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ALK upregulates POSTN and WNT signaling to drive neuroblastoma
Huang M, Fang W, Farrel A, Li L, Chronopoulos A, Nasholm N, Cheng B, Zheng T, Yoda H, Barata MJ, Porras T, Miller ML, Zhen Q, Ghiglieri L, McHenry L, Wang L, Asgharzadeh S, Park J, Gustafson WC, Matthay KK, Maris JM, Weiss WA (2024) ALK upregulates POSTN and WNT signaling to drive neuroblastoma. Cell Rep 43(3):113927. doi: 10.1016/j.celrep.2024.113927 PMID: 38451815
Objective: To determine how anaplastic lymphoma kinase (ALK) contributes to tumor formation.
Summary: ALK partially drives neuroblastoma through a feedforward loop between POSTN and WNT signaling.
Usage: AB-N07 Anti-NGFR Immunofluorescence (1:250).
Related Products: NGFR (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)
Increased systemic levels of centrally acting b-type natriuretic peptide are associated with chronic itch of different types
Nattkemper LA, Kim BS, Yap QV, Hoon MA, Mishra SK, Yosipovitch G (2024) Increased systemic levels of centrally acting b-type natriuretic peptide are associated with chronic itch of different types. J Invest Dermatol S0022-202X(24)00197-0. doi: 10.1016/j.jid.2024.02.026 PMID: 38522572
Objective: Examines plasma BNP levels and N-terminal pro-BNP levels in patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity.
Summary: Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale, particularly for patients with chronic pruritus of unknown origin. Based on this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, BNP-SAP lesions to mice determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord.
Usage: BNP-SAP was injected intrathecally (5 µg in 10 µL). One week later an itch agonist agent, ivBNP, was injected and itching was measured over an hour.
Related Products: Saporin (Cat. #PR-01)
Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement
Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement. bioRxiv 2024.03.07.583670. doi: 10.1101/2024.03.07.583670
Objective: Investigate the neuroprotective effect of treatment with the CB1 cannabinoid agonist, WIN55,212-2, against cholinergic degeneration.
Summary: The endocannabinoid (eCB) system plays a role in modulating learning and memory processes controlled by cholinergic neurotransmission. The authors propose that activation of this system is neuroprotective against cholinergic degeneration, such as what occurs in Alzheimer’s disease (AD). In a 192-IgG-SAP (Cat. IT-01) induced model of AD, a restoration of memory and learning was observed when rats were administered the CB1 cannabinoid agonist, WIN55,212-2.
Usage: Rats received injections of 192-IgG-saporin (130 ng/µl) into the nucleus basalis magnocellularis.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells
Qian C, Xin Y, Qi C, Wang H, Dong BC, Zack DJ, Blackshaw S, Hattar S, Zhou FQ, Qian J (2024) Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells. Nat Commun 15(1):2206. doi: 10.1038/s41467-024-46428-z PMID: 38467611
Objective: To explore how intercellular communication contributes to retinal ganglion cell (RGC) survival following optic nerve crush based on single-cell RNA-seq analysis.
Summary: The overall scores of the responsive interactions among the retinal cell types correlated with the distress interactions sent from RGCs.
Usage: Immunohistochemistry (1:500; AB-N38).
Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)
Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus
Luna-Munguia H, Gasca-Martinez D, Garay-Cortes A, Coutiño D, Regalado M, de Los Rios E, Villaseñor P, Hidalgo-Flores F, Flores-Guapo K, Benito BY, Concha L (2024) Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus. Mol Neurobiol 61(10):1-21. doi: 10.1007/s12035-024-04069-9 PMID: 38443731
Objective: To evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.
Summary: Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Regarding the pilocarpine-induced status epilepticus, an increased mortality rate was observed. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.
Usage: Injection of 192-IgG-SAP (375 ng/μl dissolved in sterile 0.1X PBS) and GAT1-SAP (325 ng/μl dissolved in sterile 0.1X PBS) into the MS to selectively target choline neuron or GABA populations of the medial septum, respectively.
Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)
Therapeutic peptides and proteins: Stabilization challenges and biomedical applications by means of nanodelivery systems
Berselli E, Coccolini C, Tosi G, Gokce EH, Oliveira MBPP, Fathi F, Krambeck K, Suoto EB (2024) Therapeutic peptides and proteins: Stabilization challenges and biomedical applications by means of nanodelivery systems. Int J Pept Res Ther 30:15. doi: 10.1007/s10989-024-10592-z
Objective: To discuss the stability problems of proteins and peptides that have driven the scientific community to find in nanotechnology a valid alternative for oral administration of biomolecules.
Summary: Nanoparticles have been proposed to improve the gastrointestinal stability of such macromolecules and, thus, their oral bioavailability. It has also been shown that combining different approaches, such as liposomes and hydrophobic ion pairing and hybrid systems made of polymers and lipids, may lead to synergistic advantages in modifying the release profile and the uptake of peptides/proteins through the gut.
Usage: See Fu et al. (2022). This publication showed an efficient result of a nano-encapsulated protein for cancer therapy. They encapsulate da tetra-guanidinium (TG)-modified saporin into tumor microenvironment (TME) pH-responsive polymeric NP.
Related Products: Saporin (Cat. #PR-01)
See Also:
NGFR regulates stromal cell activation in germinal centers
Hernández-Barranco A, Santos V, Mazariegos MS, Caleiras E, Nogués L, Mourcin F, Léonard S, Oblet C, Genebrier S, Rossille D, Benguría A, Sanz A, Vázquez E, Dopazo A, Efeyan A, Ortega-Molina A, Cogne M, Tarte K, Peinado H (2024) NGFR regulates stromal cell activation in germinal centers. Cell Rep 43(2):113705. doi: 10.1016/j.celrep.2024.113705 PMID: 38307025
Objective: To study the effect of NGFR loss on lymph node organization and function, demonstrating that NGFR depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment.
Summary: Results show that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.
Usage: Anti-NGFR Alexa488-labeled used in Flow Cytometry (1:200) (Cat# AB-N01AP-FLA).
Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified Alexa488-labeled (Cat. #AB-N01AP-FLA)
Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome
Chan A (2024) Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome. Univ Pennsylvania Thesis.
Objective: Studying the delivery of saporin across the cell membrane encapsulated in lipid nanoparticles.
Summary: Protein payloads, like saporin and others, are given negatively charged regions which create binding sites for cationic lipids to encapsulate the protein. The lipid nanoparticles with saporin or other proteins inside have the potential to interact with many more targets within the cell because they now cross the cell barrier more efficiently.
Usage: Encapsulated Saporin [PR-01] in lipid nanoparticles using anionic polypeptide linkers and using it in vivo (Sun, 2022) and in vitro (Rui, 2019).
Related Products: Saporin (Cat. #PR-01)
See Also:
- Rui, Y. et al. Carboxylated branched poly(β-amino ester) nanoparticles enable robustcytosolic protein delivery and CRISPR-Cas9 gene editing. Sci Adv 5, (2019).
- Sun, Y. et al. Phase-separating peptides for direct cytosolic delivery and redox-activatedrelease of macromolecular therapeutics. Nat Chem 14, 274–283 (2022).
Women’s special issue series: Biomedicines
Polito L (2024) Women’s special issue series: Biomedicines. Biomedicines 12(3):471. doi: 10.3390/biomedicines12030471 PMID: 38540085
Summary: Saporin is a single-chain ribosome-inactivating protein (RIP) with low toxicity in cells and animals. When the protein is linked to a carrier that facilitates cellular uptake, the protein can become highly and selectively toxic to the cellular target of the carrier. For this reason, saporin is often used to construct immunotoxins or other hybrid conjugates. The article by Bortolotti et al. examined the effect of the most frequently used heterobifunctional reagents on the saporin molecule, intending to insert a chemical bridge between the toxin and the carrier. The authors evaluated the capability of derivatized saporin to maintain its enzymatic properties, i.e., protein synthesis inhibition, deadenylation of DNA, and its biologic properties, i.e., in vitro cytotoxicity. Therefore, this research can be of interest for constructing saporin-based immuno conjugates when small molecules are considered carriers.
Related Products: Saporin (Cat. #PR-01)
See Also:
- Bolognesi, A.; Bortolotti, M.; Maiello, S.; Battelli, M.G.; Polito, L. Ribosome-Inactivating Proteins from Plants: A Historical Overview. Molecules 2016,21, 1627.
- Polito, L.; Djemil, A.; Bortolotti, M. Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview. Biomedicines 2016,4,12.
- Bortolotti, M.; Biscotti, F.; Zanello, A.; Bolognesi, A.; Polito, L. New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents. Biomedicines 2023,11, 1214.
Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation
Díaz-Jara E, Pereyra K, Vicencio S, Olesen MA, Schwarz KG, Toledo C, Díaz HS, Quintanilla RA, Del Rio R (2024) Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation. Redix Biol 69:102992. doi: 10.1016/j.redox.2023.102992 PMID: 38142585
Objective: To determine the impact of partial deletion of SOD2 expression on (1) O2.−accumulation in the Retrotrapezoid nucleus (RTN), (2) central ventilatory chemoreflex function, and (3) disordered-breathing as well as cellular localization of SOD2 in the RTN of healthy mice.
Summary: Results showed that SOD2+/− mice displayed reductions in SOD2 levels and high O2-formation and mitochondrial dysfunction within the RTN compared to wild type. Additionally, SOD2+/−mice displayed a heightened ventilatory response to hypercapnia and exhibited overt signs of altered breathing patterns.
Usage: Recent research has shown that removing some RTN chemoreceptor neurons using substance P-conjugated saporin toxin can normalize central chemoreflex and respiratory disorders in animals with heart disease, highlighting the significance of RTN neurons in the pathological process of central chemoreflex potentiation.
Related Products: SP-SAP (Cat. #IT-07)