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Three venomous snakes of the Gloydius genus belonging to the Viperidae family cause most snake envenomations in South Korea. Envenomation signs often include local swelling, coagulopathy, and rhabdomyolysis. The benefit of additional antivenom after the initial does is unclear. This retrospective study divided patients into four groups according to the presence of rhabdomyolysis (creatine kinase ≥1000 IU/L) and coagulopathy, which were defined using the Korean Society on Thrombosis and Hemostasis disseminated intravascular coagulation score (rhabdomyolysis, coagulopathy, combination, and local effects groups). We describe the clinical features of envenomation and the antivenom response. Greater local swelling predicted more severe snakebite pain. Ninety of the 231 enrolled patients (38.9%) developed rhabdomyolysis. The patients with severe rhabdomyolysis in the combination group displayed higher peak creatine kinase activity than the rhabdomyolysis group. Seven patients with rhabdomyolysis, including two patients requiring kidney replacement therapy, developed acute kidney injury, but the incidence of acute kidney injury did not differ between the combination group and rhabdomyolysis group. Bleeding developed in 3.5% of the patients, but its incidence did not differ between the combination and coagulopathy groups. Approximately half of all patients needed repeated antivenom administration, mainly due to the local envenomation effect. Earlier administration of additional antivenom for progressive local swelling did not reduce the hospitalization duration. Rhabdomyolysis is one of the major effects of Gloydius snake envenomation in South Korea, although it is not associated with the same risk of clinical deterioration as coagulopathy. Additionally, the ability of antivenom to ameliorate local swelling should be investigated to prevent unnecessary antivenom administration in South Korea. [ABSTRACT FROM AUTHOR]

Metorchis orientalis is a neglected zoonotic parasite of the gallbladder and bile duct of poultry, mammals, and humans. It has been widely reported in Asian, including China, Japanese, and Korea, where it is a potential threat to public health. Despite its significance as an animal and human pathogen, there are few published transcriptomic and proteomics data available. Transcriptome Illumina RNA sequencing and label-free protein quantification were performed to compare the gene and protein expression of adult and metacercariae-stage M. orientalis , resulting in 100,234 unigenes and 3,530 proteins. Of these, 13,823 differentially expressed genes and 1,445 differentially expressed proteins were identified in adult versus metacercariae. In total, 570 genes were differentially expressed consistent with the mRNA and protein level in the adult versus metacercariae stage. Differential gene transcription analyses revealed 34,228 genes to be expressed in both stages, whereas 66,006 genes showed stage-specific expression. Compared with adults, the metacercariae stage was highly transcriptional. GO and KEGG analyses based on transcriptome and proteome revealed numerous up-regulated genes in adult M. orientalis related to microtubule-based processes, microtubule motor activity, and nucleocytoplasmic transport. The up-regulated genes in metacercariae M. orientalis were mainly related to transmembrane receptor protein serine/threonine kinase activity, transmembrane receptor protein serine/threonine kinase signaling pathway. Transcriptome and proteome comparative analyses showed numerous up-regulated genes in adult stage were mainly enriched in actin filament capping, spectrin, and glucose metabolic process, while up-regulated genes in metacercariae stage were mainly related to cilium assembly, cilium movement, and motile cilium. These results highlight changes in protein and gene functions during the development of metacercariae into adults, and provided evidence for the mechanisms involved in morphological and metabolic changes at both the protein and gene levels. Interestingly, many genes had been proved associated with liver fibrosis and carcinogenic factors were identified highly expressed in adult M. orientalis , which suggests that M. orientalis is a neglected trematode with potential carcinogenic implications. These data provide attractive targets for the development of therapeutic or diagnostic interventions for controlling M. orientalis. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the expansion of myeloid lineage cells. Chronic myeloid leukemia (CML) is characterized by a BCR-ABL1 fusion gene that causes constitutive tyrosine kinase activity. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis (PMF) are frequently associated with driver mutations in genes such as JAK2, CALR, and MPL and are mutually exclusive of BCR-ABL1. Herein, we report the first case study of a patient diagnosed with accelerated-phase CML while undergoing treatment for initial JAK2 V617F–positive, BCR-ABL1 -negative PMF. This finding emphasizes the importance of BCR-ABL1 testing in patients with an atypical BCR-ABL1 -negative MPN disease course. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion—up to 30%—of the global adult female population. Several factors have been linked with NAFLD in women, such as age, obesity, and metabolic syndrome. To extract appropriate details about the topic, we conducted an extensive search using various medical subject headings and entry terms including 'Menopause', 'Non-alcoholic fatty liver disease', 'Insulin resistance', and 'BMI'. This exhaustive search resulted in a total of 180 studies, among which only 19 were able to meet the inclusion criteria. While most of these studies indicated a significant rise in NAFLD prevalence among postmenopausal women, two did not find strong evidence linking menopause with NAFLD. Moreover, it was observed that women with NAFLD had higher insulin resistance levels and BMIs compared to those without the condition. In summary, it is important to consider specific factors like risk profile, hormonal status, and age along with metabolic components when treating women presenting with NAFLD. There is need for data-driven research on how gender affects the sensitivity of biomarkers towards NAFLD as well as the development of sex-specific prediction models—this would help personalize management approaches for women, who stand to benefit greatly from such tailored interventions. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the leading causes of cancer deaths worldwide and is prevalent in East Asian countries, such as China, Japan, and South Korea, which are known to have high salt diets. The HER2 protein, which is often overexpressed in gastric and breast cancer, plays an important role in signaling for cell growth and proliferation. However, the function of the HER2 in relation to a high salt diet is not yet characterized. Salt has been shown to induce the expression of the SIK3 protein, which is associated with inflammation, tumorigenesis, cellular metabolic changes, and cell-cycle progression. The SIK3 protein is activated by Akt, a downstream protein of HER2, but a direct connection between SIK3 and HER2 has not been clearly defined. A mechanism to characterize this potential relationship begins at HER2 activation of PI3K/Akt, leading to mTORC2 activation, followed by Akt phosphorylation. Then, Akt will activate SIK3, which will phosphorylate HDAC4 and expel it from the nucleus, leading to various cellular processes known to induce cancer. If this mechanism is confirmed, it would offer insight into the synergistic effects of the HER2 protein and a high salt diet, converging on the SIK3 protein to promote cancer survival and progression. Therefore, the inhibition of SIK3 could stop cancer-promoting effects and be a useful target for chemotherapy of HER2þ gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify and validate genes specific for the survival of patients with papillary renal cell carcinoma (PRCC) in the TCGA-KIRP and Korean-KIRP databases. Using machine learning with statistical analysis, 40 survival-specific genes were identified in TCGA-KIRP. Of them, 10 were verified as survival-specific genes for Korean-KIRP patients through next-generation sequencing. Among these, BAP1, PCSK2, and SPATA13 showed significant survival specificity in both overall survival and disease-free survival. Survival gene signatures, including PCSK2, which are commonly obtained from 40 gene signatures in TCGA and 10 gene signatures in Korean databases, are expected to provide insight into predicting the survival of PRCC patients and developing new treatments. Purpose: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. Materials and Methods: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan–Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. Results: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10−7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10−7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10−7 and DFS: p = 1.21 × 10−7) databases. Conclusions: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment. [ABSTRACT FROM AUTHOR]

Background Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP). Patients and Methods Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib. Results Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses. Conclusions Our study highlights the value of NGS in detecting BRAF , NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib. [ABSTRACT FROM AUTHOR]

Background: An accurate and easily accessible method for diagnosing malignancies in local veterinary clinics has not yet been established. Objectives: To investigate the usefulness of serum thymidine kinase 1 (TK1) protein and its autoantibody as tumor biomarkers in dogs. Animals: Serum samples from 1702 dogs were collected from local animal hospitals and referral animal medical centers in South Korea. Methods: TK1 protein OD value and TK1 autoantibody ratio (TK1 autoantibody OD/total IgG OD) in serum samples of dogs classified into healthy controls, group with nontumor disease, group with benign and group with malignant tumors were measured using lateral flow immunochromatographic assay methods. Results: TK1 autoantibody levels were significantly higher in malignant tumor group (median 0.71) than in healthy controls (median 0.34), group with nontumor disease (median 0.34), and group with benign tumor (median 0.32, Welch t test, P <.0001). They were also significantly different among dogs with carcinomas (median 0.77), hematopoietic tumors (median 0.71), and sarcomas (median 0.56) than in healthy controls (median 0.34, post hoc Games‐Howell test, P <.0001). In the receiver operating characteristic curve of TK1 protein, AUC was 0.633 (95% CI: 0.592‐0.675, P <.0001). The AUC of TK1 autoantibody ratio was 0.758 (95% CI: 0.723‐0.793, P <.0001). Conclusions and Clinical Importance: TK1 autoantibody is a potentially useful biomarker for differentiating between healthy and tumor‐bearing dogs, better than TK1 protein measurement. However, both were inadequate when used as single biomarkers for screening dogs to discover occult malignant tumors. [ABSTRACT FROM AUTHOR]

Background: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma. It has been well known that NO from chronic inflammation responses are thought to be a major component of the damage and ultimate carcinogenesis ESPs such as nitric oxide synthase interacting protein (NOSIP) are thought to enhance the damage. The objective of this study was to identify the protein candidates interact with recombinant CsNOSIP (rCsNOSIP) and explore their role involved in CCA development or progression. Methods: We applied HuProt microarray containing 21,000 probe sets for a systematic identification of rCsNOSIP-binding proteins and grouped binding hits by gene function. Pull-down assays were used to confirm the interaction of rCsNOSIP with alveolar soft part sarcoma (ASPSCR-1) and sirtuins 5 (Sirt-5). ASPSCR-1/Sirt-5 over-expression and siRNA knockdown experiments were employed for obtain of ASPSCR-1/Sirt-5 high or low expression (ASP-oe/Sirt5-oe or ASP-si/Sirt5-si) cholangiocarcinoma cell line (CCLP-1) cells. Nitric oxide (NO) and reactive oxygen species assay (ROS) as well as cell proliferation and wound-healing assays were performed to observe the effect of rCsNOSIP on ASP-oe/Sirt5-oe or ASP-si/Sirt5-si CCLP-1 cells. Results: Seventy candidate proteins protein "hits" were detected as rCsNOSIP-binding proteins by HuProt microarray and bioinformatics analysis. Pull down assay showed that ASPSCR-1 and Sirt-5 could interact with rCsNOSIP. In addition, endotoxin-free-rCsNOSIP could increase the production of NO and ROS and promote the migration of CCLP-1 cells, while its effect on enhancing cell proliferation was not significant. Furthermore, ROS/NO production, proliferation, or migration were increased in ASP-si or Sirt5-si CCLP-1 cells but decreased in Asp-oe or Sirt5-oe CCLP-1 cells when stimulated with rCsNOSIP. Conclusions: Our findings suggest that CsNOSIP as a component of CsESPs might promote the development and invasion of CCA and Sirt5/ ASPSCR1 as host molecules might play a novel protective role against adverse stimulus during C. sinensis infection. This work supports the idea that CsESPs induce the occurrence and progression of CCA through ROS/RNS-induced oxidative and nitrative DNA damage. Author summary: Clonorchis sinensis (C. sinensis) is prevalent in China, Korea, and Vietnam, and 15–20 million people are estimated to be infected by this fluke, creating a socio-economic burden in epidemic regions. It is generally believed that excretory-secretory products from C. sinensis (CsESPs) can directly interact with the biliary epithelium and induce host inflammatory response. Our previous studies have manifested that CsNOSIP as a component of CsESPs can trigger nitrative and oxidative stress by enhancing the release of NO and reactive oxygen species (ROS) in macrophage. In the current study, we identified rCsNOSIP-binding proteins by HuProt microarray. In addition, we demonstrated that ASPSCR-1 and Sirt-5 could interact with rCsNOSIP by pull down assay. Moreover, rCsNOSIP could increase the production of NO and ROS and promote the migration of human CCLP-1 cells by using NO assay, detection of ROS assay as well as wound-healing assays. Our study provided new information about rCsNOSIP in promoting CCA invasion and metastasis as well as a novel protective role of SIRT5/ ASPSCR1 against adverse stimulus and support a basis for further discovery of drug targets for prevention and control of clonorchiasis. [ABSTRACT FROM AUTHOR]

Backgound: Pyeongwi-san (PWS) is a widely used formula for treating digestive disorders in Korea and China. Inflammatory bowel disease (IBD) is characterized by progressive inflammation of the gastrointestinal tract. Emerging evidence supports the protective effect of PWS against IBD, but specific mechanisms are still elusive. Methods: Active compounds of PWS were screened from the medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC) in the consideration of drug-likeness and oral bioavailability. Target candidates of active compounds were predicted using the ChEMBL database. IBD-related targets were obtained from the GeneCards and DisGeNET databases. The network of composition-targets-disease was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Molecular docking was used to simulate the binding affinity of active compounds on target proteins and molecular dynamics was used to validate the molecular docking result. Results: A total of 26 core target proteins of PWS were related to IBD. Enrichment analysis suggested that PWS is highly associated with tumor necrosis factor signaling pathway, apoptosis, and the collapse of tight junctions. Moreover, molecular docking and molecular dynamics simulation proposed β-eudesmol and (3R,6R,7S)-1,10-bisaboladien-3-ol to ameliorate IBD through the binding to TNF and MMP9, respectively. Conclusion: Present in silico analysis revealed potential pathways and insight of PWS to regulate IBD. These results imply that the therapeutic effect of PWS might be achieved via an inhibitory effect. [ABSTRACT FROM AUTHOR]

Background: Although there is strong evidence linking triglyceride to highdensity lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM). Methods: We performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women's Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM. Results: The mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%. Conclusion: Our results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis. [ABSTRACT FROM AUTHOR]

Human‐assisted movement has allowed the Asian longhorned beetle (ALB, Anoplophora glabripennis (Motschulsky)) to spread beyond its native range and become a globally regulated invasive pest. Within its native range of China and the Korean peninsula, human‐mediated dispersal has also caused cryptic translocation of insects, resulting in population structure complexity. Previous studies used genetic methods to detangle this complexity but were unable to clearly delimit native populations which is needed to develop downstream biosurveillance tools. We used genome‐wide markers to define historical population structure in native ALB populations and contemporary movement between regions. We used genotyping‐by‐sequencing to generate 6102 single‐nucleotide polymorphisms (SNPs) and amplicon sequencing to genotype 53 microsatellites. In total, we genotyped 712 individuals from ALB's native distribution. We observed six distinct population clusters among native ALB populations, with a clear delineation between northern and southern groups. Most of the individuals from South Korea were distinct from populations in China. Our results also indicate historical divergence among populations and suggest limited large‐scale admixture, but we did identify a restricted number of cases of contemporary movement between regions. We identified SNPs under selection and describe a clinal allele frequency pattern in a missense variant associated with glycerol kinase, an important enzyme in the utilization of an insect cryoprotectant. We further demonstrate that small numbers of SNPs can assign individuals to geographic regions with high probability, paving the way for novel ALB biosurveillance tools. [ABSTRACT FROM AUTHOR]

Pinellia ternata Breitenbach (PTB) is a widely used herbal medicine in China, Japan, and South Korea. It has antiemetic, anti-inflammatory, antitussive, and sedative properties. The raw material is toxic, but can be made safer using alum solution or by boiling it for a long time. In addition, PTB seems to be effective for gastrointestinal motility disorders (GMDs), but this is yet to be conclusively proven. Herein, PTB compounds, targets, and related diseases were investigated using the traditional Chinese medical systems pharmacology database and an analysis platform. Information on target genes was confirmed using the UniProt database. Using Cytoscape 3.8.2, a network was established and GMD-related genes were searched using the Cytoscape stringApp. The effects of the PTB extract on the pacemaker potential of interstitial cells of Cajal and GMD mouse models were investigated. In total, 12 compounds were found to target 13 GMD-related genes. In animal experiments, PTB was found to better regulate pacemaker potential in vitro and inhibit GMD signs compared to control groups in vivo. Animal studies showed that the mechanism underlying the effects of PTB is closely related to gastrointestinal motility. The results obtained demonstrated that PTB offers a potential means to treat GMDs, and we suggested that the medicinal mechanism of GMDs can be explained by the relationship between 12 major components of PTB, including oleic acid, and 13 GMD-related genes. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Aralia continentalis Kitagawa (Araliaceae) is a representative ethnomedicinal herbal plant traditionally prescribed in Korea to relieve various inflammatory symptoms. However, the exact molecular mechanism of its anti-inflammatory activity has not been fully investigated. Materials and methods: The effect of the ethanol extract from the roots of this plant (Ac-EE) on the production of the inflammatory mediator nitric oxide (NO) was studied in RAW264.7 cells. Its effect on inflammatory symptoms (gastritis and hepatitis) in mice was also examined. In particular, the molecular inhibitory mechanism was analysed by measuring the activation of transcription factors and their upstream signalling and the kinase activity of target enzymes. Results: Ac-EE dose-dependently suppressed NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. This extract also displayed curative activity against EtOH/HCl-induced gastritis and LPS-induced hepatitis in mice. Ac-EE-mediated anti-inflammatory activity was found to be at the transcriptional level, as it blocked the activation of the nuclear factor (NF)-κB pathway composed of Syk and Src, according to immunoblotting and immunoprecipitation analyses and a kinase assay with whole and nucleus lysates from RAW264.7 cells and mice. Conclusion: Ac-EE may be developed as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future work using pre-clinical studies will be needed to investigate this possibility. [Copyright &y& Elsevier]

Abstract: Aim of the study: Sanguisorba officinalis, a well known valuable medicinal plant in Korea, China and Japan used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. Recent studies have revealed that its aqueous or ethanolic extracts exhibit a variety of pharmacological activities such as anti-oxidative, anti-cancer, anti-lipid peroxidation, anti-atherogenic, and vasorelaxant effects. Systematic studies on the anti-inflammatory effect of this plant and its molecular mechanisms have not yet been fully investigated. Ethanol extract of Sanguisorba officinalis (So-EE) the lipopolysaccharide (LPS)-stimulated macrophages and production of inflammatory mediators were employed to assess these properties. Results: So-EE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG) E2 from LPS-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. This extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, implying that the blockade is generated at the transcriptional level. So-EE strongly blocked the activation and translocation of NF-κB and AP-1 by suppressing the upstream kinases including inhibitor of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), and mitogen activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Moreover, So-EE suppressed the phosphorylation of Src, its kinase activity, and complex formation between Src and p85. Conclusion: This study suggests that So-EE has a potent anti-inflammatory activity mediated by NF-κB, and AP-1 inhibitory properties linked to the suppression of Src and MAPK activation. [Copyright &y& Elsevier]

The prevalence of gastritis in South Korea is rapidly increasing owing to the prevalence of Helicobacter pylori infection and fast eating habit. The usual treatment for acute gastritis following a long intake of non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol is to stop the causal factors. Metronidazole and lansoprazole are recommended for the treatment of H. pylori infection gastritis. Omeprazole a proton pump inhibitor, is used to decrease gastric acid production. However, owing to the side effects and refractoriness of the drug, a safe and efficient treatment is required. Plant-derived phytochemicals have emerged as novel agents against chronic disorders. In this study, firstly, to explore the potential of pharmacological activities, including efficacy and mechanisms of Cinnamomum cassia against gastritis, a literature review was performed based on 20 studies out of a total of 749 records obtained using a search strategy. From the literature review, the therapeutic targets of C. cassia extract and cinnamaldehyde, a compound of C. cassia, were found to be related with NFκB activity, and their signaling pathway were verified by experiments. C. cassia extract plays a role in protection of gastric ulcers induced in four ways (immersion stress-induced, ethanol-induced, hydrochloric acid-induced, or NSAIDs-induced ulcer). None of the clinical studies on C. cassia extracts or compounds met our criteria. When the standardized extract of C. cassia (ECC) was orally administered repeatedly to Beagle Dog for 4 weeks, no toxicologically harmful changes were observed. Therefore, under the test condition, the no observed adverse effect level (NOAEL) of ECC was judged to be 1000 mg/kg/day for both sexes, and no toxic target organ was observed. Administration of ECC in the Sprague–Dawley rat model of acute gastric injury caused by indomethacin administration significantly increased gastric mucus volume. Administration of ECC in the acute gastric injury model caused by indomethacin administration is considered effective in improving gastric injury. However, research and efforts to develop a reliable 'standardization of natural drugs' by establishing the best quality evaluation system are limited. Despite the pharmacological potential of ECC, further well-designed experimental studies such as in vitro, in vivo, and clinical trials are required to validate these findings and the underlying mechanisms of ECC. [ABSTRACT FROM AUTHOR]

Pyropia (Porphyra, referred to as 'Gim' in Korea or 'Nori' in Japan), an economically valuable alga, has long been consumed as seafood, especially in north‐east Asian countries. Its well‐established conventional mass cultivation and harvesting methods in coastal areas widen the industrial availability of edible Pyropia sp. However, the unexpected discoloration derived from causative factors during the cultivation process gives rise to serious economic losses in the aquaculture industry. For the industrial use of discoloured laver waste (DLW), recent articles have suggested that DLW biomass could be used as a source of agar polysaccharide, porphyran, γ‐aminobutyric acid and other value‐added bioactive compound productions. Although DLW biomass has economic potential, the lack of integrated information and relevant studies still limits its industrial availability. Therefore, we discussed recent research concerning the functional ingredients, causative factors and potential availability of DLW to provide integrated information. Furthermore, this review suggested the potential industrial application of DLW as a source for other value‐added material production. [ABSTRACT FROM AUTHOR]

The prevalence of obesity has increased alarmingly both worldwide and in Korea. This has also dramatically increased the prevalence of chronic obesity-associated diseases, including type 2 diabetes (T2D). Extensive studies on the molecular etiology of T2D have revealed several potential mechanisms by which obesity induces the development of insulin resistance and T2D. One of these is low-grade chronic inflammation. Studies hinting at the existence of this phenomenon were first published about 30 years ago. Ten years later, several seminal papers confirmed its existence, which then led to a rapid and massive escalation of research in this field. Today, the notion that obesity-induced inflammation mediates T2D is now well-accepted. This paper will review the key developments in this field, including the discovery that obesity-induced inflammation and insulin resistance is mainly regulated by adipose tissue-resident immune cells, particularly those in visceral adipose tissue. This review further details the research areas, including (1) the obesity-related factors that induce adipose tissue macrophage (ATM) inflammation, (2) the precise effector functions by which adipose tissue immune cells promote insulin resistance, (3) whether there are early immunological events that have an outsize effect on later events and could be targeted to arrest the development of insulin resistance, (4) the roles played by nonimmunological functions of ATMs and other immune cells, and (5) whether there are noncanonical immune responses to obesity (i.e., immune responses that are unique to obesity and cannot be detected by following the discoveries in the classical immunity field). [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the relation of serum uric acid with prediabetes in Korea. We conducted a cross-sectional study in 4633 individuals aged 20 to 81 years who participated in the 2016 Korean National Health and Nutrition Examination Survey. Participants are considered to have prediabetes if they have one or more of the following: impaired fasting glucose (fasting blood glucose levels between 5.6 and 6.9 mmol/L); impaired hemoglobin A1c (hemoglobin A1c ranges of 5.7% to 6.4% [39-46 mmol/mol]). Multiple logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Prediabetes was more prevalent in the hyperuricemia group compared with the normal-range group among men (OR = 1.51; 95% CI = 1.11-2.05; P <.01) and women (OR = 1.84; 95% CI = 1.01-3.37; P =.04) after adjustment for age, body mass index, abdominal obesity, blood pressure, triglyceride, high-density lipoprotein cholesterol, renal function, alcohol consumption, smoking, and physical activity level. For a standard deviation increment in uric acid, the odds of having prediabetes as compared with that of not having prediabetes increased about 114% in men (P =.05) and 116% in women (P =.01). Higher levels of uric acid were associated with an increased risk of prediabetes among the general Korean population. [ABSTRACT FROM AUTHOR]

Programmed cell death ligand 1 (PD-L1) is an essential immune checkpoint protein implicated in immune evasion by malignant tumors. Overexpression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 is associated with poor prognosis in various types of cancer. Recently, multiple advances have occurred in the area of cancer immunotherapy. Inhibiting the ligation of PD-1 by PD-L1 has been the major focus of anti-tumor immunotherapy. In diagnostic pathology, it has become crucial to detect PD-L1+ tumor cases using a validated immunohistochemistry (IHC) approach. Preliminary data demonstrate that C-MET promotes survival of some (e.g., renal) cancer types through regulation of PD-L1. However, C-MET expression, and its association with PD-L1, has not been well-characterized in the context of hepatocellular carcinoma (HCC), and no anti-HCC immunotherapy is currently available in Korea. Therefore, it is crucial to investigate the expression of C-MET and PD-L1, and their association with clinicopathologic factors, to facilitate the development of targeted treatments for HCC. PD-L1 expression was examined in tumor cells (TC) and immune cells (IC) of 70 patient-derived HCC specimens using IHC. Two anti-PD-L1 monoclonal antibodies (MAbs), SP263 and SP142, were utilized. Additionally, TC C-MET expression was assessed. Correlations between PD-L1 expression (as identified by both MAbs), C-MET expression and clinicopathologic factors were assessed. More PD-L1+ cases were identified via SP263 than via SP142 when assessing both TC and IC; in the former group, SP236 identified 14/70 positive cases, while SP142 identified only 2/70. In the latter group, SP236 identified 49/70 positive cases, while SP142 identified 30/70. Both MAbs demonstrated a higher frequency of PD-L1 expression by IC than TC. The Edmondson-Steiner grade statistically correlated with a higher frequency of SP236-detected TC PD-L1 expression. C-MET was significantly associated with advanced tumor size and was positively correlated with SP263-detected PD-L1 expression in TC. These results suggest that C-MET may serve a role in regulating PD-L1 expression in HCC. Furthermore, while SP263 generally exhibited a higher sensitivity for PD-L1 detection, concordance in PD-L1+ case detection between the two different MAbs was generally good. These background data may be helpful in the development of targeted anti-HCC immunotherapy focused on PD-L1 or C-MET, and in evaluating selection criteria for target populations best suited to such treatments. [ABSTRACT FROM AUTHOR]

Purpose: The 14th Japan–Korea joint symposium on cancer and aging research was held at an auditorium of Saga University, Japan, May 31–Jun 2, 2018. Participants presented 31 oral and 21 poster presentations, two lectures at a luncheon seminar, plus special lectures from two Korean Emeritus Professors and founders of our joint symposia. The essential parts of the lectures are reviewed here. Results: This Symposium was called Japan–Korea, because the host country comes first. Our symposia are organized every 18 months and the program includes keynote and plenary lectures, and oral and poster presentations. (1) Subjects related to cancer development at this symposium were: prostate cancer progression, molecules activating GSK3β, suppressing the activation of cancer stem cells, profiling human B cell receptor repertoires, and hereditary gastrointestinal cancer syndrome. (2) Subjects related to treatment were: G-quadruplex ligands for glioma stem cells, tankyrase inhibitor for colorectal cancer, and eradication of ATL. (3) Cancer prevention subjects were: physical adsorption of EGCG to cell membrane, inhibition of immune evasion of cancer cells with EGCG, and prevention with antidiabetic agents. (4) Aging subjects were life span extension with Toll-like receptor 5 vaccine and reversal of senescence with inhibitors of ATM and ROCK. (5) The results of epidemiology focused on aldehyde dehyrogenase-2 and alcohol consumption. Conclusion: The 14th symposium demonstrated the cutting-edge of presentations with discussion of numerous ideas by the participants. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that high-density lipoprotein (HDL) cholesterol is associated with pulmonary function and pulmonary disorders. The aim of this study was to evaluate the association between HDL cholesterol and pulmonary function in healthy adolescents.Methods: This cross-sectional study was based on data collected for the JS High School study. The analysis included 644 adolescents (318 male and 326 female) aged 15-16 years old and free from asthma or chronic obstructive pulmonary disease. Fasting blood samples were collected for hematologic and biochemical assessment. Forced vital capacity volume (FVC) and forced expiratory volume in the 1 s (FEV1) were measured using dry-rolling-seal spirometry. The associations between HDL cholesterol and pulmonary function were analyzed using multiple linear regression models.Results: Among male adolescents, an increase of 1.0 mg/dL in HDL cholesterol was associated with 10 mL decrease in FVC (p = 0.013) and FEV1 (p = 0.013) after adjusting for age, height, weight, alcohol drinking, smoking, physical activity, systolic blood pressure, total cholesterol, triglyceride, and monthly household income. Percent predicted values of FVC (p = 0.036) and FEV1 (p = 0.017) were also inversely associated with HDL cholesterol. However, among female adolescents, HDL cholesterol level was not significantly associated with absolute or percent predictive value of FVC and FEV1.Conclusions: Higher HDL cholesterol level may be associated with decreased pulmonary function among healthy male adolescents. The sex differences observed in the association between HDL cholesterol and pulmonary function need further investigation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product-derived and chemotherapy agents including curcumin combined with 5-fluorouracil, resveratrol combined with cisplatin and epigallocatechin-3-gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The Akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of UA and DOX on the cell proliferation, apoptosis, migration and cell cycle of CRC cells were investigated by performing Cell proliferation assay, a soft agar colony formation assay, flow cytometry, wound healing assay and western blotting assay. Subsequently, the expression of AKT and Hippo signaling pathway-associated proteins were also assessed by western blot assay. Moreover, a xenograft nude mouse model was constructed to verify the effects of UA and DOX on the tumorigenesis of HCT116 cell in vivo. The present study reported that ursolic acid (UA) strongly enhanced the antitumor action of doxorubicin (DOX) via blocking the Akt/glycogen synthase kinase-3β (Gsk3β) signaling pathway and activating tumor-suppressive Hippo signaling (mammalian Ste20-like kinase 1 and 2, salvador family WW domain containing protein 1 and MOB kinase activator 1), thereby downregulating downstream effector yes-associated protein 1 (Yap) and connective tissue growth factor (CTGF) protein expression levels in CRC cells. Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway-associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas Akt activator SC79 exerted an opposite effect in CTGF expression. In vivo, treatment with UA combined with DOX markedly suppressed the progression of CRC without any toxic effects on a xenograft mouse model by disrupting Akt signaling and activating the Hippo signaling pathway. These results demonstrated that UA and DOX treatment successfully induced Akt/Gsk3β inactivation via Hippo signaling pathway activation to promote Yap degradation, resulting in the inhibition of colorectal tumorigenesis. In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future. [ABSTRACT FROM AUTHOR]

Age-related physiological changes are known to alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Metformin is commonly used as first-line medication for management of diabetes in elderly patients. However, the PK and PD of metformin have not been sufficiently studied in elderly subjects. Here, 12 elderly subjects, aged 65 to 85 years, and 20 younger healthy volunteers were orally administered 750 mg of metformin 2 hours after dinner, followed by administration of a second dose (500 mg) 12 hours later. An oral glucose tolerance test (OGTT) was performed 2 hours after the second dose, with 75 g of glucose administered. Blood samples were collected at specific time points after the second metformin dose for the assessment of PK and the glucose-lowering effect of metformin. Elderly subjects exhibited 1.7 and 2.0 times higher average Cmax and AUC∞ than the younger subjects, respectively ( P = .007 and .001, respectively), and t1/2 was comparable between the elderly and younger subjects. However, relative glucose level changes from baseline after metformin administration tended to be lower in elderly subjects. Systemic exposure to metformin was elevated by 50% or more in elderly subjects, whereas the glucose-lowering effect was similar compared to younger subjects after 2 doses of metformin. [ABSTRACT FROM AUTHOR]

Background: Bo-Gan-Whan (BGH), a Korean polyherbal medicine, is used as a hepatoprotective drug. It has six natural sources, and has been demonstrated to have anti-oxidative, anti-cancer, and anti-inflammatory properties; however, its effect on vascular diseases remains unclear. Methods: Cell viability and proliferation assays were employed using an EZ-Cytox Cell Viability Assay Kit. Platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (VSMC) migration was measured by scratch wound healing assay and Boyden chamber assay. The expression levels of the phosphorylated signaling proteins relevant to proliferation, including extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) were determined by western blot analysis. Chromatogram and mass analysis were employed by Ultra Performance Liquid Chromatography (UPLC) system. Cell prolife ration and migration were also explored using the PDGF-BB-induced aortic sprout assay. Results: BGH (100-500 µg/mL) significantly inhibited the proliferation and migration of PDGF-BB-stimulated VSMCs through the reduced phosphorylation of ERK1/2 and p38 MAPK in comparison to untreated PDGF-BB-stimulated VSMC. Moreover, we identified the paeoniflorin as the major composition of BGH. Conclusions: We suggest that BGH may have an anti-atherosclerosis effect by inhibiting the proliferation and migration of PDGF-BB-stimulated VSMCs through down-regulation of ERK1/2 and p38 MAPK phosphorylation. [ABSTRACT FROM AUTHOR]

Background: New-onset diabetes mellitus after transplantation (NODAT) is a serious complication following renal transplantation. The aim of this study was to identify the risk factors for the development of NODAT in Korean transplant patients.Methods: Recipients who underwent living donor kidney transplantation between January 2009 and April 2012 at Asan Medical Center were reviewed. Diagnosis of NODAT was defined according to the American Diabetes Association criteria.Results: A total of 418 patients were enrolled. NODAT was diagnosed in 85 (20.4 %) patients within 1 year. By multivariate analysis, old age (odds ratio [OR], 1.05; 95 % Confidence interval [CI]: 1.01-1.08), family history of diabetes mellitus (OR, 2.48; 95 % CI: 1.04-5.94), pre-transplant high serum glucose level (OR, 1.04; 95 % CI: 1.01-1.08), and obesity (OR, 3.46; 95 % CI: 1.55-7.73) were independent risk factors for NODAT.Conclusion: Old age, family history of diabetes, pre-transplant high plasma glucose level, and obesity are independent factors associated with the development of diabetes after renal transplantation. In contrast, serum magnesium levels and the use of tacrolimus are not associated with the development of NODAT. [ABSTRACT FROM AUTHOR]

Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI), is approved for the second-line treatment of chronic myeloid leukemia (CML) in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML) are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA). We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b+ cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b+ HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (ΔΨm) in CD11b+ cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics. [ABSTRACT FROM AUTHOR]

Jerusalem artichoke (Helianthus tuberosus Linne, HTL) and chungkookjang (CKJ; fermented soybeans) both modulate energy and glucose metabolism. However, the mechanism and their additive effects are unknown. We investigated whether the consumption of HTL and CKJ altered insulin sensitivity, insulin secretion capacity and β-cell survival in type 2 diabetic animals. Rats were divided into partially pancreatectomized (Px) diabetic rats, and sham operated non-diabetic control rats and all fed high fat diets. Diabetic rats were sub-divided into an untreated diabetic control group and those fed 5% HTL, 5% CKJ or 5% HTL+5% CKJ for 8 weeks. HTL+CKJ treatment reduced visceral fat without modulating energy intake compared to the diabetic-control. Glucose tolerance was improved in an ascending order of diabetic-control, CKJ, HTL, HTL+CKJ, and normal-control, but by different mechanisms. CKJ and CKJ+HTL, but not HTL, increased first and second phase insulin secretion in comparison to the diabetic-control at hyperglycemic clamp. However, glucose infusion rates (mg/kg bw/min) were increased by and CKJ+HTL (13.5), but not HTL (9.4) or CKJ (9.5) alone, and HTL and CKJ+ HTL decreased hepatic glucose compared to diabetic-control during the hyperinsulinemic euglycemic study and were associated with decreased triglyceride accumulation and increased glycogen storage. The improved hepatic insulin sensitivity by HTL and CKJ+HTL was explained by potentiated insulin signaling (tyrosine phosphorylation of insulin receptor substrate 2→phosphorylation of Akt) and phosphorylation of AMPK→phosphorykation of acetyl Co carboxlase in comparison to diabetic-control and decreased PEPCK expression. Absolute β-cell mass was increased by CKJ (23.4mg) and CKJ+HTL (26.3 mg) by increasing proliferation compared to the diabetic-control (21.26 mg). Although HTL lowered ?-cell apoptosis, it did not increase β-cell mass (20.8 mg). In conclusions, HTL and CKJ enhanced glucose tolerance in different manners, and exhibited partially additive and complementary effects by reversing insulin resistance and enhancing β-cell function in diabetic rats. [ABSTRACT FROM AUTHOR]

Distal myopathy with rimmed vacuoles (DMRV; MIM 605820) is an autosomal recessive neuromuscular disorder characterized by weakness of the anterior compartment of the lower limbs, sparing the quadriceps muscles. Recently, mutations in the UDP- N-acetylglucosamine-2-epimerase/ N-acetylmannosamine kinase ( GNE) gene have been identified as the genetic basis of DMRV. To investigate the mutation spectrum of the GNE gene in Korean patients with DMRV, we performed clinical and genetic analysis of nine unrelated patients suspected to have DMRV. Direct sequencing analysis revealed that eight out of nine patients (88.9%) were either homozygous or compound heterozygous for GNE gene mutations, including three known (C13S, R129Q, and V572L) and two novel mutations (M29T and A591P). The allelic frequencies of the V572L and C13S mutations were 68.8% (11/16) and 12.5% (2/16), respectively. These results suggest that screening for GNE gene mutations in patients suspected to have DMRV would be helpful for molecular diagnosis of DMRV in the Korean population. [ABSTRACT FROM AUTHOR]

The amplification and overexpression ofHer2proto-oncogene have been found to be associated with the development and progression of human breast cancer. A polymorphic valine allele at codon 655 of theHer2gene (Her2V655) was suggested by some authors to be a susceptible genetic factor for the development of breast cancer. TheHer2polymorphism at codon 655 was investigated in 304 Korean women including 177 patients with breast cancer. The association betweenHer2genotype andHer2protein overexpression was also examined in breast cancers by immunohistochemistry.Her2V655 was not associated with a significant breast cancer risk (odds ratio (OR), 1.792; 95% confidence interval (CI), 0.459–6.991). The frequency of homozygous or heterozygous valine allele increased in stage 2 patients (OR, 1.67; 95% CI, 0.67–4.19), and patients in stages 3 and 4 (OR, 3.36; 95% CI, 0.85–13.42) compared to patients in stage 0. However, an association between the presence of the valine allele and the overexpression ofHer2protein could not be demonstrated. These results suggest thatHer2polymorphism at codon 655 is not associated with the development of breast cancer in Korean women. However, there is a possibility that the valine allele at codon 655 might be related to increased risk of breast cancer progression. [ABSTRACT FROM AUTHOR]

Examines a tumor suppressor gene, homologous to the gene for human nucleoside disphosphate kinase, cloned from Scyliorhinus torazame in South Korea. Gene sequence; Tissue specificity; Sequence comparison of the gene with the kinase.

Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest. Gene set enrichment analysis indicated that the identified candidate genes were related to biological processes and functional terms that were involved in growth and lipid metabolism. In conclusion, these results suggest that the incorporation of GWAS results and network analysis can help us to better understand the genetic bases underlying growth and carcass traits. In recent years, studies on the biological mechanisms underlying complex traits have been facilitated by innovations in high-throughput genotyping technology. We conducted a weighted single-step genome-wide association study (WssGWAS) to evaluate backfat thickness, carcass weight, eye muscle area, marbling score, and yearling weight in a cohort of 1540 Hanwoo beef cattle using BovineSNP50 BeadChip. The WssGWAS uncovered thirty-three genomic regions that explained more than 1% of the additive genetic variance, mostly located on chromosomes 6 and 14. Among the identified window regions, seven quantitative trait loci (QTL) had pleiotropic effects and twenty-six QTL were trait-specific. Significant pathways implicated in the measured traits through Gene Ontology (GO) term enrichment analysis included the following: lipid biosynthetic process, regulation of lipid metabolic process, transport or localization of lipid, regulation of growth, developmental growth, and multicellular organism growth. Integration of GWAS results of the studied traits with pathway and network analyses facilitated the exploration of the respective candidate genes involved in several biological functions, particularly lipid and growth metabolism. This study provides novel insight into the genetic bases underlying complex traits and could be useful in developing breeding schemes aimed at improving growth and carcass traits in Hanwoo beef cattle. [ABSTRACT FROM AUTHOR]

Background: Rice is a major food resource for Asian countries including Korea. However, most Asian countries are facing food safety problems due to cropland contamination by heavy metals. Thus, this study was conducted to investigate genetic factors affecting the expression of cadmium (Cd) gene, and to confirm differences in Cd translocation among cultivars because the current molecular understanding of Cd uptake-transport mechanisms remains insufficient. Associations between genotypes and gene expression level of Cd-related genes such as NRAMP, MTP, and HMA gene families in the rice core collection were analyzed at the genomic level. Results: Os01g0956700, Os05g0128400 and Os11g0485200 showed strong associations between expression level and genotype in the rice core collection, the regulatory factors that associated with these genes in cis and trans were founded. The association between the expression level and genotype of the candidate gene (Os01g0611300: metal tolerance protein) predicted to affect Cd content in rice by a previous genome-wide association study (GWAS) was also analyzed. Furthermore, as a result of the phylogeny and haplotype analyses of the candidate gene, high-Cd tolerance cultivars were selected. The correlations between Cd and other inorganic components (Mg, Mn, Fe, Cu and Zn) in the roots, stems, leaves and unpolished grain of selected rice cultivars were analyzed. Conclusion: Therefore, these results may be useful for understanding the uptake-transport mechanisms of Cd and other inorganic components via molecular genetics and may help rice breeders develop new low-Cd cultivars in the near future. [ABSTRACT FROM AUTHOR]

Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radotinib on Aurora kinase expression in acute myeloid leukemia are not well studied. Interestingly, the cytotoxicity of acute myeloid leukemia cells was increased by radotinib treatment. Radotinib significantly decreased the expression of cyclin-dependent kinase 1 and cyclin B1, the key regulators of G2/M phase, and inhibited the expression of Aurora kinase A and Aurora kinase B in acute myeloid leukemia cells. In addition, radotinib decreased the expression and binding between p-Aurora kinase A and TPX2, which are required for spindle assembly. Furthermore, it reduced Aurora kinase A and polo-like kinase 1 phosphorylation and suppressed the expression of α-, β-, and γ-tubulin in acute myeloid leukemia cells. Furthermore, radotinib significantly suppressed the key regulators of G2/M phase including cyclin B1 and Aurora kinase A in a xenograft animal model. Therefore, our results suggest that radotinib can abrogate acute myeloid leukemia cell growth both in vitro and in vivo and may serve as a candidate agent or a chemosensitizer for treating acute myeloid leukemia. [ABSTRACT FROM AUTHOR]