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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Shu, X, et al.
(författare)
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Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1217-
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Tidskriftsartikel (refereegranskat)abstract
- Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Jing, X, et al.
(författare)
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COVID-19 instigates adipose browning and atrophy through VEGF in small mammals
- 2022
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:12, s. 1674-
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Tidskriftsartikel (refereegranskat)abstract
- Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
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| 18. |
- 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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| 19. |
- Li, XB, et al.
(författare)
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Novel TCF21high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix
- 2023
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 72:4, s. 710-721
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Tidskriftsartikel (refereegranskat)abstract
- Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.DesignTPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 onTCF21DNA hypermethylation. Pericyte-conditionalTcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling.ResultsThirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21highTPCs, termed ‘matrix–pericytes’, was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM).Tcf21depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21highTPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impairTCF21DNA hypermethylation in TCF21highTPCs.ConclusionThis study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.
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| 23. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 27. |
- Zhang, JX, et al.
(författare)
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The Efficacy and Safety of Revefenacin for the Treatment of Chronic Obstructive Pulmonary Disease: A Systematic Review
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12, s. 667027-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRevefenacin (REV) is a novel once-daily long-acting muscarinic antagonist (LAMA) in the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). This systematic review incorporating a dose-response meta-analysis aimed to assess the efficacy and safety of REV.MethodsPubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their inception to April 2020. We included randomized controlled trials (RCTs) which evaluated the efficacy and safety of REV in COPD patients. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Outcomes consisted of the mean change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline, adverse events (AEs), and serious adverse events (SAEs). A dose-response meta-analysis using the robust error meta-regression method was conducted. We used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.ResultsNine RCTs (3,121 participants) were included in this systematic review. The meta-analyses indicated that 175 μg/day REV could significantly improve the trough FEV1(MD=143.67, 95%CI: 129.67 to 157.68; I2=96%; 809 participants; studies=4; low quality) without increasing the risk of AEs (OR=0.98, 95%CI: 0.81 to 1.18; I2=34%; 2,286 participants; studies=7; low quality) or SAEs (OR=0.89, 95%CI: 0.55 to 1.46; I2=0%; 2,318 participants; studies=7; very low quality) compared to placebo. Furthermore, the effect of REV in increasing trough FEV1was dose-dependent with an effective threshold of 88 μg/day (R2= 0.7017). Nevertheless, only very low-quality to low-quality evidence showed that REV at a dose of 175 μg/day was inferior to tiotropium regarding the long-term efficacy, and its safety profile was not superior to tiotropium or ipratropium.ConclusionCurrent evidence shows that REV is a promising option for the treatment of moderate to very severe COPD. Due to most evidence graded as low quality, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between REV and other LAMAs in different populations.Clinical Trial Registration: [PROSPERO], identifier [CRD42020182793]
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| 32. |
- 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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