Production of Vitamin K by Wild-Type and Engineered Microorganisms

Vitamin K is a fat-soluble vitamin that mainly exists as phylloquinone or menaquinone in nature. Vitamin K plays an important role in blood clotting and bone health in humans. For use as a nutraceutical, vitamin K is produced by natural extraction, chemical synthesis, and microbial fermentation. Natural extraction and chemical synthesis methods for vitamin K production have limitations, such as low yield of products and environmental concerns. Microbial fermentation is a more sustainable process for industrial production of natural vitamin K than two other methods. Recent advanced genetic technology facilitates industrial production of vitamin K by increasing the yield and productivity of microbial host strains. This review covers (i) general information about vitamin K and microbial host, (ii) current titers of vitamin K produced by wild-type microorganisms, and (iii) vitamin K production by engineered microorganisms, including the details of strain engineering strategies. Finally, current limitations and future directions for microbial production of vitamin K are also discussed

1H, 13C, and 15N resonance assignments of FK506-binding domain of plasmodium falciparum FKBP35

The immunosuppressant FK506 binds Plasmodium falciparum FK-506 binding protein 35 (PfFKBP35) and shows anti-malarial activity. To understand molecular mechanism of the drug on the parasite, we have done NMR studies. Here, we report the assignment of FK506-binding domain of PfFKBP35.Accepted versio

Solution structure of FK506 binding domain (FKBD) of Plasmodium falciparum FK506 binding protein 35 (PfFKBP35)

No abstract available

Design of a Novel and Selective IRAK4 Inhibitor Using Topological Water Network Analysis and Molecular Modeling Approaches

Protein kinases are deeply involved in immune-related diseases and various cancers. They are a potential target for structure-based drug discovery, since the general structure and characteristics of kinase domains are relatively well-known. However, the ATP binding sites in protein kinases, which serve as target sites, are highly conserved, and thus it is difficult to develop selective kinase inhibitors. To resolve this problem, we performed molecular dynamics simulations on 26 kinases in the aqueous solution, and analyzed topological water networks (TWNs) in their ATP binding sites. Repositioning of a known kinase inhibitor in the ATP binding sites of kinases that exhibited a TWN similar to interleukin-1 receptor-associated kinase 4 (IRAK4) allowed us to identify a hit molecule. Another hit molecule was obtained from a commercial chemical library using pharmacophore-based virtual screening and molecular docking approaches. Pharmacophoric features of the hit molecules were hybridized to design a novel compound that inhibited IRAK4 at low nanomolar levels in the in vitro assay

Glycemic control and complications of type 2 diabetes mellitus in children and adolescents during the COVID-19 outbreak

Purpose This study aimed to investigate the impact of coronavirus disease 2019 (COVID-19) on type 2 diabetes mellitus (T2DM) in children and adolescents. Methods Children and adolescents diagnosed with T2DM who visited the Korea University Hospital in 2019 and 2020 were retrospectively analyzed, including changes in body mass index (BMI)-standard deviation score (SDS), glycated hemoglobin (HbA1c), diabetes complications, and diabetes management from 2019 to 2020. Results Patient mean age and disease duration were 15.48±2.15 and 2.56±1.51 years, respectively. Obese patients accounted for 70.6% of the study population. From 2019 to 2020, mean BMI-SDS (2.21±1.25 vs. 2.35±1.43, P=0.044), HbA1c level (6.5%±2.72% vs. 7.3%±3.70%, P<0.001), blood pressure (BP), total cholesterol, and non–high-density lipoprotein cholesterol level in all patients increased significantly. Obesity was an independent predictor of increased HbA1c (95% confidence interval, 1.071–50.384; P=0.042). HbA1c levels did not increase significantly in nonobese patients, whereas HbA1c (6.45%±2.30% vs. 7.20%±3.05%, P<0.001), BMI-SDS (2.88±0.75 vs. 3.08±0.98, P=0.045), diastolic BP (P=0.037), and total cholesterol values (P=0.019) increased in obese patients in 2020 compared to 2019. Conclusions During the COVID-19 outbreak, glycemic control and diabetic complications worsened in children and adolescents with T2DM, particularly in obese patients. Close monitoring for glycemic control and diabetic complications is necessary in children and adolescents with T2DM, especially those with obesity

Fucoxanthin Suppresses Osteoclastogenesis via Modulation of MAP Kinase and Nrf2 Signaling

Fucoxanthin (FX), a natural carotenoid present in edible brown seaweed, is known for its therapeutic potential in various diseases, including bone disease. However, its underlying regulatory mechanisms in osteoclastogenesis remain unclear. In this study, we investigated the effect of FX on osteoclast differentiation and its regulatory signaling pathway. In vitro studies were performed using osteoclast-like RAW264.7 cells stimulated with the soluble receptor activator of nuclear factor-κB ligand or tumor necrosis factor-alpha/interleukin-6. FX treatment significantly inhibited osteoclast differentiation and bone resorption ability, and downregulated the expression of osteoclast-specific markers such as nuclear factor of activated T cells 1, dendritic cell-specific seven transmembrane protein, and matrix metallopeptidase 9. Intracellular signaling pathway analysis revealed that FX specifically decreased the activation of the extracellular signal-regulated kinase and p38 kinase, and increased the nuclear translocation of phosphonuclear factor erythroid 2-related factor 2 (Nrf2). Our results suggest that FX regulates the expression of mitogen-activated protein kinases and Nrf2. Therefore, FX is a potential therapeutic agent for osteoclast-related skeletal disorders including osteoporosis and rheumatoid arthritis

Relationship between Onodera׳s Prognostic Nutritional Index and Subpopulation Lymphocyte Counts in Hemodialysis and Peritoneal Dialysis Patients

No standard method for assessing the nutritional status in dialysis patients. In the present study, we undertook an evaluation to determine whether estimation of geriatric nutritional risk index (GNRI) and lymphocyte subset counts can be helpful in diagnosis of malnutrition in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: We examined the GNRI and lymphocyte subset counts of 50 HD patients (55.8±12.7 years; 28 men and 22 women) and 16 CAPD patients (49.8±14.5 years; 10 men and 6 women). The GNRI is calculated based on the serum albumin level and total lymphocyte count and uses the following equation: GNRI=[14.89×albumin (g/dL)]+ [41.7×(weight/ideal body weight)]. Logistic regression analysis was performed for predicting malnutrition in dialysis patients. Results: The average GNRI value was 100.1±8.4 in HD patients and 99.2±8.1, and GNRI values were normally distributed. lymphocyte subset counts were not different between HD patients and CAPD patients. Lymphocyte subset counts were lower in patients with higher GNRI (GNRI ≥100). According to logistic regression for predicting malnutrition according to GNRI, age, female and CD 19 count predicted malnutrition in hemodialysis and peritoneal dialysis patients Conclusions: These results suggest that GNRI and lymphocyte subset counts (especially CD 19 count) may be a significant nutritional marker in HD and CAPD patients