• BMB Reports
• /
• v.56 no.3
• /
• pp.196-201
• /
• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Journal of Pharmacopuncture
• /
• v.26 no.1
• /
• pp.27-37
• /
• 2023

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.4
• /
• pp.265-272
• /
• 2022

The emergence and dissemination of carbapenemase-producing Enterobacteriaceae (CPE), particularly the Klebsiella pneumoniae carbapenemase-2 (KPC-2) producing Klebsiella pneumoniae, has been rapidly increasing worldwide and is becoming a serious public health threat. Since the epidemiology and characteristics of these KPC-2-producing K. pneumoniae vary according to the region and period under consideration, this study investigated the prevalence of carbapenemases and the epidemiological relationship of 78 carbapenem-resistant K. pneumoniae (CRKP) isolated from a tertiary hospital in Daejeon, from March 2017 to December 2020. The antimicrobial susceptibility tests were identified using the disk-diffusion method. PCR and DNA sequencing were used to determine the carbapenemase genes. In addition, molecular epidemiology was performed by multilocus sequence typing (MLST). Among the 78 CRKP isolates, 35 isolates (44.9%) were carbapenemase-producing K. pneumoniae (CPKP) and the major carbapenemase type was KPC-2 (30 isolates, 85.7%). The New Delhi metallo-enzyme-1 (NDM-1) and NDM-5 were identified in 4 isolates (11.4%) and 1 isolate (2.9%), respectively. Multilocus sequence typing (MLST) analysis showed 10 sequence types (STs) and the most prevalent ST was ST307 (51.4%, 18/35). All the ST307 isolates were KPC-2-producing K. pneumoniae and were multidrug-resistant (MDR). In addition, ST307 has gradually emerged during a four-year period. These findings indicate that continuous monitoring and proper infection control are needed to prevent the spread of KPC-2-producing K. pneumoniae ST307.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.4
• /
• pp.249-255
• /
• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Journal of the Korean Applied Science and Technology
• /
• v.40 no.1
• /
• pp.1-12
• /
• 2023

It was investigated whether a combination of PPARα activator fenofibrate and swimming exercise (H/F/S) would have a beneficial synergistic effect on improving inflammation of white adipose tissue compared to the single prescription of fenofibrate (H/F) and swimming exercise (H/S) in male mice that fed high fat diet. The body weight, weight of white adipose tissue and total cholesterol levels in the serum increased in mice-fed high fat diets (H) compared to mice-fed low fat diets (L). Compared to H, both H/F and H/S decreased these. These levels reduced by fenofibrate were more effectively reduced by the combination of fenofibrate and swimming exercise (H/F/S). As a result of examining the expression of inflammatory cytokines genes and fatty acid oxidation genes in white adipose tissue, H increased compared to L, both H/F and H/S decreased compared to H, and H/F/S decreased further compared to H/F. Thus, this study revealed that the combination of fenofibrate and swimming exercise in male mice fed high-fat diet suppresses inflammation of white adipose tissue caused by obesity through promoted fatty acid oxidation more effectively than the fenofibrate alone, and suggested a practical way to improve inflammation of adipose tissue caused by obesity.

• Journal of Food Hygiene and Safety
• /
• v.38 no.4
• /
• pp.193-201
• /
• 2023

Antimicrobials in human medicine are classified by The World Health Organization (WHO) into three groups: critically important antimicrobials (CIA), highly important antimicrobials (HIA), and important antimicrobials (IA). CIA are antibiotic classes that satisfy two main criteria: that they are the sole or the only available limited therapeutic option to effectively treat severe bacterial infections in humans (Criterion 1), and infections where bacteria are transmitted to humans from non-human sources or have the potential to acquire resistance genes from non-human sources (Criterion 2). WHO emphasizes the need for cautious and responsible use of the CIA to mitigate risk and safeguard human health. Specific antimicrobials within the CIA with a high priority for management are reclassified as "highest priority critically important antimicrobials (HP-CIA)" and include the 3^rd generation of cephalosporins and the next generation of macrolides, quinolones, glycopeptides, and polymyxins. The CIA list is the scientific basis for risk assessment and risk management policies that warrant using antimicrobials to reduce antimicrobial resistance in several countries. In addition, the CIA list ensures food safety in the food industry, including for the popular food chain companies McDonald's and KFC. The continuous update of the CIA list reflects the advancement in research and emerging future challenges. Thus, active and deliberate evaluation of antimicrobial resistance and the construction of a list that reflects the specific circumstances of a country are essential to safeguarding food security.

• The Journal of the Acoustical Society of Korea
• /
• v.42 no.5
• /
• pp.412-421
• /
• 2023

Ultrasound brain stimulation is spot-lighted by its capability of inducing brain cell activation in a localized deep brain region and ultimately treating impaired brain function while the efficiency and directivity of neural modulation are highly dependent on types of stimulus waveforms. Therefore, to optimize the types of stimulation parameters, we propose a cell-cultivable ultrasonic transducer having a series stack of a spin-coated polymer piezoelectric element (Poly-vinylidene fluoride-trifluorethylene, PVDF-TrFE) and a parylene insulating layer enhancing output acoustic pressure on a glass-coverslip which is commonly used in culturing cells. Due to the uniformity and high accuracy of stimulus waveform, tens of neuronal cell responses located on the transducer surface can be recorded simultaneously with fluorescence microscopy. By averaging the cell response traces from tens of cells, small changes to the low intensity ultrasound stimulations can be identified. In addition, the reduction of stimulus distortions made by standing wave generated from reflections between the transducers and other strong reflectors can be achieved by placing acoustic absorbers. Through the proposed ultrasound transducer, we could successfully observe the calcium responses induced by low-intensity ultrasound stimulation of 6 MHz, 0.2 MPa in astrocytes cultured on the transducer surface.

• The Journal of the Acoustical Society of Korea
• /
• v.42 no.5
• /
• pp.469-490
• /
• 2023

Survey was carried out on the acoustic outputs from 12 shock wave fields produced by the 10 extracorporeal shock wave lithotriptors whose technical documents are available, among the 33 devices approved by the Ministry of Food & Drug Safety (MFDS).The results show that the acoustic outputs (P+, P-, efd, and E), critical to the therapeutic efficacy and the patient safety, are largely different between the devices. The maximum values of P+, P-, efd, and E vary up to 2.08, 3.72, 3.89, and 15.98 times, respectively. The acoustic output parameters are not thoroughly provided in the technical documents, and some of data (eg. efd) are suspected to be abnormal outside usual ranges. The large device to device differences in the shock wave outputs are likely to undermine equivalence between the ESWL devices approved for the same indication. To verify the reliability of the data in the technical documents of the approved devices and to confirm if the acoustic outputs from the devices in clinical use are the same as those in their technical documents, an authorized test laboratory should be available. A postapproval monitoring led by the regulatory agency is suggested to maintain the acoustic outputs from the ESWL devices that suffer from degrading in performance due to aging.

• Journal of the Korean Society of Radiology
• /
• v.17 no.4
• /
• pp.497-506
• /
• 2023

In the case of radiation workers in medical institutions, radiation exposure is made for patient protection and accurate procedures, so they have a problem of low dose exposure. Low-dose radiation exposure occurs mainly in parts of the body other than the Apron area, and the most frequent place is the skin of the back of the hand. In particular, since the medical personnel's hands require senses and fine movements during the procedure, they are defenseless in the radiation exposure area and are at risk of exposure. It can solve the problem of shielding such as lead gloves, and it is difficult to use by suggesting the activity of the hand during the procedure. To solve this problem, a shielding cream capable of obtaining a functional radiation protection effect was developed and its shielding performance was compared with lead equivalent of 0.1 mmPb. In the process of manufacturing shielding cream, the shielding performance was improved by adding a defoaming process to reduce air holes to increase the density of the cream. Therefore, the shielding cream using barium sulfate as the main material has a lower shielding rate than the lead plate, and in the realm of effective energy, it is 59%, At high effective energy, a difference of about 37% was shown, indicating that there is a functional radiation protection effect. The advantage is that it can be used directly on the skin, and it is considered that it can be used before wearing surgical gloves and has a permanent protective effect.

• Journal of Korea Entertainment Industry Association
• /
• v.13 no.2
• /
• pp.253-259
• /
• 2019

Prostate cancer(PrCa) is a leading cause of cancer-related death in man. Medicinal plants are exploited for many drugs to treat various ailments. The drugs derived from the plants promote health, augmented the resistance of the body against disease. Pueraia lobata(wild) Ohwi(P. Lobata), kudzu, which is a twining perennial woody herb native to China, Korea, Japan, India, and the United States. Plants such as Moringa oleifera, have hypoglycemic properties and other beneficial properties. The objective of the study was to analyze the effects of kadzu and moringa, natural plant products on antioxidant activity and proliferation of the hormone-sensitive prostate cancer LNCaP cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 10 and 50mg/ml of concentration. kadzu and moringa reduced LNCaP cell viability in a dose dependent manner. Specially moringa extract was more potent cytotoxic than kadzu extract. Statistical analyses revealed kadzu and moringa exhibited significantly higher (P < 0.05) cytotoxicity and antioxidant activity in LNCaP. The finding of this study provides a scientific basis for using kadzu and moringa in future development of chemotherapeutic drugs against hormone-sensitive prostate cancer.