• Korean journal of applied entomology
• /
• v.59 no.4
• /
• pp.341-348
• /
• 2020

The ATP-binding cassette (ABC) transporter superfamily represents the largest transmembrane protein that transports a variety of substrates across extra- and intra-cellular membranes. In insects, the ABC transporter proteins play crucial roles in insecticide resistance. To date, no studies have investigated the involvement of ABC transporter gene for cross-resistance to insecticide chemistries. Here, we studied such possible mechanisms against six conventional insecticides using transgenic Drosophila melanogaster strains carrying Mdr49 transcript variant A. For the 91-R and 91-C strains of Drosophila melanogaster, although they have a common origin, 91-R has been intensely selected with DDT for over 60 years, while 91-C has received no insecticide selection. Our transgenic analyses showed that overexpression of 91-R-MDR49 transcript variant A along with three amino acid variations can yield a relatively low degree of cross-resistance to carbofuran (2.0~6.7-fold) and permethrin (2.5~10.5-fold) but did not show cross-resistance to abamectin, imidacloprid, methoxychlor, and prothiofos as compared to the Gal4-driver control strain without transgene expression. These results indicate that the overexpression of Mdr49A in itself leads to a cross-resistance and three amino acid changes have additional effects on positive cross-resistance to carbofuran and permethrin.

• Journal of Ginseng Research
• /
• v.47 no.2
• /
• pp.199-209
• /
• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• Archives of Plastic Surgery
• /
• v.49 no.6
• /
• pp.716-723
• /
• 2022

Background In March 2021, the United States Food and Drug Administration (FDA) safety communication cautioned against the use of acellular dermal matrix (ADM) products in breast reconstruction and reiterated that the FDA does not approve ADM use in breast surgery. This study aims to assess the safety of ADM use in breast reconstruction. Methods Women who underwent ADM and non-ADM assisted tissue expander (TE)-based breast reconstruction were identified using the National Surgical Quality Improvement Program database (2012-2019). Trends of ADM use over time, and 30-day outcomes of surgical site infection (SSI), dehiscence, and unplanned reoperation were assessed. Results Of the 49,049 TE-based breast reconstructive cases, 42.4% were ADM assisted and 57.6% non-ADM assisted. From 2012 to 2019, the use of ADM increased from 26.1 to 55.6% (relative risk [RR] =1.10; p < 0.01). Higher rates of SSI (3.9 vs. 3.4%; p = 0.003) and reoperation (7.4 vs. 6.0%; p < 0.001) were seen in the ADM cohort. There was no significant difference seen in dehiscence rates (0.7 vs. 0.7%; p = 0.73). The most common reoperation within 30 days for the ADM group (17.6%) was removal of TE without insertion of implant (current procedural terminology: 11,971). ADM-assisted breast reconstruction was associated with increased relative risk of SSI by 10% (RR = 1.10, confidence interval [CI]: 1.01-1.21; p = 0.03) and reoperation by 15% (RR = 1.15, CI: 1.08-1.23; p < 0.001). Conclusions ADM-assisted breast reconstruction more than doubled from 2012 to 2019. There are statistically higher complication rates of SSI (0.5%) and reoperation (1.4%) with ADM use in TE-based breast reconstruction, suggesting that reconstruction without ADM is safe when comparing immediate postoperative outcomes.

• Animal Bioscience
• /
• v.36 no.8
• /
• pp.1293-1303
• /
• 2023

Objective: Inflammation and pain management in postpartum hyperprolific sows is currently an important animal welfare issue in the swine industry. The present study investigates effects of ketoprofen treatment on the incidence of post-parturient disorders, feed intake, colostrum yield, piglet colostrum intake, colostrum immunoglobulin G (IgG) and piglet mortality rate during the first 3 days of postnatal life. Methods: In total, 61 Danish Landrace×Yorkshire crossbred sows and their offspring (n = 833) were included in the experiment. The sows were randomly distributed into two groups: i) control (n = 31), sows were treated with tolfenamic acid 2 mg per kg for 2 days postpartum; ii) ketoprofen (n = 30), sows were treated with ketoprofen 3 mg per kg for 2 days postpartum. The farrowing process of the sows was monitored for 24 h daily, and data associated with farrowing were collected. Piglet colostrum intake, sow colostrum yield and colostrum IgG were determined. Results: During the first 3 days postpartum, the incidence of sows that had fever did not differ between control and ketoprofen groups (51.6% and 56.7%, respectively, p = 0.692). Piglet colostrum intake did not differ between control and ketoprofen groups (p = 0.736). However, the proportions of piglets that had inadequate colostrum intake were 71.3%, 22.6%, and 5.4% in those with birth weights of <1.0 kg, 1.0 to 1.29 kg, and ≥1.30 kg, respectively (p<0.001). The piglet mortality rate did not differ between control and ketoprofen groups (p = 0.808). Conclusion: Administration of ketoprofen in postpartum sows for 2 days can control the evidence of post-parturient disorders in sows as effectively as the use of tolfenamic acid. No deleterious effect of ketoprofen was detected on sow colostrum yield, piglet colostrum intake and piglet mortality. Therefore, ketoprofen can be recommended as an alternative anti-inflammatory drug used in postpartum sows.

• Journal of Life Science
• /
• v.33 no.6
• /
• pp.490-497
• /
• 2023

Pregnant women may need to take medications to treat preexisting diseases or diseases that develop during pregnancy. However, some drugs may be fetotoxic and lead to, for example, teratogenicity and growth retardation. Predicting the fetotoxicity of drugs is thus important for the health of the mother and fetus. The fetotoxicity of many drugs has not been established because various challenges hinder the ability of researchers to determine their fetotoxicity. The need exists for in silico-based fetotoxicity assessment models, as they can modernize the testing paradigm, improve predictability, and reduce the use of animals and the costs of fetotoxicity testing. In this study, we collected data on the fetotoxicity of drugs and constructed fetotoxicity prediction models based on various machine learning algorithms. We optimized the models for more precise predictions by tuning the hyperparameters. We then performed quantitative performance evaluations. The results indicated that the constructed machine learning-based models had high performance (AUROC >0.85, AUPR >0.9) in fetotoxicity prediction. We also analyzed the feature importance of our model's predictions, which could be leveraged to identify the specific features of drugs that are strongly associated with fetotoxicity. The proposed model can be used to prescreen drugs and drug candidates at a lower cost and in less time. It provides a predictive score for fetotoxicity risk, which may be beneficial in the design of studies on fetotoxicity in human pregnancy.

• Journal of Life Science
• /
• v.33 no.11
• /
• pp.876-886
• /
• 2023

In some cases of head and neck cancers (HNC), surgical interventions may result in the loss of organs and/or changes to their functions, thereby significantly affecting the patient's quality of life. As a result, the surgical treatment of HNC patients is often limited to specific cases, and alternative treatment modalities, such as chemotherapy, are considered. However, serious adverse effects caused by chemotherapy, such as severe nausea and vomiting, necessitate the need for the development of adjunctive methods to minimize patient suffering. Chuanxiong, Ligusticum chuanxiong (L. chuanxiong), is a natural herb used in Eastern medicine to treat cerebrovascular disorders and headaches. This study aimed to predict the effect and potential of L. chuanxiong as an auxiliary anticancer drug through network-based pharmacology and molecular docking analysis. The study results showed that 40 out of 41 genes of L. chuanxiong shared common targets of HNC and their proteins could be used to target HNC cells to prevent cancer progression. The results of the functional enrichment analysis confirmed that L. chuanxiong is associated with the neuroactive-ligand metabolism and neurotransmitter pathways, indicating its potential medicinal value as an adjuvant in HNC treatment. Lastly, our findings demonstrated that the active ingredient of L. chuanxiong, (Z)-Ligustilide, has the ATP binding site of heat shock protein 90, a protein known to promote the activation of cancer cells. These results suggest that L. chuanxiong is a promising candidate for developing auxiliary anticancer drugs, and further research could potentially lead to the discovery of newer and safer anti-cancer agents.

• Journal of Biomedical Engineering Research
• /
• v.44 no.6
• /
• pp.363-376
• /
• 2023

According to the COVID-19, development of various medical software based on IoT(Internet of Things) was accelerated. Especially, interest in a central software system that can remotely monitor and control ventilators is increasing to solve problems related to the continuous increase in severe COVID-19 patients. Since medical device software is closely related to human life, this study aims to develop central monitoring system that can remotely monitor and control multiple ventilators in compliance with medical device software development standards and to verify performance of system. In addition, to ensure the safety and reliability of this central monitoring system, this study also specifies risk management requirements that can identify hazardous situations and evaluate potential hazards and confirms the implementation of cybersecurity to protect against potential cyber threats, which can have serious consequences for patient safety. As a result, we obtained medical device software manufacturing certificates from MFDS(Ministry of Food and Drug Safety) through technical documents about performance verification, risk management and cybersecurity application.The purpose of this study is to conduct a usability assessment to ensure that ergonomic design has been applied so that the ventilator central monitoring system can improve user satisfaction, efficiency, and safety. The rapid spread of COVID-19, which began in 2019, caused significant damage global medical system. In this situation, the need for a system to monitor multiple patients with ventilators was highlighted as a solution for various problems. Since medical device software is closely related to human life, ensuring their safety and satisfaction is important before their actual deployment in the field. In this study, a total of 21 participants consisting of respiratory staffs conducted usability test according to the use scenarios in the simulated use environment. Nine use scenarios were conducted to derive an average task success rate and opinions on user interface were collected through five-point Likert scale satisfaction evaluation and questionnaire. Participants conducted a total of nine use scenario tasks with an average success rate of 93% and five-point Likert scale satisfaction survey showed a high satisfaction result of 4.7 points on average. Users evaluated that the device would be useful for effectively managing multiple patients with ventilators. However, improvements are required for interfaces associated with task that do not exceed the threshold for task success rate. In addition, even medical devices with sufficient safety and efficiency cannot guarantee absolute safety, so it is suggested to continuously evaluate user feedback even after introducing them to the actual site.

• Journal of the Korean Applied Science and Technology
• /
• v.40 no.6
• /
• pp.1567-1579
• /
• 2023

Sucralose is used as a sucrose alternative in the food sector and is a globally approved pyrogenic, high-intensity artificial sweetener. However, due to the lack of studies on the effects of sweeteners on the brain, this study confirmed whether short-term consumption of sucralose has cognitive and memory protective effects in scopolamine-induced memory-injured animal models. After oral administration of sucralose 2, 5, and 10 mg/kg, scopolamine (1 mg/kg) was administered to the control group and the drug group 30 minutes later, and saline was administered intraperitoneally to the normal group, followed by behavioral experiments As a result of the experiment, Y-Maze, passive avoidance, and Morris WaterMaze recovered more than 10% of cognitive function compared to the control group. In addition, as a result of measuring proinflammatory cytokines, sucralose was found to inhibit IL-6 and TNF-α by more than 30%, and we observed that the expression level of ERK-CREB with intracellular signaling mechanisms increased in a concentration-dependent manner. Therefore, it suggests that sucralose is associated with functional foods for the prevention of functional food patients.

• IMMUNE NETWORK
• /
• v.24 no.3
• /
• pp.15.1-15.18
• /
• 2024

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5469-5475
• /
• 2012

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.