Lamivudine, a Reverse Transcriptase Inhibitor, Rescues Cognitive Deficits in a Mouse Model of Down Syndrome

An elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases. Down syndrome (DS) is the most common genetic disorder associated with intellectual disability and a genetic form of Alzheimer’s disease. For this reason, we hypothesized that treatment with reverse transcriptase inhibitors could ameliorate DS phenotypes. In this proof of concept study, we treated trisomic (Ts65Dn) mice, a model of DS, with lamivudine, a reverse transcriptase inhibitor. We detected a significant improvement of neurobehavioral phenotypes, and a complete rescue of the hippocampal-dependent recognition memory upon treatment with lamivudine. Despite clinical studies in patients with DS are warranted, this study lays the groundwork for a novel and actionable therapeutic approach.

Sickle Cell Disease- A Case Report in a theoretical approach

Sickle cell disease (SCD) is a major healthcare and societal problem affecting millions of people worldwide. In United States of America (USA), it is the most common genetic disorder affecting more than 80,000 people per year; majority of which are the African Americans Arabian and Indian (6,10). It is a genetic blood disorder affecting the red blood cells. Sickle cell pain is the hallmark of sickle cell disease and is associated with a very high mortality and morbidity rates (12). Being a genetic abnormality, the complete eradication of the disease from the affected seems to be difficult. Genetic counselling during pregnancy being the prime preventive step, Hematopoietic stem cell transplantation becomes the mainstay of treatment for complete eradication of the disease. But it is not done very often because of the significant risks involved.

FACTORS ASSOCIATED WITH THALASSAEMIA CARRIER AMONG FORM FOUR STUDENTS IN KEDAH, MALAYSIA

Thalassaemia and abnormal haemoglobins are the most common genetic disorder worldwide. School-based screening thalassaemia program for form four students was introduced with the objective to screen for the thalassaemia status. There is paucity in the data in Kedah on distribution of thalassaemia carrier and the associated factors. Hence this study aims to identify the factors associated with being a thalassaemia carrier and to describe the laboratory cost for the thalassaemia screening. This study used secondary data from the school-based thalassaemia screening in 2018 obtained from Kedah State Health Department. Results showed the prevalence of thalassaemia carrier among form four students in Kedah was 10.91%. Multivariate logistic regression showed that students from Baling, Padang Terap and Yan were 1.40, 1.34 and 1.23 times more likely to be a thalassaemia carrier respectively compared to Kota Setar (aOR Baling 1.40;95% CI 1.21,1.64; aOR Padang Terap 1.34;95% CI 1.11,1.61 and aOR Yan 1.23;95% CI 1.03,1.47). Malay and Siamese students were five times more likely be thalassaemia carriers compared to Indian (aOR Malay 5.16;95%CI 3.42,7.79, aOR Siamese 5.63;95%CI 3.19,9.97). Meanwhile, Chinese students had 2.61 higher odds to be a thalassaemia carrier compared to Indian (aOR Chinese 2.61;95%CI 1.65,4.12). The laboratory cost for the thalassaemia screening ranged from RM2.14 to RM142.14 per participant. As for conclusion, this study reported high prevalence (10.91%) of thalassaemia carriers in Kedah. Our study also confirmed that the district and the ethnicity significantly influenced the thalassaemia carrier status. The identified factors should inform future thalassaemia campaign to prevent higher prevalence of thalassaemia patients.

Zebrafish as a Biomedical Model for Stem Cells Research in Hearing Impairment

Zebrafish is an excellent model for observing human genetic disorders. Hearing impairment is the most common genetic disorder including syndromic & non-syndromic hearing loss. Stem cell therapies are considered a new hope in case of hearing impairment. Stem cells are the master cells of the human body and having the capability to differentiate into any other form of cells in more than 200 types of cells (regeneration). This review article describes zebrafish as a biomedical model for stem cell research in hearing impairment, which revolutionized the biomedical arena to compete for the challenges.

Development of Glycerol-Rose Bengal-Polidocanol (GRP) foam for enhanced sclerosis of a cyst for cystic diseases

Polycystic kidney disease (PKD) is a common genetic disorder that results in a proliferating and enlarging cyst and ultimately leads to loss of kidney function. Because an enlarged cyst is a primary factor for limited kidney function, the large cyst is surgically removed by laparoscopic deroofing or sclerosant. This a relatively nascent treatment method entails complications and sometimes fail due to the cyst fluid refilling and infection. This study proposes using a more stable and effective polidocanol foam with glycerol and Rose Bengal (GRP form) to prevent cyst regeneration and irritation, which is caused by the required body movement during the treatment. Specifically, the foam retention time and viscosity were increased by adding glycerol up to 10% (w/v). The GRP form inhibited cellular proliferation and disrupted cellular junctions, e-cadherin, and cyst formation, demonstrated by the LDH, Live and Dead, and re-plating culture assays. The GRP foam was shown to be a safe and effective treatment as a commercial grade polidocanol foam form by an in vivo study in which subcutaneously injected mice injected with commercial 3% polidocanol, and the GRP foam showed no difference in inflammation. Thus, this study provides an advanced polidocanol form by adding glycerol and Rose-Bengal to help existing sclerotherapy.

Case report of a successful pregnancy in a cystic fibrosis patient with the c.1521_1523delCTT/c.3718-2477C>t genotypes

The aim of this case report was to show the consequences of pregnancy in a cystic fibrosis (CF) patient with a rare mutation. We present a case of a patient with CF, pregnant for the second time, who gave birth to a healthy child. Her mutation status revealed the presence of relatively rare mutation c.3718-2477C>T that is associated with a milder phenotype of the disease. During pregnancy, her vital signs were within normal limits. She had no exacerbations after the third gestational month. Cystic fibrosis is the most common genetic disorder among Caucasians. Over the last few decades, the survival rate and the lifespan of patients with CF have increased progressively. This is why more affected women are choosing to become pregnant. Predictive factors for the pregnancy outcome are basal pulmonary function [measured by forced expiratory volume/1 second (FEV1)], nutritional status [measured by body mass index (BMI)], diabetes and bacterial colonization. The report of our case emphasizes the need for establishing the exact mutations in CF patients who plan to become pregnant in order to predict the possible outcomes of this specific period of life. Moreover, genetic counseling is strongly recommended for the right understanding of the pregnancy risks in such cases.

AYURVEDIC CONCEPT OF KNOWING UNKNOWN DISEASE (ANUKTA VYADHI) W.S.R. TO THALASSEMIA

Thalassemia is the most common genetic disorder resulting from abnormality of Globin chain. It is the worldwide problem of today’s era and until no answer to any medical science. It is the challenging disorder for the scientist. The nature of the disease is genetic regarding this so many literatures available in the modern science but in Ayurveda has no answer for this disease. To add the new concept of disease Thalassemia (Anukta Vyadhi In Ayurveda), aim of study is to understand the unknown disease, the concept of Beeja, Beejabhaga and Beejabhagavayava should be clear because of its genetic nature of thalassemia. Charaka mentioned Aptopadesha method of examination, we can acquire knowledge as described by wise men, or Apta, use to understand a disease:

Down syndrome with Disorder of Sex development (DSD): A Rare Presentation

Down syndrome is the most common genetic disorder among live born infants, which is associated with a number of congenital malformations and requires a huge medical and social cost. Here, we report a very rare association in an infant with Down syndrome and XY disorder of sex development (DSD). Bangladesh J Child Health 2020; VOL 44 (1) :48-51

CHOP-c-JUN complex plays a critical role in liver proteotoxicity induced by mutant Z alpha-1 antitrypsin

ABSTRACTAlpha-1 antitrypsin (AAT) deficiency is a common genetic disorder with lung and liver involvement. Most patients carry the Z allele in SERPINA1 that encodes a mutant AAT (ATZ) forming hepatotoxic polymers. We found CHOP upregulation and activation in both mouse (PiZ) and human livers expressing ATZ. Compared to controls, juvenile PiZ/Chop-/- mice showed reduction in hepatic ATZ and transcriptional response to endoplasmic reticulum stress, as consequence of CHOP-mediated increase of SERPINA1 transcription. CHOP was found to upregulate SERPINA1 though binding with c-JUN on SERPINA1 regulatory elements, thus aggravating hepatic accumulation of ATZ. Increased CHOP levels were detected in diseased livers of children homozygous for the Z allele.Compared to adults, AAT deficiency in infants has different severity and prognosis. Based on our findings, CHOP-c-JUN complex upregulates SERPINA1 transcription and play an important role in the hepatic disease pathogenesis by increasing the burden of proteotoxic ATZ, particularly in the pediatric population.

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts

Down syndrome (trisomy of human chromosome 21) is a common genetic disorder. Overproduction of the gaseous mediator hydrogen sulfide (H2S) has been implicated in the pathogenesis of neurological and metabolic deficits associated with Down syndrome. Several lines of data indicate that an important enzyme responsible for H2S overproduction in Down syndrome is cystathionine-β-synthase (CBS), an enzyme localized on chromosome 21. The current study explored the possibility that a second H2S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), may also contribute to the development of functional deficits of Down syndrome cells. Western blotting analysis demonstrated a significantly higher level of 3-MST protein expression in human Down syndrome fibroblasts compared to cells from healthy control individuals; the excess 3-MST was mainly localized to the mitochondrial compartment. Pharmacological inhibition of 3-MST activity improved mitochondrial electron transport and oxidative phosphorylation parameters (but did not affect the suppressed glycolytic parameters) and enhanced cell proliferation in Down syndrome cells (but not in healthy control cells). The findings presented in the current report suggest that in addition to the indisputable role of CBS, H2S produced from 3-MST may also contribute to the development of mitochondrial metabolic and functional impairments in Down syndrome cells.