MicroRNA Guided In Silico Drug Repositioning for Malaria.

Background: The rise in Plasmodium resistant strains, decreasing susceptibility to first-line combination therapies, and inadequate efficacy shown by vaccines developed to date necessitate innovative approaches to combat malaria. Drug repurposing refers to finding newer indications for existing medications that provide significant advantages over de novo drug discovery, leading to rapid treatment options. Growing evidence suggests that drugs could regulate the expression of disease-associated microRNAs (miRNAs), implying the potential of miRNAs as attractive targets of therapy for several diseases.

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in : a review of current knowledge and future directions.

Unlabelled: Utilizing transcriptomics, promising methods for identifying unique genes associated with gametocyte development offer a potential avenue for novel candidate targets in transmission blocking vaccine development. In this review, we identified 40 publicly available transcriptomic datasets related to parasite factors linked with sexual stage transmission, from which we analyzed two RNA-Seq datasets to identify potential genes crucial for the transmission of from humans to mosquito vectors. Differential expression analysis revealed 3500 (2489 upregulated and 1011 downregulated) common genes differentially expressed throughout sexual stage development of occurring in both humans (gametocyte stage II, V) and mosquitoes (ookinete).

Genome-wide DNA methylation profiling after Ayurveda intervention to bronchial asthmatics identifies differential methylation in several transcription factors with immune process related function.

Background: The Indian traditional medicinal system, Ayurveda, describes several lifestyle practices, processes and medicines as an intervention to treat asthma. Rasayana therapy is one of them and although these treatment modules show improvement in bronchial asthma, their mechanism of action, particularly the effect on DNA methylation, is largely understudied.

Objectives: Our study aimed at identifying the contribution of DNA methylation changes in modulating bronchial asthma phenotype upon Ayurveda intervention.

Erythrocyte miRNA-92a-3p interactions with PfEMP1 as determinants of clinical malaria.

Based on the recently added high throughput analysis data on small noncoding RNAs in modulating disease pathophysiology of malaria, we performed an integrative computational analysis for exploring the role of human-host erythrocytic microRNAs (miRNAs) and their influence on parasite survival and host homeostasis. An in silico analysis was performed on transcriptomic datasets accessed from PlasmoDB and Gene Expression Omnibus (GEO) repositories analyzed using miRanda, miRTarBase, mirDIP, and miRDB to identify the candidate miRNAs that were further subjected to network analysis using MCODE and DAVID. This was followed by immune infiltration analysis and screening for RNA degradation mechanisms.

Therapeutics through glycobiology: an approach for targeted elimination of malaria.

The emergence of drug resistance in jeopardises worldwide malaria eradication efforts necessitating novel therapeutic approaches and therefore the identification of key metabolic pathways of parasite and human host for drug development garners importance. Enzymopathies like glucose-6-phosphate-dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies have been shown to protect against the severe consequences of malaria. Glycome profiles and the regulatory mechanisms involving the microRNAs or transcription factors' expression related to the histo-blood group glycogenes may add up to resolve the underlying pathogenesis.

Malaria Epidemiology and COVID-19 Pandemic: Are They Interrelated?

Coronavirus disease 2019 (COVID-19) is a systemic disease, impacting multiple organs in the human body. But COVID-19 also impacts other diseases of relevance to public and planetary health. To understand and respond to the COVID-19 pandemic, we need an intersectional conceptual lens and systems thinking.

Erythrocyte miRNA regulators and malarial pathophysiology.

Pathophysiology of Plasmodium falciparum and Plasmodium vivax in malaria vis a vis host and the parasite genome interactions has been deciphered recently to present the biology of cerebral malaria, severe anaemia and placental malaria. Small non-coding RNAs have exhibited their potential to be considered as indicators and regulators of diseases. The malarial pathologies and their associated mechanisms mediated by miRNAs and their role in haematopoiesis and red cell-related disorders are elucidated.

A pilot randomized controlled trial to compare the effectiveness of two 14-day primaquine regimens for the radical cure of vivax malaria in South India.

Background: Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course.

Methods: A two centre, randomized, open-label, two arm study was conducted in South India.

Correction to: Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy.

The original version of this article unfortunately contained a mistake. Ambika Devi K was not listed among the authors. The corrected authorship is given below.

The promise of discovering population-specific disease-associated genes in South Asia.

The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups.

Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes.

In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case-control study of adults, individuals affected by Pf malaria (complicated n=168; uncomplicated n=282) and healthy controls (n=450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing.

Single nucleotide polymorphisms of ADRB2 gene and their association with susceptibility for Plasmodium falciparum malaria and asthma in an Indian population.

The essential route to blood parasitaemia in malaria, erythrocyte invasion is facilitated by activation of the G-protein coupled receptor signaling pathway mediated by the β2-adrenoreceptor as one of the proteins on the surface of red blood cells. The effectiveness of bronchodilators and inhaled corticosteroids in the clinical treatment for asthma patients also depend on polymorphisms in the β2-adrenoreceptor gene (ADRB2). In a case control study, individuals affected by Plasmodium falciparum malaria, asthma and controls were tested for association of six ADRB2 single nucleotide polymorphisms (SNPs) viz.

Allele, genotype, and composite genotype effects of IL-1A +4845 and IL-1B +3954 polymorphisms for chronic periodontitis in an Indian population.

Introduction: The pro-inflammatory cytokine interleukin-1 (IL-1) is a key modulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption, and polymorphisms in the IL-1 gene cluster have been associated with an increased risk of developing severe adult periodontitis. A case control study was performed to determine the role of IL-1A+4845 and IL-1B+3954 polymorphisms in the predisposition to chronic periodontitis.

Materials And Methods: The study was conducted with 103 unrelated participants recruited from Manipal College of Dental Sciences, Manipal, which included 51 chronic periodontitis patients and 52 normal periodontally healthy individuals.

Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy.

Background: There are many studies documenting increased prevalence of periodontal infection in women with preeclampsia. But, very few studies have attempted to establish causal relationship between the two.

Objective: To find out causal circumstantial evidence by isolating specific periodontal pathogens in oral and placental samples.

Thiopurine S-methyltransferase alleles, TPMT(*)2, (*)3B and (*)3C, and genotype frequencies in an Indian population.

Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6-mercaptopurine, 6-thioguanine and azathioprine. TPMT activity exhibits genetic variation and shows tri-modal distribution with 89-94% of individuals possessing high activity, 6-11% intermediate activity and approximately 0.3% low activity.

Analysis of genotype and haplotype effects of ABCB1 (MDR1) polymorphisms in the risk of medically refractory epilepsy in an Indian population.

The transmembrane P-glycoprotein that functions as a drug-efflux transporter coded by ATP-binding cassette, subfamily B, member 1/Multidrug Resistance 1 (ABCB1/MDR1) gene is considered relevant to drug absorption and elimination, with access to the central nervous system. Effects of three ABCB1 single nucleotide polymorphisms (SNPs) in genotypic and haplotypic combination have been evaluated in a south Indian population for risk of pediatric medically refractory epilepsy. The study included age and sex matched medically refractory (N=113) cases and drug responsive epilepsy patients (N=129) as controls, belonging to the same ethnic population recruited from a tertiary referral centre, of Karnataka, Southern India.

Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy.

Mutations causing familial hypertrophic cardiomyopathy (HCM) have been described in at least 11 genes encoding cardiac sarcomeric proteins. In this study, three previously unknown deletions have been identified in the human cardiac genes coding for beta-myosin heavy chain (MYH7 on chromosome 14) and myosin-binding protein-C (MYBPC3 on chromosome 11). In family MM, a 3-bp deletion in MYH7 was detected to be associated with loss of glutamic acid in position 927 (DeltaE927) of the myosin rod.