-
1.
CRISPR-Cas9 and beyond: identifying target genes for developing disease-resistant plants.
Park, HJ, Kim, M, Lee, D, Kim, HJ, Jung, HW
Plant biology (Stuttgart, Germany). 2024;(3):369-377
Abstract
Throughout the history of crop domestication, desirable traits have been selected in agricultural products. However, such selection often leads to crops and vegetables with weaker vitality and viability than their wild ancestors when exposed to adverse environmental conditions. Considering the increasing human population and climate change challenges, it is crucial to enhance crop quality and quantity. Accordingly, the identification and utilization of diverse genetic resources are imperative for developing disease-resistant plants that can withstand unexpected epidemics of plant diseases. In this review, we provide a brief overview of recent progress in genome-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technologies. In particular, we classify disease-resistant mutants of Arabidopsis thaliana and several crop plants based on the roles or functions of the mutated genes in plant immunity and suggest potential target genes for molecular breeding of genome-edited disease-resistant plants. Genome-editing technologies are resilient tools for sustainable development and promising solutions for coping with climate change and population increases.
-
2.
Integrative Multi-omics Analysis Reveals Different Metabolic Phenotypes Based on Molecular Characteristics in Thyroid Cancer.
Kim, YH, Yoon, SJ, Kim, M, Kim, HH, Song, YS, Jung, JW, Han, D, Cho, SW, Kwon, SW, Park, YJ
Clinical cancer research : an official journal of the American Association for Cancer Research. 2024;(4):883-894
Abstract
PURPOSE Thyroid cancer metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of thyroid cancers. EXPERIMENTAL DESIGN An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of thyroid cancers: BRAF-like (papillary thyroid cancer with BRAFV600E mutation; PTC-B), RAS-like (follicular thyroid cancer with RAS mutation; FTC-R), and ATC-like (anaplastic thyroid cancer with BRAFV600E or RAS mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human thyroid cancer tissues and performed in vitro analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown. RESULTS Metabolic properties differed between differentiated thyroid cancers of PTC-B and FTC-R, but were similar in dedifferentiated thyroid cancers of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all thyroid cancers and were particularly high in ATC-B/R. Knockdown of SLC7A5 or SHMT2 inhibited the migration and proliferation of thyroid cancer cell lines differently, depending on the mutational status. CONCLUSIONS These findings define the metabolic properties of each molecular subtype of thyroid cancers and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced thyroid cancer.
-
3.
Architecture of β-Lactoglobulin Coating Modulates Bioinspired Alginate Dialdehyde-Gelatine/Polydopamine Scaffolds for Subchondral Bone Regeneration.
Ghorbani, F, Kim, M, Ghalandari, B, Zhang, M, Varma, SN, Schöbel, L, Liu, C, Boccaccini, AR
Acta biomaterialia. 2024
Abstract
In this study, we developed polydopamine (PDA)-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds for subchondral bone regeneration. These polymeric scaffolds were then coated with β-Lactoglobulin (β-LG) at concentrations of 1 mg/ml and 2 mg/ml. Morphological analysis indicated a homogeneous coating of the β-LG layer on the surface of network-like scaffolds. The β-LG-coated scaffolds exhibited improved swelling capacity as a function of the β-LG concentration. Compared to ADA-GEL/PDA scaffolds, the β-LG-coated scaffolds demonstrated delayed degradation and enhanced biomineralization. Here, a lower concentration of β-LG showed long-lasting stability and superior biomimetic hydroxyapatite mineralization. According to the theoretical findings, the single-state, representing the low concentration of β-LG, exhibited homogeneous distribution on the surface of the PDA, while the dimer-state (high concentration) displayed a high likelihood of uncontrolled interactions. β-LG-coated ADA-GEL/PDA scaffolds with a lower concentration of β-LG provided a biocompatible substrate that supported adhesion, proliferation, and alkaline phosphatase (ALP) secretion of sheep bone marrow mesenchymal stem cells, as well as increased expression of osteopontin (SPP1) and collagen type 1 (COL1A1) in human osteoblasts. These findings indicate the potential of protein-coated scaffolds for subchondral bone tissue regeneration. STATEMENT OF SIGNIFICANCE This study addresses a crucial aspect of osteochondral defect repair, emphasizing the pivotal role of subchondral bone regeneration. The development of polydopamine-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds, coated with β-Lactoglobulin (β-LG), represents a novel approach to potentially enhance subchondral bone repair. β-LG, a milk protein rich in essential amino acids and bioactive peptides, is investigated for its potential to promote subchondral bone regeneration. This research explores computationally and experimentally the influence of protein concentration on the ordered or irregular deposition, unravelling the interplay between coating structure, scaffold properties, and in-vitro performance. This work contributes to advancing ordered protein coating strategies for subchondral bone regeneration, providing a biocompatible solution with potential implications for supporting subsequent cartilage repair.
-
4.
A phase II randomised controlled trial of intranasal oxytocin in anorexia nervosa.
Maguire, S, Kesby, A, Brownlow, R, Hunt, GE, Kim, M, McAulay, C, Grisham, JR, McGregor, IS, Suraev, A, Kevin, RC, et al
Psychoneuroendocrinology. 2024;:107032
Abstract
BACKGROUND Anorexia nervosa (AN) is an eating disorder (ED) with high mortality rates and limited response to existing treatments, prompting the need to identify effective agents and adjuncts. There is evidence for an emerging role for the neuropeptide oxytocin (OT) in the pathophysiology of AN, with studies showing a perturbed oxytocinergic system in patients with AN. Preliminary evidence has demonstrated that intranasal OT (IN-OT) can produce anxiolytic effects in AN, as well as reducing concern about eating, and dysfunctional attentional biases related to the disorder. IN-OT is a non-invasive treatment option for AN that requires investigation as an adjunct to nutritional rehabilitation. METHODS This multi-site study (Trial Registration:ACTRN1261000897460) sought to replicate and extend a previous randomised placebo-controlled pilot trial of repeated dose IN-OT in patients with AN hospitalised for nutritional rehabilitation. Patients with AN (N=61) received daily IN-OT (18 IU twice per day) or placebo for four weeks, whilst undergoing inpatient hospital treatment. Outcome measures included ED psychopathology (primary) as measured by the Eating Disorder Examination (EDE) and Body Mass Index (BMI; secondary). Participants were assessed pre- and post-treatment, and at six months following the intervention. The effects of the first and last doses of IN-OT on responses (anxiety ratings and salivary cortisol) to a high-energy snack were also examined. RESULTS Sixty-one female inpatients (Mage=24.36,SD=7.87) with an average BMI of 16.24 (range: 11.43-18.55), were recruited into the study. No significant differences were found between placebo and OT groups at any of the time points on the outcomes of interest, but significant improvements in almost all psychological parameters in both groups were evident over time. IN-OT did not significantly reduce anxiety nor salivary cortisol in response to a high-calorie snack. CONCLUSION This is the largest randomised placebo-controlled trial of repeated dose intranasal OT in people with AN, during refeeding. The therapeutically promising findings of the pilot study were not replicated. Limitations and reasons for the non-replication included relatively large variance, baseline psychopathology scores being higher in this patient group, potential ceiling effects in BMI and ED psychopathology as well as differing comorbidities.
-
5.
Bioproduction of porphyrins, phycobilins, and their proteins using microbial cell factories: engineering, metabolic regulations, challenges, and perspectives.
Ko, YJ, Lee, ME, Cho, BH, Kim, M, Hyeon, JE, Han, JH, Han, SO
Critical reviews in biotechnology. 2024;(3):373-387
Abstract
Porphyrins, phycobilins, and their proteins have abundant π-electrons and strongly absorb visible light, some of which bind a metal ion in the center. Because of the structural and optical properties, they not only play critical roles as an essential component in natural systems but also have attracted much attention as a high value specialty chemical in various fields, including renewable energy, cosmetics, medicines, and foods. However, their commercial application seems to be still limited because the market price of porphyrins and phycobilins is generally expensive to apply them easily. Furthermore, their petroleum-based chemical synthesis is energy-intensive and emits a pollutant. Recently, to replace petroleum-based production, many studies on the bioproduction of metalloporphyrins, including Zn-porphyrin, Co-porphyrin, and heme, porphyrin derivatives including chlorophyll, biliverdin, and phycobilins, and their proteins including hemoproteins, phycobiliproteins, and phytochromes from renewable carbon sources using microbial cell factories have been reported. This review outlines recent advances in the bioproduction of porphyrins, phycobilins, and their proteins using microbial cell factories developed by various microbial biotechnology techniques, provides well-organized information on metabolic regulations of the porphyrin metabolism, and then critically discusses challenges and future perspectives. Through these, it is expected to be able to achieve possible solutions and insights and to develop an outstanding platform to be applied to the industry in future research.
-
6.
Effects of food and race on the pharmacokinetics of lazertinib in healthy subjects and patients with EGFR mutation-positive advanced non-small cell lung cancer.
Huh, KY, Lim, Y, Yoon, DY, Hwang, JG, Sim, S, Kang, J, Wang, J, Kim, M, Jang, SB, Shreeve, SM, et al
Lung cancer (Amsterdam, Netherlands). 2023;:112-120
Abstract
OBJECTIVES Lazertinib is a potent, irreversible, brain-penetrant, mutant-selective, and wild type-sparing third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for advanced non-small cell lung cancer (NSCLC). The study aimed to evaluate the effects of food and race on the pharmacokinetics (PK) of lazertinib from a healthy volunteer trial and PK data from NSCLC patients with EGFR mutation. MATERIALS AND METHODS An open-label, single-dose, two-period, single-sequence crossover study was conducted in healthy subjects with two race groups (non-Asian and Asian). Subjects orally received a single dose of lazertinib 240 mg in fasted and fed state (high-fat meal) in each period separated by a 21-day washout. An open-label, multicenter, phase 1/2 study was conducted in Asian and non-Asian patients with NSCLC. Patients were given oral lazertinib 20-320 mg once daily in fasted state continuously in 21-day cycles. PK parameters were evaluated using non-compartmental analysis. RESULTS A total of 24 healthy subjects (12 non-Asians and 12 Asians) and 52 NSCLC patients (22 non-Asians and 30 Asians) were evaluated. The change in the overall systemic exposure of lazertinib at fed state was less than 15%. Non-Asians showed 58-76% of the systemic exposure than Asians in healthy subjects. In contrast, there were no significant differences in systemic exposure by race both after single and multiple doses among NSCLC patients. CONCLUSION Lazertinib can be taken with or without food considering the comparable systemic exposures related to food. Although effect of race was not consistent across studies, there was no evidence for dose adjustment based on race.
-
7.
Longitudinal association between eating alone and deterioration in frailty status: The Korean Frailty and Aging Cohort Study.
Park, J, Shin, HE, Kim, M, Won, CW, Song, YM
Experimental gerontology. 2023;:112078
-
-
Free full text
-
Abstract
BACKGROUND Among risk factors of developing frailty, dietary factor played an important role as a potentially modifiable risk factor. Eating alone is associated with malnutrition, depression, and social isolation, which are risk factors of frailty. We evaluated the longitudinal association between a change to eating alone and deterioration in frailty status in a cohort of community-dwelling elderly persons. METHODS The study subjects were 2072 non-frail Korean elderly persons aged 70-84 years who were recruited for the Korean Frailty and Aging Cohort Study (KFACS). The subjects were divided into 4 groups based on changes in eating with others or alone between the baseline survey (2016-2017) and the follow-up survey (2018-2019): group I (ate with others consistently), group II (ate with others at baseline but ate alone at follow-up), group III (ate alone at baseline but ate with others at follow-up), group IV (ate alone consistently). We assessed physical frailty using the Cardiovascular Health Study (CHS) frailty phenotype. The association between changes in eating with others or alone and frailty progression was assessed by multiple logistic regression analysis after adjusting for covariates. RESULTS The mean age of the study subjects was 76.2 (SD: 3.8) years old and 50.8 % were female. At follow-up, 364 new cases (34.5 %) of pre-frailty (n = 348) and frailty (n = 16) were identified among those who were robust at baseline (n = 1056), while 88 new cases (8.7 %) of frailty were identified among those who were pre-frail at baseline (n = 1016). Compared to group I, group II showed an increased risk of deterioration in frailty status after adjustments with multivariables including social isolation and malnutrition (adjusted odds ratio [aOR] = 1.61, 95 % confidence interval [CI]: 1.03-2.50). However, the association disappeared after further adjustment for depression. When we examined the longitudinal association between changes in eating with others or alone and changes in each frailty domain, group II showed an increased risk for the weight loss (aOR = 3.07, 95 % CI: 1.39-6.76) compared to group I. Group IV showed an increased risk for the weight loss (aOR = 2.39, 95 % CI: 0.95-6.00) and weakness (aOR = 2.07, 95 % CI: 1.16-3.68). CONCLUSIONS A change from eating with others to eating alone was found to significantly increase the risk of deterioration in frailty status in elderly people, and the association seemed to be mediated by depression. These findings suggest that interventions to maintain eating partners and manage depression are needed to prevent frailty progression in elderly people.
-
8.
Understanding viscoelastic behavior of hybrid nanocellulose film based on rheological and electrostatic observation in blended suspension.
Kim, M, Kim, S, Han, N, Lee, S, Kim, H
Carbohydrate polymers. 2023;:120218
Abstract
The effects of TEMPO-mediated oxidized cellulose nanofibril (TOCN) on the viscoelastic behavior and phase of cellulose nanocrystal (CNC) in suspension and film were investigated using polarized optical microscopy, rotational rheometry, and dynamic mechanical analysis. The sodium cation from TOCN changed the electrostatic state of CNC by screening the CNC surface charge. The volume inflation of TOCN locally increased the CNC concentration in the suspension. In turn, the CNC-CNC interactions increased the viscosity and the yield stress. Based on the experimental observation, the changing mechanisms of electrostatic state and particular interaction in the TOCN/CNC suspensions were suggested. In the hybrid film, the time dependency of complex moduli was changed owing to the different networking between CNCs and TOCNs. The CNC-CNC contacts easily collapsed by strain, while the TOCN-TOCN entanglements were slowly altered. This study provides a fundamental understanding of CNC behavior for optimizing processes and composite properties.
-
9.
Efficacy of Acetylcysteine and Selenium in Aneurysmal Subarachnoid Hemorrhage Patients: A Prospective, Multicenter, Single Blind Randomized Controlled Trial.
Kim, M, Jeon, H, Chung, Y, Lee, SU, Park, W, Park, JC, Ahn, JS, Lee, S
Journal of Korean medical science. 2023;(21):e161
Abstract
BACKGROUND Subarachnoid hemorrhage (SAH) patients have oxidative stress results in inflammation, tissue degeneration and neuronal damage. These deleterious effects cause aggravation of the perihematomal edema (PHE), vasospasm, and even hydrocephalus. We hypothesized that antioxidants may have a neuroprotective role in acute aneurysmal SAH (aSAH) patients. METHODS We conducted a prospective, multicenter randomized (single blind) trial between January 2017 and October 2019, investigating whether antioxidants (acetylcysteine and selenium) have the potential to improve the neurologic outcome in aSAH patients. The antioxidant patient group received antioxidants of acetylcysteine (2,000 mg/day) and selenium (1,600 µg/day) intravenously (IV) for 14 days. These drugs were administrated within 24 hours of admission. The non-antioxidant patient group received a placebo IV. RESULTS In total, 293 patients were enrolled with 103 patients remaining after applying the inclusion and exclusion criteria. No significant differences were observed in the baseline characteristics between the antioxidant (n = 53) and non-antioxidant (n = 50) groups. Among clinical factors, the duration of intensive care unit (ICU) stay was significantly shortened in patients who received antioxidants (11.2, 95% confidence interval [CI], 9.7-14.5 vs. 8.3, 95% CI, 6.2-10.2 days, P = 0.008). However, no beneficial effects were observed on radiological outcomes. CONCLUSION In conclusion, antioxidant treatment failed to show the reduction of PHE volume, mid-line shifting, vasospasm and hydrocephalus in acute SAH patients. A significant reduction in ICU stay was observed but need more optimal dosing schedule and precise outcome targets are required to clarify the clinical impacts of antioxidants in these patients. TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0004628.
-
10.
Phosphoric Acid Etch Partially Restores the Initial Bond Strength of Composite to Silver Diamine Fluoride-Treated Enamel Using Universal Adhesives.
Jabbour, Z, Kim, M, Hayashi, M, Kim, R
Dentistry journal. 2023;(7)
Abstract
BACKGROUND Restoring bonding composite to silver diamine fluoride (SDF)-treated enamel is challenging. This study investigates if phosphoric acid etch restores composite bond strength to SDF-treated enamel using universal adhesives. METHODS Twenty-four recently extracted permanent teeth were randomly divided into 4 (2 experimental (SDF) and 2 control (CTR)) groups: SDF+Water: SDF (1 min) then water rinse (15 mL); CTR+Water: no treatment and water rinse (15 mL); SDF+Etch+Water: SDF (1 min), 35% phosphoric acid (40 s) then water rinse (15 mL); CTR+Etch+Water no treatment, 35% phosphoric acid (40 s) then water rinse (15 mL). The enamel surface in all the groups was bonded (All-Bond Universal) to 4-5 mm composite blocks (Z-250). Each sample was sectioned, and 6-8 beams (1 mm × 1 mm) were selected. The micro-tensile bond strength was measured by dividing the micro-tensile force peak by the adhesive surface area. Univariate ANOVA and Chi-square were used for between-group comparisons with p < 0.05. RESULTS SDF+Water had significantly lower tensile strength compared to all the groups (p < 0.05). Although no difference was found in the tensile strength between the SDF+Etch+Water and the CTR+Etch+Water, the SDF+Etch+Water had significantly more adhesive failures compared to the CTR+Etch+Water (p = 0.047). CONCLUSIONS While phosphoric acid etch seems to restore the initial composite bond strength to SDF-treated enamel, the long-term success of composite restorations bonded to SDF-treated enamel may need further investigation.