Green Synthesis and Characterization of Silver Nanoparticles Using Moringa Peregrina and Their Toxicity on MCF-7 and Caco-2 Human Cancer Cells.

Introduction: The synthesis of nanoparticles using naturally occurring reagents such as vitamins, sugars, plant extracts, biodegradable polymers and microorganisms as reductants and capping agents could be considered attractive for nanotechnology. These syntheses have led to the fabrication of limited number of inorganic nanoparticles. Among the reagents mentioned above, plant-based materials seem to be the best candidates, and they are suitable for large-scale biosynthesis of nanoparticles. Methods: The aqueous extract of Moringa peregrina leaves was used to synthesize silver nanoparticles. The synthesized nanoparticles were characterized by various spectral studies including FT-IR, SEM, HR-TEM and XRD. In addition, the antioxidant activity of the silver nanoparticles was studied viz. DPPH, ABTS, hydroxyl radical scavenging, superoxide radical scavenging, nitric oxide scavenging potential and reducing power with varied concentrations. The anticancer potential of the nanoparticles was also studied against MCF-7 and Caco-2 cancer cell lines. Results: The results showed that silver nanoparticles displayed strong antioxidant activity compared with gallic acid. Furthermore, the anticancer potential of the nanoparticles against MCF-7 and Caco-2 in comparison with the standard Doxorubicin revealed that the silver nanoparticles produced significant toxic effects against the studied cancer cell lines with the IC50 values of 41.59 (Caco-2) and 26.93 (MCF-7) µg/mL. Conclusion: In conclusion, the biosynthesized nanoparticles using M. peregrina leaf aqueous extract as a reducing agent showed good antioxidant and anticancer potential on human cancer cells and can be used in biological applications.

Interval-valued bipolar complex fuzzy soft sets and their applications in decision making.

In this manuscript we demonstrate interval-valued bipolar complex fuzzy set (IVBCFS) and then interval-valued bipolar complex fuzzy soft set (IVBCFSS), as a generalization of fuzzy set, interval-valued fuzzy set, bipolar fuzzy set, complex fuzzy set and soft set. We also initiate operational laws and basic results and properties for IVBCFS and IVBCFSS. Further explanation is given for the basic algebraic operations like complement, extended union, extended intersection, restricted union, and restricted intersection, AND product and OR product for IVBCFSS. Moreover, we demonstrate some fundamental aggregation operators like IVBCFS average aggregation, IVBCFS geometric and as well as their properties. To emphasize the usefulness and application of the system, we also develop the decision-making method and joint instances of the IVBCFSS (set-ups 1 and 2). In order to describe the effectiveness and influence of the approaching novel work, this study uses a comparative analysis of the new creating concept with prevailing ideas.

Deep Learning-Based Ensembling Technique to Classify Alzheimer's Disease Stages Using Functional MRI.

The major issue faced by elderly people in society is the loss of memory, difficulty learning new things, and poor judgment. This is due to damage to brain tissues, which may lead to cognitive impairment and eventually Alzheimer's. Therefore, the detection of such mild cognitive impairment (MCI) becomes important. Usually, this is detected when it is converted into Alzheimer's disease (AD). AD is irreversible and cannot be cured whereas mild cognitive impairment (MCI) can be cured. The goal of this research is to diagnose Alzheimer's patients for timely treatment. For this purpose, functional MRI images from the publicly available dataset are used. Various deep-learning models have been used by the scientific community for the automatic detection of Alzheimer's subjects. These include the binary classification of scans of patients into MCI and AD stages, and limited work is carried out for multiclass classification of Alzheimer's disease up to six different stages. This study is divided into two steps. In the first step, a binary classification of the subject's scan is performed using Custom CNN. The second step involves the use of different deep learning models along with Custom CNN for multiclass classification of a subject's scan into one of the six stages of Alzheimer's disease. The models are evaluated based on different evaluation metrics, and the overall result of the models is improved using the max-voting ensembling technique. The experimental results show that an overall average accuracy of 98.8% is achieved for Alzheimer's stages classification.

Examining the Triple Burden of Malnutrition: Insights from a Community-Based Comprehensive Nutrition Survey among Indigenous Tribal Children (0-19 Years) in the Western Ghats Hills of India.

This article presents findings from a community-based cross-sectional study conducted in Attappadi, Kerala, India, aimed at assessing the prevalence of the triple burden of malnutrition among indigenous children aged 0-19 years. Historically, the indigenous population in Attappadi has faced significant developmental challenges, including high rates of malnutrition, infant mortality, and neonatal mortality. This study revealed alarming rates of undernutrition among children aged 0-59 months, with 40.9% experiencing stunting, 27.4% wasting, and 48.3% being underweight. Adolescent girls also suffered from undernutrition, with 21% classified as underweight and 43.3% experiencing stunting. Surprisingly, overweight or obesity was identified as a nutritional problem, affecting 1.4% of children aged 0-59 months, 4.2% of children aged 5-9 years, and 10.5% of adolescent girls. Additionally, a distressing proportion of young children aged 12-59 months (91.2%) were anaemic, with 50% diagnosed specifically with iron deficiency anaemia (IDA). Nearly all adolescent girls (96.6%) were reportedly suffering from anaemia. Deficiencies in vitamin B12, vitamin D, folate, and vitamin-A were prevalent among 35%, 20%, 16%, and 12% of children aged 12-59 months, respectively. The study underscores the urgent need for comprehensive interventions to address this triple burden of malnutrition. Recommendations include promoting culturally appropriate local food-based solutions, establishing participatory and community-led systems for health and nutrition information dissemination, and strengthening the nutrition surveillance system through village-level health and nutrition workers. By adopting a holistic approach, these interventions can help improve the nutritional status and well-being of the indigenous tribal children in Attappadi.

Proximate composition and mineral content of spices increasingly employed in the Mediterranean diet.

The present study aimed to investigate the nutritional constituents of common market available spices in the United Arab Emirates. Seven commonly consumed spices namely, ginger (Zingiber officinale), cinnamon (Cinnamomum verum), black seed (Nigella sativa), fenugreek (Trigonella foenum-graecum), cardamom (Elettaria cardamomum), cloves (Syzygium aromaticum) and saffron (Crocus sativus) were obtained from local markets. Proximate analyses were performed according to AOAC procedures. Assessment of major (Ca, K, Mg, Na, P and S) and minor (Co, Cu, Fe, Mn and Zn) elements was conducted using inductively coupled plasma optical emission spectrometry (ICP-OES). Findings revealed varying macronutrient, micronutrient and mineral contents which are highly valuable for dietary purposes. The present study demonstrates that these edible spices could be used for nutritional support, due to their micro and macronutrient contents.

IoMT Meets Machine Learning: From Edge to Cloud Chronic Diseases Diagnosis System.

In conventional healthcare, real-time monitoring of patient records and information mining for timely diagnosis of chronic diseases under certain health conditions is a crucial process. Chronic diseases, if not diagnosed in time, may result in patients' death. In modern medical and healthcare systems, Internet of Things (IoT) driven ecosystems use autonomous sensors to sense and track patients' medical conditions and suggest appropriate actions. In this paper, a novel IoT and machine learning (ML)-based hybrid approach is proposed that considers multiple perspectives for early detection and monitoring of 6 different chronic diseases such as COVID-19, pneumonia, diabetes, heart disease, brain tumor, and Alzheimer's. The results from multiple ML models are compared for accuracy, precision, recall, F1 score, and area under the curve (AUC) as a performance measure. The proposed approach is validated in the cloud-based environment using benchmark and real-world datasets. The statistical analyses on the datasets using ANOVA tests show that the accuracy results of different classifiers are significantly different. This will help the healthcare sector and doctors in the early diagnosis of chronic diseases.

O-glycan structures in apo(a) subunit of human lipoprotein(a) suppresses the pro-angiogenic activity of galectin-1 on human umbilical vein endothelial cells.

Apolipoprotein(a) [apo(a)] is a highly polymorphic O-glycoprotein circulating in human plasma as lipoprotein(a) [Lp(a)]. The O-glycan structures of apo(a) subunit of Lp(a) serve as strong ligands of galectin-1, an O-glycan binding pro-angiogenic lectin abundantly expressed in placental vascular tissues. But the pathophysiological significance of apo(a)-galectin-1 binding is not yet been revealed. Carbohydrate-dependent binding of galectin-1 to another O-glycoprotein, neuropilin-1 (NRP-1) on endothelial cells activates vascular endothelial growth factor receptor 2 (VEGFR2) and mitogen-activated protein kinase (MAPK) signaling. Using apo(a), isolated from human plasma, we demonstrated the potential of the O-glycan structures of apo(a) in Lp(a) to inhibit angiogenic properties such as proliferation, migration, and tube-formation in human umbilical vein endothelial cells (HUVECs) as well as neovascularization in chick chorioallantoic membrane. Further, in vitro protein-protein interaction studies have confirmed apo(a) as a superior ligand to NRP-1 for galectin-1 binding. We also demonstrated that the protein levels of galectin-1, NRP-1, VEGFR2, and downstream proteins in MAPK signaling were reduced in HUVECs in the presence of apo(a) with intact O-glycan structures compared to that of de-O-glycosylated apo(a). In conclusion, our study shows that apo(a)-linked O-glycans prevent the binding of galectin-1 to NRP-1 leading to the inhibition of galectin-1/neuropilin-1/VEGFR2/MAPK-mediated angiogenic signaling pathway in endothelial cells. As higher plasma Lp(a) level in women is an independent risk factor for pre-eclamsia, a pregnancy-associated vascular complication, we propose that apo(a) O-glycans-mediated inhibition of the pro-angiogenic activity of galectin-1 may be one of the underlying molecular mechanism of pathogenesis of Lp(a) in pre-eclampsia.

Defining atherosclerotic plaque biology by mass spectrometry-based omics approaches.

Atherosclerosis is the principal cause of vascular diseases and one of the leading causes of worldwide death. Even though several insights into its natural course, risk factors and interventions have been identified, it is still an ongoing global pandemic. Since the structure and biochemical composition of the plaques show high heterogeneity, a comprehensive understanding of the intraplaque composition, its microenvironment, and the mechanisms of the progression and instability across different vascular beds at their progression stages is crucial for better risk stratification and treatment modalities. Even though several cell-based studies, animal studies, and extensive multicentric population studies have been conducted concerning cardiovascular diseases for assessing the risk factors and plaque biology, the studies on human clinical samples are very limited. New novel approaches utilize samples from percutaneous coronary interventions, which could possibly gain more access to clinical samples at different stages of the diseases without complex invasive resections. As an emerging technological platform in disease discovery research, mass spectrometry-based omics technologies offer capabilities for a comprehensive understanding of the mechanisms linked to several vascular diseases. Here, we discuss the cellular and molecular processes of atherosclerosis, different mass spectrometry-based omics approaches, and the studies mostly done on clinical samples of atheroma plaque using mass spectrometry-based proteomics, metabolomics and lipidomics approaches.

Developing and demonstrating an atomistic and holistic model of anthropometric failure among children under five years of age using the National Family Health Survey (NFHS)-5 data from India.

Introduction: Composite Index of Anthropometric Failure (CIAF) and its further modifications have not incorporated all the combinations of malnutrition. We propose a new model incorporating all the forms of malnutrition among children under five years of age. However, the current models might misclassify a growing child as malnourished. Our objective is to develop a comprehensive scoring system using the three anthropometric Z-scores [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z-scores] and demonstrate the proposed CIAF model using the National Family Health Survey-5 (NFHS-5) data from India. Methods: A new scoring system was developed using the WAZ, HAZ, and WHZ scores to determine the child's nutritional status. We also proposed a new CIAF model by including all possible categories of malnutrition and practically demonstrated it using the NFHS-5 dataset after applying the new scoring system. Under-five children with heights, weights, and ages available were included in the analysis. The groups of malnutrition are presented as weighted proportions before and after applying the new score to the proposed model. Results: Our final analysis included individual-level data of 198,802 children under five years of age (weighted N = 195,197). After applying the new scoring system to the proposed model, the prevalence of stunting has reduced to 11.8% (95% CI 11.66-11.94) from 13.2% (95% CI 13.09-13.39) and wasting prevalence has reduced to 4.9% (95% CI 4.85-5.04) from 6.4% (95% CI 6.29-6.51). The most common forms of anthropometric failures among Indian children by using the newly developed CIAF model are: "Stunting and underweight" (30,127; 15.4%), Stunting only (23,035; 11.8%), and "wasting and underweight" (14,698; 7.5%). We found a new category called "Stunting, underweight, and overweight" (stunting = HAZ < -2SD, underweight = WAZ < -2SD, overweight = WHZ > +2SD). It constituted 0.1% (220 children) of the total sample. Conclusion: When the new scoring system is applied to the proposed CIAF model, it captures all forms and combinations of malnutrition among under-five children without overlap and prevents misclassifying a growing child as malnourished. The newly identified category shows that stunting (HAZ < -2SD), overweight (WHZ > +2SD) and underweight (WAZ < -2SD) can co-exist in the same child.

Cyclophilin A Impairs Efferocytosis and Accelerates Atherosclerosis by Overexpressing CD 47 and Down-Regulating Calreticulin.

Impairment of efferocytosis in apoptotic macrophages is a known determinant of the severity of atherosclerosis and the vulnerability of plaques to rupture. The precise mechanisms involved in impaired efferocytosis are unclear. Given the well-recognized role of the inflammatory cytokine cyclophilin A (Cyp A) in modulating several atherogenic mechanisms in high-glucose primed monocytes, we investigated the role of Cyp A in macrophage efferocytosis. The efficiency of efferocytosis in RAW 264.7 macrophages grown in vitro and primed with cyclophilin A was assessed using flow cytometry and confocal assays. Cholesterol content in cells was measured using cell-based cholesterol efflux assay. Proteomic analysis and bioinformatics tools were employed to decipher the link between cyclophilin A and the known ligand receptors involved in efferocytosis. Cyclophilin A was found to impair efferocytosis in apoptotic macrophages by reducing ABCA1-mediated cholesterol efflux in foam cells derived from macrophages. Cyclophilin A-primed macrophages showed an increase in expression of the don't-eat-me signal CD 47 and a decrease in the expression of the eat-me signal, calreticulin. Phagocytosis was restored upon silencing of cyclophilin A. New Zealand white rabbits were fed a high-fat diet, and lesions in their aortae were analyzed histologically for evidence of atherosclerosis and the expression of Cyp A, CD 47 and calreticulin, the ligand receptor involved in efferocytosis. Gene and protein expressions in aortae and macrophages were analyzed by real-time PCR and Western blotting. Cyclophilin A, via its effects on the expression of CD 47 and calreticulin, impairs efferocytosis in apoptotic macrophages. Together with its impact on cholesterol efflux from macrophages, these effects can amplify other mechanisms of Cyp A in accelerating the progression of atherosclerosis.

Yield and In Vitro Antioxidant Potential of Essential Oil from Aerva javanica (Burm. f.) Juss. ex Schul. Flower with Special Emphasis on Seasonal Changes.

The essential oil (EO) of the desert cotton (Aerva javanica (Burm. f.) Juss. ex Schul.) was extracted by hydrodistillation, from A. javanica flowers growing in the sandy soils of the United Arab Emirates (UAE) wild desert. The influence of seasonal variation on flowers' EO yield was studied. The flowers' EO yield obtained from spring samples (0.011%) was significantly the highest followed by early summer (0.009%), winter (0.007%), and autumn samples (0.006%), respectively. The flowers' EO antioxidant analysis were tested by DPPH, FRAP and ABTS assays (in vitro). Results proved that A. javanica flowers' EO, isolated during the four seasons, is a good source of natural bioactive antioxidants. Based on the three tested assays, the highest antioxidant activity was recorded in the spring. Testing of the chemical composition of the flowers' EO was conducted for the season with the highest yield and the best antioxidant performance, recorded in spring, by a combination of gas chromatograph (GC) and gas chromatograph-mass spectrometer (GC-MS). This led to the identification of 29 volatile components, in which the flowers' oil was characterized by angustione as a major compound. Photos by scanning electron microscope (SEM) showed prominent availability of star-shaped trichomes in the epidermis of the flowers.

Function of Chloroplasts in Plant Stress Responses.

The chloroplast has a central position in oxygenic photosynthesis and primary metabolism. In addition to these functions, the chloroplast has recently emerged as a pivotal regulator of plant responses to abiotic and biotic stress conditions. Chloroplasts have their own independent genomes and gene-expression machinery and synthesize phytohormones and a diverse range of secondary metabolites, a significant portion of which contribute the plant response to adverse conditions. Furthermore, chloroplasts communicate with the nucleus through retrograde signaling, for instance, reactive oxygen signaling. All of the above facilitate the chloroplast's exquisite flexibility in responding to environmental stresses. In this review, we summarize recent findings on the involvement of chloroplasts in plant regulatory responses to various abiotic and biotic stresses including heat, chilling, salinity, drought, high light environmental stress conditions, and pathogen invasions. This review will enrich the better understanding of interactions between chloroplast and environmental stresses, and will lay the foundation for genetically enhancing plant-stress acclimatization.

Ultra-Low-Power, High-Accuracy 434 MHz Indoor Positioning System for Smart Homes Leveraging Machine Learning Models.

Global navigation satellite systems have been used for reliable location-based services in outdoor environments. However, satellite-based systems are not suitable for indoor positioning due to low signal power inside buildings and low accuracy of 5 m. Future smart homes demand low-cost, high-accuracy and low-power indoor positioning systems that can provide accuracy of less than 5 m and enable battery operation for mobility and long-term use. We propose and implement an intelligent, highly accurate and low-power indoor positioning system for smart homes leveraging Gaussian Process Regression (GPR) model using information-theoretic gain based on reduction in differential entropy. The system is based on Time Difference of Arrival (TDOA) and uses ultra-low-power radio transceivers working at 434 MHz. The system has been deployed and tested using indoor measurements for two-dimensional (2D) positioning. In addition, the proposed system provides dual functionality with the same wireless links used for receiving telemetry data, with configurable data rates of up to 600 Kbauds. The implemented system integrates the time difference pulses obtained from the differential circuitry to determine the radio frequency (RF) transmitter node positions. The implemented system provides a high positioning accuracy of 0.68 m and 1.08 m for outdoor and indoor localization, respectively, when using GPR machine learning models, and provides telemetry data reception of 250 Kbauds. The system enables low-power battery operation with consumption of <200 mW power with ultra-low-power CC1101 radio transceivers and additional circuits with a differential amplifier. The proposed system provides low-cost, low-power and high-accuracy indoor localization and is an essential element of public well-being in future smart homes.

Biochemical Changes and Antioxidant Variations in Date Palm (Phoenix dactylifera L.) Varieties during Flower Induction and Development.

The present investigation was carried out to explore the biochemical changes and antioxidant variations, including non-enzymatic and enzymatic antioxidant variations, in the leaves of different varieties of date palm (Phoenix dactylifera L.) belonging to the early, mid-, and late-flowering categories in the United Arab Emirates. The changes in the protein and phenol concentration; the ascorbic acid, reduced glutathione, and α-tocopherol contents; and the activity of peroxidase and polyphenol oxidase were studied in the leaves during the preflowering, flowering, and postflowering stages of the date palms. Two varieties each from the early (Shaham, Khanezi), mid- (Barhee, Nabthasaif), and late- (Khasab, Fardh) flowering types were used in this study. The protein content in the leaves was higher in the early flowering varieties during the preflowering stage but lower in the other two varieties. The phenol content showed an opposite trend to the protein. There was significant variation in the ascorbic acid content and a reduction in glutathione and α-tocopherol between the leaves of different varieties. Similarly, the activity of the antioxidant enzyme ascorbate peroxidase in the leaves was higher during the preflowering stage in all varieties. The superoxide dismutase (SOD), polyphenol oxidase (PPO), and catalase (CAT) activity was highest in the Bharhee leaves for all the stages. The peroxidase activity (POD) was highest in the Fardh variety of date palm, whereas the Khanezi variety exhibited the lowest activity. This study can be used as a baseline for developing more protocols for understanding the possible roles of biochemicals, antioxidants, antioxidant enzymes, and their interactions in the regulation of flower development in different date palm varieties.

The Essential Oil-Bearing Plants in the United Arab Emirates (UAE): An Overview.

Essential Oils (EOs) are expensive hydrocarbons produced exclusively by specific species in the plant kingdom. Their applications have deep roots in traditional herbal medicine, which lacks scientific evidence. Nowadays, more than ever, there is a growing global interest in research-based discoveries that maintain and promote health conditions. Consequently, EOs became a much attractive topic for both research and industry, with revenues reaching billions of dollars annually. In this work, we provide key guidance to all essential oil-bearing plants growing in the United Arab Emirates (UAE). The comprehensive data were collected following an extensive, up-to-date literature review. The results identified 137 plant species, including indigenous and naturalized ones, in the UAE, citing over 180 published research articles. The general overview included plant botanical names, synonyms, common names (Arabic and English), families and taxonomic authority. The study acts as a baseline and accelerator for research, industry and discoveries in multiple disciplines relying on essential oil-bearing plants.

Contributions of TOR Signaling on Photosynthesis.

The target of rapamycin (TOR) protein kinase is an atypical Ser/Thr protein kinase and evolutionally conserved among yeasts, plants, and mammals. TOR has been established as a central hub for integrating nutrient, energy, hormone, and environmental signals in all the eukaryotes. Despite the conserved functions across eukaryotes, recent research has shed light on the multifaceted roles of TOR signaling in plant-specific functional and mechanistic features. One of the most specific features is the involvement of TOR in plant photosynthesis. The recent development of tools for the functional analysis of plant TOR has helped to uncover the involvement of TOR signaling in several steps preceding photoautotrophy and maintenance of photosynthesis. Here, we present recent novel findings relating to TOR signaling and its roles in regulating plant photosynthesis, including carbon nutrient sense, light absorptions, and leaf and chloroplast development. We also provide some gaps in our understanding of TOR function in photosynthesis that need to be addressed in the future.

Proteomics Analysis Reveals Diverse Molecular Characteristics between Endocardial and Aortic-Valvular Endothelium.

The variations in the protein profile of aortic-valvular (AVE) and endocardial endothelial (EE) cells are currently unknown. The current study's objective is to identify differentially expressed proteins and associated pathways in both the endothelial cells. We used endothelial cells isolated from the porcine (Sus scrofa) aortic valve and endocardium for the profiling of proteins. Label-free proteomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our proteomics analysis revealed that 29 proteins were highly expressed, and 25 proteins were less expressed in the valve than the endocardial endothelium. The cell surface markers, such as CD63, ICAM1, PECAM1, PROCR, and TFRC, were highly expressed in EE. In contrast, CD44 was highly expressed in AVE. The pathway analysis showed that metabolic process-related proteins and extracellular matrix-related proteins were enriched in valves. Differential enrichment of signaling pathways was observed in the endocardium. The hemostasis function-related proteins were increased in both endothelial cells. The proteins and pathways enriched in aortic-valvular and endocardial endothelial cells revealed the distinct phenotype of these two closely related cells.

Cyclophilin A induces macrophage apoptosis and enhances atherosclerotic lesions in high-fat diet-fed hyperglycemic rabbits.

Macrophage apoptosis is a key contributor to the progression of atherosclerosis. Cyclophilin A, a monocyte secretory protein associated with the initiation of atherosclerosis has an inherent nuclease activity. This study reports the mechanism by which cyclophilin A causes apoptosis of macrophages and accelerates the progression of atherosclerosis. Aortic lesion formation and apoptosis were studied in New Zealand White rabbits (NZW) which were fed high-fat diet (HFD) for 12 weeks. Using monocytes and HFD-fed rabbits we demonstrate that cyclophilin A induces mitochondrial membrane potential loss and mitochondrial pore transition protein opening through caspase 3 activation. En face staining revealed a significant increase in the lesion area in HFD-fed rabbits. Levels of glucose, cholesterol and proinflammatory cytokines were higher in these animals compared to rabbits fed with a normal diet. In the aorta of HFD-fed rabbits, medial vascular smooth muscle cells were disorganized and there was a loss of integrity of the endothelium. An 8-fold increase was seen in the number of apoptotic cells in the lesion area of HFD-fed NZW rabbits which were associated with an elevation in plasma cyclophilin A levels. siRNA knockdown of cyclophilin A gene reduced activation of caspase 3 in macrophages. Treatment with cyclosporine A, an inhibitor of cyclophilin A, significantly attenuated apoptosis in macrophages. Our study indicates that inhibitors of proinflammatory cytokines such as cyclophilin A may arrest macrophage apoptosis and result in a regression of advanced atherosclerotic lesions.

Hyperhomocysteinemia-related serum metabolome alterations not normalized by short-term folic acid treatment.

INTRODUCTION: Hyperhomocysteinemia (HHCys) is an independent risk factor for various diseases such as cardiovascular diseases, Alzheimer's, and cancers. Folate deficiency is one of the significant reasons for HHCys. However, it is not known whether folate deficiency with HHCys is associated with any serum metabolites. OBJECTIVES: Our objective was to identify the metabolic alterations in people having folate deficiency with HHCys and check whether a short-term folic acid therapy could reverse those metabolic changes. METHODS: The study enrolled 34 participants aged between 18 and 40 years having folate deficiency (< 4.6 ng/mL) with HHCys (> 15 µmol/L) and 21 normal healthy individuals. A short-term intervention of oral folic acid (5 mg/day) was done in the HHCys group for 30 days. Untargeted metabolomics analysis of serum was performed in all study subjects before and after the folic acid treatment. Different univariate methods and the multivariable-adjusted linear regression models were employed to determine an association between homocysteine level and metabolite profile. RESULTS: Metabolomics analysis data showed that many metabolites involved in the biochemical pathways of lipid metabolisms such as polyunsaturated fatty acids, glycerolipids, and phospholipids were downregulated in the HHCys group. Short-term oral folic acid therapy significantly reduced their serum homocysteine level. However, the metabolic pathway alterations observed in folate-deficient HHCys-condition were unaltered even after the folic acid treatment. CONCLUSIONS: Our study revealed that people who have a folic acid deficiency with HHCys have an altered metabolite profile related to lipid metabolism, which cannot be reversed by short-term folic acid therapy.

Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum.

Epigenetic modifications have emerged as critical regulators of virulence genes and stage-specific gene expression in Plasmodium falciparum. However, the specific roles of histone core epigenetic modifications in regulating the stage-specific gene expression are not well understood. In this study, we report an unconventional trimethylation at lysine 64 on histone 3 (H3K64me3) and characterize its functional relevance in P. falciparum. We show that PfSET4 and PfSET5 proteins of P. falciparum methylate H3K64 and that they prefer the nucleosome as a substrate over free histone 3 proteins. Structural analysis of PfSET5 revealed that it interacts with the nucleosome as a dimer. The H3K64me3 mark is dynamic, being enriched in the ring and trophozoite stages and drastically reduced in the schizont stages. Stage-specific global chromatin immunoprecipitation -sequencing analysis of the H3K64me3 mark revealed the selective enrichment of this methyl mark on the genes of exported family proteins in the ring and trophozoite stages and a significant reduction of the same in the schizont stages. Collectively, our data identify a novel epigenetic mark that is associated with the subset of genes encoding for exported proteins, which may regulate their expression in different stages of P. falciparum.