| 1. |
- Eleonora Hedlund, Eva-Maria, et al.
(author)
-
Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs
- 2013
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:2, s. 654-659
-
Journal article (peer-reviewed)abstract
- The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti-VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy.
|
|
| 2. |
- Hosaka, Kayoko, et al.
(author)
-
Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis
- 2013
-
In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:2129
-
Journal article (peer-reviewed)abstract
- Anti-platelet-derived growth factor (PDGF) drugs are routinely used in front-line therapy for the treatment of various cancers, but the molecular mechanism underlying their dose-dependent impact on vascular remodelling remains poorly understood. Here we show that anti-PDGF drugs significantly inhibit tumour growth and metastasis in high PDGF-BB-producing tumours by preventing pericyte loss and vascular permeability, whereas they promote tumour cell dissemination and metastasis in PDGF-BB-low-producing or PDGF-BB-negative tumours by ablating pericytes from tumour vessels. We show that this opposing effect is due to PDGF-beta signalling in pericytes. Persistent exposure of pericytes to PDGF-BB markedly downregulates PDGF-beta and inactivation of the PDGF-beta signalling decreases integrin alpha 1 beta 1 levels, which impairs pericyte adhesion to extracellular matrix components in blood vessels. Our data suggest that tumour PDGF-BB levels may serve as a biomarker for selection of tumour-bearing hosts for anti-PDGF therapy and unsupervised use of anti-PDGF drugs could potentially promote tumour invasion and metastasis.
|
|
| 3. |
- Iwamoto, Hideki, et al.
(author)
-
PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effects and drug resistance to Dll4-Notch inhibitors
- 2015
-
In: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 1:3
-
Journal article (peer-reviewed)abstract
- Inhibition of Dll4 (delta-like ligand 4)-Notch signaling-mediated tumor angiogenesis is an attractive approach in cancer therapy. However, inhibition of Dll4-Notch signaling has produced different effects in various tumors, and no biomarkers are available for predicting the anti-Dll4-Notch-associated antitumor activity. We show that human and mouse tumor cell-derived placental growth factor (PlGF) is a key determinant of the Dll4-Notch-induced vascular remodeling and tumor growth. In natural PlGF-expressing human tumors, inhibition of Dll4-Notch signaling markedly accelerated tumor growth by increasing blood perfusion in nonleaking tumor vasculatures. Conversely, in PlGF-negative tumors, Dll4 inhibition suppressed tumor growth by the formation of nonproductive and leaky vessels. Surprisingly, genetic inactivation of vascular endothelial growth factor receptor 1 (VEGFR1) completely abrogated the PlGF-modulated vascular remodeling and tumor growth, indicating a crucial role for VEGFR1-mediated signals in modulating Dll4-Notch functions. These findings provide mechanistic insights on PlGF-VEGFR1 signaling in the modulation of the Dll4-Notch pathway in angiogenesis and tumor growth, and have therapeutic implications of PlGF as a biomarker for predicting the antitumor benefits of Dll4 and Notch inhibitors.
|
|
| 4. |
- Ji, Hong, et al.
(author)
-
TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
- 2014
-
In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 5:4944
-
Journal article (peer-reviewed)abstract
- Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-alpha-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(+/+) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-alpha-TNFR1 pathway.
|
|
| 5. |
- Yang, Xiaojuan, et al.
(author)
-
Vascular endothelial growth factor-dependent spatiotemporal dual roles of placental growth factor in modulation of angiogenesis and tumor growth
- 2013
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:34, s. 13932-13937
-
Journal article (peer-reviewed)abstract
- Placental growth factor (PIGF) remodels tumor vasculatures toward a normalized phenotype, which affects tumor growth, invasion and drug responses. However, the coordinative and spatiotemporal relation between PIGF and VEGF in modulation of tumor angiogenesis and vascular remodeling is less understood. Here we report that PlGF positively and negatively modulate tumor growth, angiogenesis, and vascular remodeling through a VEGF-dependent mechanism. In two independent tumor models, we show that PlGF inhibited tumor growth and angiogenesis and displayed a marked vascular remodeling effect, leading to normalized microvessels with infrequent vascular branches and increased perivascular cell coverage. Surprisingly, elimination of VEGF gene (i.e., VEGF-null) in PIGF-expressing tumors resulted in (i) accelerated tumor growth rates and angiogenesis and (ii) complete attenuation of PIGF-induced vascular normalization. Thus, PIGF positively and negatively modulates tumor growth, angiogenesis, and vascular remodeling through VEGF-dependent spatiotemporal mechanisms. Our data uncover molecular mechanisms underlying the complex interplay between PIGF and VEGF in modulation of tumor growth and angiogenesis, and have conceptual implication for antiangiogenic cancer therapy.
|
|
| 6. |
- Yang, Xiaojuan, et al.
(author)
-
VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients
- 2015
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:22, s. E2900-E2909
-
Journal article (peer-reviewed)abstract
- The biological functions of VEGF-B in cancer progression remain poorly understood. Here, we report that VEGF-B promotes cancer metastasis through the remodeling of tumor microvasculature. Knockdown of VEGF-B in tumors resulted in increased perivascular cell coverage and impaired pulmonary metastasis of human melanomas. In contrast, the gain of VEGF-B function in tumors led to pseudonormalized tumor vasculatures that were highly leaky and poorly perfused. Tumors expressing high levels of VEGF-B were more metastatic, although primary tumor growth was largely impaired. Similarly, VEGF-B in a VEGF-A-null tumor resulted in attenuated primary tumor growth but substantial pulmonary metastases. VEGF-B also led to highly metastatic phenotypes in Vegfr1 tk(-/-) mice and mice treated with anti-VEGF-A. These data indicate that VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism. High expression levels of VEGF-B in two large-cohort studies of human patients with lung squamous cell carcinoma and melanoma correlated with poor survival. Taken together, our findings demonstrate that VEGF-B is a vascular remodeling factor promoting cancer metastasis and that targeting VEGF-B may be an important therapeutic approach for cancer metastasis.
|
|
| 7. |
- Yang, Yunlong, et al.
(author)
-
Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues
- 2013
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:29, s. 12018-12023
-
Journal article (peer-reviewed)abstract
- Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1-specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF-specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF-specific drugs.
|
|
| 8. |
- Yang, Yunlong, et al.
(author)
-
The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
- 2016
-
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11385
-
Journal article (peer-reviewed)abstract
- Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain-and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.
|
|
| 9. |
- Cao, Renhai, et al.
(author)
-
Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis
- 2012
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:39, s. 15894-15899
-
Journal article (peer-reviewed)abstract
- Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary and lymph-node metastases. Coimplantation of dual factors in the mouse cornea resulted in additive angiogenesis and lymphangiogenesis. At the molecular level, we showed that FGFR-1 expressed in lymphatic endothelial cells is a crucial receptor that mediates the FGF-2-induced lymphangiogenesis. Intriguingly, the VEGFR-3-mediated signaling was required for the lymphatic tip cell formation in both FGF-2- and VEGF-C-induced lymphangiogenesis. Consequently, a VEGFR-3-specific neutralizing antibody markedly inhibited FGF-2-induced lymphangiogenesis. Thus, the VEGFR-3-induced lymphatic endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting of the FGF-2- and VEGF-C-induced angiogenic and lymphangiogenic synergism could be potentially important approaches for cancer therapy and prevention of metastasis.
|
|
| 10. |
- Fang, Shu, et al.
(author)
-
Offset Spatial Modulation and Offset Space Shift Keying : Efficient Designs for Single-RF MIMO Systems
- 2019
-
In: IEEE Transactions on Communications. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0090-6778 .- 1558-0857. ; 67:8, s. 5434-5444
-
Journal article (peer-reviewed)abstract
- Spatial modulation (SM) and space shift keying (SSK) techniques have the unique advantages of their single-radio-frequency (RF) structures compared with conventional multiple-input-multiple-output (MIMO) techniques. However, the transmission rates of these techniques are decided by the maximal switching frequency or by the minimal switching time between the RF chain and transmit antennas, which has been a bottleneck for their applications in future broadband wireless communications. To alleviate this problem, we propose a class of novel offset SM (OSM) and offset SSK (OSSK) schemes, with the aid of channel state information (CSI) at the transmitter. Compared with conventional SM and SSK, the proposed OSM and OSSK schemes can reduce the switching frequency of the RF chain, by introducing an offset between the connected RF chain and the index of the spatial modulated antenna. In extreme conditions, the proposed OSM and OSSK can work without RF switching while maintaining the single-RF advantage of conventional SM and SSK schemes. Through theoretical analysis, we also develop the bit-error rate (BER) performance bounds for the proposed two schemes. Finally, our simulation results demonstrate that the proposed OSM and OSSK outperform their counterparts, including conventional SM, SSK, CSI-aided SM, and CSI-aided SSK, while having a simplified RF-switching structure.
|
|
| 11. |
- Guo, Jianqiu, et al.
(author)
-
Anthropometric measures at age 3 years in associations with prenatal and postnatal exposures to chlorophenols
- 2019
-
In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 228, s. 204-211
-
Journal article (peer-reviewed)abstract
- Background: Chlorophenols (CPs), suspected as endocrine disrupting chemicals, exposure during early life may contribute to body size. However, limited human data with inconsistent findings have examined the developmental effects of CPs exposure.Objective: To explore associations between prenatal and postnatal CPs exposure and anthropometric parameters in children aged 3 years.Methods: A subset of 377 mother-child pairs with urinary five CP concentrations were enrolled from a prospective birth cohort. Generalized linear models were conducted to evaluate associations of CPs exposure with children's anthropometric measures.Results: Maternal urinary 2,4,6-trichlorophenol (2,4,6-TCP) concentrations were significantly negatively associated with weight z scores [regression coefficient (beta)=-0.51, 95% confidence interval (Cl): -0.96, -0.05; p = 0.01], weight for height z scores (beta = -0.54, 95% Cl:-1.02, -0.06; p= 0.01) and body mass index (BMI) z scores (beta = -0.53, 95% CI;-1.03, 0.03; p = 0.01) of children aged 3 years, after adjustment for potential confounders and postnatal CPs exposure. In the sex-stratified analyses, these inverse associations remained among boys, while in girls, positive associations of prenatal 2,4,6-TCP exposure with weight for height z scores and BMI z scores were observed. Postnatal exposure to 2,5-diclorophenol (2,5-DCP) was positively associated with weight z scores (beta = 0.26, 95% CI: 0.02, 0.50; p = 0.04), after controlling for possible confounders and maternal CPs exposure during pregnancy. Considering potential sex-specific effects, these associations were only observed in girls.Conclusions: Our findings indicate that prenatal 2,4,6-TCP exposure and postnatal 2,5-DCP exposure may have adverse and sex-specific effects on children's physical development.
|
|
| 12. |
- Guo, Jianqiu, et al.
(author)
-
Associations of prenatal and childhood chlorpyrifos exposure with Neurodevelopment of 3-year-old children
- 2019
-
In: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 251, s. 538-546
-
Journal article (peer-reviewed)abstract
- Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 mu g/L and 5.34 mu g/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 [95% confidence interval (CI): -1.13, -0.09; p = 0.02] and social area DQ score 0.55 (95% CI: -1.07, -0.03; p = 0.04) per one-unit increase in the In-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.
|
|
| 13. |
- Guo, Jianqiu, et al.
(author)
-
Early life triclosan exposure and neurodevelopment of children at 3 years in a prospective birth cohort
- 2020
-
In: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 224
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations.OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years.METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs).RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 μg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, β = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (β = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (β = -0.37, 95%CI: -0.72, -0.03; p = 0.03).CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.
|
|
| 14. |
- Guo, Jianqiu, et al.
(author)
-
Maternal and childhood urinary phenol concentrations, neonatal thyroid function, and behavioral problems at 10 years of age : The SMBCS study
- 2020
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 743
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Environmental phenols, bisphenol A (BPA), triclosan (TCS), and benzophenone-3 (BP-3), are known as emerging endocrine-disrupting chemicals; however, their impacts on thyroid hormones and children's neurobehaviors are still unclear.OBJECTIVES: We aimed to examine the associations of prenatal and childhood exposure to phenols with neonatal thyroid function and childhood behavioral problems aged 10 years.METHODS: A total of 386 mother-singleton pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. We quantified urinary BPA, TCS and BP-3 concentrations in maternal and 10-year-old children's urine samples using gas chromatography tandem mass spectrometry and thyroid function parameters in cord serum samples. Caregivers completed the Strength and Difficulties Questionnaire (SDQ) for their children at 10 years of age. Multivariable linear regression models and logistic regression models were applied to estimate associations of urinary phenol concentrations with thyroid hormones and risks of children's behavioral problems, respectively.RESULTS: The median values of urinary BPA, TCS and BP-3 concentrations for pregnant women were 1.75 μg/L, 0.54 μg/L and 0.37 μg/L, while 1.29 μg/L, 6.64 μg/L and 1.39 μg/L for children, respectively. Maternal urinary BPA concentrations were in associations with 1.00% [95% confidence interval (CI): 0.20%, 1.92%] increases in cord serum FT4 concentrations and significantly associated with increased risks of total difficulties [odds ratio (OR): 1.45, 95% CI: 1.07, 1.97], while maternal urinary levels of BP-3 were significantly related to poorer prosocial behaviors (OR: 1.58, 95% CI: 1.04, 2.39) of children at 10 years of age. In sex-stratified analyses, maternal urinary BPA concentrations were related to increased total difficulty subscales only in boys.CONCLUSIONS: The findings indicated that higher prenatal urinary BPA concentrations were associated with increased risks of total difficulties, especially in boys and maternal urinary BP-3 concentrations were related to poorer prosocial behaviors at 10 years.
|
|
| 15. |
- Guo, Jianqiu, et al.
(author)
-
Prenatal exposure to multiple phenolic compounds, fetal reproductive hormones, and the second to fourth digit ratio of children aged 10 years in a prospective birth cohort
- 2021
-
In: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 263
-
Journal article (peer-reviewed)abstract
- Select phenols are known to possess hormone-disrupting properties, but no previous study has addressed the potential effects of prenatal exposure to phenol mixtures on fetal reproductive hormones and children's second to fourth digit (2D: 4D) ratio, a marker for in utero testosterone (T) exposure. We aimed to explore interrelations of prenatal phenol exposures individually and in mixtures, cord serum reproductive hormones, and 2D: 4D ratio of children aged 10 years. Urinary 11 phenol concentrations were determined from 392 pregnant women participating in a longitudinal birth cohort. We estimated associations of prenatal phenol exposures individually and in mixtures with cord reproductive hormones and children's 2D:4D ratio using three statistical approaches, including generalized linear models (GLMs), elastic net regression (ENR) models and Bayesian kernel machine regression (BKMR) models. In female newborns, the three models showed that maternal triclosan (TCS) concentrations were significantly negatively associated with cord serum T levels [regression coefficient (β) = -0.076, 95% confidence interval (CI): 0.138, -0.013; p = 0.018]. Additionally, maternal urinary bisphenol A (BPA) levels were related to decreases in 2D:4D ratio of the left hand in girls by GLMs (β = -0.003, 95% CI: 0.007, -0.001; p = 0.024) and ENR models, but not BKMR models. We provided evidence that prenatal TCS exposure predicted lower cord serum T levels, and maternal BPA exposure was related to decreased 2D:4D ratio of the left hand in females.
|
|
| 16. |
- Jiao, Yaqi, et al.
(author)
-
SUMO-specific proteases : SENPs in oxidative stress-related signaling and diseases
-
In: BioFactors. - 0951-6433.
-
Research review (peer-reviewed)abstract
- Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.
|
|
| 17. |
- Li, Wenting, et al.
(author)
-
Effects of prenatal exposure to five parabens on neonatal thyroid function and birth weight : Evidence from SMBCS study
- 2020
-
In: Environmental Research. - : Academic Press. - 0013-9351 .- 1096-0953. ; 188
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Parabens, suspected as endocrine-disrupting chemicals, are nearly ubiquitous in the human body and exposure to these chemicals during pregnancy may disrupt thyroid hormones homeostasis and even affect fetal growth, although the impacts are still unclear.OBJECTIVES: We aimed to estimate associations of maternal urinary paraben concentrations with cord serum thyroid hormones and birth weight.METHODS: A subset of 437 mother-newborn pairs were included from a prospective birth cohort with five parabens quantified in maternal urine and seven thyroid function indicators measured in cord serum samples. Multivariable linear regression models and elastic net regression (ENR) models were applied to explore associations between individual and mixtures of prenatal urinary paraben concentrations and thyroid hormones and birth weight, respectively.RESULTS: Maternal urinary ethyl-paraben (EtP) concentrations were associated with increased cord serum total triiodothyronine levels (TT3) [percent change: 1.51%; 95% confidence interval (CI): 0.20%, 2.74%; p=0.017]. Urinary propyl-paraben (PrP) levels predicted higher thyroid peroxidase antibodies (percent change: 4.19%, 95% CI: 0.20%, 8.44%; p=0.041). Maternal urinary EtP and butyl-paraben (BuP) concentrations were significantly positively associated with birth weight [regression coefficient, (β)=40.9g, 95% CI: 3.99, 76.6; p=0.030; β=62.1g, 95% CI: 8.70, 115; p=0.023, for EtP and BuP, respectively]. In sex-stratified analyses, positive relationship between EtP levels and birth weight was observed in boys. Urinary EtP concentrations predicted higher TT3 levels in cord serum samples, assessing parabens as a chemical mixture with ENR models.CONCLUSIONS: Prenatal exposure to parabens may affect thyroid hormone indicators with increased serum TT3 levels and associate with higher birth weight, especially in boys. The underlying biological mechanisms and effects of prenatal paraben exposures on disruption of thyroid function homeostasis and potential impacts of childhood growth and development needed to be further investigated.
|
|
| 18. |
- Li, Xiaojuan, et al.
(author)
-
Climate and soil properties drive soil organic and inorganic carbon patterns across a latitudinal gradient in southwestern China
- 2023
-
In: Journal of Soils and Sediments. - : Springer Science and Business Media LLC. - 1614-7480 .- 1439-0108. ; 23:1, s. 91-102
-
Journal article (peer-reviewed)abstract
- PurposeDrylands account for 47.2% of land area and contain 15.5% of global carbon (C). However, the variation in organic and inorganic C stocks across latitudinal gradients in arid and semiarid shrubland ecosystems remains understudied, and we lack in-depth understanding of the main drivers of C variation at this spatial scale.MethodsHere, we sampled soils from 95 sites across a latitudinal gradient to explore both the latitudinal patterns and potential drivers of soil organic carbon density (SOCD) and soil inorganic carbon density (SICD). We also assessed variation in SOCD and SICD down the soil profile, by sampling soils at four depths (0 – 10 cm, 10 – 20 cm, 20 – 30 cm, and 30 – 50 cm).ResultBoth SOCD and SICD exhibited a binomial relationship with latitude (P < 0.01). Soil properties accounted for the greatest variation in SOCD, with the most important explanatory factor being exchangeable calcium, followed by mean annual temperature, pH, plant diversity, and silt content. Soil pH and plant diversity were more important in explaining variation in SOCD in the subsoil (> 20 cm depth) than the topsoil. For SICD, soil properties explained the greatest variation at all depths. Soil pH explained the most variance in SICD, followed by exchangeable calcium and mean annual temperature in the topsoil (i.e., 0 – 10 cm and 10 – 20 cm). In the subsoil (i.e., 20 – 30 cm and 30 – 50 cm), exchangeable calcium was the most important predictor, followed by soil organic carbon, mean annual temperature, and pH.ConclusionOur study shows that soil properties are a strong predictor of latitudinal patterns of soil organic and inorganic C in arid and semiarid shrubland ecosystems. We also identified differences in potential drivers of SOCD and SICD with depth, advancing our understanding of large-scale patterns of C storage in arid and semiarid soils.
|
|
| 19. |
- Li, Xiaojuan, et al.
(author)
-
Latitudinal patterns of light and heavy organic matter fractions in arid and semi-arid soils
- 2022
-
In: Catena. - : Elsevier BV. - 0341-8162. ; 215
-
Journal article (peer-reviewed)abstract
- Semi-arid and arid ecosystems are important for the global C cycle. Despite this, it remains unclear how organic matter fractions vary across latitudinal gradients, and what drives this variation, in dry ecosystems. In this study, we sampled soils from 100 sites across a latitudinal gradient in the dry valleys of southwestern China to explore the latitudinal patterns of light fraction organic matter (LFOM) and heavy fraction organic matter (HFOM) at two soil depths (0–10 cm and 10–20 cm). Across the studied gradient, HFOM accounted for a larger fraction of soil organic matter than LFOM. LFOM increased exponentially with increasing latitude at both 0–10 cm and 10–20 cm depths. Heavy fraction organic C increased linearly with increasing latitude at both depths, while heavy fraction organic N only increased with latitude in soils from 10 to 20 cm depth. Latitudinal patterns of LFOM were mainly explained by climate, with the most important driver being mean annual temperature, followed by mean annual precipitation. Soil physicochemical factors – in particular cation exchange capacity and silt content – explained the most variation in HFOM. Total microbial biomass was also important in explaining variation in HFOM, especially in the 10–20 cm soil layer. Overall, our results shed light on the spatial distribution of organic matter fractions in arid and semi-arid regions. We also identify candidate drivers of the variation in LFOM and HFOM in arid and semi-arid regions, finding that climate primarily explains variation in LFOM while soil physiochemistry primarily explains variation in HFOM.
|
|
| 20. |
|
|
| 21. |
- Lim, Sharon, et al.
(author)
-
Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice
- 2012
-
In: Nature Protocols. - : Nature Publishing Group. - 1754-2189 .- 1750-2799. ; 7:3, s. 606-615
-
Journal article (peer-reviewed)abstract
- Exposure of humans and rodents to cold activates thermogenic activity in brown adipose tissue (BAT). This protocol describes a mouse model to study the activation of BAT and angiogenesis in adipose tissues by cold acclimation. After a 1-week exposure to 4 degrees C, adult C57BL/6 mice show an obvious transition from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the end of week 5 BRITE contains a high number of uncoupling protein-1-positive mitochondria, a characteristic feature of BAT. During the transition from WAT into BRITE, the vascular density is markedly increased owing to the activation of angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the mitochondrial content and metabolic rate. BAT and the increased metabolic rate result in a lean phenotype. This protocol provides an outstanding opportunity to study the molecular mechanisms that control adipose mass.
|
|
| 22. |
- Medlyn, Belinda E., et al.
(author)
-
Using models to guide field experiments : a priori predictions for the CO2 response of a nutrient- and water-limited native Eucalypt woodland
- 2016
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 22:8, s. 2834-2851
-
Journal article (peer-reviewed)abstract
- The response of terrestrial ecosystems to rising atmospheric CO2 concentration (Ca), particularly under nutrient-limited conditions, is a major uncertainty in Earth System models. The Eucalyptus Free-Air CO2 Enrichment (EucFACE) experiment, recently established in a nutrient- and water-limited woodland presents a unique opportunity to address this uncertainty, but can best do so if key model uncertainties have been identified in advance. We applied seven vegetation models, which have previously been comprehensively assessed against earlier forest FACE experiments, to simulate a priori possible outcomes from EucFACE. Our goals were to provide quantitative projections against which to evaluate data as they are collected, and to identify key measurements that should be made in the experiment to allow discrimination among alternative model assumptions in a postexperiment model intercomparison. Simulated responses of annual net primary productivity (NPP) to elevated Ca ranged from 0.5 to 25% across models. The simulated reduction of NPP during a low-rainfall year also varied widely, from 24 to 70%. Key processes where assumptions caused disagreement among models included nutrient limitations to growth; feedbacks to nutrient uptake; autotrophic respiration; and the impact of low soil moisture availability on plant processes. Knowledge of the causes of variation among models is now guiding data collection in the experiment, with the expectation that the experimental data can optimally inform future model improvements.
|
|
| 23. |
- Norby, Richard J, et al.
(author)
-
Model-data synthesis for the next generation of forest free-air CO2 enrichment (FACE) experiments.
- 2016
-
In: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 209:1, s. 17-28
-
Journal article (peer-reviewed)abstract
- The first generation of forest free-air CO2 enrichment (FACE) experiments has successfully provided deeper understanding about how forests respond to an increasing CO2 concentration in the atmosphere. Located in aggrading stands in the temperate zone, they have provided a strong foundation for testing critical assumptions in terrestrial biosphere models that are being used to project future interactions between forest productivity and the atmosphere, despite the limited inference space of these experiments with regards to the range of global ecosystems. Now, a new generation of FACE experiments in mature forests in different biomes and over a wide range of climate space and biodiversity will significantly expand the inference space. These new experiments are: EucFACE in a mature Eucalyptus stand on highly weathered soil in subtropical Australia; AmazonFACE in a highly diverse, primary rainforest in Brazil; BIFoR-FACE in a 150-yr-old deciduous woodland stand in central England; and SwedFACE proposed in a hemiboreal, Pinus sylvestris stand in Sweden. We now have a unique opportunity to initiate a model-data interaction as an integral part of experimental design and to address a set of cross-site science questions on topics including responses of mature forests; interactions with temperature, water stress, and phosphorus limitation; and the influence of biodiversity.
|
|
| 24. |
- Orozco, Gustavo A., et al.
(author)
-
Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction : A computational study
- 2022
-
In: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 40:7, s. 1505-1522
-
Journal article (peer-reviewed)abstract
- Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.
|
|
| 25. |
- Yang, Xiaojuan
(author)
-
The role of VEGF family in angiogenesis, tumor growth and metastasis
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- Tumor growth is dependent on angiogenesis, and cells in tumor tissues produce various angiogenic factors to induce neovascularization. Among tumor-derived angiogenic factors, members of the vascular endothelial growth factor (VEGF) family are most frequently and highly expressed in various solid tumors. VEGF-A, the prototype of VEGF, is the most powerful pro-angiogenic factor that binds to VEGF receptor-1 (VEGFR-1, also called FMSRelated Tyrosine Kinase-1/Flt-1) and VEGFR-2 (also called Kinase Insert Domain Receptor/KDR or Fetal Liver Kinase -1/Flk-1). While the VEGFR-2-transduced angiogenic signals, pathways, and functions are well characterized, the VEGFR-1-mediated functions are poorly understood. The angiogenic functions of placental growth factor (PlGF), which is a specific VEGFR-1-binding ligand, remain controversial. The role of VEGF-B in tumor angiogenesis is still unclear. In addition, the two other VEGF family members, VEGF-C and VEGF-D are the major lymphangiogenic factors that contribute to lymphatic metastasis. The work contained in this thesis aimed to study the role of VEGF family members in angiogenesis, tumor growth and metastasis. Our work shows that PlGF exhibits a duality in modulation of angiogenesis and tumor growth in a VEGF-A-dependent manner. This is noted when the tumor cell-derived PlGF sensitizes the tumor to the anti-angiogenic and anti-tumor effects of anti-VEGF drugs. We also noted that anti-VEGF treatment induces various vascular alterations in mouse healthy tissues. Additionally, we revealed the collaborative interaction between FGF-2 and VEGF-C in promotion of lymphangiogenesis and metastasis. In paper I, using two independent tumor models, we show that PlGF modulated tumor growth, angiogenesis, and vascular remodeling through a VEGF-dependent mechanism in either a positive or a negative manner. In the VEGF-A positive model, PlGF inhibited tumor growth and angiogenesis, leading to normalized tumor vasculature with dilated vessel lumens, infrequent vascular branches and increased perivascular cell coverage. Surprisingly, in the VEGF-A negative model, overexpression of PlGF resulted in the opposite phenotype to that seen in the VEGF-A positive model, namely accelerated tumor growth rates and abundant chaotic tumor vessels. Our data uncovered the molecular mechanisms underlying the complex interplay between PlGF and VEGF-A. These findings have conceptual implications for anti-angiogenic cancer therapy. In paper II, we show that tumors from humans and mice with high levels of expression of PlGF were hypersensitive to anti-VEGF-A and anti-VEGFR-2 therapies. We then validated this finding with a loss-of-function experiment using PLGF shRNA in a human choriocarcinoma cell line. Down-regulation of PlGF significantly accelerated tumor growth rate and led to resistance to anti-VEGF drugs. We also show that VEGFR-2 and VEGFR-1 neutralizing antibodies displayed opposing effects on tumor growth and angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and sensitizes treatment effect of anti-VEGF drugs in VEGF-A positive tumors, PlGF level in VEGF-A positive tumor may potentially be a predictive marker of anti-VEGF cancer therapy. In paper III, we investigated vascular alteration in various organs after systemic treatment with anti-VEGF-A, anti-VEGFR-1 and anti-VEGFR-2 neutralizing antibodies. This study provides functional and structural mechanisms for anti-VEGF drug-induced adverse effects in patients. In paper IV, we looked into the role of fibroblast growth factor-2 (FGF-2) and VEGF-C on angiogenesis, lymphangiogenesis and tumor metastasis. The results showed that FGF-2 and VEGF-C could both separately and collaboratively promote angiogenesis and lymphangiogenesis in the cornea of the mouse and in the mouse tumor tissue, resulting in pulmonary and lymph node metastases in animal models. By blocking VEGFR-3 and FGF receptor-1 (FGFR-1), we also revealed the fact that VEGFR-3-induced lymphatic endothelial cell (LEC) tip formation is a necessity for FGF-2-FGFR-1 signaling stimulated lymphangiogenesis. This study suggests that combined targeting of FGF-2 and VEGF-C might be an effective approach for cancer therapy and prevention of metastasis.
|
|
| 26. |
- Zhang, Jiming, et al.
(author)
-
Carbamate pesticides exposure and delayed physical development at the age of seven : Evidence from the SMBCS study
- 2022
-
In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 160
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Carbamate pesticides are widely used in agriculture and cause widespread human exposure. The health effect of carbamates on physical development remains unclear. The current study aimed to explore the carbamate's health effect on physical development.METHODS: Prenatal, 3-year-old, 7-year-old urinary carbofuranphenol concentration was measured by gas chromatography tandem mass spectrometry and adjusted by creatinine. Anthropometric indices were measured by standard method and z-score standardized. Generalized linear models (GLM) were using to assess associations between exposure measurements and anthropometric indices. The generalized estimate equation (GEE) was applied to analyze the association between multiperiod exposure and anthropometric indices, and time-interaction terms were used to exam health effect consistency of exposure in each period. Gender-stratified analysis were conducted according to results of gender-interaction terms to identify gender-specific effects.RESULTS: The gender-interaction term of prenatal exposure with height z-score was significant (β = -0.057; 95% CI: -0.113, -0.001; p = 0.045). The 3-year-old carbofuranphenol level showed negative associations with weight z-score (β = -0.019; 95% CI: -0.038, -0.000; p = 0.040), height z-score (β = -0.015; 95% CI: -0.028, -0.001; p = 0.026), chest circumference (β = -0.086; 95% CI: -0.171, -0.001; p = 0.046), and waist circumference (β = -0.128; 95% CI: -0.230, -0.026; p = 0.014). No statistically significant trend was found for prenatal and 7-year-old carbofuranphenol levels. In GEEs, carbofuranphenol level was negatively associated with weight z-score (β = -0.103; 95% CI: -0.195, -0.011; p = 0.027), height z-score (β = -0.087; 95% CI: -0.152, -0.022; p = 0.008), and chest circumference (β = -0.472; 95% CI: -0.918, -0.026; p = 0.037). Boy's height z-score was inversely associated with carbamate exposure (β = -0.140; 95% CI: -0.227, -0.053; p = 0.001).CONCLUSIONS: Prenatal and postnatal carbamate exposure may affect physical developmental process.
|
|
| 27. |
- Zhang, Jiming, et al.
(author)
-
Early-life carbamate exposure and intelligence quotient of seven-year-old children
- 2020
-
In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 145
-
Journal article (peer-reviewed)abstract
- Background: Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention.Methods: Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQ(V), IQ(P), and IQ(FS)) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window.Results: Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 mu g/L, 0.30 mu g/L, and 0.09-3.72 mu g/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQP [beta = -0.044; 95% confidence interval (CI): -0.087, -0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQP (beta =-0.100; 95% CI: -0.186, -0.014; p= 0.022) and IQFS (beta =-0.087; 95% CI: -0.173, -0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQP (beta = -0.089; 95% CI: -0.171, -0.007; p = 0.034), and IQFS (beta = -0.064; 95% CI: -0.127, -0.000; p = 0.049) of children at age of seven.Conclusion: Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children's neurodevelopment.
|
|
| 28. |
- Zhang, Jiming, et al.
(author)
-
Exposure to carbamate and neurodevelopment in children : Evidence from the SMBCS cohort in China
- 2019
-
In: Environmental Research. - : Academic Press. - 0013-9351 .- 1096-0953. ; 177
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Carbamate pesticides exposure have been linked with adverse health effects during developmental period. Based on 377 mother-child pairs from Sheyang Mini Birth Cohort Study, the present study aimed to assess carbofuranphenol exposure of three-year-old children and explore the associations between prenatal or postnatal carbofuranphenol exposures and neurodevelopmental indicators.METHODS: Urinary carbofuranphenol concentrations were measured by gas chromatography-tandem mass spectrometry. Neural developmental quotient (DQ) of children was evaluated using Gesell Developmental Schedules. Generalized linear models were used to examine the associations between carbofuranphenol concentrations and neurodevelopment.RESULTS: Geometric mean, geometric standard deviation, median, inter quartile range of postnatal urinary carbofuranphenol concentrations were 0.653 μg/L, 9.345 μg/L, 0.413 μg/L, 0.150-1.675 μg/L, respectively. Postnatal carbofuranphenol level showed negatively significant trend in language DQ [beta (β) = -0.121; 95% confidence interval (95% CI): 0.212, -0.031; p value (p) = 0.008] and total average DQ (β = -0.059, 95% CI: 0.115, -0.003; p = 0.035). Prenatal carbofuranphenol level showed negative correlations with children's adaptive DQ (β = -0.755; 95% CI: 1.257, -0.254; p = 0.003), social DQ (β = -0.341; 95% CI: 0.656, -0.027; p = 0.032) and total average DQ (β = -0.349; 95% CI: 0.693, -0.005; p = 0.047).CONCLUSION: The results of the present study supposed children in agricultural region of China are widely exposed to carbamate pesticides, and both prenatal and postnatal exposure to carbamate pesticides may lead to neurodevelopmental effect.
|
|
| 29. |
- Zhang, Jiming, et al.
(author)
-
Maternal urinary carbofuranphenol levels before delivery and birth outcomes in Sheyang Birth Cohort
- 2018
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 625, s. 1667-1672
-
Journal article (peer-reviewed)abstract
- Exposure to carbamates has been linked with adverse health effects on developmental period. This study aimed to monitor exposure to carbofuranphenol of pregnant women from Sheyang Birth Cohort and investigate associations between prenatal exposure to carbofuranphenol and birth outcomes. During June 2009 to January 2010, 1100 pregnant women living in Sheyang County participated in our study and donated urine sample. Urinary carbofuranphenol concentration was measured by gas chromatography-tandem mass spectrometry. Associations between urinary carbofuranphenol levels and infant birth outcomes were assessed by generalized linear models. Urinary carbofuranphenol concentrations varied from 0.01 to 395.40μg/L (0.01-303.93μg/g for creatinine adjusted), the geometric mean, median and inter quartile range are 0.81μg/L (1.28μg/g cr), 0.80μg/L (1.23μg/g cr) and 0.27-2.20μg/L (0.47-3.11μg/g cr), respectively. No statistically significant association between maternal urinary carbofuranphenol levels and birth outcomes was found in total infants and female infants. In male neonates, carbofuranphenol level was significantly associated with head circumference (b=-0.226; 95% confidence interval: -0.411, -0.041; P=0.01) and ponderal index (b=0.043, 95% CI: 0.004, 0.083; P=0.03). These findings suggested that the pregnant women were generally exposed to carbofuranphenol and prenatal exposure to carbofuranphenol might have adverse effects on fetal development.
|
|
| 30. |
- Zhang, Jiming, et al.
(author)
-
Multiple mediation effects on association between prenatal triclosan exposure and birth outcomes
- 2022
-
In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 215:Part 1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Triclosan is a broad-spectrum antimicrobial, and was thought to affect intrauterine development, but the mechanism remains unclear.OBJECTIVE: To explore the association between prenatal triclosan exposure and birth outcomes.METHODS: Based on 726 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS), we used the available (published) data of triclosan in maternal urines, the hormones including thyroid-related hormones, gonadal hormones in cord blood, and adipokines, trimethylamine-N-oxide (TMAO) and its precursors in cord blood to explore possible health effects of triclosan on birth outcomes through assessing different hormones and parameters, using Bayesian mediation analysis.RESULTS: Maternal triclosan exposure was associated with ponderal index (β = 0.317) and head circumference (β = -0.172) in generalized linear models. In Bayesian mediation analysis of PI model, estradiol (β = 0.806) and trimethylamine (TMA, β = 0.164) showed positive mediation effects, while total thyroxine (TT4, β = -0.302), leptin (β = -2.023) and TMAO (β = -0.110) showed negative mediation effects. As for model of head circumference, positive mediation effects were observed in free thyroxine (FT4, β = 0.493), TMA (β = 0.178), and TMAO (β = 0.683), negative mediation effects were observed in TT4 (β = -0.231), testosterone (β = -0.331), estradiol (β = -1.153), leptin (β = -2.361), choline (β = -0.169), betaine (β = -0.104), acetyl-L-carnitine (β = -0.773).CONCLUSION: The results indicated triclosan can affect intrauterine growth by interfering thyroid-related hormones, gonadal hormones, adipokines, TMAO and its precursors.
|
|
| 31. |
- Zhang, Jiming, et al.
(author)
-
Urinary para-nitrophenol levels of pregnant women and cognitive and motor function of their children aged 2 years : Evidence from the SMBCS (China)
- 2022
-
In: Ecotoxicology and Environmental Safety. - : Academia Press. - 0147-6513 .- 1090-2414. ; 244
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years.METHODS: 323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women's urine samples with cognitive and motor function of their children.RESULTS: Maternal PNP was detected in all urine samples with a median of 4.11 μg/L and a range from 0.57 μg/L to 109.13 μg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (β) = - 1.35; 95 % confidence interval (95 %CI): - 2.37, - 0.33; P < 0.01], and the children whose mothers were in the fourth quartile exposure group performed significantly worse compared to the reference group (β = - 1.11; 95 %CI: - 1.80, - 0.42; P < 0.01). As for average DQ score, children with their mothers' urinary PNP concentrations in the third quartile group had higher scores than those in the first quartile group (β = 0.39; 95 %CI: 0.03, 0.75; P = 0.04). In sex-stratified analyses, a negative trend between maternal urinary PNP concentrations and DQ scores in motor area of children was only observed in boys (β = - 1.62; 95 %CI: - 2.80, - 0.43; P < 0.01). Boys in the third quartile group had higher DQ average scores than those in the lowest quartile as reference (β = 0.53; 95 %CI: 0.02, 1.04; P = 0.04).CONCLUSIONS: The mothers from SMBCS may be widely exposed to EP and/or MP, which were associated with the cognitive and motor function of their children aged 2 years in a sex-specific manner. Our results might provide epidemiology evidence on the potential effects of prenatal exposure to EP and/or MP on children's cognitive and motor function.
|
|
| 32. |
- Zhang, Lei, et al.
(author)
-
Prenatal exposure to parabens in association with cord serum adipokine levels and offspring size at birth
- 2022
-
In: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 301
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Paraben exposure is linked to the release of adipokine such as leptin and adiponectin, and both paraben and adipokine may affect fetal growth. The present study aimed to explore the associations among maternal paraben exposure, adipokine level and offspring size.METHODS: 942 mother-newborn pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. Data of birth weight, length, head circumference and ponderal index (PI) were obtained from medical records. Maternal urinary parabens were determined by gas chromatography tandem mass spectrometry. Cord serum leptin and adiponectin were measured using ELISA assay. Generalized linear regression was applied to explore the associations among parabens, adipokines and offspring size.RESULTS: The median levels of leptin and adiponectin were 13.13 μg/L and 161.82 μg/mL. Benzylparaben level was positively associated with leptin (regression coefficient (β) = 0.06, 95% confidence interval (CI): 0.03-0.09; p < 0.01). Leptin level was positively associated with neonatal weight (β = 84.11, 95% CI: 63.22-105.01; p < 0.01), length (β = 0.25, 95% CI: 0.14-0.37; p < 0.01), head circumference (β = 0.15, 95% CI: 0.07-0.22; p < 0.01) and PI (β = 0.23, 95% CI: 0.08-0.39; p < 0.01). Adiponectin was positively associated with neonatal weight (β = 75.94, 95% CI: 29.65-122.23; p < 0.01) and PI (β = 0.43, 95% CI: 0.09-0.77; p = 0.01). Urinary propylparaben concentration (β = -0.10, 95% CI: 0.17 to -0.02; p = 0.01) was negatively associated with head circumference. Sex-stratified analyses indicated the negative association of propylparaben and head circumference was only remained in male neonates.CONCLUSIONS: Prenatal paraben exposure might affect cord serum leptin levels. Both paraben and adipokine levels may affect fetal growth, and sex-specific differences may exist.
|
|
