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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. ...