Congenital hereditary endothelial dystrophy with progressive sensorineural deafness: a case report of Harboyan syndrome

ABSTRACT We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.

A dermatological assessment of pediatric patients with tuberous sclerosis complex (TSC)

Abstract Background Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing. Objective To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations. Methods Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months. Results The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas. Study limitations Small sample and a limited number of patients with TSC1 pathogenic variants. Conclusion Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described.

Should anti-CGRP monoclonal antibodies always be the drug of first choice for migraine prophylaxis in Brazil? - a pharmacoeconomic study

Efficacy (success of therapy under ideal conditions), efficiency (the relationship between the costs and outcomes of a specific intervention), and effectiveness (the balance between efficacy and efficiency in clinical practice) are measures used to evaluate health interventions. Thus, in private practice and the public health system, the knowledge of these pharmacoeconomic data should influence the appropriate treatment choice. Migraine prophylaxis falls within this context. Traditional medications are available in the public health system, while galcanezumab is not routinely available. The present study aims to analyze the efficacy and effectiveness of galcanezumab and traditional therapeutic alternatives (amitriptyline, divalproex sodium, and topiramate). Efficacy data were obtained from the relevant literature (PubMed) and cost values from the ABCFarma magazine. The economic impact analysis considered the cost of living for an economically active adult in Brazil based on the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística, IBGE) and the Institute for Applied Economic Research (Instituto de Pesquisa Econômica Aplicada, IPEA). Efficacy: amitriptyline: 40%; divalproex sodium: 30%; topiramate: 31%; galcanezumab: 50%. Their annual costs were: amitriptyline R$ 240.00; sodium divalproate R$ 876.00; topiramate R$ 600.00; galcanezumab R$ 13,992.00. Efficiency: amitriptyline 200%; divalproex sodium 41.1%; topiramate 62%; galcanezumab 4%. Ultimately, effectiveness is amitriptyline 120%; divalproex sodium 35.7%; topiramate 46.5%; galcanezumab 27%. Galcanezumab is the most effective; however, in a broader analysis, where payers, availability, and patient conditions are considered, evaluating efficacy alone may not be feasible in practical contexts and, therefore, anti-CGRP antibodies will not always be the first-line medications in migraine prophylaxis. (AU)

Transient neonatal diabetes mellitus with subtype ZFP57 genetic defect in 6q24

Neonatal diabetes (NDM) is a rare form of diabetes that manifests in the first few months of an infant's life. The condition affects approximately one in 300,000 to 400,000 newborns and is characterized by elevated blood glucose levels. Transient and permanent NDM are the two types of this disease. In most cases of transient neonatal diabetes mellitus (TNDM), the genetic cause has been attributed to the overexpression of chromosome 6q24. Regardless of its underlying cause, the primary treatment for neonatal diabetes is insulin therapy.

CRISPR/Cas9-mediated genome editing: from basic research to gene therapy

CRISPR/Cas9 mediated genome editing is one of the most significant molecular tools discovered to edit the desired genes. It has ushered in a new era of novel possibilities of gene therapy. CRISPR/Cas9 system was originally observed as a part of the adaptive immune system in bacteria. It later on was adapted to carry precise and targeted alterations to the DNA in human cells to be used for gene therapy to correct genetic disorders and treat various severe diseases associated with the genetic changes. Besides this, the CRISPR/Cas9 system has been employed in pharmacogenomics to develop new drugs based on the patient’s genes, in modifying the organisms for research and even for diagnostic purposes in developing CRISPR based COVID-9 test. The recent approval of a CRISPR/Cas9 cellular gene therapy by FDA named “Casgevy” to treat sickle cell anemia is a testimonial to the potentials of CRISPR/Cas9 system in developing innovative gene therapies. This review details the mechanisms of CRISPR/Cas9 gene editing and its utilization in the ongoing clinical trials in the treatment of not only the monogenic disorders like sickle cell disease, thalassemia, and genetic blindness but also in treating multi-factorial diseases like cancers, cardiac diseases, diabetes, autoimmune diseases, viral infections such as human immunodeficiency virus (HIV) etc. An attempt has also been made to discuss the various limitations, challenges and ethical frameworks encompassing CRISPR/Cas9 based gene therapy in clinical settings.

REGULATORY PERSPECTIVE FOR GENE THERAPY PRODUCTS IN THE USA, EU AND JAPAN AND FUTURE ASPECTS

Gene Therapy Products (GTPs) hold immense promise in revolutionizing medical treatments by altering genetic expressions to address various diseases. This study gives a summary of gene therapy products and their prospective uses, their historical development and several treatment options, as an in-depth exploration of the regulatory considerations for GTPs in the United States of America (USA), European Union (EU), and Japan, along with insights into future aspects of this field. A comprehensive discussion follows detailing the regulatory landscape and approval pathways in the USA, EU, and Japan. Programs that are exclusive to each area, such as PRIME (Priority Medicines) in the EU, USA's RMAT (Regenerative Medicines Advanced Therapy) designation and the Sakigake system in Japan are examined. Milestone meetings, approval requirements, and specific regulatory guidelines for GTPs in each region are also thoroughly covered. A list of approved GTPs and a glimpse into the future of the field. Anticipated trends include increasing investments, challenges related to production costs, expansion of manufacturing capabilities, and regulatory updates. The various regulatory strategies in each area and their efforts to balance patient access and safety will have a big impact on GTPs marketed in the future. Japan is well-positioned to maintain it’s as a global leader in regenerative medicine and cell treatments because of its favourable regulatory environment and government backing.

A rheumatological catastrophe: case of amyopathic juvenile dermatomyositis

Juvenile-onset amyopathic dermatomyositis is rare variant of juvenile-onset dermatomyositis (JDM), characterized by the hallmark cutaneous features of dermatomyositis without clinical or laboratory evidence of muscle disease. Dermatomyositis with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody has a distinct phenotype associated with small hand joint arthritis, mucocutaneous ulceration in the absence of muscle involvement. In this article, we describe a 5-year-old child presented with mucocutaneous manifestations with no muscle weakness who responded to immunosuppressive therapy.

In silico evaluation of the gene expression profile of syndecan-4 in different breast tumor subtypes / Avaliação in silico do perfil de expressão gênica do sindecam-4 nos diferentes subtipos de tumores de mama

INTRODUCTION: Breast cancer is one of the main causes of death in women. Luminal tumors A and B show good response with hormonal treatments, tumors that overexpress HER-2 can be treated with monoclonal antibodies, whereas triple negative tumors have few treatments available because they present low or absent expression of hormone receptors and HER-2, in addition, they present worse tumor progression. Syndecans are heparan sulfate proteoglycans that have the function of interacting with growth factors, cytokines, and extracellular matrix, thus modulating important processes in tumor progression. OBJECTIVE: Analyze the expression of syndecan-4 in different subtypes of breast tumors. METHODS: Bioinformatics is a useful tool for the study of new biomarkers. In the present study, the TCGA database (514 patients) and Metabric (1,898 patients) were analyzed using the cBioportal software. Gene expression data were analyzed by RNA-Seq and Microarray from biopsies of breast tumors. RESULTS: An alteration in syndecan-4 gene expression was observed among the different subtypes of breast tumors. Patients with a triple-negative tumor had decreased expression for syndecan-4 in both databases. CONCLUSION: Syndecan-4 is a potential biomarker for breast tumor prognosis since decreased expression of syndecan-4 is related to triple-negative breast cancer.

INTRODUÇÃO: O câncer de mama corresponde a uma das principais causas de morte em mulheres. Os tumores luminais A e B apresentam boa resposta com tratamentos hormonais, os tumores que superexpressam HER-2 podem ser tratados com anticorpos monoclonais, já os tumores triplo-negativos apresentam poucos tratamentos disponíveis por apresentarem expressão baixa ou ausente dos receptores hormonais e HER-2, além de pior progressão tumoral. Os sindecans são proteoglicanos de heparam sulfato que tem função de interagir com fatores de crescimento, citocinas e matriz extracelular, modulando assim processos importantes na progressão tumoral. OBJETIVO: Analisar a expressão o sindecam-4 nos diferentes subtipos de tumores de mama. MÉTODOS: A bioinformática vem se mostrando útil para estudo de novos biomarcadores. No presente estudo, foi analisado o banco de dados TCGA (514 pacientes) e Metabric (1898 pacientes) utilizando o software cBioportal. Foram analisados os dados de expressão gênica por RNA-Seq e Microarray. RESULTADOS: Foi verificada alteração de expressão gênica do sindecam-4 entre os diferentes subtipos de tumores de mama. Pacientes com tumor triplo-negativo tiveram a expressão diminuída para sindecam-4 em ambos os bancos de dados. CONCLUSÃO: Foi verificado que sindecam-4 parece ser um potencial biomarcador em tumores de mama, a expressão diminuída de sindecam-4 parece estar relacionada a um pior prognóstico.

Effect of Swimming at Low Temperature on Uncoupling Protein Gene Expression in Skeletal Muscle of Wistar Rats / Efecto de la Natación a Baja Temperatura sobre la Expresión del Gen de la Proteína de Desacoplamiento en el Músculo Esquelético de Ratas Wistar

SUMMARY: As the economy develops and living standards improve, overweight and obesity are increasingly prevalent. Currently, weight-loss medications are primarily administered orally or intravenously, which can result in poor targeting, low bioavailability, frequent administration, and high toxicity and side effects. The study aimed to address these challenges by preparing polylactic acid- polyethylene glycol staple fibers that carry the browning drug pioglitazone hydrochloride using electrostatic spinning and freeze-cutting techniques. Animal experiments were conducted to test the effectiveness of these fibers. Additionally, the study investigated the expression of uncoupling protein genes in rats exposed to different water temperatures by measuring changes in serum urea nitrogen and mRNA expression levels of skeletal muscle uncoupling protein genes. The physiological and genetic effects of low-temperature swimming exercise on changes in energy metabolism in rats were also analyzed at both the individual and molecular levels. The results revealed that serum urea nitrogen remained more stable in hypothermic swimming rats compared to rats in the swimming group. Furthermore, the study observed an induced up-regulation of uncoupling proteins in the skeletal muscle of Wistar rats in response to external temperature stimulation, and the expression of mRNA for skeletal muscle uncoupling proteins significantly increased as the temperature decreased. And the prepared short nanofibers also had a significant promotive effect on uncoupling protein gene, COX7A1, while suppressing the expression of lipogenic gene.

A medida que la economía se desarrolla y los niveles de vida mejoran, el sobrepeso y la obesidad son cada vez más frecuentes. Actualmente, los medicamentos para bajar de peso se administran principalmente por vía oral o intravenosa, lo que puede resultar en una mala focalización, baja biodisponibilidad, administración frecuente y alta toxicidad y efectos secundarios. El estudio tuvo como objetivo abordar estos desafíos mediante la preparación de fibras cortadas de ácido poliláctico y polietilenglicol que transportan el fármaco pardo clorhidrato de pioglitazona mediante técnicas de hilado electrostático y liofilización. Se realizaron experimentos con animales para probar la eficacia de estas fibras. Además, el estudio investigó la expresión de genes de proteínas desacopladoras en ratas expuestas a diferentes temperaturas del agua midiendo los cambios en el nitrógeno ureico sérico y los niveles de expresión de ARNm de genes de proteínas desacopladoras del músculo esquelético. También se analizaron los efectos fisiológicos y genéticos del ejercicio de natación a baja temperatura sobre los cambios en el metabolismo energético en ratas, tanto a nivel individual como molecular. Los resultados revelaron que el nitrógeno ureico sérico permaneció más estable en ratas nadadoras hipotérmicas en comparación con las ratas del grupo de natación. Además, el estudio observó una regulación positiva inducida de las proteínas desacopladoras en el músculo esquelético de ratas Wistar en respuesta a la estimulación de la temperatura externa, y la expresión de ARNm para las proteínas desacopladoras del músculo esquelético aumentó significativamente a medida que disminuía la temperatura. Además, las nanofibras cortas preparadas también tuvieron un efecto promotor significativo sobre el gen de la proteína de desacoplamiento, COX7A1, al tiempo que suprimieron la expresión del gen lipogénico.

Diagnóstico prenatal de clorhidrorrea congénita: reporte de caso / Prenatal diagnosis of congenital chloride diarrhea: A case report

La clorhidrorrea congénita es un trastorno genético infrecuente pero importante caracterizado por una alteración grave del balance hidroelectrolítico como resultado de un defecto en la absorción intestinal de cloruros. Los niños afectados presentan diarrea persistente, deshidratación y malnutrición; el control médico y del desarrollo son complejos. Mejorar la detección prenatal es esencial para facilitar la atención del paciente, las intervenciones tempranas y el asesoramiento genético informado. Sin embargo, a pesar de los avances de la medicina, la naturaleza compleja y la escasa frecuencia de esta entidad, constituyen un desafío para la detección prenatal. En este estudio, se reporta el caso de una embarazada donde los estudios por imágenes de resonancia magnética fetales identificaron en forma efectiva las características típicas de la clorhidrorrea congénita. Se proveen conocimientos sobre las complejidades del diagnóstico y se sugieren caminos para las estrategias de detección temprana de esta enfermedad.

Congenital chloride diarrhea (CCD) is a rare but significant genetic disorder characterized by severe electrolyte imbalances resulting from impaired intestinal chloride absorption. Affected children experience persistent diarrhea, dehydration, and malnutrition, complicating medical and developmental care. The enhancement of prenatal detection is crucial for improved patient management, early interventions, and informed genetic counseling. However, despite advancements in medicine, the complex nature and rarity of CCD make prenatal detection challenging. In this study, we report a fetal case where prenatal magnetic resonance imaging (MRI) effectively identified the distinctive characteristics of CCD, providing insights into the complexities of diagnosis and suggesting avenues for enhanced early detection strategies.

GEN POMP: acerca de su participación en los mecanismos de autoinmunidad e inflamación

En esta revisión abordamos la autoinmunidad, destacando los mecanismos defectuosos en la tolerancia inmunológica y su relación con enfermedades autoinmunes. Nos centramos en la proteína POMP y el sistema ubiquitina-proteosoma, explicando su función en la degradación proteínica y su papel en la formación del inmunoproteosoma. Se detalla la estructura del proteosoma, la ubiquitinización, y se destaca la influencia de POMP en la respuesta inflamatoria, especialmente en la formación del inmunoproteosoma bajo la estimulación del interferón. Además, se explora la implicación de POMP en procesos autoinflamatorios, como los síndromes asociados al proteosoma, y se menciona su relación con enfermedades autoinmunes, incluyendo el lupus eritematoso sistémico. Se describen casos clínicos que resaltan la importancia de POMP en la autoinmunidad.

This publication addresses autoimmunity, and defective mechanisms in immunological tolerance as well as their connection to autoimmune diseases. It focuses on the POMP protein and the ubiquitin-proteasome system, explaining its role in protein degradation and its involvement in the formation of the immunoproteasome. The structure of the proteasome, ubiquitination, and the influence of POMP on the inflammatory response are detailed, highlighting the formation of the immunoproteasome under interferon stimulation. Additionally, the text explores the implication of POMP in autoinflammatory processes, such as proteasome-associated syndromes, and mentions its association with autoimmune diseases, including systemic lupus erythematosus. Clinical cases are described to underscore the significance of POMP in autoimmunity.

Neurodevelopmental disorder associated with NARS1 gene mutation in a child with cerebral palsy

Cerebral palsy is the most common cause of chronic motor disability in children. CP has a multitude of causes, including developmental, genetic, metabolic, ischemic, infectious, and acquired, all of which result in comparable neurologic symptoms. As of right now, the cause of CP remains unclear. Research has found a substantial link between low birth weight, birth hypoxia, and poor fetal position and placenta. When diagnosing children with cerebral palsy and determining its cause, brain imaging is crucial. The final diagnosis should consider many factors, including physiological, topographic, ICF/functional, and neuroradiological categorization, origin, time of injury, concomitant disorders, sequelae, and nutritional status. This assists with planning, management, counseling, progress tracking, and prognosis. We present a case of a 5-year-old child with cerebral palsy who has a complicated clinical presentation including delayed psychomotor development, dysmorphia, and a verified pathogenic variation in the NARS1 gene linked to a neurodevelopmental condition. The child has been receiving frequent monitoring and multimodal therapies, such as physical therapy, defectologist sessions, and omega fatty acid supplements. Genetic testing found a pathogenic variant in the NARS1 gene, emphasizing the significance of genetic screening for parents to prevent recurrence in future pregnancies. Collaboration with special education instructors and speech therapists remains active to meet the child's communicative and cognitive requirements.

A girl with synostotic plagiocephaly: unfolding as rare case

Dysmorphic head shape can be a presenting complaint of craniosynostosis which needs to be investigated in detail for any genetic or syndromic associations. Many genetic mutations have been associated with craniosynostosis but ERF gene mutation has been found to be very rare. Here, we have discussed about an 8 years old girl who presented with dysmorphic head shape. She had crouzoid features like exorbitism, malar hypoplasia with copper beaten skull appearance and pansynostosis on CT Head but genetic evaluation revealed ERF gene mutation suggestive of craniosynostosis 4. She had short stature which was the unique association with it. Thus, high index of suspicion should be kept for craniosynostosis 4 when phenotypic features are suggestive of crouzon syndrome as crouzon syndrome can phenotypically mimic craniosynostosis with ERF gene mutation and genetic analysis should be done to look for alternate cause of craniosynostosis; especially to look for ERF gene mutation.

A 5-year-old girl case of spastic paraplegia type 56, a mutation in the CYP2U1 gene

This case report details the presentation, diagnosis, and management of a 5-year-old girl from Saudi Arabia with Spastic Paraplegia Type 56 (SPG56) resulting from a novel mutation in the CYP2U1 gene. SPG56, a rare form of hereditary spastic paraplegia, exhibits genetic variability, impacting neurological and extra-neurological functions. The patient's clinical course involved a fall at age 2, subsequent motor deterioration, cognitive delays, and spasticity. Comprehensive diagnostic evaluations, including genetic testing, identified a homozygous likely pathogenic variant in CYP2U1. Despite outpatient therapy, the patient underwent a four-week intensive rehabilitation course to address spasticity and enhance daily living activities. This case highlights the challenges in diagnosing and managing SPG56 and underscores the importance of genetic testing in complex neurodegenerative cases.

Differences in Muscle Strength Performance According to the Genotypes of the rs4646994 Polymorphism of the ACE Gene in a Sedentary Population / Diferencias en el Rendimiento de la Fuerza Muscular Según los Genotipos del Polimorfismo rs4646994 del Gen ACE en una Población Sedentaria

SUMMARY: The angiotensin converting enzyme gene (ACE) has been associated with endurance and strength performance through its I/D polymorphism. Nevertheless, contradictory results exist between different populations. In this context, the purpose of this research was to determine the influence of the I/D polymorphism of the ACE gene on muscle strength in a sedentary Chilean sample. In this study 102 healthy male students (21.3 ± 2.2 years) completed the assessment. I/D genotyping, cardiovascular, anthropometric, grip strength and knee extensor peak strength were evaluated. The ACE polymorphism frequency was: II, 33.3 %; ID, 46.1 %; DD, 20.6 %. The results showed significant differences and large effect size in maximum (p = 0.004; d = 0.85) and relative handgrip strength (p = 0.004; d = 0.9) between genotype II vs DD. No difference was found for maximal or relative knee extensor strength between groups (p = 0.74), showing a low effect size (d = 0.20). In conclusion, this study provides insights into the role of the ACE gene in muscle strength and highlights the importance of investigating genetic variants in sedentary populations to better understand strength performance.

El gen de la enzima convertidora de angiotensina (ACE) se ha asociado con el rendimiento de resistencia y fuerza a través de su polimorfismo I/D. Sin embargo, existen resultados contradictorios entre diferentes poblaciones. En este contexto, el propósito de esta investigación fue determinar la influencia del polimorfismo I/D del gen ACE sobre la fuerza muscular en una muestra chilena sedentaria. En este estudio, fueron evaluados 102 estudiantes varones sanos (21,3 ± 2,2 años). Se realizaron aplicaron las siguientes evaluaciones: genotipado del polimorfismo I/D, cardiovascular, antropométrica, fuerza de prensión y fuerza máxima de extensión de rodilla. La frecuencia del polimorfismo I/D de ACE fue: II, 33,3 %; DNI, 46,1 %; DD, 20,6 %. Los resultados mostraron diferencias significativas y un gran tamaño del efecto en la fuerza máxima (p = 0,004; d = 0,85) y relativa de prensión manual (p = 0,004; d = 0,9) entre el genotipo II y el DD. No se encontraron diferencias en la fuerza máxima o relativa de los extensores de rodilla entre los grupos (p = 0,74), lo que muestra un tamaño de efecto bajo (d = 0,20). En conclusión, este estudio proporciona información sobre el papel del gen ACE en la fuerza muscular y destaca la importancia de investigar variantes genéticas en poblaciones sedentarias para comprender mejor el rendimiento de la fuerza.

Sprint and Anaerobic Power with the Soccer-Specific ACTN3 Gene: A Distintive Example / Sprint y Potencia Anaeróbica con el Gen ACTN3 Específico del Fútbol: Un Ejemplo Distintivo

SUMMARY: The aim of this study is twofold: (1) to identify differences in certain anaerobic parameters (10m sprint, 30m sprint, anaerobic power, and Illinois agility tests) between professional and amateur soccer players, and (2) to determine whether there is a difference in the ACTN3 gene polymorphism between professional and amateur soccer players. Ultimately, the goal is to reveal which parameters contribute to the differentiation in these two aspects. A total of 133 volunteer soccer players, including 71 professionals and 62 amateurs, participated in the research. DNA extraction from buccal epithelial cells was performed using a commercial kit to determine the genetic background of the athletes, and Real-Time PCR was conducted for genotyping. Statistical analysis of the findings obtained from the test results was performed using the SPSS 23 (SPSS Inc., Chicago, IL, USA) package program. The homogeneity of variance of the data was assessed using the Levene Test, and normal distribution analyses were conducted using the Shapiro-Wilk Test. Chi-square and Mann-Whitney U tests were employed for parameter analysis. The significance level was set at p0.05). However, there is a statistically significant difference in anaerobic parameters (10m sprint, 30m sprint, and anaerobic power) except for the Illinois test (p<0.05). In conclusion, our study found that gene polymorphism is not a differentiating factor between professional and amateur soccer players, but speed (10m and 30m) and anaerobic power parameters are differentiating factors.

Los objetivos de este estudio fueron: 1º identificar diferencias en ciertos parámetros anaeróbicos (sprint de 10 m, sprint de 30 m, potencia anaeróbica y pruebas de agilidad de Illinois) entre jugadores de fútbol profesionales y amateurs, y 2º determinar si existe una diferencia en el polimorfismo del gen ACTN3 entre jugadores de fútbol profesionales y aficionados. En definitiva, el objetivo fue revelar qué parámetros contribuyen a la diferenciación en estos dos aspectos. En la investigación participaron un total de 133 jugadores de fútbol voluntarios, incluidos 71 profesionales y 62 aficionados. La extracción de ADN de las células epiteliales orales se realizó utilizando un kit comercial para determinar los antecedentes genéticos de los atletas y se realizó una PCR en tiempo real para el genotipado. El análisis estadístico de los hallazgos obtenidos a partir de los resultados de las pruebas se realizó utilizando el programa de paquete SPSS 23 (SPSS Inc., Chicago, IL, EE. UU.). La homogeneidad de la varianza de los datos se evaluó mediante la prueba de Levene y los análisis de distribución normal se realizaron mediante la prueba de Shapiro-Wilk. Para el análisis de parámetros se emplearon las pruebas de Chi-cuadrado y U de Mann-Whitney. El nivel de significancia se fijó en p0,05). Sin embargo, existe una diferencia estadísticamente significativa en los parámetros anaeróbicos (sprint de 10 m, sprint de 30 m y potencia anaeróbica) excepto para la prueba de Illinois (p<0,05). En conclusión, nuestro estudio encontró que el polimorfismo genético no es un fac- tor diferenciador entre jugadores de fútbol profesionales y amateurs, pero sí los parámetros de velocidad (10 m y 30 m) y potencia anaeróbica.

Association of genetic and epigenetic modification in MTHFR gene with coronary artery disease patients in North Indian population

Background: Methylene tetra hydro folate reductase (MTHFR) gene polymorphism C677T (rs180113) and DNA methylation in promoter region of MTHFR gene may contribute to the development of coronary artery disease however the results have been inconsistent across studies with different populations, so the aim of our study is to explore the association of polymorphism in MTHFR gene and methylation in promoter region with coronary artery disease (CAD) and other risk factor (lipid profile, homocysteine, vitamin B12 and folic acid levels) leading to CAD in of north Indian population. Methods: Total 100 CAD patients and 100 healthy controls were enrolled in the study. Genotyping of rs1801133 SNP (C677T) is done by PCR-RFLP and DNA methylation study in promoter region by methylation specific PCR. Lipid profile analysis by automated chemistry analyzers, serum homocysteine, folic acid and vitamin B12 was assayed by ELISA. Results: As per our finding the T allele (OR=3.03, 95% CI=1.74-5.27) and hyper methylation in promoter region of MTHFR increases the odds of coronary artery disease, (OR=3.05, 95% CI=1.7-5.6). Study participants with CT and TT genotype had significantly higher homocysteine (Hcy) (p=0.001), lower folic acid level (p=0.0), and HDL levels (p<0.0001) than those with CC genotype. The study subjects with hyper methylated promoter region have a significantly high homocystenemia levels (p=0.001). Conclusions: The TT genotype of the MTHFR C677T gene polymorphism and hyper methylation in promoter region of MTHFR, is associated with CAD and can be useful in identification of new biomarkers, development of preventive and therapeutic strategies for CAD.

Association of methylene tetrahydrofolate reductase gene mutation in unexplained recurrent pregnancy loss

Background: Recurrent pregnancy loss (RPL) without apparent causative factor which may be identified in about 50% of cases known as unexplained recurrent pregnancy loss. RPL is very distressing and can be heartbreaking for the couple. Among the many causes of RPL Methylene Tetrahydrofolate Reductase (MTHFR) gene mutation have been postulated as a possible cause. Aim of the study was to assess the association of methylene tetrahydrofolate reductase gene mutation (C677T and A1298C) in unexplained recurrent pregnancy loss.Methods: This was a case-control study conducted at the Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from May 2020 to April 2021. A total of 34 patients with unexplained recurrent pregnancy loss (RPL) and 34 age and BMI-matched controls were selected as study subjects. Data was analyzed using SPSS software, version 22.0.Results: The frequency of heterozygous mutant genotype of MTHFR C677T and A1298C was statistically significantly higher in the case group than the control (38.2% vs 5.9%, p=0.001 and 55.9% vs 11.8%, p=0.000 respectively). No homozygous mutation for MTHFR C677T and only 1 for A1298C in the case group was found. The mutant T allele for MTHFR C677T and Mutant C allele for A1298C were found more frequently in cases compared to the controls (19.1% vs. 2.9% and 30.9% vs. 5.9%). Both the differences were statistically significant (p=0.003 and 0.000 respectively). Compound heterozygous mutant genotype CT/AC was found in 20.6% of RPL patients and not was found in the control.Conclusions: MTHFR C677T and A1298C mutations pose a risk for unexplained recurrent pregnancy loss (RPL). Individuals with these mutations and a history of recurrent pregnancy loss may benefit from tailored management strategies, including low dose aspirin and low molecular weight heparin, to address potential risks.

Mining of Gene Modules and Identification of Key Genes for Early Diagnosis of Gastric Cancer

Gastric cancer (GC) is one of the most common malignant tumors with high incidence and mortality rates. Most patients with GC are not diagnosed until the advanced stage of cancer or during tumor screening, resulting in missing the best treatment time. This study identified key modules and hub genes associated with GC by weighted gene co-expression network analysis (WGCNA). The "limma" package in R was used to identify differentially expressed genes (DEGs) in GC samples from TCGA, and a total of 4892 DEGs were identified. GO enrichment and KEGG pathway enrichment analyses were conducted to detect the related pathways and functions of DEGs. These DEGs were primarily associated with extracellular matrix organization, DNA replication, cell cycle, and p53 signaling pathway. Gene modules associated with clinical characteristics were identified with WGCNA in tumor and normal samples. Six gene modules were obtained in the WGCNA network, of which two modules were significantly correlated with GC. Hub genes of key modules were identified using survival analysis and expression analysis. Finally, one-way ANOVA was used to explore the relationship between hub gene expression in normal tissues and different pathological stages of GC. Through survival and expression analysis, a total of 19 genes with good prognosis and significantly differential expressed were identified. The hub genes were significantly differential expressed in normal tissues and different pathological stages of GC, indicating that these genes have important diagnostic value for early GC and can be used as auxiliary indicators in the diagnosis of early GC.

Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system

Abstract Introduction Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.