Tube Development Research Articles

Spina bifida as a multifactorial birth defect: Risk factors and genetic underpinnings

AbstractSpina bifida is a birth defect resulting from abnormal embryonic development of the neural tube. Though spina bifida is divided into several subtypes, myelomeningocele—the most severe form of spina bifida often associated with a markedly diminished quality of life—accounts for a significant portion of cases. A broad range of genetic and environmental factors, many of which are still unknown, influence spina bifida, making it difficult to provide a comprehensive etiology for the disorder. Folic acid supplementation aided by the mandatory fortification of food is preventive; still, spina bifida persists due to numerous other confounding factors that affect risk. This article reviews the latest studies pertaining to the risk factors and genetics involved in spina bifida in an attempt to elucidate the complex background of the congenital malformation. Additionally, this review highlights the significant impact of environmental pollutants, adverse medication effects, and maternal health conditions such as diabetes and obesity on the prevalence of spina bifida. Emerging research on gene‐environment interactions provides insight into how specific genetic variants may influence susceptibility to these environmental factors. We also discuss new technologies in genetic sequencing that show promise for the large‐scale discovery of genes associated with spina bifida risk. Understanding these intricate interactions is crucial for developing effective prevention and intervention strategies.

ApoM maintains cellular homeostasis between mitophagy and apoptosis by affecting the stability of Nnt mRNA through the Zic3-ApoM-Elavl2-Nnt axis during neural tube closure

Research on the aetiology of neural tube defects (NTDs) has made progress in recent years. However, the molecular mechanism of apolipoproteins underlying NTDs development remains unclear. This study aimed to investigate the function of apolipoprotein M (ApoM) in the pathogenesis of NTDs and its underlying mechanisms. We demonstrated that ApoM expression was reduced in the spinal cord samples of rat models and human fetuses with NTDs respectively. Specifically, lack of ApoM resulted in reduced cytosolic localization of Elavl2 and caused Nnt mRNA degradation, which further led to impaired cell homeostasis by suppressing PINK1-PRKN-mediated mitophagy and promoting apoptosis and subsequent NTDs formation. Moreover, Zic3 directly interacted with the promoter of ApoM and activated its transcription. Lastly, intra-amniotic delivery of adenoviral recombinant Zic3 or ApoM could promote mitophagy and alleviate apoptosis in spinal cords of NTDs. Collectively, these findings highlight the important role of the Zic3-ApoM-Elavl2-Nnt axis in cellular homeostasis during neural tube development, thereby revealing an intracellular molecular regulatory mechanism of ApoM, providing a mechanistic basis for understanding embryonic neural development, and offering experimental evidence for potential therapeutic targets for NTDs.

Preconceptional and Periconceptional Folic Acid Supplementation in the Visegrad Group Countries for the Prevention of Neural Tube Defects.

Neural tube defects (NTDs) are malformations of the central nervous system that represent the second most common cause of congenital morbidity and mortality, following cardiovascular abnormalities. Maternal nutrition, particularly folic acid, a B vitamin, is crucial in the etiology of NTDs. FA plays a key role in DNA methylation, synthesis, and repair, acting as a cofactor in one-carbon transfer reactions essential for neural tube development. Randomized trials have shown that FA supplementation during preconceptional and periconceptional periods reduces the incidence of NTDs by nearly 80%. Consequently, it is recommended that all women of reproductive age take 400 µg of FA daily. Many countries have introduced FA fortification of staple foods to prevent NTDs, addressing the high rate of unplanned pregnancies. These policies have increased FA intake and decreased NTD incidence. Although the precise mechanisms by which FA protects against NTDs remain unclear, compelling evidence supports its efficacy in preventing most NTDs, leading to national recommendations for FA supplementation in women. This review focuses on preconceptional and periconceptional FA supplementation in the female population of the Visegrad Group countries (Slovakia, Czech Republic, Poland, and Hungary). Our findings emphasize the need for a comprehensive approach to NTDs, including FA supplementation programs, tailored counseling, and effective national-level policies.

Anorectal manometry and urodynamics in children with spina bifida: can we predict the colonic dysmotility from bladder dysfunction?

IntroductionSpina bifida is a condition that impacts the development of the neural tube leading to urological and gastrointestinal symptoms. Both systems are influenced together due to their shared innervation and embryological origin. Despite its impact on health and well-being there has been limited research on the relationship between manometry results and urodynamic tests, in this patient population. The aim of this study was to delineate the association of neurogenic bladder/bowel dysfunction with anorectal manometry and urodynamics.Materials and methodsUrodynamics and anorectal manometry were used to analyse the neurogenic bowel and bladder dysfunctions in 29 paediatric patients with spina bifida. Those children who had previous anorectal surgical interventions were excluded from the study. Patients were grouped according to the level of spinal defect to lower or upper defect. In this study, parameters such as bladder compliance, postvoid residual volume, detrusor activity, anorectal pressures, and rectal compliance were considered. Group comparison tests were performed using standardized paediatric protocols for data analysis as well as correlation tests. A p-value less than 0.05 was considered significant at all levels.ResultsA total of 29 patients with spina bifida were identified. Of these, 14 were male and 15 were female. Bladder function differed among the patients in the lower defect (LD, n:18) and upper defect (UD, n:11) groups. LD group exhibited lower bladder volumes (175.45 ± 106.19 mL) compared to the UD group (266.83 ± 102.54 mL, p < 0.05). All LD and 72.7% of UD had detrusor sphincter dyssynergia. There was positive correlation between functional bladder parameters and bowel dysfunction, such as rectoanal inhibitory reflex (RAIR) and maximum filling pressures of the bladder (rho = 0.569, p < 0.05). There was also a significant correlation between rectal compliance and bladder volumes.ConclusionsAssociation of neurogenic bowel and bladder dysfunction is a complex issue which requires personalized approach for managing the consequences. In children with neurogenic bladder dysfunction increased RAIR activity may be a sign for colonic dysmotility of neurogenic origin. This study may also pave the way for delineation of the mechanism under the generation of RAIR which is thought to be only intrinsic in origin. To optimize treatment modalities, full assessment with anorectal manometry and urodynamic studies should be done in patients with spina bifida.Clinical trial registrationThis study was not performed on volunteer patients. Clinical study enrolment is not required as this study was obtained from urodynamics and anorectal manometry performed in patients with neurogenic bladder/bowel and during clinical follow-up.

Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation.

The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investigation revealed increased neural differentiation and decreased proliferation under heat stimulation, indicating that periodic heat exposure might lead to abnormal brain development by altering key developmental processes. Hence, our model of periodically heating brain organoids provides a platform for modelling the effects of maternal fever on foetal brain development and could be extended to applications in neurodevelopmental disorders intervention.

SLMAP3 is essential for neurulation through mechanisms involving cytoskeletal elements, ABP, and PCP.

SLMAP3 is a tail-anchored membrane protein that targets subcellular organelles and is believed to regulate Hippo signaling. The global loss of SLMAP3 causes late embryonic lethality in mice, with some embryos exhibiting neural tube defects such as craniorachischisis. We show here that SLMAP3 -/- embryos display reduced length and increased width of neural plates, signifying arrested convergent extension. The expression of planar cell polarity (PCP) components Dvl2/3 and the activity of the downstream targets ROCK2, cofilin, and JNK1/2 were dysregulated in SLMAP3 -/- E12.5 brains. Furthermore, the cytoskeletal proteins (γ-tubulin, actin, and nestin) and apical components (PKCζ and ZO-1) were mislocalized in neural tubes of SLMAP3 -/- embryos, with a subsequent decrease in colocalization of PCP proteins (Fzd6 and pDvl2). However, no changes in PCP or cytoskeleton proteins were found in cultured neuroepithelial cells depleted of SLMAP3, suggesting an essential requirement for SLMAP3 for these processes in vivo for neurulation. The loss of SLMAP3 had no impact on Hippo signaling in SLMAP3 -/- embryos, brains, and neural tubes. Proteomic analysis revealed SLMAP3 in an interactome with cytoskeletal components, including nestin, tropomyosin 4, intermediate filaments, plectin, the PCP protein SCRIB, and STRIPAK members in embryonic brains. These results reveal a crucial role of SLMAP3 in neural tube development by regulating the cytoskeleton organization and PCP pathway.

Transcriptome and Metabolome Analyses Reveal a Complex Stigma Microenvironment for Pollen Tube Growth in Tobacco.

In flowering plants, the success of fertilization depends on the rapid polar extension of a pollen tube, which delivers sperm cells to the female gametophyte for fertilization. Numerous studies have shown that the microenvironment in planta is more conducive to the growth and development of pollen tubes than that in vitro. However, how stigma factors coordinate to regulate pollen tube growth is still poorly understood. Here, we demonstrate that in tobacco, mature stigma extract, but not immature stigma extract, facilitates pollen tube growth. Comparative transcriptomic and qRT-PCR analyses showed that the differentially expressed genes during stigma maturation were mainly enriched in the metabolism pathway. Through metabolome analyses, about 500 metabolites were identified to be differently accumulated; the significantly increased metabolites in the mature stigmas mainly belonged to alkaloids, flavonoids, and terpenoids, while the downregulated differential metabolites were related to lipids, amino acids, and their derivatives. Among the different kinds of plant hormones, the cis-form contents of zeatin were significantly increased, and more importantly, cis-zeatin riboside promoted pollen tube growth in vitro. Thus, our results reveal an overall landscape of gene expression and a detailed nutritional microenvironment established for pollen tube growth during the process of stigma maturation, which provides valuable clues for optimizing in vitro pollen growth and investigating the pollen-stigma interaction.

Heart tube morphogenesis is regulated by segment-specific gene regulatory networks controlled by MEF2C.

The transcription factor MEF2C plays a critical role in the development of the linear heart tube, but the specific transcriptional networks controlled by MEF2C remain largely undefined. To address this, we performed combined single-nucleus RNA-and ATAC-sequencing on wild type and MEF2C-null embryos at distinct stages of development. We identified a broadly "posteriorized" cardiac gene signature and chromatin landscape throughout the heart tube in the absence of MEF2C. By integrating our gene expression and chromatin accessibility data in a deep-learning based model, we were able to construct developmental trajectories for each of the outflow tract, ventricular, and inflow tract lineages and determined how each of these segment-specific trajectories were distinctly altered in the MEF2C-null embryos. We computationally identified potential segment-specific MEF2C-dependent enhancers, and from these candidates, identified novel enhancers with activity in the developing heart tube using transgenesis in zebrafish. Finally, using inferred gene regulatory networks we discovered a genetic interaction between Mef2c and the atrial nuclear hormone receptor Nr2f2 , revealing that the MEF2C-null heart malformations are partly driven by a transcriptional network with increased NR2F2 activity. These studies not only provide a rich description of the genomic regulation of early heart tube development, but provide a generalizable framework for using genetic mutants to dissect the transcriptional networks that govern developmental processes.

NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos.

Our lab has identified that transcripts and proteins of the cyclooxygenase (COX-1 and COX-2) isoenzymes are expressed during the early stages of vertebrate embryonic development, and that global COX-1/2 inhibition disrupts neural crest (NC) cell maturation in Ambystoma mexicanum (axolotl) embryos, with intriguing implications for tissue regeneration and healing. NC cells are embryonic stem cells that differentiate into various adult tissues including craniofacial cartilage, bone, and neurons in the peripheral and enteric nervous systems. Naproxen (NPX), a common non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation, exerts its effects through COX-1 and COX-2 inhibition. Embryonic exposures to NSAIDs have been linked to preterm birth, neural tube closure defects, abnormal enteric innervation, and craniofacial malformations, potentially due to disrupted neural tube or NC cell development. To investigate the phenotypic and molecular effects of NPX exposure on NC development and differentiation, we exposed late neurula and early tailbud stage axolotl embryos to various concentrations of NPX and performed immunohistochemistry (IHC) for markers of migratory and differentiating NC cells. Our results reveal that NPX exposure impairs the migration of SOX9+ NC cells, leading to abnormal development of craniofacial cartilage structures, including Meckel's cartilage in the jaw. NPX exposure also alters the expression of markers associated with peripheral and central nervous system (PNS and CNS) development, suggesting concurrent neurodevelopmental changes.

Wildfire Seasons, Prenatal PM2.5 Exposure, and Respiratory Infections by Age 1 Year: A Population-Based Case-Control Analysis of Critical Developmental Windows.

The 2017 and 2018 wildfire seasons in British Columbia (BC), Canada were unprecedented. Among all the pollutants in wildfire smoke, fine particulate matter (PM2.5) poses the most significant risk to human health. There is limited research on prenatal wildfire smoke exposure and its impacts on infant health. We used a population-based nested case-control design to assess the association between daily PM2.5 exposures during specific developmental windows and the occurrence of otitis media or lower respiratory infections by age 1 year, including infections associated with dispensations of the antibiotic amoxicillin. We observed the strongest association between per 10 μg/m3 increase in PM2.5 exposure and otitis media during the fourth window of eustachian tube development (weeks 19-28) with an OR [95% confidence interval] of 1.31 [1.22, 1.41]. Similarly, the canalicular stage of lower respiratory tract development (weeks 18-27) was associated with the highest odds of lower respiratory infections, with an OR of 1.21 [1.15, 1.28]. Measures to reduce wildfire smoke exposure during pregnancy are warranted.

Spatiotemporal characteristics of eustachian tube development in C57BL/6 mice: Correlation between morphological and functional maturation.

The eustachian tube (ET), a critical conduit connecting the middle ear and nasopharynx, is essential for normal middle ear function. However, it remains one of the least understood anatomical structures due to its complexity and the challenges of in vitro manipulation. Historically, these challenges have hindered research into the morphology and function development of the ET. This study elucidates the spatiotemporal relationship of ET morpho-functional maturation in mice, identifying key periods and factors that lay the theoretical foundation for exploring the molecular mechanisms of ET-related diseases. We comprehensively characterized the ET development in C57BL/6 mice from embryonic day (E) 12.5 to postnatal day (P) 30, focusing on the development of cilia, secretory cells, surrounding glands, and macrophages. Immunostaining identified the localization and secretion patterns of the mucins Muc5b and Muc5ac within the ET. Additionally, using improved ET function assessment tools, we evaluated the developmental features of ET mucociliary clearance and ventilation functions. In C57BL/6 mice, E16.5 marks a critical period for middle ear cavity and ET formation. Muc5b plays a foundational role during early stages, while Muc5ac enhances function in later stages. During P7-11, despite morphological maturity, ET function remains underdeveloped but continues to improve with growth.

Studies on Distant Hybridization Compatibility between the Azalea (Rhododendron × hybridum hort.) and the Rhododendron decorum Franch. Native to China

Rhododendron resources are abundant in China, and hybridization breeding technology is the primary method for cultivating Rhododendron varieties. In order to optimize the utilization of wild Rhododendron resources for distant hybridization, this study took three horticultural varieties of Rhododendron subgenus Tsutsusi and the Rhododendron decorum Franch. of the subgenus Hymenanthes as the research objects, and the cross-compatibility between subgenera was analyzed from the aspects of pollen tube growth and ovary and seed development. At the same time, the statistics of ovary swelling rate and fruit bearing rate, numbers of capsule seeds, 1000 seed weight of hybrid seeds, germination rate, green seedling rate, and other indexes were analyzed to comprehensively evaluate hybrid fertility. The results showed that there was obvious pre-fertilization and post-fertilization barriers existing in the hybridization of Rhododendron × hybridum hort. and R. decorum. During the growth of pollen tubes, a large amount of callus appeared, which led to the entanglement, distortion, and abnormal development of the pollen tubes; only part of the pollen tubes entered into the ovary or ovule. The pre-fertilization barriers can be overcome by early pollination and delayed pollination. According to the observation of the ovary paraffin section, 45 d after pollination, the seed was shriveled and developed abnormally. The comprehensive evaluation of hybrid fertility showed that ‘Sima’ × R. decorum was fertile, ‘Yin Taohong’ × R. decorum was a weakly fertile, and ‘Little Taohong’ × R. decorum was sterile. This study provided a scientific basis for intergeneric hybridization breeding between the subgenus Tsutsusi and the subgenus Hymenanthes.

Ethionine-induced S-adenosylmethionine deficiency suppressed H3K27me3 and cell differentiation during neural tube development in mice.

S-adenosylmethionine (SAM) as a major methyl donor plays a key role in methylation modification in vivo, and its disorder was closely related to neural tube defects (NTDs). However, the exact mechanism between SAM deficiency and NTDs remained unclearly. Hence, we investigated the association between histone methylation modification and cell differentiation in NTDs mice induced by SAM deficiency. The levels of SAM and SAH (S-adenosylhomocysteine) were determined by enzyme linked immunosorbent assay (ELISA). The level of histone methylation, β-catenin were analyzed by Western blot, reversing transcription and quantitative PCR (RT-qPCR) and immunofluorescence. The results showed that the incidence rate of NTDs induced by ethionine were 46.2%. Post treatment of ethionine combined with SAM, the incidence rate of NTDs was reduced to 26.2%. The level of SAM was significantly decreased (p < 0.05) and a reduction in the SAM/SAH ratio was observed after entionine treatment. The SAM deficiency caused the reduction of H3K27me3 modifications and the elevated UTX activity (p < 0.05), and inhibited the expressions of β-catenin. The differentiations of NSCs into neurons and oligodendrocytes were inhibited under SAM deficiency (p < 0.05). These results indicated that the SAM deficiency led to reduce H3K27me3 modifications, prevented the β-catenin signaling pathway and NSCs differentiation, which provided an understanding of the novel function of epigenetic regulation in NTDs.

Genome-wide analysis of the S-phase kinase-association protein 1 (ClSKP1) family and the role of S-RNase targeting by an SCF (Cullin1-SKP1-F-box) complex in the self-incompatibility of ‘Xiangshui’ lemon

The SKP1 gene is an important component of the SCF (SKP1-Cullin1-F-box) complex and serves as a bridge connecting the F-box and Cullin1 genes (F-box-SKP1-Cullin1). The pattern of S-RNase being ubiquitously labelled by the SCF complex and degraded by the 26S protease accounts for the bulk of the available self-incompatibility studies. In this study, 15 ClSKP1s from the ‘Xiangshui’ lemon genome and ubiquitome exist in the same SKP1 conserved domain (CD) as SKP1s in other species. The qPCR results showed that SKP1-6 and SKP1-14 have tissue expression patterns specific for expression in pollen. In addition, SKP1-6 and SKP1-14 in the stigma, style and ovary were significantly upregulated after self-pollination compared to those after cross-pollination. A subcellular location showed that SKP1-6 and SKP1-14 were located in the nucleus. In addition, yeast two-hybrid (Y2H) assays, bimolecular fluorescence complementation (BiFC) and luciferase complementation imaging (LCI) assays showed that SKP1-6 interacted with F-box1, F-box33, F-box34, F-box17, F-box19, Cullin1-2 and 26S proteasome subunit 4 homolog A (26S PS4HA). SKP1-14 interacted with F-box17, F-box19, F-box35, Cullin1-2 and 26S PS4HA. The interaction of Cullin1-2 and the F-box with SKP1 as a bridge was verified by a yeast three-hybrid experiment. The ability of S3-RNase to inhibit pollen and pollen tube growth and development was assessed using in vitro pollen co-culture experiments with recombinant S3-RNase proteins. Overall, this study provides important experimental evidence and theoretical basis for understanding the mechanism of self-incompatibility in plants by revealing the key role of the SCF complex in ‘Xiangshui’ lemon, which is bridged by ClSKP1-6, in self-incompatibility. The results of this study are of great significance for the future in-depth exploration of the molecular mechanism of the SCF complex and its wide application in the self-incompatibility of plants.

Linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse neural tube development.

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be genetically epistatic to Gpr161 with respect to regulation of Shh signaling in mouse neural tube development. The Fuz protein biochemically interacts with Gpr161, and Fuz regulates Gpr161-mediated ciliary localization, a process that might utilize β-arrestin 2. Our study characterizes a previously unappreciated Gpr161-Fuz axis that regulates Shh signaling during mouse neural tube development.

Lava flow field development and lava tube formation during the 1858–1861 eruption of Vesuvius (Italy), unravelled by historical documentation, lidar data and 3D mapping

Somma-Vesuvius is well known for its powerful Plinian explosive eruptions, however during the last eruptive cycle (1631–1944), persistent activity took place on the stratovolcano as mild and violent Strombolian, and effusive eruptions, forming more than one hundred lava flow fields. An important mechanism of lava transport within lava flow fields is the formation and development of lava tubes. The presence of lava tubes in a flow field can greatly increase their distance of emplacement. Observations of lava tubes at Vesuvius have been documented in historical records and speleological reports but no modern scientific studies are available. This work focuses on lava tubes formed in the compound lava flow field of the long-lived 1858 eruption (from 27 May 1858 to 12 April 1861) that was fed by seven eruptive fissures. The temporal and spatial evolution of the 1858 lava flow field was reconstructed using historical documentation. The exposed lava flow field surface was analysed using a 1-m resolution lidar Digital Surface Model (DSM). Surveys to fully digitize the interior and the overlying surface of the largest lava tube found in the 1858 lava flow field were conducted using a terrestrial laser scanner, optical cameras, and an Unmanned Aerial Vehicle (UAV). The accurate 3D model obtained was used to precisely quantify the inner dimensions and to better constrain the morphologies of the lava tube. Observed internal features were described and used to gain information on the formation and activity of the lava tube. Our data allowed us to understand that the described lava tube formed as an inflated lava flow inside which lava flowed through during an extended period ultimately draining out completely at the end of the eruption. Understanding how lava flow fields develop and how lava tubes form on Vesuvius is crucial to re-evaluate the last effusive activity of the volcano and its impact on hazard assessment.

Genetic variation and molecular profiling of congenital malformations of the female genital tract based on whole-genome sequencing.

Congenital malformations of the female genital tract (CM-FGT) are characterized by abnormal development of the fallopian tubes, uterus, and vagina, often accompanied by malformations in the urinary system, bones and hearing. However, no definitive pathogenic genes and molecular genetic causes have been identified. We present the largest whole-genome sequencing study of CM-FGT to date, analyzing 590 individuals in China: 95 patients, 442 case-controls, and 53 familial controls. Among the patients, 5.3% carried known CM-FGT-related variants. Pedigree and case-control analyses in two dimensions of coding and non-coding regulatory regions revealed seven novel de novo copy number variations, 12 rare single-nucleotide variations, and 10 rare 3' untranslated region (UTR) mutations in genes related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. Single-cell sequencing data showed that the majority of CM-FGT-related risk genes are spatiotemporally specifically expressed early in uterus development. In conclusion, this study identified novel variants related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. The findings provide insights into the genetic variants underlying CM-FGT, with single-cell sequencing data revealing spatiotemporal specific expression patterns of key risk genes early in uterine development. This study significantly advances the understanding of CM-FGT etiology and genetic landscape, offering new opportunities for prenatal screening.

Surgical treatment of spinal neurenteric cysts

Background. Spinal neurenteric cysts are very rare benign space-occupying lesions in the vertebral canal emerging due to anomalies of neural tube development during prenatal development of the fetus. Clinically, neurenteric cysts can manifest both in childhood and adulthood.Aim. To evaluate the results of surgical treatment of adult patients with spinal neurenteric cysts who were operated on at the Neurosurgery Division of the Clinic of Nervous System Diseases of the I.M. Sechenov First Moscow State Medical University.Materials and methods. The study group included 3 patients (2 women and 1 man) with mean age of 33 years. The main diagnosis method was magnetic resonance imaging. In all cases, radical cyst resection was performed with subsequent histological examination of cyst walls.Results. In all observations, cyst walls had local areas of increased density and thickness: a distinctive solid component accumulating the contrast agent in magnetic resonance images. This type of structure is considered extremely rare per descriptions presented in literature, but in our case series it was detected in all patients. Cyst resection led to pain syndrome regression and almost full regression of clinical manifestations of spinal cord compression which justifies active surgical tactics in this pathology.Conclusion. Neurenteric cyst of the vertebral canal can cause spinal cord compression. The main diagnostic method of this pathology is magnetic resonance imaging, however magnetic resonance semiotics of these cyst has not been standardized. The presence of constant pain syndrome without marked clinical signs of compression myelopathy is sufficient reason for cyst resection surgery. Cyst resection allowsto achieve regression of pain syndrome and neurological abnormalities caused by spinal cord compression.

Teratogenic Effect of Valproic Acids on Neural Tube Development: A Review

Teratogenic Effect of Valproic Acids on Neural Tube Development: A Review

Design, infectability, and transcriptomic analysis of transregionally differentiated and scalable lung organoids derived from adult bronchial cells.

The lung is a primary target for many lethal respiratory viruses, leading to significant global mortality. Current organoid models fail to completely mimic the cellular diversity and intricate tubular and branching structures of the human lung. Lung organoids derived from adult primary cells have so far only included cells from the input cell region, proximal or distal. Existing models are expensive. They often require cells from invasive deep lung tissue biopsies. The present study aimed to address these limitations. The lung organoids obtained using an original protocol exhibited transregional differentiation and were derived from relatively more accessible primary cells from the trachea/bronchi. Immortal bronchial cell lines were also used to simplify organoid fabrication and improve its scalability. The lung organoids are formed starting from bronchial cells with fibroblasts feeder cells in an alginate hydrogel coated with base membrane zone proteins. Characterizations were performed using bulk RNA sequencing and tandem mass tags. The resulting organoids express markers of different lung regions and mimic to some extent the tubular and branching morphology of the lung. The proteomic profile of organoid from primary cells and from cell lines was found to evolve towards that of mature lung tissue. Upregulated genes were mostly related to the respiratory system, tube development, and various aspects of respiratory viral infections. Infection with SARS-CoV-2 and influenza H1N1 was successful and did not require organoid disassembly. The organoids matured within 21 days and did not require complex or expensive culture methods. Transregionally differentiated lung organoid may find applications for the study of emerging or re-emerging viral infections and fostering the development of novel in-vitro therapeutic strategies.