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Article ; Online: Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor.

Guo, Jingyue / Huang, Jiaxing / Lei, Shaojin / Wan, Dongdong / Liang, Boyuan / Yan, Hongyu / Liu, Yufei / Feng, Yuming / Yang, Sen / He, Ju / Kong, Deling / Shi, Jie / Wang, Shufang

ACS biomaterials science & engineering

2023 Volume 9, Issue 2, Page(s) 844–855

Abstract: Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular ... ...

Abstract	Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular graft (SDVG) products available. The design of SDVGs is promising in the future, and SDVG preparation using an
MeSH term(s)	Rats ; Humans ; Animals ; Blood Vessel Prosthesis ; Extracellular Matrix ; Bioreactors ; Hypoxia
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.2c00809
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Identifying Structural Features of Nucleotide Analogues to Overcome SARS-CoV-2 Exonuclease Activity.

Wang, Xuanting / Tao, Chuanjuan / Morozova, Irina / Kalachikov, Sergey / Li, Xiaoxu / Kumar, Shiv / Russo, James J / Ju, Jingyue

Viruses

2022 Volume 14, Issue 7

Abstract: With the recent global spread of new SARS-CoV-2 variants, there remains an urgent need to develop effective and variant-resistant oral drugs. Recently, we reported in vitro results validating the use of combination drugs targeting both the SARS-CoV-2 RNA- ...

Abstract	With the recent global spread of new SARS-CoV-2 variants, there remains an urgent need to develop effective and variant-resistant oral drugs. Recently, we reported in vitro results validating the use of combination drugs targeting both the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and proofreading exonuclease (ExoN) as potential COVID-19 therapeutics. For the nucleotide analogues to be efficient SARS-CoV-2 inhibitors, two properties are required: efficient incorporation by RdRp and substantial resistance to excision by ExoN. Here, we have selected and evaluated nucleotide analogues with a variety of structural features for resistance to ExoN removal when they are attached at the 3' RNA terminus. We found that dideoxynucleotides and other nucleotides lacking both 2'- and 3'-OH groups were most resistant to ExoN excision, whereas those possessing both 2'- and 3'-OH groups were efficiently removed. We also found that the 3'-OH group in the nucleotide analogues was more critical than the 2'-OH for excision by ExoN. Since the functionally important sequences in Nsp14/10 are highly conserved among all SARS-CoV-2 variants, these identified structural features of nucleotide analogues offer invaluable insights for designing effective RdRp inhibitors that can be simultaneously efficiently incorporated by the RdRp and substantially resist ExoN excision. Such newly developed RdRp terminators would be good candidates to evaluate their ability to inhibit SARS-CoV-2 in cell culture and animal models, perhaps combined with additional exonuclease inhibitors to increase their overall effectiveness.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; COVID-19 ; Exonucleases ; Nucleotides/chemistry ; RNA, Viral/genetics ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Nucleotides ; RNA, Viral ; Exonucleases (EC 3.1.-)
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071413
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Article ; Online: Nucleotide Analogues as Inhibitors of Viral Polymerases

Ju, Jingyue / Kumar, Shiv / Li, Xiaoxu / Jockusch, Steffen / Russo, James J.

bioRxiv

Keywords	covid19
Language	English
Publishing date	2020-01-31
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.01.30.927574
Database	COVID19

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Article: Identifying Structural Features of Nucleotide Analogues to Overcome SARS-CoV-2 Exonuclease Activity

Wang, Xuanting / Tao, Chuanjuan / Morozova, Irina / Kalachikov, Sergey / Li, Xiaoxu / Kumar, Shiv / Russo, James J. / Ju, Jingyue

Viruses. 2022 June 28, v. 14, no. 7

2022

Abstract	With the recent global spread of new SARS-CoV-2 variants, there remains an urgent need to develop effective and variant-resistant oral drugs. Recently, we reported in vitro results validating the use of combination drugs targeting both the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and proofreading exonuclease (ExoN) as potential COVID-19 therapeutics. For the nucleotide analogues to be efficient SARS-CoV-2 inhibitors, two properties are required: efficient incorporation by RdRp and substantial resistance to excision by ExoN. Here, we have selected and evaluated nucleotide analogues with a variety of structural features for resistance to ExoN removal when they are attached at the 3′ RNA terminus. We found that dideoxynucleotides and other nucleotides lacking both 2′- and 3′-OH groups were most resistant to ExoN excision, whereas those possessing both 2′- and 3′-OH groups were efficiently removed. We also found that the 3′-OH group in the nucleotide analogues was more critical than the 2′-OH for excision by ExoN. Since the functionally important sequences in Nsp14/10 are highly conserved among all SARS-CoV-2 variants, these identified structural features of nucleotide analogues offer invaluable insights for designing effective RdRp inhibitors that can be simultaneously efficiently incorporated by the RdRp and substantially resist ExoN excision. Such newly developed RdRp terminators would be good candidates to evaluate their ability to inhibit SARS-CoV-2 in cell culture and animal models, perhaps combined with additional exonuclease inhibitors to increase their overall effectiveness.
Keywords	COVID-19 infection ; RNA ; RNA-directed RNA polymerase ; Severe acute respiratory syndrome coronavirus 2 ; animals ; cell culture ; excision ; nucleotides
Language	English
Dates of publication	2022-0628
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071413
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The incorporation of phosphorylated chitosan/amorphous calcium phosphate nanocomplex into an experimental composite resin.

Niu, Ju / Li, Di / Zhou, Zeying / Zhang, Jingyue / Liu, Dandan / Zhao, Wendi / Zhao, Chengji / Liu, Xiaoqiu

Dental materials journal

2021 Volume 40, Issue 2, Page(s) 422–430

Abstract: This study evaluated the effect of incorporating phosphorylated chitosan/amorphous calcium phosphate nanocomplex (Pchi/ACP) into an experimental light-cure composite resin on mechanical-chemical properties and human dentin remineralization. The results ... ...

Abstract	This study evaluated the effect of incorporating phosphorylated chitosan/amorphous calcium phosphate nanocomplex (Pchi/ACP) into an experimental light-cure composite resin on mechanical-chemical properties and human dentin remineralization. The results showed that the mechanical strength and contact angles of the resins decreased with the increase incorporation of Pchi/ACP. Release concentrations of calcium in saline solution were measured at different time points, showing the incorporation of Pchi/ACP significantly increased calcium release within 14 days, and kept steady thereafter. Finally, the demineralized dentin slabs treated with our resins for four weeks were characterized by SEM-EDS. Various amounts of apatite were formed on the dentin slabs which were treated with the resins containing Pchi/ACP, whereas no apatite was formed without Pchi/ACP. In conclusion, the Pchi/ACP-incorporating composite resin can be a promising dental material due to its favorable mechanical and remineralization properties.
MeSH term(s)	Calcium Phosphates ; Chitosan ; Composite Resins ; Dentin ; Humans ; Tooth Remineralization
Chemical Substances	Calcium Phosphates ; Composite Resins ; amorphous calcium phosphate ; Chitosan (9012-76-4)
Language	English
Publishing date	2021-01-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	605650-7
ISSN	1881-1361 ; 0287-4547
ISSN (online)	1881-1361
ISSN	0287-4547
DOI	10.4012/dmj.2019-427
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Article: Reducing White Adipose Tissue Browning Using p38α MAPK Inhibitors Ameliorates Cancer-Associated Cachexia as Assessed by Magnetic Resonance Imaging

Zhao, Yufei / Dai, Jingyue / Jiang, Yang / Wu, Honghong / Cui, Ying / Li, Xinxiang / Mao, Hui / Wang, Binghui / Ju, Shenghong / Peng, Xin-Gui

Nutrients. 2022 July 22, v. 14, no. 15

2022

Abstract: Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen- ...

Abstract	Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC. Methods: p38 MAPK inhibitors, VCP979 or SB203580, were used in the in vitro and in vivo models of pancreatic cancer cachexia. Expression of uncoupling protein 1 (UCP1) in the p38 MARK pathway and the properties and level of white adipocytes were analyzed and correlated to browning, followed by immunohistochemistry and Western blotting validations. Changes in the volume and fat fraction of WAT in animals were monitored by magnetic resonance imaging (MRI). Results: The size of white adipocytes was increased after being treated with the p38 MAPK inhibitors, along with increase in the MRI-measured volume and fat fraction of WAT. Comparing two p38 MAPK inhibitors, the p38α subunit-specific inhibitor VCP979 had a better therapeutic effect than SB203580, which targets both p38α and β subunits. Conclusions: Blockade of p38 MAPK reduced the WAT browning that contributes to CAC. Thus, p38 MARK inhibitors can potentially be used as a therapy for treating CAC. Non-invasive MRI can also be applied to assess the progression and treatment responses of CAC.
Keywords	cachexia ; immunohistochemistry ; magnetism ; mitogen-activated protein kinase ; pancreatic neoplasms ; therapeutics ; white adipocytes ; white adipose tissue
Language	English
Dates of publication	2022-0722
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14153013
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Reducing White Adipose Tissue Browning Using p38α MAPK Inhibitors Ameliorates Cancer-Associated Cachexia as Assessed by Magnetic Resonance Imaging.

Zhao, Yufei / Dai, Jingyue / Jiang, Yang / Wu, Honghong / Cui, Ying / Li, Xinxiang / Mao, Hui / Wang, Binghui / Ju, Shenghong / Peng, Xin-Gui

Nutrients

2022 Volume 14, Issue 15

Abstract	Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC. Methods: p38 MAPK inhibitors, VCP979 or SB203580, were used in the Results: The size of white adipocytes was increased after being treated with the p38 MAPK inhibitors, along with increase in the MRI-measured volume and fat fraction of WAT. Comparing two p38 MAPK inhibitors, the p38α subunit-specific inhibitor VCP979 had a better therapeutic effect than SB203580, which targets both p38α and β subunits. Conclusions: Blockade of p38 MAPK reduced the WAT browning that contributes to CAC. Thus, p38 MARK inhibitors can potentially be used as a therapy for treating CAC. Non-invasive MRI can also be applied to assess the progression and treatment responses of CAC.
MeSH term(s)	Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Cachexia/drug therapy ; Cachexia/etiology ; Cachexia/metabolism ; Magnetic Resonance Imaging ; Mitogen-Activated Protein Kinase 14/metabolism ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Protein Kinase Inhibitors ; Mitogen-Activated Protein Kinase 14 (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14153013
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Article ; Online: Abnormal [

Jiang, Yang / Wu, Honghong / Zhao, Yufei / Cui, Ying / Dai, Jingyue / Huang, Shanshan / Li, Cheng / Mao, Hui / Ju, Shenghong / Peng, Xin-Gui

European radiology

2022 Volume 33, Issue 4, Page(s) 2561–2573

Abstract: Objectives: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose (: Methods: FDG PET/CT ... ...

Abstract	Objectives: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose ( Methods: FDG PET/CT data from 390 cancer patients were analyzed retrospectively. Patients were divided into a development cohort and a validation cohort. Cachexia was defined as weight loss > 5% in 6 months or BMI < 20 and weight loss > 2%. According to the above definitions, patients were divided into cachexia and non-cachexia groups. Results of the clinical laboratory tests for metabolic levels and organ and tissue-specific FDG uptake obtained from the cachexia and non-cachexia groups were compared statistically. Logistic regression analysis was performed to identify independent variables associated with cachexia in the development cohort for generating the regression model. The performance of the model was tested using the data from a validation cohort and evaluated by area under the receiver operating characteristic curve (AUC). Results: Based on the data from the development cohort of 286 patients and a validation cohort of 104 patients, it is found that age, white blood cell count, peak standardized uptake value (SUV) of the liver, and minimum SUV of lean body mass of visceral fat and subcutaneous fat were independently associated with cachexia. The model incorporating these variables reached an AUC of 0.777 (95% confidence interval (CI): 0.721, 0.833) in the development cohort and an AUC of 0.729 (95% CI: 0.629, 0.829) in the validation cohort. Conclusion: Organ and tissue-specific abnormal glucose metabolism as measured by PET/CT can be used as a biomarker for cancer-associated cachexia. Key points: • Patients with cancer-associated cachexia have reduced FDG uptake in the liver and increased FDG uptake in visceral fat and subcutaneous fat. • FDG uptake of the liver, visceral fat, and subcutaneous fat can be independent risk factors for identifying cancer-associated cachexia. • Cancer-associated cachexia can be classified using the model that incorporates age, white blood cell count, FDG uptake of the liver, and visceral and subcutaneous fat can diagnose with an AUC of 0.729.
MeSH term(s)	Humans ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography/methods ; Radiopharmaceuticals ; Retrospective Studies ; Neoplasms/complications ; Biomarkers ; Liver ; Obesity ; Weight Loss
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Radiopharmaceuticals ; Biomarkers
Language	English
Publishing date	2022-11-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-022-09226-z
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Article: Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase.

Chien, Minchen / Anderson, Thomas K / Jockusch, Steffen / Tao, Chuanjuan / Kumar, Shiv / Li, Xiaoxu / Russo, James J / Kirchdoerfer, Robert N / Ju, Jingyue

bioRxiv : the preprint server for biology

2020

Abstract: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously ... ...

Abstract	SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3'-fluoro-3'-deoxythymidine triphosphate, 3'-azido-3'-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-03-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.03.18.997585
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Article ; Online: Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

Minchen Chien / Thomas K. Anderson / Steffen Jockusch / Chuanjuan Tao / Shiv Kumar / Xiaoxu Li / James J. Russo / Robert Kirchdoerfer / Jingyue Ju

Abstract	SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3′-fluoro-3′-deoxythymidine triphosphate, 3′-azido-3′-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.
Keywords	covid19
Publisher	biorxiv
Document type	Article ; Online
DOI	10.1101/2020.03.18.997585
Database	COVID19

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