• Title/Summary/Keyword: Cell Resistance

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Fine Mapping of Zenith Derived Rice Stripe Virus Resistance Gene, Stv-b

  • Sais-Beul Lee;Jun-Hyun Cho;Nkulu Rolly Kabange;Sumin Jo;Ji-Yoon Lee;Yeongho Kwon;Ju-Won Kang;Dongjin Shin;Jong-Hee Lee;You-Cheon Song;Jong-Min Ko;Dong-Soo Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.12a
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    • pp.63-63
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    • 2020
  • Rice stripe virus (RSV) disease is one of the major constraints in rice production, transmitted by the small brown planthopper (SBPH; Laodelphax striatellus). Upon RSV infection, plants develop typical symptoms, which include chlorosis and weakness of newly emerged leaves, white and yellow spots, stripe on leaves, and necrotic and wilting leaves, resulting in plant growth inhibition, oxidative damage that may culminate in programmed cell death (PCD) and plant death in severe epidemics. Although RSV-resistant quantitative trait loci (QTLs), Stv-a, Stv-b, and Stv-bi, were mapped using various resistant varieties, one RSV-resistant gene, OsSOT1, has been identified so far. In this study, we used the rice cultivar Zenith, known to carry Stv-b, to investigate novel RSV-genes through fine mapping. Therefore, we crossed Zenith (Donor parent, RSV resistant) with Ilpum (Recurrent parent, RSV susceptible) to fine-map using a BC2F2 population of 2100 plants. Chromosome segment introgression lines that were heterozygous at a different region were selected, two types of heterozygous lines showed an heterozygous genotype between Sid2 and Sid75 to Indel9 and RM6680. Interestingly, we identified qSTV11Z region harboring Stv-b, covering about 171-kb region between the InDel markers Sid75 and Indel8. The localization of qSTV11Z provides useful information that could be used for marker-assisted selection and determination of genetic resources in rice breeding.

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Hydroxychavicol Inhibits In Vitro Osteoclastogenesis via the Suppression of NF-κB Signaling Pathway

  • Sirada Srihirun;Satarat Mathithiphark;Chareerut Phruksaniyom;Pitchanun Kongphanich;Wisutthaporn Inthanop;Thanaporn Sriwantana;Salunya Tancharoen;Nathawut Sibmooh;Pornpun Vivithanaporn
    • Biomolecules & Therapeutics
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    • v.32 no.2
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    • pp.205-213
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    • 2024
  • Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

Pectolinarigenin ameliorated airway inflammation and airway remodeling to exhibit antitussive effect

  • Quan He;Weihua Liu;Xiaomei Ma;Hongxiu Li;Weiqi Feng;Xuzhi Lu;Ying Li;Zi Chen
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.229-237
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    • 2024
  • Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.

P-hydroxybenzoic acid positively affect the Fusarium oxysporum to stimulate root rot in Panax notoginseng

  • Jing Zhao;Zhandi Wang;Rong Jiao;Qionglian Wan;Lianchun Wang;Liangxing Li;Yali Yang;Shahzad Munir
    • Journal of Ginseng Research
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    • v.48 no.2
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    • pp.229-235
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    • 2024
  • Background: Plant health is directly related to the change in native microbial diversity and changes in soil health have been implicated as one of the main cause of root rot. However, scarce information is present regarding allelopathic relationship of Panax notoginseng root exudates and pathogenic fungi Fusarium oxysporum in a continuous cropping system. Methods: We analyzed P. notoginseng root exudate in the planting soil for three successive years to determine phenolic acid concentration using GC-MS and HPLC followed by effect on the microbial community assembly. Antioxidant enzymes were checked in the roots to confirm possible resistance in P. notoginseng. Results: Total 29 allelochemicals in the planting soil extract was found with highest concentration (10.54 %) of p-hydroxybenzoic acid. The HPLC showing a year-by-year decrease in p-hydroxybenzoic acid content in soil of different planting years, and an increase in population of F. oxysporum. Moreover, community analysis displayed negative correlation with 2.22 mmol. L-1 of p-hydroxybenzoic acid correspond to an 18.1 % population of F. oxysporum. Furthermore, in vitro plate assay indicates that medium dose of p-hydroxybenzoic acid (2.5-5 mmol. L-1) can stimulate the growth of F. oxysporum colonies and the production of macroconidia, as well as cell wall-degrading enzymes. We found that 2-3 mmol. L-1 of p-hydroxybenzoic acid significantly increased the population of F. oxysporum. Conclusion: In conclusion, our study suggested that p-hydroxybenzoic acid have negative effect on the root system and modified the rhizosphere microbiome so that the host plant became more susceptible to root rot disease.

Effects of Fragaria Orientalis Water extract on Adipogenesis and Cell Differentiation in 3T3-L1 Cells (3T3-L1 지방 전구세포의 분화 및 지방 생성에 미치는 Fragaria Orientalis L. 물 추출물의 영향)

  • Moon-Yeol Choi;Mi Hyung Kim;Mi Ryeo Kim
    • The Korea Journal of Herbology
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    • v.39 no.3
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    • pp.49-56
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    • 2024
  • Objective : Obesity, which has recently been rapidly increasing in the obese population, is caused by an imbalance in energy intake and consumption. The reason why we need to manage obesity well is that the prevalence of complications such as diabetes, atherosclerosis, insulin resistance, and cardiovascular disease increases. In this study, the effect of FO (Fragaria orientalis) water extract on fat metabolism in 3T3-L1 cells was observed to develop a new anti-obesity material based on Mongolian medical books. Methods : The effect of FO extract on adipogenesis in 3T3-L1 cells was observed using DPPH scavenging, pancreatic lipase inhibitory activity, MTT analysis and Oil-red-O staining method. And the expression of proteins related to lipid metabolism was analyzed by Western blot. Results : The FO group significantly increased the DPPH radical scavenging activity at 5 mg/ml compared to the positive control BHA at 0.1 mg/ml. In oil red O staining at a safe concentration without cytotoxicity, lipid accumulation was significantly inhibited by less than 80% compared to the control group at all concentrations. Moreover, treatment of FO significantly increased the expression of proteins related to lipid metabolism, such as p-AMPK and p-ACC, in 3T3-L1 cells, and the expression of CPT-1 tended to increase in a dose-dependent manner. However, the expression of PPAR-γ was significantly decreased in a dose-dependent manner. Conclusion : These results suggest that FO water extract has a potential anti-obesity effect and are expected to be utilized in the development of materials for obesity prevention and treatment.

Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection with Acinetobacter baumannii in Mice

  • Min-Jung Kang;Ah-Ra Jang;Ji-Yeon Park;Jae-Hun Ahn;Tae-Sung Lee;Dong-Yeon Kim;Do-Hyeon Jung;Eun-Jung Song;Jung Joo Hong;Jong-Hwan Park
    • IMMUNE NETWORK
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    • v.20 no.3
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    • pp.25.1-25.13
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    • 2020
  • Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP-/- mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP-/- mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP-/- neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP-/- neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway

  • Zhenyu Guo;Tingqin Huang;Yingfei Liu;Chongxiao Liu
    • International Journal of Stem Cells
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    • v.16 no.3
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    • pp.315-325
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    • 2023
  • Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

Impact Tensile Properties and Intergranular Fracture Behavior with Strain Rate Variations of Al-M g-X (X = Cr,Si) Alloy

  • Chang-Suk Han;Min-Gyu Chun;Sung-Soon Park;Seung-In Lim
    • Korean Journal of Materials Research
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    • v.34 no.7
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    • pp.330-340
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    • 2024
  • Al-Mg-Si alloys are light weight and have excellent corrosion resistance, and are attracting attention as a liner material for high-pressure hydrogen containers in hydrogen fuel cell vehicles. Because it has excellent plastic hardening properties, it is also applied to car body panel materials, but it is moderate in strength, so research to improve the strength by adding Si-rich or Cu is in progress. So far, the authors have conducted research on the intergranular fracture of alloys with excessive Si addition from the macroscopic mechanical point of view, such as specimen shape. To evaluate their impact tensile properties, the split-Hopkinson bar impact test was performed using thin plate specimens of coarse and fine grain alloys of Al-Mg-X (X = Cr,Si) alloy. The effect of the shape of the specimen on the characteristics was studied through finite element method (FEM) analysis. As a result, it was found that the intergranular fracture of the alloy with excessive Si depended on the specimen width (W)/grain size (d), which can be expressed by the specimen size and grain size. As W/d decreases, the intergranular fracture transforms into a transgranular fracture. As the strain rate increases, the fracture elongation decreases, and the fracture surface of the intergranular fracture becomes more brittle. It was confirmed that intergranular fracture occurred in the high strain rate region even in materials with small grain sizes.

Preventive effects of Scutellaria baicalensis, Alisma orientale and Atractylodes japonica mixtures extract on Interleukin-6-induced intestinal tight junction dysfunction in Caco-2 cells (Caco-2 세포에서 Interleukin-6로 유도한 밀착연접 기능 장애에 대한 황금, 택사, 백출 혼합 추출물의 예방 효과)

  • Kwang-Youn Kim;Tae-In Kim;Yeon-Ji Kim;Yun-Mi Kang;Kyungho Kim
    • Herbal Formula Science
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    • v.32 no.2
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    • pp.121-128
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    • 2024
  • Objectives : This study aimed to investigate the protective effects of mixed extracts from Scutellaria baicalensis Georgi, Alisma orientale Juzepzuk, and Atractylodes japonica Koidzumi on interleukin (IL)-6-induced damage to tight junction (TJ) integrity in a Caco-2 cell model. Methods : We assessed the TJ integrity of Caco-2 monolayers by measuring the flux of FITC-labeled dextran and transepithelial electrical resistance (TEER). Additionally, we evaluated the expression of TJ proteins, such as ZO-1 and Occludin. Results : Treatment with IL-6 (50 ng/ml) increased TJ permeability and decreased TEER values of Caco-2 monolayers. Pretreatment with HTB (50-200 ㎍/ml) for 1 h significantly alleviated IL-6-induced TJ disruption, as evidenced by reduced TJ permeability and increased TEER values. Furthermore, HTB reversed the IL-6-induced inhibition of TJ protein expression, including ZO-1 and Occludin. Conclusions : These findings indicate that HTB protects barrier function by reversing the IL-6-induced decrease in TJ integrity and the suppression of TJ protein expression.

Gilteritinib Reduces FLT3 Expression in Acute Myeloid Leukemia Cells

  • Thi Lam Thai;Sun-Young Han
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.577-581
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    • 2024
  • Acute myeloid leukemia (AML) is a genetically diverse and challenging malignancy, with mutations in the FLT3 gene being particularly common and deleterious. Gilteritinib, a potent FLT3 inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory AML with FLT3 mutations. Although gilteritinib was developed based on its inhibitory activity against FLT3 kinase, it is important to understand the precise mechanisms of its antileukemic activity in managing drug resistance and discovering biomarkers. This study was designed to elucidate the effect of gilteritinib on the FLT3 expression level. The results showed that gilteritinib induced a dose-dependent decrease in both FLT3 phosphorylation and expression. This reduction was particularly pronounced after 48 h of treatment. The decrease in FLT3 expression was found to be independent of changes in FLT3 mRNA transcription, suggesting post-transcriptional regulatory mechanisms. Further studies were performed in various AML cell lines and cells with both FLT3 wild-type and FLT3 mutant exhibited FLT3 reduction by gilteritinib treatment. In addition, other FLT3 inhibitors were evaluated for their ability to reduce FLT3 expression. Other FLT3 inhibitors, midostaurin, crenolanib, and quizartinib, also reduced FLT3 expression, consistent with the effect of gilteritinib. These findings hold great promise for optimizing gilteritinib treatment in AML patients. However, it is important to recognize that further research is warranted to gain a full understanding of these mechanisms and their clinical implications in the context of FLT3 reduction.