A5059476872- Connexins and lens biology
- Pancreatitis Pathology and Treatment
- Cancer, Hypoxia, and Metabolism
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Diet, Metabolism, and Disease
- RNA Research and Splicing
- Prenatal Substance Exposure Effects
- PARP inhibition in cancer therapy
- Ion channel regulation and function
- Cancer Cells and Metastasis
- Heme Oxygenase-1 and Carbon Monoxide
- ATP Synthase and ATPases Research
- FOXO transcription factor regulation
- Aldose Reductase and Taurine
- Hippo pathway signaling and YAP/TAZ
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Metabolism, Diabetes, and Cancer
- Breast Lesions and Carcinomas
- Advanced Fluorescence Microscopy Techniques
- Nuclear Structure and Function
- Cellular transport and secretion
- Alcohol Consumption and Health Effects
University of Manchester
2013-2025
Henry Royce Institute
2024-2025
Manchester Academic Health Science Centre
2019-2025
Thomas Jefferson University
2011-2013
Sidney Kimmel Cancer Center
2012-2013
Philadelphia University
2012-2013
University of Pennsylvania
2009
Universidad de Salamanca
2001-2008
Zero to Three
2006
Here, we show that new mitochondrial biogenesis is required for the anchorage independent survival and propagation of cancer stem-like cells (CSCs). More specifically, used drug XCT790 as an investigational tool, it functions a specific inhibitor ERRα-PGC1 signaling pathway, which governs biogenesis. Interestingly, our results directly demonstrate efficiently blocks both tumor initiating (TICs), using MCF7 cell line model system. Mechanistically, suppresses activity several pathways are...
Metformin is a well-established diabetes drug that prevents the onset of most types human cancers in diabetic patients, especially by targeting cancer stem cells. exerts its protective effects functioning as weak "mitochondrial poison," it acts complex I inhibitor and oxidative mitochondrial metabolism (OXPHOS). Thus, must play an essential role promoting tumor growth. To determine functional health" breast pathogenesis, here we used uncoupling proteins (UCPs) to genetically induce...
Wireless sensor networks have become incredibly popular due to the Internet of Things' (IoT) rapid development.IoT routing is basis for efficient operation perception-layer network.As a type machine learning, reinforcement learning techniques gained significant attention their successful application in field network communication.In traditional Routing Protocol lowpower and Lossy Networks (RPL) protocol, solve fairness control message transmission between IoT terminals, fair broadcast...
Abstract Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect during cellular and in vivo models AP diabetic mice (Ins2 Akita ) Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out (PACIRKO). Caerulein palmitoleic acid (POA)/ethanol-induced was more severe both Ins2 PACIRKO vs control mice, directly...
Abstract We have previously shown that endothelin‐1 increases glucose uptake in astrocytes. In the present work we investigate mechanism through which (ET‐1) uptake. Our results show ET‐1 activates a short‐term and long‐term mechanism. Thus, induced rapid change localization of both GLUT‐1 type I hexokinase. These changes are probably aimed at rapidly increasing entry phosphorylation glucose. addition, upregulated hexokinase expression isoforms not normally expressed astrocytes, such as...
Mammography is an important screening modality for the early detection of DCIS and breast cancer lesions. More specifically, high mammographic density associated with increased risk cancer. However, biological processes underlying this phenomenon remain largely unknown. Here, we re-interrogated genome-wide transcriptional profiling data obtained from low-density (LD) mammary fibroblasts (n = 6 patients) high-density (HD) 7 derived a series 13 female patients. We used these raw to generate...
Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis that ethanol induces metabolic changes in tumor microenvironment, which then enhances epithelial growth. To experimentally test this hypothesis, we used a co-culture system consisting cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, show treatment (100 mM) ROS production oxidative stress cancer-associated fibroblasts, sufficient to induce myofibroblastic differentiation....
Abstract Liver fibrosis is a major cause of death worldwide. As progressive step in chronic liver disease, almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell transcriptomic profiling cirrhosis. Through multi-modal data integration, define molecular signatures cell state transitions disease an...
MicroRNAs (miRNAs) control organogenesis in mammals by inhibiting translation of mRNA. Skin is an excellent model to study the role miRNAs epidermis and mesenchyme. Previous research demonstrated miRNA‐29 family functions skin; however, mRNA targets downstream mechanisms miRNA‐29‐mediated regulation are missing. We used miRNA crosslinking immunoprecipitation method find direct keratinocytes fibroblasts from human skin. inhibition using modified antisense oligonucleotides 2D 3D cultures...
Elevated mitochondrial biogenesis and metabolism represent key features of breast cancer stem cells (CSCs), whose propagation is conducive to disease onset progression. Therefore, interfering with mitochondria biology function may be regarded as a useful approach eradicate CSCs. Here, we used the cell line MCF7 model system interrogate how fission contributes development dysfunction toward inhibition metabolic flux stemness. We generated an isogenic MCF-7 transduced Mitochondrial Fission...
Abstract In previous studies, we showed that endothelin‐1 increased astrocyte proliferation and glucose uptake. These effects were similar to those observed with other gap junction inhibitors, such as carbenoxolone (CBX). Because 24‐h treatment or CBX downregulates the expression of connexin43, main protein forming astrocytic junctions, which can also be involved in proliferation, this study, addressed possible role connexin43 endothelin‐1. To do so, was silenced astrocytes by siRNA. The...
Background Ethanol is a toxin responsible for the neurodevelopmental deficits of Fetal Alcohol Spectrum Disorders (FASD). Recent evidence suggests that ethanol modulates protein expression lineage specifier transcription factors Oct4 (Pou5f1) and Sox2 in early stages mouse embryonic stem (ES) cell differentiation. We hypothesized induced an imbalance differentiation, dysregulated associated target genes signaling molecules diverted cells from neuroectodermal (NE) formation....
Naturally-occurring somatic mutations in the estrogen receptor gene (ESR1) have been previously implicated clinical development of resistance to hormonal therapies, such as Tamoxifen. For example, mutation Y537S has specifically associated with acquired endocrine resistance. Briefly, we recombinantly-transduced MCF7 cells a lentiviral vector encoding ESR1 (Y537S). As first step, confirmed that MCF7-Y537S are indeed functionally resistant Tamoxifen, compared alone controls. Importantly,...
Our previous work has shown that tolbutamide increases gap junctional permeability in poorly coupled C6 glioma cells and this effect is similar additive to found with dbcAMP, a well-known activator of communication. Furthermore, the increase communication promoted by or dbcAMP concurrent inhibition proliferation cells. In present work, we show synthesis tumor suppressor protein Cx43 they decrease level Ki-67, expressed when are proliferating. These effects were accompanied reduction...
We showed previously that the inhibition of gap junctional communication in astrocytes increased bromodeoxyuridine (BrdU) incorporation and promoted changes metabolic phenotype destined to fulfil requirements cell proliferation. In present study we investigated cycle by intercellular through junctions. Thus, presence endothelin-1 carbenoxolone, two junction uncouplers, an increase percentage found S, G2 M phases cycle, with a concomitant decrease G0 G1 phases. addition, levels Ki-67, protein...
The Golgi complex comprises a connected ribbon of stacked cisternal membranes localized to the perinuclear region in most vertebrate cells. position and morphology this organelle depends upon interactions with microtubules actin cytoskeleton. In contrast, we know relatively little about relationship intermediate filaments (IFs). study, show that is close physical proximity vimentin IFs cultured mouse human We also trans-Golgi network coiled-coil protein GORAB can physically associate IFs....
We have previously reported that tolbutamide prevents the inhibition of gap junction communication in astrocytes. Here, we show increases and connexin 43 expression poorly coupled C6 glioma cells. The increase is concurrent with rate proliferation due to a block progression cells through S phase cell cycle. effects were quantitatively similar found after elevation intracellular cAMP. Furthermore, cAMP additive. possible beneficial effect on gene therapy for gliomas discussed.
MicroRNAs (miRNAs) control organogenesis in mammals but their role specific cell types is not fully explored. miRNAs exert function by binding mRNAs and inhibiting translation. Skin an excellent model to study the of primary cells epidermal (keratinocytes) mesodermal (fibroblasts) origin, because growth these tightly controlled at Previous research demonstrated that miRNA-29 family functions during skin repair, however, exact mRNA targets downstream mechanisms miRNA-29-mediated regulation...