Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020.

BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study.

AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

MYC in Brain Development and Cancer.

The MYC family of transcriptional regulators play significant roles in animal development, including the renewal and maintenance of stem cells. Not surprisingly, given MYC's capacity to promote programs of proliferative cell growth, MYC is frequently upregulated in cancer. Although members of the MYC family are upregulated in nervous system tumours, the mechanisms of how elevated MYC promotes stem cell-driven brain cancers is unknown. If we are to determine how increased MYC might contribute to brain cancer progression, we will require a more complete understanding of MYC's roles during normal brain development. Here, we evaluate evidence for MYC family functions in neural stem cell fate and brain development, with a view to better understand mechanisms of MYC-driven neural malignancies.

The Crossover Effects of Supervisors' Workaholism on Subordinates' Turnover Intention: The Mediating Role of Two Types of Job Demands and Emotional Exhaustion.

Although much research has been conducted on workaholism, its crossover effects remain uninvestigated, especially in the context of organizations. Based on the job demands-resources (JD-R) model of burnout and the conservation of resources (COR) theory, we established a dual-path structural model to examine the effects of supervisors' workaholism on subordinates' turnover intention through two types of job demands (perceived workload and interpersonal conflict) as well as subordinates' emotional exhaustion. The results revealed that supervisors' workaholism is positively related to subordinates' emotional exhaustion through increased perceived workload and interpersonal conflict, which result in subordinates' turnover intention. This study has made a contribution to the literature by extending the scope of workaholism research from self-perspective to other-perspective. The findings also have practical implications for organizations and their human resources (HR) practitioners.

The Double-Edged Sword of a Calling: The Mediating Role of Harmonious and Obsessive Passions in the Relationship between a Calling, Workaholism, and Work Engagement.

Even though research on perceiving a calling has been growing, our understanding of its double-edged sword effects and psychological mechanisms remain unclear, especially in terms of work engagement and workaholism. Based on the heavy working investment (HWI) and dualistic model of passion (DMP) theories, we established a dual-path structural model to examine the effects of callings on work engagement and workaholism through two types of passion: harmonious (HP) and obsessive (OP) passions. Our results showed that the association between perceiving a calling and work engagement was partially mediated by HP, while the association between perceiving a calling and workaholism was fully mediated by OP. This study contributes to the literature in that it reveals how perceiving a calling has different effects on work engagement and workaholism through the HWI theoretical lens, as well as the mediating roles of HP and OP, based on the DMP theory. Our findings can be practically applied in organizations and counseling.

Anti­inflammatory effects of 6­formyl umbelliferone via the NF­κB and ERK/MAPK pathway on LPS­stimulated RAW 264.7 cells.

Inhibition of over­activated inflammation has been demonstrated as one of the most efficient strategies for treating inflammatory diseases. In the present study, 6­formyl umbelliferone (6FU) was used to evaluate its anti­inflammatory effects on lipopolysaccharide (LPS)­stimulated RAW 264.7 macrophages. 6FU inhibited chronic inflammatory processes, including increasing nitric oxide levels, and the expression of pro­inflammatory genes and producing cytokines was investigated by a nitrite assay and reverse transcription­polymerase chain reaction, respectively. Nitric oxide and pro­inflammatory cytokines, including tumor necrosis factor­α, interleukin (IL)­1ß and IL­6 were decreased by treatment with 6FU, without cell cytotoxicity in LPS­stimulated RAW 264.7 cells, which was measured by a WST­1 assay. In the western blot analysis, the expression levels of phosphorylated extracellular signal­regulated kinase (ERK)1/2 was downregulated in 6FU­treated cells. Furthermore, in the western blotting and immunofluorescence staining results, translocation activities of ERK1/2 and NF­κB from the cytoplasm to the nucleus were suppressed, which may inhibit translation of numerous proteins associated with pro­inflammation, including inducible nitric oxide synthase and cyclooxygenase­2. Therefore, based on these results, it was suggested that 6FU may be a potential candidate for the development of agents against chronic inflammation.

Teneligliptin versus sitagliptin in Korean patients with type 2 diabetes inadequately controlled with metformin and glimepiride: A randomized, double-blind, non-inferiority trial.

AIM: To assess the efficacy and safety of add-on therapy with the dipeptidyl peptidase-4 inhibitor teneligliptin compared with sitagliptin in patients with type 2 diabetes (T2DM) inadequately controlled with metformin and glimepiride. MATERIALS AND METHODS: This was a phase 3, randomized, double-blind, non-inferiority study of adult Korean subjects with T2DM (n = 201), with HbA1c ranging from 7.0% to 11.0%, on stable doses of metformin plus glimepiride. Subjects were randomized in a 1:1 fashion to receive either oral teneligliptin 20 mg or sitagliptin 100 mg for 24 weeks. The primary endpoint was change from baseline in HbA1c. RESULTS: At baseline, mean age was 60.56 ± 9.41 years, body mass index was 25.23 ± 2.85 kg/m2 and HbA1c was 8.11% ± 0.79%. At 24 weeks, both groups achieved significant reductions from baseline in HbA1c (teneligliptin, -1.03% ± 0.10% [P < 0.0001]; sitagliptin, -1.02% ± 0.10% [P < 0.0001]). The inter-group difference was -0.01% (95% confidence interval [CI]: -0.28, 0.26; P = 0.9497); the upper limit of the 95% CI was within the preset limit for non-inferiority (0.4%). There were no significant differences between groups in the proportion of patients achieving HbA1c targets, or changes from baseline in fasting plasma glucose, body weight or lipid levels at 24 weeks. Rates of adverse events (teneligliptin, n = 63 [61.76%]; sitagliptin, n = 61 [62.24%]; P = 0.9442) and hypoglycaemia (teneligliptin, n = 32 [31.37%]; sitagliptin, n = 28 [28.57%]; P = 0.6656) were similar. CONCLUSION: Teneligliptin was non-inferior to sitagliptin in the context of triple therapy for T2DM and is an important option in this setting.

Anticancer activity of Sasa borealis leaf extract-mediated gold nanoparticles.

Advancements in metal nanoparticle synthesis using plant extracts and their anticancer activity have received significant attention in recent years. The green approach for the synthesis of gold nanoparticles (AuNPs) using leaf extract of Sasa borealis is reported in this study. Synthesis of AuNPs was performed at 50 °C, and nanoparticle formation was observed after 20 min incubation. AuNPs formation was confirmed by the UV-visible spectrum peak at 542 nm. The synthesized AuNPs were oval, spherical with sizes around 10-30 nm observed using the transmission electron microscope. Energy dispersive X-ray analysis was utilized for the detection of elemental compound. The face centered cubic structure was confirmed by X-ray diffraction pattern. The reduction of tetrachloroauric acid into AuNPs by the phytochemical compounds of S. borealis extract was determined by Fourier transform infrared spectroscopy and the presence of biomolecules was studied by GC-MS. The synthesized AuNPs was tested for toxic effect on HEK293 cells and anticancer activity on AGS cells by WST-1® assay. Condensation or fragmentation is a characteristics of apoptosis, which was confirmed by 4,6-diamidino-2-pheynylindole dihydrochoride (DAPI) staining. The S. borealis-mediated AuNPs have good activity as an anticancer agent and it will be beneficial in cancer therapeutics.

Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus.

The Korean Diabetes Association (KDA) recently updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not changed from those of the 2015 KDA guidelines. The Committee on Clinical Practice Guidelines of the KDA has extensively reviewed and discussed the results of meta-analyses and systematic reviews of effectiveness and safety of OHAs and many clinical trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient's clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity. In this review, we address the results of meta-analyses and systematic reviews, comparing the effectiveness and safety among OHAs. It will help to choose the appropriate drug for an individual patient with T2DM.

Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017.

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Monotherapy in patients with type 2 diabetes mellitus.

In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.

Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association.

In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.

Chronotype Differences in Health Behaviors and Health-Related Quality of Life: A Population-Based Study Among Aged and Older Adults.

This study investigates health behaviors, health-related quality of life (HRQOL) and sleep among chronotypes in a community-based sample (n = 2,976). Analysis of covariance indicated evening types (E-types) had a significantly higher percentage of current smokers and more sleep-interfering behaviors compared to intermediate and morning types (M-type), and also lower physical activity and more sleep disturbance compared to M-types. E-types also had worse mental HRQOL compared to both chronotypes, and worse physical HRQOL compared to M-types. Exploratory analyses indicated E-types consumed more caffeinated beverages at night, smoked or ate heavy meals before bedtime, kept irregular sleep-wake schedules, and took more naps. Mediational analyses indicated that sleep-interfering behavior partially mediated the relationship between chronotype and sleep disturbance, and physical activity partially mediated the relationship between chronotype and mental HRQOL. E-types had more unhealthy behaviors, which may subsequently place them at higher risk for health problems.

The novel model peptide, αAL14, regulates angiogenesis by inhibiting VEGFR 2-mediated signaling in HUVECs.

Inhibition of angiogenesis has been focused on as a strategy for treating several diseases including cancer. In this study, a novel model peptide αAL14 was synthesized and used to identify its inhibitory effects on angiogenesis. The anti-angiogenic effects of αAL14 were investigated using vascular endothelial cells, HUVECs. αAL14 inhibited critical angiogenic processes including tubule formation, cell migration and cell invasion with no influence on cell proliferation in HUVECs. Activity of VEGFR2 was inhibited by αAL14 treatment in HUVECs. Additionally, activities of major subsequent downstream factors of VEGFR2 such as ERK, FAK and Akt were decreased. αAL14 affected expression of Rac1, Cdc42, Arp2 and WAVE2 which are involved in formation of lamellipodia. Moreover, αAL14 reduced NF-κB that can promote expression of several genes relating to cell invasion such as MMP2 and MMP9. Therefore, the results suggest that αAL14 has a potential to be developed as anti-angiogenic drug for treating diseases driven by abnormal angiogenesis.

Apoptotic Cell Death Induced by ofLBP6A, Lipopolysaccharide Binding Protein Model Peptide, Derived from Paralichthy olivaceus on MKN-28 Cells.

The aim of this study was to evaluate the anti-cancer effects of lipopolysaccharide binding protein (LBP) analogs derived from the marine resource Paralichthy olivaceus on MKN-28 gastric cancer cells. Five LBP analogs were used: ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A. ofLBP6A induced cell death of MKN-28 cells at a concentration of 40 µM. While the anti-proliferation effects ofLBP6A showed on MKN-28 cells at concentration of 40 µM, it did not affect non-cancerous HEK-293 cells at the same concentration. The mechanism study showed that ofLBP6A lead to the inhibition of cell proliferation by apoptosis along with morphological changes. The phosphorylation of Fas associated death domain (FADD) as well as the expressions of cleaved caspase-8, -7, and -3 were increased by ofLBP6A treatment. Increased the expression level of cleaved caspase-3 was confirmed by immunofluorescence staining. The expressions of Bid, Bax, and cytochrome C were also increased by the treatment. However, the expressions of cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (FLIP), Bcl-XL, and Bcl-2 were decreased by ofLBP6A treatment. The results of this study were the first to demonstrate the apoptotic anti-cancer effects of ofLBP6A, derived from P. olivavaceus on gastric cancer cells.

Desmethylanhydroicaritin isolated from Sophora flavescens, shows antitumor activities in U87MG cells via inhibiting the proliferation, migration and invasion.

This study is the first report of the antitumor activities of desmethylanhydroicaritin (DMAI) isolated from Sophora flavescens on U87MG cells. Human glioblastoma is one of the most aggressive malignant type of brain tumors and highly diffuses to around normal brain tissues. DMAI showed anti-proliferation effects on U87MG cells at the concentration of 30µM, however did not affect to HEK-293 cells. DMAI induced anti-proliferation effects via ERK/MAPK, PI3K/Akt/mTOR signal pathway and G2/M phase cell cycle arrest. DMAI led to morphological change and inhibition of filapodia formation through regulation of Rac 1 and Cdc 42. In addition, migration and invasion of U87MG cells were inhibited by DMAI via down-regulation of matrix metalloproteinase (MMP) -2 and MMP -9 expressions and activities. Our results suggest that DMAI has a potential as a therapeutic agent against glioblastoma cells.

Hexane extract from Sargassum serratifolium inhibits the cell proliferation and metastatic ability of human glioblastoma U87MG cells.

The present study is the first to demonstrate the anticancer effects of a hexane extract from the brown algae Sargassum serratifolium (HES) on human cancer cell lines, including glioblastoma U87MG, cervical cancer HeLa and gastric cancer MKN-28 cells, as well as liver cancer SK-HEP 1 cells. Among these cancer cell lines, U87MG cells were most sensitive to the cell death induced by HES. HES exhibited a cytotoxic effect on U87MG cells at concentrations of 14-16 µg/ml, yet an effect was not observed in human embryonic kidney HEK293 cells. The antiproliferative effects of HES were regulated by inhibition of the MAPK/ERK signaling pathway which plays a pivotal role in the proliferation of glioblastoma U87MG cells. In addition, treatment with HES led to cell morphological changes and cell cytoskeleton degradation through regulation of actin dynamic signaling. Furthermore, migration and invasion of the U87MG cells were inhibited by HES via suppression of matrix metalloproteinase (MMP)-2 and -9 expression. Thus, our results suggest that HES is a potential therapeutic agent which has anticancer effects on glioblastoma.

Molecular Cloning and Co-Expression of Phytoene Synthase Gene from Kocuria gwangalliensis in Escherichia coli.

A phytoene synthase gene, crtB, was isolated from Kocuria gwangalliensis. The crtB with 1,092 bp full-length has a coding sequence of 948 bp and encodes a 316-amino-acids protein. The deduced amino acid sequence showed a 70.9% identity with a putative phytoene synthase from K. rhizophila. An expression plasmid, pCcrtB, containing the crtB gene was constructed, and E. coli cells containing this plasmid produced the recombinant protein of approximately 34 kDa , corresponding to the molecular mass of phytoene synthase. Biosynthesis of lycopene was confirmed when the plasmid pCcrtB was co-transformed into E. coli containing pRScrtEI carrying the crtE and crtI genes encoding lycopene biosynthetic pathway enzymes. The results obtained from this study will provide a base of knowledge about the phytoene synthase of K. gwangalliensis and can be applied to the production of carotenoids in a non-carotenoidproducing host.

Antimetastatic effects of gambogic acid are mediated via the actin cytoskeleton and NF-κB pathways in SK-HEP1 cells.

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK-HEP1 cells was evaluated. At concentrations above 0.6 µM, GA reduced cell proliferation in SK-HEP1 cells without affecting proliferation of noncancerous HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. GA downregulated the expression of the integrin ß1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP-2, MMP-9, and NF-κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC.