• Molecules and Cells
• /
• 제39권7호
• /
• pp.543-549
• /
• 2016

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

• Molecules and Cells
• /
• 제40권2호
• /
• pp.133-142
• /
• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Journal of Physiology & Pathology in Korean Medicine
• /
• 제33권2호
• /
• pp.89-101
• /
• 2019

In recent times, the number of men with late-onset hypogonadism has increased, and interest on this topic has also increased. This study was conducted to investigate effects of the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus on improve late-onset hypogonadism. The experimental subjects consisted of three groups: a control group consisting of 8-week-old male ICR mice that had undergone no treatment, an aging-elicited group (AE group) consisting of 50-week-old ICR male mice that had undergone no treatment, and a Mixed herbal extract treatment group (MT group) consisting of 50-week-old ICR male mice that had undergone the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus treatment (0.1 g/kg/day) for 6 months. After the experiment, the mice from all the experimental groups were dissected, and they were analyzed through histochemical and immunohistochemical methods. The mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus reduces aging-induced cell damage and oxidative stress and increases the secretion of serotonin and B-endorphin in aged mice, and promotes spermatogenesis in seminiferous tubules and reduces apoptosis and oxidative stress, and increases androgen receptor, $17{\beta}-HSD$ and GnRH, increases the ratio of smooth muscle to collagen fibers in the corpus cavernosum, increases eNOS, decreases PDE-5 and oxidative stress in aged mice, so it improves depression, reproductive, sexual problems caused by Late-onset hypogonadism. the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus inhibits the induction of osteoporosis by increasing decreased bone matrix distribution due to aging, increasing the activities of OPC and OPN, which are produced in osteoblasts, and decreasing RANKL, MMP-3 activity, increasing OPG activity. It also reduces muscle damage, oxidative stress, inflammation and apoptosis of muscle tissue, and increases Myo-D in the sartorius muscle of aged mice for improving muscle atrophy caused by by Late-onset hypogonadism.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권2호
• /
• pp.147-157
• /
• 2021

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

• Tuberculosis and Respiratory Diseases
• /
• 제84권2호
• /
• pp.96-104
• /
• 2021

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 ㎍ to indacaterol/glycopyrronium (IND/GLY) 110/50 ㎍ once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 ㎍ once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥50%, post-bronchodilator FEV₁/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV₁ at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. Results: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV₁ versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, -0.81), and rescue medication use (Δ, -0.09 puffs/day). Both treatments were well tolerated by patients. Conclusion: A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.

• Journal of Pharmacopuncture
• /
• 제25권3호
• /
• pp.233-241
• /
• 2022

Objectives: Asthma is a chronic disease, and the demand for herbal medicines in this field has increased in recent years. The new findings highlight the role of the gut-lung axis in the pathophysiology of asthma. Hence, this study will evaluate the safety and efficacy of Glasthma syrup, an herbal formula based on Persian medicine, in improving asthma and regulating intestinal permeability. The formula consists of five herbal ingredients that have anti-inflammatory effects on the respiratory tract, also known as gut tonics. Methods: The study will be conducted as a placebo-controlled, triple-blind, randomized trial. It will consist of a 4-week intervention followed by a 4-week follow-up period. The target sample size is 20 patients with moderate asthma aged 18 to 60 years. Eligible participants will be randomly assigned to either the experimental group or the control group in equal numbers. Patients in the experimental group will take Glasthma syrup (7.5 mL, twice a day), while patients in the control group will take a matching placebo. Both groups will receive a 4-week combination of a long-acting beta2 agonist and a leukotriene modulator as standard of care. Inhaled corticosteroids can be used as rescue medication as needed. Results: The primary outcomes are asthma symptom scale, lung function, and intestinal permeability. Secondary outcomes include quality of life, symptom recurrence rates, and blood tests. A safety assessment will also be conducted during the trial. Conclusion: In this trial, the effects of Glasthma syrup in patients with moderate asthma will be examined. The study will also assess the effects of the formulation on the gut-lung axis by simultaneously monitoring the gut permeability index, asthma symptoms, and lung function.

• IMMUNE NETWORK
• /
• 제21권4호
• /
• pp.25.1-25.16
• /
• 2021

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)⁺ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR⁺ILC3 frequencies and microbial diversity in the lung. Sputum NCR⁺ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR⁺ILC3s may contribute to a healthy commensal diversity and normal lung function.

• The Korean Journal of Physiology and Pharmacology
• /
• 제28권4호
• /
• pp.313-322
• /
• 2024

Mutations within the SCN5A gene, which encodes the α-subunit 5 (Na_V1.5) of the voltage-gated Na⁺ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the Na_V1.5 current (I_Na) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of I_Na was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the co-expression of SCN1B with p.A385T/R504T revealed significant reduction of I_Na and slower recovery from inactivation, consistent with the loss-of-function in Na⁺ channels. The SCN1B dependent reduction of I_Na was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of Na_V1.5, respectively.

• Korea Science and Art Forum
• /
• 제31권
• /
• pp.21-32
• /
• 2017

Local festivals form the regional cultures and atmosphere of communication; they increase the demand of domestic tourism businesses and thus, have an important role in ripple effects (e.g. regional image improvement, tourist influx, job creation, regional contents development, and local product sales) and economic revitalization. IoT (Internet of Thing) technologies have been developed especially, beacon-one of the IoT services has been applied as plenty of types and forms both domestically and internationally. However, notwithstanding expansion of current digital mobile technologies, it still remains as difficult for the individual to track the information about all the local festivals and to fulfill the tourists' needs of enjoying festivals given the weak strategic approaches and advertisement activities. Furthermore, current festival-related mobile applications don't function well as delivering information and have numerous contents issues (e.g. ways of information delivery within the festival places, independent application usage for each festival, one time usage due to one time event). This research, based on the background mentioned above, aims to develop the local festival mobile application and data analysis system applying beacon technology. First of all, three algorithms were developed, namely, 'festival crowding algorithm', 'visitor stats algorithm', and 'customized information algorithm', and then beta test was followed with the developed application and data analysis system. As a result, they could form the database of visitors' types and behaviors, and provide functions and services, such as personalized information, waiting time for festival contents, and 'hot place' function. Besides, in Google Play store, they also got the titles given with more than 13,000 downloads within first three months and as the most exposed application related with festivals; and, thus, got credited with their marketability and excellence. This research follows this order: chapter 2 shows the literature review of local festival related with technology development, beacon service, and festival application. In Chapter 3, design plans and conditions are described of developing local festival mobile application and data analysis system with beacon. Chapter 4 evaluates the results of the beta performance test to verify applicability of the developed application and data analysis system, and lastly, chapter 5 explains the conclusion and suggests the future research.

• Korean Journal of Microbiology
• /
• 제41권2호
• /
• pp.99-104
• /
• 2005

Corynebacterial clones which exert regulatory effects on the expression of the glyoxylate bypass genes were isolated using a reporter plasmid carrying the enteric lacZ fused to the aceB promoter of Corynebacterium glutamicum. Some clones carried common fragments as turned out by DNA mapping technique. Subcloning analysis followed by the measurement of $\beta-galactosidase$ activity in Escherichia coli identified the region responsible for the aceB-repressing activity. Sequence analysis of the DNA fragment identified two independent ORFs of ORF1 and ORF2. Among them, ORF2 was turned out to be responsible for the aceB-repressing activity. ORF1 encoded a 23,216 Da protein composed of 206 amino acids. Sequence similarity search indicated that the ORF may encode a ECF-type $\sigma$ factor and designated sigH. To identify the function of sigH, C. glutamicum sigH mutant was constructed by gene disruption technique and the sigH mutant showed growth retardation as compared to the wild type strain. In addition, the mutant strain showed sensitivity to oxidative-stress generating agent plumbagin. This result imply that sigH is probably involved in the stress response occurring during normal cell growth.