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1.
BDJ Open ; 10(1): 67, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179553

RESUMEN

OBJECTIVES: This study compared the whitening effect, microhardness, and enamel surface alterations of over-the-counter (OTC) tooth bleaching products with those of a dentist-prescribed at-home bleaching agent. MATERIALS AND METHODS: The products available on a popular online marketplace were comprehensively searched and then rated using a specific formula. The effects of the lowest-rated OTC agent (LRA) and the highest-rated OTC agent (HRA) were compared with those of a dentist-prescribed bleaching agent (DPA) on the enamel of extracted human teeth. The bleaching efficacy, post-bleaching microhardness changes, and morphological alterations were assessed by spectrophotometric analysis, Vickers hardness testing, and scanning electron microscopy (SEM) respectively. Statistical analyses included one-way ANOVA and post hoc tests, maintaining a significance level of P < 0.05. RESULTS: The search of the online marketplace revealed 15 products. The LRA (Teeth Whitening Serum Gel, GEN, China) and the HRA (Bright White-Lovely Smile Premium Teeth Whitening strips, Ray of Smile, USA) were identified on the basis of their ranking. DPA resulted in significantly better tooth whitening than did LRA. The enamel microhardness was lower in the LRA treatment group (14.2%) than in the control and HRA treatment groups (8.84% and 7.26%, respectively). LRA also caused severe topographical alterations to the enamel. CONCLUSION: Compared with the poorly rated product, the dentist-prescribed tooth bleaching product resulted in greater colour improvement, less microhardness reduction, and surface changes. The highest-rated product was comparable with the dentist-prescribed agent in this study.

2.
Chemosphere ; 364: 143064, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39142396

RESUMEN

Lead poisoning in the recent times has caused serious health threats in the exposed human population. It is estimated that about 815 million people are exposed to lead poisoning worldwide and in India total 275 million children are exposed to blood lead contamination. The present study was carried outed in 6 districts of Bihar to know the extent of lead exposure in the children through their mother's breastmilk. The biological samples such as breastmilk, mother's urine, child's urine, and mother's blood samples were collected for quantitative lead estimation. Moreover, the selected household water sources (handpump) and the food consumed by the individuals-wheat, rice and potato samples were also collected for lead quantification. The study reveals that the breastmilk had high lead content in 92% of the samples (highest value 1309 µg/L), in blood presence of lead was observed in 87% studied samples (highest value 677.2 µg/L). In mother's urine the highest lead value was 4168 µg/L (62%) and in child's urine the highest value was 875.4 µg/L (62%) respectively of the studied samples. Moreover, in the studied food samples, wheat had lead content in 45% the studied samples (highest value 7910 µg/kg). In rice in 40% of the studied samples (highest value 6972 µg/kg) and in potato 90% of the studied samples (highest value = 13786 µg/kg) were found with elevated lead content respectively. The hazard quotient (HQ) and the cancer risk (CR) for lead contamination was very much higher in mothers followed by their children. The entire study indicated that lead exposure through food (wheat, rice and potato) has reached the mother's breastmilk and from their it has reached their child's body. This could cause serious hazards in the exposed children causing serious neurological damages, low IQ, low memory, and low mental growth in them. Therefore, a strategic action is required to control the present problem.

5.
Cureus ; 15(5): e39168, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37332408

RESUMEN

Bisphenol analogues are widely used in consumer products such as disposable dinnerware, canned food, personal care products, bottled beverages, and more, and dietary exposure is the main pathway. Bisphenol A is used to manufacture synthetic resins and commercial plastics in large quantities. According to epidemiological and animal studies, bisphenols disrupt the reproductive, immunological, and metabolic systems. These analogues are estrogenic like Bisphenol A, although human studies are limited. We did a thorough search of the literature on the toxicity of bisphenol on reproductive and endocrine systems in pregnancy, focusing particularly on human studies. Hence, we present a comprehensive literature review on this topic.​​​​​​​ During our literature search, three epidemiological studies and one human observational study demonstrated a substantial link between bisphenol toxicity and recurrent miscarriages.​​​​​​​ The aforementioned research shows that bisphenol may harm pregnancy and cause miscarriages. We believe this is the first literature review on the topic.

6.
Cureus ; 15(12): e51387, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38292991

RESUMEN

AIM/OBJECTIVE: Bisphenols are widely used in the manufacturing of polycarbonate material and epoxy resins which constitute the essential component of plastic. Bisphenol A (BPA) has been reported to produce toxicity on organs in both animal and human studies. Therefore, plastic manufacturers are replacing BPA with other analogues that are considered to be safe, and BPA-free products are now available in the market. However, some studies have reported that bisphenol-S (BPS) also possesses toxic properties. It has been reported to depress ventricular contraction as well as produce ventricular arrhythmia on acute exposure. The present study was performed to examine the effect of BPS on in vitro spontaneously-beating right atria in rats. METHODS: In the present study, in vitro spontaneous contractions of right atria obtained from adult female rats of the Wistar strain were recorded. The atria were exposed to BPS (10-6-10 mM) and its effects on atrial contractions were recorded in the form of cumulative-concentration response with and without administration of antagonists namely atropine, L-NAME, and methylene blue. RESULTS: BPS decreased the rate as well as the force of atrial contractions. The changes produced in the rate and force of atrial contractions were not attributed to ethanol, which was used to prepare BPS solutions. The decrease in right atrial contractility produced by BPS was blocked by L-NAME; however, atropine and methylene blue were not able to antagonize the effects of BPS on atria. CONCLUSIONS: The present study indicates the involvement of NO-dependent but cGMP independent pathway responsible for BPS-induced cardio-toxicity.

7.
Circulation ; 146(22): 1674-1693, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36321451

RESUMEN

BACKGROUND: ALPK3 encodes α-kinase 3, a muscle-specific protein of unknown function. ALPK3 loss-of-function variants cause cardiomyopathy with distinctive clinical manifestations in both children and adults, but the molecular functions of ALPK3 remain poorly understood. METHODS: We explored the putative kinase activity of ALPK3 and the consequences of damaging variants using isogenic human induced pluripotent stem cell-derived cardiomyocytes, mice, and human patient tissues. RESULTS: Multiple sequence alignment of all human α-kinase domains and their orthologs revealed 4 conserved residues that were variant only in ALPK3, demonstrating evolutionary divergence of the ALPK3 α-kinase domain sequence. Phosphoproteomic evaluation of both ALPK3 kinase domain inhibition and overexpression failed to detect significant changes in catalytic activity, establishing ALPK3 as a pseudokinase. Investigations into alternative functions revealed that ALPK3 colocalized with myomesin proteins (MYOM1, MYOM2) at both the nuclear envelope and the sarcomere M-band. ALPK3 loss-of-function variants caused myomesin proteins to mislocalize and also dysregulated several additional M-band proteins involved in sarcomere protein turnover, which ultimately impaired cardiomyocyte structure and function. CONCLUSIONS: ALPK3 is an essential cardiac pseudokinase that inserts in the nuclear envelope and the sarcomere M-band. Loss of ALPK3 causes mislocalization of myomesins, critical force-buffering proteins in cardiomyocytes, and also dysregulates M-band proteins necessary for sarcomere protein turnover. We conclude that ALPK3 cardiomyopathy induces ventricular dilatation caused by insufficient myomesin-mediated force buffering and hypertrophy by impairment of sarcomere proteostasis.


Asunto(s)
Cardiomiopatías , Células Madre Pluripotentes Inducidas , Proteínas Musculares , Proteínas Quinasas , Adulto , Animales , Niño , Humanos , Ratones , Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Conectina/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas Musculares/genética , Miocitos Cardíacos/metabolismo , Sarcómeros/metabolismo , Proteínas Quinasas/genética
8.
Indian J Pathol Microbiol ; 65(4): 891-894, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36308200

RESUMEN

Introduction: Protocol for immunocytochemical (ICC) staining in May-Grünwald Giemsa (MGG)-stained smears has been difficult to establish. It is the need of the hour to be able to use prestained slides for ICC in specific cases to deliver timely diagnoses and reduce inconvenience to patients. Aims and Objectives: To evaluate and compare the use of MGG-stained smears for the purpose of ICC, after de-staining and saline rehydration to that of routine standard ICC. Materials and Methods: A prospective study was conducted on 40 FNAC samples: 25 cases of breast disease and 15 cases of reactive lymphoid hyperplasia known to express pancytokeratin and leukocyte common antigen (LCA)/CD45, respectively. Air-dried smears of each case were stained by standard MGG stain and after the report was dispatched, one smear was selected and sent for ICC. The smears were analyzed to determine the overall result and grade each smear semi-quantitatively with respect to staining-intensity, stain-localization, staining-uniformity, counter-staining, and background-staining. Observations and Results: The proposed protocol was inferior to conventional ICC in all the parameters, more pronounced in pancytokeratin than LCA/CD45. Only 8% of air-dried smears stained for pancytokeratin showed optimal stain intensity (as opposed to 44% of wet-fixed smears), whereas only 14.3% of air-dried smears were optimally stained for LCA (as opposed to 85.7% of wet-fixed smears). Conclusion: The proposed protocol of de-stained Giemsa smears as an alternative to conventional technique for ICC was unsuccessful in giving satisfactory results.


Asunto(s)
Colorantes , Humanos , Colorantes Azulados , Inmunohistoquímica , Estudios Prospectivos , Eosina Amarillenta-(YS) , Coloración y Etiquetado
9.
Ann Oper Res ; : 1-24, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36091932

RESUMEN

The thought to put forward a queuing model proposed in this work was its pertinence in everyday life wherever we can see the uses of computing and networking systems. Industrial software developers and system managers can consider the results of the model to evolve their system for better results. Here we present a novel queueing model having erratic server with delayed repair and balking. Two distinct breakdowns i.e. active and passive breakdown for the system are also considered with their respective amendments. This model is closely related with the smooth functioning of the system during some internal faults (virus attack, electricity failures etc.). The performance indicators which are utilized in enhancing the service standards are obtained using supplementary variable technique. Using ANFIS soft computing technique we have compared the analytical results with those of neuro fuzzy results. Furthermore single and bi-objective minimization problems are considered and minima is obtained using particle swarm optimization and multi objective genetic algorithm respectively. Also, the minimization problems are shown as a convex programming problem to ensure the global optimality of the result. The proposed approach makes it conceivable to accomplish a relevant harmony between operational expenses and administration quality.

10.
J Cytol ; 39(1): 9-13, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35341110

RESUMEN

Aims and Objectives: To study the diagnostic utility of fine-needle aspiration cytology (FNAC) and immunocytochemistry in diagnosing primary malignant mixed Mullerian tumors (MMMT). Materials and Methods: A 3-year retrospective study carried out in a tertiary care hospital, which included all the gynecological patients who underwent USG-guided FNAC of their abdominopelvic masses. Observations and Results: Out of the 324 total cases, 05 (1.5%) were reported as primary malignant mixed Mullerian tumors. Out of these 05 cases, 03 were ovarian, 01 was uterine, and 01 involved both uterus and one-sided adnexa. The FNA smears from the masses revealed cytomorphological features of a biphasic neoplasm with elongated pleomorphic spindle cells and dispersed, focal attempted acinar pattern, thus indicating the possibility of MMMT. Immunocytochemistry was further carried out which showed both vimentin and cytokeratin positivity. The diagnosis was confirmed on subsequent biopsy and immunohistochemistry (without any histopathological-cytological discrepancy). Conclusion: Though the literature is replete in establishing a histo-pathological diagnosis of MMMT, the diagnosis on USG-guided FNAC has been rarely described. Emphasis should be made on the careful examination of small sarcomatous elements in smears. Utilization of cell block and immunocytochemistry with histopathological correlation should be done to avoid misdiagnosis.

11.
Int J Legal Med ; 136(2): 465-473, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34748086

RESUMEN

With the advent of next-generation sequencing technology, SNP markers are being explored as a useful alternative to conventional capillary electrophoresis-based STR typing. Low mutation rate and short-sized amplicons are added advantages of SNP markers over the STRs. However, to achieve a sufficient level of discrimination among individuals, a higher number of SNPs need to be characterized simultaneously. Hence, the NGS technique is highly useful to analyze a sufficiently higher number of SNPs simultaneously. Though the technique is in its nascent stage, an attempt has been made to assess its usability in the central Indian population by analyzing 124 SNPs (90 autosomal and 34 Y-chromosome) in 95 individuals. Various quality parameters such as locus balance, locus strand balance, heterozygosity balance, and noise level showed a good quality sequence obtained from the Ion GeneStudio S5 instrument. Obtained frequency of SNP alleles ranged from 0.001 to 0.377 in autosomal SNPs. rs9951171 was found to be the most informative SNP in the studied population with the highest PD and lowest MP value. The cumulative MP of 90 SNPs was found to be 4.76698 × 10-37. Analysis of 34 Y-chromosome SNPs reveals 11 unique haplogroups in 54 male samples with R1a1 as the most frequent haplogroup found in 22.22% of samples. Interpopulation comparison by FST analysis, PCA plot, and STRUCTURE analysis showed genetic stratification of the studied population suggesting the utility of SNP markers present in the Precision ID Identity Panel for forensic demands of the Indian population.


Asunto(s)
Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Pueblo Asiatico , Cromosomas Humanos Y , Dermatoglifia del ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Análisis de Secuencia de ADN
12.
Ann Hum Biol ; 48(7-8): 605-613, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34866517

RESUMEN

BACKGROUND: Most of the forensic DNA laboratories have migrated to new generation STR kits of 6 dye chemistry with more than 20 autosomal STRs. The population-specific databases of such STR markers are lacking in many regions. AIM: To evaluate the effect of the inter-population database in 100 paternity trios with no inconsistencies at 23 STRs. SUBJECTS AND METHODS: 100 paternity trios were evaluated considering inter-population allelic frequency values for calculation of Combined Paternity Index (CPI) and Probability of Paternity (POP). RESULTS: No significant variation (p < 0.05) among the allele frequencies at the interpopulation level was observed. The number of obligate alleles and the likelihood of transferring obligate alleles from the putative father showed a positive correlation (p < 0.005) with Power of Discrimination (PD), Polymorphic Information Content (PIC), Power of Exclusion (PE), Paternity Index (PI), Observed and Expected Heterozygosity (Ho and He), and a statistically significant negative correlation (p < 0.005) with Matching Probability (Pm). The average Combined Paternity Index (CPI) and Probability of Paternity (POP) did not show any statistically significant difference (p < 0.05) at the interpopulation level. CONCLUSION: The allelic database showed no effect on the CPI and POP in 100 paternity trios. This suggests no urgent need for using population-specific databases for statistical evaluation of paternity trios without inconsistencies.


Asunto(s)
Repeticiones de Microsatélite , Paternidad , Alelos , Frecuencia de los Genes , Genética de Población , Humanos , Masculino , Repeticiones de Microsatélite/genética
13.
Curr Pharm Des ; 27(45): 4578-4592, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34620056

RESUMEN

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body. The dynamic gut microbiota of our body houses an astonishing number of microorganisms, mainly bacteria. The balance of the gut microbiota is essential for good health as imbalances may result in dysbiosis leading to various diseases such as cancer. The gut microbiota can be manipulated by using prebiotics, probiotics, synbiotics, postbiotics, and antibiotics for better therapeutic outcomes, as well as to improve the quality of life of patients undergoing conventional cancer treatment. Administration of bacteria as a probiotic agent accompanied with prebiotics obtained from a wide variety of herbs has been used effectively to enhance the treatment of various cancers. Although the theoretical basis of Gut therapy can be ascertained, further clinical trials will be essential to determine the scope and limitations fully. The present review provides a glimpse of conventional and novel cancer therapeutics and their drawbacks, along with the role of the gut microbiome and its modulation to design new pharmaceutics against cancer.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias , Probióticos , Simbióticos , Disbiosis , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Prebióticos , Probióticos/uso terapéutico , Calidad de Vida
14.
J Cancer Res Ther ; 17(4): 1059-1063, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34528564

RESUMEN

BACKGROUND: Hepatoblastoma (HB), rare malignancy in itself, is the most common primary liver tumor in children. Most common presenting features are abdominal distension or abdominal mass. Several patterns are associated with HB with different prognosis. Furthermore, some patterns have overlapping features with other childhood tumors. AIMS AND OBJECTIVES: The aim of this study is to discuss various patterns of HB which we came across in a tertiary care hospital during our study. H and E slides were reviewed with respect to different patterns, postchemotherapy changes including extramedullary hematopoiesis, necrosis, osteoid metaplasia, necrosis, and fibrosis. CONCLUSION: Different patterns of HB should be kept in mind by the pathologists to avoid any misdiagnosis.


Asunto(s)
Hepatoblastoma/patología , Neoplasias Hepáticas/patología , Centros de Atención Terciaria/estadística & datos numéricos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Hepatoblastoma/cirugía , Humanos , Lactante , Neoplasias Hepáticas/cirugía , Masculino , Pronóstico , Estudios Retrospectivos
15.
J Cancer Res Ther ; 17(4): 1115-1118, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34528574

RESUMEN

Acinic cell carcinoma (ACC) is a malignant salivary gland tumor characterized by tumor cells displaying acinar features. Usually presenting as a slow-growing tumor, ACC, however, may show dedifferentiation to a higher grade including neuroendocrine carcinoma. In addition, ACC may rarely show focal neuroendocrine differentiation without any frank evidence of neuroendocrine carcinoma. We describe such a case of ACC of the parotid gland in a 65-year-old female, which showed neuroendocrine differentiation. The diagnostic clues, immunohistochemistry panel, and prognostic and treatment aspects are also presented.


Asunto(s)
Carcinoma de Células Acinares/patología , Carcinoma Neuroendocrino/patología , Diferenciación Celular , Neoplasias de la Parótida/patología , Anciano , Femenino , Humanos , Pronóstico
17.
Diagn Cytopathol ; 49(4): 487-493, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33492721

RESUMEN

OBJECTIVE: Fine needle aspiration (FNA) cytology has been successfully utilized in the preoperative diagnosis of oral masses. Lymphoma involving other sites has also been diagnosed frequently on FNA. Oral cavity lymphoma (OL) is rare and is clinically indistinguishable from other lesions of the mouth. A complete excision of these may be difficult. Our experience with FNA diagnosis of 11 OLs along with histopathological correlation is reported herein in a tertiary health care setting. METHODS: In this retrospective study, clinico pathological characteristics of patients with final diagnosis of non-Hodgkin's lymphoma (NHL) were reviewed over a 7 year period. Routine cytological giemsa staining was performed in all cases along with immunocytochemistry (ICC) wherever possible. The gold standard for diagnosis of NHL was based on: (1) Histopathology and immunohistochemistry and/or (2) Flow cytometry (FC). RESULTS: A total of 11 cases were diagnosed as NHL. All showed B cell immunophenotype. Two of them were diagnosed as follicular lymphoma on histopathology. Male to female ratio was 7:4 and ranged in age from 37 to 70 years. The most common site was tonsillar fossa (N = 5), followed by hard palate (N = 3), soft palate (N = 2), and buccal mucosa (N = 1). Size ranged from 1 to 6 cm. CONCLUSIONS: Diagnosis of OLs may be hampered by its rarity and difficulties in obtaining sufficient cellularity in oral FNA but there is need for immediate and accurate diagnostic procedures, including immunohistochemical analysis to avoid delay in treatment. FNA along with ICC helps in early diagnosis of this rare entity and can also provide sample for FC.


Asunto(s)
Linfoma/patología , Neoplasias de la Boca/patología , Adulto , Anciano , Biopsia con Aguja Fina/métodos , Biopsia con Aguja Fina/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Hueso Paladar/patología , Tonsila Palatina/patología , Valor Predictivo de las Pruebas , Centros de Atención Terciaria
18.
Diagn Cytopathol ; 49(4): E187-E189, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33074579

RESUMEN

Scedosporium apiospermum (also known as Pseudallescheria boydii) is a ubiquitous filamentous fungus. This fungus is known as a cause of mycetoma, which may occur in a normal immune host following trauma and nonmycetoma-localized skin infections without grain production which are much rarer. However, in an immunocompromised host, S. apiospermum may cause a life-threatening infection. We describe a case of S. apiospermum infection of the left middle finger in an immunocompetent patient, which was diagnosed on cytology and later confirmed on culture.


Asunto(s)
Dermatomicosis/patología , Infecciones Fúngicas Invasoras/patología , Dermatomicosis/microbiología , Dedos/microbiología , Dedos/patología , Humanos , Infecciones Fúngicas Invasoras/microbiología , Masculino , Persona de Mediana Edad , Scedosporium/patogenicidad , Piel/microbiología , Piel/patología
19.
J Cancer Res Ther ; 16(6): 1408-1411, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33342805

RESUMEN

INTRODUCTION: Phyllodes tumor is a group of biphasic fibroepithelial tumors of the breast, graded as benign, borderline, and malignant. The grading of breast phyllodes remains a challenging task for the pathologists as the prognosis, and further treatment depends on it. In this study, an effort has been made to grade phyllodes tumor on the basis of immunohistochemistry. AIMS AND OBJECTIVES: Vascular endothelial growth factor, CD10, and factor 8 have been used as immunohistochemical markers for grading. RESULTS AND CONCLUSION: We have found a significant correlation between the expression of these markers and grading of phyllodes tumor. Positive correlation was also found amongst expression of all three markers. To conclude, increased expression of these markers with increasing grade can aid in diagnosis and guide treatment.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Factor VIII/análisis , Neprilisina/análisis , Tumor Filoide/diagnóstico , Factor A de Crecimiento Endotelial Vascular/análisis , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Biopsia , Mama/diagnóstico por imagen , Mama/patología , Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Niño , Factor VIII/metabolismo , Estudios de Factibilidad , Femenino , Humanos , Inmunohistoquímica , Mamografía , Persona de Mediana Edad , Clasificación del Tumor/métodos , Neprilisina/metabolismo , Tumor Filoide/patología , Tumor Filoide/cirugía , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
20.
Elife ; 92020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33054971

RESUMEN

Damaging GATA6 variants cause cardiac outflow tract defects, sometimes with pancreatic and diaphragmic malformations. To define molecular mechanisms for these diverse developmental defects, we studied transcriptional and epigenetic responses to GATA6 loss of function (LoF) and missense variants during cardiomyocyte differentiation of isogenic human induced pluripotent stem cells. We show that GATA6 is a pioneer factor in cardiac development, regulating SMYD1 that activates HAND2, and KDR that with HAND2 orchestrates outflow tract formation. LoF variants perturbed cardiac genes and also endoderm lineage genes that direct PDX1 expression and pancreatic development. Remarkably, an exon 4 GATA6 missense variant, highly associated with extra-cardiac malformations, caused ectopic pioneer activities, profoundly diminishing GATA4, FOXA1/2, and PDX1 expression and increasing normal retinoic acid signaling that promotes diaphragm development. These aberrant epigenetic and transcriptional signatures illuminate the molecular mechanisms for cardiovascular malformations, pancreas and diaphragm dysgenesis that arise in patients with distinct GATA6 variants.


Asunto(s)
Diafragma/crecimiento & desarrollo , Factor de Transcripción GATA6/genética , Corazón/crecimiento & desarrollo , Células Madre Pluripotentes Inducidas/metabolismo , Páncreas/crecimiento & desarrollo , Diferenciación Celular/genética , Epigénesis Genética/genética , Perfilación de la Expresión Génica , Humanos , Mutación Missense/genética , Miocitos Cardíacos/metabolismo
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