• IMMUNE NETWORK
• /
• 제23권6호
• /
• pp.45.1-45.22
• /
• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• 대한본초학회지
• /
• 제39권1호
• /
• pp.31-38
• /
• 2024

Objectives : Ulcerative colitis is a chronic recurrent inflammatory disease of the gastrointestinal tract. However, there are some drawbacks to long-term drug therapy such as the risk of opportunistic infections. Recently, there was an increasing interest on the use of khorasan Kamut wheat because of their higher value of selenium and fiber than modern wheat. The present study was aimed to investigate the effect of Kamut brand wheat enzyme (Kamut WE) diet on colon health in dextran sulfate sodium (DSS)-induced colitis mice. Methods : Female C57BL/6J mice were divided into 6 groups. (1) normal (Water and AIN-93G diet), (2) control (1.25% DSS and AIN-93G diet), (3) Kamut WE (1.25% DSS and Kamut WE diet), (4) normal (Water and AIN-93G diet), (5) control (2.50% DSS and AIN-93G diet), (6) Kamut WE (2.50% DSS and Kamut WE diet). Dietary intake, body weight change, disease activity index (DAI), colon length and spleen weight were monitored. Results : Kamut WE group alleviated colitis symptom, including dietary intake loss, DAI (weight loss, loose stools, bleeding), colon length shortening and spleen swelling. Further, Kamut WE diets showed a significant effect against pathological damage by the increased colon length, decreased DAI and spleen weight in DSS 1.25% as well as DSS 2.50%. Conclusions : Our study provides evidence that Kamut WE diet increased colon length, decreased DAI and spleen weight in intestinal inflammation.

• 한국재료학회지
• /
• 제34권1호
• /
• pp.1-11
• /
• 2024

This research investigated the preparation of activated carbon derived from Krabok (Irvingia malayana) seed shells to improve the quality of crude glycerol obtained during biodiesel production. The activated carbon was prepared using a dry chemical activation method with NaOH, utilizing an innovative biomass incinerator. The results revealed that the resulting KC/AC-two-step exhibited favorable physicochemical adsorption properties, with a high surface area of 758.72 m²/g and an iodine number of 611.10 mg/g. These values meet the criteria of the industrial product standard for activated carbon No. TIS 900-2004, as specified by the Ministry of Industry in Thailand. Additionally, the adsorption efficiency for methylene blue reached an impressive 99.35 %. This developed activated carbon was then used to improve the quality of crude glycerol obtained from biodiesel production. The experimental results showed that the KC/AC-two-step increased the purity of crude glycerol to 73.61 %. In comparison, commercially available activated carbon (C/AC) resulted in a higher crude glycerol purity of 81.19 %, as analyzed by the GC technique. Additionally, the metal content (Zn, Cu, Fe, Pb, Cd, and Na) in purified glycerol using KC/AC-two-step was below the standards for heavy metals permitted in food and cosmeceuticals by the Food and Drug Administration of Thailand and the European Committee for Food Contact Materials and Articles. As a result, it can be inferred that Krabok seed shells have favorable properties for producing activated carbon suitable as an adsorbent to enhance crude glycerol purity. Furthermore, the improved crude glycerol from this research has potential for various industrial applications.

• 정신신체의학
• /
• 제32권1호
• /
• pp.1-9
• /
• 2024

노쇠는 스트레스 요인에 대한 취약성이 증가하여 생리적인 예비능력이 감소되고 항상성을 유지하는 능력이 저하되는 증후군으로 입원, 장애 및 사망의 위험을 증가시킨다. 노쇠는 다양한 원인에 의해 발생하며 다차원적인 접근이 필요하고 조기에 발견해서 관리하는 것이 중요하다. 노쇠는 통증이나 우울증과 같은 신경정신과적 문제와도 깊은 관련이 있다. 노쇠를 평가하는데 있어서 질병, 영양, 움직임, 감각기능 등의 신체적 영역뿐만 아니라 심리사회적인 영역까지 포괄적으로 고려하는 것이 바람직하며, 대표적인 척도로 Fried의 신체적 노쇠 기준과 Rockwood의 노쇠 척도를 들 수 있다. 노쇠 관리를 위해서는 신체적 활동과 적절한 단백질 섭취가 중요하며, 부적절한 약물 사용을 줄이고 구강관리, 인지기능, 낙상에도 유의해야한다. 노쇠와 통증은 서로 영향을 미칠 수 있으며 통증이 노쇠를 촉진시킬 수 있다. 노쇠와 통증 연구 분야에서 호르몬과 단백질의 이상, 면역체계 활성과 염증반응, 그리고 후성 유전학의 기전이 공통적으로 작용하고 있다는 증거들이 발표되고 있다. 향후 좀 더 광범위하고 수준 높은 연구가 이루어져야 할 것이며, 그 결과를 노쇠와 통증의 억제와 치료에 적용한다면 삶의 질이 높아질 것이다.

• Korean Circulation Journal
• /
• 제53권12호
• /
• pp.843-854
• /
• 2023

Background and Objectives: We evaluated the effect of diabetes on the relationship between body mass index (BMI) and clinical outcomes in patients following percutaneous coronary intervention (PCI) with drug-eluting stent implantation. Methods: A total of 6,688 patients who underwent PCI were selected from five different registries led by Korean Multicenter Angioplasty Team. They were categorized according to their BMI into the following groups: underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight to obese (≥25.0 kg/m²). Major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, nonfatal myocardial infarction, stroke, and target-vessel revascularization, were compared according to the BMI categories (underweight, normal and overweight to obese group) and diabetic status. All subjects completed 1-year follow-up. Results: Among the 6,688 patients, 2,561 (38%) had diabetes. The underweight group compared to normal weight group had higher 1-year MACCE rate in both non-diabetic (adjusted hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.04-4.84; p=0.039) and diabetic patients (adjusted HR, 2.86; 95% CI, 1.61-5.07; p<0.001). The overweight to obese group had a lower MACCE rate than the normal weight group in diabetic patients (adjusted HR, 0.67 [0.49-0.93]) but not in non-diabetic patients (adjusted HR, 1.06 [0.77-1.46]), with a significant interaction (p-interaction=0.025). Conclusions: Between the underweight and normal weight groups, the association between the BMI and clinical outcomes was consistent regardless of the presence of diabetes. However, better outcomes in overweight to obese over normal weight were observed only in diabetic patients. These results suggest that the association between BMI and clinical outcomes may differ according to the diabetic status.

• Korean Journal of Radiology
• /
• 제23권9호
• /
• pp.911-920
• /
• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• IMMUNE NETWORK
• /
• 제20권4호
• /
• pp.32.1-32.15
• /
• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Biomolecules & Therapeutics
• /
• 제32권4호
• /
• pp.481-491
• /
• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• Biomolecules & Therapeutics
• /
• 제32권1호
• /
• pp.104-114
• /
• 2024

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

• 대한한방내과학회지
• /
• 제44권6호
• /
• pp.1327-1336
• /
• 2023

This case report presents the effectiveness of Korean medicine in the treatment of occipital neuralgia. The patient with occipital neuralgia was treated with acupuncture. Acupuncture treatment was administered to the occipital nerve area, which is commonly used in occipital nerve blocks by western medicine doctors. The severity of the symptoms was assessed daily using the Numerical Rating Scale (NRS) score of pain. The patient received outpatient treatment a total of 7 times, and only received acupuncture treatment each time. According to the patient, his symptoms decreased by about 90% two days after acupuncture treatment, and the frequency and duration of the symptoms also decreased. Seven days after all acupuncture treatments, the severity of pain was reduced from NRS 6 to NRS 0. The findings of this case report suggest that treatment with Korean medicine can be an effective option for treating occipital neuralgia. Acupuncture can be a good treatment method for occipital neuralgia, along with western drug treatment and occipital nerve block.