| 1. |
- Yin, Fengyue, et al.
(författare)
-
DSPE-PEG2000-methotrexate nanoparticles encapsulating phenobarbital sodium kill cancer cells by inducing pyroptosis
- 2023
-
Ingår i: Journal of Molecular Medicine. - 0946-2716.
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is a life-threatening disease worldwide. Nanomedicine and nanodelivery systems are recently developed scientific field that employs specific materials in the nanoscale range to deliver drugs. Lipid-based nanoparticles are an ideal delivery system since they exhibit many advantages, including high bioavailability, self-assembly, formulation simplicity, and the ability to exhibit a plethora of physicochemical properties. Herein, we report that phenobarbital sodium can kill cancer cells by using the DSPE-PEG2000-methotrexate nanoparticle delivery system, which can target folate receptors that are usually overexpressed on a variety of cancer cells. The released phenobarbital then executes cancer cells by inducing pyroptosis. Results from our animal model further indicate that the nanomedicine of nanoparticle-encapsulated phenobarbital sodium is a promising anticancer therapy.
|
|
| 2. |
- Liu, Xiaohu, et al.
(författare)
-
Biofunctionalized Gold Nanoparticles for Colorimetric Sensing of Botulinum Neurotoxin A Light Chain
- 2014
-
Ingår i: Analytical Chemistry. - : American Chemical Society. - 0003-2700 .- 1520-6882. ; 86:5, s. 2345-2352
-
Tidskriftsartikel (refereegranskat)abstract
- Botulinum neurotoxin is considered as one of the most toxic food-borne substances and is a potential bioweapon accessible to terrorists. The development of an accurate, convenient, and rapid assay for botulinum neurotoxins is therefore highly desirable for addressing biosafety concerns. Herein, novel biotinylated peptide substrates designed to mimic synaptosomal-associated protein 25 (SNAP-25) are utilized in gold nanoparticle-based assays for colorimetric detection of botulinum neurotoxin serotype A light chain (BoLcA). In these proteolytic assays, biotinylated peptides serve as triggers for the aggregation of gold nanoparticles, while the cleavage of these peptides by BoLcA prevents nanoparticle aggregation. Two different assay strategies are described, demonstrating limits of detection ranging from 5 to 0.1 nM of BoLcA with an overall assay time of 4 h. These hybrid enzyme-responsive nanomaterials provide rapid and sensitive detection for one of the most toxic substances known to man.
|
|
| 3. |
- Wang, Jinling, et al.
(författare)
-
Bcl-2 hijacks the arsenic trioxide resistance in SH-SY5Y cells
- 2022
-
Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 26:2, s. 563-569
-
Tidskriftsartikel (refereegranskat)abstract
- Aresenic trioxide (ATO) is proven to be active against leukaemia cells by inducing apoptosis and differentiation. Even though ATO could effectively induce remissions of leukaemia cells, the drug resistance was observed occasionally. To further dissect the mechanism of ATO resistance, we selected the ATO-resistant SH-SY5Y cells and found that Bcl-2 controlled the sensitivity of ATO in SH-SY5Y cells. We report that necroptosis, autophagy, NF-ƘB and MAPK signalling pathway are not involved in ATO-induced apoptosis. Moreover, the ATO-resistant cells showed distinct mitochondrial morphology compared with that of ATO-sensitive cells. Intriguingly, nude mice-bearing ATO-sensitive cells derived xenograft tumours are more sensitive to ATO treatment compared with that of ATO-resistant cells. These data demonstrate that cancer cells can acquire the ATO-resistance ability by increasing the Bcl-2 expression.
|
|
| 4. |
- Axelsson, Annika, et al.
(författare)
-
Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
|
|
| 5. |
- Hänzelmann, Sonja, et al.
(författare)
-
Thrombin stimulates insulin secretion via protease-activated receptor-3.
- 2015
-
Ingår i: Islets. - : Informa UK Limited. - 1938-2022 .- 1938-2014. ; 7:4, s. 1118195-1118195
-
Tidskriftsartikel (refereegranskat)abstract
- The disease mechanisms underlying type 2 diabetes (T2D) remain poorly defined. Here we aimed to explore the pathophysiology of T2D by analyzing gene co-expression networks in human islets. Using partial correlation networks we identified a group of co-expressed genes ('module') including F2RL2 that was associated with glycated hemoglobin. F2Rl2 is a G-protein-coupled receptor (GPCR) that encodes protease-activated receptor-3 (PAR3). PAR3 is cleaved by thrombin, which exposes a 6-amino acid sequence that acts as a 'tethered ligand' to regulate cellular signaling. We have characterized the effect of PAR3 activation on insulin secretion by static insulin secretion measurements, capacitance measurements, studies of diabetic animal models and patient samples. We demonstrate that thrombin stimulates insulin secretion, an effect that was prevented by an antibody that blocks the thrombin cleavage site of PAR3. Treatment with a peptide corresponding to the PAR3 tethered ligand stimulated islet insulin secretion and single β-cell exocytosis by a mechanism that involves activation of phospholipase C and Ca(2+) release from intracellular stores. Moreover, we observed that the expression of tissue factor, which regulates thrombin generation, was increased in human islets from T2D donors and associated with enhanced β-cell exocytosis. Finally, we demonstrate that thrombin generation potential in patients with T2D was associated with increased fasting insulin and insulinogenic index. The findings provide a previously unrecognized link between hypercoagulability and hyperinsulinemia and suggest that reducing thrombin activity or blocking PAR3 cleavage could potentially counteract the exaggerated insulin secretion that drives insulin resistance and β-cell exhaustion in T2D.
|
|
| 6. |
- Jin, Binghan, et al.
(författare)
-
Abdominal Adiposity and Total Body Fat as Predictors of Cardiometabolic Health in Children and Adolescents With Obesity
- 2020
-
Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods:In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results:Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [-29% (95% CI -36%, -20%);p< 0.0001], pubertal boys [-13% (95% CI -21%, -6%);p= 0.001], and pubertal girls [-16% (95% CI -24%, -6%);p= 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions:A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism.
|
|
| 7. |
- Piao, Jinling, et al.
(författare)
-
Northward extension of the East Asian summer monsoon during the mid-Holocene
- 2020
-
Ingår i: Global and Planetary Change. - : Elsevier BV. - 0921-8181 .- 1872-6364. ; 184
-
Forskningsöversikt (refereegranskat)abstract
- Previous studies based on multiple paleoclimate archives suggested that during the mid-Holocene (MH, similar to 6000 years before present day), the East Asian summer monsoon (EASM) had a prominent intensification and northward extension. However, current climate model simulations with orbital forcing alone present an underestimation of the magnitude of changes in the EASM. In the current work, we show that considering a vegetated and dust-reduced Sahara in the MH can significantly strengthen the EASM intensity and expand its northernmost boundary northward compared to the results with orbital forcing alone. The vegetation change over the Sahara is the dominant factor for the variation in the EASM, while the dust reduction plays a smaller role. The vegetated Sahara causes a westward shift of the Walker circulation, accompanied with enhancement of the western Pacific subtropical high (WPSH), which then results in a strengthened EASM. On one hand, the change in the Walker circulation induces decreased rainfall over the western equatorial Pacific, intensifying the WPSH through the Gill-Matsuno response. On the other hand, the shift in the Walker circulation is associated with a stronger local Hadley circulation, reinforcing the WPSH. Finally, our results show that the westward expansion of the WPSH is mainly caused by the local strengthening of the Hadley circulation.
|
|
| 8. |
- Wang, Jinling, et al.
(författare)
-
High Prevalence of Cardiometabolic Comorbidities Among Children and Adolescents With Severe Obesity From a Large Metropolitan Centre (Hangzhou, China)
- 2022
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to describe the clinical characteristics of children and adolescents with obesity, and the prevalence of cardiometabolic comorbidities over 10 years in this population from a large metropolitan centre in China.Methods: This was a cross-sectional study (2008–2017) of patients aged <18 years with obesity [body mass index (BMI) ≥ 95th percentile for age and sex] enrolled at the Department of Endocrinology, Children’s Hospital of Zhejiang University School of Medicine (Hangzhou, Zhejiang Province). Clinical assessments included anthropometry, blood pressure, liver ultrasound, lipid profile, oral glucose tolerance test, and uric acid. For examination of outcomes, our study cohort was stratified by sex and age bands (<10 vs. ≥10 years), with the study period also split into two strata (2008–2012 and 2013–2017).Results: A total of 2,916 patients (1,954 boys and 962 girls) were assessed at a mean age of 10.5 years. Patients almost invariably presented severe obesity (median BMI SDS = 2.98; Q1 = 2.60, Q3 = 3.39). Obesity-related comorbidities were common among boys and girls, including type 2 diabetes mellitus (2.6% and 3.6%, respectively), abnormal glycaemia (33.6% and 35.5%, respectively), hypertension (33.9% and 32.0%, respectively), dyslipidaemia (35.2% and 39.6%, respectively), hyperuricaemia (16.2% and 8.3%, respectively), acanthosis nigricans (71.9% and 64.0%, respectively), abnormal liver function (66.9% and 47.0%, respectively), and non-alcoholic fatty liver disease (NAFLD) (63.8% and 45.1%, respectively); 38.7% of boys and 44.4% of girls aged ≥10 years had metabolic syndrome. Notably, the incidence of many cardiometabolic comorbidities was in 2013–2017 compared to 2008–2012. For example, rates of hypertension among boys aged <10 years and aged ≥10 years rose from 28.4% and 26.5% to 48.0% and 35.8%, respectively, and in girls from 20.3% and 20.8% to 41.7% and 39.6%, respectively. In 2013–2017, 9.5% of girls in the older group had metabolic syndrome compared to 2.2% in 2008–2013.Conclusions: We observed a high incidence of obesity-related cardiometabolic comorbidities among Chinese children and adolescents with severe obesity over 10 years. It was particularly concerning that rates of several comorbidities rose markedly over the study period, highlighting the need to address the obesity epidemic early in life (in China and elsewhere) to prevent the development of obesity-related comorbidities and, subsequently, of overt disease.
|
|
| 9. |
- Wang, Jinling, et al.
(författare)
-
Urbanization in developing countries overrides catchment productivity in fueling inland water CO2 emissions
- 2022
-
Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 29:1, s. 1-4
-
Tidskriftsartikel (refereegranskat)abstract
- We compiled a nationwide dataset of carbon dioxide (CO2) efflux from 1405 measurements, and found that lakes, reservoirs, and rivers emit a total of 61.9 ± 55.3 TgC as CO2 each year, corresponding to 6.3% of the annual total national CO2 emission in 2020. Our analysis showed that the presence of anthropogenic disturbances in catchments strongly influences the emission of CO2 from these waters in the non-pristine areas, masking the catchment productivity effect on the emission of CO2. Our results highlight the need for adjusting climate change models for taking into account anthropogenic effects on CO2 emissions from inland waters.
|
|
| 10. |
- Wang, Yi, et al.
(författare)
-
Time-resolved botulinum neurotoxin A activity monitored using peptide-functionalized Au nanoparticle energy transfer sensors
- 2014
-
Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 5:7, s. 2651-2656
-
Tidskriftsartikel (refereegranskat)abstract
- We report herein on the employment of synthetic peptide-functionalized gold nanoparticles (AuNPs) with various diameters as radiative quenchers for the time-resolved monitoring of botulinum A light chain (BoLcA) activity. The results demonstrate that larger AuNPs provide higher energy transfer efficiencies between the dye and the AuNPs, but poorer BoLcA activities for the proteolysis of peptides because of steric constraints. The initial turnover number for the BoLcA proteolysis of peptides on 18 nm AuNPs was retarded by a factor of 80 as compared with 1.4 nm AuNPs. A similar phenomenon has been observed for trypsin, however, with less hindrance on large AuNPs. Thus, the use of smaller 1.4 nm AuNPs in conjunction with robust synthetic peptides provides an attractive format for the time-resolved monitoring of protease activity and for BoLcA sensing at a highly competitive limit of detection (1 pM).
|
|
