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- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)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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- Ji, Q, et al.
(författare)
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Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1211-
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Tidskriftsartikel (refereegranskat)abstract
- Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor–stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.
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- Yao, YH, et al.
(författare)
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Cognitive impairment and associated factors among the elderly in the Shanghai suburb: findings from a low-education population
- 2010
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 34:4, s. 245-252
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objective:</i> Our purpose was to investigate the prevalence of cognitive impairment and associated factors among elderly people in the Shanghai suburb. <i>Methods:</i> A population-based survey was conducted for people aged 60 years and over in a community of 2 towns (Huaxin and Xujing) in Qingpu district, located in the western suburb of Shanghai. Face-to-face interviews were carried out to collect relevant information with prepared questionnaires. The Chinese version of the Mini-Mental State Examination was used to screen subjects with cognitive impairment, and the criteria of cognitive impairment were adjusted for education level. Univariate and multivariate logistic regression analyses were performed to evaluate factors putatively associated with cognitive impairment. <i>Results:</i> There were 2,809 subjects (1,010 men and 1,799 women) aged 60 years and over (mean: 70.6, SD: 6.6) included in the study, and 198 people (42 men and 156 women) had cognitive impairment, with a prevalence of 7.0% (95% CI: 6.1–7.9) for both genders, 4.2% (95% CI: 3.6–4.8) for men and 8.7% (95% CI: 8.0–9.4) for women among the elderly. The prevalence rates of cognitive impairment increased with age. Although a number of factors were found to be significantly associated with the risk of cognitive impairment from the univariate analysis, only age (OR: 2.245, 95% CI: 1.755–2.872) and preferring a nonsalty diet (OR: 0.647, 95% CI: 0.460–0.912) were left in the final model of multivariate logistic regression analysis. <i>Conclusion:</i> The prevalence of cognitive impairment among the elderly in the Shanghai suburb is relatively high, compared with that previously reported from other areas in China, but lower than that from western countries. Factors associated with cognitive impairment need to be further investigated in the future.
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- Chen, JM, et al.
(författare)
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Cognitive impairment among elderly individuals in Shanghai suburb, China: association of C-reactive protein and its interactions with other relevant factors
- 2014
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Ingår i: American journal of Alzheimer's disease and other dementias. - : SAGE Publications. - 1938-2731 .- 1533-3175. ; 29:8, s. 712-717
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association between serum C-reactive protein (CRP) concentration and cognitive impairment as well as interactions between CRP and other relevant factors. Methods: Patients with cognitive impairment and 1 to 2 age- and sex-matched controls nested from a population-based study among residents aged 60 years and older in Shanghai suburb. The associations of serum CRP concentration and other relevant factors were examined with logistic regression analysis. Results: The mean CRP in patients with cognitive impairment was higher than that in controls ( P < .001). The highest quartile of CRP (>4.77 mg/L), abdomen obesity, hypertriglyceridemia, and hyperglycemia was associated with cognitive impairment. Significant interactions were found between increased CRP and hypertriglyceridemia as well as between increased CRP and hyperglycemia on cognitive impairment; and the attributable proportion due to interaction was 82% ( P < .0001) and 37% ( P = .007), respectively. Conclusions: Increased CRP was associated with cognitive impairment, and additive effects of increased CRP with hypertriglyceridemia and hyperglycemia on cognitive impairment were observed among elderly individuals.
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- Cheng, Q, et al.
(författare)
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Clinical features of patients with multiple sclerosis from a survey in Shanghai, China
- 2008
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 14:5, s. 671-678
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe clinical features of patients with multiple sclerosis (MS) in Shanghai, China. Methods Prevalent patients with MS were identified and investigated by a network of physicians in 11 districts of Shanghai during the period from 1 September 2004 to 31 August 2005. Admission registries of each hospital in the study area were checked systematically for patients with a diagnosis of MS, neuromyelitis optica or other demyelinating disorders. All patients with collected information were evaluated by four senior neurologists according to the McDonald criteria. Results There were 249 (146 female and 103 male) patients with a confirmed MS diagnosis, at a female-to-male ratio of 1.4. The mean age at onset of MS was 37.4 years for the 249 patients with MS and, on the prevalence day, 42.7 years. The most frequent location of clinical MS lesions in the central nervous system was the spinal cord (61%), followed by the cerebrum (55%) and optic nerves (41%). Nearly all (96%) of the patients with MS had been examined by magnetic resonance imaging, and 226 (94%) patients of those examined were suggestive of MS. No family history of MS was found in any of the patients. Most (86%) of the patients had no or mild disability on the prevalence day (31 December 2004). Almost all (96%) patients with MS had been treated with corticosteroids. Conclusion Clinical features of patients with MS are described based on the information from the largest case series reported among Chinese. Comparisons and discussions are made with findings from the other populations.
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