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1.
Am J Hum Genet ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31564438

RESUMO

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

2.
Lab Chip ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556415

RESUMO

Human intestinal organoids (HIOs) are millimeter-scale models of the human intestinal epithelium and hold tremendous potential for advancing fundamental and applied biomedical research. HIOs resemble the native gut in that they consist of a fluid-filled lumen surrounded by a polarized epithelium and associated mesenchyme; however, their topologically-closed, spherical shape prevents flow through the interior luminal space, making the system less physiological and leading to the buildup of cellular and metabolic waste. These factors ultimately limit experimentation inside the HIOs. Here, we present a millifluidic device called the gut organoid flow chip (GOFlowChip), which we use to "port" HIOs and establish steady-state liquid flow through the lumen for multiple days. This long-term flow is enabled by the use of laser-cut silicone gaskets, which allow liquid in the device to be slightly pressurized, suppressing bubble formation. To demonstrate the utility of the device, we establish separate luminal and extraluminal flow and use luminal flow to remove accumulated waste. This represents the first demonstration of established liquid flow through the luminal space of a gastrointestinal organoid over physiologically relevant time scales. Flow cytometry results reveal that HIO cell viability is unaffected by long-term porting and luminal flow. We expect the real-time, long-term control over luminal and extraluminal contents provided by the GOFlowChip will enable a wide variety of studies including intestinal secretion, absorption, transport, and co-culture with intestinal microorganisms.

3.
Biofabrication ; 11(4): 045020, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31387086

RESUMO

Bioink is of paramount importance in the process of three-dimensional extrusive bioprinting technology. Alginate is extensively used in cell-laden extrusive bioprinters with the advantage of biocompatibility, gelling and crosslinking features; however, the bioinert properties of alginate made it hard to degrade in vivo, and restrict cellular adhesion, extension and migration. In this study, we incorporated two concentrations of alginate lyase (0.5 mU ml-1 and 5 mU ml-1) into alginate/gelatin bioink to improve its degradation properties and effects on cellular behavior. The enzymatically degradable bioink demonstrated lower stiffness and higher porosity. Cellular proliferation, adhesion and extension were facilitated in the degradable bioink without sacrifice of cell viability. Additionally, the property of degradation still worked in vivo, with cellular infiltration and retention being observed in the grafted bioprinted constructs. The results suggest that alginate lyase could be incorporated into alginate/gelatin bioink. Degradation properties and cellular behavior could be promoted both in vitro and in vivo, providing a new avenue for the upgrade and modification of alginate-based bioink for further applications.

4.
Eur J Cancer ; 120: 10-19, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446212

RESUMO

BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.

5.
Chemosphere ; 237: 124426, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31362131

RESUMO

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are endocrine-disrupting chemicals and metabolized rapidly in human body. BPA exposure in late pregnancy has been suggested to be associated with preterm birth (PTB), but the associations of trimester BPA and BPS exposures with gestational age have been rarely studied. We aimed to examine maternal urinary BPA and BPS levels longitudinally measured across pregnancy in relation to gestational age and PTB. A prenatal cohort study was conducted between 2014 and 2015 in Wuhan, China. Maternal urinary BPA and BPS concentrations were measured in a complete series of urine samples collected in the 1st, 2nd and 3rd trimesters from 850 pregnant women and corrected by specific gravity. In comparison with the lowest tertile of maternal urinary BPA, higher levels of averaged BPA concentration across pregnancy was associated with a 1.97-day decrease in gestation (95% CI: 3.25, -0.68) and an adjusted odds ratio of 3.19 (95% CI: 1.00, 10.45) for PTB. Higher BPA concentrations in three trimesters were also negatively associated with gestational age and positively correlated with PTB. In contrast, only a positive association of third-trimester BPS with gestational age was found, but the significant association disappeared in the adjusted models. Both maternal trimester and averaged BPA exposure across pregnancy were significantly associated with shortened gestation and increased risk of PTB. However, the results showed little evidence of a relationship between BPS and PTB.

6.
Bull Environ Contam Toxicol ; 103(2): 308-315, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190165

RESUMO

In our study, we collected 146 surface soil samples in Xiamen City and measured the concentrations of five heavy metals (Cr, Cu, Pb, Ni, and Zn) and one metalloid (As). Multivariate statistics, geostatistics and Random Forest methods were applied to identify the potential sources and spatial variation of the six elements. The results revealed that As, Cr, and Ni originated mainly from industrial activities, and higher concentrations were found in developed areas. The amounts of Cu, Pb, and Zn in soils were mainly predetermined by soil parent material and agricultural activities. Besides, the atmospheric deposition rather than industrial activities substantially influenced the accumulation of Pb in the soils near the boundary between Tong'an and Quanzhou City, because there were few industries but many forests in this area. Because of the connections of the six elements with factor values of factor analysis, appropriate and accessible covariates could be used in co-kriging to increase the accuracies of interpolation of heavy metal and metalloid concentrations relative to that in ordinary kriging.

8.
Int J Biol Macromol ; 135: 1107-1113, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173833

RESUMO

Three-dimensional (3D) bioprinting allows embedding of cells within a bioink, creating cell-based 3D structures to promote tissue regeneration and repair. The bioink should be biocompatible with the cells and its effect on cell behavior should be determined. Alginate-gelatin (Alg-Gel) blends with mouse planta dermis (PD) induced epidermal progenitors for sweat gland regeneration, confirming the role of 3D support during the process. The present study aimed to investigate the chemical and physical properties of the Alg-Gel-PD bioink, and its effect on embedded mouse mesenchymal stem cells (MSCs). MSCs showed increased proliferation and migration in 2D culture with an Alg-Gel-based bioink extract. Gene expression analysis confirmed MSC differentiation towards sweat gland cells. The extract had no effect on protein expression in differentiated cells. Mixing MSCs with the Alg-Gel-based bioink for 3D bioprinting resulted in gene and protein expression characteristic of differentiation, including YAP1 activation. The mechanical strength of the bioink was similar to that of mouse dermal tissue and scanning electron microscopy showed that PD induced a more regular pore structure, suggesting advantages for the physical properties of the embedded cells. This study determined the influence of bioink on cellular behavior, thereby promoting therapeutic stem cell function via 3D cell printing processes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31100895

RESUMO

Sustainable transboundary water governance is often challenged by conflicts between agents, which necessitates the design of cooperative and self-enforcing alternatives to facilitate equitable water distribution. The Nash bargaining approach, which originated from game theory, could offer a good mathematical framework to simulate strategic interactions among involved agents by considering individual rational benefits. Given that river-sharing problems often involve multiple self-interested agents, the asymmetric Nash bargaining solution (ANBS) could be used to describe agents' powers, as determined by disparate social, economic, and political as well as military status, and ensure win-win strategies based on individual rationality. This paper proposed an asymmetric bargaining model by combining multi-criteria decision making, bankruptcy theory, and the ANBS for water distribution in the transboundary river context. The Euphrates River Basin (ERB) with three littoral states was used as a case study. Turkey has the highest bargaining power in ERB negotiation since it dominates in terms of economic strength, political influence, and military capacity, whereas in the two downstream countries these aspects are limited due to their internal political fragmentation and weaker military status. The water satisfaction percentages of Turkey, Syria, and Iraq under the best alternative are 96.30%, 84.23%, and 40.88%, respectively. The findings highlight the necessity for synthetically considering the agent's disagreement utility and asymmetrical power when negotiating over water allocation.

10.
Cell Death Dis ; 10(4): 272, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894517

RESUMO

Several studies have reported inducing adult cells into sweat gland-like cells; however, slow transition and low efficiency limit the potential for cell-based treatment. Here, we show that overexpression of the transcription factor FoxC1 was sufficient to reprogram epidermal cells to induced functional sweat gland-like cells (iSGCs). The iSGCs expressing secreting-related genes, had a global gene expression profile between fetal SGCs (P5) and adult SGCs (P28). Moreover, iSGCs transplanted into the burn mice model facilitated wound repair and sweat gland regeneration. We further demonstrated that the Foxc1 upregulated BMP5 transcription and BMP5 is responsible for the cell-type transition. Collectively, this study shows that lineage reprogramming of epidermal cells into iSGCs provides an excellent cell source and a promising regenerative strategy for anhidrosis and hypohidrosis.

11.
Development ; 146(5)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30745430

RESUMO

Lineage-restricted transcription factors, such as the intestine-specifying factor CDX2, often have dual requirements across developmental time. Embryonic loss of CDX2 triggers homeotic transformation of intestinal fate, whereas adult-onset loss compromises crucial physiological functions but preserves intestinal identity. It is unclear how such diverse requirements are executed across the developmental continuum. Using primary and engineered human tissues, mouse genetics, and a multi-omics approach, we demonstrate that divergent CDX2 loss-of-function phenotypes in embryonic versus adult intestines correspond to divergent CDX2 chromatin-binding profiles in embryonic versus adult stages. CDX2 binds and activates distinct target genes in developing versus adult mouse and human intestinal cells. We find that temporal shifts in chromatin accessibility correspond to these context-specific CDX2 activities. Thus, CDX2 is not sufficient to activate a mature intestinal program; rather, CDX2 responds to its environment, targeting stage-specific genes to contribute to either intestinal patterning or mature intestinal function. This study provides insights into the mechanisms through which lineage-specific regulatory factors achieve divergent functions over developmental time.

12.
Stem Cell Reports ; 12(2): 381-394, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30612954

RESUMO

Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.

13.
Chemosphere ; 219: 655-661, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557721

RESUMO

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): -0.11, -0.01) and 0.08 cm (95% CI: -0.15, -0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted ß = -27.99 g, 95% CI: -50.66, -5.31 and -19.75 g, 95% CI: -37.31, -2.19, respectively) and length (adjusted ß = -0.08 cm, 95% CI: -0.17, 0.00 and -0.08 cm, 95% CI: -0.15, -0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.


Assuntos
Benzofenonas/urina , Peso ao Nascer/efeitos dos fármacos , Exposição Materna/efeitos adversos , Adulto , China , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Masculino , Gravidez , Trimestres da Gravidez/urina , Fatores Sexuais
14.
Zhongguo Fei Ai Za Zhi ; 21(12): 907-911, 2018 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-30591098

RESUMO

Lung cancer is the one of the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. Nowadays, molecular targeted therapy has been the first-line treatment for NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are increasingly used in the clinical treatment, but the EGFR-TKIs acquired resistance becomes the bottleneck of continuation of EGFR-TKIs therapy. Epithelial-mesenchymal transition (EMT) is a biological phenomenon in which epithelial cells are transformed into mesenchymal cells. EMT promoted metastasis, invasion of lung cancer and conferred characteristic of stem cell on cancer cells. Meanwhile, EMT is one of an important cause of EGFR-TKIs resistance in NSCLC. The recent studies have found that resistant cells restored the sensitivity to EGFR-TKIs by reversing EMT which suggested that the target of EMT may contribute to inhibit or even reverse the resistance of EGFR-TKIs. Here we make a review about research progress of EMT in EGFR-TKIs resistance in NSCLC.
.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
15.
J Nat Med ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30377904

RESUMO

The present study was designed to investigate the effects of betulinic acid on human hepatic stellate cells in vitro and C57BL/6 mice in vivo, as well as the signaling pathways involved. In this study, we explored the effects of betulinic acid on expression of alpha smooth muscle actin and autophagy-related proteins. Betulinic acid reduced pathological damage associated with liver fibrosis, as well as serum platelet-derived growth factor and serum hydroxyproline levels. Furthermore, betulinic acid downregulated the expression of alpha smooth muscle actin and type I collagen in mouse liver and upregulated the expression of microtubule-associated protein light chain 3B and autophagy-related gene 7 at the gene and protein levels. LC3II expression was increased and alpha smooth muscle actin expression was decreased in betulinic acid-treated hepatic stellate cells. Interventions with bafilomycin A1 and mCherry-GFP-LC3 adenoviruses promoted the formation of autophagosomes in hepatic stellate cells and the development of autophagic flow. Our study found that mitogen-activated protein kinase/extracellular signal-regulated kinase may be involved in the effects of betulinic acid on liver fibrosis. The present study suggests that betulinic acid has anti-hepatic fibrosis activity by inducing autophagy and could serve as a promising new agent for treating hepatic fibrosis.

16.
Zhongguo Zhong Yao Za Zhi ; 43(19): 3876-3883, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30453712

RESUMO

In order to analyze the law of membrane permeation of different alkaloids, seven traditional Chinese medicine alkaloids with different parent nucleus and substituent structures, including berberine, palmatine, sinomenine, matrine, oxymatrine, sophoridine, and tetrandrine, were prepared into the simulated solution with same molar concentration, and the membrane penetrating experiments with membrane RC1K and membrane RC5K were carried out. The dynamic transmittance, the total transmittance and the total adsorption rate of each substance were measured, and the scanning electron microscopy (SEM) images of the membrane surface before and after the membrane experiment were considered to predict and analyze the reason of differences in dynamic transmittance of different alkaloids. The results showed that there were significant differences in the dynamic transmittance of the chemical constituents of different alkaloids during penetrating the two membranes. The contamination degree on the surface of the membrane material was also different. The transmittance of the same compound through the RC5K membrane was larger than that through RC1K membrane. Within a certain range, the smaller the pore size of the membrane, the better the selective screening effect on the chemical constituents of traditional Chinese medicine. All the membrane surfaces were less polluted. The difference in transmittance between different substances on the same membrane showed a positive correlation with the difference in structural complexity, providing an experimental basis for the surface modification design in contamination control of membrane materials. In the design of membrane modified material, the surface properties of the membrane can be improved by grafting different polar groups, thereby changing the adsorption characteristics of the membrane surface. The pore size was designed accordingly to achieve the high transmittance and low pollution of the corresponding compounds.

17.
Nat Protoc ; 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30356140

RESUMO

In the version of this protocol originally published, the caption for Fig. 3 was erroneously placed with Fig. 4, and that for Fig. 4 was placed with Fig. 3. This error has been corrected in the HTML and PDF versions of the paper.

18.
BMC Med Genet ; 19(1): 157, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30176854

RESUMO

BACKGROUND: Many X-linked non-syndromic hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene. This study aimed to identify allelic variants of this gene in two Chinese families displaying X-linked inheritance deafness-2 (DFNX2) and one sporadic case with indefinite inheritance pattern. METHODS: Direct DNA sequencing of the POU3F4 gene was performed in these families and in 100 Chinese individuals with normal hearing. RESULTS: There are characteristic imaging findings in DFNX2 Chinese families with POU3F4 mutations. The temporal bone computed tomography (CT) images of patients with DFNX2 are characterized by a thickened stapes footplate, hypoplasia of the cochlear base, absence of the bony modiolus, and dilated internal acoustic meatus (IAM) as well as by abnormally wide communication between the IAM and the basal turn of the cochlea. We identified three causative mutations in POU3F4 for three probands and their extended families. In family 1468, we observed a novel deletion mutation, c.973delT, which is predicted to result in a p.Trp325Gly amino acid frameshift. In family 2741, the mutation c.927delCTC was identified, which is predicted to result in the deletion of serine at position 310. In both families, the mutations were located in the POU homeodomain and are predicted to truncate the C-terminus of the POU domain. In the third family, a novel de novo transversion mutation (c.669 T > A) was identified in a 5-year-old boy that resulted in a nonsense mutation (p.Tyr223*). The mutation created a new stop codon and is predicted to result in a truncated POU3F4 protein. CONCLUSIONS: Based on characteristic radiological findings and clinical features, POU3F4 gene mutation analysis will increase the success rate of stapes operations and cochlear implantations, and improve molecular diagnosis, genetic counseling, and knowledge of the molecular epidemiology of HL among patients with DFNX2.

19.
Chemosphere ; 210: 1035-1041, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30208528

RESUMO

Heavy metal exposure has been indicated to be linked with reproductive and developmental toxicity. However, human studies on the association between heavy metal exposure and premature rupture of membranes (PROM) are limited. Thus, we aimed to evaluate the associations between urinary metal concentrations in pregnant women and the risk of PROM. The study was conducted among 7290 pregnant women from an ongoing cohort study in China. Levels of urinary metals were determined using an inductively coupled plasma-mass spectrometry and adjusted by creatinine concentration (µg/g creatinine). Adjusted odds ratios (OR) and 95% confidence intervals (CI) for PROM and preterm PROM were estimated using logistic regression models. Among 12 urinary metals detected, vanadium (V) have shown stable positive associations with PROM and preterm PROM. With one unit increase in natural logarithmically transformed urinary V concentration, adjusted OR of 1.57 (95% CI: 1.47, 1.66) for PROM was observed. Compared with the lowest tertile of urinary V, we also observed positive associations between V levels and PROM (for the medium tertile, adjusted OR = 1.66, 95% CI: 1.34, 2.05; for the highest tertile, adjusted OR = 3.75, 95% CI: 3.09, 4.54). In addition, higher adjusted ORs for preterm PROM were observed (for the highest tertile, adjusted OR = 8.14, 95% CI: 4.55, 14.55). Further stratified analysis suggested the associations were more pronounced among women delivering male infants than those with female infants. Our present epidemiological study indicated that pregnant women exposure to higher level of V might lead to an increased risk of PROM.


Assuntos
Ruptura Prematura de Membranas Fetais/etiologia , Ruptura Prematura de Membranas Fetais/urina , Exposição Materna/efeitos adversos , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Vanádio/efeitos adversos , Vanádio/urina , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Nascimento Prematuro/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
20.
Nat Protoc ; 13(9): 2102-2119, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30190557

RESUMO

In vitro differentiation of human pluripotent stem cell (hPSC)-derived organoids (HOs) facilitates the production of multicellular three-dimensional structures analogous to native human tissues. Most current methods for the generation of HOs rely on Matrigel, a poorly defined basement membrane derivative secreted by Engelbreth-Holm-Swarm mouse sarcoma cells, limiting the potential use of HOs for regenerative medicine applications. Here, we describe a protocol for the synthesis of a fully defined, synthetic hydrogel that supports the generation and culture of HOs. Modular, cell-encapsulating hydrogels are formed from a four-armed poly(ethylene glycol) macromer that has maleimide groups at each terminus (PEG-4MAL) and is conjugated to cysteine-containing adhesive peptides and cross-linked via protease-degradable peptides. The protocol also includes guidelines for the localized in vivo delivery of PEG-4MAL hydrogel-encapsulated HOs to injured mouse colon. The PEG-4MAL hydrogel supports the engraftment of the HOs and accelerates colonic wound repair. This culture and delivery strategy can thus be used to develop HO-based therapies to treat injury and disease. Hydrogel and tissue preparation and subsequent encapsulation can be performed within 2.5-3.5 h. Once HOs have been cultured in synthetic hydrogels for at least 14 d, they can be prepared and delivered to the mouse colon in under 5 h.

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