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T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain
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)
Rational engineering of cytosolic delivery systems for protein therapeutics
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)
Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning
Penna S, Zecchillo A, Di Verniere M, Fontana E, Iannello V, Palagano E, Mantero S, Cappelleri A, Rizzoli E, Santi L, Crisafulli L, Filibian M, Forlino A, Basso-Ricci L, Scala S, Scanziani E, Schinke T, Ficara F, Sobacchi C, Villa A, Capo V (2024) Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning. Front Endocrinol (Lausanne) 15:1450349. doi: 10.3389/fendo.2024.1450349 PMID: 39314524
Objective: To investigate whether gene therapy (GT) could minimize the immune-mediated complications of allogeneic hematopoietic stem cell transplantation (HSCT) and offer a prompt treatment.
Summary: Authors showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis and that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity.
Usage: Recipient oc/oc mice were conditioned by CD45-SAP injections or total body irradiation (IRR)
Related Products: Anti-CD45.2-SAP (Cat. #IT-91)
Cholinergic neurotransmission during performance of a sustained attention task after traumatic brain injury
Moschonas EH (2024) Cholinergic neurotransmission during performance of a sustained attention task after traumatic brain injury. Univ Pittsburgh School of Medicine Thesis.
Objective: To elucidate the role of basal forebrain cholinergic neurons (BFCNs) in mediating attentional performance and ACh efflux
Summary: Saporin-induced lesions to the nbM impaired signal detection accuracy during performance of the Sustained Attention Task (SAT). Similarly, in tasks of divided attention that involve both auditory and visual stimuli, cholinergic lesions to the nbM result in prolonged response times during bimodal trials compared to unimodal trials, which involve a single sensory modality.
Related Products: 192-IgG-SAP (Cat. #IT-01)
See Also:
- McGaughy J et al. Sustained attention performance in rats with intracortical infusions of 192 IgG-saporin-induced cortical cholinergic deafferentation: effects of physostigmine and FG 7142. Behav Neurosci 112(6):1519-1525, 1998.
- McGaughy J et al. The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251-263, 2000.
- Dalley JW et al. Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-Saporin-induced lesions of the medial prefrontal cortex. Cereb Cortex 14(8):922-932, 2004.
- Chudasama Y et al. Cholinergic modulation of visual attention and working memory: Dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine. Learn Mem 11(1):78-86, 2004.
- Botly LC et al. Cholinergic deafferentation of the neocortex using 192 IgG-saporin impairs feature binding in rats. J Neurosci 29:4120-4130, 2009.
- Butt AE et al. Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-Saporin lesions of the nucleus basalis magnocellularis. Behav Neurosci 116(2):241-255, 2002.
- Butt AE et al. Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-Saporin lesions of the nucleus basalis magnocellularis. Behav Neurosci 116(2):241-255, 2002.
Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss
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)
Enhancing monoclonal antibodies with natural products: Mechanisms and applications
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)
Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation
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)
Distinct cholinergic circuits underlie discrete effects of reward on attention. Front Mol Neurosci
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:
Role of the locus coeruleus arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle
Huo C, Lombardi F, Blanco-Centurion C, Shiromani PJ, Ivanov PC (2024) Role of the locus coeruleus arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle. J Neurosci 44(35):e1939232024. doi: 10.1523/JNEUROSCI.1939-23.2024 PMID: 38951035
Objective: To investigate dynamics of θ- and δ-bursts during the sleep-wake cycle of rats with lesion in the wake-promoting locus coeruleus (LC).
Summary: The findings indicate that critical dynamics of θ- and δ-bursts arise from a balanced interplay of LC and ventrolateral preoptic nucleus (VLPO), which maintains brain tuning to criticality across the sleep-wake cycle.
Usage: To confirm the efficacy of anti-DBH-SAP (IT-03) to kill noradrenergic-LC neurons and their fibers. 192 IgG-SAP (IT-01) was selected as an additional control because like anti-DBH-SAP it is a conjugate of a monoclonal antibody and saporin. Bilateral microinjection of 192-IgG-SAP and Anti-DBH-SAP were used at a volume of 0.3μL at a rate of 0.1μL/5 min using a pressure injector
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds
Langellotto MD, Rassu G, Serri C, Demartis S, Giunchedi P, Gavini E (2024) Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds. Springer Nature 11(3) doi: 10.1007/s13346-024-01698-4
Objective: This review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived extracellular vesicles (EVs).
Summary: Freeze-drying could be useful for preserving plant-derived exosomes at higher temperatures without affecting their size, morphology or other parameters. Still, it may reduce protein activity, as reported by Noguchi and coworkers, who observed a diminished biological activity of protein saporin after its encapsulation in EVs and freeze-drying.
Related Products: Saporin (Cat. #PR-01)
See Also: