Targeting heparanase/heparan sulfate proteoglycans by non‐anticoagulant heparins: Opportunities for innovative therapeutic approaches in sarcomas DOI Creative Commons
Cinzia Lanzi, Sandro Pasquali, Giuliana Cassinelli

et al.

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(4)

Published: Oct. 1, 2024

Abstract Sarcomas are a heterogeneous group of aggressive mesenchymal malignancies. They account for 1% all tumors in the general population and 15–20% pediatric age young adults. Despite differences histology pathobiology, diverse types sarcomas traditionally managed with common multi‐modal approach including surgery, radiotherapy, polychemotherapy. Unfortunately, prognosis advanced or recurrent disease remains poor. Moreover, rarity high cellular, molecular, genetic/epigenetic heterogeneity make identification therapeutic targets challenging. Therefore it an urgent need to identify effective therapies improve patients' outcome. Common peculiar biological motifs deregulation growth factor signaling, proangiogenic promigratory pathways, tumor‐microenviroment interactions, transcriptional epigenetic machinery, differentiation program, provide actionable dependencies exploitable intervention. Among these, deregulated heparan sulfate proteoglycan system due aberrant expression key components as well structural/functional modifications mediated by endosulfatases endoβ‐ d ‐glycosidase heparanase, is emerging crucial player tumor progression valuable target across different sarcoma subtypes. In preclinical studies, non‐anticoagulant heparins have been shown counteract metastatic dissemination various models according their mimetic anti‐heparanase activities. Heparin derivatives also improved anti‐sarcoma efficacy molecularly targeted agents cytotoxic drugs. this minireview, we summarize current knowledge about interplay between heparanase/heparan pathways involved sarcomagenesis progression. We illustrate understanding mechanisms action contribution anti‐heparanase, anti‐receptor tyrosine kinase, likely immunomodulatory activities effects. Finally, discuss few aspects worthy exploration highlighting how elucidation underpinning antitumor heparin contexts may suggest new vulnerabilities approaches.

Language: Английский

Hippo cell signaling and HS-proteoglycans regulate tissue form and function, age-dependent maturation, extracellular matrix remodeling, and repair DOI
James Melrose

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(3), P. C810 - C828

Published: Jan. 15, 2024

This review examined how Hippo cell signaling and heparan sulfate (HS)-proteoglycans (HSPGs) regulate tissue form function. Despite being a nonweight-bearing tissue, the brain is regulated by mechanoresponsive pathways during embryonic development. HS-proteoglycans interact with growth factors, morphogens, extracellular matrix components to development pathology. Pikachurin Eyes shut (Eys) dystroglycan stabilize photoreceptor axoneme primary cilium ribbon synapse facilitating phototransduction neurotransduction bipolar retinal neuronal networks in ocular vision, human sense. Another HSPG, Neurexin interacts structural adaptor proteins synapses ensure specificity of neural interactions, aids synaptic potentiation plasticity neurotransduction. HSPGs also blood-brain barrier motor neuron basal structures neuromuscular junction. Agrin perlecan localize acetylcholinesterase its receptors junction essential for control. The mechanosensory hub on neurons, utilized YES associated protein (YAP)-transcriptional coactivator PDZ-binding motif (TAZ) Hippo, Hh, Wnt, transforming factor (TGF)-β/bone (BMP) receptor tyrosine kinase signaling. Members glypican HSPG proteoglycan family Smoothened Patched G-protein coupled Hh Wnt Control glycosyl sulfotransferases endogenous protease expression TAZ YAP represents mechanism whereby fine structure can be potentially modulated spatiotemporally morphogenesis similar manner controls sialyltransferase mediation cell-cell recognition, dysfunctional sialic acid feature many tumors.

Language: Английский

Citations

6
Diverse and multifunctional roles for perlecan (HSPG2) in repair of the intervertebral disc DOI Creative Commons
James Melrose, Farshid Guilak

JOR Spine, Journal Year: 2024, Volume and Issue: 7(3)

Published: July 29, 2024

Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, homeostasis, optimization of biomechanical functions. Perlecan-mediated osmotic mechanotransduction serves regulate metabolic activity cells in tissues subjected tension, compression, or shear. interacts vast array matrix (ECM) proteins through it stabilizes regulates proliferation differentiation resident cell populations. Here we examine roles HS-proteoglycan perlecan normal destabilized intervertebral disc. The disc has evolved survive hostile weight bearing, acidic, low oxygen nutrition environment, provides cytoprotection, shields from excessive compressive forces, sequesters range growth factors where they aid survival, proliferation, differentiation. mechanically connective attempt re-establish optimal composition functional properties by changing their ECM, process chondroid metaplasia. We explore possibility that assists these cell-mediated remodeling responses regulating anabolism. Perlecan's mechano-osmotic transductive property may be potential therapeutic application.

Language: Английский

Citations

4
Cancer stem cell analysis and targeting DOI

Mishal Safdar,

Z. M. Amin,

Muneeb Ullah

et al.

Methods in cell biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Influence of the Silkworm-Derived (Bombyx mori) Functional Substance (Silkrose-BM) on the Fish Meat Quality of Yellowtail (Seriola quinqueradiata) DOI Creative Commons

Athira Athira,

H. Nishiguchi, Daichi Hayashi

et al.

Fishes, Journal Year: 2025, Volume and Issue: 10(3), P. 130 - 130

Published: March 17, 2025

Popular foods such as sushi and sashimi depend on the quality of raw fish meat to maintain consumer satisfaction. Recently, dietary insect meal insect-derived substances have been extensively studied for application in aquaculture a protein alternative or immunostimulant. However, impact functional teleosts remains unclear. Here, we investigated influence inclusion silkrose-BM, novel bioactive polysaccharide derived from silkworm, Bombyx mori, yellowtail (Seriola quinqueradiata). This study was conducted by comparing two groups given different feeds, commercial EP feeds containing Silkrose-BM (0.1%), after culture period six months separate floating-net cages. The were specifically cut into loins several parameters observed, including proximate, color changes, total collagen, drip loss, muscle histology, gene expression (qRT-PCR). results color-change analysis showed that discoloration red feed group occurred faster than silkrose-BM group, indicating an antioxidant property silkrose-BM. Dietary also significantly reduced loss increased collagen content meat. Furthermore, qRT-PCR genes related lipid degradation downregulated muscles fed In contrast, proximate indicated no significant change nutritional composition between groups. Taken together, our suggest could improve minimizing denaturation inhibiting oxidation during storage.

Language: Английский

Citations

0
Exploiting regulatory T cells (Tregs): Cutting-edge therapy for autoimmune diseases DOI Creative Commons
Marwa Hassan, Mohamed Elzallat, Dina Mostafa Mohammed

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114624 - 114624

Published: April 10, 2025

Regulatory T cells (Tregs) are a specialized subset of suppressive that essential for maintaining self-tolerance, regulating effector cells, managing microbial infections, preventing tumors, allergies, and autoimmune disorders, facilitating allograft transplantation. Disruptions in Treg function or abundance contribute to an imbalance between pathogenic protective immune diseases. Recently, one promising treatment strategy restore balance involves the selective expansion manipulation Tregs using low-dose IL-2 therapy, adoptive cell transfer, chimeric antigen receptor (CAR)-Treg approaches. have been shown increasing number research studies prevent even treat variety such as allergic diseases, transplant rejection, graft-versus-host disease. A thorough comprehension is anticipated provide clear prospects effective immunotherapy wide range This review provides overview biology, including their functions, mechanisms, phenotypic markers, well involvement disease settings. Furthermore, we discuss therapeutic potential different subpopulations translational applications

Language: Английский

Citations

0
Glycosaminoglycans: Mechanisms and Therapeutic Potential in Neurological Diseases: A Mini-Review DOI
Shupeng Li, Iram Murtaza, Hongling Guo

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151861 - 151861

Published: April 1, 2025

Language: Английский

Citations

0
CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity DOI Creative Commons
James Melrose

Journal of Neuroscience Research, Journal Year: 2024, Volume and Issue: 102(7)

Published: July 1, 2024

Abstract Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space‐filling, cell supportive, stabilizing structure maintaining compartments, ionic microenvironments, microgradients that regulate neuronal activity maintain the neuron in an optimal microenvironment. contains high glycosaminoglycan content (60% hyaluronan, HA) range of PGs. Immobilization HA brain tissues by interactive hyalectan PGs preserves hydration activity, paucity results pro‐convulsant epileptic phenotype. Diverse CS, KS, HSPGs stabilize blood–brain barrier neurovascular unit, provide smart gel neurotransmitter vesicle storage delivery, organize neuromuscular junction basement membrane, motor synaptic plasticity, photoreceptor functions. PG‐HA networks fluxes compartments contribute to membrane polarization dynamics essential activation neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing memory, cognitive learning. Sialoglycoprotein associated with cones rods (SPACRCAN), binding CSPG, stabilizes inter‐photoreceptor ECM. pikachurin eyes shut synapse aiding phototransduction neurotransduction retinal bipolar neurons crucial visual acuity. This achieved through Laminin G motifs pikachurin, shut, neurexins interact dystroglycan–cytoskeleton–ECM‐stabilizing interconnections, specificity, co‐ordination regulatory action potentials neural networks.

Language: Английский

Citations

3
Expression, characterization and antivascular activity of amino acid sequence repeating collagen hexadecapeptide DOI
Wen‐Jing Yan, Changjin Huang,

Yumiao Yan

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 270, P. 131886 - 131886

Published: April 25, 2024

Language: Английский

Citations

2
Dichotomous Effects of Glypican-4 on Cancer Progression and Its Crosstalk with Oncogenes DOI Open Access

Victor Hansson,

Fang Cheng, Grigorios Georgolopoulos

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3945 - 3945

Published: April 2, 2024

Glypicans are linked to various aspects of neoplastic behavior, and their therapeutic value has been proposed in different cancers. Here, we have systematically assessed the impact GPC4 on cancer progression through functional genomics transcriptomic analyses across a broad range Survival analysis using TCGA patient data reveals divergent effects expression types, revealing elevated levels be associated with both poor favorable prognoses cancer-dependent manner. Detailed investigation role glioblastoma non-small cell lung adenocarcinoma by genetic perturbation studies displays opposing these cancers, where knockout CRISPR/Cas9 attenuated proliferation augmented cells overexpression exhibited significant opposite effect. Further, GPC4-knocked-down restored proliferation, indicating its mitogenic effect this type. Additionally, survival substantiated findings, an association between prognosis glioblastoma, while outcome carcinoma patients. Finally, analysis, attempted assign mechanisms action GPC4, as find it implicated cycle control core pathways. The revealed upregulation oncogenes, including FGF5, TGF-β superfamily members, ITGA-5 which were downregulated Our findings illuminate pleiotropic cancer, underscoring potential putative prognostic biomarker implications type dependent

Language: Английский

Citations

1
Bioengineered heparin: Advances in production technology DOI Creative Commons
Razia Sultana, Masamichi Kamihira

Biotechnology Advances, Journal Year: 2024, Volume and Issue: unknown, P. 108456 - 108456

Published: Sept. 1, 2024

Language: Английский

Citations

1