LPS-induced cytokines, such as TNF-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein 1, were significantly inhibited in AdPPT-LS-Ref-1-treated mice. However, LPS-induced myeloperoxidase activities were not suppressed by treatment with the redox mutant of secretory Ref-1, AdPPT-LS-Ref-1(C65A/C93A), or wild-type AdRef-1. Collectively, these results suggest that secreted Ref-1 has anti-inflammatory properties and that its redox cysteine residue is associated with the anti-inflammatory activity in vivo. Furthermore, our findings indicate that secretory Ref-1 may be useful as a therapeutic biomolecule against systemic inflammation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bilirubin (BR) is generated by the reduction of biliverdin (BV), a metabolite that results from the catalytic degradation of heme by the isoforms of heme oxygenase (HO). BV is nontoxic and water-soluble but BR is potentially toxic and lipophilic. Therefore, a further metabolic step is required for BR before excretion is possible. The reductive conversion of BV to BR costs energy and is evolutionarily conserved in human physiology. There must be a compelling reason for this apparently nonsensical evolutionary conservation. In addition to the differences between BR and BV-such as water solubility, antioxidant activity, and participation as a receptor ligand-in the present study, we focused on the chemistry of the two metabolites with regard to an electrophilic functional group called a Michael reaction acceptor (MRA). Our data reveal that the BR reacts with thiol compounds forming adducts, whereas no reaction occurs with BV. Furthermore, the binding of biotin-tagged BR to Kelch-like ECH-associated protein 1 (KEAP1)-a biological electrophile sensor-was prevented by pretreatment with BR or a thiol compound, but was not by pretreatment with BV. In cells, BR could bind to KEAP1 to release and activate nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, a cytoprotective transcription factor, leading to the induction of HO-1. These findings may provide a physiological rationale for the energy-consuming conversion of BV to BR., (Copyright © 2018. Published by Elsevier Inc.)

Siglec-3/CD33 is a myeloid-specific inhibitory receptor that is expressed on cells of the immune system, where it is believed to play a regulatory role, modulating the inflammatory and immune responses. We characterized CD33 (RbCD33) in rock bream which is a transmembrane protein with two IG-like domains and a cytoplasmic tail. It has a deduced amino acid sequence of 390 residues and has tyrosine-based signaling motifs in the cytoplasmic tail. The RbCD33 mRNA was highly expressed in peripheral blood leukocytes and was also detected in the muscle, spleen, skin, head kidney, gills, trunk kidney, heart, stomach, brain, intestine and liver by quantitative real-time PCR. A temporal variation in expression of RbCD33 was observed in different tissues after stimulating with E. tarda, S. iniae and red seabream iridovirus (RSIV). In the head kidney tissue, E. tarda and S. iniae induced RbCD33, while a down regulation was observed with RSIV. In addition, in spleen tissue, S. iniae caused a very high induction of RbCD33 in comparison with an E. tarda and RSIV challenge. In the liver and gill tissues, all three pathogens induced a high expression of RbCD33. The expression pattern in various tissues and its high induction after pathogen stimulation suggests that RbCD33 plays an important role in initiating the immune response via the inhibition of signal transduction of the myeloid lineage cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We previously reported that MDR-1339, an inhibitor of β-amyloid protein aggregation, was likely to be eliminated by biotransformation in rats. The objective of this study was to determine the chemical identity of metabolites derived from this aggregate inhibitor and to characterize the kinetics of formation of these metabolites in rats. Using high performance liquid chromatography coupled with mass spectrometry with a hybrid triple quadrupole-linear ion trap, 7 metabolites and 1 potential metabolic intermediate were identified in RLM incubations containing MDR-1339. In addition to these, 3 glucuronide metabolites were detected in urine samples from rats receiving a 10 mg/kg oral dose of MDR-1339. When the kinetics of the formation of two major metabolites, M1 and M2, were analyzed assuming simple Michaelis-Menten kinetics, the V max and K m values were found to be 0.459 ± 0.0196 nmol/min/mg protein and 28.3 ± 3.07 μM for M1, and 0.101 ± 0.00537 nmol/min/mg protein and 14.7 ± 2.37 μM for M2, respectively. When chemically synthesized M1 and M2 were individually administered to rats intravenously at the dose of 5 mg/kg respectively, the volume of distribution and elimination clearance were determined to be 4590 ± 709 mL/kg and 68.4 ± 5.60 mL/min/kg for M1 and 15300 ± 8110 mL/kg and 98.0 ± 19.5 mL/min/kg for M2, respectively. When MDR-1339 was intravenously administered to rats at a dose of 5 mg/kg, the parent drug and M1 were readily detected for periods of up to 6 h after the administration, but M2 was observed only from 2 to 4 h. A standard moment analysis indicates that the formation clearance of M1 is 6.01 mL/min/kg, suggesting that 19.7% of the MDR-1339 dose was eliminated in rats. These observations indicate that the hepatic biotransformation of MDR-1339 results in the formation of at least 10 metabolites and that M1 is the major metabolite derived from this aggregation inhibitor in rats., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dietary factors play a role in normal biological processes and are involved in the regulation of pathological progression over a lifetime. Evidence has emerged indicating that dietary factor-dependent epigenetic modifications can significantly affect genome stability and the expression of mRNA and proteins, which are involved in metabolic dysfunction. Since metabolic syndrome is a progressive phenotype characterized by insulin resistance, obesity, hypertension, dyslipidemia, or type 2 diabetes, gene-diet interactions are important processes involved in the initiation of particular symptoms of metabolic syndrome and their progression. Some epigenetic risk markers can be initiated or reversed by diet and environmental factors. In this review, we discuss recent advances in our understanding of the interactions between dietary factors and epigenetic changes in metabolic syndrome. We discuss the contribution of nutritional factors in transgenerational inheritance of epigenetic markers and summarize the current knowledge of epigenetic modifications by dietary bioactive components in metabolic diseases. The intake of dietary components that regulate epigenetic modifications can provide significant health effects and, as an epigenetic diet, may prevent various pathological processes in the development of metabolic disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

CD4 + T cell activation and adequate differentiation into effector T helper (Th) cells are crucial for mediating adaptive immune responses to cope with foreign pathogens. Despite the significant role of Th cells, excessive increases in their numbers result in inflammatory and autoimmune diseases. In this study, we investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating Th cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation. Furthermore, costunolide inhibited the expression level of Th subset-polarizing master genes such as T-bet, GATA3, and RORγt, indicating that costunolide inhibits the differentiation of CD4 + T cells into Th subsets. Additionally, costunolide suppressed the proliferative activity of CD4 + T cells and the expression of CD69 activation marker on CD4 + T cells. When the molecular targets of costunolide were investigated, phosphorylation of ERK and p38 was found to be decreased under Th subset-polarizing conditions, whereas activity of JNK remained unchanged. U0126, an ERK inhibitor, and SB203580, a p38 inhibitor, decreased the expression of CD69 upon TCR stimulation and inhibited CD4 + T cell differentiation, indicating that both ERK and p38 are suggested to be critical molecular targets of costunolide. Taken together, these results suggest that costunolide inhibits the differentiation of CD4 + T cells by suppressing ERK and p38 activities and can be an effective therapeutic agent for T cell-mediated immune diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Classic colon cancer surgery refers to a wide resection of the tumor-bearing segment and the lymphatics draining along the named artery. The concept of TME has been applied to colon cancer and complete mesocolic excision (CME) in conjuction with central vascular ligation (CVL) has been introduced as the surgical treatment for colon cancer. Here, we discuss appropriate CME procedure with regard to the oncologic backgrounds, essential components, applied anatomy, laparoscopic technique, short-term, and oncologic outcomes. The introduction of CME has improved oncologic outcomes greatly in patients with colon cancer. The improved outcomes with CME can be attributed to underlying sound oncologic principles such as dissection through the proper plane of mesocolic excision, central vascular ligation, and sufficient length of proximal and distal margins. Thereby, CME technique can achieve en bloc removal of the diseased lesion with the increased amount of the colonic mesentery even though the length of for both bowel and mesentery resection remains a matter of debate. CME is a technically demanding operation thus, comprehensive understanding of the applied vascular anatomy is essential for successful CME. Favorable outcomes of open CME have been replicated with a laparoscopic approach. In future perspective, incorporating a structured education program on minimally invasive (laparoscopy or robot) CME would be beneficial., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To compare the expression of calpain and caspase-12 in human lens epithelial cells (LECs) of cataract patients with or without diabetic retinopathy (DR)., Design: Prospective, comparative case series., Methods: Patients were divided into 4 groups: patients without diabetes mellitus (DM) (Group 1), patients with DM and without diabetic retinopathy (DR) (Group 2), diabetic patients with nonprolifeative DR (NPDR) (Group 3), and diabetic patients with proliferative DR (PDR) (Group 4). Data on DM duration and glycated hemoglobin (HbA1c) level were collected. The LECs were obtained during cataract surgery and immunohistochemical staining was performed for calpain and caspase-12. The reactivity score of each specimen was determined using confocal microscopy., Results: A total of 40 patients (40 eyes) were evaluated, and each group was composed of 10 patients. The expression of calpain and caspase-12 was highest in Group 4, followed by Group 3, Group 2, and Group 1 (P < .001). The expressions were significantly higher with a longer duration of DM, increased HbA1c level, or advanced DR., Conclusions: Endoplasmic reticulum stress may be associated with apoptosis of LECs, resulting in cataract formation in diabetic patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Biochemical, genetic, physiological, and molecular research in plants has demonstrated a central role of glucose (Glc) in the control of plant growth, metabolism, and development, and has revealed networks that integrate light, stresses, nutrients, and hormone signaling. Previous studies have reported that AtPGR protein as potential candidates for Glc signaling protein. In the present study, we characterized transcription factors that bind to the upstream region of the AtPGR gene isolated using the yeast one-hybrid screening with an Arabidopsis cDNA library. One of the selected genes (AtSTKL) appeared to confer elevated sensitivity to Glc response. Overexpression of AtSTKLs (AtSTKL1 and AtSTKL2) increased the sensitivity to Glc during the post-germination stages. In contrast, atstkl1 and atstkl2 antisense lines displayed reduced sensitivity to high Glc concentration during the early seedling stage. Furthermore, we showed that the two AtSTKLs bind to the 5'-GCCT-3' element of the upstream promoter region of the AtPGR gene in vitro and repress the beta-glucuronidase (GUS) activity in AtPGR promoter-GUS (P999-GUS) transgenic plants. Green fluorescent protein (GFP)-tagged AtSTKLs were localized in the nuclei of transgenic Arabidopsis cells. Collectively, these results suggest that AtSTKL1 and AtSTKL2 function both as repressors of AtPGR transcription and as novel transcription factors in the Glc signaling pathway., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the clinical and urodynamic features of patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) according to their prostate size., Materials and Methods: We analyzed 2039 LUTS/BPH patients who underwent urodynamic study between October 2004 and August 2013. We divided the patients into three groups according to their prostate size: small (≤30 mL), moderately enlarged (31-80 mL), and large prostate (≥81 mL) groups. We compared the groups regarding age, International Prostatic Symptom Score, maximal flow rate (Qmax), postvoided residual (PVR), serum prostate-specific antigen, prostate volume measured by ultrasonography, and urodynamic findings., Results: Patients with a small prostate had better urodynamic outcomes than those with larger prostates in overall population. Although the total prostate volume significantly correlated with the bladder outlet obstruction (BOO) index (r  =  0.51), BOO patients with a small prostate had similar Qmax, higher PVR, and lower voiding efficiency, compared to those with larger prostates. Moreover, urodynamic parameters indicating bladder abnormalities, including low compliance and involuntary detrusor contraction positivity, were similar among the groups in BOO patients. A higher proportion of detrusor underactivity was also observed in the small prostate group in BOO patients. Finally, when adjusting for potential confounding variables, we identified serum prostate-specific antigen levels (odds ratio, 1.34) and Qmax (odds ratio, 0.77) as significant predictors for BOO in LUTS/BPH patients with a small prostate., Conclusion: BOO patients with a small prostate showed higher PVR and poor voiding efficiency, as well as similar urodynamic bladder abnormalities, compared to those with moderately enlarged and large prostates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Undescended ovaries are typically detected during infertility evaluations and are frequently associated with uterine malformations. Ruptured hemorrhagic corpus luteum cyst of an undescended ovary is an unusual cause of acute abdomen in an adolescent., Case: A 15-year-old girl presented with right lower quadrant pain, nausea, and vomiting, and transabdominal sonography and magnetic resonance imaging of the pelvis showed a 10 cm × 5 cm sized cystic mass at the level of the pelvic brim, anterior to the psoas muscle suggestive of a retroperitoneal hemorrhagic cyst. At surgery, the uterus and left adnexa appeared normal, but the right ovary was not visible within the pelvic cavity, and the right pelvic retroperitoneum was distended. After opening the retroperitoneum and aspirating blood clots, the undescended ovary with a ruptured cyst was visualized within the retroperitoneum. Right ovarian wedge resection was performed and the right ovary was repositioned in the pelvic cavity., Summary and Conclusion: Rupture of a corpus luteum cyst in an undescended ovary should be included in the differential diagnosis of acute abdomen in adolescents., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated the effect of cPKAα conformational states during protein immobilization on an array platform for cPKA autoantibody assays for sensitive and high-throughput profiling of protein kinase A (PKA) autoantibody levels in human sera., Design and Methods: We prepared activated human cPKAα protein arrays by addition of cofactors including ATP, MgCl2, and Triton X-100 to incubation buffer. Anti-human cPKAα antibody or PKA autoantibody levels in human sera were analyzed using activated human cPKAα protein arrays., Results: Activation of cPKAα with ATP, Mg(2+), and Triton X-100 enhanced the sensitivity of the assay by increasing the signal/noise ratio and lowering the limit of detection. cPKAα activation also enhanced the sensitivity of cPKA autoantibody detection in human sera. We successfully applied this assay to determine cPKA autoantibody levels in human sera from normal individuals (n=30) and hepatic cancer patients (n=30)., Conclusions: Our results demonstrate that cPKAα activation enhanced the sensitivity of array-based PKA autoantibody assays, and that this assay is suitable for high-throughput analyses of cPKA autoantibodies in human sera., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

In this study, we synthesized (E)-2-cyano-3-(substituted phenyl)acrylamide (CPA) derivatives which possess a linear β-phenyl-α,β-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory activity against mushroom tyrosinase. Results from the docking simulation indicated that CPA2 could bind directly to the active site of mushroom tyrosinase and the binding affinity of CPA2 for tyrosinase might be higher than that of kojic acid, a well-known potent tyrosinase inhibitor. In B16F10 cells, CPA2 significantly suppressed tyrosinase activity and melanogenesis in a dose-dependent manner. At the concentration of 25μM, CPA2 exhibited tyrosinase inhibitory activity comparable to that of kojic acid with no cytotoxic effect. Results from the present study suggest that CPA2 bearing a linear β-phenyl-α,β-unsaturated carbonyl scaffold may be the potential candidate for treatment of diseases associated with hyperpigmentation and that a linear β-phenyl-α,β-unsaturated carbonyl scaffold might be closely related to potent tyrosinase inhibition., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The primary goal of surgical intervention for rectal cancer is to achieve an oncologic cure while preserving function. Since the introduction of total mesorectal excision (TME), the oncologic outcome has improved greatly in terms of local recurrence and cancer-specific survival. However, there are still concerns regarding functional outcomes such as sexual and urinary dysfunction, even among experienced colorectal surgeons. Intraoperative nerve damage is the primary reason for sexual and urinary dysfunction and occurs due to lack of anatomical knowledge and poor visualization of the pelvic autonomic nerves. The rectum is located concavely along the curved sacrum and both the ischial tuberosity and iliac wing limit the pelvic cavity boundary. Thus, pelvic autonomic nerve preservation during dissection in a narrow or deep pelvis, with adherence to the TME principles, is very challenging for colorectal surgeons. Recent developments in robotic technology enable overcoming these difficulties caused by complex pelvic anatomy. This system can facilitate better preservation of the pelvic autonomic nerve and thereby achieve favorable postoperative sexual and voiding functions after rectal cancer surgery. The nerve-preserving TME technique includes identification and preservation of the superior hypogastric plexus nerve, bilateral hypogastric nerves, pelvic plexus, and neurovascular bundles. Standardized procedures should be performed sequentially as follows: posterior dissection, deep posterior dissection, anterior dissection, posterolateral dissection, and final circumferential pelvic dissection toward the pelvic floor. In future perspective, a structured education program on nerve-preserving robotic TME should be incorporated in the training for minimally invasive surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection and poses a major public health threat worldwide. No effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. Recent studies have shown that p38 mitogen-activated protein kinase (MAPK) activity is implicated in infection by and replication of viruses such as RSV and the influenza virus. Because berberine has previously been implicated in modulating the activity of p38 MAPK, its effects on RSV infection and RSV-mediated p38 MAPK activation were examined. Replication of RSV in epithelial cells was significantly reduced by treatment with berberine. Berberine treatment caused decrease in viral protein and mRNA syntheses. Similar to previously reported findings, RSV infection caused phosphorylation of p38 MAPK at a very early time point of infection, and phosphorylation was dramatically reduced by berberine treatment. In addition, production of interleukin-6 mRNA upon RSV infection was significantly suppressed by treatment with berberine, suggesting the anti-inflammatory role of berberine during RSV infection. Taken together, we showed that berberine, a natural compound already proven to be safe for human consumption, suppresses the replication of RSV. In addition, the current study suggests that inhibition of RSV-mediated early p38 MAPK activation, which has been implicated as an early step in viral infection, as a potential molecular mechanism., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To evaluate whether anticholinergic medication contributes to early recovery of continence and improvement of other voiding symptoms after radical prostatectomy (RP)., Patients and Methods: A total of 78 patients with clinically localized prostate cancer who had incontinence at 1 week after RP were enrolled prospectively. The patients were allocated to one of the 2 groups: group 1 (α-adrenergic agonist [midodrine] plus an anticholinergic [solifenacin]) or group 2 (α-adrenergic agonist only). A urodynamic study and the International Continence Society male Short Form questionnaire were completed preoperatively and 4 months after RP. One-hour pad test and 3-day frequency volume chart at 1 and 4 months after medication were also analyzed., Results: The rate of continence, defined as being pad free, did not differ between the groups at 4 months (both 71.8%; P >.05). However, the decreased value of mean weight of daily pads worn by groups 1 and 2 were 51.5 vs 11.7 g, respectively (P = .005). The incontinence (P = .008) and quality of life (P = .044) subscale scores significantly worsened in group 2, whereas they remained unchanged in group 1. Maximal detrusor pressure and maximal urethral closure pressure significantly decreased in both groups, whereas maximal cystometric capacity increased significantly in group 1 only (290.8-332.0 cm H2O; P <.001)., Conclusion: Anticholinergics may facilitate early recovery from incontinence and prevent worsening of quality of life, which might be attributed to increased cystometric capacity after their use., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Obesity has been reported to impair immune functions and lead to low-grade long-term inflammation; however, studies that have investigated the impact of weight loss on these among the young and slightly obese are limited. Thus, we investigated the effect of a 12-week weight management program with behavioral modifications on cell-mediated immune functions and inflammatory responses in young obese participants. Our hypothesis was that weight loss would result in improved immune functions and decreased inflammatory responses. Sixty-four participants (45 obese and 19 normal weight) finished the program. Obese (body mass index ≥25) participants took part in 5 group education and 6 individual counseling sessions. Normal-weight (body mass index 18.5-23) participants only attended 6 individual sessions. The goal for the obese was to lose 0.5 kg/wk by reducing their intake by 300 to 500 kcal/d and increasing their physical activity. Program participation resulted in a modest but significant decrease in weight (2.7 ± 0.4 kg, P < .001) and lipopolysaccharide-stimulated interleukin-1β production (from 0.85 ± 0.07 to 0.67 ± 0.07 ng/mL, P < .05) in the obese. In the obese group, increase in phytohemagglutinin-stimulated interleukin-10 production, a TH2 and anti-inflammatory cytokine, approached significance after program participation (from 6181 ± 475 to 6970 ± 632 pg/mL, P = .06). No significant changes in proliferative responses to the optimal concentration of concanavalin A or phytohemagglutinin were observed in the obese after program participation. Collectively, modest weight loss did not change the cell-mediated immune functions significantly but did attenuate the inflammatory response in young and otherwise healthy obese adults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To ascertain the association of cystourethroscopic findings of bladder neck elevation with urodynamic bladder outlet obstruction (BOO) in patients with lower urinary tract symptoms and benign prostatic hyperplasia (LUTS-BPH)., Materials and Methods: Study subjects were 646 consecutive men aged >40 years diagnosed with LUTS-BPH at Seoul National University Hospital from December 2005 through January 2012. We collected the International Prostatic Symptom Score, serum prostate-specific antigen levels, prostate volume measured by transrectal ultrasonography, uroflowmetry with postvoid residual volume, and urodynamics with a pressure flow study. We examined the degree of lateral lobe protrusion of prostate, bladder neck elevation degree (BNE-D), and bladder neck elevation angle (BNE-A) under a cystourethroscopic examination., Results: When we examined BNE by cystourethroscope, the mean BNE-A was 26.1°. Higher BNE-D was strongly positively correlated with BNE-A, but neither was associated with the degree of lateral lobe protrusion of prostate. Patients with higher BNE-A (≥ 35°) had higher BOO index and more obstructed voiding patterns than those with lower BNE-A (<35°). BNE-A was positively correlated with BOO index (r = 0.186). However, we identified only total prostate volume (odds ratio [OR], 1.036), maximal flow rate (Qmax; OR, 0.843), and detrusor pressure at Qmax (PdetQmax; OR, 1.278) as significant predictors of BOO in the multivariate analysis., Conclusion: In sum, patients with higher BNE-A (≥ 35°) by cystourethroscope had higher BOO index and more obstructed voiding patterns than those with lower BNE-A (<35°). Moreover, both BNE-D and BNE-A were positively correlated with BOO index. Thus, cystourethroscopic findings of BNE status can be helpful to predict urodynamic BOO in the patients with LUTS-BPH., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To examine the effect of the side of the allograft (left vs right) on early graft failure and long-term graft survival rates after conventional open living-donor nephrectomy (OLDN) or video-assisted minilaparotomy living-donor nephrectomy (VLDN)., Materials and Methods: We evaluated 2704 living-donor transplantations using OLDN or VLDN between 1991 and 2011 at a single institution. For analysis, the entire period was divided into "era 1" (1991-1997), when OLDN was prevalent; "era 2" (1998-2004), when both OLDN and VLDN were conducted; and "era 3" (2005-2011), when VLDN became prevalent., Results: There were 822, 650, and 685 transplantations analyzed in eras 1, 2, and 3, respectively. There were no differences in causes of early graft failure between left and right allografts in any era. The right allograft survival rate in eras 1 and 2 was slightly lower than the left allograft survival rate. In era 2, during which both OLDN and VLDN were conducted, Kaplan-Meier analysis showed lower right allograft survival rate for OLDN. However, the long-term survival rates of the left and right VLDN grafts did not differ., Conclusion: Right OLDN allografts demonstrated worse long-term survival rate than left OLDN allografts, but the right and left VLDN allografts had similar long-term survival rate. VLDN appears to be an appropriate treatment option when right donor nephrectomy is desired., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Protein kinase C (PKC) induces mitochondrial dysfunction, which is an important pathological factor in cardiovascular diseases. The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) on PKC-induced mitochondrial dysfunction has not been variously investigated. In this study, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, induced mitochondrial hyperpolarization and reactive oxygen species generation and also increased mitochondrial translocation of APE1/Ref-1. APE1/Ref-1 overexpression suppressed PMA-induced mitochondrial dysfunction. In contrast, gene silencing of APE1/Ref-1 increased the sensitivity of mitochondrial dysfunction. Moreover, mitochondrial targeting sequence (MTS)-fused APE1/Ref-1 more effectively suppressed PMA-induced mitochondrial dysfunctions. These results suggest that mitochondrial APE1/Ref-1 is contributed to the protective role to protein kinase C-induced mitochondrial dysfunction in endothelial cells., (Copyright © 2014 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.)

Objective: To show the noninferiority of silodosin 8-mg once-daily (QD) to 4-mg twice-daily (BID) in efficacy and safety in patients with lower urinary tract symptoms or benign prostatic hyperplasia in the Korean population., Methods: A prospective, multicenter, double-blind, randomized, comparative study was conducted. A total of 532 male patients aged ≥50 years with lower urinary tract symptoms or benign prostatic hyperplasia were included. All patients received silodosin QD or BID for 12 weeks. The primary end point was the change from baseline in total International Prostate Symptom Score (IPSS) at 12 weeks. Adverse drug reactions, vital signs, and laboratory tests were recorded., Results: A total of 424 patients were randomized to the silodosin QD or BID groups. These groups were not significantly different in baseline characteristics. The mean total IPSS change in QD group was not inferior to that in BID group (-6.70 and -6.94, respectively; 95% confidence interval, -0.88 to 1.36). The QD and BID groups did not significantly differ in the following: percentages of patients with ≥25% (63.41% and 67.82%, respectively; P = .349) or ≥4-point improvement in total IPSS (65.85% and 69.31%, respectively; P = .457), maximum urinary flow rate improvement ≥30% (47.32% and 40.59%, respectively; P = .172), changes in IPSS voiding subscore (-4.42 ± 4.93 and -4.65 ± 4.77; P = .641), IPSS storage subscore (-2.05 ± 3.07 and -2.52 ± 2.97; P = .117), quality of life (-1.19 ± 1.49 and -1.40 ± 1.42; P = .136), maximum urinary flow rate (3.55 ± 5.93 and 3.74 ± 6.79 mL/s; P = .768), International Continence Society male questionnaire score, Patient Goal Achievement Score, or Treatment Satisfaction Question. The 2 groups had similar frequencies of adverse drug reactions., Conclusion: QD administration of silodosin was not inferior to BID in efficacy. The 2 groups had similar adverse drug reaction profiles., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Formalin killed Pseudomonas anguilliseptica bacterial vaccine was prepared and administered to farm reared olive flounder, Paralichthys olivaceus reared at 17 °C and 20 °C for 4 weeks. Non-vaccinated fishes (n=150) served as positive control. Vaccinated fishes were divided into two groups (n=150 each in replicate). Both the vaccinated and non-vaccinated fishes were challenged intraperitoneally with P. anguilliseptica (1×10(7) CFU ml(-1)) isolates and PBS (negative control). Fishes were sampled from zero hour post injection (hpi) for 28 days (each hour and each day); the mean percent mortality and relative percent survival (RPS) were calculated for the challenged and control groups. The vaccinated fishes had a significant increase in RPS (69 and 89, respectively); the percentage mortality declined from 83±0.6 and 74±0.7 in challenged and control fishes to 25%±0.8% and 8%±0.8% in vaccinated and challenged fish groups, respectively. The immune gene expression assay was analyzed using real-time PCR. Vaccinated fishes registered a significant increase in the expression of TNFR-1, FasL, IRF7, TLR2, IL-1b and CD40 gene transcripts when compared to the control group. The upregulation of these genes along with the increased RPS values suggest that the formalin-killed cells of P. anguilliseptica could play an important role in immunizing olive flounder against P. anguilliseptica., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In this study we describe the generation and influences on in vitro and in vivo osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with growth and differentiation factor 5 (GDF-5). Prior to loading GDF-5, we characterized the release profiles from these hydrogels and tested their respective cell viability, differentiation and in vivo bone regeneration. The results from this testing indicated that GDF-5 was observed to release in a sustained manner from the HA hydrogels I-III. MTT and Live/Dead assays showed that the HA hydrogels I-III have good biocompatibility for use as scaffolds for bone tissue regeneration. In vitro cell tests showed a higher level of MC3T3-E1 cell proliferation and differentiation on HA hydrogels I-III than on HA hydrogel 0. Moreover, in vivo animal tests showed that the HA hydrogels I and III had a significant improvement on osteogenesis. Overall, our results suggest that the HA-based hydrogel is a good biomaterial to deliver osteogenic differentiation factors such as GDF-5, and GDF-5 can be useful as an effective alternative to aid new bone formation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Oleanolic acid, a naturally occurring triterpenoid widely distributed in foods and medicinal plants, has anticancer, antioxidant, and antiaging properties. We hypothesized that oleanolic acid would suppress the production of the inflammatory adipokine resistin during adipogenic differentiation of 3T3-L1 adipocytes. 3T3-L1 adipocytes were cultured in adipogenic media with and without 1 to 25 μM oleanolic acid for up to 8 days to stimulate adipocyte differentiation. Adipocyte production of resistin was markedly enhanced during differentiation and was dose dependently attenuated by 1 to 25 μM oleanolic acid. This study further investigated whether Tyk2-Stat1/3 signaling was responsible for cellular production of resistin. Signal transducer and activator of transcription factor (STAT) 1 and STAT3 were activated during differentiation in a disparate temporal fashion; STAT1 was maximally phosphorylated on day 5 after initiating differentiation, whereas STAT3 was rapidly activated within 1 day of differentiation. When oleanolic acid was supplied to differentiating adipocytes, STAT1 and STAT3 phosphorylation was substantially suppressed. Upstream Tyk2 was rapidly activated in a manner similar to STAT3 and reactivated on days 3 to 5 after initiating differentiation, which was attenuated by incubating adipocytes with oleanolic acid. In addition, cellular expression of suppressor of cytokine signaling 3 (SOCS3), which inhibits Tyk2 activity, was markedly promoted from day 5 of adipocyte differentiation. Oleanolic acid attenuated SOCS3 expression, which was highly enhanced during the late phase of differentiation. Taken together, oleanolic acid suppressed adipocyte differentiation-associated resistin and adipogenesis production by disturbing the Tyk2-STAT1/3 signaling pathway and promoting SOCS3 expression. Therefore, oleanolic acid may be a possible bioactive agent that blunts adipogenesis and adipokine inflammation., (Copyright © 2013. Published by Elsevier Inc.)

Objective: Because of an initial activation of proinflammatory cytokines that facilitates leukocyte transmigration, atherosclerosis is a chronic inflammatory disease and its severity is accelerated by the occurrence of complex interactions of oxidatively modified low-density lipoprotein (LDL) with monocyte-derived macrophages., Methods: The present study investigated whether luteolin suppresses adheren junction-associated monocyte transmigration and platelet-derived growth factor-BB-mediated foam cell formation. The involvement of monocyte integrins and macrophage scavenger receptors (SRs) also was determined., Results: Luteolin, non-toxic at 1 to 20 μmol/L, blocked the monocyte-endothelium interactions by inhibiting the cytokine-associated monocyte induction of integrin-β2. Luteolin retarded the transendothelial migration of monocytes by firmly localizing the occludin present in paracellular endothelial junctions and by blunting the monocyte activity of matrix-degrading matrix metalloproteinase-9. Treatment with luteolin showed inhibitory effects on oxidized LDL-triggered foam cell formation by decreasing SR-A and SR-B1 induction in THP-1 cell-derived macrophages, which was confirmed by Oil red O and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate staining. Furthermore, luteolin attenuated the oxidized LDL-induced macrophage secretion of platelet-derived growth factor-BB, entailing the induction of SR-A and SR-B1. These results demonstrate that luteolin encumbered monocyte cytokine-instigated endothelial transmigration and oxidized LDL-elicited macrophage foam cell formation., Conclusion: Luteolin may qualify as an antiatherogenic agent in LDL systems, which may have implications for strategies attenuating monocyte/macrophage dysfunction-related atherosclerosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We describe in this study whether the gold nanoparticle (AuNP) surface-functionalized with PEG, biotin, paclitaxel (PTX) and rhodamine B linked beta-cyclodextrin (β-CD) (AuNP-5') can be useful as a theranostic agent for cancer therapy without the cytotoxic effect on normal cells. Prior to surface-functionalizing AuNPs, the cytotoxicity of the nanoparticles was evaluated, followed by their cytocompatibility. PTX, an anti-cancer agent, formed inclusion complexations with β-CD conjugated AuNPs, and effectively released from the AuNP-2' surface-functionalized with PEG, beta-cyclodextrin (β-CD) and paclitaxel (PTX) using the intracellular glutathione (GSH) level (10 mm). Two types of AuNP-4 surface-functionalized with PEG and rhodamine B linked β-CD and AuNP-5 surface-functionalized PEG, biotin and rhodamine B linked β-CD were used for evaluating their specific interaction on cancer cells such as HeLa, A549 and MG63. These were also tested against normal NIH3T3 cell, determining that the AuNP-5 was more effectively involved with the cancer cells. Confocal laser scanning microscopy (CLSM), fluorescence-activated cell-sorting (FACS) and cell viability analyses showed that the AuNP-5' plays a significant role in the diagnosis and therapy of the cancer cells, and may be used in theranostic agents., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

An increased risk of iron deficiency has been reported in obese individuals. We investigated hepatic iron status and serum levels of both adipokines and inflammatory markers in obese mice to test the hypothesis that high-fat-diet (HFD)-induced obesity leads to reduced iron storage associated with inflammation. Four-week-old C57BL mice were fed a HFD containing 60% energy from fat for 16 weeks and were compared with mice on a control diet with 10% energy from fat. The HFD group had significantly higher levels of leptin (43.7 ng/mL in control, n = 16 vs 104.3 ng/mL in HFD, n = 17; P < .001) and significantly lower amounts of high-molecular-weight adiponectin (4.80 μg/mL in control, n = 16 vs 3.67 μg/mL in HFD, n = 18; P = .002) compared with the control group. Higher serum amyloid A levels in the HFD group (60.4 μg/mL in control, n = 17 vs 117.9 μg/mL in HFD, n = 18; P < .001) suggest inflammation in the HFD-induced obese animals. The HFD group had lower hepatic nonheme iron (3.12 μg/mg protein in control, n = 17 vs 0.869 μg/mg protein in HFD, n = 16; P < .001). Expression of hepcidin messenger RNA (mRNA) was only 54% of the control levels in HFD mice (P = .016). However, the ratio of hepcidin mRNA expression to nonheme iron was 2.5-fold higher in the HFD compared with the control animals. Hepcidin is a homeostatic regulator of iron metabolism that restricts intestinal iron absorption and is also known as a mediator of inflammation. Increased serum amyloid A levels and a higher ratio of hepatic hepcidin mRNA expression to nonheme iron suggest that lower hepatic iron status in obese animals might be associated with inflammation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We describe in this study the positive influences on in vitro and in vivo osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with simvastatin (SIM). Prior to loading SIM, we first characterized the HA hydrogels for their mechanical properties and swelling ratios. The results from this testing indicated that these two factors improved as the substitution degree of 2-aminoethyl methacrylate (AEMA) increased. MTT and live/dead assays showed that the HA hydrogels have good biocompatibility for use as scaffolds for bone tissue regeneration. Moreover, another MTT assay showed that the photo-cured HA hydrogels III fabricated with 30% AEMA (300 mg) conjugated HA (HA-AEMA iii) loaded with between 0.1 and 1 mg of SIM had a similar cytotoxicity as compared to the HA hydrogel III itself. The sustained release of SIM was observed to occur in the HA hydrogel III loaded with 1 mg of SIM. In vitro and in vivo experiments showed that the HA hydrogel III loaded with 1 mg of SIM had a significant influence on osteogenesis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the efficacy of alfuzosin treatment on voiding and storage in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) with respect to bladder outlet obstruction and contractility., Methods: A 12-month, multicenter, observational, prospective study was conducted at four university hospitals in Korea. Patients were divided into four groups: group 1 (bladder outlet obstruction index (BOOI) ≥20, bladder contractility index (BCI) ≥100), group 2 (BOOI ≥20, BCI <100), group 3 (BOOI <20, BCI ≥100), and group 4 (BOOI <20, BCI <100), with respect to BOOI and BCI evaluated by pressure-flow study. Treatment efficacy was analyzed by validated symptom scores., Results: Two-hundred thirty-two men with LUTS/BPH were enrolled, and 165 (41, 50, 30, and 44 in groups 1-4, respectively) were followed to the end of the study. After 12 months of alfuzosin treatment, all International Prostate Symptom Score (IPSS) parameters improved in all four groups. Mean improvement in IPSS subscore for voiding was 4.0 points in group 1, 5.5 points in group 2, 5.5 points in group 3, and 3.0 points in group 4. Change in IPSS subscore for storage was 2.5 points in group 1, 3.6 points in group 2, 2.9 points in group 3, and 1.8 points in group 4. There was no difference among four groups in improvements seen in storage or voiding IPSS subscore. International Continence Society male questionnaire scores significantly improved in all four groups with no between-group differences., Conclusions: Alfuzosin treatment in men with LUTS indicative of BPH effectively improved voiding and storage symptoms regardless of BOOI or BCI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Obesity accompanies various metabolic and immunologic changes. Evidence from epidemiological, animal, and human studies has linked obesity to impaired immunity. However, human studies that have investigated the immunocompetence of the obese are still limited. We studied the immune and inflammatory responses of obese (body mass index [BMI], 28.3 ± 0.5 kg/m²; n = 30) and normal-weight (BMI, 21.2 ± 0.3 kg/m²; n = 15) young adults to test the hypothesis that obesity is associated with an impaired immune function and dysregulated inflammatory response. Serum levels of adipokines and subpopulations of immune cells were examined. In vitro proliferative response of whole blood lymphocytes, the production of inflammatory cytokines (interleukin [IL] 1β, IL-6, and tumor necrosis factor α) and T helper 1/T helper 2 cytokines (IL-2, interferon γ, IL-4, and IL-10) were determined. Serum leptin levels were significantly higher (P < .001) and CD8+ T-cell subpopulation was significantly lower (P = .044) in the obese than normal-weight subjects. There was no difference in the proliferative response of whole-blood lymphocytes to T-cell mitogens between 2 groups. Phytohemagglutinin-stimulated peripheral blood mononuclear cells from the obese group produced significantly higher levels of IL-2 (P = .002) and tended to produce higher levels of IL-4 (P = .053) than those from the normal-weight group. No significant differences in the production of inflammatory cytokines by either whole-blood lymphocytes or peripheral blood mononuclear cells stimulated with lipopolysaccharide were observed between the obese and normal-weight subjects. These results suggest that obesity with a BMI less than 30 does not significantly impair immune function in young adults. However, further research is needed to investigate the clinical significance of a lower CD8+ T-cell population associated with obesity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The most popular technique of photoselective vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH) involves vaporization only. We developed a modified vaporization-resection technique that consists of vaporizing a prostate along outlined margins and retrieving the wedge-shaped prostate tissue. We report the operative procedure and clinical outcomes of our technique with the GreenLight high performance system (HPS)., Methods: A total of 104 patients with a prostate volume greater than 40 mL who underwent PVP were included in this retrospective study. Forty patients were treated with the vaporization-only technique (Group non-S) and 64 patients with the Seoul technique (group S). The clinical outcomes were assessed at 1, 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum flow rate (Q(max.)), and postvoid residual urine volume (PVR)., Results: The Q(max.), PVR, IPSS, and QoL scores improved significantly from 1 to 12 months after the PVP compared with the baseline in both groups (P <.05). In the S group, the volume reduction of the prostate per operative time, lasing time, and laser energy were significantly smaller than in the non-S group (P <.05). In general, the overall complication rates were low in the 2 groups. Two patients were found to have prostate cancer on pathology., Conclusions: The Seoul technique for PVP showed good short-term efficacy and safety for the treatment of BPH. With this technique, we can conserve on the operative time, lasing time, and energy, and obtain prostatic tissue for pathologic evaluation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate biologic function of bone morphorgenic protein-2 (rhBMP-2) immobilized on the heparin-grafted Ti surface. Ti surfaces were first modified by 3-aminopropyltriethoxysilane (ATPES), followed by grafting of heparin. BMP-2 was then immobilized on the heparin-grafted Ti surfaces. Pristine Ti and functionalized Ti surfaces were characterized by X-ray photoelectron spectroscopy (XPS), measurement of water contact angles, and protein adsorption. The biological activity of MG-63 cells on pristine and functionalized Ti surfaces was investigated by cell proliferation assays, measurement of alkaline phosphate (ALP) activity, and determination of calcium deposition. Anti-inflammatory effects were assessed by RT-PCR to measure the transcript levels of IL-6 and TNF-α. XPS revealed that heparin and BMP-2 were successfully grafted and immobilized on the Ti surfaces, respectively. In addition, Ti surfaces with BMP-2 immobilized were more hydrophilic than pristine Ti. Furthermore, BMP-2 immobilized Ti promoted significantly higher ALP activity and calcium deposition by MG-63 cells than pristine Ti. The inflammatory response was also decreased when cells were grown on heparin-grafted, BMP-2-immobilized Ti surfaces. The results of this study suggest that by grafting heparin and immobilizing BMP-2 on Ti surfaces, inflammation can be inhibited and osteoblast function promoted., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Cocaine and amphetamine regulated transcript (CART) has been implicated in the regulation of the stress response. Although the forced swimming test (FST), in which rats are forced to swim for 15 min (pretest swim) and then again for 5 min (test swim) 24 h later, has been used to study the effects of antidepressants, there have been few studies examining the effects of antidepressants on FST-induced changes in CART mRNA levels in the brain. To answer this question, we injected reboxetine and citalopram into male Sprague-Dawley rats 1, 5, and 23.5 h before the test swim and then sacrificed rats 2 h after the test swim, at the peak of the FST-induced increase in CART expression. The FST significantly increased CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus 2 h after the test session. Both reboxetine and citalopram pretreatment blocked FST-induced increases in CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus, despite the fact these antidepressants exert their therapeutic effect by different mechanisms. In addition, the FST significantly increased plasma corticosterone levels, and this effect was also blocked by reboxetine and citalopram pretreatment. These results suggest that inhibition of FST-induced increases in CART expression in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus may be a common mechanism of antidepressant effects during the FST., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objectives: To assess the prognostic value of the width of a healthy surgical margin in the enucleoresection of small renal cell carcinoma, in which 68% of cases had a margin width of 3.0 mm or less., Methods: We retrospectively reviewed 98 consecutive enucleoresections regarding the width of healthy margin and tumor recurrence in 96 patients followed up for more than 3 years after surgery. The mean follow-up was 70.8 months., Results: The mean tumor size was 2.8 cm (range, 1.0-6.1). Three cases had a positive surgical margin, and 2 of them had positive frozen biopsy results with additional negative biopsies. The other case did not have a frozen biopsy and did not show any evidence of recurrence during follow-up. The mean width of the surgical margin of the remaining 95 enucleoresections was 2.9 mm (0.5-15.0): 26.3% were 1 mm or less, 42.1% were 1.1-3.0 mm, 23.2% were 3.1-5.0 mm, and 8.4% were 5.1 mm or more. Only 1 patient developed tumor recurrence during follow-up, excluding a patient with von Hippel Lindau disease. This patient with a 2-mm width healthy margin but capsular invasion had enlarged abdominal lymph nodes at 38 months of follow-up., Conclusions: The width of the surgical margin was not associated with the oncological prognosis in our enucleoresection series of small renal cell carcinoma, in which the width of the margin was 3.0 mm or less in more than two-thirds of the cases., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: No studies have been published comparing the U- and H-type methods of the TVT SECUR (TVT-S) procedure., Objective: Our aim was to compare the efficacy and safety of the two types of TVT-S for female stress urinary incontinence (SUI)., Design, Setting, and Participants: Women with urodynamic SUI were enrolled in this 12-mo multicenter randomized study., Intervention: Subjects were randomly allocated to either the U- or H-type method of TVT-S., Measurements: Pre- and postoperative evaluations included a standing stress test, the Sandvik questionnaire, the Incontinence Quality of Life (I-QOL) questionnaire, and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS). Patients' satisfaction and complications were evaluated. Objective and subjective cures were defined as no leakage on the stress test and responses on the Sandvik questionnaire, respectively. We compared the surgical outcomes between the two methods., Results and Limitations: Of 285 women, 144 had the U-type method and 141 had the H-type method. Objective cure rates were 87.5% for the U-type method and 80.1% for the H-type method (p=0.091). Subjective cure rates were 77.1% for the U-type method and 75.7% for the H-type method (p=0.786). Improvement in I-QOL and domain scores of the ICIQ-FLUTS (filling and incontinence sum, QOL score), and patients' satisfaction favored the U-type method. There were three cases of intraoperative vaginal wall perforation, one case of increased bleeding, and three cases of temporary postoperative retention. A power calculation was not performed, and some baseline characteristics were not balanced between the two methods., Conclusions: Both methods of TVT-S provided comparable cure rates for female SUI. However, QOL and treatment satisfaction favored the U-type method., Trial Registration: The protocol of this study was not registered., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We studied the effects of supraspinally administered morphine on the expression of the hypothalamic pro-opiomelanocortin (POMC) gene and beta-endorphin. Mice were administered morphine intracerebroventricularly (i.c.v.) either once or 5 times for 5 days (once/day). A single morphine administration significantly increased the hypothalamic POMC gene and beta-endorphin expression at 2h after application in dose-dependent fashion; however, repeated morphine administration had no effect on the hypothalamic POMC gene and beta-endorphin expression. In the immunoblot and immunohistochemical study, the increase of beta-endorphin was observed in the arcuate nucleus of the hypothalamus. Moreover, the expressions of c-Fos, phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK-IIalpha), and phosphorylated cAMP response element-binding protein (pCREB) were increased by a single i.c.v. morphine injection at various time points, but the expressions of phosphorylated extracellular signal-regulated protein kinase1/2 (pERK1/2) and phosphorylated IkappaB (pIkappaB) were not. We also found that the expressions of c-Fos, pCaMKIIalpha, and pCREB were co-localized with the POMC expression. Meanwhile, naloxone as well as muscimol and baclofen significantly attenuated the increases of the POMC gene expression induced by a single morphine administration. Furthermore, the pretreatment of muscimol and baclofen 10 min before morphine injection robustly attenuated the withdrawal behavior induced by a single morphine administration. These results imply that the hypothalamic POMC gene and beta-endorphin expression may play an important role in the development of an acute physical dependency of morphine. In that, GABAergic neurotransmission appear to be involved in the regulation of the hypothalamic POMC gene expression induced by supraspinal morphine administration.