Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias.

Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.

Background: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.

High Homocysteine-Thiolactone Leads to Reduced MENIN Protein Expression and an Impaired DNA Damage Response: Implications for Neural Tube Defects.

DNA damage is associated with hyperhomocysteinemia (HHcy) and neural tube defects (NTDs). Additionally, HHcy is a risk factor for NTDs. Therefore, this study examined whether DNA damage is involved in HHcy-induced NTDs and investigated the underlying pathological mechanisms involved.

Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile.

Introduction: Type 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited.

Double whammy: the genetic variants in CECR2 and high Hcy on the development of neural tube defects.

Neural tube defects (NTDs) are serious congenital malformations. The etiology of NTDs involves both genetic and environmental factors. Loss of CECR2 in mice has been shown to result in NTDs.

Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children.

The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics.

Increasing angiotensin-converting enzyme 1 regulated by histone 3 lysine 27 hyperacetylation in high-fat diet-induced hypertensive rat kidney.

Background: Obesity is a key risk factor of hypertension. Angiotensin-converting enzyme 1 (ACE1) is a key enzyme involved in the renin-angiotensin-aldosterone system (RAAS), which contributes to obesity-related hypertension (OrHTN). Emerging evidence has shown that histone acetylation is also involved in OrHTN.

Quantitative Proteomics Reveals Association of Neuron Projection Development Genes ARF4, KIF5B, and RAB8A With Hirschsprung Disease.

Hirschsprung disease (HSCR) is a heterogeneous group of neurocristopathy characterized by the absence of the enteric ganglia along a variable length of the intestine. Genetic defects play a major role in the pathogenesis of HSCR, whereas family studies of pathogenic variants in all the known genes (loci) only demonstrate incomplete penetrance and variable expressivity for unknown reasons. Here, we applied large-scale, quantitative proteomics of human colon tissues from 21 patients using isobaric tags for relative and absolute quantification.

Identification of histone malonylation in the human fetal brain and implications for diabetes-induced neural tube defects.

Background: Neural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes.

Identification of histone acetylation markers in human fetal brains and increased H4K5ac expression in neural tube defects.

Background: Neural tube defects (NTDs) are severe common birth defects that result from a failure in neural tube closure (NTC). Our previous study has shown that decreased histone methylation altered the regulation of genes linked to NTC. However, the effect of alterations in histone acetylation in human fetuses with NTDs, which are another functional posttranslation modification, remains elusive.

Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects.

Neural tube defects (NTDs) are serious congenital malformations. Excessive maternal homocysteine (Hcy) increases the risk of NTDs, while its mechanism remains elusive. Here we report the role of histone homocysteinylation in neural tube closure (NTC).

CBP/p300 inhibitor C646 prevents high glucose exposure induced neuroepithelial cell proliferation.

Background: Maternal diabetes related neural tube defects (NTDs) are a result of oxidative stress and apoptosis. However, the molecular mechanism behind the pathogenesis is not fully understood. Here, we report that high glucose exposure-induced epigenetic changes influence histone H4 acetylation and neuroepithelial cell proliferation.

Regulation of the expression of tumor necrosis factor‑related genes by abnormal histone H3K27 acetylation: Implications for neural tube defects.

The association between apoptosis and neural tube defects (NTDs) is recognized as important, however, the precise link remains to be elucidated. Epigenetic modifications in human NTDs have been detected previously. In the present study, the occurrence of epigenetic modifications in apoptosis‑related genes was investigated in a retinoic acid (RA)‑induced mouse NTD model.

Genetic screening and functional analysis of CASP9 mutations in a Chinese cohort with neural tube defects.

Aim: Neural tube defects (NTDs) are birth defects of the nervous system and are the second most frequent cause of birth defects worldwide. The etiology of NTDs is complicated and involves both genetic and environmental factors. CASP9 is an initiator caspase in the intrinsic apoptosis pathway, which in Casp9 mice has been shown to result in NTDs because of decreased apoptosis.

MARK2/Par1b Insufficiency Attenuates DVL Gene Transcription via Histone Deacetylation in Lumbosacral Spina Bifida.

Dishevelled (DVL/Dvl) genes play roles in canonical and noncanonical Wnt signaling, both of which are essential in neural tube closing and are involved in balancing neural progenitor growth and differentiation, or neuroepithelial cell polarity, respectively. In mouse Dvl haploinsufficiency leads to neural tube defects (NTDs), which represent the second most common birth defects. However, DVL genes' genetic contributions in human NTDs are modest.

Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans.

Neural tube defects (NTDs) are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC). We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1 DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse.

Abnormal epigenetic regulation of the gene expression levels of Wnt2b and Wnt7b: Implications for neural tube defects.

The association between Wnt genes and neural tube defects (NTDs) is recognized, however, it remains to be fully elucidated. Our previous study demonstrated that epigenetic mechanisms are affected in human NTDs. Therefore, the present study aimed to evaluate whether Wnt2b and Wnt7b are susceptible to abnormal epigenetic modification in NTDs, using chromatin immunoprecipitation assays to evaluate histone enrichments and the MassARRAY platform to detect the methylation levels of target regions within Wnt genes.

Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues.

Functional variant in methionine synthase reductase intron-1 is associated with pleiotropic congenital malformations.

Congenital malformations, such as neural tube defects (NTDs) and congenital heart disease (CHD), cause significant fetal mortality and childhood morbidity. NTDs are a common congenital anomaly, and are typically induced by higher maternal homocysteine (Hcy) levels and abnormal folate metabolism. The gene encoding methionine synthase reductase (MTRR) is essential for adequate remethylation of Hcy.

Different epigenetic alterations are associated with abnormal IGF2/Igf2 upregulation in neural tube defects.

The methylation status of DNA methylation regions (DMRs) of the imprinted gene IGF2/Igf2 is associated with neural tube defects (NTDs), which are caused by a failure of the neural tube to fold and close and are the second-most common birth defect; however, the characterization of the expression level of IGF2/Igf2 in neural tissue from human fetuses affected with NTDs remains elusive. More importantly, whether abnormal chromatin structure also influences IGF2/Igf2 expression in NTDs is unclear. Here, we investigated the transcriptional activity of IGF2/Igf2 in normal and NTD spinal cord tissues, the methylation status of different DMRs, and the chromatin structure of the promoter.

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

Objective: To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers.

Methods: A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420).

Association of folate metabolism genes MTHFR and MTRR with multiple complex congenital malformation risk in Chinese population of Shanxi.

Birth defects are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for birth defects. In the present study 250 Chinese birth defects cases who suffered 1-8 types of birth defect disease phenotypes were subjected and two genetic variants in two folate metabolism key enzymes, rs1801394 of methionine synthase reductase (MTRR) and rs1801133 of methylenetetrahydrofolate reductase (MTHFR) were genotyped by using SNaPshot method.