References

Jin X, Yang GY (2023) Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases. Prog Lipid Res 101241. doi: 10.1016/j.plipres.2023.101241 PMID: 37524133

Objective: The authors review the tumor-related biological functions of GSLs and recent progress in using GSLs and related enzymes to diagnose and treat tumor diseases.

Summary: Glycosphingolipids (GSLs) are glycolipids present on the surface of living cell membranes. Specific GSLs and related enzymes are abnormally expressed in many cancer diseases and affect the malignant characteristics of tumors. The regulatory roles of GSLs in signaling pathways suggest that they are involved in tumor pathogenesis. GSLs have therefore been widely studied as diagnostic markers of cancer diseases and important targets of immunotherapy.

Usage: The stage-specific embryonic antigen-4 (SSEA4) mAb, MC-813-70, was mixed with Mab-ZAP at a molar ratio of approximately 3:1 with the complex used at nanomolar concentrations on MDA-MB-231 cells, a triple negative breast cancer cell known to express SSEA-4. The conjugate was able to reduce tumor viability in vitro.

Related Products: Mab-ZAP (Cat. #IT-04)

See Also:

• Ruggiero FM et al. Exploiting the internalization feature of an antibody against the glycosphingolipid SSEA-4 to deliver immunotoxins in breast cancer cells. Immunol Cell Biol 98(3):187-202, 2020.

Zhang H, Zhu Y, Chen S, Deng K, Zheng M, Zeng Z, Wang Q, Cai H, Lu Z (2023) Autonomic nerve and its modulation approaches for heart failure. Brain & Heart doi: 10.36922/bh.0913

Objective: Authors review neural modulation approaches that can assist in the management of heart failure.

Summary: The autonomic nervous system governs the heart’s neurological regulation through opposing functions of its sympathetic and parasympathetic components. Potential treatments for heart failure include inhibiting the sympathetic nerve’s overactivity and restoring parasympathetic activity in the heart. CTB-SAP was used to ablate cardiac sympathetic neurons via retrograde transport on stellate ganglion neurons.

Usage: CTB-SAP was injected into the right superior vervical ganglion of adult male Sprague-Dawley rats (50 ug/rat).

Related Products: CTB-SAP (Cat. #IT-14)

See Also:

• Llewellyn-Smith IJ et al. Retrogradely transported CTB-saporin kills sympathetic preganglionic neurons. Neuroreport 10(2):307-312, 1999.

Canarutto D, Omer Javed A, Pedrazzani G, Ferrari S, Naldini L (2023) Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation. Br Med Bull ldad017. doi: 10.1093/bmb/ldad017 PMID: 37460391

Objective: The authors review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.

Summary: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient’s. Ex vivo HSC gene therapy (HSC GT) is a form of HSCT in which HSCs are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow niche, which is required for the engraftment of infused cells. One approach reviewed by the authors involves Anti-CD45-SAP. The conjugate was shown to clear the white blood cell compartment. Administration into mice prior to HSCT resulted in comparable haematopoietic reconstitution as total body irradiation, with less side effects (Palchaudhuri R. et al, 2016) and faster T-cell repopulation likely due to sparing radio damage to the thymic stroma (Schiroli G et al., 2017).

Related Products: Anti-CD45.2-SAP (Cat. #IT-91)

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Schiroli G et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9(411):eaan0820, 2017.

Kfoury YS, Ji F, Jain E, Mazzola MC, Schiroli G, Papazian A, Mercier FE, Sykes DB, Kiem A, Randolph MA, Abdel-Wahab OI, Calvi LM, Sadreyev R, Scadden DT (2023) The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression. Blood Adv bloodadvances.2022008268. doi: 10.1182/bloodadvances.2022008268 PMID: 37450380

Objective: Evaluate mesenchymal cell molecular features searching for modifications that could impact Myelodysplastic syndrome (MDS) and offer potential therapeutics.

Summary: MDS is a heterogenous group of diseases affecting hematopoietic stem cells and are curable only by stem cell transplantation. Animal models of MDS indicate that changes in specific mesenchymal progenitor subsets in the BM can induce or select for abnormal hematopoietic cells. The authors identified that osteopontin (SPP1) is overexpressed in human bone marrow mesenchymal cells. SPP1 expression in comparable mesenchymal stromal cell populations plays protective roles in disease progression in an MDS mouse model.

Usage: Streptavidin-ZAP was combined with biotinylated CD117 (cKit) Ab in a 1:1 molar ratio. Mice were dosed with the conjugate at 3 mg/kg. The authors used the antibody-drug conjugate as a conditioning strategy that spares the non-hematopoietic microenvironment in the BM from genotoxic injury. This approach has been shown to deplete host hematopoietic stem cells with minimal toxicity effectively.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Sun Z, Huang J, Fishelson Z, Wang C, Zhang S (2023) Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress. Biomedicines 11(7):1971.

Objective: Review the development process of cell penetrating peptides and summarize the composition and classification of the penetrating peptide-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers.

Summary: Delivery of macromolecular drugs (like saporin) with a cell penetrating peptide can be an effective way to create bioavailability. The principle underlying these approaches is to briefly destroy the cell membrane so that macromolecular drugs can enter the cell, after which the cell membrane is repaired and can restore cell homeostasis. Compared to other methods, the use of Cell Penetrating Peptides causes less damage to the cell membrane and is more effective and safe offering itself as a useful tool for macromolecular drug delivery.

Usage: Saporin as a conjugate to cell penetrating peptides. Nakase (2016) uses Saporin as a part of an extracellular vesicle conjugated with octaarginine, a cell penetrating peptide.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Nakase, I.; Noguchi, K.; Fujii, I.; Futaki, S. Vectorization of biomacromolecules into cells using extracellular vesicles with enhancedinternalization induced by macro-pinocytosis. Sci. Rep. 2016, 6, 34937.

Yang Q, Liu N, Zhao Z, Liu X, Yin L (2023) Dynamically crosslinked nanocapsules for the efficient and serum-resistant cytosolic protein delivery. Nano Research doi: 10.1007/s12274-023-5978-2

Objective: Improve protein delivery with the synthesis of epigallocatechin gallate/low-molecular-weight polyethylenimine/2-acetylphenylboric acid (EPP)-protein nano-capsules.

Summary: A protein delivery strategy was created through the crosslinking of various markers on the protein surface, hence forming the EPP-protein nano-capsules. The EPP-protein nano-capsule allowed for acid-triggered dissociation of EPP-protein nano-capsules in the endolysosomes, which triggered efficient intracellular release of the native proteins. Acid dissociation showed high efficiency and universality for diversities of proteins with different molecular weights and isoelectric points, including enzymes, toxins, antibodies, and CRISPR-Cas9 ribonucleoprotein.

Usage: Delivered into in vivo 4T1 tumors in mice (PBS, saporin, or EPP-saporin nano-capsules were i.v. injected (0.5 mg saporin/kg) on day 0, 2, 4, and 6) and in vitro HeLa cells (seeded with 0, 0.05, 0.1, 0.2, 0.5, 1, and 2 μg/mL concentrations of Saporin or EPP-Saporin).

Related Products: Saporin (Cat. #PR-01)

Low ZXB, Lee XR, Soga T, Goh BH, Alex D, Kumari Y (2023) Cannabinoids: Emerging sleep modulator. Biomed Pharmacother 165:115102. doi: 10.1016/j.biopha.2023.115102 PMID: 37406510

Objective: To review the modulation of sleep by cannabinoids and the endocannabinoid system.

Summary: This review article discusses the role of cannabinoids, including endocannabinoids like anandamide and phytocannabinoids like THC and CBD, in regulating the sleep-wake cycle. The authors review evidence that cannabinoids act on areas of the brain involved in promoting sleep, like the ventrolateral preoptic nucleus, and inhibit wake-promoting areas, like the locus coeruleus.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Watts NR, Eren E, Palmer I, Huang PL, Huang PL, Shoemaker RH, Lee-Huang S, Wingfield PT (2023) The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2. PLoS One 18(6):e0286370. doi: 10.1371/journal.pone.0286370 PMID: 37384752

Summary: Saporin is mentioned in the discussion of RIPs and their usage as antivirals.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Arslan I et al. Saporin, a Polynucleotide-Adenosine Nucleosidase, May Be an Efficacious Therapeutic Agent for SARS-CoV-2 Infection. SLAS Discov. 2021; 26(3):330–5. PMID: 33155515

Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023

Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.

Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.

Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

Souza GMPR, Stornetta DS, Shi Y, Lim E, Berry FE, Bayliss DA, Abbott SBG (2023) Neuromedin B-expressing neurons in the retrotrapezoid nucleus regulate respiratory homeostasis and promote stable breathing in adult mice. J Neurosci JN-RM-0386-23. doi: 10.1523/JNEUROSCI.0386-23.2023 PMID: 37290937

Objective: To develop a transgenic mouse model and demonstrate that retrotrapezoid nucleus (RTN) neurons are fundamental for respiratory homeostasis and mediate the stimulatory effects of CO2 on breathing.

Summary: This study uses a transgenic Nmb-Cre mouse model to demonstrate that RTNNmb neurons are crucial for CO2-dependent breathing in mice. It provides evidence that these neurons play a key role in respiratory homeostasis and might be linked to sleep-disordered breathing in humans. Cre-dependent cell ablation and optogenetics show RTNNmb neurons’ essential function in mediating the hypercapnic ventilatory response, highlighting the importance of these neurons in maintaining eupneic breathing.

Usage: This publication references the use of SSP-SAP (IT-11) to target RTN neurons.

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Takakura AC et al. Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585, 2014.