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Article ; Online: MG53 protein rejuvenates hUC-MSCs and facilitates their therapeutic effects in AD mice by activating Nrf2 signaling pathway

Shanshan Ma / Xinkui Zhou / Yaping Wang / Zhe Li / Yingying Wang / Jijing Shi / Fangxia Guan

Redox Biology, Vol 53, Iss , Pp 102325- (2022)

2022

Abstract: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in vitro easily exhibit replicative senescence, which restricts their application. Although ... ...

Abstract	Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in vitro easily exhibit replicative senescence, which restricts their application. Although MG53 protein demonstrates multiple roles for a variety of cells and tissues repair, it remains unknown whether MG53 could rejuvenate senescent hUC-MSCs and enhance their efficacy in AD model. Here, we firstly presented that MG53 reinstated senescent hUC-MSCs via the activation of the Nrf2 signaling pathway by increasing cell proliferation and migration, ameliorating senescence and oxidative stress, and decreasing the release of senescence-associated secretory phenotype. In vivo studies showed that MG53 treatment improved the therapeutic effect of senescent hUC-MSCs in AD mice. Furthermore, MG53 combined with young hUC-MSCs transplantation alleviated cognitive deficit and depression-like behavior in AD mice, reduced Aβ deposition and Tau phosphorylation, promoted neurogenesis, and inhibited glia cells activation and oxidative stress by activating the Nrf2 signaling. Moreover, these neuroprotective effects mediated by MG53 and hUC-MSCs were partly reversed by Brusatol, a specific inhibitor of Nrf2 signaling. Taken together, our study revealed that MG53 could rejuvenate senescent hUC-MSCs and facilitate their efficacy in AD mice at least partly through activating Nrf2 signaling pathway, which suggest that the combined therapy of MG53 and hUC-MSCs may be a novel and effective strategy for AD.
Keywords	MG53 protein ; Human umbilical cord-derived mesenchymal stem cells ; Alzheimer's disease ; Senescence ; Nrf2 signaling pathway ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MG53 protein rejuvenates hUC-MSCs and facilitates their therapeutic effects in AD mice by activating Nrf2 signaling pathway.

Ma, Shanshan / Zhou, Xinkui / Wang, Yaping / Li, Zhe / Wang, Yingying / Shi, Jijing / Guan, Fangxia

Redox biology

2022 Volume 53, Page(s) 102325

Abstract	Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in vitro easily exhibit replicative senescence, which restricts their application. Although MG53 protein demonstrates multiple roles for a variety of cells and tissues repair, it remains unknown whether MG53 could rejuvenate senescent hUC-MSCs and enhance their efficacy in AD model. Here, we firstly presented that MG53 reinstated senescent hUC-MSCs via the activation of the Nrf2 signaling pathway by increasing cell proliferation and migration, ameliorating senescence and oxidative stress, and decreasing the release of senescence-associated secretory phenotype. In vivo studies showed that MG53 treatment improved the therapeutic effect of senescent hUC-MSCs in AD mice. Furthermore, MG53 combined with young hUC-MSCs transplantation alleviated cognitive deficit and depression-like behavior in AD mice, reduced Aβ deposition and Tau phosphorylation, promoted neurogenesis, and inhibited glia cells activation and oxidative stress by activating the Nrf2 signaling. Moreover, these neuroprotective effects mediated by MG53 and hUC-MSCs were partly reversed by Brusatol, a specific inhibitor of Nrf2 signaling. Taken together, our study revealed that MG53 could rejuvenate senescent hUC-MSCs and facilitate their efficacy in AD mice at least partly through activating Nrf2 signaling pathway, which suggest that the combined therapy of MG53 and hUC-MSCs may be a novel and effective strategy for AD.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/therapy ; Animals ; Membrane Proteins/metabolism ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/metabolism ; Mice ; NF-E2-Related Factor 2/metabolism ; Signal Transduction ; Umbilical Cord/metabolism
Chemical Substances	MG53 protein, mouse ; Membrane Proteins ; NF-E2-Related Factor 2
Language	English
Publishing date	2022-04-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2022.102325
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Article ; Online: Decreased Plasma Level of Lipoprotein Lipase Predicted Verbal Disfluency in Chinese Type 2 Diabetes Mellitus Patients with Early Cognitive Deficits.

An, Ke / Guo, Peng / Zhang, Haoqiang / Zhu, Wenwen / Cao, Wuyou / Shi, Jijing / Wang, Shaohua

Current Alzheimer research

2021 Volume 18, Issue 8, Page(s) 656–666

Abstract: Background: Lipoprotein Lipase (LPL) is the rate-limiting enzyme catalyzing the hydrolysis of triglycerides and contributes to the amyloid-β formation, which shows promise as a pathological factor of cognitive decline in Type 2 Diabetes Mellitus (T2DM). ...

Abstract	Background: Lipoprotein Lipase (LPL) is the rate-limiting enzyme catalyzing the hydrolysis of triglycerides and contributes to the amyloid-β formation, which shows promise as a pathological factor of cognitive decline in Type 2 Diabetes Mellitus (T2DM). This study aimed to investigate the pathogenetic roles of LPL and rs328 polymorphism in Mild Cognitive Impairment (MCI) in patients with T2DM. Methods: Chinese patients with T2DM were recruited and divided into two groups based on the Montreal Cognitive Assessment score. Demographic data were collected, LPL was measured and neuropsychological test results were examined. Results: Seventy-nine patients with diabetes and MCI had significantly decreased plasma LPL levels (p = 0.007) when compared with health-cognition controls (n = 91). Correlation analysis revealed that LPL was positively correlated with clock drawing test (r = 0.158, p = 0.043) and logical memory test (r = 0.162, p = 0.037), while lipoprotein a (r = -0.214, p = 0.006) was inversely associated with LPL. Logistic regression analysis further demonstrated that LPL concentration was an independent factor for diabetic MCI (p = 0.036). No significant differences were observed in the distributions of rs328 variants between patients with MCI and the controls. Moreover, no remarkable association was found among plasma LPL levels, cognitive performances, and lipid levels between the genotypic subgroups. The trail making test A was increased in the GC group when compared with the CC genotype in the control group. Conclusion: Decreased plasma level of LPL could probably predict early cognitive deficits, especially verbal disfluency.
MeSH term(s)	Biomarkers ; China ; Cognition ; Cognitive Dysfunction ; Diabetes Mellitus, Type 2 ; Humans ; Lipoprotein Lipase/genetics
Chemical Substances	Biomarkers ; Lipoprotein Lipase (EC 3.1.1.34)
Language	English
Publishing date	2021-10-19
Publishing country	United Arab Emirates
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/1567205018666210922105850
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Article ; Online: Optimal duration of dual antiplatelet therapy followed by monotherapy in diabetic patients after percutaneous coronary intervention with drug‑eluting stent implantation: a Bayesian network meta-analysis.

An, Ke / Guo, Peng / Qiu, Shanhu / Zhu, Wenwen / Cao, Wuyou / Shi, Jijing / Wang, Shaohua

Polish archives of internal medicine

2021 Volume 131, Issue 9, Page(s) 781–789

Abstract: Introduction: The standard 12-month dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation that is recommended for the general population may not be suitable for patients with ... ...

Abstract	Introduction: The standard 12-month dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation that is recommended for the general population may not be suitable for patients with diabetes. Objectives: The study aimed to evaluate the efficacy and safety of short-term (≤3 months), medium-term (6 months), standard-term (12 months), and extended-term (>12 months) DAPT in diabetic patients with DES implantation and to compare the outcomes of DAPT discontinuation followed by monotherapy with aspirin versus a P2Y12 receptor inhibitor. Patients and methods: Randomized controlled trials published up to October 10, 2020 were searched in the PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov databases. A Bayesian network meta-analysis with a random-effects model was performed. A total of 18 randomized trials involving 20 536 patients with diabetes were included. Results: The network analysis showed that short-term DAPT was the most optimal in terms of reducing the primary endpoint and was superior to extended-term DAPT (odds ratio [OR], 0.48; 95% CI, 0.25–0.85). Standard-term DAPT was also associated with a reduced primary endpoint in comparison with extended-term DAPT (OR, 0.56; 95% CI, 0.32–0.90). There was no noticeable difference with respect to the primary endpoint between short-term DAPT followed by monotherapy with aspirin and a P2Y12 inhibitor. No significant differences were observed in secondary endpoints, including all-cause mortality, cardiac mortality, myocardial infarction, stroke, target vessel revascularization, definite or probable stent thrombosis, and major bleeding event. Conclusions: Short-term DAPT, as compared with extended-term therapy, was associated with a reduced primary endpoint in patients with diabetes after PCI with DES implantation.
MeSH term(s)	Bayes Theorem ; Diabetes Mellitus ; Drug-Eluting Stents ; Humans ; Network Meta-Analysis ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use ; Treatment Outcome
Chemical Substances	Platelet Aggregation Inhibitors
Language	English
Publishing date	2021-06-16
Publishing country	Poland
Document type	Journal Article ; Meta-Analysis
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.16032
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Article ; Online: Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer.

Cui, Yuanbo / Guo, Wenna / Li, Ya / Shi, Jijing / Ma, Shanshan / Guan, Fangxia

Esophagus : official journal of the Japan Esophageal Society

2020 Volume 18, Issue 2, Page(s) 326–338

Abstract: Background: Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described.!# ...

Abstract	Background: Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described. Methods and results: In this study, we used The Cancer Genome Atlas (TCGA) analysis databases to explore the expression level and prognostic significance of ESM1 in 33 types of human cancer. ESM1 was shown to be over-expressed in 12 cancer types, including BLCA, BRCA, COAD, CHOL, ESCA, HNSC, KIRC, KICH, LIHC, STAD, THCA, and UCEC. The expression of ESM1 was significantly correlated with the overall survival (OS) of patients in CESC, ESCA, KIRC, and KIRP. In addition, high ESM1 level indicated poor disease-free survival (DFS) of patients with ACC, ESCA, PRAD, LIHC, KIRP, and UCS. Through comparative analysis, we discovered that ESM1 was dramatically up-regulated in esophageal cancer (ESCA) and associated with worse patient OS and DFS. The elevation of ESM1 in ESCA was confirmed by the datasets from Cancer RNA-Seq Nexus (CRN) and Gene Expression Omnibus (GEO). Based on Gene Set Enrichment Analysis (GSEA), we analyzed the co-expressed genes of ESM1 in ESCA, and found that ESM1 was closely implicated in cell proliferation and migration and the regulation of Janus kinase (JAK) signaling pathway. Functionally, knockdown of ESM1 significantly suppressed cell proliferation and migration, and decreased the protein level of JAK1. Conclusions: Taken together, our results suggest for the first time that ESM1 functions as an oncogene and may be a clinical biomarker and/or therapeutic target in ESCA.
MeSH term(s)	Cell Proliferation/genetics ; Disease-Free Survival ; Esophageal Neoplasms/genetics ; Humans ; Neoplasm Proteins/genetics ; Oncogenes/genetics ; Prognosis ; Proteoglycans/genetics
Chemical Substances	ESM1 protein, human ; Neoplasm Proteins ; Proteoglycans
Language	English
Publishing date	2020-11-11
Publishing country	Japan
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133367-1
ISSN	1612-9067 ; 1612-9059
ISSN (online)	1612-9067
ISSN	1612-9059
DOI	10.1007/s10388-020-00796-9
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Article: PDGF-BB/SA/Dex injectable hydrogels accelerate BMSC-mediated functional full thickness skin wound repair by promoting angiogenesis

Zhang, Zhenkun / Li, Zhe / Wang, Yingying / Wang, Qianqian / Yao, Minghao / Zhao, Liang / Shi, Jijing / Guan, Fangxia / Ma, Shanshan

Journal of materials chemistry B. 2021 Aug. 11, v. 9, no. 31

2021

Abstract: Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of ... ...

Abstract	Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of PDGF-BB limits its efficacy. In the present study, we successfully synthesized an injectable hydrogel with sodium alginate (SA) and dextran (Dex) as a delivery system to simultaneously deliver PDGF-BB and bone marrow-derived mesenchymal stem cells (BMSCs) in the wound. Our work demonstrates that the PDGF-BB protein enhanced the survival, migration and endothelial cell (EC) differentiation of BMSCs in vitro. The PDGF-BB/SA/Dex hydrogels could sustainably release PDGF-BB with excellent biocompatibility in vitro and in vivo. Besides, these composite hydrogels loaded with BMSCs could accelerate wound healing by improving epithelialization and collagen deposition. In addition, the PDGF-BB/SA/Dex hydrogels promoted the EC-differentiation of transplanted BMSCs and proliferation of hair follicle stem cells in the wound. Furthermore, the expressions of angiogenesis-specific markers, PDGFR-β, p-PI3K, p-Akt, and p-eNOS, were obviously increased in the PDGF-BB/SA/Dex/BMSCs group. In conclusion, the PDGF-BB/SA/Dex injectable hydrogels could accelerate BMSC-mediated skin wound healing by promoting angiogenesis via the activation of the PDGF-BB/PDGFR-β-mediated PI3K/Akt/eNOS pathway, which may provide a new therapeutic strategy for stem cell therapy in wound healing.
Keywords	angiogenesis ; biocompatibility ; collagen ; dextran ; endothelial cells ; hair follicles ; half life ; hydrogels ; sodium alginate ; stem cells ; therapeutics
Language	English
Dates of publication	2021-0811
Size	p. 6176-6189.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d1tb00952d
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Article ; Online: Glucagon-like peptide-1 attenuated carboxymethyl lysine induced neuronal apoptosis via peroxisome proliferation activated receptor-γ.

Zhang, Haoqiang / Song, Bing / Zhu, Wenwen / Liu, Lili / He, Xiqiao / Wang, Zheng / An, Ke / Cao, Wuyou / Shi, Jijing / Wang, Shaohua

Aging

2021 Volume 13, Issue 14, Page(s) 19013–19027

Abstract: Backgrounds and aims: The role of peroxisome proliferator activated receptor-γ (PPAR-γ) in neuronal apoptosis remains unclear. We aim to investigate the role of PPAR-γ in glucagon-like peptide-1 (GLP-1) alleviated neuronal apoptosis induced by ... ...

Abstract	Backgrounds and aims: The role of peroxisome proliferator activated receptor-γ (PPAR-γ) in neuronal apoptosis remains unclear. We aim to investigate the role of PPAR-γ in glucagon-like peptide-1 (GLP-1) alleviated neuronal apoptosis induced by carboxymethyl-lysine (CML). Materials and methods: In vitro Results: In vitro Conclusions: GLP-1 could attenuate neuronal apoptosis induced by CML. Additionally, PPAR-γ involves in this process.
MeSH term(s)	Alzheimer Disease/metabolism ; Animals ; Apoptosis ; Brain/drug effects ; Brain/metabolism ; Cognition ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/metabolism ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide 1/pharmacology ; Glycation End Products, Advanced/metabolism ; Lysine/adverse effects ; Lysine/analogs & derivatives ; Lysine/metabolism ; Male ; Maze Learning ; Neurons ; Neuroprotective Agents ; PC12 Cells ; PPAR gamma/metabolism ; Peroxisomes ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein/metabolism
Chemical Substances	Bax protein, rat ; Bcl2 protein, rat ; Glycation End Products, Advanced ; Neuroprotective Agents ; PPAR gamma ; Proto-Oncogene Proteins c-bcl-2 ; bcl-2-Associated X Protein ; N(6)-carboxymethyllysine (70YDX3Z2O7) ; Glucagon-Like Peptide 1 (89750-14-1) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203351
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Article: Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes.

Shi, Jijing / Jia, Jianhong / Tian, Sai / Zhang, Haoqiang / An, Ke / Zhu, Wenwen / Cao, Wuyou / Yuan, Yang / Wang, Shaohua

Frontiers in aging neuroscience

2021 Volume 13, Page(s) 619916

Abstract: Background: Abnormal cholesterol metabolism is common in type 2 diabetes mellitus (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol homeostasis in the ... ...

Abstract	Background: Abnormal cholesterol metabolism is common in type 2 diabetes mellitus (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol homeostasis in the brain. Objective: This study aimed to investigate the roles of 24-OHC and the CYP46A1 (rs754203) polymorphism in patients with T2DM and mild cognitive impairment (MCI). Methods: A total of 193 Chinese patients with T2DM were recruited into two groups according to the Montreal Cognitive Assessment (MoCA). Demographic and clinical data were collected, and neuropsychological tests were conducted. Enzyme-linked immunosorbent assay (ELISA) and Seqnome method were used to detect the concentration of plasma 24-OHC and the CYP46A1 rs754203 genotype, respectively. Results: Compared with 118 healthy cognition participants, patients with MCI ( Conclusion: In patients with T2DM, high plasma level of 24-OHC and the CC genotype carrier of CYP46A1 rs754203 may portend a high risk of developing early cognitive impairment, including attention and executive deficits.
Language	English
Publishing date	2021-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.619916
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Article ; Online: Single-Cell Transcriptomic Profiling of MAIT Cells in Patients With COVID-19.

Shi, Jijing / Zhou, Jianglin / Zhang, Xiaochang / Hu, Wei / Zhao, Jin-Fang / Wang, Shengqi / Wang, Fu-Sheng / Zhang, Ji-Yuan

Frontiers in immunology

2021 Volume 12, Page(s) 700152

Abstract: Background: Mucosal-associated invariant T (MAIT) cells are considered to participate of the host immune response against acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, single-cell transcriptomic profiling of MAIT ...

Abstract	Background: Mucosal-associated invariant T (MAIT) cells are considered to participate of the host immune response against acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, single-cell transcriptomic profiling of MAIT cells in patients with COVID-19 remains unexplored. Methods: We performed single-cell RNA sequencing analyses on peripheral MAIT cells from 13 patients with COVID-19 and 5 healthy donors. The transcriptional profiles of MAIT cells, together with assembled T-cell receptor sequences, were analyzed. Flow cytometry analysis was also performed to investigate the properties of MAIT cells. Results: We identified that differentially expressed genes (DEGs) of MAIT cells were involved in myeloid leukocyte activation and lymphocyte activation in patients with COVID-19. In addition, in MAIT cells from severe cases, more DEGs were enriched in adaptive cellular and humoral immune responses compared with those in moderate cases. Further analysis indicated that the increase of cell cytotoxicity (killing), chemotaxis, and apoptosis levels in MAIT cells were consistent with disease severity and displayed the highest levels in patients with severe disease. Interestingly, flow cytometry analysis showed that the frequencies of pyroptotic MAIT cells, but not the frequencies of apoptotic MAIT cells, were increased significantly in patients with COVID-19, suggesting pyroptosis is one of leading causes of MAIT cell deaths during SARS-CoV-2 infection. Importantly, there were more clonal expansions of MAIT cells in severe cases than in moderate cases. Conclusions: The results of the present study suggest that MAIT cells are likely to be involved in the host immune response against SARS-CoV-2 infection. Simultaneously, the transcriptomic data from MAIT cells provides a deeper understanding of the immune pathogenesis of the disease.
MeSH term(s)	Base Sequence ; COVID-19/immunology ; COVID-19/pathology ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Gene Expression Regulation/immunology ; Humans ; Lymphocyte Activation/genetics ; Mucosal-Associated Invariant T Cells/immunology ; Pyroptosis/physiology ; SARS-CoV-2/immunology ; Sequence Analysis, RNA ; Severity of Illness Index ; Transcriptome/genetics ; VDJ Exons/genetics
Language	English
Publishing date	2021-07-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.700152
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Article ; Online: Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus.

Zhang, Haoqiang / Zhu, Wenwen / Niu, Tong / Wang, Zheng / An, Ke / Cao, Wuyou / Shi, Jijing / Wang, Shaohua

Lipids in health and disease

2021 Volume 20, Issue 1, Page(s) 103

Abstract: Background: Low-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes. The role of LDL-C in mild cognitive impairment (MCI) remains to be explored. We aim to investigate the associations between LDL-C at ... ...

Abstract	Background: Low-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes. The role of LDL-C in mild cognitive impairment (MCI) remains to be explored. We aim to investigate the associations between LDL-C at different levels and details of cognition decline in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (n = 497) were recruited. Clinical parameters and neuropsychological tests were compared between patients with MCI and controls. Goodness of fit was assessed to determine the linear or U-shaped relationship between LDL-C and cognitive function. The cut-off point of LDL-C was calculated. Correlation and regression were carried out to explore the relationship between cognitive dysfunction and LDL-C levels above and below the cut-off point. Results: Although no significant difference in LDL-C levels was detected in 235 patients with MCI, compared with 262 patients without MCI, inverted-U-shaped association was determined between LDL-C and Montreal Cognitive Assessment (MoCA). The cut-off point of LDL-C is 2.686 mmol/l. LDL-C (>2.686 mmol/l) is positively related to Trail Making Test B (TMTB) indicating executive function. LDL-C (<2.686 mmol/l) is positively associated with Clock Drawing Test (CDT) reflecting visual space function in patients with T2DM. Conclusion: Inverted U-shaped correlation was found between serum LDL-C and cognitive function in patients with T2DM. Despite that the mechanisms of different LDL-C levels involved in special cognitive dysfunctions remain incompletely clarified, excessive LDL-C damages executive function, while the deficient LDL-C impairs visual space function. Trial registration: ChiCTR-OCC-15006060 .
MeSH term(s)	Aged ; Case-Control Studies ; Cholesterol, LDL/blood ; Cognition/physiology ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/physiopathology ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/physiopathology ; Executive Function/physiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Risk Factors ; Spatial Processing/physiology
Chemical Substances	Cholesterol, LDL
Language	English
Publishing date	2021-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2091381-3
ISSN	1476-511X ; 1476-511X
ISSN (online)	1476-511X
ISSN	1476-511X
DOI	10.1186/s12944-021-01534-5
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