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1.
Front Bioeng Biotechnol ; 10: 786755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528207

RESUMO

Objectives: To investigate metabolomic perturbations caused by twin-twin transfusion syndrome, metabolic changes associated with fetoscopic laser coagulation in both placental tissue and cord plasma, and to investigate differential metabolites pertinent to varying fetal outcomes, including hemodynamic status, birth weight, and cardiac function, of live-born babies. Methods: Placental tissue and cord plasma samples from normal term or uncomplicated preterm-born monochorionic twins and those complicated by twin-twin transfusion syndrome treated with or without fetoscopic laser coagulation were analyzed by high-performance liquid chromatography metabolomic profiling. Sixteen comparisons of different co-twin groups were performed. Partial least squares-discriminant analysis, metabolic pathway analysis, biomarker analysis, and Spearman's correlation analysis were conducted based on differential metabolites used to determine potential biomarkers in different comparisons and metabolites that are pertinent to neonatal birth weight and left ventricular ejection fraction. Results: These metabolomic investigations showed that the cord plasma metabolome has a better performance in discriminating fetuses among different hemodynamic groups than placental tissue. The metabolic alteration of twin-twin transfusion syndrome in these two types of samples centers on fatty acid and lipid metabolism. The fetoscopic laser coagulation procedure improves the metabolomic change brought by this syndrome, making the metabolomes of the treated group less distinguishable from those of the control and preterm birth groups. Certain compounds, especially lipids and lipid-like molecules, are noted to be potential biomarkers of this morbid disease and pertinent to neonatal birth weight and ejection fraction. Conclusions: Fetoscopic laser coagulation can ameliorate the metabolomic alteration caused by twin-twin transfusion syndrome in placental tissue and cord plasma, which are involved mainly in fatty acid and lipid-like molecule metabolism. Certain lipids and lipid-like molecules are helpful in differentiating co-twins of different hemodynamic statuses and are significantly correlated with neonatal birth weight or ejection fraction.

2.
Front Nutr ; 9: 775557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529458

RESUMO

Background: Studies assessing links between maternal diet and pregnancy outcomes have focused predominantly on individual nutrients or foods. However, nutrients are typically consumed in combinations of foods or beverages (i.e., dietary patterns). Taking into account the diet as a whole appreciates that nutrient absorption and metabolism are influenced by other nutrients and the food matrix. Objective: The aim of this study was to investigate the relationship between dietary pattern consumption in early pregnancy and pregnancy/infant outcomes, including gestational diabetes mellitus, gestational weight gain, preeclampsia, placental weight, gestational age at delivery, small-for-gestational-age, large-for-gestational-age, macrosomia, measures of infant body composition, and scores on two main indices of the Bayley Scales of Infant Development [Mental Development Index (MDI) and the Psychomotor Development Index (PDI)] at 12 months. Design: Our study included 1,437 participants from a mother-infant cohort in Chongqing, China. Maternal diet was assessed using a 96-item food frequency questionnaire at 11-14 weeks gestation. Dietary patterns were constructed using principal component analysis. Multivariate regressions were performed to assess associations between maternal dietary pattern scores and pregnancy and infant outcomes, adjusting for confounders. Results: Two dietary patterns were derived: a pattern high in pasta, sweetened beverages, and oils and condiments (PSO-based dietary pattern) and a pattern high in fish, poultry, and vegetables (FPV-based dietary pattern). Higher scores on the PSO-based dietary pattern were associated with lower infant standardized scores on the PDI of the Bayley Scales of Infant Development, ß (95% confidence interval) = -1.276 (-2.392, -0.160); lower placental weight, ß (95% CI) = -6.413 (-12.352g, -0.473); and higher infant's tricep skinfold thickness at 6 weeks of age. ß (95% CI) = 0.279 (0.033, 0.526). Higher scores on the FPV-based dietary pattern were associated with higher gestational weight gain between visit 1 (11-14 week's gestation) and 3 (32-34 week's gestation). ß (95% CI) = 25.612 (13.255, 37.969). No significant associations were observed between dietary pattern scores and the remaining pregnancy/infant outcomes investigated or MDI scores on the Bayley Scales of Infant Development. This was the first study to investigate the association between dietary patterns in early pregnancy and infant neurocognition in a Chinese cohort.

3.
Harm Reduct J ; 19(1): 45, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562829

RESUMO

INTRODUCTION: The emergence of widespread amphetamine-type stimulants (ATSs) usage has created significant challenges for drug control and treatment policies in Southeast Asian countries. This study analyses the development of drug policies and examines current treatment program constraints in Vietnam to deal with ATS misuse. The aim was to gain insights that may be useful for national and international drug-related policy development and revision. METHODS: A desk review of national policy documents and 22 in-depth key informant interviews were conducted from 2019 to 2021. Thematic content analysis was employed to identify key themes and their connections. RESULTS: Analysis identified Vietnam's 30-year history of developing policies and formulating strategies to reduce supply, demand, and harm from illicit drugs. With the increasing number of people who use ATS (PWUA), Vietnam has recently promoted harsh policy and law enforcement to deter drug use and supply. This policy trend prevails in many Asian countries. The three main constraints in dealing with ATS misuse emerged from punitive and restrictive drug policies. First, the general public believed that Centre-based compulsory treatment (CCT) is the only appropriate treatment for all types of illicit drug addiction despite its low-quality service provision. The rigid drug policy has led to social persuasion with impractical expectations for CCT effectiveness. Second, the emphasis on punishment and detention has hampered new drug treatment service development in Vietnam. CCT has become monopolistic in the context of impoverished services. Third, people who use drugs tend to hide their needs and avoid formal treatment and support services, resulting in declined social coherence. CONCLUSION: While new drugs are constantly evolving, the current law enforcement approach potentially constrains expertise to adopt effective treatment services. This study suggests that the top-down policing mechanism presently hinders the development of an appropriate intervention strategy for ATS misuse and diminishes social support to service providers.

4.
Front Med (Lausanne) ; 9: 802666, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492315

RESUMO

Objective: To evaluate alterations in the fetal Doppler parameters of pump fetuses before and 24 h after radiofrequency ablation surgery for twin reversed arterial perfusion sequence (TRAPs). Methods: This is a retrospective study of 28 pump fetuses in TRAPs and 28 normal control twins between 2016 and 2021. The fetal Doppler parameters, including the umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR), of the controls, and pump fetuses before and 24 h after surgery were compared. Results: An increasing trend and a further increase in the MCA-PSV, MCA-PI, MCA-PSV Z score, and MCA-PI Z score after surgery were observed in pump fetuses with gestational age (GA) ≥20 weeks; however, such changes were not observed in those with a GA of <20 weeks. The UA-PI and CPR before and after surgery were not different between control and pump fetuses, whether the GA was ≥20 or <20 weeks. Conclusion: In the middle second trimester, the pump fetus might suffer from high cardiac output rather than hypoxemia before surgery and congestive heart failure, or hemodilutional anemia after surgery. This may provide some theoretical evidence in favor of early intervention, rather than waiting for a more advanced GA, to avoid unnecessary hemodynamic alterations.

5.
Front Mol Biosci ; 9: 799902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463954

RESUMO

Introduction: Single intrauterine fetal death (sIUFD) in monochorionic diamniotic (MCDA) twin pregnancy may be associated with adverse clinical outcomes and possible metabolic changes in the surviving co-twin. Metabolomic profiling has not been undertaken before in these complex twin pregnancies. Methods: In this prospectively collected case-control study, three cross-cohort comparisons were made between sIUFD MCDA (n = 16), uncomplicated MCDA (n = 16, eight pairs), and uncomplicated singleton pregnancies (n = 8). To identify major sources of variation within the sIUFD MCDA cohort, a secondary comparison was conducted between spontaneous sIUFD (n = 8) and sIUFD in MCDA twins due to selective termination of a single abnormal fetus by radiofrequency ablation (RFA) (n = 8). Metabolomics analysis of placental tissue and umbilical cord plasma was performed using LC-MS profiling. The underlying metabolic networks and pathways were analyzed by web-based platforms. Associations and statistical correlations of all identified differential metabolites with neonatal birthweight and birth length were assessed by multivariable linear regression, adjusted for maternal age and gestation. Results: Across four comparisons, 131 and 111 differential metabolites were identified in placental tissue and cord plasma, respectively, with the highest variation seen between the spontaneous vs. single-induced IUFD in MCDA twins by RFA in the cord plasma. Conversely, the number of viable fetuses and the presence of sIUFD in MCDA twins had the highest impact on metabolite variation in placental tissue. Compounds correlated with fetal growth including placental acylcarnitines and gangliosides, along with specific amino acids (e.g., histidinyl-hydroxyproline), xenobiotics and biliverdin in cord plasma. Conclusion: sIUFD in MCDA twin pregnancy correlates with distinctive metabolic signatures, mostly in fatty acyls and complex lipids, in placental tissue and cord plasma of the surviving cotwin. Some metabolites are also associated with fetal growth.

6.
PLoS One ; 17(4): e0267313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35446907

RESUMO

BACKGROUND: Preeclampsia causes substantial maternal and perinatal morbidity and mortality and significant societal economic impact. Effective screening would facilitate timely and appropriate prevention and management of preeclampsia. OBJECTIVES: To develop an early cost-effectiveness analysis to assess both costs and health outcomes of a new screening test for preeclampsia from a healthcare payer perspective, in the United Kingdom (UK), Ireland, the Netherlands and Sweden. METHODS: A decision tree over a 9-month time horizon was developed to explore the cost-effectiveness of the new screening test for preeclampsia compared to the current screening strategy. The new test strategy is being developed so that it can stratify healthy low risk nulliparous women early in pregnancy to either a high-risk group with a risk of 1 in 6 or more of developing preeclampsia, or a low-risk group with a risk of 1 in 100 or less. The model simulated 25 plausible scenarios in a hypothetical cohort of 100,000 pregnant women, in which the sensitivity and specificity of the new test were varied to set a benchmark for the minimum test performance that is needed for the test to become cost-effective. The input parameters and costs were mainly derived from published literature. The main outcome was incremental costs per preeclampsia case averted, expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Base case results showed that the new test strategy would be more effective and less costly compared to the current situation in the UK. In the Netherlands, the majority of scenarios would be cost-effective from a threshold of €50,000 per preeclampsia case averted, while in Ireland and Sweden, the vast majority of scenarios would be considered cost-effective only when a threshold of €100,000 was used. In the best case analyses, ICERs were more favourable in all four participating countries. Aspirin effectiveness, prevalence of preeclampsia, accuracy of the new screening test and cost of regular antenatal care were identified as driving factors for the cost-effectiveness of screening for preeclampsia. CONCLUSION: The results indicate that the new screening test for preeclampsia has potential to be cost-effective. Further studies based on proven accuracy of the test will confirm whether the new screening test is a cost-effective additional option to the current situation.


Assuntos
Pré-Eclâmpsia , Análise Custo-Benefício , Feminino , Humanos , Programas de Rastreamento , Paridade , Pré-Eclâmpsia/diagnóstico , Gravidez , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido/epidemiologia
7.
BMC Pregnancy Childbirth ; 22(1): 174, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236326

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation. METHODS: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). RESULTS: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. CONCLUSION: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.


Assuntos
Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Diabetes Gestacional/urina , Idade Materna , Metaboloma , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Metabolômica/métodos , Plasma/metabolismo , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Terceiro Trimestre da Gravidez/metabolismo , Estudos Prospectivos , Curva ROC
8.
Front Immunol ; 13: 813218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222389

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-ß-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-ß (TGF-ß) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-ß-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences.


Assuntos
Aborto Habitual , Células Matadoras Naturais , Aborto Habitual/metabolismo , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Gravidez , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta/metabolismo
9.
J Clin Med ; 11(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35160245

RESUMO

Hypertensive disorders of pregnancy (HDP) are the most common medical complication in pregnancy, affecting approximately 10-15% of pregnancies worldwide. HDP are a major cause of maternal and perinatal morbidity and mortality, and each year, worldwide, around 70,000 mothers and 500,000 babies die because of HDP. Up-to-date high-quality systematic reviews quantifying the role of exercise and the risks of developing HDP are currently lacking. Physical exercise is considered to be safe and beneficial to pregnant women. Supervised exercise has been shown to be safe and to be more beneficial than unsupervised exercise in the general population, as well as during pregnancy in women with obesity and diabetes. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of women performing supervised exercise during pregnancy compared to a control group (standard antenatal care or unsupervised exercise) on the development of HDP. We searched Medline, Embase, CINHAL, and the Cochrane Library, which were searched from inception to December 2021. We included only randomized controlled trials (RCTs) investigating the development of HDP compared to a control group (standard antenatal care or unsupervised exercise) in pregnant women performing supervised exercise. Two independent reviewers selected eligible trials for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020176814. Of 6332 articles retrieved, 16 RCTs met the eligibility criteria, comparing a total of 5939 pregnant women (2904 pregnant women in the intervention group and 3035 controls). The risk for pregnant women to develop HDP was significantly reduced in the intervention compared to the control groups, with an estimated pooled cumulative incidence of developing HDP of 3% in the intervention groups (95% CI: 3 to 4) and of 5% in the control groups (95% CI: 5 to 6), and a pooled odds ratio (OR) comparing intervention to control of 0.54 (95% CI:0.40 to 0.72, p < 0.001). A combination of aerobic and anaerobic exercise, or yoga alone, had a greater beneficial effect compared to performing aerobic exercise only (mixed-OR = 0.50, 95% CI:0.33 to 0.75, p = 0.001; yoga-OR = 0.28, 95% CI:0.13 to 0.58, p = 0.001); aerobic exercise only-OR = 0.87, 95% CI:0.55 to 1.37, p = 0.539). Pregnancy is an opportunity for healthcare providers to promote positive health activities, thus optimizing the health of pregnant women with potential short- and long-term benefits for both mother and child. This systematic review and meta-analysis support a beneficial effect of either structured exercise (combination of aerobic, strength, and flexibility workouts) or yoga for preventing the onset of HDP. Yoga, considered a low-impact physical activity, could be more acceptable and safer for women in pregnancy in reducing the risk of developing HDP.

11.
J Med Ethics ; 48(3): 205-212, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33298600

RESUMO

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband's duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen's (2004) 'joint account model', we adapt Kilbride's (2018) application of the rule of rescue and balance it against the relative's right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband's objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband's privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive.

12.
FEBS J ; 289(2): 336-354, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33529475

RESUMO

Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide, impacting the long-term health of both mother and offspring. PE has long been characterized by deficient trophoblast invasion into the uterus and consequent placental hypoperfusion, yet the upstream causative factors and effective interventional targets for PE remain unknown. Alterations in the metabolism of preeclamptic placentas are thought to result from placental ischemia, while disturbances of the metabolism and of metabolites in PE pathogenesis are largely ignored. In fact, as one of the largest fetal organs at birth, the placenta consumes a considerable amount of glucose and fatty acid. Increasing evidence suggests glucose and fatty acid exist as energy substrates and regulate placental development through bioactive derivates. Moreover, recent findings have revealed that the placental metabolism adapts readily to environmental changes, altering its response to nutrients and endocrine signals; this adaptability optimizes pregnancy outcomes by diversifying available carbon sources for energy production, hormone synthesis, angiogenesis, immune activation, and tolerance, and fetoplacental growth. These observations raise the possibility that carbohydrate and lipid metabolism abnormalities play a role in both the etiology and clinical progression of PE, sparking a renewed interest in the interrelationship between PE and metabolic dysregulation. This review will focus on key metabolic substrates and regulatory molecules in the placenta and aim to provide novel insights with respect to the metabolism's role in modulating placental development and functions. Further investigations from this perspective are poised to decipher the etiology of PE and suggest potential therapies.


Assuntos
Metabolismo Energético/genética , Doenças Metabólicas/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/patologia , Placenta/patologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Gravidez
13.
Int J Food Sci Nutr ; 73(2): 263-273, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34412548

RESUMO

Childhood obesity is a major public health problem with no effective intervention. We explored the influence of feeding patterns on infants' growth indices within the first 2 years in a twin birth cohort. Dietary intake at 12 months was recorded with a food frequency questionnaire, and dietary patterns were identified by principal component analysis. Milk feeding methods in first 6 months were categorised as breastfeeding or exclusive formula feeding. Correlations between feeding patterns and infants' growth indices were examined via generalised estimating equations. Two dietary patterns were identified and neither of which was related to growth indices. Breastfed infants had a higher body fat mass (BFM) percentage at 12 months, a higher body mass index (BMI) increment from birth to 6 months and a lower BMI increment from 6 to 12 months. Breastfed infants were likely positively correlated with BFM at 12 months; as complementary food was added, the effect of breastfeeding on growth gradually decreased.


Assuntos
Obesidade Pediátrica , Tecido Adiposo , Índice de Massa Corporal , Aleitamento Materno , Criança , Comportamento Alimentar , Feminino , Humanos , Lactente , Fórmulas Infantis , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/etiologia
14.
Hypertension ; 79(2): 399-412, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34865521

RESUMO

Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized human trophoblst cells) cell invasion in a Hippo-signaling-dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA (Ras homolog gene family, member A)/ROCK (Rho-associated protein kinase) induced actin polymerization. Mutation-based YAP-5SA (S61A, S109A, S127A, S164A, S381A) demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.


Assuntos
Actinas/metabolismo , Lisofosfolipídeos/metabolismo , Pré-Eclâmpsia/metabolismo , Proteínas Proto-Oncogênicas c-yes/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Esfingosina/análogos & derivados , Trofoblastos/metabolismo , Animais , Feminino , Humanos , Lisofosfolipídeos/genética , Camundongos , Placenta/metabolismo , Placentação/fisiologia , Gravidez , Proteínas Proto-Oncogênicas c-yes/genética , Transdução de Sinais/fisiologia , Esfingosina/genética , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/genética
15.
Matern Child Nutr ; 18(2): e13301, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34935291

RESUMO

Most babies in France are fed with infant formula and then commercial complementary foods, many of which are ultra-processed and harmful to health. Internationally, there is opposition by the baby food industry to the introduction of public health policies that would limit the marketing and consumption of such products. Our aim was to identify the key baby food industry actors, describe their history and corporate political activity (CPA) in France. We sourced publicly available information, which we triangulated with data from 10 semi-structured interviews. Qualitative thematic analysis was undertaken simultaneously to data collection, guided by an existing classification of the CPA of the food industry. The baby food industry in France has shaped the science on infant and young child nutrition and nurtured long-established relationships with health professionals. This corporate science and these relationships helped baby food companies to portray themselves as experts on child-related topics. The baby food industry has also engaged with a broad range of civil society organisations, particularly through the concept of the first 1000 days of life, and during the covid-19 pandemic. We found evidence, although limited, that the baby food industry directly lobbied the French government. Since its early development in France in the 19th century, the baby food industry used its CPA to promote its products and protect and sustain its market. Our findings can be used to recognise, anticipate and address the CPA of this industry, and to minimise any negative influence it may have on babies' and mother's health.


Assuntos
COVID-19 , Mães , Feminino , Indústria Alimentícia , Ocupações em Saúde , Humanos , Lactente , Fórmulas Infantis , Pandemias
16.
Front Cell Dev Biol ; 9: 694261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917606

RESUMO

Impaired invasion of extravillous trophoblasts and severe oxidative stress manifest the poor placentation in preeclampsia, which is life-threatening and more than a hypertensive disease of pregnancy. Previous studies have reported that G protein-coupled receptor kinases (GRKs) play a key role in initiating hypertension and hypertensive renal damage, yet little evidence so far suggests a link between GRKs and preeclampsia-related hypertension. Here, we demonstrate GRK2 expression is significantly downregulated (P < 0.0001) in preeclamptic placentae compared to normotensive controls. Knockdown or inhibition of GRK2 in placentae caused insufficient arterial remodeling and elevated trophoblast necroptosis in vivo. These further induced preeclampsia-like phenotype in mice: hypertension, proteinuria, and elevated pro-angiogenic cytokines. By human extra-villous invasive trophoblast cell line (HTR8/SVneo cells), we revealed the knockdown or inhibition of GRK2 triggered excessive death with typical necroptotic characteristics: nuclear envelope rupture and the activation of RIPK1, RIPK3, and MLKL. Necrostatin-1, an inhibitor of RIPK1, is able to restore the survival of trophoblasts. Together, our findings demonstrated that insufficient GRK2 activity compromises spiral artery remodeling and initiates necrotic events in placentae, thereby leading to preeclampsia. These findings advance our understanding of GRK2 in the pathogenesis of preeclampsia and could shed light on a potential treatment for preeclampsia.

17.
PLoS One ; 16(11): e0259537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34739512

RESUMO

Urban areas are associated with high levels of habitat fragmentation. For some terrestrial species with limited climbing abilities, property boundaries can pose a significant problem by limiting access to residential gardens. The West European hedgehog (Erinaceus europaeus) has declined markedly in the UK but is commonly found in areas of human habitation, including residential gardens. 'Hedgehog Street' is a public engagement campaign aimed at recruiting volunteers ('Hedgehog Champions') to create access points ('hedgehog highways') across garden boundaries to improve habitat connectivity. In this study, we used a series of questionnaire surveys to explore motivations for and obstacles to the creation of highways. Householders were more likely to have created a highway if they were already aware of the Hedgehog Street campaign, if their garden contained a high number of wildlife-friendly features and if they considered watching wildlife to be important. Hedgehog Champions created, on average, 1.69 highways each with 52.0% creating none; this would equate to an estimated >120,000 across all registered Champions. In comparison, 6.1-29.8% of non-Champions stated that they had made a highway. However, most highways had been created in boundaries that could already be traversed via naturally occurring holes: only 11.4% of garden boundaries could be traversed, and 3.2% of gardens accessed, just via a hedgehog highway. In addition, only 5.0% of gardens were considered totally inaccessible to hedgehogs. The most common reasons cited for not having made a highway were that householders' gardens were already accessible to hedgehogs followed by concerns relating to boundary ownership and / or communicating with neighbours. Future studies need to identify strategies for overcoming these obstacles to maximize citizen engagement, particularly with those householders who are not innately "wildlife-friendly", and to quantify the degree to which networks of highways affect patterns of individual movement and, ultimately, populations.


Assuntos
Jardinagem , Motivação , Animais , Conscientização , Ouriços-Cacheiros , Movimento
18.
Front Cell Dev Biol ; 9: 722024, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796169

RESUMO

AMP-activated protein kinase (AMPK) is an important regulator of glucose metabolism, and glucose transporter 3 (GLUT3) is an efficient glucose transporter in trophoblasts. Whether placental AMPK and GLUT3 respond accordingly to gestational diabetes mellitus (GDM) remains uncertain. Here, we explored the regulatory role of AMPK in the GLUT3-dependent uptake of glucose by placental trophoblasts and the viability of the cells. In this study, the level of glycolysis in normal and GDM-complicated placentas was assessed by LC-MS/MS. The trophoblast hyperglycemia model was induced by the incubation of HTR8/SVneo cells with a high glucose concentration. GDM animal models were generated with db/ + mice and C57BL/6J mice fed a high-fat diet, and AMPK was manipulated by the oral administration of metformin. The uptake of glucose by trophoblasts was assessed using 2-NBDG or 2-deoxy-D-[3H] glucose. The results showed that GDM is associated with impaired glycolysis, AMPK activity, GLUT3 expression in the plasma membrane (PM) and cell survival in the placenta. Hyperglycemia induced similar changes in trophoblasts, and these changes were rescued by AMPK activation. Both hyperglycemic db/ + and high-fat diet-induced GDM mice exhibited a compromised AMPK-GLUT3 axis and suppressed cell viability in the placenta as well as excessive fetal growth, and all of these effects were partially alleviated by metformin. Taken together, our findings support the notion that AMPK activation upregulates trophoblast glucose uptake by stimulating GLUT3 translocation, which is beneficial for viability. Thus, the modulation of glucose metabolism in trophoblasts by targeting AMPK might ameliorate the adverse intrauterine environment caused by GDM.

19.
BMC Pregnancy Childbirth ; 21(1): 786, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34802426

RESUMO

BACKGROUND: Since the effectiveness of low-dose aspirin (LDA) in twin pregnancies is uncertain, we aimed to preliminarily assess whether LDA is beneficial in preventing preeclampsia in twin pregnancies. METHODS: This study is an observational study in two hospitals in China. Among 932 women, 277 in the First Affiliated Hospital of Chongqing Medical University were routinely treated with aspirin (100 mg daily) from 12 to 16 weeks to 35 weeks of gestational age, while 655 in Chongqing Health Center for Women and Children were not taking aspirin during pregnancy. We followed each subject and the individual details were recorded. RESULTS: LDA significantly reduced the risk of preeclampsia (RR 0.48; 95% CI 0.24-0.95) and preterm birth 34 weeks (RR 0.50; 95% CI 0.29-0.86) and showed possible benefits to lower the rate of SGA babies (RR 0.74; 95% CI 0.55-1.00). Moreover, the risk of postpartum hemorrhage was not increased by LDA (RR 0.89; 95% CI 0.35-2.26). CONCLUSIONS: Treatment with low-dose aspirin in twin pregnancies could offer some protection against adverse pregnancy outcomes in the absence of significantly increased risk of postpartum hemorrhage. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR); ChiCTR-OOC-16008203 , Retrospectively registered date: April 1st, 2016.


Assuntos
Aspirina/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Gravidez de Gêmeos/efeitos dos fármacos , Nascimento Prematuro/prevenção & controle , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Pontuação de Propensão
20.
Sci Rep ; 11(1): 20469, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650122

RESUMO

Preeclampsia (PE) is a severe multisystem pregnancy complication characterized by gestational hypertension and proteinuria. Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) is a mediator of mitophagy and has been proven to be associated with PE, but the mechanism is not well understood. This study aimed to investigate the role of BNIP3 in PE. Placentae from preeclamptic and normal pregnancies were analyzed by western-blot and transmission electron microscopy to quantify the level of BNIP3 expression and observe the organelle morphologies. Trophoblast cells with knockdown BNIP3 were analyzed by western-blot, immunofluorescence, flow cytometry, migration and invasion assays. BNIP3 expression was suppressed in PE patients. Impaired autophagy and increased mitochondrial damage were observed in PE placentae when compared with normal placentae. Suppression of BNIP3 inhibited Beclin-1 expression and reduced the transformation of LC3-I to LC3-II. In the knockdown BNIP3 group, p62 was overexpressed, ROS accumulated and the apoptotic process was elevated under oxidative stress condition. The knockdown of BNIP3 reduced the colocalization of GFP-LC3 and mitochondria. The findings of this study suggest that dysregulated BNIP3 is associated with impaired mitophagy, oxidative stress, and apoptosis in PE. The study provides new insights into the role of BNIP3 in the pathophysiology of PE.


Assuntos
Proteínas de Membrana/metabolismo , Mitofagia , Placenta/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Proteínas Proto-Oncogênicas/metabolismo , Adulto , Apoptose , Células Cultivadas , Feminino , Humanos , Proteínas de Membrana/genética , Mitocôndrias , Estresse Oxidativo , Placenta/metabolismo , Gravidez , Proteínas Proto-Oncogênicas/genética , Espécies Reativas de Oxigênio , Trofoblastos/metabolismo
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