Abnormal Development Research Articles

Surgical approach with minimally invasive intervention in lusoria dysphagia.

The lusoria artery has a prevalence of 0.5-2% in the general population. The abnormal development of the aortic arch forms vascular rings around the trachea and esophagus, causing pressure on them and leading to characteristic symptoms such as chest pain, difficulty breathing, and/or swallowing. Conventionally, only the subclavian artery was severed to release the esophagus, as done in neonates. However, this can lead to long-term hypotrophy of the thoracic limb. The surgical intervention remains controversial, with limitations, and it is only to be performed when the patient presents with symptoms. In the following two cases, a two-stage minimally invasive approach is described: first, a left lateral minithoracotomy for lusoria artery sectioning, and second, a supraclavicular approach for reimplantation into the right carotid artery.

The impact of bull breeding management on reproductive function (review)

Providing the population with quality food products is currently relevant. High-tech production of meat and dairy products requires breeding animals with high genetic potential. The main role is given to bull sires, since they are responsible for the constant reproduction of the breeding stock, which depends on the non-stop renovation of the herd with high breeding value’s calves. Management of growing and breeding of young bulls can directly affect the reproductive function of sires and the physiological health. The article provides analytical data based on literary sources containing research by various authors on this topic, and reviews methods and technologies for keeping breeding bulls on various farms in the Russia and abroad. Currently, there is a many problems of getting high-quality breeding young bulls to an artificial insemination center. Currently, there are problems with obtaining high-quality breeding bulls of the enterprise. There are animals with abnormal development of the musculoskeletal system, joints, hooves, with signs of osteomalacia, etc. Such animals require additional costs for veterinary and breeding services. The quality of the sperm products they produce often does not comply with state normative. The reason is related either to the choice of maintenance technology or feeding technology. It is necessary to competently organize management, breeding and veterinary work in farms that are purposefully engaged in breeding young animals.

Portal Cavernoma

Portal cavernoma corresponds to the abnormal development of a venous network whose caliber is initially microscopic, with hepatopetal portal blood flow. It is a consequence of chronic portal thrombosis in a healthy or slightly fibrous liver. The causes are essentially those of portal thrombosis. However, portal thrombosis remains an undetermined cause in 50% of the cases. The clinical manifestations of cavernoma reflect extrahepatic portal hypertension and are exceptionally biliary. The diagnosis of portal cavernoma is radiological. Ultrasound Doppler and CT confirmed the diagnosis. MRI offers a better analysis of biliary impact. The treatment is essentially medically based on anticoagulants. Recording to surgery was reserved for complications.

Molecular and morphofunctional bases of development of the horse multiple congenital eye anomalies with the silver gene presence on the example of the <i>Soviet draft</i> breed

The article concretizes clinical data on the molecular and morphofunctional foundations of the development of multiple congenital eye abnormalities (MСOA) linked to the silver gene, using the example of the Soviet heavy-duty horse breed. Recommendations for owners on their maintenance and medical support and work with them are provided. The study was conducted on the basis of data from the VNIIK breeding center for the specified horse breed, genetic testing and ophthalmological examination. The focus group included 26 horses of the Soviet heavy-duty breed, examined for the presence of the silver gene. The results of the study showed that horses of the Soviet heavy-duty breed should undergo genetic testing for the presence of a silver gene in the genotype. However, the presence of MCOA linked to the silver gene is not an indication for the culling of horses due to the status of this breed as endangered, if it is necessary to select a mate for mating without genetic abnormalities so that they do not spread during uncontrolled crossing. Regular observation of an ophthalmologist and strict implementation of his recommendations are necessary to prevent the development of infectious complications and rapid progression of the disease with the onset of blindness. Horses homozygous for the silver gene should be kept in conditions that limit the possibility of injury to the eyeballs, including secondary damage to eye structures by the UV spectrum of solar radiation, for which translucent/opaque masks or sunglasses should be used. Working on homozygous horses with partial or complete loss of vision is potentially dangerous and possible only if a number of conditions are met and the owner is ready to bear legal responsibility for possible consequences.

Genetic Association Between Blood Metabolites and Craniosynostosis: A Mendelian Randomization Study.

Craniosynostosis is a congenital disorder characterized by the premature fusion of cranial sutures, leading to abnormal skull development and potential neurodevelopmental complications. The role of metabolic influences in craniosynostosis remains underexplored. This study investigates the causal relationship between specific blood metabolites and the risk of craniosynostosis using a 2-sample Mendelian randomization (MR) approach. Genetic instruments were selected from a genome-wide association study on blood metabolites and craniosynostosis data from the FinnGen database. The MR analysis was conducted using inverse variance weighted regression as the primary method, with MR-Egger and weighted median methods as sensitivity analyses. Additional tests for pleiotropy and heterogeneity were performed to validate the robustness of the findings. The analysis identified significant associations between elevated levels of gamma-glutamylglycine [odds ratio (OR) = 2.379, 95% CI = 1.261-4.488, P = 0.007], N6-acetyllysine (OR = 2.731, 95% CI = 1.081-6.901, P = 0.034), phosphocholine (OR = 2.205, 95% CI = 1.226-3.658, P = 0.038) and glycine (OR = 2.118, 95% CI = 1.226-3.658, P = 0.007) with an increased risk of craniosynostosis. Conversely, higher levels of 3-hydroxy-2-methylpyridine sulfate (OR = 0.411, 95% CI = 0.1717-0.988, P = 0.047) and 5,6-dihydrothymine (OR = 0.293, 95% CI = 0.098-0.876, P = 0.028) were associated with reduced risk. Sensitivity analyses confirmed the robustness of these findings, with no significant evidence of pleiotropy or heterogeneity detected. This study provides evidence that specific blood metabolites may causally influence the risk of craniosynostosis, suggesting potential metabolic pathways that could be targeted for therapeutic intervention. These findings help to develop metabolite-based strategies for the prevention and treatment of craniosynostosis.

Probiotic-rich fermented milk from Lactiplantibacillus plantarum IIA-1A5: Effects on pregnancy health in the animal model

Previous studies of Lactiplantibacillus plantarum IIA-1A5 have shown its potential as a probiotic in modulating gut microbiota and providing health benefits; however, its effects during pregnancy remain underexplored. The aim of this study was to assess the safety of fermented milk enriched with L. plantarum IIA-IA5 in pregnant mice. An experimental study was conducted at Universitas Andalas, Padang, Indonesia. Two groups of pregnant mice (Mus musculus L.) were used, each with six mice. The control group received sterilized milk (10 mL/kg body weight (BW)), while the intervention group was given fermented milk containing L. plantarum IIA-1A5 (107 colony forming unit (CFU)/mL). The evaluated outcomes included maternal weight changes, fetal counts and measurements, and assessments of fetal morphology and skeletal development. Results indicated that the morphology of fetuses showed no significant differences between the control and intervention groups; both groups demonstrated normal development with no detected resorption sites, growth retardation, or hemorrhage. For skeletal development, both groups had the same bone counts, including frontal, parietal, intraparietal, exoccipital, supraoccipital, nasal, pre-maxilla, mandibular, thoracal, lumbar, sternum, and extremities. This study highlights that L. plantarum IIA-1A5-enriched fermented milk was safe, as no significant morphological or bone developmental abnormalities were observed, indicating its potential as a dietary supplement to support pregnancy health. However, further studies involving larger sample sizes may be needed to provide a more comprehensive assessment of its outcomes and safety.

Additives in Processed Foods as a Potential Source of Endocrine-Disrupting Chemicals: A Review

Processed foods, accounting for most consumable food categories today, contain considerable amounts of food additives. Food additives are substances added to food products to improve taste, consistency, appearance, or shelf life. Various food additives, such as phthalates, bisphenol A, tartrazine, erythrosine, artificial sweeteners, and parabens, have been identified as potential sources of endocrine-disrupting chemicals (EDCs) in processed foods. EDCs are substances that frequently interfere with the regular functioning of the endocrine system, creating an unusual environment in the biological system, which leads to adverse health effects such as the disruption of hormone synthesis, receptor binding, and signal transduction pathways, as well as energy metabolic homeostatic disorders which potentially increasing the risk of obesity, type-2 diabetes, cardiometabolic diseases and may also trigger allergic reactions. Consequently, they can also impact mammary gland development, and reproductive function, further leading to developmental abnormalities. This review aims to insights into the various food additives that act as potential endocrine-disrupting chemicals (EDCs) and to describe their applications in the food industry, as well as the failure of hormonal homeostatic mechanisms, which eventually result in hazardous health effects. It also outlines strategies to reduce the use of food additives and suggests alternative additives with minimal or no endocrine-disrupting properties, highlighting their importance for maintaining human health.

Production of second-generation sheep clones via somatic cell nuclear transfer using amniotic cells as nuclear donors

Somatic Cell Nuclear Transfer (SCNT) has transformed animal genetic improvement, gene-editing in model production, xenotransplantation, and conservation efforts for endangered species. However, SCNT-derived embryos occasionally display developmental abnormalities, and following embryo transfer, the miscarriage rate is high. Gene-edited fetuses may experience birth defects, resulting in decreased survival rates. Correct selection of nuclear donor cells is essential for the success of somatic cell cloning. Fibroblasts are the most commonly used cells, but their rapid proliferation increases the risk of genetic mutation, impairing embryo development and production. Conversely, amniotic cells have slower proliferation rates, decreasing the mutation risk during cultivation. Amniotic cells are thus better SCNT candidates than fibroblasts because they offer genomic stability, low tumorigenic and teratogenic risks, reduced immunogenicity, high differentiation potential, ease of accessibility, and fewer ethical concerns. Cells derived from first-generation gene-edited animals exhibit stable genetic structures, reduced susceptibility to genetic alterations and artificial modifications, closely resembling natural cells, and enhanced compatibility with SCNT procedures. Amniotic cells derived from gene-edited sheep fetuses used as nuclear donor cells for SCNT successfully recloned three healthy second-generation gene-edited sheep. Using amniotic cells as nuclear donor cells for SCNT did not significantly alter embryo cleavage rates, blastocyst formation, or fetal birth compared to edited fibroblasts (p > 0.05). However, fetal survival rates were significantly higher than edited fibroblasts (p < 0.05). The results support the potential of amniotic cells as SCNT alternatives, suggesting a promising strategy to improve gene-edited fetus survival rates using first-generation gene-edited sheep-derived amniotic cells.

CUL3-Related Neurodevelopmental Disorder: Clinical Phenotype of 20 New Individuals and Identification of a Potential Phenotype-Associated Episignature.

Neurodevelopmental disorder with or without autism or seizures (NEDAUS; OMIM #619239) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, seizures, autistic features and/or behavior abnormalities. It is caused by CUL3 (Cullin-3 ubiquitin ligase; OMIM #603136) haploinsufficiency. We collected clinical and molecular data from twenty-six individuals carrying pathogenic variants and variants of uncertain significance (VUS) in the CUL3 gene, including twenty previously unreported cases. By comparing their DNA methylation (DNAm) classifiers with those of healthy controls and other neurodevelopmental disorders characterized by established episignatures, we aimed to create a diagnostic biomarker (episignature) and gain more knowledge into the molecular pathophysiology. We discovered a sensitive and specific DNAm episignature for patients with pathogenic variants in CUL3 and utilized it to reclassify patients carrying a VUS in the CUL3 gene. Comparative epigenomic analysis revealed similarities between NEDAUS and several other rare genetic neurodevelopmental disorders with previously identified episignatures, highlighting the broader implication of our findings. In addition, we preformed genotype-phenotype correlation studies to explain the variety in clinical presentation between the cases. We discovered a highly accurate DNAm episignature serving as a robust diagnostic biomarker for NEDAUS. Furthermore, we broadened the phenotypic spectrum by identifying twenty new individuals and confirming five previously reported cases of NEDAUS.

Pathogenicity and sub-lethal activity of orally administered entomopathogenic fungi against two adult mosquito species, Aedes aegypti (Diptera: Culicidae) and Anopheles stephensi (Diptera: Culicidae)

Entomopathogenic fungi (EPF) are known for their efficacy in controlling adult mosquito populations by penetrating through their cuticle. However, the effect of oral administration of EPF on the biological parameters of Aedes aegypti and Anopheles stephensi remains largely unexplored. This study aimed to assess the effect of orally administrated EPF isolates on the survival, feeding behavior, fecundity, fertility, follicle development and host-searching behavior in response to yeast-generated CO2 of Ae. aegypti and An. stephensi. An initial screening of 50 isolates involved exposure of adult Ae. aegypti and An. stephensi by integument inoculation. Subsequently, the entomopathogenic effect of the five highly virulent isolates was confirmed through oral administration revealing Beauveria pseudobassiana 42–51 as a potent mosquito killer. B. pseudobassiana 42–51 was administered orally to evaluate sub-lethal effects. The results showed a 63 % and 43 % reduction in blood feeding of Ae. aegypti and An. stephensi, respectively. Furthermore, a decrease in egg hatching rate was observed, with a reduction of 83% for Ae. aegypti and 74% for An. stephensi on the seventh day following fungal administration, showing decreased hatchability in both species. Poor and abnormal follicle development was observed in both mosquito species. Also, the host-searching behavior was evaluated by attraction to CO2 utilizing a Y-tube olfactometer. A tendency of reduction in the attraction rate towards the odor was observed three days post-fungal administration. These findings underscore the significant impact of oral administration of B. pseudobassiana 42–51 on mosquitoes, highlighting not only its lethal effects but also sub lethal impacts on their biology. Moreover, this fungus may exhibit the potential to simultaneously control both mosquito species and serve as a biocontrol agent for the management of vector-borne diseases.

CHILDREN WITH THIS DISEASE AND THEIR EPIDEMIOLOGY, ETIOLOGY, PREVENTION, TREATMENT

Congenital cleft lip, alveolar process and cleft palate are among the most difficult deformities of the maxillofacial region, the number of children with such deformities is 1 per 1000 newborns and continues to grow [3, 4, 13, 18]. Treatment and rehabilitation of such patients is an urgent problem due to abnormal facial development and secondary deformities, speech and chewing disorders, a long recovery period and the need for social adaptation of the child [8]. Modern literature describes the treatment of children with complications of cleft lip and palate, and there is an opinion about the need for an integrated approach [11, 19]. Children with this disease can receive full-fledged rehabilitation and social adaptation in specialized medical centers [7, 14]. The aim of the work is to demonstrate the effectiveness of interaction between orthodontists and maxillofacial surgeons on the example of a clinical case of complex rehabilitation of a patient with congenital cleft of the left upper lip, alveolar process and cleft palate.

Binding of PtoRAP2.12 to demethylated and accessible chromatin regions in the PtoGntK promoter stimulates growth of poplar.

DNA methylation is an essential epigenetic modification for gene regulation in plant growth and development. However, the precise mechanisms of DNA methylation remain poorly understood, especially in woody plants. We employed whole-genome bisulfite sequencing (WGBS), assays for transposase-accessible chromatin using sequencing (ATAC-seq), and RNA-Seq to investigate epigenetic regulatory relationships in Populus tomentosa treated with DNA methylation inhibitor 5-azacitidine. Expression-quantitative trait methylation analysis (eQTM), epigenome-wide association study (EWAS), and joint linkage-linkage disequilibrium mapping were used to explore the epigenetic regulatory genes, and using CRISPR/Cas9 to identify the role of candidate genes. Plant developmental abnormalities occurred when DNA methylation levels were substantially reduced. DNA methylation regulated 112 expressed genes via chromatin accessibility, of which 61 genes were significantly influenced by DNA methylation variation at the population level. One DNA methylation-regulated gene, PtoGntK, was located in a major quantitative trait locus (QTL) for poplar growth. Overexpression and CRISPR/Cas9 of PtoGntK revealed it affected poplar height and stem diameter. The PtoRAP2.12 was found to bind to the demethylated accessible region in the PtoGntK promoter, thereby promoting growth in poplar. This study identified key genes with epigenetic regulation for plant growth and provides insights into epigenetic regulation mechanisms in woody plants.

Categorical classification of skin cancer using a weighted ensemble of transfer learning with test time augmentation

Skin cancer is the abnormal development of cells on the surface of the skin and is one of the most fatal diseases in humans. It usually appears in locations that are exposed to the sun, but can also appear in areas that are not regularly exposed to the sun. Due to the striking similarities between benign and malignant lesions, skin cancer detection remains a problem, even for expert dermatologists. Considering the inability of dermatologists to diagnose skin cancer accurately, a convolutional neural network (CNN) approach was used for skin cancer diagnosis. However, the CNN model requires a significant number of image datasets for better performance; thus, image augmentation and transfer learning techniques have been used in this study to boost the number of images and the performance of the model, because there are a limited number of medical images. This study proposes an ensemble transfer-learning-based model that can efficiently classify skin lesions into one of seven categories to aid dermatologists in skin cancer detection: (i) actinic keratoses, (ii) basal cell carcinoma, (iii) benign keratosis, (iv) dermatofibroma, (v) melanocytic nevi, (vi) melanoma, and (vii) vascular skin lesions. Five transfer learning models were used as the basis of the ensemble: MobileNet, EfficientNetV2B2, Xception, ResNext101, and DenseNet201. In addition to the stratified 10-fold cross-validation, the results of each individual model were fused to achieve greater classification accuracy. An annealing learning rate scheduler and test-time augmentation (TTA) were also used to increase the performance of the model during the training and testing stages. A total of 10,015 publicly available dermoscopy images from the HAM10000 (Human Against Machine) dataset, which contained samples from the seven common skin lesion categories, were used to train and evaluate the models. The proposed technique attained 94.49% accuracy on the dataset. These results suggest that this strategy can be useful for improving the accuracy of skin cancer classification. However, the weighted average of f1-score, recall, and precision were obtained to be 94.68%, 94.49%, and 95.07%, respectively.

Cerebral palsy: potential risk factors and functional status among children under three years, a case-control study in northwest Iran

BackgroundCerebral palsy (CP) is one of the most common motor-postural disorders in childhood. It occurs due to impairment in the developing brain—before, during, or after birth—and has a significant burden on the public health system. This study aimed to investigate the potential risk factors and detect the associated CP-related disorders.MethodsThis case-control study was conducted on 46 children with CP and 175 matched healthy children less than three years old who referred to the Children’s Hospital, Tabriz, Iran in 2022. Then, a checklist related to the mother’s medical history during current and previous pregnancies, a questionnaire related to perinatal factors of the newborn, types of CP, concurrent disorders, the Gross Motor Function Classification System (GMFCS), and Age and Stage Questionaire (ASQ) were completed. Data was analyzed using Statistical Package for the Social Sciences) SPSS(-21 software by descriptive and analytical statistics consisted of Chi-square, Independent t-test, and Binary logistic regression.ResultsFinally, 35 children with CP and 122 healthy children completed the study and were analyzed. The mean (standard deviation: SD) age of children in the CP group was 15.3 (6.2) and in the healthy group was 14.4 (6.6) months (p = 0.635). Spastic CP (82.9%) was the common type, and the most common prevailing form of the involved limb was quadriplegia (54.3%). The severity of the functional disorder in 39.3% of CP cases was at levels 4 and 5 (severe form). The most prevalent comorbidities were inability to walk (31.4%), speech delay (22.9%), epilepsy (11.4), and strabismus (8.6%). Children with CP had abnormal development in gross motor (82.9%), problem-solving (68.6%), personal-social (65.7%), fine motor (60%), and communication (54.3%). Moreover, duration of pregnancy (p = 0.023), birth weight lower than 2500 g (p = 0.002), problems in the current pregnancy [adjusted odds ratio (aOR) [95% CI]: 3.06 (1.87 to 8.54); p = 0.013] and problems in previous pregnancy ([aOR (95% CI): 4.8 (1.6 to 14.2); p = 0.005) were potential risk factors.ConclusionDue to accompanying movement, vision, and speech problems, especially high developmental disorders in children with CP, necessary measures to prevent the identified risk factors are very important.

Minimally invasive intervention for gynecomastia excision: two case reports

Gynecomastia is characterized by abnormal and excessive development of breast tissue in male patients. Depending on the volume of the breasts and the amount of excess skin, it may be unilateral or bilateral. Surgery is considered the standard of care, with several techniques documented, including different types of incisions made in the periareolar or intra-areolar skin. The most common surgical technique is conventional open surgery, which utilizes a semicircular inferior periareolar incision. To achieve superior aesthetic outcomes, various alternatives to open surgery have been proposed, including vacuum-assisted excision, endoscopic mastectomy, and liposuction Herein, we present two cases involving male patients, aged 29 and 24, who reported bilateral breast enlargement. We used the same incision for both liposuction and glandular excision. Our patients underwent combined liposuction on two planes: subcutaneous and subglandular, accompanied by sharp parenchymal excision. These small incisions, measuring 1–1.5 cm, are discreetly placed within the inframammary fold across the breast width. The patients experienced an uneventful recovery without any complications.

Novel association of LBX1 mutation with tetralogy of Fallot and hypertrophic cardiomyopathy: implications for cardiac development.

Tetralogy of Fallot (TOF) and hypertrophic cardiomyopathy (HCM) are common types of congenital heart disease with unique pathophysiologic features. Mutations in LBX1, a key regulator of muscle precursor cell migration, may disrupt these critical developmental processes, resulting in severe developmental abnormalities. This case reports on a 4-year-old girl diagnosed with both TOF and HCM. Genetic analysis revealed iUPI-F (uniparental disomy) on the entire chromosome 10, with a c.808G > A (p. Glu270Lys) pure mutation in the LBX1. This patient exhibited both TOF and HCM with mutations in the LBX1 gene, suggesting a potentially novel genetic link. This case study emphasizes the need for further studies on the function of the LBX1 gene in cardiac development and its potential impact on TOF and HCM.

First detection of fungal diversity associated with Prunus salicina Lindl malformation syndrome

The Chinese deciduous fruit Prunus salicina Lindl is loved by people because of its distinctive flavor and significant industrial worth. This study presents the first report of abnormal leaf bud in Prunus salicina Lindl. Malformation of Prunus salicina Lindl leaf buds leads to abnormal development and growth, causing deformities and a decrease in fruit yield. Identifying the underlying causes and causative pathogens is essential for effective disease management. In this experiment, we observed the Malformation Syndrome in Prunus salicina Lindl and used the internal transcribed spacer (ITS) to compare fungal diversity between malformed and healthy leaf buds. These results show a higher level of fungal diversity in diseased leaf buds. Alternaria, Curvibasidium, Symmetrospora, Fonsecazyma, and other genera among the identified fungi are suspected to induce the malformations. Potential contributors to these malformations include Endophyte-plant_Pathogen and Plant_pathogen-Undefined_saprotroph. These findings provide valuable insights for further research on the etiology of plum bud diseases, identifying potential pathogens, and formulating control strategies.

Floral Developmental Morphology and Biochemical Characteristics of Male Sterile Mutants of Lagerstroemia indica.

Male sterility is a common phenomenon in higher plants and often plays an important role in the selection of superior offspring. 'Xiang Yun' is a mutant of Lagerstroemia indica that does not bear fruit after flowering, and its flowering period is significantly longer than that of normal L. indica. To explore the timing and molecular mechanisms of sterility in 'Xiang Yun', this study determined the period of sterility through anatomical observation and compared the content of nutrients and the activity of antioxidative enzymes at different stages of flower development. Finally, sequence alignment and qPCR were used to analyze the differences in pollen development genes between 'Xiang Yun' and 'Hong Ye'. The results showed that the anthers of 'Xiang Yun' dispersed pollen normally, but the pollen grains could not germinate normally. Observations with scanning electron microscopy revealed that the pollen grains were uneven in size and shriveled in shape. Further observation of anther sections found that abnormal development of the microspores began at the S2 stage, with the callose wall between microspores of 'Xiang Yun' being thicker than that of 'Hong Ye'. In addition, during the flower development of 'Xiang Yun', the contents of soluble sugar, soluble protein, free proline, and triglycerides were deficient to varying degrees, and the activities of POD, SOD, and MDA were lower. Sequence alignment and qPCR showed that there were several mutations in EFD1, TPD1, and DEX1 of 'Xiang Yun' compared with 'Hong Ye', and the expression levels of these genes were abnormally elevated in the later stages of development. Our results clarified the timing and phenotype of male sterility in 'Xiang Yun'. This provides solid and valuable information for further research on the molecular mechanism of sterility in 'Xiang Yun' and the genetic breeding of crape myrtle.

Reduced Sox7 contributes to abnormal valve development resulting in congenital aortic stenosis

Abstract Background Abnormal valve development is the most common congenital heart malformation. During valve remodeling, abnormal changes in valve cell proliferation, apoptosis, and extracellular matrix synthesis affect valve development, resulting in malformations. The molecular mechanisms underlying pathophysiology of aortic stenos is remain unclear. Purpose We would like to explore how Sox7 is involved in aortic valve development. Methods and Results We proved Sox7 was mainly expressed in endocardial and mesenchymal cells of aortic valves by immunofluorescence staining determined by at different stages of mice (E10.5～8 weeks) and human embryos and RNA-seq of E9.5 mouse embryonic hearts. We constructed a conditional Sox7 floxed allele in endothelial cells using an endocardial specific Cre. Echocardiography data showed that Nfat-KO mice had increased blood velocity, pressure gradient across aortic valves, left ventricular mass and dilated aortic roots. Then, HE and Sirius red staining to examine histological changes in aortic valves of Nfat-KO mice were performed, and we observed a remarkable increase in the size and increased staining of fibrotic cells in aortic valves of KO mice. Next, we collected embryonic hearts of Sox7 CNC-specific knockout mice (WNT1-KO) and controls at E16.5. According to HE staining results and echocardiography analysis, there was no difference in aortic valves between WNT1-KO mice and controls. Meanwhile, we collected Nfat-KO mice and control embryos at E11.5 days. HE staining results showed that EndMT process was not impaired. Interestingly, leaflets and cusps of Nfat-KO mice showed significantly augmented proliferation levels, decreased apoptosis levels, and calcium deposition in fibrin layer. A significant decrease in MMP9 levels were observed in both mRNA and protein levels. Co-transfection of Sox7-expressing vector and MMP9 luciferase in MEEC suggested that Sox7 significantly activated MMP9. We used adenovirus to overexpress Sox7 in valvular interstitial cells. Compared with that in control group, the Sox7-overexpression group increased protein level of MMP9 and cleaved caspase-3, and increased Tunel-positive rate and lower Ki-67 positive rate. Finally, we detected expression of Sox7 protein in human fetal aortic valves derived from patients with aortic stenosis using immunofluorescence. The results demonstrated that the number of Sox7 positive mesenchymal cells in human fetal aortic valves of patients was significantly lower than that in control group. Conclusion We demonstrated that targeted inactivation of Sox7 in the endocardium of mice affects valve development and leads to aortic stenosis. Mechanistically, no influence of Sox7 on the EndMT process of the OFT cushion. Moreover, CNC-derived Sox7 was not involved in aortic valve development. Interestingly, we found that Sox7 regulated ECM remodeling through matrix MMP9 and Sox7 had an impact on apoptosis, proliferation, and calcification.

Anemia in patients with chronic kidney disease and its association with cardiac abnormalities

Abstract Introduction Chronic kidney disease (CKD) is a pathology characterized by multisystemic comorbidities, predominantly associated with cardiovascular disease and anemia. However, the precise association between the degree of anemia and the development of cardiac abnormalities in patients with CKD undergoing hemodialysis remains unclear. Purpose To determine the association between the degree of anemia and cardiac abnormalities in patients with CKD receiving hemodialysis treatment. Methods A cross-sectional multicenter study that included individuals with CKD undergoing hemodialysis was conducted. Electronic medical records containing information regarding medical conditions and pertinent laboratory parameters was collected, and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the associated between the degree of anemia and echocardiographic parameters, with significant set at p &amp;lt;0.05. Results Ninety-nine individuals were included, with a median age of 48 years. The population was categorized based on hemoglobin (Hb) levels into non/mild anemia (Hb &amp;gt;10 mg/dL) and moderate/severe anemia (Hb &amp;lt;9.9 mg/dL) groups (table). Significant differences were observed in left ventricle (LV) posterior wall thickness (10mm in non/mild vs. 11mm in moderate/severe, p&amp;lt;0.015), left atrial (LA) volume (34 mL/m2 in non/mild vs. 39 mL/m2 in moderate/severe, p&amp;lt;0.007) and left ventricular ejection fraction (LVEF) (59% in non/mild vs. 55% in moderate/severe, p&amp;lt;0.025). Negative correlations (figure) were observed between Hb levels and LV mass index (r= -0.21, p= 0.03) and pulmonary artery systolic pressure (PASP)(r= -0.27, p= 0.006). Conclusion The degree of anemia demonstrated an association with cardiac abnormalities, as evidenced by alterations in echocardiographic parameters such as LVEF, LA volume and PSAP. This study underscores the importance of further prospective investigations to enhance early identification and stratification of anemia in patients with CKD aiming to mitigate further cardiac complications.Clinical demographics tableScatter plots with correlation graphs