38 results on '"Wenyu Fu"'
Search Results
2. Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice
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Meng Chen, Wenyu Fu, Huiyun Xu, and Chuan-ju Liu
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Tau ,Collagen-induced arthritis ,Macrophage polarization ,Inflammation ,Autoimmune diseases ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Tau protein serves a pro-inflammatory function in neuroinflammation. However, the role of tau in other inflammatory disorders such as rheumatoid arthritis (RA) is less explored. This study is to investigate the role of endogenous tau and the potential mechanisms in the pathogenesis of inflammatory arthritis. Methods We established collagen-induced arthritis (CIA) model in wild-type and Tau-/- mice to compare the clinical score and arthritis incidence. Micro-CT analysis was used to evaluate bone erosion of ankle joints. Histological analysis was performed to assess inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Serum levels of pro-inflammatory cytokines were measured by ELISA. The expression levels of macrophage markers were determined by immunohistochemistry staining and quantitative real-time PCR. Results Tau expression was upregulated in joints under inflammatory condition. Tau deletion in mice exhibited milder inflammation and protected against the progression of CIA, evidenced by reduced serum levels of pro-inflammatory cytokines and attenuated bone loss, inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Furthermore, tau deficiency led to the inhibition of classically activated type 1 (M1) macrophage polarization in the synovium. Conclusion Tau is a previously unrecognized critical regulator in the pathogenesis of RA and may provide a potential therapeutic target for autoimmune and inflammatory joint diseases.
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- 2023
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3. Vector Partially Coherent Beams With Twisted Sinc-Correlation Structure and Their Statistical Properties
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Xianyan Yang and Wenyu Fu
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Coherence ,vector partially coherent beams ,sinc-correlated structure ,statistics properties ,turbulent atmosphere ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
We define a new kind of radially polarized twisted sinc-correlation Schell-model (RPTSCSM) source and establish the source parameter conditions necessary to produce a physical beam. With the help of the extended Huygens-Fresnel integral, Several typical numerical examples are provided to study the influence of the source parameter and turbulent parameter on the statistical properties of such beams on propagation. It is shown that the intensity profiles of such beams always exhibit rotation and self-splitting on propagation, which is caused by the twisted phase of the beams. Moreover, the light intensity splits into an array and maintains its array distribution in free space. While the array gradually evolves to a hollow distribution with a dark core in a turbulence medium, indicating that the light beam may automatically restore the radial polarized light intensity distribution in atmospheric turbulence after a certain distance of propagation. Compared with the intensity, the impact of the twisted factor on the degree of polarization is to produce noticeable distortion around its distribution centre. When propagating in a turbulent atmosphere, the degree of polarization of such beams exhibits well-turbulent resistance. The degree of coherence would also experience self-splitting and rotation caused by the twisted factor, and a turbulent atmosphere has an important influence on the degree of coherence. Our results will benefit multi-particle manipulation and free-space optical communication.
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- 2023
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4. The relationship between inflammatory response markers and the prognosis of non-muscle invasive bladder cancer and the development of a nomogram model
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Xinping Yi, Jiangchuan Pi, Chuan Liu, Yongjiang Xiong, Jiaji Liu, Wenyu Fu, Lanxi Wang, and Tao Zhao
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inflammatory factors ,prognostic risk factors ,tumor recurrence ,Kaplan-Meier survival ,intravesical instillation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PurposePatients with non-muscle invasive bladder cancer (NMIBC) have a high possibility of recurrence after surgery. We aimed to assess the factors associated with tumor recurrence and to construct a nomogram model that can contribute to personalized treatment plans of each patient.Methods496 patients with primary bladder cancer (BC) from 2 centers were retrospectively analyzed. Preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and traditional clinical parameters were collected, then using univariate and multivariate Cox regression analysis to find out the independent risk factors associated with tumor recurrence among them, and then these independent factors were incorporated into the nomogram model. The internal calibration curves and the external calibration curves were used to verify their usefulness.ResultsIn the training cohort, 150 patients (43.1%) experienced recurrence. After Cox regression analysis, the independent risk factors affecting recurrence-free survival (RFS) were tumor grade, immediate postoperative instillation therapy (IPPIT), NLR, and SII. These factors were used to construct a model to predict RFS 1, 2, 3, and 5 years of NMIBC patients after surgery. And then, we found that the constructed model outperforms the conventional model in terms of accuracy and predictability, the results were verified by statistical tests.ConclusionPreoperative inflammatory response markers have a predictive value for postoperative recurrence in patients with NMIBC. The constructed nomogram model can be helpful in guiding personalized clinical evaluation and subsequent treatment.
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- 2023
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5. Unraveling the mechanisms behind joint damage
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Wenyu Fu and Chuan-ju Liu
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toll-like receptor 2 ,sialylation ,osteoclast ,fusion ,rheumatoid arthritis ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
A subtype of myeloid monocyte mediates the transition from autoimmunity to joint destruction in rheumatoid arthritis.
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- 2023
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6. A Nomogram Model to Predict Recurrence of Non-Muscle Invasive Bladder Urothelial Carcinoma After Resection Based on Clinical Parameters and Immunohistochemical Markers
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Jiangchuan Pi, Yongjiang Xiong, Chuan Liu, Juan Liao, Jiaji Liu, Chuan Li, Wenyu Fu, and Tao Zhao
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non-muscle invasive bladder urothelial carcinoma ,traditional clinical parameters ,immunohistochemical markers ,nomogram model ,recurrence ,prognosis ,Surgery ,RD1-811 - Abstract
Objective This study aims to establish a nomogram model by combining traditional clinical parameters with immunohistochemical markers to predict the recurrence of non-muscle invasive bladder urothelial carcinoma (NMIBUC) after resection. Methods In total, 504 patients were included in this study. Of these patients, 353 underwent transurethral resection of bladder tumor (TURBT) in the Yongchuan Hospital of Chongqing Medical University and were identified as a training cohort. Univariate and multivariate Cox regression analyses were used to determine the risk factors associated with recurrence in the training cohort and to establish a nomogram model. A total of 151 patients who were hospitalized in the Second Affiliated Hospital of Chongqing Medical University (validation cohort) were used for further validation. The calibration curve was generated for internal and external model validation. The clinical practicability of this model was further verified by comparing the consistency index (C-index) among various models. Results The mean follow-up time of the training cohort was 45.6 months (range 4–90). In total, 146 patients relapsed in training cohort. After univariate analysis, multivariate analysis further confirmed tumor grade (p=.034), immediate postoperative instillation therapy (p=.025), Ki67 (p=.047), P53 (p=.038) and CK20 (p=.049) as independent risk factors for recurrence, and these factors were included in the nomogram model. The model more accurately predicted recurrence compared with other models based on the highest C-index of 0.82 (95% CI, 0.78–0.86) in the training cohort and 0.80 (95% CI, 0.77–0.83) in the validation cohort. Conclusions This proposed nomogram model based on traditional clinical parameters and immunohistochemical markers can more accurately predict postoperative recurrence in patients with NMIBUC.
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- 2022
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7. Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis
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Xiangfen Li, Xiaofang Zhu, Hongle Wu, Thomas E. Van Dyke, Xiaoyang Xu, Elise F. Morgan, Wenyu Fu, Chuanju Liu, Qisheng Tu, Dingming Huang, and Jake Chen
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irisin ,osteoarthritis ,cartilage ,gene knockout ,transgenics ,Biology (General) ,QH301-705.5 - Abstract
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.
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- 2021
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8. p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice
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Young-Su Yi, Jinlong Jian, Elena Gonzalez-Gugel, Yong-Xiang Shi, Qingyun Tian, Wenyu Fu, Aubryanna Hettinghouse, Wenhao Song, Ronghan Liu, Michun He, Huabing Qi, Jing Yang, Xiaolan Du, GuoZhi Xiao, Lin Chen, and Chuan-ju Liu
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Medicine ,Medicine (General) ,R5-920 - Abstract
p204, a murine member of an interferon-inducible p200 family, was reported to recognize intracellular viral and bacterial DNAs, however, its role in the innate immunity in vivo remains unknown due to the lack of p204-deficient animal models. In this study we first generated the p204−/− mice. Unexpectedly, p204 deficiency led to significant defect in extracellular LPS signaling in macrophages, as demonstrated by dramatic reductions of LPS-mediated IFN-β and pro-inflammatory cytokines. The serum levels of IFN-β and pro-inflammatory cytokines were also significantly reduced in p204−/− mice following LPS challenge. In addition, p204−/− mice were resistant to LPS-induced shock. LPS-activated NF-ĸB and IRF-3 pathways were all defective in p204-deficient macrophages. p204 binds to TLR4 through its Pyrin domain, and it is required for the dimerization of TLR4 following LPS-challenge. Collectively, p204 is a critical component of canonical LPS-TLR4 signaling pathway, and these studies also suggest that p204 could be a potential target to prevent and treat inflammatory and infectious diseases. Keywords: p204, LPS, TLR4, IFN-β, Inflammatory responses, Macrophages
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- 2018
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9. Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease
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Jinlong Jian, Yuehong Chen, Rossella Liberti, Wenyu Fu, Wenhuo Hu, Rachel Saunders-Pullman, Gregory M. Pastores, Ying Chen, Ying Sun, Gregory A. Grabowski, and Chuan-ju Liu
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Progranulin ,Gaucher disease ,Chitinase-3-like-1 ,Lysosomal storage diseases ,Medicine ,Medicine (General) ,R5-920 - Abstract
We recently reported that progranulin (PGRN) is a novel regulator of glucocerebrosidase and its deficiency associates with Gaucher Diseases (GD) (Jian et al., 2016a; Jian et al., 2018). To isolate the relevant downstream molecules, we performed a whole genome microarray and mass spectrometry analysis, which led to the isolation of Chitinase-3-like-1 (CHI3L1) as one of the up-regulated genes in PGRN null mice. Elevated levels of CHI3L1 were confirmed by immunoblotting and immunohistochemistry. In contrast, treatment with recombinant Pcgin, a derivative of PGRN, as well as imigluerase, significantly reduced the expressions of CHI3L1 in both PGRN null GD model and the fibroblasts from GD patients. Serum levels of CHIT1, a clinical biomarker for GD, were significantly higher in GD patients than healthy controls (51.16 ± 2.824 ng/ml vs 35.07 ± 2.099 ng/ml, p
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- 2018
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10. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
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Jian-lu Wei, Wenyu Fu, Yuan-jing Ding, Aubryanna Hettinghouse, Matin Lendhey, Ran Schwarzkopf, Oran D. Kennedy, and Chuan-ju Liu
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Atsttrin ,Progranulin ,TNFα ,TNFR2 ,TNFR1 ,Osteoarthritis ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Atsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved. Methods Surgically induced and noninvasive rupture OA models were established in mouse and rat, respectively. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry, and ELISA. Additionally, expressions of pain-related markers, degenerative factors, and anabolic and catabolic markers known to be involved in OA were analyzed. Furthermore, the anabolic and anti-catabolic effects and underlying mechanisms of Atsttrin were determined using in-vitro assays with primary chondrocytes. Results Herein, we found Atsttrin effectively prevented the accelerated OA phenotype associated with PGRN deficiency. Additionally, Atsttrin exhibited a preventative effect in OA by protecting articular cartilage and reducing OA-associated pain in both nonsurgically induced rat and surgically induced murine OA models. Mechanistic studies revealed that Atsttrin stimulated TNFR2-Akt-Erk1/2-dependent chondrocyte anabolism, while inhibiting TNFα/TNFR1-mediated inflammatory catabolism. Conclusions These findings not only provide new insights into the role of PGRN and its derived engineered protein Atsttrin in cartilage homeostasis as well as OA in vivo, but may also lead to new therapeutic alternatives for OA as well as other relative degenerative joint diseases.
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- 2017
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11. Interaction between Flow Diverter and Parent Artery of Intracranial Aneurysm: A Computational Study
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Wenyu Fu and Qixiao Xia
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Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 - Abstract
To evaluate the influence of deployment strategy on the mechanical interaction between braided stent and parent artery of intracranial aneurysm (the elasticity of the arterial wall is considered), finite-element analyses are carried out by referring to computational models of flow-diverter device and arterial wall. Two implantation strategies are used to virtually implant the braided stent into the ideal intracranial aneurysm model. One is the noncompacted implantation method, and the other is the implantation method of using push-pull technique. During the process of the implantation, the changes of the arterial shape around the aneurysm and the changes of the wall pressure at the contact area between the braided stent and the inner wall of the artery are analyzed. The results indicate that the average contact pressure in the area of low porosity is 57 mmHg using the push-pull technique, and the average contact pressure of the parent artery is 10.45 mmHg using the non-push-pull technique. The diameter of the parent artery at the aneurismal orifice increased about 0.2 mm when using the push-pull technique, so the elasticity of the vessel should be considered in the mechanical analysis of interaction between stent and vessel.
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- 2017
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12. Parallel Computing Based Dynamic Programming Algorithm of Track-before-Detect
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Qiang Guo, Zhenwu Li, Wenming Song, and Wenyu Fu
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parallel computing ,track-before-detect ,dynamic programming ,weak target ,computational complexity ,Mathematics ,QA1-939 - Abstract
The conventional dynamic programming-based track-before-detect (DP-TBD) methods are usually intractable in multi-target scenarios. The adjacent targets may interfere with each other, and the computational complexity is increased with the number of targets. In this paper, a DP-TBD method using parallel computing (PC-DP-TBD) is proposed to solve the above problems. The search region of the proposed PC-DP-TBD is divided into several parts according to the possible target movement direction. The energy integration is carried out independently and parallel in each part. This contributes to reducing the computational complexity in each part, since the divided search region is smaller than the whole one. In addition, the target energy can only be integrated adequately in the part in which the search direction matches the target movement. This is beneficial to improve the ability to detect the targets with various movement directions in different parts with different search directions. The solution to the problem of the adjacent targets interfering with each other is discussed. The procedure of the parallel computing in the proposed PC-DP-TBD is presented in detail. Simulations are conducted to verify the superiority of the proposed PC-DP-TBD in terms of detection probability and computational complexity.
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- 2018
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13. Twisted electromagnetic sinc Schell-model beam and its transmission in a turbulent atmosphere.
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CHANGYOU ZHANG and WENYU FU
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RADIANT intensity , *ATMOSPHERIC turbulence , *OPTICAL communications , *WAREHOUSES , *ATMOSPHERE , *INTEGRALS - Abstract
We present the twisted electromagnetic sinc-correlation Schell-model (EM TSSM) beam as an extension of the cylindrical sinc Schell-model beam and analyze the necessary source parameter conditions to generate a physically viable beam. Furthermore, we thoroughly investigate the propagation properties of the EM TSSM beam in atmospheric turbulence using the extended Huygens-Fresnel integral, explicitly focusing on spectral intensity, degree of polarization (DOP), and degree of coherence (DOC). It shows that the twisted phase has a noticeable impact on the intensity profiles of these beams, causing them to exhibit rotation and self-splitting while still maintaining their shape in free space. Moreover, during propagation through a turbulent atmosphere, it exhibits self-combining properties over a long range and recovers the plat-topped distribution. Compared with the sinc Schell-model beam without the twisted phase, the DOP distribution of such a beam can rotate around its distribution center. As these beams propagate through turbulent atmospheres, they can self-heal their DOP distribution within specific ranges affected by atmospheric turbulence. A twist factor causes non-unidirectional rotation of the DOC distribution in free space. The DOC gradually transforms from multi-strip profiles into a Gaussian-like distribution. Furthermore, the beam parameters play a crucial role in shaping the DOC. The results will be useful in optical trapping and optical communication. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Propagation properties of partially coherent array beams with a non-uniform polarization.
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XIANYANG YANG and WENYU FU
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OPTICAL lattices , *COHERENCE (Optics) , *PERIODICAL circulation , *FREE-space optical technology - Abstract
We study a new class of partially coherent array beams with a non-uniform polarization, named radially polarized Gaussian Schell-model array (RPGSMA) beams and analyze the reliability conditions for the array beams based on the unified theory of coherence and polarization, Moreover, the statistical properties of such beam propagating in free space are investigated in detail. It is found that, the propagation properties of the RPGSMA beams are closely related to initial beam parameters. With an appropriate choice of the beam parameters, the average intensity will evolve into optical lattice patterns, and the degree of coherence (DOC) from the lattice distribution on the original plane evolves into a Gaussian profile in the far field, and the degree of polarization (DOP) appears a periodical grid-like distribution on propagation. These results may be beneficial to particle trapping and free-space optical communications. [ABSTRACT FROM AUTHOR]
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- 2023
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15. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases.
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Xiangli Zhao, Yi Lin, Benjamin Liou, Wenyu Fu, Jinlong Jian, Fannie, Venette, Wujuan Zhang, Setchell, Kenneth D. R., Grabowski, Gregory A., Ying Sun, and Chuan-ju Liu
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PATHOLOGY ,LYSOSOMAL storage diseases ,PARKINSON'S disease ,GAUCHER'S disease ,BLOOD-brain barrier - Abstract
Mutations in GBA1, encoding glucocerebrosidase (GCase), cause Gaucher disease (GD) and are also genetic risks in developing Parkinson's disease (PD). Currently, the approved therapies are only effective for directly treating visceral symptoms, but not for primary neuronopathic involvement in GD (nGD). Progranulin (PGRN), encoded by GRN, is a novel modifier of GCase, but the impact of PGRN in GBA1 mutation-associated pathologies in vivo remains unknown. Herein, Grn-/- mice crossed into Gba9v/9v mice, a Gba1 mutant line homozygous for the Gba1 D409V mutation, generating Grn-/-Gba9v/9v (PG9V) mice. PG9V mice exhibited neurobehavioral deficits, early onset, and more severe GD phenotypes compared to Grn-/- and Gba9v/9v mice. Moreover, PG9V mice also displayed PD-like phenotype. Mechanistic analysis revealed that PGRN deficiency caused severe neuroinflammation with microgliosis and astrogliosis, along with impaired autophagy associated with the Gba1 mutation. A PGRN-derived peptide, termed ND7, ameliorated the disease phenotype in GD patient fibroblasts ex vivo. Unexpectedly, ND7 penetrated the blood-brain barrier (BBB) and effectively ameliorated the nGD manifestations and PD pathology in Gba9v/null and PG9V mice. Collectively, this study not only provides the first line of in vivo but also ex vivo evidence demonstrating the crucial role of PGRN in GBA1/Gba1 mutation-related pathologies, as well as a clinically relevant mouse model for mechanistic and potential therapeutics studies for nGD and PD. Importantly, a BBB penetrant PGRN-derived biologic was developed that may provide treatment for rare lysosomal storage diseases and common neurodegenerative disorders, particularly nGD and PD. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Properties of an electromagnetic twisted Gaussian Schell-model array beam propagating in anisotropic atmosphere turbulence.
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XIANYANG YANG, WENYU FU, XUEHUA HU, and XUE LI
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TURBULENCE , *ATMOSPHERIC turbulence , *ELECTROMAGNETIC pulses , *RADIANT intensity , *ATMOSPHERE , *SPECTRAL energy distribution - Abstract
The effect of anisotropic atmosphere turbulence on propagation characteristics of an electromagnetic twisted Gaussian Schell-model array (EM TGSMA) beam is investigated. An analytical expression for the cross-spectral density function of such beam propagating through anisotropic turbulent atmosphere is derived and used to explore the evolutionary behavior of the spectral intensity, degree of polarization (DOP) and degree of coherence (DOC). An example illustrates the fact that twisted strength and anisotropic turbulent factors have an important impact on the behavior of spectral density, DOC and DOP, in particular. The rotation angle of the array beams can also be controlled by adjusting twisted strength. Furthermore, strong anisotropic turbulence was also found to cause significant mergence of the array beams. Our results might be beneficial for free-space communications of the partially coherent beams endowed with twist. [ABSTRACT FROM AUTHOR]
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- 2022
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17. In vitro physical and functional interaction assays to examine the binding of progranulin derivative Atsttrin to TNFR2 and its anti-TNFα activity
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Wenyu Fu, Aubryanna Hettinghouse, and Chuan-ju Liu
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0301 basic medicine ,Cell ,Arthritis ,Enzyme-Linked Immunosorbent Assay ,Article ,Pathogenesis ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Progranulins ,Osteogenesis ,Protein Interaction Mapping ,medicine ,Receptors, Tumor Necrosis Factor, Type II ,Cells, Cultured ,biology ,Chemistry ,Tumor Necrosis Factor-alpha ,Acid phosphatase ,Physical inhibition ,medicine.disease ,In vitro ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Direct binding ,Cancer research ,biology.protein ,Tumor necrosis factor alpha ,Protein Binding - Abstract
TNFα/TNFR signaling plays a critical role in the pathogenesis of various inflammatory and autoimmune diseases, and anti-TNFα therapies have been accepted as the effective approaches for treating several autoimmune diseases. Progranulin (PGRN), a multi-faced growth factor-like molecule, directly binds to TNFR1 and TNFR2, particularly to the latter with higher affinity than TNFα. PGRN derivative Atsttrin is composed of three TNFR-binding domain of PGRN and exhibits even better therapeutic effects than PGRN in several inflammatory disease models, including collagen-induced arthritis. Herein we describe the detailed methodology of using (1) ELISA-based solid phase protein-protein interaction assay to demonstrate the direct binding of Atsttrin to TNFR2 and its inhibition of TNFα/TNFR2 interaction; and (2) tartrate-resistant acid phosphatase (TRAP) staining of in vitro osteoclastogenesis to reveal the cell-based anti-TNFα activity of Atsttrin. Using the protocol described here, the investigators should be able to reproducibly detect the physical inhibition of TNFα binding to TNFR and the functional inhibition of TNFα activity by Atsttrin and various kinds of TNF inhibitors.
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- 2021
18. Modeling by disruption and a selected‐for partner for the nude locus
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Anne M Whalen, Jian Li, Wenyu Fu, Lorin Weiner, Mario Clemente Estable, Laurel A. Raftery, Yun-Kyoung Lee, Janice L. Brissette, and Kristin White
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flash‐forward genetics ,skin ,Mice, Nude ,Locus (genetics) ,Thymus Gland ,Biology ,Biochemistry ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Transcription (biology) ,multimolecular positive selection ,Gene expression ,Genetics ,Transcriptional regulation ,Animals ,News & Views ,transcriptional regulation ,Molecular Biology ,Transcription factor ,Gene ,developmental mechanisms ,030304 developmental biology ,0303 health sciences ,integumentary system ,fungi ,FOXN1 ,Forkhead Transcription Factors ,Articles ,Phenotype ,Biological Evolution ,Gene Expression Regulation ,Development & Differentiation ,Hair Follicle ,030217 neurology & neurosurgery - Abstract
A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it will be in its natural, formative contexts (mammals). The approach identifies Aff4 as the first nude‐like locus, as murine AFF4 and FOXN1 cooperatively induce similar cutaneous/thymic phenotypes, similar gene expression programs, and the same step of transcription, pre‐initiation complex formation. These AFF4 functions are unexpected, as AFF4 also serves as a scaffold in common transcriptional‐elongation complexes. Most likely, the approach works because an interaction's power to disrupt is the inevitable consequence of its selected‐for power to benefit., A genetic screen in Drosophila for genes that synergize with mammalian FOXN1 identifies Aff4 as a nude‐like locus. AFF4 cooperates with FOXN1 in mammalian hair and thymus development.
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- 2020
19. Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction
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Zi Ning Lei, Wenyu Fu, Zhe-Sheng Chen, Kaidi Wang, Yujianan Chen, Jing Quan Wang, Chuan-ju Liu, Wenhuo Hu, Aubryanna Hettinghouse, and Kenneth A. Stapleford
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Peptidyl-Dipeptidase A ,Cell Biology ,Virology ,Biochemistry ,Human genetics ,Drug repositioning ,Drug Discovery ,Medicine ,Stem cell ,business ,Repurposing ,Biotechnology - Published
- 2020
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20. Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge
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Philipp Berg, Kristian Valen-Sendstad, Alistair G. Brown, Stephen P. Broderick, Leonid Goubergrits, David A. Steinman, Nicolas Aristokleous, G. Albert Einstein, Kent-Andre Mardal, Masanori Tsuji, Satoshi Koizumi, Yuji Shimogonya, Neil Ashton, Masaaki Shojima, Alistair Revell, Simona Hodis, Salvatore Cito, Fujimaro Ishida, Kerem Pekkan, A. J. Geers, Prahlad G. Menon, Jordi Pallares, Charles B. L. M. Majoie, Bart M. W. Cornelissen, Wenyu Fu, Hernán G. Morales, Senol Piskin, Justin Tran, Yahia M. Al-Smadi, Kartik Jain, Shawn C. Shadden, Sreeja Vaippummadhom, Jan Bruening, Aike Qiao, Michael Barbour, Adam Updegrove, Sylvia Saalfield, M. Owais Khan, Shin Ichiro Sugiyama, Sabine Roller, Kuniyasu Niizuma, Ignacio Larrabide, Sherif Rashad, Thierry Lefevre, Aslak W. Bergersen, Alison L. Marsden, Kristian Debus, Viorel Mihalef, Alberto Aliseda, Leonard D. Browne, J. Graeme Houston, Saikiran Rapaka, Thomas Spirka, Ramji Kamakoti, Kenichi Kono, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, ANS - Neurovascular Disorders, and Radiology and Nuclear Medicine
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Patient-Specific Modeling ,Middle Cerebral Artery ,Computer science ,02 engineering and technology ,Inflow ,Wall shear stress ,0302 clinical medicine ,Statistics ,Rupture risk ,UNCERTAINTY QUANTIFICATION ,Uncertainty quantification ,Models, Cardiovascular ,Solver ,Prognosis ,Cerebrovascular Circulation ,cardiovascular system ,Radiographic Image Interpretation, Computer-Assisted ,PATIENT-SPECIFIC MODELLING ,Cardiology and Cardiovascular Medicine ,CIENCIAS NATURALES Y EXACTAS ,Blood Flow Velocity ,Patient-specific modelling ,0206 medical engineering ,Biomedical Engineering ,Computational fluid dynamics ,RUPTURE RISK ,Article ,03 medical and health sciences ,Imaging, Three-Dimensional ,Aneurysm ,Predictive Value of Tests ,WALL SHEAR STRESS ,Shear stress ,medicine ,Humans ,INTRACRANIAL ANEURYSM ,business.industry ,Hemodynamics ,Reproducibility of Results ,Intracranial Aneurysm ,medicine.disease ,020601 biomedical engineering ,Cerebral Angiography ,Regional Blood Flow ,3d rotational angiography ,Ciencias de la Computación e Información ,Stress, Mechanical ,business ,Ciencias de la Información y Bioinformática ,030217 neurology & neurosurgery - Abstract
Purpose—Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline. Methods—3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters. Results—A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability. Conclusions—Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters. Fil: Valen-Sendstad, Kristian. Simula Research Laboratory and Center for Cardiological Innovation; Noruega Fil: Bergersen, Aslak W.. University of Oslo; Noruega Fil: Shimogonya, Yuji. Nihon University; Japón Fil: Goubergrits, Leonid. Charite´ – Universita¨tsmedizin Berlin; Alemania Fil: Bruening, Jan. Charité – Universitätsmedizin Berlin; Alemania Fil: Pallares, Jordi. Universitat Rovira I Virgili; España Fil: Cito, Salvatore. Universitat Rovira I Virgili; España Fil: Piskin, Senol. University Of Texas At San Antonio.; Estados Unidos Fil: Pekkan, Kerem. Koc University; Turquía Fil: Geers, Arjan J.. Universitat Pompeu Fabra; España Fil: Larrabide, Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rapaka, Saikiran. Siemens Medical Solutions USA Inc; Estados Unidos Fil: Mihalef, Viorel. Siemens Medical Solutions USA Inc; Estados Unidos Fil: Fu, Wenyu. Beijing Union University; China Fil: Qiao, Aike. Beijing University of Technology; China Fil: Jain, Kartik. Simula Research Laboratory and Center for Cardiological Innovation; Noruega. University of Siegen; Alemania. University of Zürich; Suiza Fil: Roller, Sabine. University of Siegen; Alemania Fil: Mardal, Kent-Andre. Simula Research Laboratory and Center for Cardiological Innovation; Noruega. University of Oslo; Noruega Fil: Kamakoti, Ramji. Dassault Systemes; Francia Fil: Spirka, Thomas. Simpleware Software Solutions; Reino Unido Fil: Ashton, Neil. University of Oxford; Reino Unido Fil: Revell, Alistair. University of Manchester; Reino Unido Fil: Aristokleous, Nicolas. University of Limerick; Irlanda Fil: Houston, J. Graeme. University of Dundee; Reino Unido Fil: Tsuji, Masanori. Mie Chuo Medical Center; Japón Fil: Ishida, Fujimaro. Mie Chuo Medical Center; Japón Fil: Menon, Prahlad G.. University of Pittsburgh; Estados Unidos Fil: Browne, Leonard D.. University of Limerick; Irlanda Fil: Broderick, Stephen. University of Limerick; Irlanda Fil: Shojima, Masaaki. University of Tokyo; Japón Fil: Koizumi, Satoshi. University of Tokyo; Japón Fil: Barbour, Michael. University of Washington; Estados Unidos Fil: Aliseda, Alberto. University of Washington; Estados Unidos Fil: Morales, Hernán G.. Medisys - Philips Research Paris; Francia Fil: Lefèvre, Thierry. Medisys - Philips Research Paris; Francia Fil: Hodis, Simona. Texas A&M University - Kingsville; Estados Unidos Fil: Al-Smadi, Yahia M.. Jordan University of Science and Technology; Jordania Fil: Tran, Justin S.. Stanford University; Estados Unidos Fil: Marsden, Alison L.. Stanford University; Estados Unidos Fil: Vaippummadhom, Sreeja. EinNel Technlogies; India Fil: Einstein, G. Albert. EinNel Technlogies; India Fil: Brown, Alistair G.. Siemens PLM Software; Estados Unidos Fil: Debus, Kristian. Siemens PLM Software; Estados Unidos Fil: Niizuma, Kuniyasu. Tohoku University; Japón Fil: Rashad, Sherif. Tohoku University; Japón Fil: Sugiyama, Shin-ichiro. Kohnan Hospital; Japón Fil: Owais Khan, M.. University of Toronto; Canadá Fil: Updegrove, Adam R.. University of California at Berkeley; Estados Unidos Fil: Shadden, Shawn C.. University of California at Berkeley; Estados Unidos Fil: Cornelissen, Bart M. W.. Academic Medical Center; Países Bajos Fil: Majoie, Charles B. L. M.. Academic Medical Center; Países Bajos Fil: Berg, Philipp. University of Magdeburg; Alemania Fil: Saalfield, Sylvia. University of Magdeburg; Alemania Fil: Kono, Kenichi. Wakayama Rosai Hospital; Japón Fil: Steinman, David A.. University of Toronto; Canadá
- Published
- 2018
21. Properties of the Rotation and Mergence of Twisted Gaussian Schell Model Array Beams Propagating in Turbulent Biological Tissues.
- Author
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Xianyang, Yang and Wenyu, Fu
- Subjects
ROTATIONAL motion ,TISSUES - Abstract
In this paper, an analytical expression for describing propagation properties of twisted Gaussian Schell model array (TGSMA) beams through turbulent biological tissues is derived based on the extended Huygens Fresnel integral. With the help of the formulae, properties of the rotation and mergence for the TGSMA beams in turbulent biological tissues are researched in detail. It is found that the TGSMA beams go through the distinct mergence period in the far field besides phenomena of abruption and rotation in the near field, and turbulent biological tissues play a dominated role in mergence of the TGSMA beams. These novel results may be helpful in optical trapping. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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22. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis.
- Author
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Wenyu Fu, Hettinghouse, Aubryanna, Yujianan Chen, Wenhuo Hu, Xiang Ding, Meng Chen, Yuanjing Ding, Mundra, Jyoti, Wenhao Song, Ronghan Liu, Young-Su Yi, Attur, Mukundan, Samuels, Jonathan, Strauss, Eric, Leucht, Philipp, Schwarzkopf, Ran, Chuan-ju Liu, Fu, Wenyu, Chen, Yujianan, and Hu, Wenhuo
- Subjects
PROTEIN metabolism ,CARTILAGE cells ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,CELL receptors ,MEDICAL cooperation ,EVALUATION research ,CELLULAR signal transduction ,COMPARATIVE studies ,OSTEOARTHRITIS ,DNA-binding proteins ,RESEARCH funding ,ARTICULAR cartilage ,CARRIER proteins ,MICE - Abstract
Objectives: Osteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA.Methods: Biochemical copurification and proteomics screen were performed to isolate the intracellular cofactors of TNFR2 complex. Bulk and single cell RNA-seq were employed to determine 14-3-3 epsilon (14-3-3ε) expression in human normal and OA cartilage. Transcription factor activity screen was used to isolate the transcription factors downstream of TNFR2/14-3-3ε. Various cell-based assays and genetically modified mice with naturally occurring and surgically induced OA were performed to examine the importance of this pathway in chondrocytes and OA.Results: Signalling molecule 14-3-3ε was identified as an intracellular component of TNFR2 complexes in chondrocytes in response to progranulin (PGRN), a growth factor known to protect against OA primarily through activating TNFR2. 14-3-3ε was downregulated in OA and its deficiency deteriorated OA. 14-3-3ε was required for PGRN regulation of chondrocyte metabolism. In addition, both global and chondrocyte-specific deletion of 14-3-3ε largely abolished PGRN's therapeutic effects against OA. Furthermore, PGRN/TNFR2/14-3-3ε signalled through activating extracellular signal-regulated kinase (ERK)-dependent Elk-1 while suppressing nuclear factor kappa B (NF-κB) in chondrocytes.Conclusions: This study identifies 14-3-3ε as an inducible component of TNFR2 receptor complex in response to PGRN in chondrocytes and presents a previously unrecognised TNFR2 pathway in the pathogenesis of OA. [ABSTRACT FROM AUTHOR]- Published
- 2021
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23. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis
- Author
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Yazhou Cui, Shuya Wang, Yuehong Chen, Xiangli Zhao, Ronghan Liu, Jody Liu, Chao Wang, Chen Zhang, Yufei Bi, Guozhi Xiao, Wenyu Fu, Chuan-ju Liu, Zhe-Sheng Chen, Aubryanna Hettinghouse, and Zi-Ning Lei
- Subjects
0301 basic medicine ,Inflammatory arthritis ,Immunology ,Arthritis ,Phospholipases A2, Cytosolic ,Inflammation ,Mice, Transgenic ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Phospholipase A2 ,Rheumatology ,In vivo ,medicine ,Immunology and Allergy ,Animals ,030203 arthritis & rheumatology ,Fexofenadine ,biology ,business.industry ,Tumor Necrosis Factor-alpha ,medicine.disease ,Arthritis, Experimental ,In vitro ,030104 developmental biology ,Mice, Inbred DBA ,biology.protein ,Tumor necrosis factor alpha ,Tumor Necrosis Factor Inhibitors ,Terfenadine ,medicine.symptom ,business ,medicine.drug ,Signal Transduction - Abstract
ObjectiveTumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis.MethodsIn vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice. Identification and characterisation of the binding of fexofenadine to cytosolic phospholipase A2 (cPLA2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, information field dynamics and molecular dynamics; various assays for examining fexofenadine inhibition of cPLA2 as well as the dependence of fexofenadine’s anti-TNF activity on cPLA2.ResultsSerial screenings of a library composed of FDA-approved drugs led to the identification of fexofenadine as an inhibitor of TNF-α signalling. Fexofenadine potently inhibited TNF/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signalling in vitro and in vivo, and ameliorated disease symptoms in inflammatory arthritis models. cPLA2 was isolated as a novel target of fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished fexofenadine’s anti-TNF activity.ConclusionCollectively, these findings not only provide new insights into the understanding of fexofenadine action and underlying mechanisms but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly inflammatory rheumatic diseases.
- Published
- 2019
24. TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity.
- Author
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Wenyu Fu, Wenhuo Hu, Young-Su Yi, Hettinghouse, Aubryanna, Guodong Sun, Yufei Bi, Wenjun He, Lei Zhang, Guanmin Gao, Liu, Jody, Kazuhito Toyo-oka, Guozhi Xiao, Solit, David B., Loke, Png, Chuan-ju Liu, Fu, Wenyu, Hu, Wenhuo, Yi, Young-Su, Sun, Guodong, and Bi, Yufei
- Subjects
- *
MACROPHAGES , *AUTOIMMUNE diseases , *AUTOIMMUNITY , *INFLAMMATION , *MASS spectrometry , *PATHOGENESIS , *PROTEIN metabolism , *PROTEINS , *ANIMAL experimentation , *CELL receptors , *CELLULAR signal transduction , *IMMUNITY , *ARTHRITIS , *CARRIER proteins , *MICE - Abstract
TNFR1 and TNFR2 have received prominent attention because of their dominance in the pathogenesis of inflammation and autoimmunity. TNFR1 has been extensively studied and primarily mediates inflammation. TNFR2 remains far less studied, although emerging evidence demonstrates that TNFR2 plays an antiinflammatory and immunoregulatory role in various conditions and diseases. Herein, we report that TNFR2 regulates macrophage polarization, a highly dynamic process controlled by largely unidentified intracellular regulators. Using biochemical copurification and mass spectrometry approaches, we isolated the signaling molecule 14-3-3ε as a component of TNFR2 complexes in response to progranulin stimulation in macrophages. In addition, 14-3-3ε was essential for TNFR2 signaling-mediated regulation of macrophage polarization and switch. Both global and myeloid-specific deletion of 14-3-3ε resulted in exacerbated inflammatory arthritis and counteracted the protective effects of progranulin-mediated TNFR2 activation against inflammation and autoimmunity. TNFR2/14-3-3ε signaled through PI3K/Akt/mTOR to restrict NF-κB activation while simultaneously stimulating C/EBPβ activation, thereby instructing macrophage plasticity. Collectively, this study identifies 14-3-3ε as a previously unrecognized vital component of the TNFR2 receptor complex and provides new insights into the TNFR2 signaling, particularly its role in macrophage polarization with therapeutic implications for various inflammatory and autoimmune diseases with activation of the TNFR2/14-3-3ε antiinflammatory pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. Interaction between Flow Diverter and Parent Artery of Intracranial Aneurysm: A Computational Study
- Author
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Qixiao Xia and Wenyu Fu
- Subjects
Materials science ,Article Subject ,QH301-705.5 ,medicine.medical_treatment ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Parent artery ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Aneurysm ,medicine ,Elasticity (economics) ,Biology (General) ,Stent ,medicine.disease ,medicine.anatomical_structure ,Implant ,Contact area ,030217 neurology & neurosurgery ,Body orifice ,TP248.13-248.65 ,Artery ,Biomedical engineering ,Research Article ,Biotechnology - Abstract
To evaluate the influence of deployment strategy on the mechanical interaction between braided stent and parent artery of intracranial aneurysm (the elasticity of the arterial wall is considered), finite-element analyses are carried out by referring to computational models of flow-diverter device and arterial wall. Two implantation strategies are used to virtually implant the braided stent into the ideal intracranial aneurysm model. One is the noncompacted implantation method, and the other is the implantation method of using push-pull technique. During the process of the implantation, the changes of the arterial shape around the aneurysm and the changes of the wall pressure at the contact area between the braided stent and the inner wall of the artery are analyzed. The results indicate that the average contact pressure in the area of low porosity is 57 mmHg using the push-pull technique, and the average contact pressure of the parent artery is 10.45 mmHg using the non-push-pull technique. The diameter of the parent artery at the aneurismal orifice increased about 0.2 mm when using the push-pull technique, so the elasticity of the vessel should be considered in the mechanical analysis of interaction between stent and vessel.
- Published
- 2017
26. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis.
- Author
-
Ronghan Liu, Yuehong Chen, Wenyu Fu, Shuya Wang, Yazhou Cui, Xiangli Zhao, Zi-Ning Lei, Hettinghouse, Aubryanna, Jody Liu, Chao Wang, Chen Zhang, Yufei Bi, Guozhi Xiao, Zhe-Sheng Chen, Chuan-Ju Liu, Liu, Ronghan, Chen, Yuehong, Fu, Wenyu, Wang, Shuya, and Cui, Yazhou
- Abstract
Objective: Tumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis.Methods: In vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice. Identification and characterisation of the binding of fexofenadine to cytosolic phospholipase A2 (cPLA2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, information field dynamics and molecular dynamics; various assays for examining fexofenadine inhibition of cPLA2 as well as the dependence of fexofenadine's anti-TNF activity on cPLA2.Results: Serial screenings of a library composed of FDA-approved drugs led to the identification of fexofenadine as an inhibitor of TNF-α signalling. Fexofenadine potently inhibited TNF/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signalling in vitro and in vivo, and ameliorated disease symptoms in inflammatory arthritis models. cPLA2 was isolated as a novel target of fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished fexofenadine's anti-TNF activity.Conclusion: Collectively, these findings not only provide new insights into the understanding of fexofenadine action and underlying mechanisms but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly inflammatory rheumatic diseases. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
27. Twist phase-induced characteristics changes of a radially polarized Gaussian Schell-Model beam in a uniaxial crystal orthogonal to the optical axis.
- Author
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Pengfei Cao and Wenyu Fu
- Published
- 2017
- Full Text
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28. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models.
- Author
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Wei, Jian-lu, Wenyu Fu, Yuan-jing Ding, Hettinghouse, Aubryanna, Lendhey, Matin, Schwarzkopf, Ran, Kennedy, Oran D., and Chuan-ju Liu
- Published
- 2017
- Full Text
- View/download PDF
29. Second-order statistics of a radially polarized partially coherent twisted beam in a uniaxial crystal.
- Author
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WENYU FU and PENGFEI CAO
- Published
- 2017
- Full Text
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30. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis.
- Author
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Wenyu Fu, Wenhuo Hu, Lei Shi, Mundra, Jyoti Joshi, GuoZhi Xiao, Dustin, Michael L., and Chuan-ju Liu
- Abstract
Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN. In addition, PGRN-mediated expansion and activation of Treg cells, as well as IL-10 production, depends on JNK signaling, but not on known PGRN-activated ERK and PI3K pathways. Furthermore, microarray and chromatin immunoprecipitation sequencing screens led to the discovery of forkhead box protein O4 and signal transducer and activator of transcription 3 as the transcription factors required for PGRN induction of IL-10 in Treg cells. These findings define a previously unrecognized signaling pathway that underlies IL-10 production by PGRN in Treg cells and present new insights into the mechanisms by which PGRN resolves inflammation in inflammatory conditions and autoimmune diseases, particularly inflammatory arthritis.--Fu, W., Hu, W., Shi, L., Mundra, J. J. Xiao, G., Dustin, M. L., Liu, C. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
31. The Computational Fluid Dynamics Rupture Challenge 2013-Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.
- Author
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Berg, Philipp, Roioff, Christoph, Beuing, Oliver, Voss, Samuel, Shin-lchiro Sugiyama, Aristokleous, Nicolas, Ashton, Neil, Revell, Alistair, Bressloff, Neil W., Brown, Alistair G., Bong Jae Chung, Cebral, Juan R., Copelli, Gabriele, Wenyu Fu, Geers, Arjan J., Hodis, Simona, Dragomir-Daescu, Dan, and Qiao, Aike
- Published
- 2015
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32. Analysis of Fluid Structure Interaction based on patient-specific internal carotid aneurysm model.
- Author
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Wenyu Fu and Aike Qiao
- Published
- 2011
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- View/download PDF
33. Approaches to the Reconstruction of Numerical Simulation Oriented Patient-Specific Model of Aortic Arch Aneurysm.
- Author
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Xianlong Meng, Wenyu Fu, Yun Zhang, and Aike Qiao
- Published
- 2010
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34. An effective inducer of dopaminergic neuron-like differentiation.
- Author
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Wenyu Fu, Cui Lv, Wenxin Zhuang, Dandan Chen, Lv, E., Fengjie Li, and Xiaocui Wang
- Abstract
The article discusses a study which aims to determine an effective inducer for dopaminerergic neuron differentiation. The study utilized cultured mesenchymal stem cells derived from bone marrow of rat which were induced into dopaminergic neurons. Results reveal that bone marrow-derived mesynchymal cells demonstrates typical neuronal morphological characteristics after induction.
- Published
- 2013
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35. Identification of Temporal Differentially Expressed Protein Responses to Microcystin in Human Amniotic Epithelial Cells.
- Author
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Wenyu Fu, Yingnian Yu, and Lihong Xu
- Subjects
- *
GENETIC regulation , *P53 protein , *MICROCYSTINS , *EPITHELIAL cells , *UBIQUITIN , *AMNIOTIC liquid - Abstract
The increased distribution of microcystins (MCs) has become a global issue. However, the MC response machinery has not been completely studied and elucidated until now. Our previous dose-related analysis has revealed that different concentrations of mirocystin-RR (MC-RR) can trigger comprehensive and various alterations in the protein expression profile using a proteomic approach. To further dissect the kinetics of cellular responses associated with MC-RR cytotoxic effects, the present study has set out to investigate the temporal protein expression pattern at three time points (3, 12, and 24 h after exposure). The relative intensity has changed significantly in MC-RR-treated FL cells, as compared with the control, in a total of 127 protein spots. One hundred and two proteins have been further identified with high confidence by peptide mass fingerprinting. These proteins can be categorized into diverse functional classes such as signal transduction, apoptosis, protein degradation, cell cycle, cell differentiation, transporter, and so forth. The wide range of different proteins involved suggests that MC-RR has profound effects on the biological response and toxic consequences of the affected cells. The identification of p53 and its potential targets confirms a known role for p53 in the MC-RR response. Moreover, it is noteworthy that MC-RR can up-regulate the expression of the PP2A A subunit and down-regulate the expression of a number of proteins implicated in the ubiquitin-proteasome pathway. Therefore, the present expression data provide a global view of dynamic changes in cell responses to MC-RR and, more importantly, generate novel hypotheses regarding MC-RR-responsive mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
36. An improved measurement method of size of mechanical parts based on monocular vision.
- Author
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Qiang Guo and Wenyu Fu
- Published
- 2020
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37. Microcystin-LR (MCLR) Induces a Compensation of PP2A Activity Mediated by α4 Protein in HEK293 Cells
- Author
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Tan Li, Pu Huang, Jing Liang, Wenyu Fu, Zonglou Guo, Lihong Xu
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Protein phosphatase 2A (PP2A) is a major protein phosphatase with important cell functions. Known and utilized as a potent inhibitor of PP2A, microcystin-LR (MCLR) targets PP2A as a core element that affects numerous cellular mechanisms. But apart from direct inhibition, the exact effect of MCLR on PP2A in cell is largely unknown, specifically with regard to cellular response and autoregulation. Here, we show that a low concentration of MCLR stimulates, rather than inhibits, PP2A activity in HEK293 cells. Immunoprecipitation and immunofluorescence assays reveal that the catalytic subunit and a regulatory subunit of PP2A, termed α4, dissociate from inactive complex upon MCLR exposure, suggesting that the released catalytic subunit regains activity and thereby compensates the activity loss. At high concentrations of MCLR, PP2A activity decreases along with dissociation of the core enzyme and altered post-translational modification of its catalytic subunit. In addition, the dissociation of α4 and PP2A may contribute to destabilization of HEK293 cells cytoskeleton architecture, detachment to extracellular matrix and further anoikis. Our data provide a novel PP2A upregulation mechanism and challenge the recognition of MCLR only as a PP2A inhibitor in cells.
- Published
- 2011
38. Clinicopathologic significance of cytokine levels in esophageal squamous cell carcinoma.
- Author
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Xin Z, Wenyu F, and Shenhua X
- Subjects
- Adult, Carcinoma, Squamous Cell pathology, Case-Control Studies, Esophageal Neoplasms pathology, Female, Flow Cytometry, Humans, Interferon-gamma immunology, Interleukin-10 immunology, Interleukin-2 immunology, Interleukin-4 immunology, Interleukin-5 immunology, Male, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Statistics, Nonparametric, Tumor Necrosis Factor-alpha immunology, Carcinoma, Squamous Cell immunology, Cytokines immunology, Esophageal Neoplasms immunology
- Abstract
Background/aims: Treatment's effect on esophageal squamous cell carcinoma (ESCC) patients' immune functions may influence outcomes. Here, we address the scarcity of information about immune responses of treated and untreated ESCC patients., Methodology: Levels of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5 and IL-10 were detected in 36 untreated patients (UPs), and 82 treated patients (TPs) with ESCC, and in 70 healthy controls, using cytometric bead arrays., Results: Levels of IL-2, IL-4 and IL-5 were higher (p < 0.001), and TNF-alpha was lower (p < 0.01), in UPs than in controls; IFN-gamma, IL-2, IL-4, IL-5 and IL-10 levels were higher in TPs than in controls (p < 0.001); IFN-gamma, TNF-alpha and IL-10 levels were higher in TPs than in UPs (p < 0.05); IFN-gamma/IL-4 ratios of UPs were lower than controls (p < 0.05). Levels did not significantly differ by age or weight index, but did differ by clinical stages, differentiation degree and tumor location. Patients' survival was affected by clinical stage (p = 0.001), differentiation degree (p = 0.012), tumor location (p = 0.043) and lymph node involvement (p = 0.039); clinical stage was an independent prognostic factor (p = 0.014)., Conclusions: We found that Th1/Th2 imbalance and immune function turbulence correlate with differentiation degree, clinical stage and tumor location. Moreover, clinical stage is currently the best predictor of survival.
- Published
- 2010
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