targeted-toxins

Nie Y, Liang J, Sun J, Li J, Zhai X, Zhao P (2023) Orexin A alleviates LPS-induced acute lung injury by inhibiting macrophage activation through JNK-mediated autophagy. Int Immunopharmacol 124(Pt B):111018. doi: 10.1016/j.intimp.2023.111018 PMID: 37801969

Objective: To investigate the crosstalk between the central nervous system and immune response through the inflammatory response caused by lung injury.

Summary: By modeling acute respiratory distress in mice, the role of orexin-A and orexin-B was investigated through their inflammatory response. Orexin neurons were eliminated through lesions with Orexin-B-SAP (IT-20). Inflammatory cell infiltration and pro-inflammatory cytokines generation were aggravated after orexin neurons were ablated.

Usage: Mice were injected in the bilateral hypothalamus with 1 μL of Orexin-B-SAP (0.36 μg/μL) using a permanent stainless steel internal cannula connected at a speed of 16.5 ng/23 nl/second.

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

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421

Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).

Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.

Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Metz M, Kolkhir P, Altrichter S, Siebenhaar F, Levi-Schaffer F, Youngblood BA, Church MK, Maurer M (2023) Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. Allergy doi: 10.1111/all.15850 PMID: 37605867

Objective: Authors review the role of mast cells (MC) in the pathogenesis of chronic urticaria (CU), explore current therapeutic strategies, and introduce the concept of MC silencing as a strategy to block activation of MCs without eliciting immunosuppressive adverse effects.

Summary: CU is a MC-dependent disease with limited therapeutic options. Current strategies are directed at inhibiting IgE-mediated activation of MCs. MC depletion or silencing strategies are being developed to overcome limitations of singularly targeted agents. MC silencers, such as monoclonal antibodies that engage inhibitory receptor like sialic acid-binding immunoglobulin-like lectin8 (Siglec-8) have reached preclinical stages of development. Siglecs have been shown to be internalized upon antibody engagement, such as Siglec-8, and is being used to deplete MCs via conjugating saporin to the internalizing Siglec-8 antibody to cause cell death in human mast cells.

Usage: Usage: Anti-Siglec-8 (2C4)-SAP was used at 2.5 µg/ml to eliminate eosinophils and at 1.25 µg/ml to eliminate the HMC-1.2 human mast cell line.

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

See Also:

• O’Sullivan J et al. Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e1777, 2018.

Dobryakova YV, Gerasimov K, Spivak YS, Korotkova T, Koryagina A, Deryabina A, Markevich VA, Bolshakov AP (2023) The induction of long-term potentiation by medial septum activation under urethane anesthesia can alter gene expression in the hippocampus. Int J Mol Sci 24(16):12970. doi: 10.3390/ijms241612970 PMID: 37629149

Related Products: 192-IgG-SAP (Cat. #IT-01)

Jorgensen MD (2023) Designing coiled-coil peptide materials for biomedical applications. Purdue University Thesis.

Objective: Using saporin [PR-01] containing hydrogel to target and eliminate cancer cells.

Summary: Hydrogels can bind molecular cargo and be used to shuttle cytotoxic drugs across the body. Using a pH-responsive hyaluronic acid nanogel containing saporin, cancer cells with overexpressed CD44 receptor are eliminated.

Related Products: Saporin (Cat. #PR-01), Anti-CD44-SAP (Cat. #IT-72)

See Also:

• Ding L, Jiang Y, Zhang J, Klok HA, Zhong Z (2018) pH-Sensitive Coiled-Coil Peptide-Cross-Linked Hyaluronic Acid Nanogels: Synthesis and Targeted Intracellular Protein Delivery to CD44 Positive Cancer Cells. Biomacromolecules 19(2):555-562. doi: 10.1021/acs.biomac.7b01664 PMID: 29284258

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 1(2):0913. 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.

Akmese C, Sevinc C, Halim S, Unal G (2023) Differential role of GABaergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. Prog Neuropsychopharmacol Biol Psychiatry 125:110760. doi: 10.1016/j.pnpbp.2023.110760 PMID: 37031946

Objective: To investigate the role of the ventral pallidum (VP) in regulating the brain’s reward circuitry in appetitive behaviors and emotional regulation through GABAergic and Cholinergic lesions.

Summary: Using GAT1-SAP (GABAergic) or 192-IgG-SAP (cholinergic), injections were made into the VP to eliminate neurons in rats. These lesioned rats were subjected to fear conditioning tests, and it was shown that the VP may contribute to emotion regulation by suppressing active coping and promoting species-specific passive behaviors.

Usage: Bilateral injections of GAT1-SAP (325 ng/μl, 0.5 μl volume, 0.1 μl/min), 192-IgG-SAP (500 ng/μl in PBS, 0.5 μl volume, 0.1μl/min), or PBS (0.5 μl volume, 0.1 μl/min) into the Ventral Pallidum.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-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)