References

Lusk S, Moushey AM, Li A, Ray R (2024) Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats. Front Physiol 15:1341649. doi: 10.3389/fphys.2024.1341649 PMID: 39469444

Objective: To investigate whether an increase in postnatal neurogenesis of orexin (OX) neurons in spontaneously hypertensive rats (SHRs) precedes and contributes to elevated mean arterial pressure (MAP) and heightened responses to elevated CO2 (hypercapnia) during development.

Summary: Postnatal increase in OX neurons may be essential for the development of higher MAP and an exaggerated chemoreflex (the body’s response to CO2) in SHRs. Targeting the overactive OX system could provide a potential therapeutic strategy during the early stages of hypertension development.

Usage: Orexin-SAP (0.5 μL, 90 ng/μL) was injected into the hypothalamus to eliminate excess OX neurons and study their effect on elevated MAP and exaggerated chemoreflex responses in adult SHRs.

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

Morrison G, Henry N, Kopytynski M, Chen R (2024) A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways. Biomater Sci 12(19):5010-5022. doi: 10.1039/d4bm00600c PMID: 39177215

Objective: To overcome Saporin’s poor plasma membrane permeability.

Summary: To overcome this barrier, authors used a bioinspired intracellular delivery platform based on the pH-responsive pseudo peptide, poly (L-lysine isophthalamide) grafted with L-phenylalanine at a stoichiometric molar percentage of 50% (PP50). PP50 was co-incubated with saporin (PP50/saporin) in a mildly acidic pH environment to aid intracellular delivery and increase saporin’s therapeutic potential. It was shown that PP50 is a potential intracellular delivery platform for the internalization of protein therapeutic.

Usage: PP50/saporin formulations were prepared with D-PBS solutions at pH 6.5 containing PP50 at a specific concentration of 0.025, 0.1, 0.2, 0.5 or 5 mg mL−1 and Saporin (PR-01) at varying concentrations.

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

O’Sullivan JA, Youngblood BA, Schleimer RP, Bochner BS (2024) Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases. Semin Immunol 69:101799. doi: 10.1016/j.smim.2023.101799 PMID: 37413923

Objective: To review a subset of Siglecs and their various endogenous or synthetic sialoside ligands that regulate eosinophil and mast cell function and survival.

Summary: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are vertebrate glycan-binding cell-surface proteins. Many Siglecs mediate cellular inhibitory activity and are of interest as part of a strategy to therapeutically lessen unwanted cellular responses. Human eosinophils and mast cells express overlapping but distinct patterns of Siglecs, and certain Siglecs have become the focus of novel therapies for allergic and other eosinophil and mast cell-related diseases.

Usage: Saporin in conjunction with CD22 glycomimetic ligand BPCNeuAc leads to cells death induction in a ligand-dependent manner on B-lymphoma cells (Collins et al.). Incubation with anti-Siglec-8 monoclonal antibody conjugated to saporin led to the death of malignant mast cells and eosinophils (O’Sullivan et al.)

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

See Also:

• Collins BE, Blixt O, Han S, Duong B, Li H, Nathan JK, Bovin N, Paulson JC (2006) High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol 177(5):2994-3003. doi: 10.4049/jimmunol.177.5.2994 PMID: 16920935
• 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.

Rosado M, Mahamed I, Garcia-Sampedro A, MacRoberts S, Selbo P, Pereira S, Acedo P (2024) Enhancing pancreatic cancer chemotherapy through photochemical internalisation. Cancer Res 84 (17_Supplement_2):A027. doi: 10.1158/1538-7445.PANCREATIC24-A027

Objective: The aim is to use the technique called Photochemical Internalisation (PCI), a light-triggered intracellular drug delivery method which combines low dose PhotodynamicTherapy (PDT) with chemotherapy, to induce efficient cytosolic delivery of therapeutic compounds to their specific subcellular targets.

Summary: Observation of minimal cytotoxicity induced by saporin, gemcitabine or TPPS2a+ light monotherapies. However, PCI synergistically enhanced saporin and gemcitabine cytotoxicity (p<0.001) using very low concentrations in all tumor models. Findings demonstrate the potential of PCI to enhance the efficacy of cancer chemotherapy for pancreatic cancer using lower doses than in monotherapy and open a new window for future translational studies.

Usage: Saporin was used as monotherapy or in combination with a light-activated photosensitizer.

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

Dai SP, Yang CC, Chin Y, Sun WH (2024) T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain. iScience 27(10):110955. doi: 10.1016/j.isci.2024.110955 PMID: 39381739

Objective: To elucidate how T cell death-associated gene 8 (TDAG8)-mediated signaling modulates neuron activities in a mouse model of chronic constriction injury-induced neuropathic pain.

Summary: TDAG8 participated alone in mechanical allodynia induced by constriction injury. TDAG8-Nav1.8 signaling in small-diameter isolectin B4-positive [IB4(+)] neurons initiate mechanical allodynia; it also modulated substance P release from IB4(-) neurons to facilitate the development of early mechanical allodynia. TDAG8-mediated signaling increased medium-to large-diameter IB4(-) neuron activity to maintain late mechanical allodynia; it also modulated substance P release in soma to reduce satellite glial number and Nav1.7 expression, thus attenuating chronic mechanical allodynia.

Usage: Mice were intrathecally injected with IB4-saporin (IB4-SAP, 0.06 mg/mL) or Saporin (0.06 mg/mL)

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Lv J, Liu X, Yin L, Cheng Y (2024) Rational engineering of cytosolic delivery systems for protein therapeutics. Acc Mater Res doi: 10.1021/accountsmr.4c00149

Objective: To summarize recent advances in the rational design of cytosolic protein delivery systems.

Summary: Saporin, a cell membrane-impermeable toxin, kills cancer cells by inhibiting protein synthesis. To fully utilize the therapeutic potential of saporin, the authors developed a series of polymeric carriers to deliver saporin into tumor cells.

Usage: Polymeric carriers were used to deliver saporin into tumor cells

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

Keilhoz A, Pathak I, Smith CL, Osman KL, Smith L, Oti G, Golzy M, Mz L, Lever TE, Nichols NL (2024) Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss. Front Neurol 15:1441529. doi: 10.3389/fneur.2024.1441529 PMID: 39296960

Objective: To investigate the effects of a strength endurance tongue exercise program on upper airway structure and function.

Summary: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to rats treated with CTB-SAP and exercise and control rats with/without tongue exercise, which were ameliorated with tongue exercise. Additionally, CTB-SAP treated, sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP treated exercise rats or control rats with/without tongue exercise.

Usage: Intralingual injection of either unconjugated CTB+SAP (20 μg CTB+25 μg SAP) or conjugated CTB-SAP (25 μg of CTB conjugated to SAP).

Related Products: CTB-SAP (Cat. #IT-14), Recombinant Cholera Toxin B (Cat. #PR-14), Saporin (Cat. #PR-01)

Gunasekaran M, L S, Premarathna AD, (2024) Enhancing monoclonal antibodies with natural products: Mechanisms and applications. Intelligent Pharmacy doi: 10.1016/j.ipha.2024.09.002

Objective: To investigate the novel application of beta-glucan analogs engineered for enhanced immunomodulatory effects, targeting not only malignant cells but also the tumor microenvironment to optimize mAb penetration.

Summary: By combining plant-based expression systems with synthetic biology tools, creating a hybrid platform that surpasses traditional plant or mammalian systems in both yield and safety. This approach not only reduces production costs but also introduces a scalable method for the rapid adaptation of mAbs in response to emerging pathogens or tumor mutations.

Usage: Combining trastuzumab and cetuximab with the plant-derived toxin saporin (PR-01) resulted in a significant increase in cytotoxicity against tumor cells. This approach, especially when paired with plant glycosides, promotes the release of toxins into the cytoplasm, resulting in total cell death in select cancer cell types.

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

Kostenko A, Prezzavento O, de Leo G, D’Arco D, Gulion R, Caccamo A, Leanza G (2024) Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation. J Alzheimers Dis 101(3) doi: 10.3233/JAD-240618 PMID: 39240642

Objective: This study sought to assess the role of (±)-cyclopropane carboxylate (PPCC) on working memory deficits caused by noradrenergic depletion.

Summary: While (±)-PPCC alone at a dose of 1 mg/kg/day failed to affect working memory in lesioned animals, its association with the α2 adrenergic receptor agonist clonidine, completely blocked noradrenaline release, significantly improving rat performance. This effect, distinct from noradrenaline activity, is likely to result from a direct action of the (±)-PPCC compound onto sigma-1 receptors, as pre-treatment with the selective sigma-1 receptor antagonist BD-1047 reversed the improved working memory performance. Despite such clear functional effects, the treatment did not affect noradrenergic neuron survival or terminal fiber proliferation.

Usage: Bilateral intraventricular injections of anti-DBH-saporin (IT-03). Either 1.25μg or 2.5μg of the immunotoxin was dissolved in 7μl of sterile PBS and administered into each lateral ventricle (resulting in a total of 2.5μg or 5.0μg per rat in a 7 + 7μl volume of vehicle).

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

Runyon K, Bui T, Mazanek S, Hartle A, Marschalko K, Howe WM (2024) Distinct cholinergic circuits underlie discrete effects of reward on attention. Front Mol Neurosci. Front Mol Neurosci 17:1429316. doi: 10.3389/fnmol.2024.1429316 PMID: 39268248

Objective: Review the basic neuroanatomy of attention, reward, and cholinergic systems.

Summary: Authors examined specific contexts in which attention and reward computations interact. They proposed two discrete neural circuits whereby acetylcholine, released from cell groups located in different parts of the brain, mediates the impact of stimulus-reward associations as well as motivation on attentional control. Authors concluded by examining these circuits as a potential shared loci of dysfunction across diseases states associated with deficits in attention and reward.

Usage: Lesions of basal forebrain via ACh-immunotoxin 192-IgG-SAP (IT-01) impaired performance on a sustained attention task designed for rodents, selectively reducing the capacity of rats to report the presence of instructive cues, while having no effect on their ability to report the absence of these cues0

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

See Also:

• McGaughy J et al. Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density. Behav Neurosci 110:247-265, 1996.