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BACKGROUND: Streptococcus mutans, the main pathogen associated with tooth decay, forms cariogenic biofilms on tooth surfaces. Therefore, controlling oral biofilm helps prevent dental caries. Hen's egg is a nutrient‐dense food, and egg white is a good source of protein. Ovomucoid is one of the major proteins in egg white, with a 28 kDa molecular weight. The present study aimed to investigate the inhibitory effects of ovomucoid on the biofilm formation of S. mutans by suppressing virulence factors, including bacterial adherence, cellular aggregation and exopolysaccharide (EPS) production. RESULTS: Crystal violet staining showed that biofilm formation by S. mutans was inhibited by ovomucoid at 0.25–1 mg mL−1 levels. Field emission scanning electron microscopy also confirmed this inhibition. In addition, ovomucoid reduced mature biofilm, water‐insoluble EPS synthesis and the metabolic activity of bacterial cells in the biofilm. The bacterial adhesion and aggregation abilities of S. mutans were also decreased in the presence of ovomucoid. Ovomucoid downregulated the expression of comDE and vicR genes involved in the two‐component signal transduction system and gtfA and ftf genes involved in EPS production. CONCLUSION: Ovomucoid has the potential for use as an anti‐biofilm agent for dental caries treatment because of its inhibitory effects on the virulence factors of S. mutans. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Paik Ki-wan, an 89-year-old Korean democracy activist, passed away on 15 February in 2021. He wrote the original poem, from which the lyrics of the song "March for the Beloved" (im-eul wihan haengjingog) originated. Many protesters across Asia sing this song, even in an ani-coup protest in Yangon recently. He has fought against dictatorship, and was tortured by it. As a result of the torture, he lost 38 kilograms, while he was in prison from his normal 82 kilograms. He never went to college or earned wages stably. He was an awakened warrior, poet, and teacher who helped poor children learn how to read. The dictatorial government broke down in 1987, and the Korean society went onto the transition road to democracy. In the presidential election in December 1987, the two representative democratic leaders—Kim Dae-jung and Kim Young-sam—both ran for the president and were divided into hostile competition. At this historical point, he was honored to run for president and pressured those two candidates in order to prevent the military candidate from coming into power. As they got old, many of those who fought for democracy on the streets together in 1987 were included in the middle-class group or became high-ranking officialis, but he insisted to stand on the streets beside the underprivileged and the weakest people, fighting against the military dictatorship, and even the liberal democratic government led by Kim Dae-jung and even the current Moon Jae-in. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a major foodborne pathogen that causes listeriosis and poses potential threats to human health. Ovotransferrin (OT) is an egg white protein with many functional properties. In this study, the anti-biofilm effect of OT and OT hydrolysates (OTH) of enzymes (bromelain, Flavourzyme®, Neutrase®, papain, and Protamex®) against L. monocytogenes was investigated. The OTH prepared with bromelain (OTBM), Flavourzyme® (OTFV), and papain (OTPP) significantly inhibited the biofilm formation of L. monocytogenes strains. The OTFV and OTPP showed higher biofilm eradication activities than the OT, with the maximum activity (48.61–74.43%, 40.89–67.75%, and 37.51–61.07% in L. monocytogenes ATCC 15313, H7962, and NADC Scott A, respectively) found in the OTPP. The L. monocytogenes treated with the OTPP exhibited decreased cell surface hydrophobicity, auto-aggregation, exopolysaccharides production, biofilm metabolic activity, and the expression of genes (actA , agrD , dltB , flaA , flgE , and prfA) related to the biofilm-forming activity of L. monocytogenes. The biofilm formation of L. monocytogenes on glass coupon was significantly inhibited by the OT and OTPP treatments. These results suggested that the OT and OTH, especially the OTPP, exerted anti-biofilm effects against L. monocytogenes. Therefore, OTPP could be used as a potential natural anti-biofilm agent to control food poisoning in the food industry. • Ovotransferrin (OT) and its hydrolysates the reduced biofilm formation of L. monocytogenes. • OT hydrolysate prepared with papain (OTPP) inhibited cell characteristics, EPS production, and biofilm metabolic activity. • OTPP downregulated the expression level of biofilm-related genes in L. monocytogenes. • OTPP could be used as a natural anti-biofilm agent to control food poisoning in the food industry. [ABSTRACT FROM AUTHOR]

Background: Many patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma. Results: TMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals. Conclusion: Our results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC. [ABSTRACT FROM AUTHOR]

Intermolecular oxidative cyclotrimerization reactions of alkenes and aromatic compounds with DDQ and trifluoromethanesulfonic acid are described. Scholl-type oxidation reactions involving alkenes have not previously been demonstrated. Moreover, the DDQ/acid system has never been used for intermolecular oxidative cyclization reactions. This convenient, metal-free reagent system (DDQ/TfOH) is advantageous with respect to metal-based Scholl-type oxidants because it eliminates the possibility of halogenation of aromatic compounds as a competing side reaction. [ABSTRACT FROM AUTHOR]

The alkylating agent temozolomide (TMZ) represents an important component of current melanoma therapy, but overexpression of O6-methyl-guanine DNA methyltransferase (MGMT) in tumor cells confers resistance to TMZ and impairs therapeutic outcome. We investigated a novel perillyl alcohol (POH)-conjugated analog of TMZ, NEO212, for its ability to exert anticancer activity against MGMT-positive melanoma cells. Human melanoma cells with variable MGMT expression levels were treated with NEO212, TMZ, or perillyl alcohol in vitro and in vivo, and markers of DNA damage and apoptosis, and tumor cell growth were investigated. NEO212 displayed substantially greater anticancer activity than any of the other treatments. It reduced colony formation of MGMT-positive cells up to eight times more effectively than TMZ, and much more potently induced DNA damage and cell death. In a nude mouse tumor model, NEO212 showed significant activity against MGMT-positive melanoma, whereas TMZ, or a mix of TMZ plus POH, was ineffective. At the same time, NEO212 was well tolerated. NEO212 may have potential as a more effective therapy for advanced melanoma, and should become particularly suitable for the treatment of patients with MGMT-positive tumors. [ABSTRACT FROM AUTHOR]

Background. Bartter syndrome (BS) is clinically classified into antenatal or neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS IV) and CASR (BS V). Methods. Clinico-genetic features of a nationwide cohort of 26 Korean children with BS were investigated. Results. The clinical diagnosis was aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter–Gitelman phenotype in 3 cases (11.5%). Five of eight patients with aBS and all 18 patients with either cBS or mixed Bartter–Gitelman phenotype had CLCNKB mutations. Among the 23 patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no genotype–phenotype correlation in patients with CLCNKB mutations. Conclusions. Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype–phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter–Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required. [ABSTRACT FROM PUBLISHER]

Abstract: We carried out this study to describe the difference between intention to receive vaccine against influenza A (H1N1) before the vaccination campaign and actual vaccine coverage rate after vaccination campaign; and to find out the factors affecting the acceptability. We analyzed data on intention to receive vaccine against influenza A (H1N1) and actual vaccination coverage rate from IR (immunization registry). In a survey of pre-vaccination, the sample size was 1042 and the survey results were weighted with gender and age distribution for sample distribution to be similar to population distribution. Although the intention to receive vaccine against influenza A (H1N1) was high, the actual vaccination coverage was lower than their intention. The factors affecting their intention were the degree of fear for novel influenza A (H1N1), the possibility to be infected with the virus, priority for production of novel influenza vaccine between timing and safety, and belief for effectiveness of novel influenza vaccine. Besides 2009 influenza A (H1N1) vaccination experience developing to resolve the effecting factors on intentions to receive vaccine, which would be the effective way to prepare for anther pandemic in the future. [ABSTRACT FROM AUTHOR]

Abstract: Moderate activity of the endoplasmic reticulum (ER) stress response system exerts anti-apoptotic function and supports tumor cell survival and chemoresistance, whereas its more severe aggravation may exceed the protective capacity of this system and turn on its pro-apoptotic module. In this study, we investigated whether the combination of two pharmacologic agents with known ability to trigger ER stress via different mechanisms would synergize and lead to enhanced tumor cell death. We combined the HIV protease inhibitor nelfinavir (Viracept®) and the cyclooxygenase 2 (COX-2) inhibitor celecoxib (Celebrex®) and investigated their combined effect on ER stress and on the viability of breast cancer cells. We found that this drug combination aggravated ER stress and caused pronounced toxicity in human breast cancer cell lines, inclusive of variants that were highly resistant to other therapeutic treatments, such as doxorubicin, paclitaxel, or trastuzumab. The anti-tumor effects of celecoxib were mimicked at increased potency by its non-coxib analog, 2,5-dimethyl-celecoxib (DMC), but were substantially weaker in the case of unmethylated-celecoxib (UMC), a derivative with superior COX-2 inhibitory efficacy. We conclude that the anti-tumor effects of nelfinavir can be enhanced by celecoxib analogs in a COX-2 independent fashion via the aggravation of ER stress, and such drug combinations should be considered as a beneficial adjunct to the treatment of drug-resistant breast cancers. [Copyright &y& Elsevier]

This essay tries to trace the life trajectory of an intellectual, in terms of his intellectual and social practices, who wants to live through modern Korean history via progressive activism. The trajectory can be divided into three different stages: the first comes with the military developmental dictatorship in 1961, ending in 1987. The next is during the democratic transition since the Democratic Uprising in June 1987, which put the Korean society onto the road of democratization. The last one should be the so-called 'post-democratization' period in which we now find ourselves. This is more a story than an analysis of the progressive intellectual movement in the form of the personal recollections. The story is, however, not just about an individual but it is a window giving a glimpse into the larger trajectory that many progressive intellectuals have gone through, and that directly reflects the huge changes in contemporary history of South Korea, such as the interaction between the domination and social movements. [ABSTRACT FROM AUTHOR]

This paper tries to analyze the historical change in the Third World in its emergent stage, in the authoritarian stage and in the current democratic stage and, thereafter, find a way to revive the Bandung spirit in the current globalization context. I define the Bandung spirit as one of a ‘non‐aligned self‐helped “organization against” the dominant powerful countries’; that is, spirit of ‘anti‐predominance’. This spirit has emerged on the base of such domestic orientation and realities as economic self‐reliance, nationally integrated political regime, convergence of the state and civil society around anti‐colonialism. However, according to intensification of the Cold War confrontation on the international level and its centrifugal influence, the early Third World changed to a ‘new’ authoritarian Third World. The Third World in this stage could be characterized by an exclusive authoritarian political regime, dependent‐developmentalist economic orientation and coercively repressed and mobilized, in the top‐down way, civil society. This authoritarian Third World began to be confronted with a strong struggle from the bottom for democratization. In order for democratization of the Third World to become its true revival in the context of globalization, the following tasks should be considered. First, the democratic Third World should be a great driving force for the institutionalization of the transnational public regulatory mechanism. Second, the democratic Third World countries try to go over a kind of ‘transformed’ dependent development strategy. Third, democratization should go along with recovery of political inclusiveness and openness of the state to civil society’s demands. Thereafter, I tried to construct globalist re‐interpretation of the Bandung, by way of conceptualizing the current globalization as imperial globalization, unlike the imperialist globalization which the historical Bandung wanted to confront. I argue that the Bandung spirit of collective self‐help organizations against the newly emerging dominant order should be revived in this worse imperial globalization context. In addition, I argue that a nationalist resistance is also one component of the multiple resistances in the current imperial globalization. [ABSTRACT FROM AUTHOR]

Abstract: Homeobox genes are essential regulators of the development of plants as well as other organisms. We chose eight putative Arabidopsis homeobox genes not previously characterized and examined their expression in response to treatment with auxin/cytokinin. One of them, ATHB53, was further studied because it was auxin-inducible and its induction was inhibited by cytokinin. Its full-length cDNA was cloned and found to encode a protein of the HD-Zip superfamily. Whole-mount in situ hybridization and RT-PCR showed that it was expressed in the root meristem, and auxin treatment increased its expression, especially in a region from 0.3 to 0.6mm from the root tip. These results suggest that ATHB53 plays a regulatory role in auxin/cytokinin signaling during root development. [Copyright &y& Elsevier]

Focuses on the challenges of globalization in the U.S. Militarism in globalization; Impact of militarism on global struggle; Strategy against armored globalization.

Examines the sacrifices made by the citizens under the military authoritarianism in South Korea. Implementation of democratic principles after the uprising; Interactions between state violence and numerous sacrifices while confronting undemocratic violence; Dismissal of people from jobs and imprisonment.

Reviews the overall transition and changes in nongovernmental organizations (NGO) in South Korea. Comparison of the directories of NGO in 1999 and 1996; Role of authoritarianism and democratization in the changes in the NGO; History of Korea's modern NGO; Structural conditions peculiar to Korea that have contributed to the rapid growth in Korea's civil social movement.

In patients with type 1 diabetes (T1D), compromised pancreatic β-cell functions are compensated through daily insulin injections or the transplantation of pancreatic tissue or islet cells. However, both approaches are associated with specific challenges. The transplantation of mesenchymal stem cells (MSCs) represents a potential alternative, as MSCs have tissue-forming capacity and can be isolated from various tissues. The human umbilical cord (hUC) is a good source of freely available MSCs, which can be collected through pain-free, non-invasive methods subject to minimal ethical concerns. We sought to develop a method for the in vitro generation of insulin-producing cells (IPCs) using MSCs. We examined the potential therapeutic uses and efficacy of IPCs generated from hUC-derived MSCs (hUC-IPCs) and human adipose tissue (hAD)-derived MSCs (hAD-IPCs) through in vitro experiments and streptozotocin (STZ)-induced C57BL/6 T1D mouse models. We discovered that compared to hAD-IPCs, hUC-IPCs exhibited a superior insulin secretion capacity. Therefore, hUC-IPCs were selected as candidates for T1D cell therapy in mice. Fasting glucose and intraperitoneal glucose tolerance test levels were lower in hUC-IPC-transplanted mice than in T1D control mice and hAD-IPC-transplanted mice. Our findings support the potential use of MSCs for the treatment of T1D. [ABSTRACT FROM AUTHOR]

The article focuses on the inception of the Inter-Asia Cultural Studies: Movements project. The fundamental concern of the project is the third world countries. The globalization effect has somewhat set aside the and erased relevance of the Third World. There are efforts to counter the neo-liberal globalization.

Wiley‐VCH, Weinheim, 2012. 452 pp., hardcover, € 129.00.—ISBN 978‐3527329465 (softcover, € 59.00.—ISBN 978‐3527329342) [ABSTRACT FROM AUTHOR]

Wiley ‐ VCH, Weinheim, 2012. 452 S., geb., 129.00 €—ISBN 978 ‐ 3527329465 (Broschur, € 59.00.—ISBN 978 ‐ 3527329342) [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Oxidative Cyclotrimerization of Unsaturated Compounds with DDQ and Triflic Acid: An Efficient Synthetic Route to Triply-Fused Benzene Rings" published in the periodical "Tetrahedron Letters" in 2015.

Review: [44 refs. [ABSTRACT FROM AUTHOR]

Abstract: The Korea Advisory Committee on Immunization Practices (KACIP), established by law in the early 1990s, makes recommendations on a range of issues related to the National Immunization Program. The Committee consists of 15 members and always includes the two government officials who belong to the Korea Centers for Disease Control and Prevention and the Korea Food and Drug Administration. Other members usually come from affiliated organizations and serve for 2-year terms. The KACIP depends on special-topics sub-committees or temporary advisory committees to gather and analyze data and to make recommendations which are normally reached by consensus and implemented by public sector health providers and private providers. [Copyright &y& Elsevier]

Abstract: Ventricular arrhythmia is a major cause of death in end-stage renal disease (ESRD). Corrected QT (QTc) interval prolongation, which is one of the predictors of ventricular arrhythmia, may be associated with ESRD. We report an 11-year-old boy who had ESRD with marked QTc interval prolongation and developed torsade de pointes with subsequent ventricular fibrillation during the induction of anesthesia. QTc interval was normalized completely after renal transplantation. [Copyright &y& Elsevier]

Discusses the role of civic action for global democracy as a response to neo-liberal globalization. Reorganization of the capital's domination without public regulatory mechanism; History of capitalism as a process for public regulation of the free market; Revival of internationalism in the social movement and sensitivity to new cultural resources.

Several biaryls have been subjected to flash vacuum pyrolysis (FVP) at 1100°C and 0.8-0.9 hPa. Product compositions are reported for the FVP of 9-phenylanthracene (1), 2-bromobiphenyl (5), biphenyl (8), 1,10-diphenylanthracene (12), 9-(2-naphthyl)anthracene (17), and 9,90-bianthracenyl (20). The experimental results have been used to evaluate four possible mechanistic pathways for the cleavage of aryl-aryl bonds under these conditions: (1) the 'explosion' of substituted phenyl radicals; (2) hydrogen atom attachment to an ipso-carbon atom of the biaryl followed by C-C bond cleavage; (3) direct homolysis; and (4) loss of a fragment as an aryne. None of these mechanisms by itself successfully accommodates all of the experimental facts. The data suggest that aryl-aryl bond cleavages under FVP conditions involve at least two different mechanistic pathways and that the relative contributions of the competing pathways probably vary from one biaryl to the next. [ABSTRACT FROM AUTHOR]

Abstract: Evidence of dysregulation of the CREB/CRE transcriptional pathway in animal models of Huntington''s disease (HD) suggests that strategies designed to augment CRE-mediated transcription may be of therapeutic value. Here, we investigated the consequences of CREB activation and repression in chemical and transgenic mouse models of HD. In the 3-nitropropionic acid (3-NP) model, CREB phospho-activation in the striatum was potently repressed within the neurotoxic “core” region prior to cell death. Conversely, marked expression of phospho-CREB, as well the CREB-regulated cytoprotective gene Bcl-2, was detected in the “penumbral” region. To examine potential contributory roles for the CREB/CRE transcriptional pathway in striatal degeneration, we used both CREB loss- (A-CREB) and gain- (VP16-CREB) of-function transgenic mouse strains. 3-NP-induced striatal lesion size and motor dysfunction were significantly increased in A-CREB mice compared to controls. Conversely, striatal damage and motor deficits were diminished in VP16-CREB mice. Furthermore, transgenic A-CREB significantly accelerated motor impairment in the YAC128 mouse model of HD. Together, these results indicate that CREB functionality is lost during the early stages of striatal cell stress and that the repression of CREB-mediated transcription contributes to the pathogenic process. [Copyright &y& Elsevier]

Abstract: Here we analyzed the light-responsiveness of the mammalian target of rapamycin (mTOR) cascade, a key regulator of inducible translation, in the suprachiasmatic nuclei (SCN), the locus of the master circadian clock. Brief light exposure during the subjective night, but not during the subjective day, triggered rapid phosphorylation (a marker of catalytic activity) of the mTOR translation effectors p70 S6K, ribosomal S6 protein (S6) and 4E-BP1. In the absence of photic stimulation, marked S6 and 4E-BP1 phosphorylation was detected, indicating tonic mTOR activity in the SCN. Light stimulated the colocalized activation of p70 S6K and extracellular signal-regulated protein kinase (ERK), and pharmacological disruption of ERK signaling abolished light-induced mTOR activity, revealing that the MAPK cascade is an essential intermediate that couples light to mTOR. Together these data identify a light-responsive mTOR cascade in the SCN, and thus, raise the possibility that inducible translation contributes to the clock entrainment process. [Copyright &y& Elsevier]

EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0‐68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield. [ABSTRACT FROM AUTHOR]

The prognosis for patients with glioblastoma (GB) remains grim. Concurrent temozolomide (TMZ) radiation—the cornerstone of glioma control—extends the overall median survival of GB patients by only a few months over radiotherapy alone. While these survival gains could be partly attributed to radiosensitization, this benefit is greatly minimized in tumors expressing O6-methylguanine DNA methyltransferase (MGMT), which specifically reverses O6-methylguanine lesions. Theoretically, non-O6-methylguanine lesions (i.e., the N-methylpurine adducts), which represent up to 90% of TMZ-generated DNA adducts, could also contribute to radiosensitization. Unfortunately, at concentrations attainable in clinical practice, the alkylation capacity of TMZ cannot overwhelm the repair of N-methylpurine adducts to efficiently exploit these lesions. The current therapeutic application of TMZ therefore faces two main obstacles: (i) the stochastic presence of MGMT and (ii) a blunted radiosensitization potential at physiologic concentrations. To circumvent these limitations, we are developing a novel molecule called NEO212—a derivatization of TMZ generated by coupling TMZ to perillyl alcohol. Based on gas chromatography/mass spectrometry and high-performance liquid chromatography analyses, we determined that NEO212 had greater tumor cell uptake than TMZ. In mouse models, NEO212 was more efficient than TMZ at crossing the blood-brain barrier, preferentially accumulating in tumoral over normal brain tissue. Moreover, in vitro analyses with GB cell lines, including TMZ-resistant isogenic variants, revealed more potent cytotoxic and radiosensitizing activities for NEO212 at physiologic concentrations. Mechanistically, these advantages of NEO212 over TMZ could be attributed to its enhanced tumor uptake presumably leading to more extensive DNA alkylation at equivalent dosages which, ultimately, allows for N-methylpurine lesions to be better exploited for radiosensitization. This effect cannot be achieved with TMZ at clinically relevant concentrations and is independent of MGMT. Our findings establish NEO212 as a superior radiosensitizer and a potentially better alternative to TMZ for newly diagnosed GB patients, irrespective of their MGMT status. [ABSTRACT FROM AUTHOR]

Background: Pediatric as well as adult patients with chronic kidney disease (CKD) are susceptible to cardiovascular disease (CVD) events, which increase their mortality. Dyslipidemia is thought to be one of the most important contributing risk factors for developing CVD. This study aimed to evaluate the prevalence of dyslipidemia and assess clinical and laboratory risk factors associated with dyslipidemia in East Asian pediatric patients with CKD. Methods: From April 2011 to April 2016, 469 patients with CKD aged < 20 years were enrolled in KNOW-PedCKD (the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease); 356 patients were included in the final analysis. Using the baseline data of the cohort cross-sectionally, a multivariable logistic regression analysis was performed to assess the risk factors for dyslipidemia; a subanalysis for each lipid abnormality was also done. Results: The prevalence of dyslipidemia was 61.5% (n = 219). For dyslipidemia, nephrotic range proteinuria and 25-hydroxyvitamin D deficiency significantly increased the adjusted odds ratio. In the subanalysis, glomerulonephropathy as the origin of CKD and nephrotic range proteinuria significantly increased the risks for high total cholesterol and high low-density lipoprotein cholesterol. Overweight or obese body mass index z-score, elevated proteinuria, hypocalcemia, and 1,25-dihydroxyvitamin D deficiency were significantly associated with low high-density lipoprotein cholesterol. Glomerular filtration rate stage 3b or higher and hyperphosphatemia significantly increased the risk for high triglycerides. Conclusions: Long-term data accumulation and prospective analysis are needed to clarify the relationship between CKD progression and dyslipidemia and to find additional risk factors for dyslipidemia. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study was designed to investigate the impact of paediatric end‐stage renal disease (ESRD) on parents, based on the PedsQL Family Impact Module (FIM), and the relationship to the quality of life (QOL) of paediatric ESRD patients measured by PedsQL 3.0 ESRD module. Methods: We performed a cross‐sectional study using Korean translations of the PedsQL FIM and the PedsQL 3.0 ESRD module. In all, 79 patients were enrolled, including 47 children receiving dialysis and 32 children who underwent renal transplant. Results: FIM scores, analyzed for every category according to treatment modality, were significantly lower in haemodialysis (HD) than in peritoneal dialysis (PD) or renal transplant patients. Mother's age, duration since diagnosis of ESRD and the existence of comorbidity were variables to have significant effects on FIM scores. The correlation between total FIM and QOL scores of paediatric patients were significant, in both parent‐proxy and child‐self report. Conclusions: The PedsQL FIM appears to be a useful tool for the assessment of family impact on children with ESRD. Further prospective studies focused on the QOL of parents and caregivers should be performed with the goal of improving clinical outcomes for paediatric ESRD patients. [ABSTRACT FROM AUTHOR]

Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination. The cytotoxic mechanism of NEO214 involved severe ER stress and prolonged induction of CCAAT/enhancer-binding protein homologous protein (CHOP), a key pro-apoptotic component of the ER stress response. These effects were prevented by salubrinal, a pharmacologic inhibitor of ER stress, and by CHOP gene knockout. Conversely, combination of NEO214 with bortezomib, a drug in clinical use for patients with MM, resulted in synergistic enhancement of MM cell death. Combination with the adenylate cyclase stimulant forskolin did not enhance NEO214 impact, indicating that cyclic adenosine 30,50-monophosphate (AMP) pathways might play a lesser role. Our study introduces the novel agent NEO214 as a potent inducer of ER stress with significant anti-MM activity in vitro. It should be further investigated as a potential MM therapy aimed at exploiting this tumor's distinct sensitivity to ER stress. [ABSTRACT FROM AUTHOR]

Background Atypical hemolytic uremic syndrome ( aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. Methods A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor- H autoantibody (anti- CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor- H related protein genes ( CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. Results Fifteen patients (group A, 29.7%) had anti- CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti- CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. Conclusions The incidence of anti- CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children. [ABSTRACT FROM AUTHOR]

Background: Anterior gradient 2 (AGR2) has been implicated in tumor-associated phenotypes such as cell viability, invasion and metastasis in various human cancers. However, the tumor promoting activity of AGR2 has not yet been determined in biliary tract cancers. Thus, we examined the expression of AGR2 and its tumor-promoting activity in biliary tract cancer cells in this study.Methods: Expression of AGR2 mRNA and protein was analyzed by real time RT-PCR and western blotting, respectively. MTT assay was employed to measure cell viability and pulsed BrdU incorporation by proliferating cells was monitored by flow cytometry. Soft agar colony formation assay and transwell invasion assay were employed to determine anchorage-independent growth and in vitro invasion of the tumor cells, respectively. In vivo tumor formation was examined by injection of tumor cells into immunocompromised mice subcutaneously. Statistical analysis was performed with 2-tailed unpaired Student's t-test for continuous data and with one-way ANOVA for multiple group comparisons. Bonferroni tests were used for post hoc 2-sample comparisons.Results: AGR2 mRNA was detected in SNU-245, SNU-478, and SNU-1196 cell lines, and its protein expression was confirmed in SNU-478 and SNU-245 cell lines by western blot analysis. Knockdown of AGR2 expression with an AGR2-specific short hairpin RNA (shRNA) in SNU-478, an ampulla of Vater cancer cell line resulted in decreased cell viability and in decreased anchorage-independent growth by 98%. The AGR2 knockdown also increased the sensitivity of the cells to chemotherapeutic drugs, including gemcitabine, 5-fluorouracil and cisplatin. In addition, SNU-478 cells expressing AGR2-shRNA failed to form detectable tumor xenografts in nude mice, whereas control cells formed tumors with an average size of 179 ± 84 mm3 in 3 weeks. Overexpression of AGR2 in SNU-869 cells significantly increased cell viability through enhanced cell proliferation and the number of Matrigel™-invading cells compared with AGR2-negative SNU-869 cells.Conclusions: Our findings implicate that AGR2 expression augments tumor-associated phenotypes by increasing proliferative and invasive capacities of the ampulla of Vater cancer cells. [ABSTRACT FROM AUTHOR]