Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.

To examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA).

Novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) causes mild to severe respiratory illness. The early symptoms may be fever, dry cough, sour throat, and difficulty in breathing which may lead to death in severe cases. Compared to previous outbreaks like SARS-CoV and Middle East Respiratory Syndrome (MERS), SARS-CoV2 disease (COVID-19) outbreak has been much distressing due to its high rate of infection but low infection fatality rate (IFR) with 1.4% around the world. World Health Organization (WHO) has declared (COVID-19) a pandemic on March 11, 2020. In the month of January 2020, the whole genome of SARS-CoV2 was sequenced which made work easy for researchers to develop diagnostic kits and to carry out drug repurposing to effectively alleviate the pandemic situation in the world. Now, it is important to understand why this virus has high rate of infectivity or is there any factor involved at the genome level which actually facilitates this virus infection globally? In this study, we have extensively analyzed the whole genomes of different coronaviruses infecting humans and animals in different geographical locations around the world. The main aim of the study is to identify the similarity and the mutational adaptation of the coronaviruses from different host and geographical locations to the SARS-CoV2 and provide a better strategy to understand the mutational rate for specific target-based drug designing. This study is focused to every annotation in a comparative manner which includes SNPs, repeat analysis with the different categorization of the short-sequence repeats and long-sequence repeats, different UTR's, transcriptional factors, and the predicted matured peptides with the specific length and positions on the genomes. The extensive analysis on SNPs revealed that Wuhan SARS-CoV2 and Indian SARS-CoV2 are having only eight SNPs. Collectively, phylogenetic analysis, repeat analysis, and the polymorphism revealed the genomic conserveness within the SARS-CoV2 and few other coronaviruses with very less mutational chances and the huge distance and mutations from the few other species.

Emerging resistance to the tyrosine kinase inhibitors that target the BCR-ABL1 oncoprotein has prompted research for novel therapeutics against chronic myeloid leukemia (CML). Herein, we evaluated the tumor inhibitory properties of the human Wharton's jelly stem cells (hWJSCs) co-culture (hWJSC-CC) and their extracts, namely, the hWJSC-conditioned medium (hWJSC-CM; 100%) and hWJSC-lysate (hWJSC-L; 15 μg/ml), on a CML cell line K562 in vitro. The hWJSCs expressed mesenchymal stem cell (MSC)-related cluster of differentiation (CD) markers and demonstrated mesodermal tissue differentiation potential. The cell metabolic activity showed a mean maximal decrease in the K562 cells by 49.12, 41.98, and 68.80% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, respectively, at 72 h. The sub-G1 population in the cell cycle was decreased by 3.2, 4.5, and 3.8% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, whereas the G2/M cell population was increased by 13.7 and 12.5% with the hWJSC-CM and hWJSC-L, respectively, at 48 h. Annexin V-allophycocyanin (APC) assay showed an increase in the apoptotic cells by 4.0, 3.9, and 4.5% at 48 h. The expression of pro-apoptotic BAX and CASP3 genes were increased, whereas BIRC5 (Survivin) was decreased compared with the control. The pro-inflammation-related genes, namely, IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-12A, were decreased, whereas the anti-inflammatory genes, namely, IL-4 and IL-10, were increased following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L at 48 h. Multiplex bead-based cytokine assay also demonstrated decreases in the pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6, and IL-12) and an increase in the anti-inflammatory cytokine (IL-10) compared with the control. The pro-inflammatory cytokine IL-8 showed an increase with the hWJSC-CC and decreases with both the hWJSC-CM and the hWJSC-L. The hWJSCs and their extracts inhibited the K562 cells by causing cell cycle arrest and inducing apoptosis via the soluble cellular factors. However, an in vivo evaluation is necessary to unravel the true potential of the hWJSCs and their extracts before its use in CML inhibition.

Beta-thalassemia is described as a group of hereditary blood disorders characterized by abnormalities in the synthesis of beta chains of hemoglobin. These anomalies result in different phenotypes ranging from moderate to severe clinical symptoms to no symptoms at all. Most of the defects in hemoglobin arise directly from the mutations in the structural β-globin gene (HBB). Recent advances in computational tools have allowed the study of the relationship between the genotype and phenotype in many diseases including β-thalassemia. Due to high prevalence of β-thalassemia, these analyses have helped to understand the molecular basis of the disease in a better way. In this direction, a relational database, named HbVar, was developed in 2001 by a collective academic effort to provide quality and up-to-date information on the genomic variations leading to hemoglobinopathies and thalassemia. The database recorded details about each variant including the altered sequence, hematological defects, its pathology, and its occurrence along with references. In the present study, an attempt was made to investigate nondeletion mutations in the HBB picked up from HbVar and their effects using the in silico approach. Our study investigated 12 nucleotides insertion mutations in six different altered sequences. These 12 extra nucleotides led to the formation of a loop in the protein structure and did not alter its function. It appears that these mutations act as 'silent' mutations. However, further in vitro studies are required to reach definitive conclusions.

Since the beginning of COVID-19 pandemic, many associated factors have been investigated to clarify the susceptibility and severity among the affected individuals. Biological markers can play an important role in identification of individual susceptibility to such pandemic. Growing evidence suggest the influence of different blood group systems on susceptibility to COVID-19 virus, with a particular blood type conferring selection advantage.

Introduction Beta-thalassemia is among the most common monogenic disorders in the Arabian Peninsula. This study aimed to investigate the β-globin (HBB) haplotypes among β-thalassemia patients in Saudi cohort which have potential implications in understanding the clinical care of patients and population genetic factors associated with β-thalassemia. Methods We analyzed 60 β-thalassemia patients. Male/female distribution for β-thalassemia was 58.33%/41.66%. Results of hematological parameters and indices were obtained from the database. HBB haplotyping assay was performed for four specific loci of the HBB gene cluster using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results HBB haplotyping assay identified three novel patterns namely haplotype 1, haplotype 2, and haplotype 3 and three common African haplotypes including Benin, Senegal, and Cameron. The frequency of haplotype 1 was the highest among the studied samples (62%, n = 37) with 56.76% (n = 21) observed in males compared to 43.24% (n = 16) in females. This was followed by Senegal, haplotype 2, Benin and haplotype 3 with similar percentage, and Cameron haplotype with 18%, 12%, 3% and 2%, respectively. The relationship between these haplotypes and various hematological parameters was calculated and our study found no significant relationship (p-value >0.05). Conclusion Our study indicated the importance of finding out types of β-globin haplotypes as novel types being discovered. Though no statistically significant association was identified among all the haplotypes in terms of hematological parameters, Cameroon or Benin haplotypes had the mildest form because they have the highest means among all parameters. Further studies need to be carried out on a larger population to detect the frequency of each specific mutation in each haplotype among β-thalassemia patients. This would help to re-address the question of the origin(s) of the β-thalassemia.