160 results on '"Tang, D."'
Search Results
2. Complex dynamics in nonlinear small time-delayed optoelectronic oscillator and application in fast reservoir computing and pulse generation.
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Tang D, Liang E, Lu Q, Zhao H, and Li Z
- Abstract
We investigated a time-delayed optoelectronic oscillator (OEO) that displays a wide range of complex dynamic behavior under small time delay. The phase-space trajectory distributions in different dynamic regimes were compared which brings a new perspective on the underlying mechanism of the transition process. It was found that bifurcation is always possible no matter how small the time delay is even if the universal adiabatic approximation model is invalid. Hereby we proposed a versatile simple oscillator which has a potential capacity as memory carrier and high-dimensional state spatial mapping ability that brings 1000 times computing-efficiency improvements of reservoir computing over the large time delay one. Furthermore, we demonstrated a new approach for a tunable optoelectronic pulse generator (repetition rate at 0.2 MHz and 0.25 GHz) which depends critically on time-delayed input electrical pulse. The proposed oscillator is also a promising system for the applications of fast chaos-based communication., (© 2024. The Author(s).)
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- 2024
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3. Maternal linoleic acid-rich diet ameliorates bilirubin neurotoxicity in offspring mice.
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Yan D, Wu X, Chen X, Wang J, Ge F, Wu M, Wu J, Zhang N, Xiao M, Wu X, Xue Q, Li X, Chen J, Wang P, Tang D, Wang X, Chen X, and Liu J
- Abstract
Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring. We assessed histomorphological indices, including cerebellar Nissl staining, and Calbindin staining, and hippocampal hematoxylin and eosin staining. Furthermore, we observed the transmission of linoleic acid, enriched in sunflower seeds, to offspring through lactation. The oral administration of linoleic acid-rich sunflower seed oil by lactating mothers significantly prolonged the survival time of hyperbilirubinemic offspring mice. Mechanistically, linoleic acid counteracts the bilirubin-induced accumulation of ubiquitinated proteins and neuronal cell death by activating autophagy. Collectively, these findings elucidate the novel role of a maternal linoleic acid-supplemented diet in promoting child health., (© 2024. The Author(s).)
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- 2024
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4. Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.
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Hu Y, Tang W, Liu Y, Zhang N, Zhu X, Tang D, Zhang Y, Xu H, Zhuoma D, Yang T, Yu Z, Xu C, Xiao X, and Zhao X
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- Humans, Middle Aged, Male, Female, Aged, Adult, China epidemiology, Non-alcoholic Fatty Liver Disease physiopathology, Non-alcoholic Fatty Liver Disease epidemiology, Hypertension physiopathology, Blood Pressure physiology, Cardiovascular Diseases etiology, Cardiovascular Diseases physiopathology, Cardiovascular Diseases epidemiology
- Abstract
The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with β
FLI→SBP = 0.081, P < 0.001 versus βSBP→FLI = 0.020, P = 0.031; βFLI→DBP = 0.082, P < 0.001 versus βDBP→FLI = -0.006, P = 0.480 for CEMC, and βFLI→SBP = 0.057, P < 0.001 versus βSBP→FLI = -0.001, P = 0.727; βFLI→DBP = 0.061, P < 0.001, versus βDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)- Published
- 2024
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5. Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.
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Xia H, Zhang H, Ruan Z, Zhang H, Sun L, Chen H, Zhou Y, Zhang L, Bian D, Zhu X, Zhang J, Sun F, Yu H, Song N, Liu X, Zhu Y, Zhang H, He W, Chen J, Yang J, Chen G, Xie S, Tang D, Zhang X, Duan L, Zhao D, Li Q, Zhang P, and Jiang G
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- Humans, Female, Male, Middle Aged, Aged, Adult, Neoplasm Staging, Vascular Endothelial Growth Factor Receptor-2 genetics, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Programmed Cell Death 1 Receptor antagonists & inhibitors, Pyridines administration & dosage, Pyridines therapeutic use, Pyridines adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Neoadjuvant Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacology
- Abstract
This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC., (© 2024. The Author(s).)
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- 2024
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6. Divergence and convergence: a cross-generational study on local food consumption.
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Chen J, Xu A, Tang D, and Zheng M
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- Humans, Female, Male, Adult, Middle Aged, Surveys and Questionnaires, Choice Behavior, Young Adult, Feeding Behavior, Consumer Behavior, Food Preferences psychology
- Abstract
In the context of the expanding local food market, grasping the evolutionary trajectory of consumer purchasing behavior is crucial for understanding market dynamics. This study adopts a cross-generational perspective to delve into and elucidate the similarities and differences in local food consumption behaviors between Gen Z and Gen Y. Through the analysis of online survey data from 251 individuals of Gen Z and 319 of Gen Y and utilizing the Theory of Planned Behavior as a theoretical framework, and the study identifies eight key variables. The findings reveal that while Gen Z and Gen Y exhibit a range of common characteristics in their choice of local food,including attention to word of mouth, health consciousness, subjective norms, perceived behavioral control, and attitude.there is a significant divergence in their motivating factors for purchasing. Specifically, convenience is the primary driver for Gen Z when selecting local food; conversely, price is the decisive factor in the decision-making process of Gen Y. By unveiling these significant differences and similarities, the research offers significant understanding beneficial to the food sector, particularly in formulating market strategies targeted at different generations., (© 2024. The Author(s).)
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- 2024
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7. Evaluation of recoverable potential of deep coalbed methane in the Linxing Block, Eastern Margin of the Ordos Basin.
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Chen B, Li S, Tang D, Pu Y, and Zhong G
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The deep coalbed methane (CBM) resources are widely developed in the Linxing Block. However, the evaluation of CBM geological areas suitable for CBM exploitation remains unexplored, hindering further development. This research optimizes the key geological parameters that influence the development of deep CBM from the perspectives of resource and development conditions. The evaluation system for deep CBM recoverability has been established, and the multi-fuzzy evaluation method has been used to perform the quantitative evaluation of recoverability. The results indicate that the resource conditions of No.8 + 9 coal seam are superior to those of No.4 + 5 coal seam. Favorable resource conditions are predominantly concentrated in the northeast and specific southern portions of the research area. Favorable development conditions for both coal seams are mostly concentrated in the northeastern area. Based on the classification standard of recoverable favorable areas, the Level II area is crucial for the development of No.4 + 5 coal seam. This area is primarily distributed in the northeast of the research area., Both Level I and Level II areas for the No. 8 + 9 coal seam are situated in the northeast. The Level III area is earmarked for deep CBM production and shows potential for exploration. Further analysis reveals that the resource conditions in the favorable area are generally superior to the development conditions. These areas are classified as Class A, including categories such as I-A, II-A, and III-A, indicating relatively complex reservoir transformation., (© 2024. The Author(s).)
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- 2024
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8. Diverse functions of cytochrome c in cell death and disease.
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Zhou Z, Arroum T, Luo X, Kang R, Lee YJ, Tang D, Hüttemann M, and Song X
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- Humans, Animals, Cell Death, Apoptosis, Nucleophosmin, Mitochondria metabolism, Protein Processing, Post-Translational, Neoplasms metabolism, Neoplasms pathology, Cytochromes c metabolism
- Abstract
The redox-active protein cytochrome c is a highly positively charged hemoglobin that regulates cell fate decisions of life and death. Under normal physiological conditions, cytochrome c is localized in the mitochondrial intermembrane space, and its distribution can extend to the cytosol, nucleus, and extracellular space under specific pathological or stress-induced conditions. In the mitochondria, cytochrome c acts as an electron carrier in the electron transport chain, facilitating adenosine triphosphate synthesis, regulating cardiolipin peroxidation, and influencing reactive oxygen species dynamics. Upon cellular stress, it can be released into the cytosol, where it interacts with apoptotic peptidase activator 1 (APAF1) to form the apoptosome, initiating caspase-dependent apoptotic cell death. Additionally, following exposure to pro-apoptotic compounds, cytochrome c contributes to the survival of drug-tolerant persister cells. When translocated to the nucleus, it can induce chromatin condensation and disrupt nucleosome assembly. Upon its release into the extracellular space, cytochrome c may act as an immune mediator during cell death processes, highlighting its multifaceted role in cellular biology. In this review, we explore the diverse structural and functional aspects of cytochrome c in physiological and pathological responses. We summarize how posttranslational modifications of cytochrome c (e.g., phosphorylation, acetylation, tyrosine nitration, and oxidation), binding proteins (e.g., HIGD1A, CHCHD2, ITPR1, and nucleophosmin), and mutations (e.g., G41S, Y48H, and A51V) affect its function. Furthermore, we provide an overview of the latest advanced technologies utilized for detecting cytochrome c, along with potential therapeutic approaches related to this protein. These strategies hold tremendous promise in personalized health care, presenting opportunities for targeted interventions in a wide range of conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)
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- 2024
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9. Targeting paraptosis in cancer: opportunities and challenges.
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Chen F, Tang H, Cai X, Lin J, Xiang L, Kang R, Liu J, and Tang D
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- Humans, Paraptosis, Cell Death, Endoplasmic Reticulum metabolism, Cell Line, Tumor, Apoptosis, Neoplasms drug therapy, Neoplasms metabolism
- Abstract
Cell death can be classified into two primary categories: accidental cell death and regulated cell death (RCD). Within RCD, there are distinct apoptotic and non-apoptotic cell death pathways. Among the various forms of non-apoptotic RCD, paraptosis stands out as a unique mechanism characterized by distinct morphological changes within cells. These alterations encompass cytoplasmic vacuolization, organelle swelling, notably in the endoplasmic reticulum and mitochondria, and the absence of typical apoptotic features, such as cell shrinkage and DNA fragmentation. Biochemically, paraptosis distinguishes itself by its independence from caspases, which are conventionally associated with apoptotic death. This intriguing cell death pathway can be initiated by various cellular stressors, including oxidative stress, protein misfolding, and specific chemical compounds. Dysregulated paraptosis plays a pivotal role in several critical cancer-related processes, such as autophagic degradation, drug resistance, and angiogenesis. This review provides a comprehensive overview of recent advancements in our understanding of the mechanisms and regulation of paraptosis. Additionally, it delves into the potential of paraptosis-related compounds for targeted cancer treatment, with the aim of enhancing treatment efficacy while minimizing harm to healthy cells., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2024
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10. Effects of different colors of plastic-film mulching on soil temperature, yield, and metabolites in Platostoma palustre.
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Chen H, Huang S, Quan C, Chen Z, Xu M, Wei F, and Tang D
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- Temperature, Plastics, Agriculture methods, Soil chemistry, Trehalose
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Platostoma palustre is an annual herb and an important medicinal and edible plant in southern China. Plastic-film mulching is an effective agronomic practice in the cultivation system of P. palustre, of which black-film mulching is the most common. However, fewer researches have been focused on the use of other colors of plastic films in P. palustre cultivation. In this study, different colors (white, black, red, and green) of plastic film were adopted, and the effects of different colors of plastic film mulching on the soil temperature, yield, and metabolites of P. palustre were investigated. The results showed that the fresh weight of a single plant of the green film treatment was significantly higher than that of the white film treatment (n = top 28). Based on the results of three temperature measurements, the soil temperature was almost the highest in the red film treatment and lowest in the white film treatment. The metabolomic analysis revealed that a total of 103 differential metabolites were identified. Among these, the gluconic acid, deoxyribose, and N-Acetylmannosamine in the red film treatment presented the highest abundance compared with the other treatments, meanwhile, the abundances of the five monosaccharides in the red film treatment were significantly higher than those of the green film treatment. Moreover, the sucrose, trehalose, and D-(+)-trehalose in the green film treatment exhibited the highest abundance, and the abundances of eight different amino acids in the red film treatment were almost the lowest while those in the black film treatment were almost the highest. Further analysis of the membership function values indicated that the black and red film treatments might be more suitable for the cultivation and quality production of P. palustre in comparison with the other two treatments. This study will provide a theoretical basis for improving the efficient cultivation technology of P. palustre and forming a theoretical system of P. palustre film mulching cultivation., (© 2024. The Author(s).)
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- 2024
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11. The role of physical literacy and mindfulness on health-related quality of life among college students during the COVID-19 pandemic.
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Gao TY, Huang FH, Liu T, Sum RKW, De Liu J, Tang D, Cai DY, Jiang ZK, and Ma RS
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- Humans, Quality of Life, Pandemics, Literacy, Surveys and Questionnaires, Students, Mindfulness, COVID-19 epidemiology
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This study aimed to examine the role played by the physical literacy and mindfulness in the health-related quality of life (QoL) of college students. In early 2022, 24,236 college students from three universities in southern China were recruited in the study. R software and the lavvan package was utilized to build the structural equation model. The measurement model was composed of three latent factors (physical literacy, mindfulness, and quality of life) and 16 observed variables in total. The results of the measurement model indicated goodness fit with p > .05 in Chi-square result, and GFI = .92. In addition, the comparative fit index (.92), Tucker-Lewis index (.91), root-mean-square error of approximation (.07), and root of mean square residual (.11) were in accord with the cutoff model-fit criteria. The results confirm that physical literacy and mindfulness can play a significant and positive role in the structural equation model of quality of life. In addition, this study provides initial evidence that mindfulness and physical literacy could potentially buffer declines in student QoL during the COVID-19 pandemic. Moreover, this study is the first to develop a structural equation model of QoL with multiple indicators, making it a strong addition to existing research on QoL during a pandemic., (© 2024. The Author(s).)
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- 2024
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12. Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice.
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Zhou K, Yuan M, Sun J, Zhang F, Zong X, Li Z, Tang D, Zhou L, Zheng J, Xiao X, and Wu X
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- Mice, Animals, Mice, Inbred mdx, Sildenafil Citrate pharmacology, Sildenafil Citrate therapeutic use, Sildenafil Citrate metabolism, Immunoglobulin G genetics, Dependovirus genetics, Dependovirus metabolism, Genetic Vectors genetics, Muscle, Skeletal metabolism, Dystrophin genetics, Dystrophin metabolism, Muscular Dystrophy, Duchenne genetics, Muscular Dystrophy, Duchenne therapy
- Abstract
Adeno-associated virus (AAV) vectors have been successfully used to deliver genes for treating rare diseases. However, the systemic administration of high AAV vector doses triggers several adverse effects, including immune response, the asymptomatic elevation of liver transaminase levels, and complement activation. Thus, improving AAV transduction and reducing AAV dosage for treatment is necessary. Recently, we found that a phosphodiesterase-5 inhibitor significantly promoted AAV9 transduction in vitro by regulating the caveolae and macropinocytosis pathways. When AAV9-Gaussian luciferase (AAV9-Gluc) and AAV9-green fluorescent protein (AAV9-GFP) were injected intravenously into mice pre-treated with sildenafil, the expressions of Gluc in the plasma and GFP in muscle tissues significantly increased (P < 0.05). Sildenafil also improved Evans blue permeation in tissues. Additionally, we found that sildenafil promoted Treg proliferation, inhibited B-cell activation, and decreased anti-AAV9 IgG levels (P < 0.05). Furthermore, sildenafil significantly promoted Duchenne muscular dystrophy gene therapy efficacy using AAV9 in mdx mice; it increased micro-dystrophin gene expression, forelimb grip strength, and time spent on the rotarod test, decreased serum creatine kinase levels, and ameliorated histopathology by improving muscle cell morphology and reducing fibrosis (P < 0.05). These results show that sildenafil significantly improved AAV transduction, suppressed the levels of anti-AAV9 IgG, and enhanced the efficacy of gene therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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13. Correction: The KRAS-G12C inhibitor: activity and resistance.
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Liu J, Kang R, and Tang D
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- 2023
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14. LINC00665 activating Wnt3a/β-catenin signaling by bond with YBX1 promotes gastric cancer proliferation and metastasis.
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Wang J, Shen D, Li S, Li Q, Zuo Q, Lu J, Tang D, Feng Y, Yin P, Chen C, and Chen T
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- Animals, Humans, beta Catenin genetics, beta Catenin metabolism, Cell Line, Tumor, Wnt Signaling Pathway genetics, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Cell Movement genetics, Y-Box-Binding Protein 1 genetics, Stomach Neoplasms pathology, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
Long noncoding RNAs (lncRNAs) play a key role in human cancer development; nevertheless, the effect of lncRNA LINC00665 on the progression of gastric cancer (GC) still unclear. In this study, we found that LINC00665 expression is upregulated in GC than normal gastric mucosa tissues and higher LINC00665 expression is associated with a poor prognosis in GC patients. Downregulated LINC00665 inhibited GC cells proliferation, invasion, and migration in vitro. Pulmonary metastasis animal models showed that downregulated LINC00665 could reduce the lung metastasis of GC in vivo. Tumor organoids were generated from human malignant GC tissues, downregulated LINC00665 could inhibit the growth of the organoids of GC tissues. Mechanistically, downregulated LINC00665 could inhibit GC cells EMT. RNA pulldown, RIP, and RIP-seq studies found that LINC00665 can bind to the transcription factor YBX1 and form a positive feed-forward loop. The luciferase reporter and CHIP results showed that YBX1 could regulate the transcriptional activity of Wnt3a, and downregulation of LINC00665 could block the activation of Wnt/β-catenin signaling. In conclusion, our results identified a feedback loop between LINC00665 and YBX1 that activates Wnt/β-catenin signaling, and it may be a potential therapeutic approach to suppress GC progression., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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15. Retraction Note: Silencing of long non-coding RNA XIST represses gastric cancer progression through blocking NFκB pathway via inhibiting HNF4A-mediated transcription of EPHA1.
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Li P, Wang L, Li P, Hu F, Cao Y, Tang D, Ye G, Li H, and Wang D
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- 2023
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16. Retraction Note: Targeting KDM1B-dependent miR-215-AR-AGR2-axis promotes sensitivity to enzalutamide-resistant prostate cancer.
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Tang D, He J, Dai Y, Geng X, Leng Q, Jiang H, Sun R, and Xu S
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- 2023
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17. EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer.
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Wang Y, Liu Y, Wang C, Kang R, Tang D, and Liu J
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- Humans, Acetylation, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal genetics, E1A-Associated p300 Protein, Endoplasmic Reticulum Chaperone BiP, Ferroptosis, Pancreatic Neoplasms genetics
- Abstract
Ferroptosis is a form of regulated cell death characterized by oxidative injury-induced lipid peroxidation. However, the detailed protein post-translational modification regulatory mechanism of ferroptosis remains largely unknown. Here, we report that E1A binding protein P300 (EP300) acetyltransferase promotes ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells via the acetylation of heat shock protein family A (Hsp70) member 5 (HSPA5), also known as GRP78 or BIP) on the site of K353. Acetylated HSPA5 loses its ability to inhibit lipid peroxidation and subsequent ferroptotic cell death. Genetic or pharmacological inhibition of EP300-mediated HSPA5 acetylation on K353 increases PDAC cell resistance to ferroptosis. Moreover, histone deacetylase 6 (HDAC6) limits HSPA5 acetylation and subsequent ferroptosis. Collectively, these findings not only identify regulatory pathways for HSPA5 acetylation during ferroptosis, but also highlight promising strategies to increase ferroptosis sensitivity in PDAC cells., (© 2023. Springer Nature Limited.)
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- 2023
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18. Author Correction: Comparison of rabbit corneal changes during different preservation techniques using optisol-GS and airlift.
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Tang D, Uematsu M, Harada K, Mohamed YH, Kusano M, Inoue D, and Kitaoka T
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- 2023
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19. Reductive cell death: the other side of the coin.
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Zhang R, Kang R, and Tang D
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- Humans, Cell Death
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- 2023
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20. Association between obstructive sleep apnea symptoms and gout in US population, a cross-sectional study.
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Gu X, Tang D, Xuan Y, Shen Y, and Lu LQ
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- Humans, Male, Female, Middle Aged, Cross-Sectional Studies, Nutrition Surveys, Logistic Models, Risk Factors, Sleep Apnea, Obstructive complications, Sleep Apnea, Obstructive epidemiology, Sleep Apnea, Obstructive diagnosis, Gout complications, Gout epidemiology
- Abstract
The results of association between Obstructive Sleep Apnea (OSA) and gout are not consistent. Participants aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2015-2018 were included. Weighted univariable and multivariable logistic regressions were used to evaluate the association between OSA symptoms and gout. The subgroup and sensitivity analyses were also performed. Among the 15,947 participants in this study, the mean age was 47.8 years old, 48.87% of whom were male, 4891 had OSA symptoms, and 842 had gout. In multivariable logistic regression analyses, OSA symptoms were positively associated with gout in all models. The odds ratio (OR) was 1.315 and 95% confidence interval (CI) was 1.070-1.616 in fully adjusted model 4. In the subgroup analyses, we found a considerable interaction between OSA symptoms and gender with gout (P for interaction = 0.003). In the sensitivity analyses, the association between OSA symptoms and gout remained stable after adjustment for congestive heart failure and diuretics using. OSA symptoms were associated with an increased likelihood of gout. This association could especially be found in female participants., (© 2023. The Author(s).)
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- 2023
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21. Apoptotic cell death in disease-Current understanding of the NCCD 2023.
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Vitale I, Pietrocola F, Guilbaud E, Aaronson SA, Abrams JM, Adam D, Agostini M, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Aqeilan RI, Arama E, Baehrecke EH, Balachandran S, Bano D, Barlev NA, Bartek J, Bazan NG, Becker C, Bernassola F, Bertrand MJM, Bianchi ME, Blagosklonny MV, Blander JM, Blandino G, Blomgren K, Borner C, Bortner CD, Bove P, Boya P, Brenner C, Broz P, Brunner T, Damgaard RB, Calin GA, Campanella M, Candi E, Carbone M, Carmona-Gutierrez D, Cecconi F, Chan FK, Chen GQ, Chen Q, Chen YH, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Ciliberto G, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D'Angiolella V, Daugaard M, Dawson TM, Dawson VL, De Maria R, De Strooper B, Debatin KM, Deberardinis RJ, Degterev A, Del Sal G, Deshmukh M, Di Virgilio F, Diederich M, Dixon SJ, Dynlacht BD, El-Deiry WS, Elrod JW, Engeland K, Fimia GM, Galassi C, Ganini C, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Gerlic M, Ghosh S, Green DR, Greene LA, Gronemeyer H, Häcker G, Hajnóczky G, Hardwick JM, Haupt Y, He S, Heery DM, Hengartner MO, Hetz C, Hildeman DA, Ichijo H, Inoue S, Jäättelä M, Janic A, Joseph B, Jost PJ, Kanneganti TD, Karin M, Kashkar H, Kaufmann T, Kelly GL, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Kluck R, Krysko DV, Kulms D, Kumar S, Lavandero S, Lavrik IN, Lemasters JJ, Liccardi G, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Luedde T, MacFarlane M, Madeo F, Malorni W, Manic G, Mantovani R, Marchi S, Marine JC, Martin SJ, Martinou JC, Mastroberardino PG, Medema JP, Mehlen P, Meier P, Melino G, Melino S, Miao EA, Moll UM, Muñoz-Pinedo C, Murphy DJ, Niklison-Chirou MV, Novelli F, Núñez G, Oberst A, Ofengeim D, Opferman JT, Oren M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pentimalli F, Pereira DM, Pervaiz S, Peter ME, Pinton P, Porta G, Prehn JHM, Puthalakath H, Rabinovich GA, Rajalingam K, Ravichandran KS, Rehm M, Ricci JE, Rizzuto R, Robinson N, Rodrigues CMP, Rotblat B, Rothlin CV, Rubinsztein DC, Rudel T, Rufini A, Ryan KM, Sarosiek KA, Sawa A, Sayan E, Schroder K, Scorrano L, Sesti F, Shao F, Shi Y, Sica GS, Silke J, Simon HU, Sistigu A, Stephanou A, Stockwell BR, Strapazzon F, Strasser A, Sun L, Sun E, Sun Q, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Troy CM, Turk B, Urbano N, Vandenabeele P, Vanden Berghe T, Vander Heiden MG, Vanderluit JL, Verkhratsky A, Villunger A, von Karstedt S, Voss AK, Vousden KH, Vucic D, Vuri D, Wagner EF, Walczak H, Wallach D, Wang R, Wang Y, Weber A, Wood W, Yamazaki T, Yang HT, Zakeri Z, Zawacka-Pankau JE, Zhang L, Zhang H, Zhivotovsky B, Zhou W, Piacentini M, Kroemer G, and Galluzzi L
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- Animals, Humans, Cell Death, Carcinogenesis, Mammals metabolism, Apoptosis genetics, Caspases genetics, Caspases metabolism
- Abstract
Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease., (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)
- Published
- 2023
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22. Comparison of rabbit corneal changes during different preservation techniques using optisol-GS and airlift.
- Author
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Tang D, Uematsu M, Harada K, Mohamed YH, Kusano M, Inoue D, and Kitaoka T
- Subjects
- Rabbits, Humans, Animals, Cornea, Chondroitin Sulfates, Dextrans, Gentamicins, Complex Mixtures, Culture Media, Serum-Free, Endothelium, Corneal, Organ Preservation methods, Epithelium, Corneal
- Abstract
A previous study suggested that the airlift condition is superior to the Optisol-GS condition for preserving the limbal tissue of the human cornea. The purpose of this research is to investigate a new preservation device that preserves the cornea while separating epithelial and endothelial areas. The differences after preserving the corneal epithelium under different conditions were compared. A total of 24 corneas of New Zealand rabbits were divided into four groups in which the corneal epithelia were submersed in Optisol-GS or under airlift conditions for 1 and 2 weeks at 4 [Formula: see text]C. Transparency, optical coherence tomography (OCT), hematoxylin and eosin (H &E) staining, and epithelial migration tests were used to assess corneal status. The epithelial migration examination showed significantly greater migration ability after the airlift condition. Corneas in the 1-week Optisol-GS group were the most transparent, followed by the 1-week airlift group. OCT showed a progressive increase in corneal thickness to the end of the study. H &E staining showed that the epithelial cells retained intact cellular structure and morphology of the cells for both 1-week-preserved groups. However, there was disruption of the corneal epithelial cell structure for both 2-week-preserved groups. Corneal epithelium preserved under the hypothermic airlift condition was comparable to that under the Optisol-GS condition., (© 2023. The Author(s).)
- Published
- 2023
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23. Association between nonalcoholic fatty liver disease and peripheral neuropathy in US population, a cross-sectional study.
- Author
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Gu X, Tang D, Xuan Y, Shen Y, and Lu LQ
- Subjects
- Adult, Humans, Middle Aged, Aged, Aged, 80 and over, Cross-Sectional Studies, Nutrition Surveys, Risk Factors, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease epidemiology, Diabetes Mellitus, Type 2 complications, Peripheral Nervous System Diseases etiology, Peripheral Nervous System Diseases complications
- Abstract
Nonalcoholic fatty liver disease (NAFLD) has become an important risk of type 2 diabetes mellitus (T2DM). Peripheral neuropathy (PN) is regarded as one of the main microvascular complications of diabetes. But the association of NAFLD with PN is still unclear. We aimed to investigate the association between NAFLD and PN in US population by conducting a cross-sectional study. We enrolled 3029 participants aged 40-85 years from National Health and Nutrition Examination Survey (NHANES) 1999-2004. NAFLD was defined as a US Fatty Liver Index (FLI) score ≥ 30, and PN was defined as having one or more insensate areas on either foot. Participants were divided into two groups (with or without PN). We performed multivariate logistic regression models to evaluate the association between NAFLD and PN. Subgroup analyses were used to find out whether the association was stable in different stratified groups. Sensitivity analyses were conducted to assess the robustness of the results. All the analyses were weighted. Among the individuals, 524 (17.3%) had PN and 1250 (41.27%) had NAFLD. In the multivariate logistic regression models, NAFLD was associated with an increased risk of PN (OR 1.44 [1.03 ~ 2.02]) after fully adjusting for covariates. In the subgroup analyses, NAFLD was significantly associated with PN in the age group (40-64 years), compared with those in the age group (65-85 years), (P for interaction: 0.004). The results of association of NAFLD with PN were stable in sensitivity analyses. In this cross-sectional study among US adults aged 40-85 years old, NAFLD was associated with an increased likelihood of prevalent PN., (© 2023. The Author(s).)
- Published
- 2023
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24. Cardiogenic control of affective behavioural state.
- Author
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Hsueh B, Chen R, Jo Y, Tang D, Raffiee M, Kim YS, Inoue M, Randles S, Ramakrishnan C, Patel S, Kim DK, Liu TX, Kim SH, Tan L, Mortazavi L, Cordero A, Shi J, Zhao M, Ho TT, Crow A, Yoo AW, Raja C, Evans K, Bernstein D, Zeineh M, Goubran M, and Deisseroth K
- Subjects
- Animals, Mice, Anxiety physiopathology, Brain Mapping, Electrophysiology, Optogenetics, Insular Cortex physiology, Heart Rate, Channelrhodopsins, Tachycardia physiopathology, Pacemaker, Artificial, Brain physiology, Emotions physiology, Heart physiology, Behavior, Animal physiology
- Abstract
Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart
1-3 . However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8 . Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9 . Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour., (© 2023. The Author(s).)- Published
- 2023
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25. Glimmers of hope for targeting oncogenic KRAS-G12D.
- Author
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Tang D and Kang R
- Subjects
- Humans, Proto-Oncogene Proteins p21(ras) genetics, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics
- Abstract
KRAS mutations are one of the most common genetic abnormalities in cancer, especially lung, colon, and pancreatic cancers. Strategies targeting the oncogenic KRAS pathway include direct and indirect approaches. KRAS-G12C inhibitors developed based on binding to the switch II pocket structure of KRAS mutant protein represent a breakthrough in the development of targeted therapeutic strategies against oncogenic proteins previously considered undruggable. The covalent KRAS-G12C inhibitors sotorasib (AMG510) and adagrasib (MRTX849) are used to treat patients with KRAS-G12C-mutated non-small cell lung cancer. Emerging research shows that other host point mutations in KRAS can also be directly targeted by small-molecule compounds. Recently, through extensive structure-based drug design from Mirati Therapeutics, a novel non-covalent KRAS-G12D inhibitor, MRTX1133, showed significant preclinical antitumor activity in KRAS-G12D-bearing tumor cells, especially pancreatic ductal adenocarcinoma. Here, we discuss the selectivity, efficacy, toxicity, and potential application challenges of this novel targeted protein inhibitor., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2023
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26. Theoretical and experimental study of the "superelastic collision effects" used to excite high-g shock environment.
- Author
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Duan Z, Zeng Q, Tang D, and Peng Y
- Abstract
The excitation technology for high-g-level shock environment experiments is currently a topic of interest, for which velocity amplification by collisions of vertically stacked bodies has been used to develop high-g shock tests with great success. This study investigated the superelastic collision effects generated during high-velocity one-dimensional three-body impacts. Theoretical formulae were derived in brief for an analytical investigation of the collisions. Four experiments were performed with different initial velocities obtained from free-falls from different heights. Velocity gains larger than 5 were obtained for the three-body collisions, and coefficients of restitution larger than 2.5 were observed for the second impact. The experimental results well verified the existence of superelastic collision effects in the one-dimensional three-body impacts., (© 2023. The Author(s).)
- Published
- 2023
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27. ACSS2-mediated NF-κB activation promotes alkaliptosis in human pancreatic cancer cells.
- Author
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Que D, Kuang F, Kang R, Tang D, and Liu J
- Subjects
- Humans, NF-kappa B, Aminoquinolines, Benzamides, Cell Line, Tumor, Acetate-CoA Ligase metabolism, Pancreatic Neoplasms, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal genetics
- Abstract
Alkaliptosis is a recently discovered type of pH-dependent cell death used for tumor therapy. However, its underlying molecular mechanisms and regulatory networks are largely unknown. Here, we report that the acetate-activating enzyme acetyl-CoA short-chain synthase family member 2 (ACSS2) is a positive regulator of alkaliptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Using qPCR and western blot analysis, we found that the mRNA and protein expression of ACSS2 was upregulated in human PDAC cell lines (PANC1 and MiaPaCa2) in response to the classic alkaliptosis activator JTC801. Consequently, the knockdown of ACSS2 by shRNAs inhibited JTC801-induced cell death in PDAC cells, and was accompanied by an increase in cell clone formation and a decrease in intracellular pH. Mechanically, ACSS2-mediated acetyl-coenzyme A production and subsequent histone acetylation contributed to NF-κB-dependent CA9 downregulation, and this effect was enhanced by the histone deacetylase inhibitor trichostatin A. These findings may provide new insights for understanding the metabolic basis of alkaliptosis and establish a potential strategy for PDAC treatment., (© 2023. The Author(s).)
- Published
- 2023
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28. Extracellular vesicles-transferred SBSN drives glioma aggressiveness by activating NF-κB via ANXA1-dependent ubiquitination of NEMO.
- Author
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Chen H, Chen X, Zhang Z, Bao W, Gao Z, Li D, Xie X, Zhou P, Yang C, Zhou Z, Pan J, Kuang X, Tang R, Feng Z, Zhou L, Zhu D, Yang J, Wang L, Huang H, Tang D, Liu J, and Jiang L
- Subjects
- Humans, Antigens, Differentiation metabolism, Cell Line, Tumor, Neoplasm Proteins metabolism, NF-kappa B genetics, NF-kappa B metabolism, Ubiquitination, Extracellular Vesicles metabolism, Glioma pathology
- Abstract
Glioma is the most common malignant primary brain tumor with aggressiveness and poor prognosis. Although extracellular vesicles (EVs)-based cell-to-cell communication mediates glioma progression, the key molecular mediators of this process are still not fully understood. Herein, we elucidated an EVs-mediated transfer of suprabasin (SBSN), leading to the aggressiveness and progression of glioma. High levels of SBSN were positively correlated with clinical grade, predicting poor clinical prognosis of patients. Upregulation of SBSN promoted, while silencing of SBSN suppressed tumorigenesis and aggressiveness of glioma cells in vivo. EVs-mediated transfer of SBSN resulted in an increase in SBSN levels, which promoted the aggressiveness of glioma cells by enhancing migration, invasion, and angiogenesis of recipient glioma cells. Mechanistically, SBSN activated NF-κB signaling by interacting with annexin A1, which further induced Lys63-linked and Met1-linear polyubiquitination of NF-κB essential modulator (NEMO). In conclusion, the communication of SBSN-containing EVs within glioma cells drives the formation and development of tumors by activating NF-κB pathway, which may provide potential therapeutic target for clinical intervention in glioma., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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29. Testosterone promotion effect of Eucommia ulmoides staminate flower via the steroidogenic pathway and potential hormonal mechanism.
- Author
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Li Z, Yang P, Xue S, Yuan S, Yuan L, Yan R, Tang D, and Li J
- Subjects
- Kaempferols pharmacology, Kaempferols metabolism, Leydig Cells metabolism, Androgens metabolism, Flowers, Testosterone metabolism, Eucommiaceae
- Abstract
Eucommia ulmoides staminate flowers (EUF), a newly approved functional food in China, have great potential for hormonal regulation. Herein, we aim to demonstrate the chemical composition and pharmacological activity of EUF in testosterone production and hormonal regulation. EUF extract and its components, kaempferol and geniposidic acid, exhibited a strong stimulating effect by increasing testosterone secretion, reducing ROS production, or promoting viability in Leydig cells. Meanwhile, the increased testosterone production was related to the upregulation of mRNA and protein expression of the steroidogenic pathway, such as steroidogenic acute-regulatory protein (StAR), 3β -hydroxysteroid dehydrogenase type 1 (HSD3B1), 17α-hydroxylase/17,20-lyase (CYP17A1), and nuclear receptor subfamily 5 group A member 1 (NR5A1). However, PKA inhibitor H89 or adenylyl cyclase inhibitor SQ22536 could block their effect. The results of transgenic yeast models showed the androgenic agonistic effects of kaempferol and naringenin and the estrogenic agonistic effects of rutin. These results indicated that the testosterone promotional effect of EUF was related to the activation of the steroidogenic pathway and potential hormonal regulation. Kaempferol and geniposidic acid might be the key active ingredients., (© 2022. The Author(s).)
- Published
- 2022
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30. UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination.
- Author
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Ma M, Zhang C, Cao R, Tang D, Sang X, Zou S, Wang X, Xu H, Liu G, Dai L, Tian Y, Gao X, and Fu X
- Subjects
- Animals, Mice, Lipids, Ubiquitination, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics, Mitochondrial Trifunctional Protein, alpha Subunit metabolism, Ubiquitin-Conjugating Enzymes metabolism
- Abstract
Cancer cells rely on heightened protein quality control mechanisms, including the ubiquitin-proteosome system that is predominantly driven by ubiquitination comprising E1, E2, and E3 trienzyme cascades. Although E3s have been extensively studied, the implication of E2s in tumorigenesis is poorly defined. Here we reveal a critical E2 in the pathogenesis of hepatocellular carcinoma (HCC). Among all of E2s, UBE2O shows the strongest association with HCC survival prognosis, and its expression is increased in HCC tumors. Accordingly, UBE2O deficiency inhibits HCC growth and metastasis both in vitro and in vivo, while its overexpression has opposite effects. Depending on both E2 and E3 enzymatic activities, UBE2O can interact with and mediate the ubiquitination and degradation of HADHA, a mitochondrial β-oxidation enzyme, thereby modulating lipid metabolic reprogramming. HADHA is reduced in HCC tumors and inversely correlated with UBE2O levels. Importantly, HADHA acts as a tumor suppressor and primarily mediates UBE2O's function on HCC. Moreover, liver-specific deletion of Ube2o in mice are resistant to DEN-induced hepatocarcinogenesis, along with HADHA upregulation and reduced hepatic lipid accumulation. These data reveal UBE2O as a novel oncogenic driver for metabolic reprogramming and HCC development, highlighting the potential of targeting UBE2O/HADHA axis for HCC therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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31. The V-ATPases in cancer and cell death.
- Author
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Chen F, Kang R, Liu J, and Tang D
- Subjects
- Humans, Cell Membrane metabolism, Cell Death, Vacuolar Proton-Translocating ATPases genetics, Vacuolar Proton-Translocating ATPases chemistry, Vacuolar Proton-Translocating ATPases metabolism, Neoplasms metabolism
- Abstract
Transmembrane ATPases are membrane-bound enzyme complexes and ion transporters that can be divided into F-, V-, and A-ATPases according to their structure. The V-ATPases, also known as H
+ -ATPases, are large multi-subunit protein complexes composed of a peripheral domain (V1) responsible for the hydrolysis of ATP and a membrane-integrated domain (V0) that transports protons across plasma membrane or organelle membrane. V-ATPases play a fundamental role in maintaining pH homeostasis through lysosomal acidification and are involved in modulating various physiological and pathological processes, such as macropinocytosis, autophagy, cell invasion, and cell death (e.g., apoptosis, anoikis, alkaliptosis, ferroptosis, and lysosome-dependent cell death). In addition to participating in embryonic development, V-ATPase pathways, when dysfunctional, are implicated in human diseases, such as neurodegenerative diseases, osteopetrosis, distal renal tubular acidosis, and cancer. In this review, we summarize the structure and regulation of isoforms of V-ATPase subunits and discuss their context-dependent roles in cancer biology and cell death. Updated knowledge about V-ATPases may enable us to design new anticancer drugs or strategies., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2022
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32. The deubiquitinating enzyme STAMBP is a newly discovered driver of triple-negative breast cancer progression that maintains RAI14 protein stability.
- Author
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Yang Q, Yan D, Zou C, Xue Q, Lin S, Huang Q, Li X, Tang D, Chen X, and Liu J
- Subjects
- Humans, Female, Cell Proliferation genetics, Cell Line, Tumor, Signal Transduction, Protein Stability, Deubiquitinating Enzymes genetics, Gene Expression Regulation, Neoplastic, Cell Movement genetics, Cytoskeletal Proteins metabolism, Transcription Factors metabolism, Ubiquitin Thiolesterase genetics, Endosomal Sorting Complexes Required for Transport genetics, Endosomal Sorting Complexes Required for Transport metabolism, Endosomal Sorting Complexes Required for Transport therapeutic use, Triple Negative Breast Neoplasms metabolism
- Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous malignancy in women. It is associated with poor prognosis, aggressive malignant behavior, and limited treatment options. In the ubiquitin‒proteasome system (UPS), deubiquitinases (DUBs) are potential therapeutic targets for various tumors. In this study, by performing unbiased siRNA screening, we identified STAMBP, a JAMM metalloprotease in the DUB family, as a driver of human TNBC tumor growth. Functionally, the knockdown of STAMBP inhibited the proliferation, migration, and invasion of multiple TNBC cell lines. Immunoprecipitation-mass spectrometry combined with functional and morphological analysis verified the interaction between STAMBP and the actin-binding protein RAI14. Mechanistically, STAMBP stabilized the RAI14 protein by suppressing the K48-linked ubiquitination of RAI14 and thus prevented its proteasomal degradation. Therefore, knocking down STAMBP resulted in the reduction in RAI14 protein levels and suppression of tumor growth in vitro and in vivo. Importantly, high levels of STAMBP were correlated with poor prognosis in TNBC patients. In summary, we reveal a previously unrecognized DUB pathway that promotes TNBC progression and provides a rationale for potential therapeutic interventions for the treatment of TNBC., (© 2022. The Author(s).)
- Published
- 2022
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33. Addendum: Genome evolution and diversity of wild and cultivated potatoes.
- Author
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Tang D, Jia Y, Zhang J, Li H, Cheng L, Wang P, Bao Z, Liu Z, Feng S, Zhu X, Li D, Zhu G, Wang H, Zhou Y, Zhou Y, Bryan GJ, Buell CR, Zhang C, and Huang S
- Published
- 2022
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- View/download PDF
34. Adeno-associated virus-delivered alpha synuclein inhibits bladder cancer growth via the p53/p21 signaling pathway.
- Author
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Wu Z, Xia C, Zhang C, Tang D, Liu F, Ou Y, Gao J, Yi H, Yang D, and Ma K
- Subjects
- Dependovirus genetics, Dependovirus metabolism, Humans, Signal Transduction, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Urinary Bladder Neoplasms pathology, alpha-Synuclein genetics, alpha-Synuclein metabolism
- Abstract
Alpha-synuclein (α-syn), encoded by the SNCA gene, is a major participant in the pathophysiology of Parkinson's disease (PD). Its functions have been reported to be related to apoptosis induction, the elevation of oxidative stress, mitochondrial homeostasis, cell-cycle aberrations, and DNA-related interactions. Evidence obtained in recent studies suggests a possible link between α-syn and cancer development. Bladder cancer (BCa) is the second most common genitourinary malignancy, with the population of survivors of BCa increasing worldwide. In this study, we show that α-syn expression was significantly downregulated in BCa. In vitro and in vivo experiments showed that α-syn could significantly inhibit BCa cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages. Further experiments showed that overexpression of α-syn delivered by adeno-associated viruses (AAVs) exerted inhibitory effects on the growth of BCa tumors. These findings indicate that αα-syn is a functional tumor suppressor that can inhibit the proliferation of BCa cells by activating the p53/p21 signaling pathway. Our present study provides insights into the roles of α-syn in BCa and suggests that α-syn may be a novel therapeutic target for the treatment of BCa., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
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- View/download PDF
35. The KRAS-G12C inhibitor: activity and resistance.
- Author
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Liu J, Kang R, and Tang D
- Subjects
- Acetonitriles, Humans, Mutation, Piperazines, Pyrimidines, Tumor Microenvironment genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Proto-Oncogene Proteins p21(ras) antagonists & inhibitors, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Although it has long been deemed "undruggable", with the development of drugs specifically binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS have recently made promising improvements. In particular, the covalent KRAS-G12C inhibitors sotorasib and adagrasib are used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS-G12C mutations. Unfortunately, the vast majority of patients do not respond to KRAS-G12C inhibitor therapy, mainly due to intrinsic or acquired resistance caused by cellular, molecular, and genetic mechanisms. Improving the understanding of drug response in the tumor microenvironment may continue to promote the design, testing, and clinical application of KRAS-G12C inhibitors., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
36. MTA1 aggravates experimental colitis in mice by promoting transcription factor HIF1A and up-regulating AQP4 expression.
- Author
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Li P, Shi DP, Jin T, Tang D, Wang W, and Wang LH
- Abstract
Experimental colitis can persist as a chronic disease, accompanied with an underlying risk of development into colorectal cancer. Metastasis-associated protein 1 (MTA1), as a chromatin modifier, exerts notable association with multiple diseases, including colitis. The current study aims to investigate the mechanism of MTA1/HIF1A/AQP4 axis in experimental colitis in mice. First, experimental colitis mouse models were established using dextran sulfate sodium (DSS) and in vitro colonic epithelial cells FHC inflammation models were with lipopolysaccharide (LPS) for determination of MTA1 and HIF1A expressions. It was found that MTA1 and HIF1A were both highly-expressed in experimental colitis samples. Results of dual-luciferase reporter gene assay and ChIP assay further revealed that MTA1 activated HIF1A, and subsequently induced AQP4 transcription to up-regulate AQP4 in experimental colitis. Following loss- and gain-function, the effects of MTA1/HIF1A/AQP4 axis on apoptosis and viability of colon epithelial cells were detected by a combination of TUNEL staining and flow cytometry, and CCK-8 assay. It was observed that silencing of MAT1 in the FHC and NCM460 cells reduced IL-1β and TNF-α expressions induced by LPS. Meanwhile, AQP4 promoted LPS-induced inflammation, and exacerbated apoptosis of colon epithelial cells and augmented experimental colitis development in mice. In vivo experiments further verified that TGN-020 treatment effectively alleviated DSS-induced experimental colitis in mice and diminished apoptosis of colon epithelial cells. Altogether, MTA1 may promote AQP4 transcription by activating HIF1A, thus exacerbating DSS-induced experimental colitis in mice, which provides a novel direction for the treatment of experimental colitis., (© 2022. The Author(s).)
- Published
- 2022
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37. Genome evolution and diversity of wild and cultivated potatoes.
- Author
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Tang D, Jia Y, Zhang J, Li H, Cheng L, Wang P, Bao Z, Liu Z, Feng S, Zhu X, Li D, Zhu G, Wang H, Zhou Y, Zhou Y, Bryan GJ, Buell CR, Zhang C, and Huang S
- Subjects
- Plant Breeding, Plant Tubers genetics, Crops, Agricultural genetics, Evolution, Molecular, Genome, Plant genetics, Solanum tuberosum genetics
- Abstract
Potato (Solanum tuberosum L.) is the world's most important non-cereal food crop, and the vast majority of commercially grown cultivars are highly heterozygous tetraploids. Advances in diploid hybrid breeding based on true seeds have the potential to revolutionize future potato breeding and production
1-4 . So far, relatively few studies have examined the genome evolution and diversity of wild and cultivated landrace potatoes, which limits the application of their diversity in potato breeding. Here we assemble 44 high-quality diploid potato genomes from 24 wild and 20 cultivated accessions that are representative of Solanum section Petota, the tuber-bearing clade, as well as 2 genomes from the neighbouring section, Etuberosum. Extensive discordance of phylogenomic relationships suggests the complexity of potato evolution. We find that the potato genome substantially expanded its repertoire of disease-resistance genes when compared with closely related seed-propagated solanaceous crops, indicative of the effect of tuber-based propagation strategies on the evolution of the potato genome. We discover a transcription factor that determines tuber identity and interacts with the mobile tuberization inductive signal SP6A. We also identify 561,433 high-confidence structural variants and construct a map of large inversions, which provides insights for improving inbred lines and precluding potential linkage drag, as exemplified by a 5.8-Mb inversion that is associated with carotenoid content in tubers. This study will accelerate hybrid potato breeding and enrich our understanding of the evolution and biology of potato as a global staple food crop., (© 2022. The Author(s).)- Published
- 2022
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- View/download PDF
38. Targeting KDM1B-dependent miR-215-AR-AGR2-axis promotes sensitivity to enzalutamide-resistant prostate cancer.
- Author
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Tang D, He J, Dai Y, Geng X, Leng Q, Jiang H, Sun R, and Xu S
- Subjects
- Benzamides therapeutic use, Cell Line, Tumor, Cell Proliferation, Humans, Male, Mucoproteins genetics, Nitriles therapeutic use, Oncogene Proteins genetics, Phenylthiohydantoin therapeutic use, Receptors, Androgen genetics, Drug Resistance, Neoplasm genetics, Histone Deacetylases genetics, MicroRNAs genetics, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology
- Abstract
Post-translational modifications of histones by histone demethylases plays an important role in the regulation of gene transcription and are implicated in cancers. Castrate resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. However, the role of KDM1B involved in next generation anti-enzalutamide resistance and the mechanisms of KDM1B regulation are poorly defined. Here, we show that KDM1B is upregulated and correlated with prostate cancer progression and poor prognosis. Downregulation of miR-215 is correlated with overexpression of KDM1B in enzalutamide-resistant prostate cancer cells, which promotes AR-dependent AGR2 transcription and regulates the sensitivity to next generation AR-targeted therapy. Inhibition of KDM1B significantly inhibits prostate tumor growth and improves enzalutamide treatments through AGR2 suppression. Our studies demonstrate inhibition of KDM1B can offer a viable therapeutic option to overcome enzalutamide resistance in tumors with deregulated miR-215-KDM1B-AR-AGR2 signaling axis., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
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- View/download PDF
39. Cuproptosis: a copper-triggered modality of mitochondrial cell death.
- Author
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Tang D, Chen X, and Kroemer G
- Subjects
- Cell Death, Copper metabolism, Copper pharmacology, Mitochondria metabolism, Apoptosis
- Published
- 2022
- Full Text
- View/download PDF
40. Low voltage environmentally friendly plasma electrolytic oxidation process for titanium alloys.
- Author
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Hou F, Gorthy R, Mardon I, Tang D, and Goode C
- Abstract
Plasma electrolytic oxidation (PEO) is a surface-treatment process extensively used to protect the surfaces of light metals such as Mg, Al, and Ti. Here, we report an environmentally friendly PEO process that uses nitrogen-containing electrolytes and low voltages (120 V) to form ~ 12 micron thick, uniform, adherent and porous oxide coatings on T1 titanium alloy surfaces. We evaluated the influence of nitrogenation by comparing the coatings to alloys treated in PEO baths without nitrogen-containing compounds. Both sets of samples exhibited basalt-like morphologies with distinct variation in the pore structures. The composition analyses showed that the coatings were primarily composites of titanium oxides and silicates. The T1 Ti alloys treated with nitrogen-containing electrolytes also contained TiC and TiN. This is the first ever report of producing Ti
x Oy , Ti-Si-O, TiC, and TiN composite coatings using a single PEO bath without carbide/nitride nanoparticles. The bandgaps of the coatings suggested visible light functionality. The use of nitrogen-based compounds in the PEO baths improved the hardness of the oxide layers but introduced stress-induced cracking which are potentially responsible for the reduction in corrosion resistance of the nitride and carbide containing coatings., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
41. Author Correction: Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice.
- Author
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Wang X, Wang Z, and Tang D
- Published
- 2022
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42. Simultaneous strength and ductility enhancements of high thermal conductive Ag7.5Cu alloy by selective laser melting.
- Author
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Xiong W, Hao L, Peijs T, Yan C, Cheng K, Gong P, Cui Q, Tang D, Al Islam S, and Li Y
- Abstract
High electrical and thermal conductive metals (HETCM) play a key role in smart electronics, green energy, modern communications and healthcare, however, typical HETCM (e.g., Ag, Au, Cu) usually have relatively low mechanical strength, hindering further applications. Selective laser melting (SLM) is a potentially transformative manufacturing technology that is expected to address the issue. Ag is the metal with the highest thermal conductivity, which induces microscale grain refinement, but also leads to high internal stresses by SLM. Here, we select Ag7.5Cu alloy as an example to demonstrate that multi-scale (micro/meso/macro) synergies can take advantage of high thermal conductivity and internal stresses to effectively strengthen Ag alloy. The mimicry of metal-hardened structures (e.g., large-angle boundary) is extended to the mesoscale by controlling the laser energy density and laser scanning strategy to manipulate the macroscale internal stress intensity and mesoscale internal stress direction, respectively, to form mesoscale large-angle "grains", resulting in multiple mutual perpendicular shear bands during fracture. The presented approach achieved a significant enhancement of yield strength (+ 145%) and ductility (+ 28%) without post-treatment. The results not only break the strength-ductility trade-off of conventional SLM alloys, but also demonstrate a multi-scale synergistic enhancement strategy that exploits high thermal conductivity and internal stresses., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
43. The mechanism of HMGB1 secretion and release.
- Author
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Chen R, Kang R, and Tang D
- Subjects
- Alarmins, Apoptosis physiology, Autophagy physiology, Cell Death, HMGB1 Protein
- Abstract
High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein. After its active secretion or passive release, extracellular HMGB1 usually acts as a damage-associated molecular pattern (DAMP) molecule, regulating inflammation and immune responses through different receptors or direct uptake. The secretion and release of HMGB1 is fine-tuned by a variety of factors, including its posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, and methylation) and the molecular machinery of cell death (e.g., apoptosis, pyroptosis, necroptosis, alkaliptosis, and ferroptosis). In this minireview, we introduce the basic structure and function of HMGB1 and focus on the regulatory mechanism of HMGB1 secretion and release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases and tissue damage., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
44. NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent manner.
- Author
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Huang C, Santofimia-Castaño P, Liu X, Xia Y, Peng L, Gotorbe C, Neira JL, Tang D, Pouyssegur J, and Iovanna J
- Abstract
Ferroptosis is an iron-dependent cell death characterized by the accumulation of hydroperoxided phospholipids. Here, we report that the NUPR1 inhibitor ZZW-115 induces ROS accumulation followed by a ferroptotic cell death, which could be prevented by ferrostatin-1 (Fer-1) and ROS-scavenging agents. The ferroptotic activity can be improved by inhibiting antioxidant factors in pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells. In addition, ZZW-115-treatment increases the accumulation of hydroperoxided lipids in these cells. We also found that a loss of activity and strong deregulation of key enzymes involved in the GSH- and GPX-dependent antioxidant systems upon ZZW-115 treatment. These results have been validated in xenografts induced with PDAC- and HCC-derived cells in nude mice during the treatment with ZZW-115. More importantly, we demonstrate that ZZW-115-induced mitochondrial morphological changes, compatible with the ferroptotic process, as well as mitochondrial network disorganization and strong mitochondrial metabolic dysfunction, which are rescued by both Fer-1 and N-acetylcysteine (NAC). Of note, the expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. Altogether, these results demonstrate that the mitochondrial cell death mediated by NUPR1 inhibitor ZZW-115 is fully rescued by Fer-1 but also via TFAM complementation. In conclusion, TFAM could be considered as an antagonist of the ferroptotic cell death., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
45. Organelle-specific regulation of ferroptosis.
- Author
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Chen X, Kang R, Kroemer G, and Tang D
- Subjects
- Humans, Cell Death physiology, Ferroptosis physiology, Lipid Peroxidation physiology, Mitochondria metabolism
- Abstract
Ferroptosis, a cell death modality characterized by iron-dependent lipid peroxidation, is involved in the development of multiple pathological conditions, including ischemic tissue damage, infection, neurodegeneration, and cancer. The cellular machinery responsible for the execution of ferroptosis integrates multiple pro-survival or pro-death signals from subcellular organelles and then 'decides' whether to engage the lethal process or not. Here, we outline the evidence implicating different organelles (including mitochondria, lysosomes, endoplasmic reticulum, lipid droplets, peroxisomes, Golgi apparatus, and nucleus) in the ignition or avoidance of ferroptosis, while emphasizing their potential relevance for human disease and their targetability for pharmacological interventions., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)
- Published
- 2021
- Full Text
- View/download PDF
46. Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice.
- Author
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Wang X, Wang Z, and Tang D
- Subjects
- Animals, Blood Glucose analysis, Bronchoalveolar Lavage Fluid cytology, Cytokines analysis, Endotoxemia chemically induced, Endotoxemia complications, Glucose Transporter Type 1 blood, HMGB1 Protein blood, Humans, Immunity, Innate, Insulin blood, Lactates blood, Lipopolysaccharides toxicity, Lung pathology, Male, Mice, Mice, Inbred ICR, Multiple Organ Failure etiology, Multiple Organ Failure immunology, Multiple Organ Failure pathology, Neutrophils pathology, Oxidative Stress, Random Allocation, Viscera pathology, Endotoxemia therapy, Exercise, Glycolysis physiology, Multiple Organ Failure prevention & control, Physical Conditioning, Animal physiology
- Abstract
We investigated the impact of aerobic exercise (AE) on multiple organ dysfunction syndrome (MODS), aortic injury, pathoglycemia, and death during sepsis. ICR mice were randomized into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Mice were trained with low-intensity for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ morphology and damage. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, and bronchoalveolar lavage fluid (BALF) cell count, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, serum insulin levels, plasma high-mobility group box 1 (HMGB1) levels, glucose transporter 1 (Glut1) and HMGB1, silent information regulator 1 (Sirt-1), and nuclear factor erythroid 2-related factor 2 (Nrf-2) mRNA expression levels in lung tissue. AE improved sepsis-associated multiple organ dysfunction syndrome (MODS), aortic injury, hypoglycemia, and death. AE prominently decreased pulmonary inflammation, pulmonary edema, and modulated redox balance during sepsis. AE prominently decreased neutrophil content in organ. AE prominently downregulated CXCL-1, CXCL-8, IL-6, TNF-α, Glu1, and HMGB1 mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung during sepsis. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels and serum insulin levels during sepsis. A 4-week AE improves sepsis-associated MODS, aortic injury, pathoglycemia, and death. AE impairs LPS-induced lactate and HMGB1 release partly because AE increases serum insulin levels and decreases the levels of Glut1. AE is a novel therapeutic strategy for sepsis targeting aerobic glycolysis., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
47. Postoperative severe visual impairment: surgical outcome of 165 patients with orbital tumours in the muscle cone.
- Author
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Jian T, Sun F, Wu T, Zhao L, Huang X, Wang L, He Y, and Tang D
- Subjects
- Humans, Muscles, Retrospective Studies, Treatment Outcome, Vision Disorders epidemiology, Vision Disorders etiology, Orbital Neoplasms surgery
- Abstract
Objective: This study aimed to evaluate the risk factors of postoperative severe vision impairment (PSVI) for a primary orbital tumour in the muscle cone., Methods: A retrospective analysis of the patients who underwent orbitotomy for primary intraconal tumours at the Tianjin Medical University Eye Hospital from January 2010 to December 2015., Results: A total of 165 cases of orbitotomy for primary orbital tumours in the muscle cone were included in the study. Postoperatively, 12 cases with vision acuity ≤20/400 or ≥4 rows of vision decline and without any corrected effect were analysed as PSVI, including no light perception (NLP) for 3 cases. The multivariate logistic regression indicated that the tumour in orbital apex (P = 0.048, OR = 4.912, 95% CI: 1.011-23.866), severe optic nerve displacement (P = 0.030, OR = 6.007, 95% CI: 1.184-30.473) and intraoperative tight adhesion (P = 0.003, OR = 12.031, 95% CI: 2.282-63.441) were the independent risk factors for PSVI., Conclusions: The incidence of PSVI for the intraconal tumour was 7.3%, and the incidence of NLP was 1.8%. The tumour in orbital apex, severe optic nerve displacement and intraoperative tight adhesion were independent risk factors for PSVI., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)
- Published
- 2021
- Full Text
- View/download PDF
48. The STING1 network regulates autophagy and cell death.
- Author
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Zhang R, Kang R, and Tang D
- Subjects
- Animals, Humans, Inflammation immunology, Autophagy immunology, Membrane Proteins immunology, Signal Transduction immunology
- Abstract
Cell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.
- Published
- 2021
- Full Text
- View/download PDF
49. A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance.
- Author
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Liao Y, Liu Y, Shao Z, Xia X, Deng Y, Cai J, Yao L, He J, Yu C, Hu T, Sun W, Liu F, Tang D, Liu J, and Huang H
- Subjects
- Animals, Castration, Cell Line, Tumor, Cell Proliferation genetics, Disease Progression, Gene Expression Regulation, Neoplastic genetics, HEK293 Cells, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, PC-3 Cells, Prostate pathology, Prostatic Neoplasms, Castration-Resistant pathology, Proteolysis, Receptors, Androgen genetics, Signal Transduction genetics, Transcription Factors genetics, Ubiquitination genetics, HSP70 Heat-Shock Proteins genetics, Homeodomain Proteins genetics, Mitochondrial Proteins genetics, Prostatic Neoplasms, Castration-Resistant genetics, Ubiquitin-Specific Proteases genetics
- Abstract
Prostate cancer (PC) is the second most common cancer with limited treatment option in males. Although the reactivation of embryonic signals in adult cells is one of the characteristics of cancer, the underlying protein degradation mechanism remains elusive. Here, we show that the molecular chaperone GRP75 is a key player in PC cells by maintaining the protein stability of SIX1, a transcription factor for embryonic development. Mechanistically, GRP75 provides a platform to recruit the deubiquitinating enzyme USP1 to inhibit K48-linked polyubiquitination of SIX1. Structurally, the C-terminus of GRP75 (433-679 aa) contains a peptide binding domain, which is required for the formation of GRP75-USP1-SIX1 protein complex. Functionally, pharmacological or genetic inhibition of the GRP75-USP1-SIX1 protein complex suppresses tumor growth and overcomes the castration resistance of PC cells in vitro and in xenograft mouse models. Clinically, the protein expression of SIX1 in PC tumor tissues is positively correlated with the expression of GRP75 and USP1. These new findings not only enhance our understanding of the protein degradation mechanism, but also may provide a potential way to enhance the anti-cancer activity of androgen suppression therapy.
- Published
- 2021
- Full Text
- View/download PDF
50. Cellular degradation systems in ferroptosis.
- Author
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Chen X, Yu C, Kang R, Kroemer G, and Tang D
- Subjects
- Animals, Autophagy physiology, Humans, Lysosomes metabolism, Lysosomes pathology, Molecular Chaperones metabolism, Signal Transduction physiology, Autophagic Cell Death physiology, Ferroptosis physiology
- Abstract
In eukaryotic cells, macromolecular homeostasis requires selective degradation of damaged units by the ubiquitin-proteasome system (UPS) and autophagy. Thus, dysfunctional degradation systems contribute to multiple pathological processes. Ferroptosis is a type of iron-dependent oxidative cell death driven by lipid peroxidation. Various antioxidant systems, especially the system xc
- -glutathione-GPX4 axis, play a significant role in preventing lipid peroxidation-mediated ferroptosis. The endosomal sorting complex required for transport-III (ESCRT-III)-dependent membrane fission machinery counteracts ferroptosis by repairing membrane damage. Moreover, cellular degradation systems play a dual role in regulating the ferroptotic response, depending on the cargo they degrade. The key ferroptosis repressors, such as SLC7A11 and GPX4, are degraded by the UPS. In contrast, the overactivation of selective autophagy, including ferritinophagy, lipophagy, clockophagy and chaperone-mediated autophagy, promotes ferroptotic death by degrading ferritin, lipid droplets, circadian proteins, and GPX4, respectively. Autophagy modulators (e.g., BECN1, STING1/TMEM173, CTSB, HMGB1, PEBP1, MTOR, AMPK, and DUSP1) also determine the ferroptotic response in a context-dependent manner. In this review, we provide an updated overview of the signals and mechanisms of the degradation system regulating ferroptosis, opening new horizons for disease treatment strategies.- Published
- 2021
- Full Text
- View/download PDF
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