المؤلفون: Hsin-Yi Chen, Shu-Jou Chan, Xinxin Liu, An-Chi Wei, Ru-In Jian, Kuan-Wei Huang, Yaw-Dong Lang, Jou-Ho Shih, Chun-Chieh Liao, Chiu-Lin Luan, Yu-Tung Kao, Shang-Yin Chiang, Pei-Wen Hsiao, Yuh-Shan Jou, Yunching Chen, Ruey-Hwa Chen

المصدر: Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-24 (2022)

مصطلحات موضوعية: LncRNA, TGF-β, Smad, c-Myc, EMT, Metastasis, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Metastasis and chemoresistance are major culprits of cancer mortality, but factors contributing to these processes are incompletely understood. Methods Bioinformatics methods were used to identify the relations of Smyca expression to clinicopathological features of human cancers. RNA-sequencing analysis was used to reveal Smyca-regulated transcriptome. RNA pull-down and RNA immunoprecipitation were used to examine the binding of Smyca to Smad3/4 and c-Myc/Max. Chromatin immunoprecipitation and chromatin isolation by RNA purification were used to determine the binding of transcription factors and Smyca to various gene loci, respectively. Real-time RT-PCR and luciferase assay were used to examine gene expression levels and promoter activities, respectively. Xenograft mouse models were performed to evaluate the effects of Smyca on metastasis and chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target Smyca in vivo. Results We identify lncRNA Smyca for its association with poor prognosis of many cancer types. Smyca potentiates metabolic reprogramming, migration, invasion, cancer stemness, metastasis and chemoresistance. Mechanistically, Smyca enhances TGF-β/Smad signaling by acting as a scaffold for promoting Smad3/Smad4 association and further serves as a Smad target to amplify/prolong TGF-β signaling. Additionally, Smyca potentiates c-Myc-mediated transcription by enhancing the recruitment of c-Myc/Max complex to a set of target promoters and c-Myc binding to TRRAP. Through potentiating TGF-β and c-Myc pathways, Smyca synergizes the Warburg effect elicited by both pathways but evades the anti-proliferative effect of TGF-β. Targeting Smyca prevents metastasis and overcomes chemoresistance. Conclusions This study uncovers a lncRNA that coordinates tumor-relevant pathways to orchestra a pro-tumor program and establishes the clinical values of Smyca in cancer prognosis and therapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-8722Test

الوصول الحر: https://doaj.org/article/a8ced82434e347259ea6f0bb87743738Test

المؤلفون: Cheng-Ru Wu, Yi-Da Huang, Yong-Huei Hong, Ya-Hsin Liu, Manmath Narwane, Yu-Hsiang Chang, Trinh Kieu Dinh, Hsin-Tzu Hsieh, Yi-Jen Hseuh, Ping-Ching Wu, Chih-Wen Pao, Ting-Shan Chan, I-Jui Hsu, Yunching Chen, Hung-Chi Chen, Ting-Yu Chin, Tsai-Te Lu

المصدر: JACS Au, Vol 1, Iss 7, Pp 998-1013 (2021)

مصطلحات موضوعية: Chemistry, QD1-999

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2691-3704Test

الوصول الحر: https://doaj.org/article/ddb4c49c3a7a4208ad4b7b0866cf72c1Test

المؤلفون: Rui-Lin Huang, Yi-Chen Fu, Yung-Chih Wang, Chitsung Hong, Wei-Chieh Yang, I-Jen Wang, Jun-Ren Sun, Yunching Chen, Ching-Fen Shen, Chao-Min Cheng

المصدر: Vaccines, Vol 10, Iss 2, p 271 (2022)

مصطلحات موضوعية: coronavirus disease 2019 (COVID-19), lateral flow immunoassay, neutralizing antibody, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), AstraZeneca, Medicine

الوصف: As of August 2021, there have been over 200 million confirmed case of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus and more than 4 million COVID-19-related deaths globally. Although real-time polymerase chain reaction is considered to be the primary method of detection for SARS-CoV-2 infection, the use of serological assays for detecting COVID-19 antibodies has been shown to be effective in aiding with diagnosis, particularly in patients who have recovered from the disease and those in later stages of infection. Since it has a high detection rate and few limitations compared to conventional enzyme-linked immunosorbent assay protocols, we used a lateral flow immunoassay as our diagnostic tool of choice. Since lateral flow immunoassay results interpreted by the naked eye may lead to erroneous diagnoses, we developed an innovative, portable device with the capacity to capture a high-resolution reflectance spectrum as a means of promoting diagnostic accuracy. We combined this spectrum-based device with commercial lateral flow immunoassays to detect the neutralizing antibody in serum samples collected from 30 COVID-19-infected patients (26 mild cases and four severe cases). The results of our approach, lateral flow immunoassays coupled with a spectrum-based reader, demonstrated a 0.989 area under the ROC curve, 100% sensitivity, 95.7% positive predictive value, 87.5% specificity, and 100% negative predictive value. As a result, our approach exhibited great value for neutralizing antibody detection. In addition to the above tests, we also tested plasma samples from 16 AstraZeneca-vaccinated (ChAdOx1nCoV-19) patients and compared our approach and enzyme-linked immunosorbent assay results to see whether our approach could be applied to vaccinated patients. The results showed a high correlation between these two approaches, indicating that the lateral flow immunoassay coupled with a spectrum-based reader is a feasible approach for diagnosing the presence of a neutralizing antibody in both COVID-19-infected and vaccinated patients.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-393X/10/2/271Test; https://doaj.org/toc/2076-393XTest

الوصول الحر: https://doaj.org/article/e7145dca430d42918e212b33add5db1fTest

المؤلفون: Anthony Yan‐Tang Wu, Yun‐Chieh Sung, Yen‐Ju Chen, Steven Ting‐Yu Chou, Vanessa Guo, Jasper Che‐Yung Chien, John Jun‐Sheng Ko, Alan Ling Yang, Hsi‐Chien Huang, Ju‐Chen Chuang, Syuan Wu, Meng‐Ru Ho, Maria Ericsson, Wan‐Wan Lin, Chantal Hoi Yin Cheung, Hsueh‐Fen Juan, Koji Ueda, Yunching Chen, Charles Pin‐Kuang Lai

المصدر: Advanced Science, Vol 7, Iss 19, Pp n/a-n/a (2020)

مصطلحات موضوعية: biodistribution, bioluminescence resonance energy transfer, exomeres, exosomes, extracellular vesicles, microvesicles, Science

الوصف: Abstract Extracellular particles (EPs) including extracellular vesicles (EVs) and exomeres play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. Therefore, a bioluminescence resonance energy transfer (BRET)‐based reporter, PalmGRET, is created to enable pan‐EP labeling ranging from exomeres (200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking, and quantification of the EPs from whole animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET, and fluorescence. Using PalmGRET, it is shown that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. It is further demonstrated that gene knockdown of lung‐tropic membrane proteins, solute carrier organic anion transporter family member 2A1, alanine aminopeptidase/Cd13, and chloride intracellular channel 1 decreases HCC‐EP distribution to the lungs and yields distinct biodistribution profiles. It is anticipated that EP‐specific imaging, quantitative assays, and detailed in vivo characterization are a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2198-3844Test

الوصول الحر: https://doaj.org/article/507974afa10f4003ae2bcbf96bda1580Test

المؤلفون: Pei-Ru Jin (11478023), Yen-Nhi Ngoc Ta (11478026), I-Ting Chen (3084588), Yan-Ning Yu (11478029), Hsin Tzu Hsieh (11478032), Van-Anh Thi Nguyen (4232779), Shang-Ying Hsieh (11478035), Tiffaney Hsia (11478038), Hao Liu (12832), Chan-Wei Hsu (4692385), Jeng-Liang Han (2073691), Yunching Chen (2371885)

مصطلحات موضوعية: Biochemistry, Molecular Biology, Pharmacology, Biotechnology, Cancer, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, prevented distant metastasis, mediates tumor progression, hypoxic tumor microenvironment, exhibited potential cytotoxicity, desirable safety profile, >- glycolic acid, combines autophagy modulation, also blocked autophagy, promising therapeutic option, nanoscale drug carriers, c1 , inhibited autophagy, therapeutic stress, co <, various cancers, systemic administration, single molecule, s6k pathway, pegylated lipid, metabolic stress, inspired urea, induced apoptosis

الوصف: Autophagy is upregulated in response to metabolic stress, a hypoxic tumor microenvironment, and therapeutic stress in various cancers and mediates tumor progression and resistance to cancer therapy. Herein, we identified a cinchona alkaloid derivative containing urea ( C1 ), which exhibited potential cytotoxicity and inhibited autophagy in hepatocellular carcinoma (HCC) cells. We showed that C1 not only induced apoptosis but also blocked autophagy in HCC cells, as indicated by the increased expression of LC3-II and p62, inhibition of autophagosome–lysosome fusion, and suppression of the Akt/mTOR/S6k pathway in the HCC cells. Finally, to improve its solubility and efficacy, we encapsulated C1 into PEGylated lipid-poly­(lactic- co -glycolic acid) (PLGA) nanoscale drug carriers. Systemic administration of nanoscale C1 significantly suppressed primary tumor growth and prevented distant metastasis while maintaining a desirable safety profile. Our findings demonstrate that C1 combines autophagy modulation and apoptosis induction in a single molecule, making it a promising therapeutic option for HCC.

العلاقة: https://figshare.com/articles/journal_contribution/Cinchona_Alkaloid-Inspired_Urea-Containing_Autophagy_Inhibitor_Shows_Single-Agent_Anticancer_Efficacy/16677626Test

الإتاحة: https://doi.org/10.1021/acs.jmedchem.1c01036.s001Test

المؤلفون: Venkanagouda S. Goudar (11547067), Manohar Prasad Koduri (11547070), Yen-Nhi Ngoc Ta (11478026), Yunching Chen (2371885), Li-An Chu (11547073), Long-Sheng Lu (443330), Fan-Gang Tseng (1660861)

مصطلحات موضوعية: Medicine, Cell Biology, Molecular Biology, Pharmacology, Biotechnology, Developmental Biology, Cancer, Plant Biology, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, poly ­( dimethylsiloxane, paracrine signaling molecules, individual spheroid growth, cancer drug resistance, targeted collagen homeostasis, intratumor collagen quality, damaged collagen structure, 2 ± 3, 9 ± 1, 8 ± 9, significantly increased stiffness, cancer cells localized, intraspheroidal collagen network, tumor organoid formation, 2 μm ), nih3t3 cells promoted, culture array platform, colon cancer ctss, 4 ± 1

الوصف: Three-dimensional (3D) spheroid culture provides opportunities to model tumor growth closer to its natural context. The collagen network in the extracellular matrix supports autonomic tumor cell proliferation, but its presence and role in tumor spheroids remain unclear. In this research, we developed an in vitro 3D co-culture model in a microwell 3D (μ-well 3D) cell-culture array platform to mimic the tumor microenvironment (TME). The modular setup is used to characterize the paracrine signaling molecules and the role of the intraspheroidal collagen network in cancer drug resistance. The μ-well 3D platform is made up of poly­(dimethylsiloxane) that contains 630 round wells for individual spheroid growth. Inside each well, the growth surface measured 500 μm in diameter and was functionalized with the amphiphilic copolymer. HCT-8 colon cancer cells and/or NIH3T3 fibroblasts were seeded in each well and incubated for up to 9 days for TME studies. It was observed that NIH3T3 cells promoted the kinetics of tumor organoid formation. The two types of cells self-organized into core–shell chimeric tumor spheroids (CTSs) with fibroblasts confined to the shell and cancer cells localized to the core. Confocal microscopy analysis indicated that a type-I collagen network developed inside the CTS along with increased TGF-β1 and α-SMA proteins. The results were correlated with a significantly increased stiffness in 3D co-cultured CTS up to 52 kPa as compared to two-dimensional (2D) co-culture. CTS was more resistant to 5-FU (IC 50 = 14.0 ± 3.9 μM) and Regorafenib (IC 50 = 49.8 ± 9.9 μM) compared to cells grown under the 2D condition 5-FU (IC 50 = 12.2 ± 3.7 μM) and Regorafenib (IC 50 = 5.9 ± 1.9 μM). Targeted collagen homeostasis with Sclerotiorin led to damaged collagen structure and disrupted the type-I collagen network within CTS. Such a treatment significantly sensitized collagen-supported CTS to 5-FU (IC 50 = 4.4 ± 1.3 μM) and to Regorafenib (IC 50 = 0.5 ± 0.2 μM). In summary, the efficient formation of colon cancer CTSs ...

العلاقة: https://figshare.com/articles/journal_contribution/Impact_of_a_Desmoplastic_Tumor_Microenvironment_for_Colon_Cancer_Drug_Sensitivity_A_Study_with_3D_Chimeric_Tumor_Spheroids/16783891Test

الإتاحة: https://doi.org/10.1021/acsami.1c18249.s001Test

المؤلفون: Cheng-Ru Wu (10933241), Yi-Da Huang (9240040), Yong-Huei Hong (10933244), Ya-Hsin Liu (114610), Manmath Narwane (10933247), Yu-Hsiang Chang (644091), Trinh Kieu Dinh (9428020), Hsin-Tzu Hsieh (10933250), Yi-Jen Hseuh (10933253), Ping-Ching Wu (2263201), Chih-Wen Pao (1573852), Ting-Shan Chan (1438513), I-Jui Hsu (1733785), Yunching Chen (2371885), Hung-Chi Chen (165980), Ting-Yu Chin (10933256), Tsai-Te Lu (1975147)

مصطلحات موضوعية: Biochemistry, Medicine, Cell Biology, Neuroscience, Physiology, Pharmacology, Mental Health, Chemical Sciences not elsewhere classified, OH, mucin-bound dinitrosyl iron, 16 weeks activates, Hippocampal Neurogenesis Nitric oxide, CH, Biomimetic Dinitrosyl Iron Complex, dinitrosyl iron unit, DNIC, serum albumin, DNIU

الوصف: Nitric oxide (NO), a pro-neurogenic and antineuroinflammatory gasotransmitter, features the potential to develop a translational medicine against neuropathological conditions. Despite the extensive efforts made on the controlled delivery of therapeutic NO, however, an orally active NO prodrug for a treatment of chronic neuropathy was not reported yet. Inspired by the natural dinitrosyl iron unit (DNIU) [Fe­(NO) 2 ], in this study, a reversible and dynamic interaction between the biomimetic [(NO) 2 Fe­(μ-SCH 2 CH 2 OH) 2 Fe­(NO) 2 ] ( DNIC-1 ) and serum albumin (or gastrointestinal mucin) was explored to discover endogenous proteins as a vehicle for an oral delivery of NO to the brain after an oral administration of DNIC-1 . On the basis of the in vitro and in vivo study, a rapid binding of DNIC-1 toward gastrointestinal mucin yielding the mucin-bound dinitrosyl iron complex (DNIC) discovers the mucoadhesive nature of DNIC-1 . A reversible interconversion between mucin-bound DNIC and DNIC-1 facilitates the mucus-penetrating migration of DNIC-1 shielded in the gastrointestinal tract of the stomach and small intestine. Moreover, the NO-release reactivity of DNIC-1 induces the transient opening of the cellular tight junction and enhances its paracellular permeability across the intestinal epithelial barrier. During circulation in the bloodstream, a stoichiometric binding of DNIC-1 to the serum albumin, as another endogenous protein vehicle, stabilizes the DNIU [Fe­(NO) 2 ] for a subsequent transfer into the brain. With aging mice under a Western diet as a disease model for metabolic syndrome and cognitive impairment, an oral administration of DNIC-1 in a daily manner for 16 weeks activates the hippocampal neurogenesis and ameliorates the impaired cognitive ability. Taken together, these findings disclose the synergy between biomimetic DNIC-1 and endogenous protein vehicles for an oral delivery of therapeutic NO to the brain against chronic neuropathy.

العلاقة: https://figshare.com/articles/journal_contribution/Endogenous_Conjugation_of_Biomimetic_Dinitrosyl_Iron_Complex_with_Protein_Vehicles_for_Oral_Delivery_of_Nitric_Oxide_to_Brain_and_Activation_of_Hippocampal_Neurogenesis/14743856Test

الإتاحة: https://doi.org/10.1021/jacsau.1c00160.s001Test

المؤلفون: Hsi-Chien Huang, Yun-Chieh Sung, Chung-Pin Li, Dehui Wan, Po-Han Chao, Yu-Ting Tseng, Bo-Wen Liao, Hui-Teng Cheng, Fu-Fei Hsu, Chieh-Cheng Huang, Yi-Ting Chen, Yu-Hui Liao, Hsin Tzu Hsieh, Yu-Chuan Shih, I-Ju Liu, Han-Chung Wu, Tsai-Te Lu, Jane Wang, Yunching Chen

المصدر: Gut; Sep2022, Vol. 71 Issue 9, p1843-1855, 13p

مصطلحات موضوعية: NITRIC oxide, PANCREATIC tumors, TRAIL protein, OLIGOPEPTIDES, KUPFFER cells, TUMORS

المؤلفون: Pei-Ru Jin, Yen-Nhi Ngoc Ta, I-Ting Chen, Yan-Ning Yu, Hsin Tzu Hsieh, Van-Anh Thi Nguyen, Shang-Ying Hsieh, Hsia, Tiffaney, Hao Liu, Chan-Wei Hsu, Jeng-Liang Han, Yunching Chen

المصدر: Journal of Medicinal Chemistry; 10/14/2021, Vol. 64 Issue 19, p14513-14525, 13p

المؤلفون: Jen-Shin Song, Chih-Chun Chang, Chien-Huang Wu, Trinh Kieu Dinh, Jiing-Jyh Jan, Kuan-Wei Huang, Ming-Chen Chou, Ting-Yun Shiue, Kai-Chia Yeh, Yi-Yu Ke, Teng-Kuang Yeh, Yen-Nhi Ngoc Ta, Chia-Jui Lee, Jing-Kai Huang, Yun-Chieh Sung, Kak-Shan Shia, Yunching Chen

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 3/30/2021, Vol. 118 Issue 13, p1-11, 11p

مصطلحات موضوعية: HEPATOCELLULAR carcinoma, CXCR4 receptors, CYTOTOXIC T cells, CHEMOKINE receptors, CELL migration, CURCUMIN, COMMERCIAL products

مستخلص: The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly. [ABSTRACT FROM AUTHOR]

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