Reversing PAI-1 deficiency in blood using mRNA lipid nanoparticles.

Plasminogen activator inhibitor-1 (PAI-1) deficiency is a rare disorder that causes moderate to severe bleeding and cardiac fibrosis, caused by mutation in the gene and no detectable circulating PAI-1 protein. There are currently no therapies that can effectively replace PAI-1 because the protein has a short half-life. An alternative approach to using recombinant protein is to endogenously increase circulating PAI-1 levels using mRNA therapy.

Physical and mental well-being of older adults: examining the impact of financial support from male migrant children on Indian left-behind parents.

Background: Amid high youth out-migration, India's older parents face severe social, economic, psychological, and health crises due to their children's separation. However, remittances from their migrant children alleviate economic hardships, improve healthcare access, and partially compensate for their absence. So, this study examines how adult-child migration affects older parents' physical and mental health and how remittance support helps mitigate these challenges.

Gelsolin controls the release of phosphatidylserine (PS)-positive microvesicles (MVs) from platelets.

Upon activation by vascular injury or extracellular agonists, platelets undergo rapid change shape, a process regulated by the actin cytoskeleton and accessory proteins. Platelet shape change is accompanied by the secretion of hemostatic factors and immunomodulatory cytokines from their intracellular granules, as well as the release of microvesicles (MVs) containing pro-inflammatory cytokines and procoagulant phosphatidylserine (PS). However, the role of actin dynamics in MV generation remains unclear.

Gelsolin regulates receptor-mediated and fluid-phase endocytosis in platelets.

Background: Endocytosis is the process by which platelets incorporate extracellular molecules into their secretory granules. Endocytosis is mediated by the actin cytoskeleton in nucleated cells; however, the endocytic mechanisms in platelets are undefined.

Objectives: To better understand platelet endocytosis, we studied gelsolin (Gsn), an actin-severing protein that promotes actin assembly.

Oxidative Stress-Induced Platelet Apoptosis/Activation: Alleviation by Purified Curcumin via ASK1-JNK/p-38 Pathway.

Platelets are known for their indispensable role in hemostasis and thrombosis. However, alteration in platelet function due to oxidative stress is known to mediate various health complications, including cardiovascular diseases and other health complications. To date, several synthetic molecules have displayed antiplatelet activity; however, their uses are associated with bleeding and other adverse effects.

Genetically engineered transfusable platelets using mRNA lipid nanoparticles.

Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors.

Does early-life migration experience determine health and health-risk behavior in later life? Evidence from elderly returns migrants in Kerala, India.

Becoming elderly is an intrinsic part of life, and the burden of disease increases with age. However, the early life migration experience and occupational hazards at the destination can lead to serious health problems later in life. This study aims to understand the association between early life migration and the health and risky behavior of elderly return migrants using data from the Kerala Migration Survey in 2018.

A novel association between platelet filamin A and soluble N-ethylmaleimide sensitive factor attachment proteins regulates granule secretion.

Background And Objective: The molecular mechanisms that underpin platelet granule secretion remain poorly defined. Filamin A (FLNA) is an actin-crosslinking and signaling scaffold protein whose role in granule exocytosis has not been explored despite evidence that gene mutations confer platelet defects in humans.

Methods And Results: Using platelets from platelet-specific conditional -knockout mice, we showed that the loss of FLNA confers a severe defect in alpha (α)- and dense (δ)-granule exocytosis, as measured based on the release of platelet factor 4 (aka CXCL4) and adenosine triphosphate (ATP), respectively.

Gelsolin Modulates Platelet Dense Granule Secretion and Hemostasis via the Actin Cytoskeleton.

Background And Objective:  The mechanisms underlying platelet granule release are not fully understood. The actin cytoskeleton serves as the platelet's structural framework that is remodeled upon platelet activation. Gelsolin is a calcium-dependent protein that severs and caps existing actin filaments although its role in modulating platelet granule exocytosis is unknown.

Apoptosis in platelets is independent of the actin cytoskeleton.

Homeostasis between platelet production and clearance is essential for human health. A critical facet of the balance that facilitates platelet clearance from the circulation is apoptosis (programmed cell death). The precise cellular mechanisms that underpin platelet apoptosis are not defined.

Implementation of Genetic Engineering and Novel Omics Approaches to Enhance Bioremediation: A Focused Review.

Bioremediation itself is considered to be a cost effective soil clean-up technique and preferred over invasive physical and chemical treatments. Besides increasing efficiency, application of genetic engineering has led to reduction in the time duration required to achieve remediation, overcoming the so called 'Achilles heel' of Bioremediation. Omics technologies, namely genomics, transcriptomics, proteomics, and metabolomics, are being employed extensively to gain insights at genetic level.

Bisphenol AF elevates procoagulant platelets by inducing necroptosis via RIPK1-inflammasome axis.

Bisphenol AF, an analogue of Bisphenol A, is an important raw material used in the production of plastic and rubber substances like plastic bottles and containers, toys, and medical supplies. Increased contamination of air, water, dust, and food with BPA/BPAF, poses an enormous threat to humans, globally. BPAF/BPA are endocrine-disrupting chemicals that mimic estrogen hormone, thus increasing the risks of various metabolic and chronic disorders.

Harnessing symbiosis for phytoremediation of soil contaminated with lead, cadmium, and arsenic.

This study investigates the impact of on heavy metal(loid) (HM) uptake efficiency of pea ( L.) plants along with physiological and biochemical parameters. Plants were grown in soil spiked with HMs (Pb and As: 50 and 100 mg kg; Cd: 25 and 50 mg kg) and a multi-metal(loid) (Mm: Pb + Cd + As) combination, inoculated/non-inoculated with .

Bisdemethoxycurcumin promotes apoptosis in human platelets via activation of ERK signaling pathway.

Curcumin, a major bioactive component of turmeric (Curcuma longa), is known for its multiple health benefits. Curcumin as such is a mixture of its analogs: bisdemethoxycurcumin (BDMC)-3%, and demethoxycurcumin (DMC)-17%. Although the effect of curcumin on platelets is documented, the effect of BDMC and DMC on platelets is less studied.

Anatomical locations of air for rapid diagnosis of pneumothorax in blunt trauma patients.

Background: Bedside diagnostic ultrasound for traumatic pneumothorax is easy and reliable. However, the thoracic anatomical locations to be examined are debateable. We aimed to study the anatomical locations of blunt traumatic pneumothoraces as defined by chest CT scan to identify the areas that should be scanned while performing bedside diagnostic ultrasound.

Polar Switching and Cybotactic Nematic Ordering in 1,3,4-Thiadiazole-Based Short-Core Hockey Stick-Shaped Fluorescent Liquid Crystals.

We report here the synthesis and thermotropic properties of novel short-core hockey stick-shaped liquid crystalline molecules based on the 1,3,4-thiadiazole core. Polar switching behavior is observed in the cybotactic nematic and smectic mesophases for the bent-core thiadiazole derivatives. The presence of the lateral methoxy moiety in the outer phenyl ring of the four-ring molecules facilitates the formation of spontaneous ordering in the nematic phase observed via X-ray diffraction measurements.

Metal(loid) induced toxicity and defense mechanisms in Spinacia oleracea L.: Ecological hazard and Prospects for phytoremediation.

A pot study was conducted to assess the phytoremediation potential of Spinach plants along with their physiological and biochemical response when grown in soil contaminated with heavy metal(loid)s (HMs). Plants were grown under different doses of Pb, Cd and As; and their metal(loid) accumulation efficiency was studied upon harvest; expressed in terms of bioabsorption coefficient (BAC), bioconcentration factor (BCF) and translocation factor (TF). Results showed significant (p ≤ 0.

EDTA-Assisted Metal Uptake in Raphanus sativus L. and Brassica oleracea L.: Assessment of Toxicity and Food Safety.

A study was conducted to determine the effect of ethylenediaminetetraacetic acid (EDTA) on phytoextraction potential of radish and cabbage. Plant biomass, photosynthetic pigments, proline and phenolics were significantly affected by the accumulation of heavy metals (HM). The metal uptake potential was increased significantly by the application of EDTA.

Porphyromonas gingivalis lipopolysaccharide activates platelet Cdc42 and promotes platelet spreading and thrombosis.

Background: Periodontitis confers an increased risk for cardiovascular diseases, including thrombosis. However, the molecular mechanisms that potentially link periodontitis with thrombosis are undefined. Here we test the hypothesis that Gram-negative periodontal infection promotes pathological platelet activation and amplifies shape change.

A new pyrrole based small molecule from Tinospora cordifolia induces apoptosis in MDA-MB-231 breast cancer cells via ROS mediated mitochondrial damage and restoration of p53 activity.

Approximately 15% of globally diagnosed breast cancers are designated as triple negative breast cancer (TNBC). In this study, we investigated the effect of the natural compound, Bis(2- ethyl hexyl) 1H-pyrrole-3,4-dicarboxylate (TCCP), purified from Tinospora cordifolia on MDA-MB-231, a TNBC cell line. The pro-apoptotic nature of TCCP on MDA-MB-231 was determined by assessing various apoptotic markers.

Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity.

Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities.

Effect of Glomus mossae on accumulation efficiency, hazard index and antioxidant defense mechanisms in tomato under metal(loid) Stress.

In the present study, the phytoremedation potential along with growth, physiological and biochemical response of tomato (Solanum lycopersicum) was assessed under heavy metal(loid) (HM) and arbuscular mycorrhizal fungus (AMF) amendment. Effect of AMF on uptake and accumulation of metal(loid)s was assessed and accumulation characteristics were expressed in terms of bioabsorption coefficient (BAC), bioconcentration factor (BCF), translocation factor (TLF) and transfer factor (TF). Results showed that AMF-inoculated plants showed not only a better growth, chlorophyll content, strengthened non-enzymatic and enzymatic defense mechanism, but also accumulated higher concentration of metal(loid)s.

Aggregation is impaired in starved platelets due to enhanced autophagy and cellular energy depletion.

Platelet hyperactivity is the hallmark of thrombosis and hemostasis disorders including atherosclerosis, diabetes, stroke, arthritis, and cancer causing significant mortality and morbidity. Therefore, regulating platelet hyperactivity is an ever growing interest. Very recently, basal autophagic process has been demonstrated to be essential for normal functioning of platelets.

Citrus Epicarp-Derived Biochar Reduced Cd Uptake and Ameliorates Oxidative Stress in Young Abelmoschus esculentus (L.) Moench (okra) Under Low Cd Stress.

Due to the important role of biochar (BC) in reducing metal-toxicity in plants, this study was aimed at assessing the potential of citrus epicarp-derived BC in ameliorating Cd toxicity in young Abelmoschus esculentus (okra) under low Cd toxicity. Okra was grown in soil amended with BC at four treatment levels for 49 days as follows: control (A), sole 1.4 mg Cd/kg-spiked soil (B), 1.

Metal(loid) accumulation in aquatic plants of a mining area: Potential for water quality biomonitoring and biogeochemical prospecting.

Aquatic bryophytes can accumulate extremely high levels of chemical elements because of their unique morphology and physiology which is markedly different from vascular plants. Four aquatic mosses-Fontinalis squamosa, Brachythecium rivulare, Platyhypnidium riparioides, Thamnobryum alopecurum-and a freshwater red alga Lemanea fluviatilis along with water samples from the streams of Góis mine region in Central Portugal were analyzed for 46 elements. Despite being below detection levels in the water samples, the elements Zr, V, Cr, Mo, Ru, Os, Rh, Ir, Pt, Ag, Ge and Bi were obtained in the plant samples.