References

Chuang KH, Zhou XA, Xia Y, Li z, Qian L, Eeles E, Ngiam G, Fripp J, Coulson EJ (2024) Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux. bioRxiv 2024.08.25.609536. doi: 10.1101/2024.08.25.609536

Objective: To show that vascular-CSF coupling correlates with cortical cholinergic activity in non-demented aged humans.

Summary: Waste from the brain is cleared via a cerebrospinal fluid (CSF) exchange pathway. Problems in this pathway is suggested to underlie the pathogenesis of many brain conditions. Cerebrovascula oscillation that couples with pulsatile CSF inflow is suggested to drive the flow of fluid, however how this coupling is regulated in unlcear. The resultsfor the study suggest a neurovascular mechanism by which CSF/glymphatic flux is modulated by cholinergic neuronal activity, thereby providing a conceptual basis for the development of diagnostics and treatments for glymphatic dysfunction.

Usage: Injections of mu-p75-SAP (0.5 mg/ml, IT-16) or control Rabbit-IgG-SAP (0.5 mg/ml, IT-35) were performed into the border between the medial septum and ventral diagonal band. In the first study, the toxin was infused at a rate of 0.4 μl/min (1.5μl total volume), which resulted in a large amount of ablation. In the second study, the toxin concentration was reduced to 0.3 mg/ml to preserve more cholinergic neurons and was infused at a rate of 0.18μl/min (1.0μl total volume).

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Mohammadi F, Zahraee H, Zibadi F, Khoshbin Z, Ramezani M, Alibolandi M, Abnous K, Taghdisi SM (2024) Progressive cancer targeting by programmable aptamer-tethered nanostructures. MedComm (2020) 5(11):e775. doi: 10.1002/mco2.775 PMID: 39434968

Objective: This review focuses on the significance of different aptamer-assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery.

Summary: Saporin was attached to a βCD-conjugated aptamer. After treating HeLa cells with the circular bivalent aptamer (Cb-Apt)‒saporin complex, cell viability decreased by 20%, whereas mono-apt‒saporin showed no significant toxicity. The Cb-Apt‒βCD complex effectively improved the intracellular delivery of saporin.

Usage: 1:50 molar ratio (nanostructure:saporin).

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

Jiang H, Cui H, Chen M, Li F, Shen X, Guo CJ, Hoekel GE, Zhu Y, Han L, Wu K, Holtzman MJ, Liu Q (2024) Divergent sensory pathways of sneezing and coughing. Cell 187(21):5981-5997. doi: 10.1016/j.cell.2024.08.009 PMID: 39243765

Objective: To study the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing.

Summary: Sneezing and coughing are frequently associated with allergies and respiratory viral infections and it’s assumed both involve common sensory receptors and neurotransmission mechanisms. The author’s work show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3−) mediates sneezing. Although this same population innervates the trachea, it does not mediate coughing, and instead, a distinct sensory population (somatostatin SST) mediates coughing but not sneezing. NMB-SAP was used to ablate neruomedin B (NMB) receptor expressing and nucleus tractus solitarius (NTS) neurons. Deletion of these neurons did not affect the coughing responses to Ly344864 and IL-31 (agonists to SST neurons) suggesting that NMB-sensitive NTS neurons do not mediate coughing.

Usage: Neuronal ablation by SST-saporin and NMB-saporin. SST-saporin was made by mixing biotin-labeled somatostatin and Streptavidin-ZAP (IT-27) at a 1:1 molar ratio at room temperature for 20 minutes. SST-Saporin (10 μM, 50 nL), NMB-saporin (#IT-70; 50 ng in 50 nL) or Blank-SAP (#IT-21; 10 μM in 50 nL or 50 ng in 50 nL) was injected into the NTS region.

Related Products: Streptavidin-ZAP (Cat. #IT-27), NMB-SAP (Cat. #IT-70), Blank-SAP (Cat. #IT-21)

Limonta P, Chiaramonte R, Casati L (2024) Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies. Cancers (Basel) 16(16):2861. doi: 10.3390/cancers16162861 PMID: 39199632

Objective: To review the bidirectional communication between melanoma cancer stem cells (CSCs) and the tumor microenvironment, highlighting its role in drug resistance and tumor relapse.

Summary: Melanoma CSCs evade immune surveillance and recruit immune cells with immunosuppressive and tumor-promoting properties, establishing a supportive microenvironment. They also transfer stemness and aggressive traits to neighboring non-CSCs, driving tumor progression and metastasis. Targeting these interactions may offer novel therapeutic strategies for combating melanoma.

Usage: This review publication highlights the usage of Anti-CD271-SAP and CD133-SAP in previous publications.

Related Products: ME20.4-SAP (Cat. #IT-15), Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01)

See Also:

• Ngo M et al. Antibody therapy targeting CD47 and CD271 effectively suppresses melanoma metastasis in patient-derived xenografts. Cell Rep 16:1701-1716, 2016.
• Bostad M et al. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48, 2015.

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)

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)

Guo SS, Gong Y, Zhang TT, Su XY, Wu YJ, Yan YX, Cao Y, Song XL, Xie JC, Wu D, Jiang Q, Li Y, Zhao X, Zhu MX, Xu TL, Liu MG (2024) A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch. Sci Adv 10(33):eadn6272. doi: 10.1126/sciadv.adn6272 PMID: 39150998

Objective: To investigate anxiety-like behaviors in mouse models of chronic itch and identify lateral septum (LS) GABAergic neurons as key mediators through thalamic and hypothalamic circuit interactions.

Summary: Chronic itch amplifies excitatory inputs from the thalamic nucleus reuniens to LS GABAergic neurons, promoting anxiety-like behaviors. Inhibiting the Re → LS circuit reduces anxiety related to chronic itch but not restraint stress, highlighting its specificity. LS GABAergic neurons suppress lateral hypothalamus activity to mediate chronic itch-induced anxiety, with Bombesin-SAP targeting spinal itch neurons to confirm this pathway’s role.

Usage: Mice were intrathecally injected with Bombesin-SAP (IT-40) (400 ng/5 μl). Blank-SAP (IT-21) (400 ng/5 μl) was administered similarly to a control.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Zhang Q, Xue J, Tang J, Wu S, Liu Z, Wu C, Liu C, Liu Y, Lin J, Han J, Liu L, Chen Y, Yang J, Li Z, Zhao L, Wei Y, Li Y, Zhuo Y (2024) Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function. Sci Adv 10(31):eado0866. doi: 10.1126/sciadv.ado0866 PMID: 39093964

Objective: To identify a unique subtype of amacrine cells (ACs), dopaminergic ACs (DACs), that respond early to optic nerve crush by downregulating neuronal activity and reducing retinal dopamine (DA) release.

Summary: Activation of DACs or augmentation of DA release using levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. The dopamine receptor D1 (DRD1) was also identified as a critical mediator of DAC-derived DA, and retinal ganglion cell (RGC)-specific DRD1 overexpression effectively overcame subtype-specific barriers to regeneration.

Usage: Immunostaining of retinal cryosections and whole mounts (1:1000) (AB-N39).

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)