• BMB Reports
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• 제56권2호
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• pp.78-83
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• 2023

Chronic myeloid leukemia (CML) has a markedly improved prognosis with the use of breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitors (BCR-ABL1 TKIs). However, approximately 40% of patients are resistant or intolerant to BCR-ABL1 TKIs. Hypoxia-inducible factor 1α (HIF-1α) is a hypoxia response factor that has been reported to be highly expressed in CML patients, making it a therapeutic target for BCR-ABL1 TKI-sensitive CML and BCR-ABL1 TKI-resistant CML. In this study, we examined whether HIF-1α inhibitors induce cell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death in BCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrations while the cell sensitivity was not affected with imatinib or dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition, echinomycin and PX-478 inhibited the c-Jun N-terminal kinase (JNK), Akt, and extracellular-regulated protein kinase 1/2 (ERK1/2) activation via suppression of BCR-ABL1 and Met expression in BCR-ABL1 sensitive and resistant CML cells. Moreover, treatment with HIF-1α siRNA induced cell death by inhibiting BCR-ABL1 and Met expression and activation of JNK, Akt, and ERK1/2 in BCR-ABL1 TKIs sensitive and resistant CML cells. These results indicated that HIF-1α regulates BCR-ABL and Met expression and is involved in cell survival in CML cells, suggesting that HIF-1α inhibitors induce cell death in BCR-ABL1 TKIs sensitive and resistant CML cells and therefore HIF-1α inhibitors are potential candidates for CML treatment.

• 대한방사선기술학회지:방사선기술과학
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• 제46권2호
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• pp.141-149
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• 2023

The Korea Institute of Radiological and Medical Sciences plans to produce ²²⁵Ac, a therapeutic radio-pharmaceutical for precision oncology, such as prostate cancer. Radon, a radioactive gas, is generated by radium, the target material for producing ²²⁵Ac. The radon concentration is expected to be about 2000 Bq·m^-3. High-concentration radon-generating facilities must meet radioactive isotope emission standards by lowering the radon concentration. However, most existing studies concerning radon removal using activated carbon filters measured radon levels at concentrations lower than 1000 Bq·m^-3. This study measured ²²²Rn removal of coconut-based activated carbon filter under a high radon concentration of about 2000 Bq·m^-3. The ²²²Rn removal efficiency of activated carbon impregnated with triethylenediamine was also measured. As a result, the ²²²Rn removal amount of the activated carbon filter showed sufficient removal efficiency in a ²²²Rn concentration environment of about 2000 Bq·m^-3. In addition, despite an expectation of low radon reduction efficiency of Triethylenediamine-impregnated activated carbon, it was difficult to confirm a significant difference in the results. Therefore, it is considered that activated carbon can be used as a radioisotope exhaust filter regardless of whether or not Triethylenediamine is impregnated. The results of this study are expected to be used as primary data when building an air purification system for radiation safety management in facilities with radon concentrations of about 2000 Bq·m^-3.

• Clinical and Experimental Reproductive Medicine
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• 제49권4호
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• pp.239-247
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• 2022

Objective: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Methods: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. Results: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Conclusion: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.340-354
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• 2023

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

• Journal of Veterinary Science
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• 제24권2호
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• pp.20.1-20.13
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• 2023

Background: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. Objectives: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. Methods: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. Results: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. Conclusions: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.

• Genomics & Informatics
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• 제21권1호
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• pp.3.1-3.10
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• 2023

Characterization as well as prediction of the secondary and tertiary structure of hypothetical proteins from their amino acid sequences uploaded in databases by in silico approach are the critical issues in computational biology. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), which is responsible for pneumonia alike diseases, possesses a wide range of proteins of which many are still uncharacterized. The current study was conducted to reveal the physicochemical characteristics and structures of an uncharacterized protein Q6S8D9_SARS of SARS-CoV. Following the common flowchart of characterizing a hypothetical protein, several sophisticated computerized tools e.g., ExPASy Protparam, CD Search, SOPMA, PSIPRED, HHpred, etc. were employed to discover the functions and structures of Q6S8D9_SARS. After delineating the secondary and tertiary structures of the protein, some quality evaluating tools e.g., PROCHECK, ProSA-web etc. were performed to assess the structures and later the active site was identified also by CASTp v.3.0. The protein contains more negatively charged residues than positively charged residues and a high aliphatic index value which make the protein more stable. The 2D and 3D structures modeled by several bioinformatics tools ensured that the proteins had domain in it which indicated it was functional protein having the ability to trouble host antiviral inflammatory cytokine and interferon production pathways. Moreover, active site was found in the protein where ligand could bind. The study was aimed to unveil the features and structures of an uncharacterized protein of SARS-CoV which can be a therapeutic target for development of vaccines against the virus. Further research are needed to accomplish the task.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.365-374
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• 2023

Crohn's disease (CD) is a chronic inflammatory illness of the digestive system with unknown etiology, and its incidence is increasing worldwide. However, there are currently no effective treatments or medications available for individuals with CD. Therefore, novel therapeutic strategies are urgently needed. The bioactive compounds and targets associated with compounds of Qinghua Xiaoyong Formula (QHXYF) were examined using The Traditional Chinese Medicine Systems Pharmacology database, and 5 disease target databases were also used to identify CD-related disease targets. A total of 166 overlapping targets were identified from QHXYF-related and CD-related disease targets and they were found to be enriched in oxidative stress-related pathways and the PI3K/AKT signaling pathway. Molecular docking was then used to predict how the bioactive compounds would bind to the hub targets. It was found that quercetin could be the core bioactive compound and had good binding affinity to the top 5 hub targets. Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.

• Journal of Radiation Protection and Research
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• 제48권4호
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• pp.204-212
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• 2023

Background: Isotopes of the projectile may be produced along the beam path during the irradiation of a target by a heavy ion due to inelastic interactions with the media. This study analyzed the production cross-section of carbon (C) and Helium (He) projectile's isotopes resulting from the interactions of these beams with different materials along the beam path. Materials and Methods: In this study, we transport C and He ion beams through different materials. This transportation was made by the Monte Carlo simulation. Particle and Heavy Ion Transport code System (PHITS) has been used for this calculation. Results and Discussion: It has been found that ¹⁰C, ¹¹C, and ¹³C from the ¹²C ion beam and ³He from the ⁴He ion beam are significant projectile's isotopes that have higher flux than other isotopes of these projectiles. The ⁴He ion beam has a higher projectile's isotope production cross-section along the beam path, which adds more impurities to the beam than the ¹²C ion beam. These projectile's isotopes from both the ¹²C and ⁴He ion beams have higher production cross-sections in hydrogenous materials like water or polyethylene. Conclusion: It is important to distinguish these projectile's isotopes from the primary beam particles to obtain a precise and accurate cross-section result by minimizing the error during measurement with a nuclear track detector. This study will show the trend of the production probability of projectile's isotopes for these ion beams.

• Advances in nano research
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• 제15권5호
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• pp.451-466
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• 2023

Gastrointestinal cancer (GC) is a prevalent malignant tumor of the digestive system that poses a severe health risk to humans. Due to the specific organ structure of the gastrointestinal system, both endoscopic and MRI diagnoses of GIC have limited sensitivity. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high recurrence rates in surgical and pharmacological therapy. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for the detection and treatment of cancer. Because of its deep location and complex surgery, diagnosing and treating gastrointestinal cancer is very difficult. The early diagnosis and urgent treatment of gastrointestinal illness are enabled by nanotechnology. As diagnostic and therapeutic tools, nanoparticles directly target tumor cells, allowing their detection and removal. XGBoost was used as a classification method known for achieving numerous winning solutions in data analysis competitions, to capture nonlinear relations among many input variables and outcomes using the boosting approach to machine learning. The research sample included 300 GC patients, comprising 190 males (72.2% of the sample) and 110 women (27.8%). Using convolutional neural networks (CNN) and artificial neural networks (ANN)-EXtreme Gradient Boosting (XGBoost), the patients mean± SD age was 50.42 ± 13.06. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.037), distant metastasis (P = 0.004), and tumor stage (P = 0.015) were shown to have a statistically significant link with GC patient survival. AUC was 0.92, sensitivity was 81.5%, specificity was 90.5%, and accuracy was 84.7 when analyzing stomach picture.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.103-103
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• 2022

Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.