Human myocardial-derived highly proliferative cells improve cardiac remodeling after myocardial infarction in mice.

Human highly proliferative cells (hHiPCs) isolated from the adult heart have progenitor and angiogenic properties. However, the mechanisms underlying hHiPCs in myocardial repair in vivo have yet to be investigated. We characterized the hHiPC proteome and secretome and found that hHiPCs express and secrete proangiogenic and proreparative proteins, including CXCL6, CTHRC1, and CD73, and are ontologically enriched in pathways related to cytokine signaling and glucose metabolism.

Lipidomic and proteomic insights from extracellular vesicles in the postmortem dorsolateral prefrontal cortex reveal substance use disorder-induced brain changes.

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD.

Altered metabolomics and inflammatory transcriptomics in human bone marrow adipocytes after acute high calorie diet and acute fasting.

Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here, we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting.

Short-term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice.

Dietary methionine restriction (MetR) promotes metabolic health, and we tested the impact of short durations of MetR on high fat diet (HFD)-induced metabolic dysfunction with the maintenance of HFD. Male C57BL/6J mice were fed HFD from 10 to 25 weeks of age, then maintained on HFD or fed HFD with 80% reduced methionine (HFD-MetR) for 3, 5, or 10 days. Blood, liver, adipose tissue, and aortae underwent phenotypic assessment, proteomics, and metabolomics.

Dietary effects on cardiac lipid composition, mitochondrial respiration, stress proteins and thermal tolerance in the American lobster (Homarus americanus).

Lipids are fundamental components of many biological structures, and their composition is partially diet dependent. Differences in lipid composition can impact the functioning of cellular membranes and proteins, subsequently altering the organism's ability to respond to environmental conditions. The American lobster (Homarus americanus) is an economically important shellfish in New England and is frequently kept in lobster impoundments (pounds) for prolonged periods, typically on a diet of herring, which differs from the natural diet of wild-caught lobsters.

The bronchoalveolar proteome changes in obesity.

Obesity contributes to pulmonary dysfunction through poorly understood biochemical mechanisms. Chronic inflammation and altered cellular metabolism have emerged as pathological changes across organ systems in obesity, but whether similar changes occur in lungs with obesity is unknown. We collected bronchoalveolar lavage fluid (BALF) from right upper lobe and lingula pulmonary subsegments of 14 adults (7 males/7 females) with body mass indexes (BMIs) ranging from 24.

Expression Results in Secretion-Mediated, SOX9-Dependent Suppression of Adipogenesis: Implications for the Regulatory Role of Newly Identified CTHRC1/PDGFR-Alpha Stromal Cells of Adipose.

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors including PPAR-gamma and C/EBP alpha, while dysregulated adipogenesis can predispose adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that -null mice have increased adiposity compared to wildtype mice, supporting the notion that CTHRC1 regulates body composition. Herein, we derived conditioned medium from 3T3-L1 cells expressing human and investigated its anti-adipogenic activity.

Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.

Vitamin A deficiency and male-specific effects on heart function in mice.

Hepatic stores of Vitamin A (retinol) are mobilized and metabolized in the heart following myocardial infarction. The physiological consequences of this mobilization are poorly understood. Here we used dietary depletion in a lecithin retinol acyltransferase mutant mouse line to induce Vitamin A deficiency and investigate the effects on cardiac function and recovery from myocardial infarction.

Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease.

: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. : We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease.

ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.

Pro-angiogenic paracrine/autocrine signaling impacts myocardial repair in cell-based therapies. Activin A receptor-like type 1 (, ALK1) signaling plays a pivotal role in cardiovascular development and maintenance, but its importance in human-derived therapeutic cardiac cells is not well understood. Here, we isolated a subpopulation of human highly proliferative cells (hHiPCs) from adult epicardial tissue and found that they express ALK1, a high affinity receptor for bone morphogenetic protein-9 (BMP9), which signals via SMAD1/5 to regulate paracrine/autocrine signaling and angiogenesis.

Magnitude of obesity alone does not alter the alveolar lipidome.

Obesity may lead to pulmonary dysfunction through complex and incompletely understood cellular and biochemical effects. Altered lung lipid metabolism has been identified as a potential mechanism of lung dysfunction in obesity. Although murine models of obesity demonstrate changes in pulmonary surfactant phospholipid composition and function, data in humans are lacking.

Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes.

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to glial activation and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD.

Endothelial IL17RD promotes Western diet-induced aortic myeloid cell infiltration.

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor) belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent leukocyte adhesion.

Purification of functional mouse skeletal muscle mitochondria using percoll density gradient centrifugation.

Objective: Our goal was to isolate purified mitochondria from mouse skeletal muscle using a Percoll density gradient and to assess bioenergetic function and purity via Seahorse Extracellular Flux (XF) Analyses and mass spectrometry.

Results: Mitochondria isolated from murine quadriceps femoris skeletal muscle using a Percoll density gradient method allowed for minimally contaminated preparations with time from tissue harvest to mitochondrial isolation and quantification in about 3-4 h. Percoll purification from 100 to 200 mg fresh tissue yielded ~ 200-400 ug protein.

Exploratory mass spectrometry of cerebrospinal fluid from persons with autopsy-confirmed LATE-NC.

Background: Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management.

Methods: Participants were recruited from a longitudinal cohort of older adults at the University of Kentucky AD Research Center.

Purification of functional mouse skeletal muscle mitochondria using Percoll density gradient centrifugation.

Objective: Our goal was to isolate purified mitochondria from mouse skeletal muscle using a Percoll density gradient and to assess bioenergetic function and purity via Seahorse Extracellular Flux (XF) Analyses and mass spectrometry.

Results: Mitochondria isolated from murine quadriceps femoris skeletal muscle using a Percoll density gradient method allowed for minimally contaminated preparations with time from tissue harvest to mitochondrial isolation and quantification in about 3-4 hours. Percoll purification from 100-200 mg fresh tissue yielded ∼200-400 ug protein.

Targeting the fatty acid binding proteins disrupts multiple myeloma cell cycle progression and MYC signaling.

Multiple myeloma is an incurable plasma cell malignancy with only a 53% 5-year survival rate. There is a critical need to find new multiple myeloma vulnerabilities and therapeutic avenues. Herein, we identified and explored a novel multiple myeloma target: the fatty acid binding protein (FABP) family.

Development and characterization of three cell culture systems to investigate the relationship between primary bone marrow adipocytes and myeloma cells.

The unique properties of the bone marrow (BM) allow for migration and proliferation of multiple myeloma (MM) cells while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. BM adipocytes (BMAds) have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary BM cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and, reciprocally, BMAds support MM cells .

Sclerostin antibody increases trabecular bone and bone mechanical properties by increasing osteoblast activity damaged by whole-body irradiation in mice.

Irradiation therapy causes bone deterioration and increased risk for skeletal-related events. Irradiation interferes with trabecular architecture through increased osteoclastic activity, decreased osteoblastic activity, and increased adipocyte expansion in the bone marrow (BM), which further compounds bone-related disease. Neutralizing antibodies to sclerostin (Scl-Ab) increase bone mass and strength by increasing bone formation and reducing bone resorption.

An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.

The growth and spread of malignant tumors, such as ovarian carcinomas, are governed in part by complex interconnected signaling cascades occurring between stromal and tumor cells. These reciprocal cross-talk signaling networks operating within the local tissue microenvironment may enhance malignant tumor progression. Understanding how novel bioactive molecules generated within the tumor microenvironment regulate signaling pathways in distinct cellular compartments is critical for the development of more effective treatment paradigms.