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- Wu, ZC, et al.
(författare)
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Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake
- 2020
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:5, s. 1693-1708
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Tidskriftsartikel (refereegranskat)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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- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)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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- Li, J, et al.
(författare)
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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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Ingår i: Acupuncture in medicine : journal of the British Medical Acupuncture Society. - : SAGE Publications. - 1759-9873. ; 38:5, s. 310-318
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Tidskriftsartikel (refereegranskat)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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- Ma, J, et al.
(författare)
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Climate Change Drives the Transmission and Spread of Vector-Borne Diseases: An Ecological Perspective
- 2022
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Ingår i: Biology. - : MDPI AG. - 2079-7737. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Climate change affects ecosystems and human health in multiple dimensions. With the acceleration of climate change, climate-sensitive vector-borne diseases (VBDs) pose an increasing threat to public health. This paper summaries 10 publications on the impacts of climate change on ecosystems and human health; then it synthesizes the other existing literature to more broadly explain how climate change drives the transmission and spread of VBDs through an ecological perspective. We highlight the multi-dimensional nature of climate change, its interaction with other factors, and the impact of the COVID-19 pandemic on transmission and spread of VBDs, specifically including: (1) the generally nonlinear relationship of local climate (temperature, precipitation and wind) and VBD transmission, with temperature especially exhibiting an n-shape relation; (2) the time-lagged effect of regional climate phenomena (the El Niño–Southern Oscillation and North Atlantic Oscillation) on VBD transmission; (3) the u-shaped effect of extreme climate (heat waves, cold waves, floods, and droughts) on VBD spread; (4) how interactions between non-climatic (land use and human mobility) and climatic factors increase VBD transmission and spread; and (5) that the impact of the COVID-19 pandemic on climate change is debatable, and its impact on VBDs remains uncertain. By exploring the influence of climate change and non-climatic factors on VBD transmission and spread, this paper provides scientific understanding and guidance for their effective prevention and control.
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- Wang, HX, et al.
(författare)
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Depressive symptoms, social isolation, and progression of coronary artery atherosclerosis: the Stockholm Female Coronary Angiography Study
- 2006
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Ingår i: Psychotherapy and psychosomatics. - : S. Karger AG. - 0033-3190 .- 1423-0348. ; 75:2, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Although both depressive symptoms and social isolation in relation to coronary heart disease have been studied previously, few have examined their joint effects on coronary atherosclerosis progression in women. <i>Method:</i> Among the women enrolled in the Stockholm Female Coronary Angiography Study, Sweden, between 1991 and 1994, 102 were evaluated for coronary atherosclerosis progression using a computer-assisted standardized assessment, repeated quantitative coronary angiographic documentation, of the mean luminal diameter change over 3 years in 10 predefined coronary segments. Depressive symptoms and social isolation were assessed by standard questionnaires. <i>Results:</i> Multivariable controlled mixed model ANOVAs revealed that women who were both depressed and socially isolated had the greatest disease progression: their absolute mean luminal diameter decreased by 0.18 mm [95% confidence interval (CI) = 0.11–0.24] and their percent narrowing was 5.5% (95% CI = 3.6–7.4), whereas in women who lacked both psychological risk factors, the mean luminal diameter decrease was 0.04 mm and their percent narrowing was 0.9%. These associations were independent of the baseline luminal diameter and standard risk factors, including age, smoking history, hypertension, and high-density lipoproteins. <i>Conclusions:</i>In women with coronary disease, depressive symptoms and social isolation in combination accelerated disease progression, suggesting a direct psychosocial effect on the atherosclerotic process. These findings provide an additional opportunity for therapeutic and preventive efforts against progression of coronary disease in women.
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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. ; 3231:112, 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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