المؤلفون: Yu‐Chan Chang, Yi‐Fang Yang, Chien‐Hsiu Li, Ming‐Hsien Chan, Meng‐Lun Lu, Ming‐Huang Chen, Chi‐Long Chen, Michael Hsiao

المصدر: Journal of Extracellular Biology, Vol 3, Iss 2, Pp n/a-n/a (2024)

مصطلحات موضوعية: AGR2, colon cancer, epithelial‐mesenchymal transition, oxaliplatin resistance, RAB31, Cytology, QH573-671

الوصف: Abstract Epithelial‐mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G‐proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin‐resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta‐databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial‐type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal‐type markers SNAI1 and SNAI2 increased. Notably, RAB31‐induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31/AGR2 axis‐mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2768-2811Test

الوصول الحر: https://doaj.org/article/91bff575744145e79f660e623345075fTest

المؤلفون: Yi-Fang Yang, Xi-Rui Yan, Rui-Xin Wu, Ning Li, Min Chu, Yang Dong, Shu-Ping Fu, Jian-Rong Shi, Qing Liu

المصدر: Pharmaceutical Biology, Vol 60, Iss 1, Pp 1478-1490 (2022)

مصطلحات موضوعية: Molecular docking, molecular dynamics simulation, HEI-OC1, apoptosis, mitochondrial membrane potential, AKT1, Therapeutics. Pharmacology, RM1-950

الوصف: Context Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly.Objective To explore the mechanism of YQCM decoction in the treatment of ARHL.Materials and methods The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 μM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot.Results The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 μg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels.Conclusions Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1388-0209Test; https://doaj.org/toc/1744-5116Test

الوصول الحر: https://doaj.org/article/26a6b2f2836b4e1e8675f1114146c01dTest

المؤلفون: Yi-Fang Yang, Kuo-Wang Tsai, Peter Mu-Hsin Chang, Yu-Chan Chang

المصدر: Frontiers in Oncology, Vol 13 (2023)

مصطلحات موضوعية: metabolism, omics, tumor microenvironment, fatty acid, cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2023.1159545/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/bef9d1b1b2c74e1ba341e76d6b684aa8Test

المؤلفون: Yi-Fang Yang, Chuang-Ming Wang, I.-Hsin Hsiao, Yi-Liang Liu, Wen-Hao Lin, Chih-Li Lin, Hui-Chih Hung, Guang-Yaw Liu

المصدر: Cellular & Molecular Biology Letters, Vol 27, Iss 1, Pp 1-25 (2022)

مصطلحات موضوعية: Peptidylarginine deiminase 2, Cytokines, Activated T cell-autonomous death, Endoplasmic reticulum stress, Autophagy, Cytology, QH573-671

الوصف: Abstract Peptididylarginine deiminase type 2 (PADI2) catalyzes the conversion of arginine residues to citrulline residues on proteins. We demonstrate that PADI2 induces T cell activation and investigate how PADI2 promotes activated T cell autonomous death (ACAD). In activated Jurkat T cells, overexpression of PADI2 significantly increases citrullinated proteins and induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling, ultimately resulting in the expression of autophagy-related proteins and autophagy. PADI2 promoted autophagy and resulted in the early degradation of p62 and the light chain 3B (LC3B)-II accumulation. In Jurkat T cells, silencing the autophagy-related gene (Atg) 12 protein inhibits PADI2-mediated autophagy and promotes ER stress and apoptosis, whereas overexpression of Atg12 decreased ER stress and prolonged autophagy to promote cell survival. Additionally, PADI2 regulates T cell activation and the production of Th17 cytokines in Jurkat T cells (interleukins 6, IL-17A, IL-17F, IL-21, and IL-22). In Jurkat T cells, silencing IL-6 promotes autophagy mediated by PADI2 and inhibits PADI2-induced apoptosis, whereas silencing Beclin-1 increases the activation and survival of Th17-like T cells while decreasing autophagy and apoptosis. PADI2 silencing alleviates ER stress caused by PADI2 and decreases cytokine expression associated with Th17-like T cell activation and ACAD. We propose that PADI2 was involved in Th17 lymphocyte ACAD via a mechanism involving ER stress and autophagy that was tightly regulated by PADI2-mediated citrullination. These findings suggest that inhibiting Th17 T cell activation and the development of severe autoimmune diseases may be possible through the use of novel antagonists that specifically target PADI2.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1425-8153Test; https://doaj.org/toc/1689-1392Test

الوصول الحر: https://doaj.org/article/802dbea7a5d24e36b93b82939b615eb4Test

المؤلفون: Yi-Chen Lee, Kuo-Wang Tsai, Jia-Bin Liao, Wei-Ting Kuo, Yu-Chan Chang, Yi-Fang Yang

المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-10 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Tight junction proteins 1–3 (TJP1–3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. However, the role of the TJP family in bladder cancer has not been adequately evaluated. In this study, we evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. We found that TJP1 was amplified in bladder cancer tissue and that the protein expression levels were significantly associated with age (p = 0.03), grade (p = 0.007), and stage (p = 0.011). We also examined the correlation between TJP1 and other high-frequency mutation genes using TIMER. TJP1 mRNA levels were positively correlated with TTN and RYR3 mRNA levels in bladder cancer tissue. Taken together, TJP1 expression is associated with poor clinical outcomes in patients with bladder cancer and can be a useful predictive biomarker for bladder cancer staging.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/a62538d7361942d5a10511c363979268Test

المؤلفون: CHING-YUAN HUANG, TZU-YU HOU, YI-FANG YANG, YU-HSUAN LIN

المصدر: In Vivo; Jul/Aug2024, Vol. 38 Issue 4, p1947-1956, 10p

مصطلحات موضوعية: VISUAL acuity, VISION disorders, SPHENOID sinus, ENDOSCOPIC surgery, MYCETOMA

مستخلص: Background/Aim: To investigate the treatment outcomes and determinants of prognosis in patients experiencing visual acuity (VA) deterioration due to inflammatory isolated sphenoid sinus disease (ISSD) who underwent endonasal endoscopic surgery (EES). Patients and Methods: Thirteen patients with 14 lesions treated with EES between March 2010 and April 2022 were included. Evaluation included improvements in VA using the logarithm of the minimum angle of resolution (LogMAR) scale, resolution rates of associated symptoms, and identification of factors predicting VA recovery. A literature review was conducted to assess the outcomes for ISSD-related VA impairments. Results: The most common etiology is mycetoma (n=5), followed by an equal representation of mucocele and sphenoiditis (n=4). The mean interval from symptom onset to intervention was 4.7 months, with an average follow-up duration of 14.4 months. Seven eyes exhibited preoperative VA of 2.1 LogMAR or worse, with diplopia/ptosis (n=8) and headache (n=5) being the predominant co-occurring symptoms. After surgery, all ancillary symptoms improved, with an overall VA recovery rate of 87.5% (improvement more than 0.2 logMAR units). Mucocele exhibited the best improvements, whereas sphenoiditis showed the least progress (p=0.021). Poor baseline VA (p=0.026) and combined diplopia/ptosis (p=0.029) were identified as negative prognostic factors for VA recovery. Conclusion: Our findings suggest a favorable prognosis for VA recovery following EES in patients with inflammatory ISSDs, with response variations based on disease entity. However, further research is needed to personalize therapeutic strategies for enhanced outcomes. [ABSTRACT FROM AUTHOR]

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المؤلفون: Hui-Hwa Tseng, You-Zuo Chen, Nan-Hua Chou, Yen-Chih Chen, Chao-Chuan Wu, Li-Feng Liu, Yi-Fang Yang, Chung-Yu Yeh, Mei-Lang Kung, Ya-Ting Tu, Kuo-Wang Tsai

المصدر: Molecular Therapy: Oncolytics, Vol 22, Iss , Pp 180-194 (2021)

مصطلحات موضوعية: metformin, lncRNA, Loc100506691, gastric cancer, miRNA, CHAC1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2372770521001170Test; https://doaj.org/toc/2372-7705Test

الوصول الحر: https://doaj.org/article/53ad4a5d90ed4dd893975cb56e04cfd3Test

المؤلفون: Yi Fang Yang, 楊宜芳

مرشدي الرسالة: J. S. Yu, 余兆松

الوصف: 100
Photodynamic therapy (PDT) is a minimally invasive therapeutic clinical treatment for some cancer and non-tumor disorders. This process requires a photosensitizer which can absorb light and produce reactive oxygen species to damage biomolecules in target cells. Photofrin is the most widely used photosensitizer. Our previous studies showed that different distribution of Photofrin in cells results in distinct cell death after PDT and Photofrin can selectively interact with some proteins. Using human epidermoid carcinoma A431 cells as model, we herein applied SILAC-based quantitative proteome approach to systemically analyze the relationship between the subcellular location of Photofrin and the Photofrin-PDT-mediated protein oxidization (on Met residues). In addition, we try to identify Photofrin-interacting proteins in A431 cells. Our data showed that when Photofrin mainly localized to plasma membrane (condition I), intracellular organelles (condition II) and whole cell (condition III), there were 116, 84 and 199 proteins quantified greater than mean+2SD Met-oxidized proteins, respectively. Further analysis revealed that (i) the percentage of highly oxidized membrane proteins is significantly higher in condition I (13.33%) than in condition II (3.03%) and III (0.76%); (ii) the percentage of highly oxidized Golgi proteins is drastically higher in condition II (18.18%) than in condition I (3.33%) and III (9.09%); and (iii) the percentage of highly oxidized mitochondrial proteins is largely higher in condition III (30.3%) than in condition I (4.44%) and II (15.66%). The results indicate that PDT with Photofrin targeted to distinct subcellular localizations can affect the redox proteome in a site-specific manner in living cells. Regarding the Photofrin-interacting proteins, we have identified 66 such candidates via in vitro pull down assay (using Photofrin-coupled beads) combined with MS analysis. Among those highly oxidized proteins detected post Photofrin-PDT, we select protein A and B for further study. Mapping the observed oxidized Met residues into the 3D structure of the two proteins showed that these oxidized Met residues mainly distribute on the surface of the protein. We also provided evidence to show that Photofrin-PDT can directly inhibit the activity of protein A in vitro. Collectively, our data demonstrate for the first time that the relationship between protein Met oxidation and PDT with site-specific location of Photofrin in living cells. Our results also unravel many potential Photofrin-interacting proteins that deserve further investigation.

وصف الملف: 161

الإتاحة: http://ndltd.ncl.edu.tw/handle/52121421771566331555Test

المؤلفون: Yi-Fang Yang, Chien-Hsiu Li, Huei-Yu Cai, Bo-Syuan Lin, Cheorl-Ho Kim, Yu-Chan Chang

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 24, p 15831 (2022)

مصطلحات موضوعية: cancer metabolism, metabolic reprogramming, molecular imaging, cellular uptake, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/24/15831Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/7292f4a8eab44e6bac9833095f01c920Test

المؤلفون: Tsung-Ching Lai, Chih-Yeu Fang, Yi-Hua Jan, Hsiao-Ling Hsieh, Yi-Fang Yang, Chun-Yu Liu, Peter Mu-Hsin Chang, Michael Hsiao

المصدر: Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-14 (2020)

مصطلحات موضوعية: TAOK3, NF-κB, Breast cancer, Anti-microtubule drug resistance, Medicine, Cytology, QH573-671

الوصف: Abstract Background Chemotherapy is currently one of the most effective treatments for advanced breast cancer. Anti-microtubule agents, including taxanes, eribulin and vinca-alkaloids are one of the primary major anti-breast cancer chemotherapies; however, chemoresistance remains a problem that is difficult to solve. We aimed to discover novel candidate protein targets to combat chemoresistance in breast cancer. Methods A lentiviral shRNA-based high-throughput screening platform was designed and developed to screen the global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The phenotypes were confirmed with alternative expression in vitro and in vivo. Molecular mechanisms were investigated using global phosphoprotein arrays and expression microarrays. Global microarray analysis was performed to determine TAOK3 and genes that induced paclitaxel resistance. Results A serine/threonine kinase gene, TAOK3, was identified from 724 screened kinase genes. TAOK3 shRNA exhibited the most significant reduction in IC50 values in response to paclitaxel treatment. Ectopic downregulation of TAOK3 resulted in paclitaxel-resistant breast cancer cells sensitize to paclitaxel treatment in vitro and in vivo. The expression of TAOK3 also was correlated to sensitivity to two other anti-microtubule drugs, eribulin and vinorelbine. Our TAOK3-modulated microarray analysis indicated that NF-κB signaling played a major upstream regulation role. TAOK3 inhibitor, CP43, and shRNA of NF-κB both reduced the paclitaxel resistance in TAOK3 overexpressed cells. In clinical microarray databases, high TAOK3 expressed breast cancer patients had poorer prognoses after adjuvant chemotherapy. Conclusions Here we identified TAOK3 overexpression increased anti-microtubule drug resistance through upregulation of NF-κB signaling, which reduced cell death in breast cancer. Therefore, inhibition of the interaction between TAOK3 and NF-κB signaling may have therapeutic implications for breast cancer patients treated with anti-microtubule drugs. Video abstract

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12964-020-00600-2Test; https://doaj.org/toc/1478-811XTest

الوصول الحر: https://doaj.org/article/1683d5ee42944104aa461294edd4784fTest