Search

Background and objective This study was conducted to determine the effect of NaCl on the growth, antioxidants (superoxide dismutase, proline), maximum quantum yield, and chlorophyll contents of Pseudolysimachion pusanensis. Methods Five levels of NaCl concentrations (0, 50, 100, 200, 400 mM) were used for treatment. Results The growth according to NaCl concentrations was highest at 50 and 100 mM, but root growth declined before the top from 200 mM or higher. The increase in NaCl concentrations also led to the increase in SOD and proline content compared to the control plot, whereas it decreased chlorophyll content. There was no difference in the maximum quantum yield at 0, 50, 100, and 200 mM, but it decreased at 400 mM. Conclusion The results proved that P. pusanensis showed an increase in SOD and proline content at 50 and 100 mM of NaCl treatment compared to the control plot, indicating that it receives salt stress, but the growth was excellent at 50 and 100 mM. In addition, there was no difference in top growth up to 200 mM compared to the control plot, and there was no significant difference in the maximum quantum yield, which proved that P. pusanensis has strong tolerance to salt stress.

Background and objective This study was conducted to establish a stable seedling production system for Veronica pusanensis Y.N. Lee, a plant that is endemic to the Korean Peninsula and is a critically endangered species, distributed along the coast of Busan, Korea. Methods In order to investigate the plug cell size (72, 128, 200 cells), soil type (commercial substrate, and mixed substrates with peat moss and perlite at ratios of 1:1, 3:1, and 4:1), and fertilizer concentration (Peters 0, 500, 1,000, and 2,000 mg·L−1) conditions, the plug tray was filled with soil and seeds were sown. The sown trays were placed in the growth chamber (25°C, 70% RH, PPFD 100 μmol·m−2·s−1) for three repetitions per treatment. Results There was no difference in the growth of seedlings according to plug cell size. Therefore, it appears to be economically superior to produce seedlings in a 200-cell plug tray. In soil type, the seedling growth increased as the ratio of peat increased, but leaf chlorosis occurred from the 7th week after sowing. Examining the growth of seedlings based on fertilizer concentration, the greatest increase in growth was found to have occurred in the 1,000 mg·L−1 treatment. Conclusion Therefore, for the production of V. pusanesis seedlings, it was noted that when mixed soil with peatmoss and perlite at a ratio of 4:1 is filled in 200-cell plug trays, and the seedlings are fertilized with Peters 1,000 mg·L−1 once a week, growth will increase the most, demonstrating excellent cost-effectiveness. However, to mass-produce high-quality seedlings in a short period, it will be necessary to use a plug tray smaller than 200 cells or to conduct various fertilization composition studies.

Background and objective Particulate matter (PM) is the most dangerous form of air pollution, and causes many diseases. Plants act as bio-filters to help reduce PM in the atmosphere. PM also influences the growth of plants, so selecting suitable plant species for specific environmental conditions is very important. The air pollution tolerance index (APTI) was used to determine the tolerance level of each plant species to air pollution. The purpose of this study was to determine the tolerance to air pollution of various plant species in order to identify plant species that can be grown in polluted environments; this was achieved by evaluating the APTI of plants. This study analyzed the biochemical parameters of 12 plant species at two sites with different air pollution levels (urban forest and roadside) to assess and compare the APTI of plant species. Methods The healthy leaves of 12 plant species (6 broad leaves and 6 needle leaves) that are commonly used in landscapes in Korea were chosen for this study. The same plant species were collected from two sites with different pollution levels and were analyzed immediately; one site was an urban forest (Chungcheongbuk-do Forest Environment Research Institute) with an area of 25 ha and featuring high vegetation coverage, while the other was at a high-traffic roadside next to a crossroads near the Cheongju Express Bus Terminal. We used the leaf samples to analyze four biochemical parameters of each plant: leaf extract pH (pH), relative leaf water content (RWC), total chlorophyll (TChl), and ascorbic acid. Finally, based on these values, APTI values were calculated. Results The APTI values were different between all 12 plant species at both sites with different levels of pollution. APTI had a significant correlation with the biochemical parameters of plants. Plants in the urban forest and at the roadside showed APTI values ranging from 6.89–9.37 and 7.57–9.94, respectively. The APTI of the roadside plant species tended to be higher than that of the plants from the urban forest. Among 12 plant species, Acer palmatum, Acer buergerianum, and Pinus densiflora had high APTI values. These plant species can serve as biofilters in environments with high air pollution. Conclusion The APTI of the 12 plant species in this study can aid in the selection of suitable plant species from environments with different levels of air pollution. The high APTI of some roadside plant species may show their tolerance under environmental pollution-related stress, or demonstrate their adaptability to the polluted environment. In the future, we need to examine more plant species under various environmental conditions to understand their tolerance levels to air pollution and to correlate plants with air pollution. Further, more studies on other air pollutants that can influence plant growth, such as SO2 and NOx, should be conducted.

This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients.This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores.A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval -0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (-0.78; Pnoninferiority0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred.The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

Background: To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.Methods: This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.Results: After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).Conclusion: Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

p53-binding protein 1 (53BP1) regulates the DNA double-strand break (DSB) repair pathway and maintains genomic integrity. Here we found that 53BP1 functions as a molecular scaffold for the nucleoside diphosphate kinase-mediated phosphorylation of ATP-citrate lyase (ACLY) which enhances the ACLY activity. This functional association is critical for promoting global histone acetylation and subsequent transcriptome-wide alterations in gene expression. Specifically, expression of a replication-dependent histone biogenesis factor, stem-loop binding protein (SLBP), is dependent upon 53BP1-ACLY-controlled acetylation at the SLBP promoter. This chain of regulation events carried out by 53BP1, ACLY, and SLBP is crucial for both quantitative and qualitative histone biogenesis as well as for the preservation of genomic integrity. Collectively, our findings reveal a previously unknown role for 53BP1 in coordinating replication-dependent histone biogenesis and highlight a DNA repair-independent function in the maintenance of genomic stability through a regulatory network that includes ACLY and SLBP.

Background Cancer cells have developed molecular strategies to cope with evolutionary stressors in the dynamic tumor microenvironment. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) is a metabolic rheostat that regulates diverse cellular adaptive behaviors, including growth and survival. However, the mechanistic role of PGC1α in regulating cancer cell viability under metabolic and genotoxic stress remains elusive. Methods We investigated the PGC1α-mediated survival mechanisms in metabolic stress (i.e., glucose deprivation-induced metabolic stress condition)-resistant cancer cells. We established glucose deprivation-induced metabolic stress-resistant cells (selected cells) from parental tumor cells and silenced or overexpressed PGC1α in selected and parental tumor cells. Results Several in vitro and in vivo mouse experiments were conducted to elucidate the contribution of PGC1α to cell viability in metabolic stress conditions. Interestingly, in the mouse xenograft model of patient-derived drug-resistant cancer cells, each group treated with an anti-cancer drug alone showed no drastic effects, whereas a group that was co-administered an anti-cancer drug and a specific PMCA inhibitor (caloxin or candidate 13) showed marked tumor shrinkage. Conclusions Our results suggest that PGC1α is a key regulator of anti-apoptosis in metabolic and genotoxic stress-resistant cells, inducing PMCA expression and allowing survival in glucose-deprived conditions. We have discovered a novel therapeutic target candidate that could be employed for the treatment of patients with refractory cancers.

Hypoglycemia is common but can lead to life-threatening consequences. Accurate diagnosis is important to establish the appropriate treatment strategy. Most cases of hypoglycemia are caused by hypoglycemic agents, although it can occur in individuals without diabetes. A systemic and comprehensive diagnostic approach is required to diagnose hypoglycemia in patients without diabetes. It is important to perform appropriate blood testing during an episode of hypoglycemia. This review will focus on the definition, differential diagnosis, causes, and treatment of hypoglycemia, particularly in people without diabetes.

Background and objective This study was carried out to develop an effective technique for raising seedlings of Veronica pyrethrina Nakai, a native plant species in the Korean Peninsula, in plug trays. Methods To investigate the optimum plug cell size and sowing media, we sowed seed in to plug trays with 34, 21, and 10 mL cells and filled with a commercial horticultural substrate and mixtures of peatmoss and perlite in 1:1, 3:1, and 4:1 ratios. Fertilization levels were set at 0, 500, 1000 and 2000 mg • L−1. Results Plug cell size did not significantly influence the seedling growth of V. pyrethrina. By substrate type, the growth rate was highest in the horticultural substrate, followed by 4:1, 3:1, and 1:1. Growth by fertilization level was higher in all fertilized treatment groups than in the control group, and there was no difference among 500, 1000, and 2000 mg • L−1. Conclusion The results of this study proved that it is most suitable for raising seedlings of V. pyrethrina to sow the seeds in a 10 mL cell plug tray filled with horticultural substrates, and apply fertilizers with less than 500 mg • L−1 concentration.

Background and objective Particulate matter (PM) has a serious impact on health. Recently, studies are conducted to reduce PM in an environmentally friendly way using plants. This study investigated the physiological responses of plants and their ability to remove PM by continuously spraying different PM sources (loam, fly ash, carbon black) to four native plant species, such as Iris sanguinea, Pteris multifida, Vitis coignetiae, and Viburnum odoratissimum var. awabuki. Methods The four plant species were randomly placed in four chambers, and 0.1 g of different PM was injected into each chamber twice a week. We measured chlorophyll, carotenoid, chlorophyll fluorescence (Fv/Fm), total leaf area, amount of leaf wax, PM10 (sPM10) and PM2.5 (sPM2.5) on the leaf surface, and PM10 (wPM10) and PM2.5 (wPM2.5) on the wax layer. Results For I. sanguinea and V. coignetiae, the sources of PM did not affect the growth response. P. multifida showed high chlorophyll a, b, total chlorophyll, and carotenoid content in carbon black as well as high Fv/Fm and total leaf area, thereby proving that carbon black helped plant growth. By PM sources, sPM10 showed a significant difference in three plant species, sPM2.5 in two plant species, and wPM10 in one plant species, indicating that sPM10 was most affected by PM sources. Conclusion Carbon black increased the leaf area by affecting the growth of P. multifida. This plant can be effectively used for PM reduction by increasing the adsorption area. I. sanguinea and V. coignetiae can be used as economical landscaping plants since they can grow regardless of PM sources.

IntroductionIntestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses ofHeligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known.ResultsUsing a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels ofAdamtsgene expression.DiscussionTo our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost.

The effects of switching DPP-4 inhibitors in type 2 diabetes mellitus (T2DM) patients are being widely studied. However, information of which factors affect the therapeutic response is limited. We evaluated the difference in HbA1c lowering effect by comorbidity and other variables after switching to anagliptin in patients with T2DM inadequately controlled by other DPP-4 inhibitors.In a multicenter, open-label, single-arm, prospective observational study, patients with T2DM, HbA1c ≥ 7.0% who have taken DPP-4 inhibitors other than anagliptin, either alone or in combination (DPP-4 inhibitors + metformin/sulfonylurea (SU)/thiazolidinedione (TZD)/insulin), for at least 8 weeks were enrolled. After the switch to anagliptin, HbA1c and available clinical characteristics were determined.The change in HbA1c levels from baseline to week 12 and 24 was - 0.40% and - 0.42% in all patients. However, comparing the subgroups without and with comorbidities, the change in HbA1c levels at weeks 12 and 24 was - 0.68% and - 0.89% vs. - 0.27% and 0.22%, respectively. In addition, the proportion of patients achieving HbA1c 7% from baseline to week 12 and 24 was increased to 70% and 70% vs. 20% and 24%, respectively. Duration of T2DM and different subtype classes of DPP-4 inhibitor did not significantly contribute to the change in HbA1c.In patients with T2DM poorly controlled by other DPP-4 inhibitors, HbA1c levels were significantly decreased after switching to anagliptin. Given that the change in HbA1c was greater in patients without comorbidities than in patients with comorbidities, switching to anagliptin before adding other oral hypoglycemic agents (OHAs) may be an option in patients without comorbidities.

Choline is an essential nutrient and in macrophages, mainly supports phosphatidylcholine (PC) synthesis. Cellular uptake and incorporation of choline into PC is critical for LPS-induced macrophage inflammation. Here, we examined choline metabolism in the context of IL-4 polarization of mouse macrophages in vitro and in vivo. Like LPS, IL-4 increased the levels of choline transporter-like protein 1, the rate of choline uptake, and incorporation into PC. Targeted lipidomics analysis revealed higher PC content in IL-4-polarized macrophages, with enrichment in low-saturated species. Pharmacological inhibition of choline metabolism significantly suppressed the transcription of certain hallmark IL-4 genes (Retnla) but not others (Chil3, Mrc1, Arg1). Blocking choline metabolism diminished the expression and secretion of RELMα protein (encoded by Retnla), while also limiting PD-L2 up-regulation and increasing PD-L1 expression. In vivo administration of RSM-932a, a choline kinase inhibitor, caused a dramatic shift in the peritoneal immune cell profile and up-regulated macrophage CD86 and PD-L1, while down-regulating CD206 and PD-L2. Strikingly, blocking choline metabolism lowered RELMα expression in multiple cell-types and tissues in naïve mice as well as mice infected with the helminth pathogens Heligmosomoides polygyrus and Nippostrongylus brasiliensis. There were no changes in pathogen burden or clearance in the two separate helminth models. In contrast, in dextran sulfate sodium-induced colitis, loss of colon length as a marker of inflammation was mitigated by choline metabolism inhibition. These data demonstrate a critical link between choline and macrophage effector functions and suggest that targeting choline metabolism could be leveraged to fine-tune immunopathology.Abstract Figure

Allium L. is a perennial plant in the Amaryllidaceae family and includes 1,000 species. There are 24 indigenous Allium species in Korea, and they have a high value as genetic resources. However, there is a lack of research on indigenous Allium species and little research on recently classified or unknown Allium species, such as A. pseudojaponicum, A. dumebuchum, and A. ulleungense. Therefore, this study determined the effects of environmental control (temperature and light) on germination responses of four indigenous Allium seeds (A. longistylum, A. taquetii, A. pseudojaponicum, and A. thunbergii). Germination responses were evaluated by germination percentage (GP), days to 50% of germination of final germination rates (T50), mean germination time (MGT), germination uniformity (GU), and germination speed (GS). GP of A. longistylum and A. pseudojaponicum was more than 50% at 5°C, but A. taquetii and A. thunbergii did not germinate at 5°C. A. pseudojaponicum inhabits beaches in the southern region, and but A. longistylum inhabits near rivers and streams. However, A. taquetii and A. thunbergii mainly inhabit mountainous areas. Therefore, this difference is estimated to be in accordance with the environmental conditions of their habitat. At 5°C, the GP of A. longistylum was improved in dark conditions (90.0%) than in light conditions (68.3%); T50 and MGT were also shortened. The GP of A. taquetti increased at 15°C in the dark than light conditions, and T50 and MGT were shortened at 15°C and 20°C. Also, the GP and GU increased. At 5°C, the GP of A. pseudojaponicum was higher in the dark (83.3%) than in light conditions (70.0%); T50 and MGT were shortened at 15°C, and GS increased in the dark. At 15°C and 20°C of A. thunbergii, T50 and MGT were shortened, and GP increased in the dark. Therefore, in the relatively low-temperature group, dark conditions improved some germination responses than the light condition. Most of the four Allium seeds used in the experiment showed more than 90% GP at 15°C - 25°C, but other germination responses showed differences according to temperature and light. The T50, MGT, and GS of A. longistylum and A. thunbergii were the most improved at 20°C and 25°C, while A. taquetii and A. pseudojaponicum had the shortest T50 and MGT at 25°C, and the GS was the fastest. As a result, regardless of light, the proper temperature was 20°C – 25°C for A. longistylum, 25°C for A. taquetii, 25°C for A. pseudojaponicum, and 25°C in darkness and 20°C – 25°C in light for A. thunbergii.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

Veronica dahurica Steven (family Scrophulariaceae) is an ornamental plant from Korea. The aim of the present study was to produce multiple-branched plants by using 6-benzylaminopurine (BA) spray application at several time intervals after pinching. All 10 cm long plants were sprayed with 0, 500, 1000, and 2000 mg·L-1 BA at 0, 7, and 14 days after pinching. Growth characteristics were examined 10 weeks after pinching and flowering time was recorded. The number of branches was highest in the group sprayed with 1000 mg·L-1 BA at 0 d after pinching. The greatest plant height was observed in the group treated with 1000 mg·L-1 BA 14 d after pinching and the minimum plant height was observed in the group sprayed with 500 mg·L-1 BA at 0 d after pinching. The groups sprayed with higher BA concentrations and with longer intervals between pinching and spraying showed greater delay in the time to first flower. The flower length was decreased in the pinched and BA-treated group compared with the control. Thus, BA application and pinching could promote multiple branch induction and control flowering time in V. dahurica Steven.

We isolated S-formylglutathione hydrolase (scSFH) from Sphingobium chungbukense strain KCTC2955 and expressed it in Escherichia coli. The extracted scSFH showed activity toward p-nitrophenyl butyrate (p-NB), and a protein–substrate interaction was confirmed through 3D molecular docking simulation. The DNA sequence of the cloned scSFH gene (900 bp) has an open reading frame encoding 300 amino acids with a predicted molecular mass of 32.82 kDa; the sequence contains Ser-His-Asp conserved in the active site and a GHSMGG motif. The cloned scSFH gene successfully overproduced scSFH protein under the T7 promoter of the expression vectors pET21a and pGEX4T-1 in E. coli BL21(DE3). We analyzed E. coli-expressed scSFH protein for esterase activity using p-NB as a substrate. Furthermore, we confirmed the interaction between the scSFH protein and p-NB substrate. The scSFH protein of the SFH family was overexpressed in E. coli BL21(DE3) and purified using affinity Ni–NTA agarose resin. The activity of purified scSFH against p-NB was 6.87 mg L−1 for Km and 131.16 mg L−1 protein min−1 for Vmax. Additionally, we confirmed that the serine residue of the GHSMGG motif in the obtained protein interacts with p-NB through molecular docking prediction by the molecular operating environment. We identified a novel scSFH gene from S. chungbukense and overexpressed it in E. coli. The recombined scSFH protein showed activity toward p-NB, and the interaction was confirmed through 3D molecular docking prediction. This research could be applied to identify new genes and confirm their functions.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.