An update on the cell-free DNA-derived methylome as a non-invasive biomarker for coronary artery disease.

Cardiovascular diseases are the foremost contributor to global mortality, presenting a complex etiology and an expanding array of risk factors. Coronary artery disease characterized by atherosclerotic plaque build-up in the coronary arteries, imposes significant mortality and financial burdens, especially in low- and middle-income nations. The pathogenesis of coronary artery disease involves a multifaceted interplay of genetic, environmental, and epigenetic factors. Epigenetic regulation contributes to the dynamic control of gene expression without altering the underlying DNA sequence. The mounting evidence that highlights the pivotal role of epigenetic regulation in coronary artery disease development and progression, offering potential avenues for the development of novel diagnostic biomarkers and therapeutic targets. Abnormal DNA methylation patterns are linked to the modulation of gene expression involved in crucial processes like lipid metabolism, inflammation, and vascular function in the context of coronary artery disease. Cell-free DNA has become invaluable in tumor biology as a liquid biopsy, while its applications in coronary artery disease are limited, but intriguing. Atherosclerotic plaque rupture causes myocardial infarction, by depriving heart muscles of oxygen, releasing cell-free DNA from dead cardiac cells, and providing a minimally invasive source to explore tissue-specific epigenetic alterations. We discussed the methodologies for studying the global methylome and hydroxy-methylome landscape, their advantages, and limitations. It explores methylome alterations in coronary artery disease, considering risk factors and their relevance in coronary artery disease genesis. The review also details the implications of MI-derived cell-free DNA for developing minimally invasive biomarkers and associated challenges.

Gametogenesis in Plasmodium: Delving Deeper to Connect the Dots.

In the coming decades, eliminating malaria is the foremost goal of many tropical countries. Transmission control, along with an accurate and timely diagnosis of malaria, effective treatment and prevention are the different aspects that need to be met synchronously to accomplish the goal. The current review is focused on one of these aspects i.e., transmission control, by looking deeper into the event called gametogenesis. In the Plasmodium life cycle, gametocytes are the first life forms of the sexual phase. The transmission of the parasite and the disease is critically dependent on the number, viability and sex ratio of mature gametocytes and their further development inside mosquito vectors. Gametogenesis, the process of conversion of gametocytes into viable gametes, takes place inside the mosquito midgut, and is a tightly regulated event with fast and multiple rounds of DNA replication and diverse cellular changes going on within a short period. Interrupting the gametocyte-gamete transition is ought to restrict the successful transmission and progression of the disease and hence an area worth exploring for designing transmission-blocking strategies. This review summarizes an in-depth and up-to-date understanding of the biochemical and physiological mechanism of gametogenesis in Plasmodium, which could be targeted to control parasite and malaria transmission. This review also raises certain key questions regarding gametogenesis biology in Plasmodium and brings out gaps that still accompany in understanding the spectacular process of gametogenesis.

Teerakanchana's equation transcends over 12 other LDL-C quantification formulae in the North Indian population.

BACKGROUND: Over the last 3 decades, there has been a steady rise in global mortality due to cardiovascular diseases (CVDs). Therefore, timely diagnosis of CVDs is paramount. Low-Density Lipoprotein-cholesterol (LDL-C) in blood serum is one of the biomarkers for the risk assessment of CVDs, measured by direct assays and indirect approaches. The indirect method of LDL-C quantification by Friedewald's formula is more widely used in Indian clinical settings than direct assays due to its time and cost-effectiveness. However, its accuracy has been questioned for a long. We tried to find the formula that work in best agreement with the direct method. METHODS: Lipid profiling was done following a direct homogenous method (LDL-C_M) and LDL-C was calculated by 13 formula. The LDL-C values were categorized into groups based on TG. All the formula were statistically correlated with LDL-C_M. RESULTS: Teerakanchana's formula has shown a strong positive correlation (r = 0.914) and good agreement M (Lin's CCC = 0.929, CI = 0.918-0.939) with LDL-C_M, followed by Vujovic's formula (r = 0.903, Lin's CCC = 0.925, CI = 0.912-0.936). CONCLUSIONS: Teerakanchana and Vujovic's formula may replace Friedewald to quantify LDL-C in the public health care settings of the North Indian population.

Putative circumsporozoite protein (CSP) of Plasmodium vivax is considerably distinct from the well-known CSP and plays a role in the protein ubiquitination pathway.

Amidst technical challenges which limit successful culture and genetic manipulation of P. vivax parasites, we used a computational approach to identify a critical target with evolutionary significance. The putative circumsporozoite protein on chromosome 13 of P. vivax (PvpuCSP)is distinct from the well-known vaccine candidate PfCSP. The aim of this study was to understand the role of PvpuCSP and its relatedness to the well-known CSP. The study revealed PvpuCSP as a membrane bound E3 ubiquitin ligase involved in ubiquitination. It has a species-specific tetra-peptide unit which is differentially repeated in various P. vivax strains. The PvpuCSP is different from CSP in terms of stage-specific expression and function. Since E3 ubiquitin ligases are known antimalarial drug targets targeting the proteasome pathway, PvpuCSP, with evolutionary connotation and a key role in orchestrating protein degradation in P. vivax, can be explored as a potential drug target.

Putative circumsporozoite protein (CSP) of Plasmodium vivax is considerably distinct from the well-known CSP and plays a role in the protein ubiquitination pathway.

Amidst technical challenges which limit successful culture and genetic manipulation of P. vivax parasites, we used a computational approach to identify a critical target with evolutionary significance. The putative circumsporozoite protein on chromosome 13 of P. vivax (PvpuCSP)is distinct from the well-known vaccine candidate PfCSP. The aim of this study was to understand the role of PvpuCSP and its relatedness to the well-known CSP. The study revealed PvpuCSP as a membrane bound E3 ubiquitin ligase involved in ubiquitination. It has a species-specific tetra-peptide unit which is differentially repeated in various P. vivax strains. The PvpuCSP is different from CSP in terms of stage-specific expression and function. Since E3 ubiquitin ligases are known antimalarial drug targets targeting the proteasome pathway, PvpuCSP, with evolutionary connotation and a key role in orchestrating protein degradation in P. vivax, can be explored as a potential drug target.

Malaria diagnosis by PCR revealed differential distribution of mono and mixed species infections by Plasmodium falciparum and P. vivax in India.

Malaria is a vector-borne infectious disease, caused by five different species of the genus Plasmodium, and is endemic to many tropical and sub-tropical countries of the globe. At present, malaria diagnosis at the primary health care level in India is conducted by either microscopy or rapid diagnostic test (RDT). In recent years, molecular diagnosis (by PCR assay), has emerged as the most sensitive method for malaria diagnosis. India is highly endemic to malaria and shoulders the burden of two major malaria parasites, Plasmodium falciparum and P. vivax. Previous studies using PCR diagnostic assay had unraveled several interesting facts on distribution of malaria parasites in India. However, these studies had several limitations from small sample size to limited geographical areas of sampling. In order to mitigate these limitations, we have collected finger-prick blood samples from 2,333 malaria symptomatic individuals in nine states from 11 geographic locations, covering almost the entire malaria endemic regions of India and performed all the three diagnostic tests (microscopy, RDT and PCR assay) and also have conducted comparative assessment on the performance of the three diagnostic tests. Since PCR assay turned out to be highly sensitive (827 malaria positive cases) among the three types of tests, we have utilized data from PCR diagnostic assay for analyses and inferences. The results indicate varied distributional prevalence of P. vivax and P. falciparum according to locations in India, and also the mixed species infection due to these two species. The proportion of P. falciparum to P. vivax was found to be 49:51, and percentage of mixed species infections due to these two parasites was found to be 13% of total infections. Considering India is set for malaria elimination by 2030, the present malaria epidemiological information is of high importance.