| 1. |
- Hu, Jinhong, et al.
(författare)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 2. |
- Chen, Jie, et al.
(författare)
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Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. Methods We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. Results Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 x 10(-10)]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 x 10(-19)] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. Conclusion Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC.
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| 3. |
- Jin, Zhichao, et al.
(författare)
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A retrospective survey of research design and statistical analyses in selected Chinese medical journals in 1998 and 2008
- 2010
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High quality clinical research not only requires advanced professional knowledge, but also needs sound study design and correct statistical analyses. The number of clinical research articles published in Chinese medical journals has increased immensely in the past decade, but study design quality and statistical analyses have remained suboptimal. The aim of this investigation was to gather evidence on the quality of study design and statistical analyses in clinical researches conducted in China for the first decade of the new millennium.METHODOLOGY/PRINCIPAL FINDINGS: Ten (10) leading Chinese medical journals were selected and all original articles published in 1998 (N = 1,335) and 2008 (N = 1,578) were thoroughly categorized and reviewed. A well-defined and validated checklist on study design, statistical analyses, results presentation, and interpretation was used for review and evaluation. Main outcomes were the frequencies of different types of study design, error/defect proportion in design and statistical analyses, and implementation of CONSORT in randomized clinical trials. From 1998 to 2008: The error/defect proportion in statistical analyses decreased significantly ( = 12.03, p<0.001), 59.8% (545/1,335) in 1998 compared to 52.2% (664/1,578) in 2008. The overall error/defect proportion of study design also decreased ( = 21.22, p<0.001), 50.9% (680/1,335) compared to 42.40% (669/1,578). In 2008, design with randomized clinical trials remained low in single digit (3.8%, 60/1,578) with two-third showed poor results reporting (defects in 44 papers, 73.3%). Nearly half of the published studies were retrospective in nature, 49.3% (658/1,335) in 1998 compared to 48.2% (761/1,578) in 2008. Decreases in defect proportions were observed in both results presentation ( = 93.26, p<0.001), 92.7% (945/1,019) compared to 78.2% (1023/1,309) and interpretation ( = 27.26, p<0.001), 9.7% (99/1,019) compared to 4.3% (56/1,309), some serious ones persisted.CONCLUSIONS/SIGNIFICANCE: Chinese medical research seems to have made significant progress regarding statistical analyses, but there remains ample room for improvement regarding study designs. Retrospective clinical studies are the most often used design, whereas randomized clinical trials are rare and often show methodological weaknesses. Urgent implementation of the CONSORT statement is imperative.
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| 4. |
- Li, Yuchen, et al.
(författare)
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Associations of parental and perinatal factors with subsequent risk of stress-related disorders : a nationwide cohort study with sibling comparison
- 2022
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 27, s. 1712-1719
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity >= 4, mothers with BMI >= 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.
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| 5. |
- Sun, Zhendong, et al.
(författare)
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4-Hexylphenol influences adipogenic differentiation and hepatic lipid accumulation in vitro
- 2021
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 268:Part A
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Tidskriftsartikel (refereegranskat)abstract
- Finding the potential environmental obesogens is crucial to explain the prevalence of obesity and the related pathologies. Increasing evidence has showed that many chemicals with endocrine disrupting effects can disturb lipid metabolism. Whether 4-hexylphenol (4-HP), a widely-used surfactant and a potential endocrine disrupting chemical (EDC), is associated to influence adipogenesis and hepatic lipid accumulation remained to be elucidated. In this study, both the 3T3-L1 differentiation model and oleic acid (OA)-treated HepG2 cells were used to investigate the effects of 4-HP on lipid metabolism, and the underlying estrogen receptor (ER)-involved mechanism was explored using MVLN assay, molecular docking simulation and the antagonist test. The results based on lipid droplet staining and triglyceride accumulation assay showed that 4-HP treatment promoted the adipogenic differentiation of 3T3-L1 cells and increased hepatic cellular OA accumulation in exposure concentration-dependent manners. The study on the elaborated transcription networks indicated that 4-HP activated peroxisome proliferator-activated receptor γ (PPARγ) as well as the subsequent adipogenic gene program in 3T3-L1 cells. This chemical also induced the increase of OA uptake and decreases of de novo lipogenesis and fatty acid oxidation in HepG2 cells. The agonistic activity of 4-HP in triggering ER-mediated pathway was shown to correlate with its perturbation in lipid metabolism, as evidenced by the enhanced development of mature lipid-laden adipocytes and suppression of excessive hepatic lipid accumulation upon its co-treatment with ER antagonist. Altogether, these findings provide new insights into the potential health impacts of 4-HP exposure as it may relate to obesity and nonalcoholic fatty liver disease.
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| 6. |
- Sun, Zhendong, et al.
(författare)
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Butylated hydroxyanisole isomers induce distinct adipogenesis in 3T3-L1 cells
- 2019
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 379
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Tidskriftsartikel (refereegranskat)abstract
- Butylated hydroxyanisole (BHA) isomers, as the widely used anthropogenic antioxidants in food, have been revealed to induce endocrine disrupting effects, while the mechanism how BHA isomers regulate the lipogenic differentiation remains to be elucidated. Using 3T3-L1 differentiation model, the effects of BHA isomers, including 2-tert-butyl-4-hydroxyanisole (2-BHA), 3-tert-butyl-4-hydroxyanisole (3-BHA) and their mixture (BHA), on adipogenesis were tested. The results showed that 3-BHA and BHA promoted adipocyte differentiation and enhanced the cellular lipid accumulation through the regulation of the transcriptional and protein levels of the adipogenetic biomarkers, while 2-BHA had no effect. The effective window for 3-BHA induced lipogenesis was the first four days during 3T3-L1 differentiation. BHA isomers showed no binding affinities for peroxisome proliferator activated receptor gamma (PPAR gamma). Instead, the upstream of PPAR gamma signaling pathway, i.e. the phosphorylation of cAMP-response element binding protein (CREB), upregulation of CAAT/enhancer-binding proteins beta (C/EBP beta) and elevated cell proliferation during postconfluent mitosis stage were induced by 3-BHA exposure. Altogether, this study revealed the adipogenic effect of 3-BHA through interference with the upstream events of the PPAR gamma signaling pathway. The authorized usage of BHA as food additives and its occurrence in human sera can potentially contribute to the incidence of obesity, which is of high concern.
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| 7. |
- Sun, Zhendong, et al.
(författare)
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Perturbation of 3-tert-butyl-4-hydroxyanisole in adipogenesis of male mice with normal and high fat diets
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 703
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Tidskriftsartikel (refereegranskat)abstract
- As one of the widely used anthropogenic food additives, 3-tert-butyl-4-hydroxyanisole (3-BHA) has been found to perturb adipogenesis in vitro and induce lipid accumulation in some strains of oleaginous microalgae. The impact of this chemical on adipocyte development and lipid metabolism in mammals remains to be elucidated. In this study, we performed 18-week oral administration of 3-BHA to male C57BL/6J mice with normal diet (ND) or high-fat diet (HFD) and investigated its impacts on adipogenesis and lipid accumulation in vivo. The results indicated that long-term exposure to 3-BHA impacted the mouse body weight gain, white adipose tissue accumulation, and plasma lipids through transcriptional regulation of adipogenesis, lipid metabolism, and adipocyte endocrine function, while glucose metabolism and insulin sensitivity remained unaffected. HFD-fed mice responded to 3-BHA stimulation differently from ND-fed animals, suggesting potential risks for the human burden of 3-BHA in lean and obese subjects. The findings herein validate 3-BHA as an environmental obesogen, and more caution is recommended for its authorized use as a food antioxidant against lipid rancidity.
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| 8. |
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| 9. |
- Webster, Natasha A., 1978-, et al.
(författare)
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Thinking through digital mediations and spatialities of platform based work : A roundtable reflection
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper is a unique roundtable discussion between geographers to explore, contextualizeand problematize the role of geography in the gig economy. It brings together eight researchersfrom across Europe all working with qualitative methods and studying the gig economy. Basedon reflections and commentaries regarding the spatialities and temporalities in and of the gigeconomy, we offer an innovative approach to exploring complicated factors in an emerging andrapidly growing field. We highlight the multiple layers of geography in physical and digitalspaces and the, sometimes blurry, interactions between these. We also show howtemporalities shape the geographies of the gig economy. This paper contributes to developing,deepening and advancing theoretical challenges in understanding the gig economy. It alsobrings these challenges into an accessible, yet thorough publication that can be used inteaching about the gig economy and digital geography. We provide a pedagogical tool tosupport university teachers in using this document in their courses.
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| 10. |
- Zhang, Haiyan, et al.
(författare)
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Facile preparation of glutathione-stabilized gold nanoclusters for selective determination of chromium (III) and chromium (VI) in environmental water samples
- 2013
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 770, s. 140-146
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Tidskriftsartikel (refereegranskat)abstract
- A novel method for selective determination of Cr(III) and Cr(VI) in environmental water samples was developed based on target-induced fluorescence quenching of glutathione-stabilized gold nanoclusters (GSH-Au NCs). Fluorescent GSH-Au NCs were synthesized by a one-step approach employing GSH as reducing/protecting reagent. It was found that Cr(III) and Cr(VI) showed pH-dependent fluorescence quenching capabilities for GSH-Au NCs, and thus selective determination of Cr(III) and Cr(VI) could be achieved at different pHs. Addition of EDTA was able to effectively eliminate the interferences from other metal ions, leading to a good selectivity for this method. Under optimized conditions, Cr(III) showed a linear range of 25-3800 μg L(-1) and a limit of detection (LOD) of 2.5 μg L(-1). The Cr(VI) ion demonstrated a linear range of 5-500 μg L(-1) and LOD of 0.5 μg L(-1). The run-to-run relative standard deviations (n=5) for Cr(III) and Cr(VI) were 3.9% and 2.8%, respectively. The recoveries of Cr(III) and Cr(VI) in environmental water samples were also satisfactory (76.3-116%). This method, with its simplicity, low cost, high selectivity and sensitivity, could be used as a promising tool for chromium analysis in environmental water samples.
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