Publications by authors named "Sruti Shiva"

Communication between intracellular organelles including lysosomes and mitochondria has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction, LMI) is, emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival.

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  • - Alzheimer's Disease (AD) and related dementias are becoming a major worldwide issue due to the aging population, characterized by damage to neurological tissue and the presence of amyloid plaques and neurofibrillary tangles.
  • - Recent research has focused on the role of reactive oxygen species (ROS), particularly the NADPH Oxidase 2 (NOX2) protein, which is linked to inflammation and vascular processes in the brain and plays a key role in AD development.
  • - This review highlights the latest findings on how NOX2 contributes to the progression of AD and discusses promising therapies targeting NOX2 for managing and treating the disease.
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  • Reproductive status significantly affects metabolism and health throughout an organism's lifespan, with mitochondrial function being a key mediator in this relationship.
  • Research using a germline ablation model showed that loss of germline stem cells (GSC) decreases mitochondrial volume and respiratory function in young adults, yet helps preserve mitochondrial activity as organisms age and when facing cold stress, leading to better survival rates.
  • The study identified that the transcription factor NHR-49/PPARα is crucial for maintaining mitochondrial health and cold stress resistance, highlighting the complex interplay between reproductive signals and overall health.
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The monomeric heme protein myoglobin (Mb) is aberrantly expressed in approximately 40 % of breast tumors. Mb expression is associated with better patient prognosis, yet the molecular mechanisms underlying this effect are unclear. In muscle, Mb's heme moiety confers oxygen storage and delivery.

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There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice.

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  • Ischemic strokes disrupt mitochondrial function in brain endothelial cells, leading to long-term neurological issues.
  • A study found that using extracellular vesicles (EVs) from mouse brain endothelial cells (mBECs) showed better therapeutic effects in mouse models than those from human cells (hBECs).
  • mBEC-derived EVs enhanced ATP production and mitochondrial function while reducing brain damage and improving neurological outcomes in stroke-affected mice.
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Background: Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.

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Introduction: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI.

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Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice at 20% of daily caloric intake for nine weeks.

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Thrombosis and inflammation are intimately linked and synergistically contribute to the pathogenesis of numerous thromboinflammatory diseases, including sickle cell disease (SCD). While platelets are central to thrombogenesis and inflammation, the molecular mechanisms of crosstalk between the 2 remain elusive. High-mobility group box 1 (HMGB1) regulates inflammation and stimulates platelet activation through Toll-like receptor 4.

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Background: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ).

Objective: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region.

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The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation.

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  • Ischemic strokes cause long-term neurological issues due to mitochondrial dysfunction in brain endothelial cells, which form the blood-brain barrier.
  • A pilot study indicated that using extracellular vesicles (EVs) from human brain endothelial cells may help post-stroke, but mouse-derived EVs (mBEC-EVs) showed better results in mice, particularly in enhancing mitochondrial function and ATP levels.
  • The study found that mBEC-EVs significantly reduced brain damage and improved neurological scores in mice after a stroke, suggesting that mBEC-EVs could be a more effective therapy in preclinical models.
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  • The study explores how hypoxia affects blood vessel behavior in pulmonary arterial hypertension (PAH) through a genetic and epigenetic mechanism involving HIF-2α.
  • HIF-2α enhances the expression of certain genes and long noncoding RNAs that contribute to increased vascular dysfunction, creating a feedback loop that further boosts HIF-2α activity.
  • A specific genetic variant (rs73184087) is linked to an increased risk of PAH; interventions that either inhibit this pathway or reduce HIF-2α levels showed protective effects against the disease in animal models.
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  • Metabolic changes in pediatric diffuse midline glioma are influenced by the H3K27M histone mutation, which activates oncogenic pathways.
  • The RAS pathway and ERK5 kinase are crucial for tumor growth in these gliomas, with ERK5 playing a key role in cell proliferation and glycolysis.
  • Targeting the ERK5-PFKFB3 signaling axis with multi-targeted drugs could be an effective treatment strategy for patients with this type of cancer.
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Introduction: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation.

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Clinical studies report that viral infections promote acute or chronic bacterial infections at multiple host sites. These viral-bacterial co-infections are widely linked to more severe clinical outcomes. In experimental models in vitro and in vivo, virus-induced interferon responses can augment host susceptibility to secondary bacterial infection.

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Rationale & Objective: To address the need for an intradialytic exercise program that is easily delivered in clinical setting, engaging and scalable, we developed a novel COMprehensive EXercise (COMEX) program based on input from patients receiving hemodialysis (HD), dialysis staff members and nephrologists. The objective of this study was to determine the feasibility, safety, and acceptance of COMEX during HD.

Study Design: Single-arm prospective pilot feasibility study.

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Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on the basis of shared etiology are required to ensure the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD.

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Introduction: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation.

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Tumor growth and proliferation are regulated by numerous mechanisms. Communication between intracellular organelles has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction) is emerging as a major determinant of tumor proliferation and growth.

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General control of amino acid synthesis 5-like 1 (GCN5L1) was previously identified as a key regulator of protein lysine acetylation in mitochondria. Subsequent studies demonstrated that GCN5L1 regulates the acetylation status and activity of mitochondrial fuel substrate metabolism enzymes. However, the role of GCN5L1 in response to chronic hemodynamic stress is largely unknown.

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Deficiency of iron‑sulfur (FeS) clusters promotes metabolic rewiring of the endothelium and the development of pulmonary hypertension (PH) in vivo. Joining a growing number of FeS biogenesis proteins critical to pulmonary endothelial function, recent data highlighted that frataxin (FXN) reduction drives Fe-S-dependent genotoxic stress and senescence across multiple types of pulmonary vascular disease. Trinucleotide repeat mutations in the FXN gene cause Friedreich's ataxia, a disease characterized by cardiomyopathy and neurodegeneration.

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