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  • Frontiers Media SA  (12)
  • Liu, Yuhong  (12)
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  • Frontiers Media SA  (12)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-7-19)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-7-19)
    Abstract: Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-12-20)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-12-20)
    Abstract: Small-diameter vascular grafts (diameter & lt;6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-8-30)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-8-30)
    Abstract: Background: Neointima formation contributes to vascular grafts stenosis and thrombosis. It is a complex reaction that plays a significant role in the performance of vascular grafts. Despite its critical implications, little is known about the mechanisms underlying neointima formation. This study compares neointima proteome in different stages and plasma samples. Methods: Heterogenous acellular native arteries were implanted as abdominal aortic interposition grafts in a rabbit model. Grafts were harvested at 0.5, 1, 4, 6, 7, 14, 21, and 28 days post-surgery for histological and proteomic analysis of the neointima. Results: Histological examination showed a transformed morphological pattern and components, including serum proteins, inflammatory cells, and regenerative cells. Proteomics analysis of the neointima showed distinct characteristics after 14 days of implantation compared to early implantation. Early changes in the neointima samples were proteins involved in acute inflammation and thrombosis, followed by the accumulation of extracellular matrix (ECM) proteins. A total of 110 proteins were found to be differentially expressed in later samples of neointima compared to early controls. The enriched pathways were mainly protein digestion and adsorption, focal adhesion, PI3K-Akt signaling pathway, and ECM-receptor interaction in the late stage. All distributions of proteins in the neointima are different compared to plasma. Conclusion: The biological processes of neointima formation at different stages identified with proteome found developmental characteristics of vascular structure on a decellularized small vascular graft, and significant differences were identified by proteomics in the neointima of early-stage and late-stage after implantation. In the acute unstable phase, the loose and uniform neointima was mainly composed of plasma proteins and inflammatory cells. However, in the relatively stable later stage, the most notable results were an up-regulation of ECM components. The present study demonstrates an interaction between biological matter and vascular graft, provides insights into biological process changes of neointima and facilitates the construction of a functional bioengineered small vascular graft for future clinical applications.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-9-5)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-9-5)
    Abstract: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Bioengineering and Biotechnology Vol. 11 ( 2023-3-27)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 11 ( 2023-3-27)
    Abstract: The durability of bioprosthetic heart valves is always compromised by the inherent antigenicity of biomaterials. Decellularization has been a promising approach to reducing the immunogenicity of biological valves. However, current methods are insufficient in eliminating all immunogenicity from the biomaterials, necessitating the exploration of novel techniques. In this study, we investigated using a novel detergent, fatty alcohol polyoxyethylene ether sodium sulfate (AES), to remove antigens from bovine pericardium. Our results demonstrated that AES treatment achieved a higher pericardial antigen removal rate than traditional detergent treatments while preserving the mechanical properties and biocompatibility of the biomaterials. Moreover, we observed excellent immune tolerance in the in vivo rat model. Overall, our findings suggest that AES treatment is a promising method for preparing biological valves with ideal clinical application prospects.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2719493-0
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-8-25)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-8-25)
    Abstract: Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β -patchoulene ( β -PAE) is an active ingredient isolated from Pogostemon cablin (Blanco) Benth (Labiatae) and has shown a marked protective effect against gastrointestinal diseases in previous studies. However, whether β -PAE plays a positive role in IM is still unknown. Herein, we explore the effects and the underlying mechanism of β -PAE against 5-fluorouracil (5-FU)-induced IM in IEC-6 cells and rats. β -PAE significantly recovered cell viability, upregulated the IM-induced rat body weight and food intake and improved the pathological diarrhea symptoms. Aquaporin is critical for regulating water fluid homeostasis, and its abnormal expression was associated with pathological diarrhea in IM. β -PAE displayed an outstanding effect in inhibiting aquaporin 3 (AQP3) via the cAMP/protein kinase A (PKA)/cAMP-response element-binding protein (CREB) signaling pathway. Besides, inflammation-induced mucus barrier injury deteriorated water transport and aggravated diarrhea in IM-induced rats. β -PAE’s effect on suppressing inflammation and recovering the mucus barrier strengthened its regulation of water transport and thus alleviated diarrhea in IM-induced rats. In sum, β -PAE improved IM in rats mainly by improving water transport and the mucus barrier, and these effects were correlated with its function on inhibiting the cAMP/PKA/CREB signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-3-30)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-3-30)
    Abstract: Coptisine (COP) is a bioactive isoquinoline alkaloid derived from Coptis Chinemsis Franch, which is traditionally applied for the management of colitis. However, the blood concentration of COP was extremely low, and its gut microbiota-mediated metabolites were thought to contribute to its prominent bioactivities. To comparatively elucidate the protective effect and underlying mechanism of COP and its novel gut microbiota metabolite (8-oxocoptisine, OCOP) against colitis, we used dextran sulfate sodium (DSS) to induce colitis in mice. Clinical symptoms, microscopic alternation, immune-inflammatory parameters for colitis were estimated. The results indicated that OCOP dramatically ameliorated disease activity index (DAI), the shortening of colon length and colonic histopathological deteriorations. OCOP treatment also suppressed the mRNA expression and release of inflammatory mediators (TGF-β, TNF-α, IL-6, IL-18, IL-1β and IFN-γ) and elevated the transcriptional and translational levels of anti-inflammatory cytokine (IL-10) as well as the mRNA expression levels of adhesion molecules ( ICAM-1 and VCAM-1 ). Besides, the activation of NF-κB pathway and NLRP3 inflammasome was markedly inhibited by OCOP. Furthermore, OCOP displayed superior anti-colitis effect to COP, and was similar to MSZ with much smaller dosage. Taken together, the protective effect of OCOP against DSS-induced colitis might be intimately related to inhibition of NF-κB pathway and NLRP3 inflammasome. And the findings indicated that OCOP might have greater potential than COP to be further exploited as a promising candidate in the treatment of colitis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-5-19)
    Abstract: Bioprosthetic heart valves (BHVs) used in clinics are fabricated via glutaraldehyde (GLUT) crosslinking, which results in cytotoxicity and causes eventual valve calcification after implantation into the human body; therefore, the average lifetime and application of BHVs are limited. To address these issues, the most commonly used method is modification with amino acids, such as glycine (GLY), which is proven to effectively reduce toxicity and calcification. In this study, we used the l -glutathione (GSH) in a new modification treatment based on GLUT-crosslinked bovine pericardium (BP) as the GLUT + GSH group, BPs crosslinked with GLUT as GLUT-BP (control group), and GLY modification based on GLUT-BP as the GLUT + GLY group. We evaluated the characteristics of BPs in different treatment groups in terms of biomechanical properties, cell compatibility, aldehyde group content detection, and the calcification content. Aldehyde group detection tests showed that the GSH can completely neutralize the residual aldehyde group of GLUT-BP. Compared with that of GLUT-BP, the endothelial cell proliferation rate of the GLUT + GSH group increased, while its hemolysis rate and the inflammatory response after implantation into the SD rat were reduced. The results show that GSH can effectively improve the cytocompatibility of the GLUT-BP tissue. In addition, the results of the uniaxial tensile test, thermal shrinkage temperature, histological and SEM evaluation, and enzyme digestion experiments proved that GSH did not affect the ECM stability and biomechanics of the GLUT-BP. The calcification level of GLUT-BP modified using GSH technology decreased by 80%, indicating that GSH can improve the anti-calcification performance of GLUT-BP. Compared with GLUT-GLY, GLUT + GSH yielded a higher cell proliferation rate and lower inflammatory response and calcification level. GSH can be used as a new type of anti-calcification agent in GLUT crosslinking biomaterials and is expected to expand the application domain for BHVs in the future.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-3-24)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-3-24)
    Abstract: Small-diameter vascular grafts have a significant need in peripheral vascular surgery and procedures of coronary artery bypass graft (CABG); however, autografts are not always available, synthetic grafts perform poorly, and allografts and xenografts dilate, calcify, and induce inflammation after implantation. We hypothesized that cross-linking of decellularized xenogeneic vascular grafts would improve the mechanical properties and biocompatibility and reduce inflammation, degradation, and calcification in vivo . To test this hypothesis, the bovine internal mammary artery (BIMA) was decellularized by detergents and ribozymes with sonication and perfusion. Photooxidation and pentagalloyl glucose (PGG) were used to cross-link the collagen and elastin fibers of decellularized xenografts. Modified grafts’ characteristics and biocompatibility were studied in vitro and in vivo ; the grafts were implanted as transposition grafts in the subcutaneous of rats and the abdominal aorta of rabbits. The decellularized grafts were cross-linked by photooxidation and PGG, which improved the grafts’ biomechanical properties and biocompatibility, prevented elastic fibers from early degradation, and reduced inflammation and calcification in vivo . Short-term aortic implants in the rabbits showed collagen regeneration and differentiation of host smooth muscle cells. No occlusion and stenosis occurred due to remodeling and stabilization of the neointima. A good patency rate (100%) was maintained. Notably, implantation of non-treated grafts exhibited marked thrombosis, an inflammatory response, calcification, and elastin degeneration. Thus, photooxidation and PGG cross-linking are potential tools for improving grafts’ biological performance within decellularized small-diameter vascular xenografts.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 10
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-7-12)
    Abstract: More than 200,000 patients with aortic diseases worldwide undergo surgical valve replacement each year, and transcatheter heart valves (THV) have been more widely used than ever before. However, THV made by the glutaraldehyde (Glut) crosslinking method has the disadvantage of being prone to calcification, which significantly reduces the durability of biomaterials. In this study, we applied a novel crosslinking method using ribose in THV for the first time, which can decrease calcification and increase the stability of the extracellular matrix (ECM). We incubated the bovine pericardium (BP) in ribose solution at 37°C by shaking for 12 days and confirmed that the structure of the BP was more compact than that of the Glut group. Moreover, the ribose method remarkably enhanced the biomechanical properties and provided reliable resistance to enzymatic degradation and satisfactory cellular compatibility in THV. When the BP was implanted subcutaneously in vivo , we demonstrated that ECM components were preserved more completely, especially in elastin, and the immune-inflammatory response was more moderate than that in the Glut treatment group. Finally, the ribose-cross-linked materials showed better anti-calcification potential and improved durability of THV than Glut-cross-linked materials.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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