Publications by authors named "Gagan Deep"
Background: Animal studies provide evidence of a link between exosome profile, obesity and insulin resistance (IR). Although it is known that exosomes mediate cell-cell communication via their macromolecular cargo, the factors regulating exosomes in humans are unknown.
Methods: Leveraging genome-wide expression and genotype data from the African American Genetics of expression and Metabolism (AAGMEx) cohort, we focused on 262 genes in "Exosome pathway", curated by us, to examine the relationship of the expression of these genes with IR and obesity and tested the role of single nucleotide polymorphisms (SNPs) in determining the variability in the expression of these genes in adipose and muscle tissue.
Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral insulin resistance (PIR) and neuronal insulin signaling abnormalities (NISAs) relate to executive function and functional brain network topology. Older adults (n = 71) with obesity but without type 2 diabetes were included. PIR was quantified by HOMA2-IR.
View Article and Find Full Text PDFIntroduction: Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders.
Methods: We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts.
Introduction: Osteoarticular TB contributes to roughly 10% of the cases of extrapulmonary TB. The incidence of osteoarticular tuberculosis is one of the lowest in extrapulmonary tuberculosis, probably only next to cutaneous tuberculosis in non-HIV patients. Considering the low incidence of primary osteoarticular tuberculosis without pulmonary tuberculosis, we hypothesise that there is an element of tissue-specific immunity against tuberculosis in the body, which appears to be very high in bone and joints.
View Article and Find Full Text PDFEffects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed With Positron Emission Tomography Imaging and Neuronally Derived Exosomes.
Biol Psychiatry
March 2025
Background: The current study utilized positron emission tomography (PET) imaging to examine how long-term cocaine self-administration (SA) and time off cocaine affected kappa opioid receptor (KOR) availability in the brain of previously cocaine-naïve monkeys. In addition, neuronally derived small extracellular vesicles (NDEs) were measured from plasma to identify peripheral measures of KORs.
Methods: Female (n = 6) and male (n = 7) cynomolgus monkeys, living in stable same-sex social groups, were trained to self-administer intravenous cocaine.
Objective: Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology.
Methods: Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR.
Extracellular vesicles (EVs) have emerged as novel blood-based biomarkers for various pathologies. The development of methods to enrich cell-specific EVs from biofluids has enabled us to monitor difficult-to-access organs, such as the brain, in real time without disrupting their function, thus serving as liquid biopsy. Burgeoning evidence indicates that the contents of neuron-derived EVs (NDEs) in blood reveal dynamic alterations that occur during neurodegenerative pathogenesis, including Alzheimer's disease (AD), reflecting a disease-specific molecular signature.
View Article and Find Full Text PDFGut dysbiosis contributes to multiple pathologies, yet the mechanisms of the gut microbiota-mediated influence on systemic and distant responses remain largely elusive. This study aimed to identify the role of nanosized bacterial extracellular vesicles (bEVs) in mediating allodynia, i.e.
View Article and Find Full Text PDFArticle Synopsis
- Aging leads to loss of muscle mass and function, resulting in poorer health outcomes, decreased quality of life, and increased mortality risk among older adults.
- Small extracellular vesicles (sEV), which can be isolated from body fluids and contain specific biomarkers, offer a minimally invasive way to assess muscle health.
- Research on vervet monkeys showed that sEV from different age groups can reveal molecular changes related to muscle metabolism and regulation, suggesting they may serve as effective biomarkers for muscle health monitoring.
Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance.
View Article and Find Full Text PDFEffect of controlled release of HGF on extracellular vesicle secretion by urine-derived stem cells.
Front Bioeng Biotechnol
August 2024
Article Synopsis
- - The study investigates the impact of hepatic growth factor (HGF) on the secretion of small extracellular vesicles (sEV) from urine-derived stem cells (USCs), focusing on two methods of HGF delivery: bolus administration and controlled release using alginate microbeads.
- - Results indicate that the group receiving HGF through controlled release from microbeads showed a significantly higher concentration of proteins and sEV compared to both the bolus and control groups after 7 days.
- - The findings suggest that using a controlled release method for HGF significantly boosts sEV secretion from USCs, which could have implications for tissue regeneration and protection.
Chymase Activity in Plasma and Urine Extracellular Vesicles in Primary Hypertension.
Kidney360
November 2024
Key Points: Blood and urine extracellular vesicles isolated from hypertensive patients possess high chymase enzymatic activity. Chymase activity was significantly higher in small extracellular vesicles obtained from hypertensive patients with suboptimal BP control.
Background: Circulating extracellular vesicles (EVs) carry protected cargoes of nucleic acids, proteins, and metabolites.
Mitochondria-derived vesicles: potential nano-batteries to recharge the cellular powerhouse.
Extracell Vesicles Circ Nucl Acids
June 2024
Article Synopsis
- - Mitochondrial dysfunction is a key factor in various diseases, and maintaining mitochondrial quality is essential for cell survival through mechanisms like the generation of mitochondria-derived vesicles (MDVs).
- - Recent findings suggest that MDVs vary in type and have not been fully characterized, but they play significant roles beyond quality control, including communication between organelles.
- - A study highlighted that MDVs can release functional mitochondria proteins and maintain energy production capabilities, potentially revitalizing dysfunctional mitochondria and offering insights into cellular health and disease mechanisms.
Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis.
J Extracell Vesicles
July 2024
Article Synopsis
- Gut microbiome dysbiosis contributes to various health issues, and the study explores the role of bacterial extracellular vesicles (bEVs) in communication between gut microbiota and other organs.
- The research developed a method to isolate LPS+ bEVs from various biological samples and used multiple techniques to characterize them, particularly focusing on their effect on liver tissues in diet-induced obese (DIO) mice.
- Findings showed that DIO mice had lower total bEVs but higher LPS+ bEVs, with increased immune-related gene expressions in liver, indicating that bEVs might play a crucial role in the influence of gut bacteria on other body systems.
Article Synopsis
- The study investigates the effects of co-using nicotine with cocaine in monkeys, highlighting that most cocaine research doesn't consider nicotine despite its common co-use in humans.
- In the first experiment with rhesus monkeys, the combination of nicotine and cocaine significantly increased drug self-administration rates, indicating a stronger reinforcing effect when both drugs were used together.
- A second experiment with cynomolgus monkeys showed that adding nicotine to cocaine enhanced its appeal, particularly in females, and the study found important changes in blood biomarkers that could provide insights into cocaine use disorders and potential treatments.
Article Synopsis
- * Experience with adult airway equipment doesn't guarantee skill in using the same tools effectively with children.
- * A specific case of a 4-year-old with a difficult airway due to postburn neck contracture was successfully managed using a video laryngoscope after an initial unsuccessful attempt with a flexible fiberoptic bronchoscope.
Emergence of Extracellular Vesicles as "Liquid Biopsy" for Neurological Disorders: Boom or Bust.
Pharmacol Rev
February 2024
Article Synopsis
- Extracellular vesicles (EVs) are being explored as a promising liquid biopsy tool for diagnosing and monitoring various diseases, particularly neurological disorders.
- Researchers have focused on isolating EVs from different brain cells to gain molecular insights and potentially improve early diagnosis and treatment predictions for conditions like Alzheimer's, Parkinson's, and more.
- Despite challenges such as issues with specificity and standardization, advancements in EV research are paving the way for less invasive and more informative diagnostic techniques for brain-related illnesses.
The β-Secretase 1 Enzyme as a Novel Therapeutic Target for Prostate Cancer.
Cancers (Basel)
December 2023
Article Synopsis
- - Recent studies link BACE1 activity, along with APP and Aβ, to cancer development, highlighting BACE1's potential as a target for prostate cancer (PCa) treatment.
- - The study used various techniques to confirm BACE1 expression in human PCa tissues and cell lines and showed that BACE1 activity leads to the production of Aβ1-42, which was also detected in both tissue samples and through imaging methods.
- - Inhibition of BACE1 with MK-8931 significantly reduced PCa cell growth in laboratory models and inhibited tumor growth in mice, suggesting BACE1 has potential as a novel therapeutic target for advanced PCa.
Article Synopsis
- Brain-derived extracellular vesicles (EVs) are key players in Alzheimer's disease, acting as potential biomarkers due to the protection of their internal cargo from degradation.
- * A new method was developed to collect EVs from the hippocampal interstitial fluid of live mice, with specific techniques used for isolation and characterization.
- * Findings indicate that, in a model of Alzheimer’s, the protein concentration in EVs increases while protein diversity decreases with amyloid-beta deposition, and notable differences were observed based on sex regarding microglial EV proteome.
Article Synopsis
- - Extracellular vesicles (EVs) from plasma and urine show promise as a liquid biopsy for analyzing the renin-angiotensin system (RAS) activity in patients with primary hypertension.
- - The study found that urinary EVs from patients with uncontrolled hypertension had larger sizes and significantly higher chymase activity, a key enzyme in the RAS, compared to controlled patients.
- - The presence of bioactive RAS enzymes, particularly chymase, in EVs indicates a potential new mechanism for angiotensin II formation and may play a role in cell communication and signaling in the body.
Article Synopsis
- Extracellular vesicles (EVs) are tiny vesicles released by nearly all cell types, playing a crucial role in cell communication and maintenance, and are being explored as 'liquid biopsies' and cell-free therapeutics for various diseases.
- Stem cell-derived EVs (SC-EVs) have shown potential as a treatment for aging-related issues and disorders, enhancing tissue regeneration and reversing functions associated with aging, such as cognitive decline and reproductive dysfunctions.
- Research highlights the benefits of SC-EVs specifically for Alzheimer's disease, demonstrating their effectiveness in combating key disease features like amyloid plaques and neuroinflammation, along with improved cognitive performance in models studied.
Article Synopsis
- * Researchers are exploring extracellular vesicles (EVs) as promising biomarkers for various conditions, which can provide crucial information about hard-to-reach tissues in a less invasive way, akin to "liquid biopsies".
- * This study identified specific proteins in small EVs from the adipose tissue of lean and obese mice, suggesting that these EVs can help predict disease and indicate significant changes related to inflammation and amino acid metabolism associated with obesity.
MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease.
Alzheimers Dement
November 2023
Article Synopsis
- - The study investigates small extracellular vesicles (sEVs) derived from brain cells in blood to find potential biomarkers for Alzheimer's disease (AD) by analyzing microRNA (miRNA) levels in older adults with varying cognitive abilities.
- - Researchers isolated sEVs from participants with normal cognition, mild cognitive impairment (MCI), and AD, revealing that miRNA expression patterns significantly differentiated between these groups and correlated with brain imaging results.
- - The findings suggest that analyzing miRNAs in sEVs provides a promising, non-invasive blood-based method for detecting and monitoring Alzheimer's disease progression.
Article Synopsis
- Brain-derived extracellular vesicles (EVs) are important in Alzheimer's disease (AD) as they contain physiological information about brain regions and could serve as AD biomarkers due to their stability in circulation.
- A new method was developed to collect these EVs from the hippocampal interstitial fluid of live mice, revealing specific characteristics and size dimensions alongside conducting proteomic analyses.
- In a mouse model of cerebral amyloidosis, findings indicated that while protein concentration in EVs increased with amyloid plaque deposition, the diversity of proteins decreased, and that these changes varied based on genotype, age, and sex, highlighting different microglial responses in female mice.