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PMC4606567
An automated shotgun lipidomics platform for high throughput, comprehensive, and quantitative analysis of blood plasma intact lipids
Blood plasma has gained protagonism in lipidomics studies due to its availability, uncomplicated collection and preparation, and informative readout of physiological status. At the same time, it is also technically challenging to analyze due to its complex lipid composition affected by many factors, which can hamper th...
PMC10513930
Dynamic lipidome alterations associated with human health, disease and ageing
Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling. Here, we report >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation, as well as cy...
PMC6691112
Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons leading to muscle paralysis and death. While a link between dysregulated lipid metabolism and ALS has been proposed, lipidome alterations involved in disease progression are still understudied. Using a rodent model...
PMC9352691
Comprehensive lipid and lipid-related gene investigations of host immune responses to characterize metabolism-centric biomarkers for pulmonary tuberculosis
Despite remarkable success in the prevention and treatment of tuberculosis (TB), it remains one of the most devastating infectious diseases worldwide. Management of TB requires an efficient and timely diagnostic strategy. In this study, we comprehensively characterized the plasma lipidome of TB patients, then selected ...
PMC11127996
Lipidome atlas of the adult human brain
Lipids are the most abundant but poorly explored components of the human brain. Here, we present a lipidome map of the human brain comprising 75 regions, including 52 neocortical ones. The lipidome composition varies greatly among the brain regions, affecting 93% of the 419 analyzed lipids. These differences reflect th...
PMC6097988
Phospholipidome of endothelial cells shows a different adaptation response upon oxidative, glycative and lipoxidative stress
Endothelial dysfunction has been widely associated with oxidative stress, glucotoxicity and lipotoxicity and underlies the development of cardiovascular diseases (CVDs), atherosclerosis and diabetes. In such pathological conditions, lipids are emerging as mediators of signalling pathways evoking key cellular responses ...
PMC5050431
LC-MS Based Sphingolipidomic Study on A2780 Human Ovarian Cancer Cell Line and its Taxol-resistant Strain
Drug resistance elicited by cancer cells continue to cause huge problems world-wide, for example, tens of thousands of patients are suffering from taxol-resistant human ovarian cancer. However, its biochemical mechanisms remain unclear. Sphingolipid metabolic dysregulation has been increasingly regarded as one of the d...
PMC9011034
Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish
Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distributi...
PMC8342504
Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction
For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction ...
PMC9170690
Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease
We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Stu...
PMC7417482
A Quantitative Analysis of Cellular Lipid Compositions During Acute Proteotoxic ER Stress Reveals Specificity in the Production of Asymmetric Lipids
The unfolded protein response (UPR) is central to endoplasmic reticulum (ER) homeostasis by controlling its size and protein folding capacity. When activated by unfolded proteins in the ER-lumen or aberrant lipid compositions, the UPR adjusts the expression of hundreds of target genes to counteract ER stress. The prote...
PMC5286405
Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung
Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported...
PMC8748654
Lipidomic profiling of human serum enables detection of pancreatic cancer
Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipi...
PMC10175254
Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson’s disease
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are progressive neurodegenerative diseases characterized by the accumulation of misfolded α-synuclein in the form of Lewy pathology. While most cases are sporadic, there are rare genetic mutations that cause disease and more common variants that increase inci...
PMC5779697
Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure
Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysi...
PMC11413214
Deciphering metabolomics and lipidomics landscape in zebrafish hypertrophic cardiomyopathy model
To elucidate the lipidomic and metabolomic alterations associated with hypertrophic cardiomyopathy (HCM) pathogenesis, we utilized cmybpc3-/- zebrafish model. Fatty acid profiling revealed variability of 10 fatty acids profiles, with heterozygous (HT) and homozygous (HM) groups exhibiting distinct patterns. Hierarchica...
PMC9301695
Are n-3 PUFAs from Microalgae Incorporated into Membrane and Storage Lipids in Pig Muscle Tissues?—A Lipidomic Approach
For the study of molecular mechanisms of to lipid transport and storage in relation to dietary effects, lipidomics has been rarely used in farm animal research. A feeding study with pigs (German Landrace sows) and supplementation of microalgae (Schizochytrium sp.) was conducted. The animals were allocated to the contro...
PMC11269705
Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer’s disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics
Dysregulated glycerophospholipid (GP) metabolism in the brain is associated with the progression of neurodegenerative diseases including Alzheimer’s disease (AD). Routine liquid chromatography-mass spectrometry (LC-MS)-based large-scale lipidomic methods often fail to elucidate subtle yet important structural features ...
PMC11458896
Glycerophospholipid remodeling is critical for orthoflavivirus infection
Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some ...
PMC10491837
Differential intracellular management of fatty acids impacts on metabolic stress-stimulated glucose uptake in cardiomyocytes
Stimulation of glucose uptake in response to ischemic metabolic stress is important for cardiomyocyte function and survival. Chronic exposure of cardiomyocytes to fatty acids (FA) impairs the stimulation of glucose uptake, whereas induction of lipid droplets (LD) is associated with preserved glucose uptake. However, th...
PMC8259984
LAMP3 deficiency affects surfactant homeostasis in mice
Lysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary s...
PMC7449968
Maternal lipid levels across pregnancy impact the umbilical cord blood lipidome and infant birth weight
Major alterations in metabolism occur during pregnancy enabling the mother to provide adequate nutrients to support infant development, affecting birth weight (BW) and potentially long-term risk of obesity and cardiometabolic disease. We classified dynamic changes in the maternal lipidome during pregnancy and identifie...
PMC5339821
Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry
The lipid composition of human skin is essential for its function; however the simultaneous quantification of a wide range of stratum corneum (SC) and sebaceous lipids is not trivial. We developed and validated a quantitative high-throughput shotgun mass spectrometry-based platform for lipid analysis of tape-stripped S...
PMC10469212
The elucidation of plasma lipidome profiles during severe influenza in a mouse model
Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic anal...
PMC9546883
Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis
Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brai...
PMC7897626
Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus
The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have her...
PMC8481471
Mouse lipidomics reveals inherent flexibility of a mammalian lipidome
Lipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus mus...
PMC11564093
Nonlinear dynamics of multi-omics profiles during human aging
Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related dise...
PMC10902711
Lipotype acquisition during neural development is not recapitulated in stem cell–derived neurons
We report a time-resolved resource of lipid molecule abundance across brain development. Using the resource as a reference, we find that stem cell–derived neurons do not acquire a neural lipotype in vitro, unless supplemented with adequate metabolic precursors.Lipids are a diverse category of biomolecules that constitu...
PMC8755711
A multi-omics study of circulating phospholipid markers of blood pressure
High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure...
PMC6461633
Changes in the Canine Plasma Lipidome after Short- and Long-Term Excess Glucocorticoid Exposure
Glucocorticoids (GCs) are critical regulators of metabolic control in mammals and their aberrant function has been linked to several pathologies. GCs are widely used in human and veterinary clinical practice as potent anti-inflammatory and immune suppressive agents. Dyslipidaemia is a frequently observed consequence of...
PMC4906355
Gender, Contraceptives and Individual Metabolic Predisposition Shape a Healthy Plasma Lipidome
Lipidomics of human blood plasma is an emerging biomarker discovery approach that compares lipid profiles under pathological and physiologically normal conditions, but how a healthy lipidome varies within the population is poorly understood. By quantifying 281 molecular species from 27 major lipid classes in the plasma...
PMC8521299
Shortening of membrane lipid acyl chains compensates for phosphatidylcholine deficiency in choline‐auxotroph yeast
Phosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes, including yeast, and has been assigned multiple functions in addition to acting as building block of the lipid bilayer. Here, by isolating S. cerevisiae suppressor mutants that exhibit robust growth in the absence of PC, we show that P...
PMC10630469
Q-RAI data-independent acquisition for lipidomic quantitative profiling
Untargeted lipidomics has been increasingly adopted for hypothesis generation in a biological context or discovery of disease biomarkers. Most of the current liquid chromatography mass spectrometry (LC–MS) based untargeted methodologies utilize a data dependent acquisition (DDA) approach in pooled samples for identific...
PMC6760179
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511...
PMC9599481
Integrated Quantitative Targeted Lipidomics and Proteomics Reveal Unique Fingerprints of Multiple Metabolic Conditions
Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may provide a powerful approach to inform early disease diagnosis and pre...
PMC6629680
Integrated targeted metabolomic and lipidomic analysis: A novel approach to classifying early cystic precursors to invasive pancreatic cancer
Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic...
PMC6128551
Quantitative lipidomic analysis of mouse lung during postnatal development by electrospray ionization tandem mass spectrometry
Lipids play very important roles in lung biology, mainly reducing the alveolar surface tension at the air-liquid interface thereby preventing end-expiratory collapse of the alveoli. In the present study we performed an extensive quantitative lipidomic analysis of mouse lung to provide the i) total lipid quantity, ii) d...
PMC11075828
Direct and indirect effects of CYTOR lncRNA regulate HIV gene expression
The implementation of antiretroviral therapy (ART) has effectively restricted the transmission of Human Immunodeficiency Virus (HIV) and improved overall clinical outcomes. However, a complete cure for HIV remains out of reach, as the virus persists in a stable pool of infected cell reservoir that is resistant to thera...
PMC12118871
PCYT2 overexpression induces mitochondrial damage and promotes apoptosis in hepatocellular carcinoma cells
Phosphatidylethanolamine cytidyltransferase 2 (PCYT2) is commonly regarded as the rate-limiting enzyme in eukaryotic phosphatidylethanolamine synthesis. However, the role of PCYT2 in the development of hepatocellular carcinoma (HCC) unknow. In this study, the role of PCYT2 overexpression in the development of HCC was e...
PMC1462997
Derivation of normal macrophages from human embryonic stem (hES) cells for applications in HIV gene therapy
Many novel studies and therapies are possible with the use of human embryonic stem cells (hES cells) and their differentiated cell progeny. The hES cell derived CD34 hematopoietic stem cells can be potentially used for many gene therapy applications. Here we evaluated the capacity of hES cell derived CD34 cells to give...
PMC1160574
Derivation of Multipotent Mesenchymal Precursors from Human Embryonic Stem Cells
Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors. Here, we present cultu...
PMC12396968
Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age
The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues ...
PMC12435838
Organ-specific features of human kidney lymphatics are disrupted in chronic transplant rejection
Lymphatic vessels maintain tissue fluid homeostasis and modulate inflammation, yet their spatial organization and molecular identity in the healthy human kidney, and how these change during chronic transplant rejection, remain poorly defined. Here, we show that lymphatic capillaries initiate adjacent to cortical kidney...
PMC11578878
An integrated transcriptomic cell atlas of human neural organoids
Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. H...
PMC12595314
Establishment and comprehensive characterization of a subline with highly bone-metastatic propensity derived from the lung adenocarcinoma A549 cell line
Lung cancer remains a leading cause of cancer-related mortality worldwide , with bone metastases representing one of the most common and devastating complications in non-small cell lung cancer (NSCLC). At the time of diagnosis, 20–30 % of NSCLC patients already exhibit bone involvement, and during disease progression, ...
PMC8809252
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi...
PMC11699618
Bivalent SMAC mimetic APG-1387 reduces HIV reservoirs and limits viral rebound in humanized mice
Latent viral reservoirs (VRs) represent a main barrier to HIV cure. Thus, developing new approaches that can purge and eliminate VRs paves the path toward achieving an HIV-1 cure. APG-1387, a bivalent SMAC mimetic (SM), efficiently reactivates latent HIV expression in T cell line models and enhances active caspase 3 ex...
PMC12479362
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues
Fibroblasts sculpt the architecture and cellular microenvironments of various tissues. Here we constructed a spatially resolved atlas of human skin fibroblasts from healthy skin and 23 skin diseases, with comparison to 14 cross-tissue diseases. We define six major skin fibroblast subtypes in health and three that are d...
PMC2211323
A large-scale proteomic analysis of human embryonic stem cells
Much of our current knowledge of the molecular expression profile of human embryonic stem cells (hESCs) is based on transcriptional approaches. These analyses are only partly predictive of protein expression however, and do not shed light on post-translational regulation, leaving a large gap in our knowledge of the bio...
PMC2238795
Adherent Self-Renewable Human Embryonic Stem Cell-Derived Neural Stem Cell Line: Functional Engraftment in Experimental Stroke Model
Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cel...
PMC12115102
Stilbene Glycosides in Pinus cembra L. Bark: Isolation, Characterization, and Assessment of Antioxidant Potential and Antitumor Activity on HeLa Cells
Stilbenes are plant secondary metabolites with remarkable antidiabetic, anti-inflammatory, antimicrobial, antioxidant, antitumor, and neuroprotective properties. As these compounds are valuable constituents in healthcare products and promising drug candidates, exploring new sources of stilbenes is essential for therape...
PMC1885650
Real-time PCR mapping of DNaseI-hypersensitive sites using a novel ligation-mediated amplification technique
Mapping sites within the genome that are hypersensitive to digestion with DNaseI is an important method for identifying DNA elements that regulate transcription. The standard approach to locating these DNaseI-hypersensitive sites (DHSs) has been to use Southern blotting techniques, although we, and others, have recentl...
PMC12559006
MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that commonly support cancer development and progression. Here we show that different cancer cells transfer mitochondria to fibroblasts in cocultures and xenograft tumors, thereby inducing protumorigenic CAF features. Transplantation ...
PMC12141184
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells
Immune evasion in non-small cell lung cancer (NSCLC) is largely mediated by programmed death-ligand 1 (PD-L1), which is upregulated by interferon-gamma (IFN-γ)-induced STAT1 activation. Targeting this pathway may improve immunotherapy outcomes. Curcumin, a natural polyphenol, has been reported to modulate various oncog...
PMC11419360
Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal
The persistence of HIV-1 in long-lived latent reservoirs during suppressive antiretroviral therapy (ART) remains one of the principal barriers to a functional cure. Blocks to transcriptional elongation play a central role in maintaining the latent state, and several latency reversal strategies focus on the release of p...
PMC1523200
Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines
In order to compare the gene expression profiles of human embryonic stem cell (hESC) lines and their differentiated progeny and to monitor feeder contaminations, we have examined gene expression in seven hESC lines and human fibroblast feeder cells using Illuminabead arrays that contain probes for 24,131 transcript pro...
PMC12101583
Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells
Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclear whether Endostar h...
PMC12612255
YTHDF2 regulates self non-coding RNA metabolism to control inflammation and tumorigenesis
The role of mA RNA methylation of self non-coding RNA remains poorly understood. Here we show that mA-methylated self U6 snRNA is recognized by YTHDF2 to reduce its stability and prevent its binding to Toll-like receptor 3 (TLR3), leading to decreased inflammatory responses in human and mouse cells and mouse models. At...
PMC12116388
Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of C-labelled glucose metabolism
Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities. Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sect...
PMC12081701
PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub
Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine methyltransferase 3 (PRMT3) w...
PMC1802744
"NeuroStem Chip": a novel highly specialized tool to study neural differentiation pathways in human stem cells
Human stem cells are viewed as a possible source of neurons for a cell-based therapy of neurodegenerative disorders, such as Parkinson's disease. Several protocols that generate different types of neurons from human stem cells (hSCs) have been developed. Nevertheless, the cellular mechanisms that underlie the developme...
PMC11116453
Single-cell and spatial transcriptomics analysis of non-small cell lung cancer
Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,0...
PMC10968586
Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine
The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative...
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations †
Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong rege...
PMC12133578
Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease
The immune–epithelial–stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD i...
PMC12408821
Mapping the arterial vascular network in an intact human kidney using hierarchical phase-contrast tomography
The architecture of kidney vasculature is essential the organ's specialised functions, yet is challenging to structurally map in an intact human organ. Here, we combined hierarchical phase-contrast tomography (HiP-CT) with topology network analysis to enable quantitative assessment of the intact human kidney vasculatur...
PMC6892818
CD40 induces renal cell carcinoma-specific differential regulation of TRAF proteins, ASK1 activation and JNK/p38-mediated, ROS-dependent mitochondrial apoptosis
A unique feature of CD40 among the TNF receptor (TNFR) superfamily is its exquisitely contextual effects, as originally demonstrated in normal and malignant B-lymphocytes. We studied renal cell carcinoma (RCC) in comparison to normal (human renal proximal tubule) cells, as a model to better understand the role of CD40 ...
PMC12256823
Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy
POPDC2 encodes the Popeye domain-containing protein 2, which has an important role in cardiac pacemaking and conduction, due in part to its cyclic AMP (cAMP)-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia, and morpholino-mediated knockdown o...
PMC12105127
Chemical profiling and anticancer activity of Alnus incana dichloromethane fraction on HeLa cells via cell cycle arrest and apoptosis
Cervical cancer remains a global health challenge with persistently high incidence and mortality rates despite advancements in conventional treatments. The therapeutic potential of natural products has gained attention, particularly for their selective cytotoxicity and ability to modulate cancer pathways. Alnus incana ...
PMC10287567
An integrated cell atlas of the lung in health and disease
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the populat...
PMC2063610
Loss of stem cell regenerative capacity within aged niches
This work uncovers novel mechanisms of aging within stem cell niches that are evolutionarily conserved between mice and humans and affect both embryonic and adult stem cells. Specifically, we have examined the effects of aged muscle and systemic niches on key molecular identifiers of regenerative potential of human emb...
PMC12819543
Evaluation of agmatine’s anti-cancer efficacy in Caco-2 colorectal adenocarcinoma cells
This study aimed to evaluate the potential effects of agmatine on cell viability, migration, invasion, apoptosis, and the expression of the ABCB1, ABCC1, and ABCG2 genes in the Caco-2 colon cancer cell line. Agmatine efficacy was assessed thruogh proliferation, migration, and invasion assays at various concentrations. ...