Organ Defects Research Articles

Dental-Pulp Stem Cells as a Therapeutic Strategy for Ischemic Stroke.

Regenerative medicine aims to restore human functions by regenerating organs and tissues using stem cells or living tissues for the treatment of organ and tissue defects or dysfunction. Clinical trials investigating the treatment of cerebral infarction using mesenchymal stem cells, a type of somatic stem cell therapy, are underway. The development and production of regenerative medicines using somatic stem cells is expected to contribute to the treatment of cerebral infarction, a central nervous system disease for which there is no effective treatment. Numerous experimental studies have shown that cellular therapy, including the use of human dental pulp stem cells, is an attractive strategy for patients with ischemic brain injury. This review describes the basic research, therapeutic mechanism, clinical trials, and future prospects for dental pulp stem cell therapy, which is being investigated in Japan in first-in-human clinical trials for the treatment of patients with acute cerebral ischemia.

ENKD1 promotes CP110 removal through competing with CEP97 to initiate ciliogenesis.

Despite the importance of cilia in cell signaling and motility, the molecular mechanisms regulating cilium formation remain incompletely understood. Herein, we characterize enkurin domain-containing protein 1 (ENKD1) as a novel centrosomal protein that mediates the removal of centriolar coiled-coil protein 110 (CP110) from the mother centriole to promote ciliogenesis. We show that Enkd1 knockout mice possess ciliogenesis defects in multiple organs. Super-resolution microscopy reveals that ENKD1 is a stable component of the centrosome throughout the ciliogenesis process. Simultaneous knockdown of ENKD1 and CP110 significantly reverses the ciliogenesis defects induced by ENKD1 depletion. Protein interaction analysis shows that ENKD1 competes with centrosomal protein 97 (CEP97) in binding to CP110. Depletion of ENKD1 enhances the CP110-CEP97 interaction and detains CP110 at the mother centriole. These findings thus identify ENKD1 as a centrosomal protein and uncover a novel mechanism controlling CP110 removal from the mother centriole for the initiation of ciliogenesis.

Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies.

Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synthetic insecticides and is considered less harmful to beneficial insects, yet its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad antagonize its neuronal target, the nicotinic acetylcholine receptor subunit alpha 6 (nAChRα6), reducing the cholinergic response. We show that the nAChRα6 receptors are transported to lysosomes that become enlarged and increase in number upon low doses of spinosad treatment. Lysosomal dysfunction is associated with mitochondrial stress and elevated levels of reactive oxygen species (ROS) in the central nervous system where nAChRα6 is broadly expressed. ROS disturb lipid storage in metabolic tissues in an nAChRα6-dependent manner. Spinosad toxicity is ameliorated with the antioxidant N-acetylcysteine amide. Chronic exposure of adult virgin females to low doses of spinosad leads to mitochondrial defects, severe neurodegeneration, and blindness. These deleterious effects of low-dose exposures warrant rigorous investigation of its impacts on beneficial insects.

Organ defects of the Usp7K444R mutant mouse strain indicate the essential role of K63-polyubiquitinated Usp7 in organ formation

BackgroundK63-linked polyubiquitination of proteins have nonproteolytic functions and regulate the activity of many signal transduction pathways. USP7, a HIF1α deubiquitinase, undergoes K63-linked polyubiquitination under hypoxia. K63-polyubiquitinated USP7 serves as a scaffold to anchor HIF1α, CREBBP, the mediator complex, and the super elongation complex to enhance HIF1α-induced gene transcription. However, the physiological role of K63-polyubiquitinated USP7 remains unknown. MethodsUsing a Usp7K444R point mutation knock-in mouse strain, we performed immunohistochemistry and standard molecular biological methods to examine the organ defects of liver and kidney in this knock-in mouse strain. Mechanistic studies were performed by using deubiquitination, immunoprecipitation, and quantitative immunoprecipitations (qChIP) assays. ResultsWe observed multiple organ defects, including decreased liver and muscle weight, decreased tibia/fibula length, liver glycogen storage defect, and polycystic kidneys. The underlying mechanisms include the regulation of protein stability and/or modulation of transcriptional activation of several key factors, leading to decreased protein levels of Prr5l, Hnf4α, Cebpα, and Hnf1β. Repression of these crucial factors leads to the organ defects described above. ConclusionsK63-polyubiquitinated Usp7 plays an essential role in the development of multiple organs and illustrates the importance of the process of K63-linked polyubiquitination in regulating critical protein functions.

Aminoglycoside treatment alters hearing-related genes and depicts behavioral defects in Drosophila.

The hearing organ of Drosophila is present within the second segment of antennae. The hearing organ of Drosophila (Johnston's organ [JO]) shares much structural, developmental, and functional similarity with the vertebrate hearing organ (Organ of Corti). JO is evolving as a potential model system to examine the hearing-associated defects in vertebrates. In the vertebrates, aminoglycosides like gentamicin, kanamycin, and neomycin have been known to cause defects in the hearing organ. However, a complete mechanism of toxicity is not known. Taking the evolutionary conservation into account the current study aims to test various concentrations of aminoglycoside on the model organism, Drosophila melanogaster. The current study uses the oral route to check the toxicity of various aminoglycosides at different concentrations (50, 100, 150, 200, and 250 μg ml- 1 ). In Drosophila, many foreign particles enter the body through the gut via food. The aminoglycoside treated third instar larvae show defective crawling and sound avoidance behavior. The adult flies release lower amounts of acetylcholine esterase and higher amounts of reactive oxygen species than control untreated animals, accompanied by defective climbing and aggressive behavior. All these behavioral defects are further confirmed by the altered expression level of hearing genes such as nompC, inactive, nanchung, pyrexia. All the behavioral and genetic defects are reported as a readout of aminoglycoside toxicity.

The carboxyl-terminal region of SDCCAG8 comprises a functional module essential for cilia formation as well as organ development and homeostasis

In humans, ciliary dysfunction causes ciliopathies, which present as multiple organ defects, including developmental and sensory abnormalities. Sdccag8 is a centrosomal/basal body protein essential for proper cilia formation. Gene mutations in SDCCAG8 have been found in patients with ciliopathies manifesting a broad spectrum of symptoms, including hypogonadism. Among these mutations, several that are predicted to truncate the SDCCAG8 carboxyl (C) terminus are also associated with such symptoms; however, the underlying mechanisms are poorly understood. In the present study, we identified the Sdccag8 C-terminal region (Sdccag8-C) as a module that interacts with the ciliopathy proteins, Ick/Cilk1 and Mak, which were shown to be essential for the regulation of ciliary protein trafficking and cilia length in mammals in our previous studies. We found that Sdccag8-C is essential for Sdccag8 localization to centrosomes and cilia formation in cultured cells. We then generated a mouse mutant in which Sdccag8-C was truncated (Sdccag8ΔC/ΔC mice) using a CRISPR-mediated stop codon knock-in strategy. In Sdccag8ΔC/ΔC mice, we observed abnormalities in cilia formation and ciliopathy-like organ phenotypes, including cleft palate, polydactyly, retinal degeneration, and cystic kidney, which partially overlapped with those previously observed in Ick- and Mak-deficient mice. Furthermore, Sdccag8ΔC/ΔC mice exhibited a defect in spermatogenesis, which was a previously uncharacterized phenotype of Sdccag8 dysfunction. Together, these results shed light on the molecular and pathological mechanisms underlying ciliopathies observed in patients with SDCCAG8 mutations and may advance our understanding of protein–protein interaction networks involved in cilia development.

К вопросу дифференциальной диагностики, классификации и дифференцированного лечения гидроцефалии и гидроцефальных синдромов у детей

Целью исследования было определение соотношения двух основных механизмов гидроцефалии и гидроцефальных синдромов — внутричерепной гипертензии и церебральной атрофии (гипотрофии) в структуре различных болезненных состояний у детей. Методом комплексного динамического определения структурно-органического внутричерепного дефекта у детей проведена дифференциальная диагностика двух основных патогенетических типов гидроцефалии и гидроцефальных синдромов у 483 детей, пролеченных в отделении для детей с поражением центральной нервной системы и психики в 2011–2014 годах. В результате исследования установлено значительное преобладание церебральной гипотрофии. Ликворная гипертензия была достоверной причиной расширения ликворных пространств только в 5,1 % случаев у больных с детским церебральным параличом в 19 % случаев в группе детей с последствиями пре-, перинатальной патологии нервной системы.Обсуждение результатов исследования позволило определить пути совершенствования методов диагностики и классификации гидроцефалии и гидроцефальных синдромов для проведения их адекватной дифференцированной терапии.Выводы. Учитывая вторичный характер расширения ликворных пространств при гипотрофии мозга предложено использовать термин «гипотрофически-гидроцефальный синдром» в структуре диагноза первичного заболевания, вызвавшего гипотрофию головного мозга.

Aorto-digestive fistula: a rare cause of gastrointestinal bleeding

Aorto-digestive fistulas are a rare but extremely dangerous cause of massive gastrointestinal bleeding with a high risk of death. The aim of the review was to examine the modern principles of aorto-digestive fistula diagnosis and optimal treatment modalities.Scientific publications and their reference lists were searched on PubMed database, Google Scholar and Russian Science Citation Index. Articles relevant to the topic, published over the past 25 years (1996-2021), were included and they were searched and categorised using the following key words: ‘gastrointestinal bleeding’, ‘aorto-digestive fistulas’, ‘diagnosis’ and ‘treatment’. Inclusion criteria were limited to gastrointestinal bleeding associated with aorto-digestive fistulas.Patients with aortic aneurysms or those who have undergone prosthetics should have increased alertness regarding the formation of aorto-digestive fistulas. With a presence of gastrointestinal bleeding and exclusion of other sources based on multispiral computed tomography data with intravenous bolus contrast enhancement, this will allow for quick verification of the diagnosis and also enable timely medical measures to be taken. In an emergency situation, to achieve rapid hemostasis in unstable patients, endovascular aortic replacement is most justified. Open reconstruction of the aorta in situ with simultaneous elimination of the hollow organ defect and sanitation of fistula-associated foci of infection should be considered as a radical intervention for aorto-digestive fistulas.Received 19 May 2021. Revised 7 July 2021. Accepted 9 July 2021.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Contribution of the authors: The authors contributed equally to this article.

A VIN3-like Protein OsVIL1 Is Involved in Grain Yield and Biomass in Rice.

In chromatin remodeling, the post-translational modification of histone proteins is mediated by multimeric protein complexes. VERNALIZATION INSENSITIVE3 (VIN3) forms a complex with Polycomb Repressive Complex 2 (PRC2), which mediates the trimethylation of H3K27 to repress target gene expression. In rice, four genes (OsVIL1-OsVIL4) encoding the VIN3-like proteins are expressed ubiquitously in various tissues. Null mutants of osvil2 display pleiotropic phenotypes such as altered flowering time, floral organ defects, and reduced tiller size. In contrast, osvil1 mutants did not show significant phenotypes except in fertilization compared with the wild type. However, transgenic plants overexpressing OsVIL1 showed phenotypes of increased biomass and grain yield. Cross-sections of the basal region of elongating stems revealed that the increased biomass was mediated by inducing cell proliferation in the meristem. Chromatin immunoprecipitation assay indicated that OsVIL1 repressed expression of cytokinin oxidase/dehydrogenase gene (OsCKX2) by binding to the promoter and genic regions of OsCKX2. We also observed that OsVIL1 modified the levels of H3K27me3 in the OsCKX2 chromatin. Because OsCKX2 encodes an enzyme that degrades active cytokinin, we conclude that OsVIL1 functions in the regulation of endogenous active cytokinin levels, thereby increasing plant height and productivity.

SLL1-ZH Regulates Spikelets Architecture and Grain Yield in Rice

The spikelet developmental processes that control structure and floral organ identity play critical roles in rice grain yield formation. In this study, we characterized a novel rice mutant, SLL1-ZH, which exhibits a variety of defective agronomic characters, including semi-dwarf, rolling leaf, deformed panicles, and reduced grains production. Morphological analysis also revealed that the SLL1-ZH mutant shows numerous defects of floral organs, such as cracked glumes, hooked and thin lemmas, shrunken but thickened paleas, an indeterminate number of stamens and stigmas, and heterotopic ovaries. Map-based cloning identified a single nucleotide substitution (C to G) in the first exon of LOC_Os09g23200 that is responsible for the SLL1-ZH phenotype. In addition, qPCR analysis showed a significant change in the relative expression of SLL1-ZH in the mutant during inflorescence differentiation and in the different floral organs. Transcription of rice floral organ development-related factors also changed significantly in the mutant. Therefore, our results suggested that SLL1-ZH plays a great role in plant growth, spikelet development, and grain yield in rice.

Abstract 13259: IRX5 Transcription Factor Cooperate With TBX5/GATA4/NKX2-5 Complex to Regulate Several Human Cardiomyocyte Functions

Introduction: The transcription factor (TF) Iroquois homeobox 5 (Irx5) is a key patterning and differentiation regulator. In humans, IRX5 regulates the expression of the main cardiac sodium ion channel gene, SCN5A . However, its global mechanistic role in human cardiomyocytes is still to be fully understood. Hamamy syndrome patients, carrying IRX5 mutations, have defects in various organs including the heart and the limbs. Interestingly, heart and limbs defects are also found in Holt-Oram syndrome patients ( TBX5 mutations), suggesting a functional link between TBX5 and IRX5. Moreover, a cooperation of TBX5 with GATA4 and NKX2-5 in cardiac development and functions has already been shown. Hypothesis: We hypothesized that IRX5 may cooperate with the TF complex TBX5/GATA4/NKX2-5 to regulate key cardiac functions in humans. Methods & Results: First, immunoprecipitations in HEK293 cells showed that IRX5 can bind to TBX5, GATA4 and NKX2-5, individually and together as a complex. Using five truncated forms of IRX5 protein, its homeodomain was identified as being the essential protein region for these interactions. Second, we showed by luciferase assays, that each combination of these TFs impacted differently SCN5A expression: e.g. by itself, NKX2-5 has a strong activator effect (increased activity by 10 fold vs . no TF) that is potentialized by IRX5 (12 fold vs . no TF) but inhibited by TBX5 (8 fold vs . no TF). Third, genes bound by IRX5 (n=2253) were identified by ChIP-Seq on cardiomyocytes derived from induced pluripotent stem cells generated from 2 healthy individuals. Analyzing published ChIP-Seq datasets for TBX5, GATA4 or NKX2-5 in the same cellular model, we identified 2990 genes that were bound by these 3 TFs, and associated with cardiac biological pathways, such as muscle contraction. Among these genes, 848 were also bound by IRX5 and were associated with the function of electrical activity and with the fibrosis signaling, suggesting a specific role for IRX5 in these cardiac processes. Conclusions: Overall, our data show new physical and functional interactions between IRX5 and 3 key cardiac TFs (TBX5, GATA4 and NKX2-5), and suggest an unexpected regulatory role for IRX5 in specific human heart functions.

The clinical aspects of peritonitis developing after cystectomy

Background. Surgical morbidities of radical cystectomy, which are, as a rule, complicated intraabdominal infections, appear to be the main causes of repeated surgeries and fatal outcomes. The elimination of the infection Indus and an-timicrobic therapy are the currently accepted standard of treatment for postoperative peritonitis in cancer urology, as well as in general surgery hospital.Objective: defining the most reasonable option of surgical aid for peritonitis developing after cystectomy.Materials and methods. In the time period from 2000 through 2014, 58 cancer patients with postoperative peritonitis developing after cystectomy received indoor treatment at N.N. Alexandrov Republican Research and Practical Center for Oncology and Medical Radiology. Their mean age was 64.9 years, the range 44-90 years, 53 (91.4 %) of them being male. Primary urinary bladder cancer was present in 51 (87.9 %) patients. Peritoneal infection was microbiologically verified in 57 (98.3 %) patients. Each case of fatal outcome was associated with ineffective treatment of peritonitis. Depending on the intraoperative findings (presence or absence of a hollow organ defect) and the surgical approach undertaken (obstructive resection or operation maintaining the continuity of the intestinal and/or urinary tract), the patients were stratified into three groups: group 1 (n = 28), group 2 (n = 20) and group 3 (n = 10). There were no significant differences in the basic parameters specifying peritoneal infection severity between the patients of groups 1 and 2 vs group 3 (p >0.05).Results. Overall mortality amounted to 25.9 %, 15 patients died. Among the 28 (48.3 %) patients (group 1) who underwent obstructive elimination of the peritonitis focus by means of urointestinal reservoir ablation, resection of small or large intestine with ileo- or colostomy, 6 patients died, mortality 21.4 %. In the 10 (17.2 %) patients (group 3) who succeeded in preserving the urinary conduit or continuity of the bowels by anastomosis defect closure, resection of enteroentero-anastomosis or urointestinal reservoir with repeated anastomosing or defect closure, mortality was higher (60 %) (p = 0.045); 6 patients died.Conclusion. The most effective option of surgical treatment of postoperative peritonitis developing after cystectomy is obstructive reoperation on the bowels and urinary tracts: compared with the intervention consisting in preserving the urinary conduit and/or continuity of the intestinal tract, this type of surgery caused a 2.8-fold lower mortality.

Disruptive NADSYN1 Variants Implicated in Congenital Vertebral Malformations.

Genetic perturbations in nicotinamide adenine dinucleotide de novo (NAD) synthesis pathway predispose individuals to congenital birth defects. The NADSYN1 encodes the final enzyme in the de novo NAD synthesis pathway and, therefore, plays an important role in NAD metabolism and organ embryogenesis. Biallelic mutations in the NADSYN1 gene have been reported to be causative of congenital organ defects known as VCRL syndrome (Vertebral-Cardiac-Renal-Limb syndrome). Here, we analyzed the genetic variants in NADSYN1 in an exome-sequenced cohort consisting of patients with congenital vertebral malformations (CVMs). A total number of eight variants in NADSYN1, including two truncating variants and six missense variants, were identified in nine unrelated patients. All enrolled patients presented multiple organ defects, with the involvement of either the heart, kidney, limbs, or liver, as well as intraspinal deformities. An in vitro assay using COS-7 cells demonstrated either significantly reduced protein levels or disrupted enzymatic activity of the identified variants. Our findings demonstrated that functional variants in NADSYN1 were involved in the complex genetic etiology of CVMs and provided further evidence for the causative NADSYN1 variants in congenital NAD Deficiency Disorder.

Dental Pulp Stem Cells Derived From Adult Human Third Molar Tooth: A Brief Review.

The fields of regenerative medicine and stem cell-based tissue engineering have the potential of treating numerous tissue and organ defects. The use of adult stem cells is of particular interest when it comes to dynamic applications in translational medicine. Recently, dental pulp stem cells (DPSCs) have been traced in third molars of adult humans. DPSCs have been isolated and characterized by several groups. DPSCs have promising characteristics including self-renewal capacity, rapid proliferation, colony formation, multi-lineage differentiation, and pluripotent gene expression profile. Nevertheless, genotypic, and phenotypic heterogeneities have been reported for DPSCs subpopulations which may influence their therapeutic potentials. The underlying causes of DPSCs’ heterogeneity remain poorly understood; however, their heterogeneity emerges as a consequence of an interplay between intrinsic and extrinsic cellular factors. The main objective of the manuscript is to review the current literature related to the human DPSCs derived from the third molar, with a focus on their physiological properties, isolation procedures, culture conditions, self-renewal, proliferation, lineage differentiation capacities and their prospective advances use in pre-clinical and clinical applications.

The influence of the <i>TBX6</i> gene on the development of congenital spinal deformities in children

BACKGROUND: Congenital deformities of the spine are a group of serious congenital defects of the vertebrae, which can manifest themselves in the clinical picture as an isolated pathology of the axial musculoskeletal system, and are associated with congenital defects of internal organs and other systems. Recently, the TBX6 gene has been identified as the genetic cause of congenital scoliosis in about 11% of cases. This subtype of scoliosis is classified as TBX6-associated congenital scoliosis. The TBX6-associated congenital scoliosis phenotype is characterized by butterfly-shaped vertebrae and hemivertebrae in the lower thoracic and lumbar regions without pronounced malformations of the spinal cord.
 AIM: Our aim is to study and evaluate data from foreign and domestic scientific publications devoted to the study of the candidate gene for congenital scoliosis TBX6.
 MATERIALS AND METHODS: The following databases of scientific publications such as PubMed, Cochrane Library, Web of Science, SCOPUS, MEDLINE, e-Library, Cyberleninka were used to write this review. The inclusion criteria were systematic reviews, meta-analyses, multicenter studies, controlled cohort studies, uncontrolled cohort studies of patients with congenital spinal deformities. The exclusion criteria were clinical cases, observations, conference proceedings, congenital scoliosis in genetic syndromes, congenital scoliosis associated with defects of the nervous system.
 RESULTS: In order to achieve this goal, 70 scientific publications were studied relating to the data analysis of the candidate gene for congenital scoliosis TBX6. Among 49 publications that were identified, 2 were domestics, and the rest were foreign publications. These studies provided information on the molecular analysis of genes that cause congenital spinal deformities in humans and animals.
 CONCLUSIONS: An analysis of the published research work on this topic indicates the presence of a significant effect of mutations in the TBX6 gene, leading to the appearance of congenital scoliosis.
 Advances in elucidating the genetic contribution to the development of congenital spinal deformities and the molecular etiology of clinical phenotypes may uncover the opportunities for further refinement of the classification of signs of congenital scoliosis in accordance with the underlying genetic etiology.

Growth defects of organic crystals: A review

During the growth of organic crystals, crystal defects can be formed. Microscopic defects, which include point, line, and planar defects, appearing as vacancies, growth dislocations, striations, and others, play an important role in the mechanical properties, optical properties, and electrical conductivity of organic crystals. In addition, macroscopic defects, such as fluid inclusions and cavities, may cause toxicity during crystal dehydration and degradation while favorable cavity defects can satisfy certain functions. Herein, this paper summarizes the growth defects of organic crystals from four perspectives; formation mechanism, characterization methods, control methods, and applications. We conclude three kinds of formation mechanism which are related to diffusion of solute molecules, impurities participating in the crystal growth, and structure of solute molecules respectively. Next, the characterization methods are exhibited from the perspectives of microscopy, spectroscopy, and others for different research areas. Then, we offer some control methods of defects which include adjustment of crystallization operation parameters, assistant of ultrasound and additives, irradiation, and ion implantation. As for applications, organic crystal defects have application potential in the fields of pharmacy and materials, for example, nonlinear optical materials, energetic materials, and semiconductor materials. Finally, we put forward the future outlooks on the growth defects of organic crystals.

Loss of Ift74 Leads to Slow Photoreceptor Degeneration and Ciliogenesis Defects in Zebrafish.

Cilia are microtubule-based structures projecting from the cell surface that perform diverse biological functions. Ciliary defects can cause a wide range of genetic disorders known collectively as ciliopathies. Intraflagellar transport (IFT) proteins are essential for the assembly and maintenance of cilia by transporting proteins along the axoneme. Here, we report a lack of Ift74, a core IFT-B protein, leading to ciliogenesis defects in multiple organs during early zebrafish development. Unlike rapid photoreceptor cell death in other ift-b mutants, the photoreceptors of ift74 mutants exhibited a slow degeneration process. Further experiments demonstrated that the connecting cilia of ift74 mutants were initially formed but failed to maintain, which resulted in slow opsin transport efficiency and eventually led to photoreceptor cell death. We also showed that the large amount of maternal ift74 transcripts deposited in zebrafish eggs account for the main reason of slow photoreceptor degeneration in the mutants. Together, our data suggested Ift74 is critical for ciliogenesis and that Ift proteins play variable roles in different types of cilia during early zebrafish development. To our knowledge, this is the first study to show ift-b mutant that displays slow photoreceptor degeneration in zebrafish.

The role of sonic hedgehog homologue signal pathway in hypospadias aetiology

Hypospadias is one of the most common congenital anomalies of the male genitalia. Sonic hedgehog homologue (SHH) signalling pathway is believed to be involved in the development of the male genital system. In this clinical prospective study, the role of the SHH pathway in hypospadias aetiology was investigated. In this study, 200 healthy children (boys without hypospadias, control group), 118 patients (boys with distal hypospadias) and 82 patients (boys with proximal hypospadias) of age 0-16 years were included. The expression of the genes suppressor of fused protein (SUFU), SHH, protein patched homologue (PTCH; PTCH1 and PTCH2), glioma-associated oncogene homologue (GLI; GLI1, GLI2, GLI3 and GLI4), smoothened, frizzled-class receptor (SMO) and serine/threonine-protein kinase 36 (STK36) that are involved in SHH pathway were investigated. Furthermore, polymorphism analyses of GLI2, SHH and PTCH1 genes were performed. The history of hypospadias in the first and second-degree relatives of the patients in boys with distal hypospadias and boys with proximal hypospadias was inquired. Ten patients in the boys with distal hypospadias and twenty patients in the boys with proximal hypospadias had a history of hypospadias in first or second-degree relatives (p<0.05). There was a significant decrease in mRNA expressions of SHH and PTCH1 genes in boys with proximal hypospadias compared to boys without hypospadias (p<0.05). Besides, a significant decrease in mRNA fold-change of GLI2 gene was detected in boys with both distal hypospadias and proximal hypospadias compared to boys without hypospadias (p<0.05). In contrast, there was no significant difference in the mRNA fold-changes of PTCH2, SUFU, GLI1, GLI3, GLI4, SMO and STK36 genes among the groups. Moreover, there were no significant differences in the frequencies of variant genotypes and alleles rs735557, rs12711538 and rs4848632 (GLI2 gene), rs104894049 (SHH gene) and rs41313327 (PTCH1 gene) (p>0.05). SHH expression is required for the growth and differentiation of the genital bulge. Developmental defects in the external genital organs were demonstrated in mice with SHH deletion. It has been demonstrated that SHH mainly plays a role in the formation of sinusoid morphology of the penis. In the present study, although SHH and PTCH gene expressions were found to be decreased only in the penile tissues of proximal hypospadias, GLI2 gene expression was decreased in penile tissues of boys with both distal hypospadias and boys with proximal hypospadias. Genes involved in the SHH pathway might play a role in the aetiology of hypospadias. Furthermore, there is a correlation between molecular defects in this pathway and severity of hypospadias.

Vascular and Lymphatic Malformations: Perspectives From Human and Vertebrate Studies.

Vascular malformations, affecting ≈1% to 1.5% of the population, comprise a spectrum of developmental patterning defects of capillaries, arteries, veins, and/or lymphatics. The majority of vascular malformations occur sporadically; however, inherited malformations exist as a part of complex congenital diseases. The malformations, ranging from birthmarks to life-threatening conditions, are present at birth, but may reveal signs and symptoms-including pain, bleeding, disfigurement, and functional defects of vital organs-in infancy, childhood, or adulthood. Vascular malformations often exhibit recurrent patterns at affected sites due to the lack of curative treatments. This review series provides a state-of-the-art assessment of vascular malformation research at basic, clinical, genetic, and translational levels.

Assessment of the quality of life of orthodontic and surgical patients. Analysis of the factors that motivate the initiation of treatment within the masticatory system

IntroductionAccording to Angle's classification, a correct bite should have, inter alia, the following regularities: the median line of the face should coincide with the line between the central incisors of the upper and lower arches, the lower incisors should be overlapped by the incisal edges of the upper incisors, the top of the canine in the upper arch is inserted between the lower canine and the tangent premolar, each tooth is in contact with two opposing teeth, adjacent teeth both in the upper and lower arch are in contact with each other. Any deviation from these rules may indicate the presence of a malocclusion. We can distinguish here, for example: posteroclusion, open bite, retrusive occlusion, protrusive occlusion, supraclusion bite. They seem to be important not only in terms of functionality, but also psychology. Research shows that the correction of mandibular prognathism increases the level of self-confidence and self-acceptance, which may improve the quality of life of patients.Purpose of researchThe aim of the study was to check the quality of life of orthodontic and surgical patients as well as what factors motivate these people to start treatment in the area of the masticatory system.Material and methods208 people aged 18 to 55 participated in the survey. They were both people with malocclusion and no malocclusion, who constituted the control group. The questionnaire was created on the basis of standardized OQLQ and OHIP-14 questionnaires. It also included questions about the factors that motivate to start treatment in the masticatory system.ResultsThe most common malocclusion among the respondents was progenia (58.8%), followed by retrogenia (34.3%), then open bite (4%) and posteroclusion (2.9%). According to the OHIP-14 form, statistically significant (p &lt;.0001) higher quality of life was seen in people without a masticatory organ defect, compared to people with the malocclusion. A statistically significant difference (p &lt;.0001) between people with present or recent malocclusion (M = 54.29, SD = 16.71) and people without malocclusion (M = 31.93, SD = 18.31) was also visible in the study with using the OQLQ questionnaire.ConclusionsA malocclusion worsens the comfort and quality of life.Incorrect bite, face and smile aesthetics as well as psychological aspects are the most important factors motivating to undertake surgical and orthodontic treatment.Bruxism and facial pain are not factors prompting the initiation of treatment of malocclusion.