• Title/Summary/Keyword: alternative pathways

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Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy

  • Jin, Hyung-seung;Park, Yoon
    • BMB Reports
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    • v.54 no.1
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    • pp.2-11
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    • 2021
  • Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

  • Park, Deokbae;Lee, Jung-Hee;Yoon, Sang-Pil
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.5
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    • pp.377-387
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    • 2022
  • Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

Biological Control of Oomycete Soilborne Diseases Caused by Phytophthora capsici, Phytophthora infestans, and Phytophthora nicotianae in Solanaceous Crops

  • Elena Volynchikova;Ki Deok Kim
    • Mycobiology
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    • v.50 no.5
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    • pp.269-293
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    • 2022
  • Oomycete pathogens that belong to the genus Phytophthora cause devastating diseases in solanaceous crops such as pepper, potato, and tobacco, resulting in crop production losses worldwide. Although the application of fungicides efficiently controls these diseases, it has been shown to trigger negative side effects such as environmental pollution, phytotoxicity, and fungicide resistance in plant pathogens. Therefore, biological control of Phytophthora-induced diseases was proposed as an environmentally sound alternative to conventional chemical control. In this review, progress on biological control of the soilborne oomycete plant pathogens, Phytophthora capsici, Phytophthora infestans, and Phytophthora nicotianae, infecting pepper, potato, and tobacco is described. Bacterial (e.g., Acinetobacter, Bacillus, Chryseobacterium, Paenibacillus, Pseudomonas, and Streptomyces) and fungal (e.g., Trichoderma and arbuscular mycorrhizal fungi) agents, and yeasts (e.g., Aureobasidium, Curvibasidium, and Metschnikowia) have been reported as successful biocontrol agents of Phytophthora pathogens. These microorganisms antagonize Phytophthora spp. via antimicrobial compounds with inhibitory activities against mycelial growth, sporulation, and zoospore germination. They also trigger plant immunity-inducing systemic resistance via several pathways, resulting in enhanced defense responses in their hosts. Along with plant protection, some of the microorganisms promote plant growth, thereby enhancing their beneficial relations with host plants. Although the beneficial effects of the biocontrol microorganisms are acceptable, single applications of antagonistic microorganisms tend to lack consistent efficacy compared with chemical analogues. Therefore, strategies to improve the biocontrol performance of these prominent antagonists are also discussed in this review.

The Cone (Pinus densiflora) Induced Apoptosis and Autophagy in Hepatic Stellate Cells

  • Tae-Won Jang;Da-Yoon Lee;So-Yeon Han;Hye-Jeong Park;Seo-Yoon Park;Jun-Hwan Jeong;Yoon-Jae Kwon;Jae-Ho Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2022.09a
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    • pp.106-106
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    • 2022
  • The cone of Red Pine (Pinus densiflora), which has been used as a drug in traditional medicine. Its ethyl acetate fraction was reported to exert antioxidant, anti-melanogenesis, and anti-inflammation activites. Apoptosis of hepatic stellate cells (LX-2) is regarding as a potential strategy for alleviation of hepatic fibrosis. We conducted to investigated whether the treatment of cone has a potential to control of some factors related in apoptosis and autophagy in cell signaling pathways. We suggest that the cone induced apoptosis through confirming the expression levels of genes (cPARP, Bcl-XL, Bax, p53, and caspase-3) in LX-2 cells. Also, the cone may regulate autophagy (LC3, p62, Beclin-1, and ATG12). Remarkably, the treatment of cone may affect to formation of autophagosomes in the immunofluorescence image in live cells. These findings suggest that the ethyl acetate fraction from the cone of Red Pine (P. densiflora) may have potential as an alternative therapeutic agent for the alleviation and prevention of liver fibrosis.

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Visualization of University Curriculum for Multidisciplinary Learning: A Case Study of Yonsei University, South Korea

  • Geonsik Yu;Sunju Park
    • Journal of Information Science Theory and Practice
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    • v.12 no.1
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    • pp.77-86
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    • 2024
  • As the significance of knowledge convergence continues to grow, universities are making efforts to develop methods that promote multidisciplinary learning. To address this educational challenge, our paper applies network theory and text mining techniques to analyze university curricula and introduces a graphical syllabus rendering method. Visualizing the course curriculum provides a macro and structured perspective for individuals seeking alternative educational pathways within the existing system. By visualizing the relationships among courses, students can explore different combinations of courses with comprehensive search support. To illustrate our approach, we conduct a detailed demonstration using the syllabus database of Yonsei University. Through the application of our methods, we create visual course networks that reveal the underlying structure of the university curriculum. Our results yield insights into the interconnectedness of courses across various academic majors at Yonsei University. We present both macro visualizations, covering 18 academic majors, and visualizations for a few selected majors. Our analysis using Yonsei University's database not only showcases the value of our methodology but also serves as a practical example of how our approach can facilitate multidisciplinary learning.

Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives

  • Fazila Sirajudeen;Lara J. Bou Malhab;Yasser Bustanji;Moyad Shahwan;Karem H. Alzoubi;Mohammad H. Semreen;Jalal Taneera;Waseem El-Huneidi;Eman Abu-Gharbieh
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.38-55
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    • 2024
  • Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome

  • Yu-Rim Chae;Yu Ra Lee;Young-Soo Kim;Ho-Young Park
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.747-756
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    • 2024
  • Chronic gut inflammation promotes the development of metabolic diseases such as obesity. There is growing evidence which suggests that dysbiosis in gut microbiota and metabolites disrupt the integrity of the intestinal barrier and significantly impact the level of inflammation in various tissues, including the liver and adipose tissues. Moreover, dietary sources are connected to the development of leaky gut syndrome through their interaction with the gut microbiota. This review examines the effects of these factors on intestinal microorganisms and the communication pathways between the gut-liver and gut-brain axis. The consumption of diets rich in fats and carbohydrates has been found to weaken the adherence of tight junction proteins in the gastrointestinal tract. Consequently, this allows endotoxins, such as lipopolysaccharides produced by detrimental bacteria, to permeate through portal veins, leading to metabolic endotoxemia and alterations in the gut microbiome composition with reduced production of metabolites, such as short-chain fatty acids. However, the precise correlation between gut microbiota and alternative sweeteners remains uncertain, necessitating further investigation. This study highlights the significance of exploring the impact of diet on gut microbiota and the underlying mechanisms in the gut-liver and gut-brain axis. Nevertheless, limited research on the gut-liver axis poses challenges in comprehending the intricate connections between diet and the gut-brain axis. This underscores the need for comprehensive studies to elucidate the intricate gut-brain mechanisms underlying intestinal health and microbiota.

The Effect of Oral Chamomile on Anxiety: A Systematic Review of Clinical Trials

  • Sogand Saadatmand;Foad Zohroudi;Hadith Tangestani
    • Clinical Nutrition Research
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    • v.13 no.2
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    • pp.139-147
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    • 2024
  • Anxiety disorder is a prevalent psychiatric issue that affects 4.05% of the global population. As complementary and alternative medicine gains popularity, many individuals with anxiety symptoms seek herbal remedies. This systematic review aims to explore the sedative efficacy of chamomile as an herbal medicine for anxiety treatment. Our search was conducted in PubMed, Google Scholar, and Scopus databases until August 2023. Among 389 papers found, after removing duplicates and irrelevant papers, 10 clinical trials investigating the effect of oral consumption of chamomile on anxiety were included. Two researchers independently completed all steps, including the screening process and data extraction. Out of the 10 articles selected, 9 studies have concluded that chamomile is effective in reducing anxiety. Even though, the exact mechanism of chamomile's anxiolytic action is not well understood, evidence suggests that its active compounds, including apigenin, may modulate the function of the hypothalamic-pituitary-adrenocortical axis by affecting neurotransmitter pathways. This systematic review showed that chamomile potentially has an anxiolytic effect. In addition, due to the side effects of drugs used to treat anxiety disorders, the use of chamomile seems to be effective and less dangerous.

Potential of fascaplysin and palauolide from Fascaplysinopsis cf reticulata to reduce the risk of bacterial infection in fish farming

  • Mai, Tepoerau;Toullec, Jordan;Wynsberge, Simon Van;Besson, Marc;Soulet, Stephanie;Petek, Sylvain;Aliotti, Emmanuelle;Ekins, Merrick;Hall, Kathryn;Erpenbeck, Dirk;Lecchini, David;Beniddir, Mehdi A.;Saulnier, Denis;Debitus, Cecile
    • Fisheries and Aquatic Sciences
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    • v.22 no.12
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    • pp.30.1-30.11
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    • 2019
  • Marine natural products isolated from the sponge Fascaplysinopsis cf reticulata, in French Polynesia, were investigated as an alternative to antibiotics to control pathogens in aquaculture. The overuse of antibiotics in aquaculture is largely considered to be an environmental pollution, because it supports the transfer of antibiotic resistance genes within the aquatic environment. One environmentally friendly alternative to antibiotics is the use of quorum sensing inhibitors (QSIs). Quorum sensing (QS) is a regulatory mechanism in bacteria which control virulence factors through the secretion of autoinducers (AIs), such as acyl-homoserine lactone (AHL) in gram-negative bacteria. Vibrio harveyi QS is controlled through three parallel pathways: HAI-1, AI-2, and CAI-1. Bioassay-guided purification of F. cf reticulata extract was conducted on two bacterial species, i.e., Tenacibaculum maritimum and V. harveyi for antibiotic and QS inhibition bioactivities. Toxicity bioassay of fractions was also evaluated on the freshwater fish Poecilia reticulata and the marine fish Acanthurus triostegus. Cyclohexanic and dichloromethane fractions of F. cf reticulata exhibited QS inhibition on V. harveyi and antibiotic bioactivities on V. harveyi and T. maritimum, respectively. Palauolide (1) and fascaplysin (2) were purified as major molecules from the cyclohexanic and dichloromethane fractions, respectively. Palauolide inhibited QS of V. harveyi through HAI-1 QS pathway at 50 ㎍ ml-1 (26 μM), while fascaplysin affected the bacterial growth of V. harveyi (50 ㎍ ml-1) and T. maritimum (0.25 ㎍). The toxicity of fascaplysin-enriched fraction (FEF) was evaluated and exhibited a toxic effect against fish at 50 ㎍ ml-1. This study demonstrated for the first time the QSI potential of palauolide (1). Future research may assess the toxicity of both the cyclohexanic fraction of the sponge and palauolide (1) on fish, to confirm their potential as alternative to antibiotics in fish farming.

Assessment of a rain barrel sharing network in Korea using storage-reliability-yield relationship (저류용량-신뢰도-수요량 관계를 이용한 레인배럴 공유 네트워크의 국내 성능 평가)

  • Kwon, Youjeong;Seo, Yongwon;Park, Chang Kun
    • Journal of Korea Water Resources Association
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    • v.53 no.11
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    • pp.961-971
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    • 2020
  • The Intergovernmental Panel on Climate Change (IPCC) reported that the amount of precipitation in South Korea would increase regardless of the reduction of Greenhouse Gas (GHG) emissions. Moreover, the temporal and spatial rainfall variation would also increase in the future. Due to the geographic allocation of Korea, more than 80% of the annual precipitation occurs in the wet season from early July to late September. It is expected that the average precipitation in this period will increase from the Representative Concentration Pathways (RCP) scenario projections. These predictions imply an increased variability of available water resources. Rainwater harvesting system is widely used as an alternative water resources today. This study introduces a RBSN (rain barrel sharing network) as an efficient way to utilize alternative water resources under the RCP scenarios. The concept of RBSN combines individual rainwater harvesting system to a sharing network, which make the whole system more reliable. This study evaluated a RBSN in South Korea composed of four users based on a storage-reliability-yield (SRY) relationship. The study area comprises all 17 provincal areas in South Korea. The result showed a huge benefit from a RBSN in Korea under the historical rainfall condition. Even in the climate change condition, the results showed that a RBSN is still beneficial but the changes in reliability are different depending on provinces in Korea. The results of this study shows that a RBSN is a very effective and alternative measure that can deal with the impacts of climate change in the near future.