• Molecules and Cells
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• v.46 no.10
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• pp.592-610
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• 2023

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

• BMB Reports
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• v.57 no.6
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• pp.281-286
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• 2024

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

• International Journal of Molecular Medicine
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• v.43 no.6
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• pp.2409-2419
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• 2019

The use of finasteride for alleviating hair loss has been investigated, and it has been applied as an oral dose medication. However, due to the inconvenience of daily drug administration over long period of time, novel controllable finasteride delivery has been actively investigated. As a novel method of finasteride delivery, the development of finasteride-loaded microspheres for subcutaneous administration is becoming increasingly pharmaceutically important. Therefore, the present study aimed to use finasteride-loaded microspheres in a controlled manner in an attempt to overcome the limitations of the oral administration of finasteride and to cause fewer adverse effects. Finasteride-loaded microspheres containing poly(lactic-co-glycolic acid) and finasteride at a ratio of 4:1 were prepared, and a testosterone-induced androgenic alopecia mouse model was used. Following observation for 10 weeks, the percentage hair growth was 86.7% (total hair growth 60%, partial hair growth 26.7%) in the orally-applied finasteride-treated group as a positive control, and 93.3% (total hair growth 60%, partial hair growth 33.3%) in the finasteride-loaded microspheres-treated group. Serum dihydrotestosterone levels began to decrease at week 6 in the orally-applied finasteride- and finasteride-loaded microsphere-treated groups. In addition, the finasteride-loaded microspheres-treated group exhibited similar follicular number, follicular length, anagen/telogen ratio and hair bulb diameter values to those of the orally-applied finasteride-treated group. Furthermore, the finasteride-loaded microspheres increased the activities of phosphoinositide 3-kinase/protein kinase B and Wnt/β-catenin in relation to hair follicle cell growth signaling in mouse skin, and suppressed the apoptosis of hair follicle cells by reducing the expression of transforming growth factor-β2 and caspase-3, which are indicators of apoptosis. In conclusion, the administration of a single injection of finasteride-loaded microspheres was effective in treating testosterone-induced alopecia. Furthermore, it led to equivalent hair growth effects when compared with orally-applied finasteride, thus revealing the possibility of effective treatment via different routes of administration.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.413-422
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• 2012

The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine HCl. Lidocaine HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.834-840
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• 2022

Objective : C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count are inflammatory markers used to evaluate postoperative infections. Although these markers are non-specific, understanding their normal kinetics after surgery may be helpful in the early detection of postoperative infections. To compliment the recent trend of reducing the duration of antibiotic use, this retrospective study investigated the inflammatory markers of patients who had received antibiotics within 24 hours after surgery according to the Health Insurance Review & Assessment Service guidelines and compared them with those of patients who had received antibiotics for 5 days, which was proven to be non-infectious. Methods : We enrolled 74 patients, divided into two groups. Patients underwent posterior lumbar interbody fusion (PLIF) at a single institution between 2019 and 2020. Group A included 37 patients who received antibiotics within 24 hours after the PLIF procedure, and group B comprised 37 patients who had used antibiotics for 5 days. A 1 : 1 nearest-neighbor propensity-matched analysis was used. The clinical variables included age, sex, medical history, body mass index, estimated blood loss, and operation time. Laboratory data included CRP, ESR, and WBC, which were measured preoperatively and on postoperative days (POD) 1, 3, 5, and 7. Results : CRP dynamics tended to decrease after peaking on POD 3, with a similar trend in both groups. The average CRP level in group B was slightly higher than that in group A; however, the difference was not statistically significant. Multiple linear regression analysis revealed operation time, number of fused levels, and estimated blood loss as significant predictors of a greater CRP peak value (r²=0.473, p<0.001) in patients. No trend (a tendency to decrease from the peak value) could be determined for ESR and WBC count on POD 7. Conclusion : Although slight differences were observed in numerical values and kinetics, sequential changes in inflammatory markers according to the duration of antibiotic administration showed similar patterns. Knowledge of CRP kinetics allows the assessment of the degree of difference between the clinical and expected values.

• BMB Reports
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• v.40 no.5
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• pp.723-730
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• 2007

Kinesin is an ATP-driven microtubule motor protein that plays important roles in control of microtubule dynamics, intracellular transport, cell division and signal transduction. The kinesin superfamily is composed of numerous members that are classified into 14 subfamilies. Animal kinesins have been well characterized. In contrast, plant kinesins have not yet to be characterized adequately. Here, a novel plant-specific kinesin gene, GhKCH2, has been cloned from cotton (Gossypium hirsutum) fibers and biochemically identified by prokaryotic expression, affinity purification, ATPase activity assay and microtubule-binding analysis. The putative motor domain of GhKCH2, $M_{396-734}$ corresponding to amino acids Q396-N734 was fused with 6$\times$His-tag, soluble-expressed in E. coli and affinity-purified in a large amount. The biochemical analysis demonstrated that the basal ATPase activity of $M_{396-734}$ is not activated by $Ca^{2+}$, but stimulated 30-fold max by microtubules. The enzymatic activation is microtubule-concentration-dependent, and the concentration of microtubules that corresponds to half-maximum activation was about 11 ${\mu}M$, much higher than that of other kinesins reported. The cosedimentation assay indicated that $M_{396-734}$ could bind to microtubules in vitro whenever the nucleotide AMP-PNP is present or absent. As a plant-specific microtubule-dependent kinesin with a lower microtubule-affinity and a nucleotide-independent microtubule-binding ability, cotton GhKCH2 might be involved in the function of microtubules during the deposition of cellulose microfibrils in fibers or the formation of cell wall.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.1
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• pp.129-138
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• 1999

If rumen bacteria can be manipulated to utilize nutrients (i.e., ammonia and plant cell wall carbohydrates) more completely and efficiently, the need for protein supplementation can be reduced or eliminated and the digestion of fiber in forage or agricultural residue-based diets could be enhanced. However, these approaches require a complete and accurate description of the rumen community, as well as methods for the rapid and accurate detection of microbial density, diversity, phylogeny, and gene expression. Molecular ecology techniques based on small subunit (SSU) rRNA sequences, nucleic acid probes and the polymerase chain reaction (PCR) can potentially provide a complete description of the microbial ecology of the rumen of ruminant animals. The development of these molecular tools will result in greater insights into community structure and activity of gut microbial ecosystems in relation to functional interactions between different bacteria, spatial and temporal relationships between different microorganisms and between microorganisms and reed panicles. Molecular approaches based on SSU rRNA serve to evaluate the presence of specific sequences in the community and provide a link between knowledge obtained from pure cultures and the microbial populations they represent in the rumen. The successful development and application of these methods promises to provide opportunities to link distribution and identity of gastrointestinal microbes in their natural environment with their genetic potential and in situ activities. The use of approaches for assessing pupulation dynamics as well as for assessing community functionality will result in an increased understanding and a complete description of the gastrointestinal communities of production animals fed under different dietary regimes, and lead to new strategies for improving animal growth.

• Korean Journal of Community Nutrition
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• v.6 no.2
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• pp.243-249
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• 2001

This study investigated how acculturation varies with demographic variables and is related to dietary habits among Korean Americans. The respondents were 162 Korea Americans aged at least 18 years old residing in the Greater New York metropolitan area. The level of acculturation was measured using a modified Suinn-Lew Asian Self-Identity Acculturation(SL-ASIA) scale. Acculturation was operationally defined to be composed of 6 factors, which are language, media use, friendship, food, pride, and ethnic self-identity. Each factor in the level of acculturation was identified by how it is related to demographics and dietary habits in the method of correlation coefficients and stepwise multiple regressions analyses. The reliability of the modified SL-ASIA scale was high as measured by Cronbach alpha of .92. The level of acculturation was related to place of birth, age, length of residence in the U.S., and education. The younger, the longer they had lived in the U.S., and the more they were educated, the more acculturated. Acculturation could be predictable for 52% of its variance with all demographic variables. Among the 6 factors in the level of acculturation, five of them, language, media use friendship, food, and ethnic self-identity were correlated with dietary habit changes after immigration and type of meals. All 6 acculturation factors could predict 21% of change in dietary habits. the information from this study can be used to describe usual describe usual dietary habits according to various aspects of acculturation to better understand the dynamics among acculturation, demographics, and dietary habits.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.5
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• pp.763-769
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• 2020

Objective: The experiment was conducted to study the effect of rambutan (Nephelium lappaceum) fruit peel powder (RP) on feed consumption, digestibility of nutrients, ruminal fermentation dynamics and microbial population in Thai breed cattle. Methods: Four, 2-year old (250±15 kg) beef bull crossbreds (75% Brahman×25% local breed) were allotted to experimental treatments using a 4×4 Latin square design. Four dietary supplementation treatments were imposed; non-supplementation (control, T1); supplementation of RP fed at 2% of dry matter intake (DMI) (low, T2); supplementation of RP fed at 4% of DMI (medium, T3) and supplementation of RP fed at 6% of DMI (high, T4). All cattle were given a concentrate supplement at 1% of body weight while Napier grass was provided as a free choice. Results: The findings revealed that RP supplementation did not negatively affect (p>0.05) DMI of Napier grass, while RP intake and total DMI were the greatest in the RP supplementation at 4% and 6% DMI. Nevertheless, the nutrients (dry matter, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber) digestibilities were not changed in the RP supplementation groups. Rumen fermentation parameters especially those of total volatile fatty acids, acetate and butyrate were not significantly changed. However, the propionate concentration was remarkably increased (p<0.05) in the RP supplementation. Notably, the ratio of acetate to propionate, the number of protozoa, as well as the methane estimation were significantly reduced in the RP supplemented groups (4% and 6% of DMI), while the counts of bacteria was not altered. Conclusion: Supplementation of RP (4% of DMI) improved rumen propionate production, reduced protozoal population and methane estimation (p<0.05) without a negative effect on feed consumption and nutrients total tract digestibilities in beef cattle. Using dietary rambutan fruit peel powder has potential promise as a rumen regulator.

• Journal of Microbiology and Biotechnology
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• v.24 no.6
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• pp.740-747
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• 2014

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a very serious disease in rice-growing regions of the world. In spite of their economic importance, there are no effective ways of protecting rice plants from this disease. Bacteriophages infecting Xoo affect the population dynamics of the pathogen and consequently the occurrence of the disease. In this study, we investigated the diversity, host range, and infectivity of Xoo phages, and their use as a bicontrol agent on BLB was tested. Among the 34 phages that were isolated from floodwater in paddy fields, 29 belonged to the Myoviridae family, which suggests that the dominant phage in the ecosystem was Myoviridae. The isolated phages were classified into two groups based on plaque size produced on the lawn of Xoo. In general, there was a negative relationship between plaque size and host range, and interestingly the phages having a narrow host range had low efficiency of infectivity. The deduced protein sequence analysis of htf genes indicated that the gene was not a determinant of host specificity. Although the difference in host range and infectivity depending on morphotype needs to be addressed, the results revealed deeper understanding of the interaction between the phages and Xoo strains in floodwater and damp soil environments. The phage mixtures reduced the occurrence of BLB when they were treated with skim milk. The results indicate that the Xoo phages could be used as an alternative control method to increase the control efficacy and reduce the use of agrochemicals.