References

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.

Coutinho EA, Esparza LA, Steffen PH, Liaw R, Bolleddu S, Kauffman AS (2024) Selective depletion of kisspeptin neurons in the hypothalamic arcuate nucleus in early juvenile life reduces pubertal LH secretion and delays puberty onset in mice. FASEB J 28(19):e70078. doi: 10.1096/fj.202401696R PMID: 39377760

Objective: To investigate the specific kisspeptin population timing pubertal onset.

Summary: This study teases apart the contributions of different kisspeptin neural populations to the control of puberty onset, demonstrating that a majority of KNDy neurons in the arcuate nucleus are necessary for the proper timing of puberty in both sexes.

Usage: See also these studies where ~70% of ARC kisspeptin (KNDy) neurons were selectively ablated in rats using NKB-SAP (IT-63).

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

See Also:

• Mittelman-Smith MA et al. Arcuate kisspeptin/neurokinin b/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology 153(6):2800-2812 , 2012 .
• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.
• Mittelman-Smith M et al. Ablation of KNDy neurons results in hypogonadotropic hypogonadism and amplifies the steroid-induced LH surge in female rats. Endocrinology 157:2015-2027, 2016.
• Campideli-Santana AC et al. Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol. J Neuroendocrinol 34(11):e13204, 2022.

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)

Konofal E (2024) From past to future: 50 years of pharmacological interventions to treat narcolepsy. Pharmacol Biochem Behav 241:173804. doi: 10.1016/j.pbb.2024.173804 PMID: 38852786

Objective: This review article discusses the historical progression and transformative insights that have characterized the treatment of narcolepsy from its initial documentation to the present day.

Summary: The research continues to push the boundaries of what is known about this complex sleep disorder, the hope for treatments that can fundamentally alter the disease trajectory becomes increasingly tangible. This paradigm shift towards addressing the autoimmune, neuroinflammatory, and neurodegenerative aspects of narcolepsy promises to revolutionize patient care.

Usage: See also these references using Orexin-B-SAP (IT-20) to create a narcoleptic-like rat model via LH lesions.

See Also:

• Gerashchenko D et al. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 21(18):7273-7283, 2001.
• Gerashchenko K et al. Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience 116:223-235, 2003.

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)