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1.
Int J Epidemiol ; 53(4)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38981140

RESUMO

BACKGROUND: Our aim was to evaluate the prevalence, mortality, regional and sex distribution of neural tube defects (NTDs) in Finland. METHODS: Data for this population-based study were collected from 1987 to 2018 from the national health and social welfare registers. RESULTS: There were in total 1634 cases of NTDs, of which 511 were live births, 72 pregnancies ended in stillbirth and 1051 were terminations of pregnancy due to fetal anomaly (TOPFA). The total prevalence of NTDs was 8.6 per 10 000 births and it increased slightly annually (OR 1.008; 95% CI: 1.002, 1.013) during the 32-year study period. The birth prevalence of NTDs decreased (OR 0.979; 95% CI: 0.970, 0.987), but the prevalence of TOPFA increased annually (OR 1.024; 95% CI 1.017, 1.031). The perinatal mortality of NTD children was 260.7 per 1000 births and the infant mortality was 184.0 per 1000 live births, whereas these measures in the general population were 4.6 per 1000 births and 3.3 per 1000 live births, respectively. There was no difference in the NTD prevalence between males and females (P-value 0.77). The total prevalence of NTDs varied from 7.1 to 9.4 per 10 000 births in Finland by region. CONCLUSIONS: Although the majority of NTDs are preventable with an adequate folic acid supplementation, the total prevalence increased in Finland during the study period when folic acid supplementation was mainly recommended to high-risk families and to women with folic acid deficiency. NTDs remain an important cause of infant morbidity and mortality in Finland.


Assuntos
Defeitos do Tubo Neural , Sistema de Registros , Natimorto , Humanos , Finlândia/epidemiologia , Feminino , Defeitos do Tubo Neural/epidemiologia , Masculino , Prevalência , Recém-Nascido , Gravidez , Natimorto/epidemiologia , Lactente , Distribuição por Sexo , Nascido Vivo/epidemiologia , Mortalidade Infantil/tendências , Adulto , Mortalidade Perinatal/tendências
2.
Iran J Child Neurol ; 18(3): 103-115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988851

RESUMO

Objectives: Maternal smoking is a potent teratogen among congenital malformations, however its role in the development of Neural Tube Defects (NTDs) is still unclear. In this systematic review, we intend to further investigate the interaction of smoking during pregnancy and the incidence of NTDs. Materials & Methods: This article was written according to PRISMA criteria from February 2015 and August 2022. After examining the four stages of PRISMA criteria, we selected clinical articles. These articles were selected from PubMed, Scopus and Google scholar (for results follow-up) databases. We gathered NTDs effect and types, smoking type and habit of parents, from neonates. Results: Eventually, 8 articles were included by two separated authors, Smoking was associated with an increase NTDs in the population of pregnant mothers and also among children whose fathers smoked. The main side effects that were considered to be the cause of NTDs besides smoking were alcohol and BMI (18.5-24.9). Smoking also affects the level of folic acid as a substance with an essential role that affects the closure of the neural tube. folic acid available to infants changing along with the level of other blood elements such as zinc, that necessary prevent for NTDs condition. Conclusion: Parental smoking can be considered as one of the strong teratogens in the occurrence of NTDs. Smoking, whether active or passive by the mother, or by the father, is associated with the occurrence of NTDs, In order to reduce the prevalence this disorder, we advise pregnant mothers and neonate's fathers to quit smoking.

3.
Acta Vet Scand ; 66(1): 29, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965607

RESUMO

BACKGROUND: Chiari malformation type II (CMII) was originally reported in humans as a rare disorder characterized by the downward herniation of the hindbrain and towering cerebellum. The congenital brain malformation is usually accompanied by spina bifida, a congenital spinal anomaly resulting from incomplete closure of the dorsal aspect of the spinal neural tube, and occasionally by other lesions. A similar disorder has been reported in several animal species, including cattle, particularly as a congenital syndrome. A cause of congenital syndromic Chiari-like malformation (CSCM) in cattle has not been reported to date. We collected a series of 14 CSCM-affected Holstein calves (13 purebred, one Red Danish Dairy F1 cross) and performed whole-genome sequencing (WGS). WGS was performed on 33 cattle, including eight cases with parents (trio-based; group 1), three cases with one parent (group 2), and three single cases (solo-based; group 3). RESULTS: Sequencing-based genome-wide association study of the 13 Holstein calves with CSCM and 166 controls revealed no significantly associated genome region. Assuming a single Holstein breed-specific recessive allele, no region of shared homozygosity was detected suggesting heterogeneity. Subsequent filtering for protein-changing variants that were only homozygous in the genomes of the individual cases allowed the identification of two missense variants affecting different genes, SHC4 in case 4 in group 1 and WDR45B in case 13 in group 3. Furthermore, these two variants were only observed in Holstein cattle when querying WGS data of > 5,100 animals. Alternatively, potential de novo mutational events were assessed in each case. Filtering for heterozygous private protein-changing variants identified one DYNC1H1 frameshift variant as a candidate causal dominant acting allele in case 12 in group 3. Finally, the presence of larger structural DNA variants and chromosomal abnormalities was investigated in all cases. Depth of coverage analysis revealed two different partial monosomies of chromosome 2 segments in cases 1 and 7 in group 1 and a trisomy of chromosome 12 in the WDR45B homozygous case 13 in group 3. CONCLUSIONS: This study presents for the first time a detailed genomic evaluation of CSCM in Holstein cattle and suggests an unexpected genetic and allelic heterogeneity considering the mode of inheritance, as well as the type of variant. For the first time, we propose candidate causal variants that may explain bovine CSCM in a certain proportion of affected calves. We present cattle as a large animal model for human CMII and propose new genes and genomic variants as possible causes for related diseases in both animals and humans.


Assuntos
Malformação de Arnold-Chiari , Doenças dos Bovinos , Estudo de Associação Genômica Ampla , Animais , Bovinos/genética , Doenças dos Bovinos/genética , Doenças dos Bovinos/congênito , Doenças dos Bovinos/patologia , Malformação de Arnold-Chiari/veterinária , Malformação de Arnold-Chiari/genética , Feminino , Estudo de Associação Genômica Ampla/veterinária , Masculino , Sequenciamento Completo do Genoma/veterinária
4.
J Ethnopharmacol ; 334: 118587, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39025160

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.

5.
Stem Cell Res Ther ; 15(1): 212, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020391

RESUMO

BACKGROUND: Sciatic nerve repair becomes a focus of research in neurological aspect to restore the normal physical ability of the animal to stand and walk. Tissue engineered nerve grafts (TENGs) provide a promising alternative therapy for regeneration of large gap defects. The present study investigates the regenerative capacity of PRP, ADSCs, and PRP mixed ADSCs on a long sciatic nerve defect (40-mm) bridged by a polyglycolic polypropylene (PGA-PRL) mesh which acts as a neural scaffold. MATERIALS AND METHODS: The study was conducted on 12 adult male mongrel dogs that were randomly divided into 4 groups: Group I (scaffold group); where the sciatic defect was bridged by a (PGA-PRL) mesh only while the mesh was injected with ADSCs in Group II (ADSCs group), PRP in Group III (PRP group). Mixture of PRP and ADSCs was allocated in Group IV (PRP + ADSCs group). Monthly, all animals were monitored for improvement in their gait and a numerical lameness score was recorded for all groups. 6 months-post surgery, the structural and functional recovery of sciatic nerve was evaluated electrophysiologically, and on the level of gene expression, and both sciatic nerve and the gastrocnemius muscle were evaluated morphometrically, histopathologically. RESULTS: Numerical lameness score showed improvement in the motor activities of both Group II and Group III followed by Group IV and the scaffold group showed mild improvement even after 6 months. Histopathologically, all treated groups showed axonal sprouting and numerous regenerated fascicles with obvious angiogenesis in proximal cut, and distal portion where Group IV exhibited a significant remyelination with the MCOOL technique. The regenerative ratio of gastrocnemius muscle was 23.81%, 56.68%, 52.06% and 40.69% for Group I, II, III and IV; respectively. The expression of NGF showed significant up regulation in the proximal portion for both Group III and Group IV (P ≤ 0.0001) while Group II showed no significant difference. PDGF-A, and VEGF expressions were up-regulated in Group II, III, and IV whereas Group I showed significant down-regulation for NGF, PDGF-A, and VEGF (P ≤ 0.0001). CONCLUSION: ADSCs have a great role in restoring the damaged nerve fibers by secreting several types of growth factors like NGF that have a proliferative effect on Schwann cells and their migration. In addition, PRP therapy potentiates the effect of ADSCs by synthesis another growth factors such as PDGF-A, VEGF, NGF for better healing of large sciatic gap defects.


Assuntos
Regeneração Nervosa , Polipropilenos , Nervo Isquiático , Animais , Cães , Regeneração Nervosa/fisiologia , Nervo Isquiático/lesões , Masculino , Polipropilenos/química , Plasma Rico em Plaquetas/metabolismo , Tecido Adiposo/citologia , Ácido Poliglicólico/química , Células-Tronco/citologia , Células-Tronco/metabolismo , Modelos Animais de Doenças , Alicerces Teciduais/química , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos
6.
Childs Nerv Syst ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847879

RESUMO

INTRODUCTION: Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies. METHODS: This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test. RESULTS: The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02). CONCLUSION: This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients.

7.
Birth Defects Res ; 116(6): e2375, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923368

RESUMO

BACKGROUND: On May 29, 2023, the 76th World Health Assembly (WHA) unanimously adopted the resolution entitled, "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." The Society for Birth Defects Research and Prevention published their resolution in 2015 supporting mandatory fortification of staple foods with folic acid and recommendations aiming to achieve global total prevention of folate-sensitive spina bifida and anencephaly, setting a goal to achieve by the year 2024. The WHA resolution provides another global push for the cause, with recommendations to member nations for food fortification to be achieved by the year 2030. METHODS: This short communication documents the steps, from inception up to the passage, of the 76th WHA resolution on food fortification, with a narrative on the nature of strategic advocacy efforts by multiple governmental and nongovernmental organizations. RESULTS: WHA resolutions can take many years to be introduced and passed by the assembly; however, this is a case study of the swiftness of the process enabled by powerful global partnership. CONCLUSION: The documentation of this process serves as an example for developing and processing future WHA resolutions aiming to improve global maternal and child health.


Assuntos
Alimentos Fortificados , Saúde Global , Micronutrientes , Defeitos do Tubo Neural , Humanos , Defeitos do Tubo Neural/prevenção & controle , Micronutrientes/deficiência , Ácido Fólico , Organização Mundial da Saúde , Cooperação Internacional
8.
Clin Nutr ESPEN ; 63: 57-67, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38923466

RESUMO

BACKGROUND & AIMS: Folate is crucial for the development of the fetal neurological system. Moroccan Health authorities promote Folic acid (FA) supplementation, before and during pregnancy, as a significant protection against fetal neural tube defects (NTDs). Thus, the current study aims to investigate the effect of FA supplementation guidelines on NTDs prevalence and to assess the health professionals' (HPs) knowledge, attitude, and practice (KAP) regarding FA supplementation in Morocco. METHODS: To assess the prevalence of NTDs, epidemiological data were collected from local and regional medical facilities and enhanced through a literature study. In addition, an auto-administered questionnaire was implemented to evaluate KAP among HPs on the FA supplementation national program. RESULTS: The study results showed that from 2017 to 2023, the national prevalence rate of NTDs ranged from 4.26 to 21 per 10,000 live births, according to the region. Lack of information about FA supplementation is evident among HPs; while, 13.7% of the participants confused FA with vitamin B12; merely 50% recognized the significance of FA; and 11.9% had no idea which foods contained the most folate. Consequently, HPs' attitude and practice towards FA supplementation were deemed inadequate. Additionally, only 35.8% of respondents stated that they occasionally inquire about their patients' nutrition, 55.9% do not prescribe FA, and 44.1% are unwilling to report cases of NTDs. CONCLUSION: NTDs remain a serious public health problem in Morocco. Despite the significant incidence of these diseases, HPs' knowledge, attitudes and practices in terms of prevention present gaps and inadequacies. According to the results of this study, the preparation of specific training sessions and the start of preconception consultations constitute an urgent and important issue.

9.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891776

RESUMO

Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.


Assuntos
Peptidilprolil Isomerase de Interação com NIMA , Defeitos do Tubo Neural , Tretinoína , Animais , Feminino , Humanos , Camundongos , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Tubo Neural/metabolismo , Tubo Neural/efeitos dos fármacos , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/induzido quimicamente , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Estresse Oxidativo/efeitos dos fármacos , Receptor Notch1/metabolismo , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Tretinoína/metabolismo , Tretinoína/farmacologia
10.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891790

RESUMO

Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of sclerotome-derived vertebrae and ribs, and of lateral mesoderm-derived sternum. To this end, Hedgehog interacting protein (Hhip) was electroporated at various times between days 2 and 5. While the vertebral body and rib primordium showed consistent size reduction, rib expansion into the somatopleura remained unaffected, and the sternal bud developed normally. Additionally, we compared these effects with those of locally inhibiting BMP activity. Transfection of Noggin in the lateral mesoderm hindered sternal bud formation. Unlike Hhip, BMP inhibition via Noggin or Smad6 induced myogenic differentiation of the lateral dermomyotome lip, while impeding the growth of the myotome/rib complex into the somatic mesoderm, thus affirming the role of the lateral dermomyotome epithelium in rib guidance. Overall, these findings underscore the continuous requirement for opposing gradients of Shh and BMP activity in the morphogenesis of proximal and distal flank skeletal structures, respectively. Future research should address the implications of these early interactions to the later morphogenesis and function of the musculo-skeletal system and of possible associated malformations.


Assuntos
Proteínas Hedgehog , Costelas , Coluna Vertebral , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Costelas/metabolismo , Costelas/embriologia , Coluna Vertebral/metabolismo , Coluna Vertebral/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/metabolismo , Mesoderma/embriologia , Codorniz , Somitos/metabolismo , Somitos/embriologia , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas de Transporte
11.
FASEB J ; 38(11): e23738, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38855924

RESUMO

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.


Assuntos
Inositol , Defeitos do Tubo Neural , Inositol/metabolismo , Inositol/farmacologia , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/prevenção & controle , Animais , Feminino , Camundongos , Gravidez , Embrião de Mamíferos/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Metaboloma , Ácido Fólico/metabolismo
12.
Birth Defects Res ; 116(6): e2370, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888449

RESUMO

BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.


Assuntos
Desinfecção , Água Potável , Exposição Materna , Defeitos do Tubo Neural , Humanos , Feminino , Água Potável/efeitos adversos , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/epidemiologia , Gravidez , Exposição Materna/efeitos adversos , Exposição Materna/estatística & dados numéricos , Desinfecção/métodos , Adulto , Estudos de Casos e Controles , Desinfetantes/efeitos adversos , Desinfetantes/análise , Purificação da Água/métodos , Trialometanos/análise , Trialometanos/efeitos adversos , Masculino , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Disrafismo Espinal/etiologia , Disrafismo Espinal/epidemiologia
13.
Phenomics ; 4(2): 187-202, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38884059

RESUMO

The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization of Rho-associated kinase (ROCK), which remodels the actomyosin cytoskeleton and changes cellular morphology via its ability to phosphorylate and activate non-muscle myosin II. Therefore, the Shrm-ROCK complex is critical for the cellular shape and the development of many tissues, including the neural tube, eye, intestines, heart, and vasculature system. Importantly, the structure and expression of Shrm proteins are also associated with neural tube defects, chronic kidney disease, metastasis of carcinoma, and X-link mental retardation. Therefore, a better understanding of Shrm-mediated signaling transduction pathways is essential for the development of new therapeutic strategies to minimize damage resulting in abnormal Shrm proteins. This paper provides a comprehensive overview of the various Shrm proteins and their roles in morphogenesis and disease.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38841745

RESUMO

Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like ( Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p ( Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.

15.
Acta Med Philipp ; 58(6): 74-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846167

RESUMO

We report the case of a 33-week-old female fetus born with craniorachischisis to a gravida 5, para 4 (3104) mother with no previous history of conceiving a child with a neural tube defect. Craniorachischisis is characterized by anencephaly and an open defect extending from the brain to the spine and is the most severe and fatal type of neural tube defect. Although the cause of neural tube defects is hypothesized to be multifactorial and is usually sporadic, the risk is increased in neonates born to mothers with a family history or a previous pregnancy with neural tube defect, both of which are not present in the index case. This case is unique in that only during the fifth pregnancy did the couple conceive a child with a neural tube defect, emphasizing that folic acid supplementation, the sole preventive measure proven to decrease the risk of neural tube defects, remains to be important in the periconceptual period for all women of childbearing age.

16.
Childs Nerv Syst ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850295

RESUMO

OBJECTIVE: The objective of this study was to explore the effect of intraoperative neurophysiological monitoring (IONM) on tethered spinal cord release in children. METHODS: The clinical data of 454 children with tethered cord syndrome who underwent surgery for tethered cord release were retrospectively analyzed. The children were divided into two groups: the non-IONM group and the IONM group. SPSS 26.0 software was used for statistical analysis. The evaluation indices included the effective rate and incidence of new neurological dysfunction. RESULTS: The short-term results showed that the effective rate of the non-IONM group was 14.8%, while that of the IONM group was 15.2%. Additionally, the incidence of new neurological dysfunction was 7.8% in the non-IONM group and 5.6% in the IONM group. However, there was no significant difference between the two groups (P > 0.05). The medium- to long-term follow-up had significant difference (P < 0.05), the response rate was 32.1% in the IONM group and 23.7% in the non-IONM group, and deterioration rates regarding neurological dysfunction were 3.3% in the IONM group and 8.5% in the non-IONM group. CONCLUSION: This study revealed that the use of IONM does not significantly improve the short-term treatment effect of patients undergoing surgery for tethered cord release or reduce the short-term incidence of postoperative new neurological dysfunction. However, the medium- to long-term prognoses of patients in the IONM group were better than those of patients in the non-IONM group.

17.
Dev Dyn ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877839

RESUMO

BACKGROUND: The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and stem cell homeostasis. Modulation of the actin cytoskeleton via the non-canonical Wnt pathway regulate cell polarity and cell migration that are required for proper vertebrate gastrulation and subsequent neurulation. However, the mechanism(s) of how the non-canonical pathway mediates actin cytoskeleton modulation is not fully understood. RESULTS: Herein, we characterize the role of the Formin-homology protein; dishevelled associated activator of morphogenesis 2 (Daam2) protein in the Wnt signaling pathway. Co-immunoprecipitation assays confirm the binding of Daam2 to dishevelled2 (Dvl2) as well as the domains within these proteins required for interaction; additionally, the interaction between Daam2 and Dvl2 was Wnt-regulated. Sub-cellular localization studies reveal Daam2 is cytoplasmic and regulates the cellular actin cytoskeleton by modulating actin filament formation. During Xenopus development, a knockdown or loss of Daam2 specifically produces neural tube closure defects indicative of a role in non-canonical signaling. Additionally, our studies did not identify any role for Daam2 in canonical Wnt signaling in mammalian culture cells or the Xenopus embryo. CONCLUSIONS: Our studies together identify Daam2 as a component of the non-canonical Wnt pathway and Daam2 is a regulator of neural tube morphogenesis during vertebrate development.

18.
Adv Exp Med Biol ; 1441: 125-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884708

RESUMO

This chapter discusses the role of cardiac neural crest cells in the formation of the septum that divides the cardiac arterial pole into separate systemic and pulmonary arteries. Further, cardiac neural crest cells directly support the normal development and patterning of derivatives of the caudal pharyngeal arches, including the great arteries, thymus, thyroid, and parathyroids. Recently, cardiac neural crest cells have also been shown to indirectly influence the development of the secondary heart field, another derivative of the caudal pharynx, by modulating signaling in the pharynx. The contribution and function of the cardiac neural crest cells has been learned in avian models; most of the genes associated with cardiac neural crest function have been identified using mouse models. Together these studies show that the neural crest cells may not only critical for normal cardiovascular development but also may be involved secondarily because they represent a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Cardiac neural crest cells span from the caudal pharynx into the outflow tract, and therefore may be susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations resulting from genetic and/or environmental insults necessarily requires better understanding the role of cardiac neural crest cells in cardiac development.


Assuntos
Crista Neural , Crista Neural/embriologia , Crista Neural/citologia , Crista Neural/metabolismo , Animais , Humanos , Coração/embriologia , Camundongos
19.
Birth Defects Res ; 116(6): e2372, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38877667

RESUMO

OBJECTIVE: To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). METHODS: ARA, EPA, and DHA composition was assessed using capillary gas chromatography. RESULTS: ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. CONCLUSIONS: More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.


Assuntos
Ácido Araquidônico , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácido Fólico , Metilenotetra-Hidrofolato Redutase (NADPH2) , Defeitos do Tubo Neural , Humanos , Ácido Eicosapentaenoico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Defeitos do Tubo Neural/genética , Ácido Araquidônico/sangue , Ácido Araquidônico/metabolismo , Ácido Fólico/sangue , Adulto , Tunísia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Homocisteína/sangue , Homocisteína/genética , Gravidez , Vitamina B 12/sangue , Estudos de Casos e Controles , Genótipo , Vitamina D/sangue , Vitamina D/genética
20.
Vet Res Commun ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884867

RESUMO

Two 1-day-old full-term female calves from different farms located in the Brazilian state of Rio Grande do Sul were unable to stand due to paresis of the pelvic limbs. Both calves had spina bifida on the spinal lumbar segment and were submitted to euthanasia due to poor prognosis. Postmortem examination revealed cerebellar herniation, caudal displacement of the brainstem, rostral deviation of the cranial nerves, caudal extension of occipital lobes, absence of dorsal lamina of lumbar vertebrae with exposed spinal cord, myelodysplasia, kyphosis, segmental spinal agenesis, renal fusion, muscular atrophy, and arthrogryposis. Histology highlighted myelodysplasia (syringomyelia and diplomyelia) and muscular atrophy. The reverse transcription-polymerase chain reactions for ruminant pestivirus were negative. Based on these lesions, the diagnosis of complex neural tube and skeletal malformations was made. A review of previous publications on calves diagnosed with these malformations, originally called Chiari or Arnold-Chiari malformations, revealed a wide range of nervous system and skeletal lesions. These variations amplified the uncertainty regarding whether all cases represent the same disorder and reinforced the importance of reconfiguring the terminology.

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