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| 10. |
- Zhu, RJ, et al.
(author)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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In: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Journal article (peer-reviewed)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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- Chen, DS, et al.
(author)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Journal article (peer-reviewed)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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| 13. |
- Li, J, et al.
(author)
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A prospective pilot study of the effect of acupuncture on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance
- 2020
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In: Acupuncture in medicine : journal of the British Medical Acupuncture Society. - : SAGE Publications. - 1759-9873. ; 38:5, s. 310-318
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Journal article (peer-reviewed)abstract
- To test the hypothesis that acupuncture improves insulin sensitivity in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Design: Prospective pilot study. Setting: Guangzhou, China, 2014–2016. Participants: Eighty women with PCOS aged 18–40 years with body mass index (BMI) above 18.5 kg/m2 and with homeostatic model assessment for insulin resistance (HOMA-IR) index ⩾2.14. Interventions: Subjects received acupuncture with combined manual and low-frequency electrical stimulation of the needles three times per week for 6 months. Primary and secondary outcome measures: The primary outcome was the change in HOMA-IR after 6 months of acupuncture relative to baseline. Secondary outcomes included changes after 6 months of acupuncture and at 3 months of follow-up (both relative to baseline) in oral glucose tolerance test (OGTT) parameters (glucose and insulin levels), anthropometric measurements, and circulating metabolic and endocrine variables. Results: HOMA-IR and fasting plasma glucose and insulin levels were significantly decreased after 6 months of acupuncture, and both HOMA-IR and fasting insulin remained significantly decreased at 3 months of follow-up. In a subgroup analysis of normal-weight and overweight/obese women, HOMA-IR was reduced after 6 months of acupuncture in both subgroups, but there was no significant difference between the two groups. Conclusions: Acupuncture treatment in Chinese women with PCOS and IR was associated with an encouraging improvement in insulin sensitivity. Further randomized controlled studies are required to confirm the efficacy of acupuncture for this indication.
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- Li, HX, et al.
(author)
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Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems
- 2021
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 777606-
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Journal article (peer-reviewed)abstract
- Toll-like receptors (TLRs) are a class of proteins playing a key role in innate and adaptive immune responses. TLRs are involved in the development and progression of neuroimmune diseases via initiating inflammatory responses. Thus, targeting TLRs signaling pathway may be considered as a potential therapy for neuroimmune diseases. However, the role of TLRs is elusive and complex in neuroimmune diseases. In addition to the inadequate immune response of TLRs inhibitors in the experiments, the recent studies also demonstrated that partial activation of TLRs is conducive to the production of anti-inflammatory factors and nervous system repair. Exploring the mechanism of TLRs in neuroimmune diseases and combining with developing the emerging drug may conquer neuroimmune diseases in the future. Herein, we provide an overview of the role of TLRs in several neuroimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorder, Guillain-Barré syndrome and myasthenia gravis. Emerging difficulties and potential solutions in clinical application of TLRs inhibitors will also be discussed.
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| 21. |
- Meng, L, et al.
(author)
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Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study
- 2021
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In: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:12, s. 939-951
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Journal article (peer-reviewed)abstract
- Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.
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| 22. |
- Wu, ZC, et al.
(author)
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Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake
- 2020
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:5, s. 1693-1708
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Journal article (peer-reviewed)abstract
- Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD–HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD–HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
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| 26. |
- Chen, W, et al.
(author)
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Pressure dependence of Mn2+ fluorescence in ZnS:Mn2+ nanoparticles
- 2000
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In: Journal of Luminescence. - 0022-2313. ; 91:3-4, s. 139-145
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Journal article (peer-reviewed)abstract
- The photoluminescence of Mn2+ in ZnS : Mn2+ nanoparticles with an average size of 4.5 nm has been measured under hydrostatic pressure from 0 to 6 GPa. The emission position is red-shifted at a rate of −33.3±0.6 meV/GPa, which is in good agreement with the calculated value of −30.4 meV/GPa using the crystal field theory.
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| 31. |
- Li, HX, et al.
(author)
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PD-1/PD-L1 Axis as a Potential Therapeutic Target for Multiple Sclerosis: A T Cell Perspective
- 2021
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In: Frontiers in cellular neuroscience. - : Frontiers Media SA. - 1662-5102. ; 15, s. 716747-
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Journal article (peer-reviewed)abstract
- The programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1) axis is a widely studied immune checkpoint that modulates signaling pathways related to T cell activation. The use of PD-1/PD-L1 inhibitors is a promising immune therapy strategy for cancer patients. However, individuals treated with PD-1/PD-L1 inhibitors may develop immune-related adverse events due to excessive immune reactions. Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system. T cells and the PD-1/PD-L1 axis play vital roles in the pathogenesis of MS. A better understanding of the complex relationship between the PD-1/PD-L1 axis and T cells may extend our knowledge of the molecular mechanisms and therapeutic approaches for MS. In this review, we summarize the most recent findings regarding the role of the PD-1/PD-L1 axis in MS and discuss the potential therapeutic strategies to modulate the expression of PD-1/PD-L1 in MS.
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| 36. |
- Liu, RN, et al.
(author)
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HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5093-
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Journal article (peer-reviewed)abstract
- The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
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| 37. |
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| 38. |
- Lu, HX, et al.
(author)
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Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs
- 2007
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 104:29, s. 12140-12145
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Journal article (peer-reviewed)abstract
- Establishment of functional and stable collaterals in the ischemic myocardium is crucial to restoring cardiac function after myocardial infarction. Here, we show that only dual delivery of a combination of angiogenic and arteriogenic factors to the ischemic myocardium could significantly reestablish stable collateral networks and improve myocardial perfusion and function. A combination of FGF-2 with PDGF-BB, two factors primarily targeting endothelial cells and vascular smooth muscle cells, remarkably promotes myocardial collateral growth and stabilizes the newly formed collateral networks, which significantly restore myocardial perfusion and function. Using various members of the PDGF family together with FGF-2 in an angiogenesis assay, we demonstrate that PDGFR-α is mainly involved in angiogenic synergism, whereas PDGFR-β mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.
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| 46. |
- Zeng, WY, et al.
(author)
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Inner product truth valued flow inference
- 2005
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In: INTERNATIONAL JOURNAL OF UNCERTAINTY FUZZINESS AND KNOWLEDGE-BASED SYSTEMS. - 0218-4885. ; 13:6, s. 601-612
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Journal article (other academic/artistic)
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