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Identification of an essential spinoparabrachial pathway for mechanical itch
Ren X, Liu S, Virlogeux A, Kang SJ, Brusch J, Liu Y, Dymecki SM, Han S, Goulding M, Acton D (2023) Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 30:S0896-6273. doi: 10.1016/j.neuron.2023.03.013 PMID: 37023756
Objective: Study pathways of mechanical and chemical itch.
Summary: Mechanical and chemical itch are controlled by separate pathways within the body. Gpr83ligand PEN peptide conjugated to saporin (PEN-SAP) was used to selectively ablate CAlcrl projection neurons, alleviating mechanical itch sensitivity in wild-type mice. Substance-P saporin (SSP-SAP) was injected into mice and used as a negative control for the ablation of itch-sensitive neurons in the areas targeted. The ablated mice maintained mechanical itch sensitivity.
Usage: Intrathecal injections of SSP-SAP (IT-11; 100 ng/10 ml 0.9% sterile saline), biotinylated Gpr83 ligand (PEN) conjugated to Strepavidin-ZAP (IT-27), PEN-SAP, 3 ug/10 ml, 0.9% sterile saline, or control Blank-SAP (IT-21) in mice.
Related Products: SSP-SAP (Cat. #IT-11), Streptavidin-ZAP (Cat. #IT-27), Blank-SAP (Cat. #IT-21)
Recent progress in nanomedicine-mediated cytosolic delivery
Son H, Shin J, Park J (2023) Recent progress in nanomedicine-mediated cytosolic delivery. RSC Adv 13(15):9788-9799. doi: 10.1039/D2RA07111H PMID: 36998521
Summary: Cytosolic delivery of drugs, like saporin, through nanocapsules offers ways to move proteins through the body with greater specificity and efficacy. A nanoparticle that released a modified saporin protein at pH conditions correlative conditions to a tumor micro-environment was discussed as a model to deliver peptide-drugs to the cytosol.
KNDy neurons as the GnRH pulse generator: Recent studies in ruminants
Nestor CC, Merkley CM, Lehman MN, Hileman SM, Goodman RL (2023) KNDy neurons as the GnRH pulse generator: Recent studies in ruminants. Peptides 164:171005. doi: 10.1016/j.peptides.2023.171005 PMID: 36990389
Objective: This publication aims to summarize and provide an overview of recent studies investigating the role of KNDy neurons as the pulse generator for gonadotropin-releasing hormone (GnRH) release in ruminants.
Summary: Recent studies in ruminants, specifically sheep and cows, have investigated the role of KNDy neurons in driving the pulsatile release of GnRH. These studies have demonstrated the rhythmic electrical activity of KNDy neurons, coinciding with the pulsatile secretion of GnRH in ewes, suggesting their central role as the pulse generator. Additionally, the expression patterns of genes related to KNDy neurons and GnRH pulsatility have been examined in cows, revealing variations throughout the estrous cycle and indicating a potential involvement of KNDy neurons in regulating GnRH release in this species. These findings contribute to our understanding of reproductive physiology in ruminants and have implications for both animal and human reproductive health.
Related Products: NKB-SAP (Cat. #IT-63)
Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age
Konturek-Ciesla A, Dhapola P, Zhang Q, Säwén P, Wan H, Karlsson G, Bryder D (2023) Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age. Cell Rep 42(4):112304. doi: 10.1016/j.celrep.2023.112304 PMID: 36961818
Objective: Using single-cell transcriptome and epitope profiling to study hematopoiesis and the effects from aging.
Summary: The contribution from Hematopoietic stem cells (HSCs) to mature blood cells decline with age. The authors used transcriptome and epitope profiling to reconstruct early hematopoiesis and assessed HSC-specific lineage tracing. Their analysis identified previously uncharacterized cell populations which included multipotent progenitor cells (MPP) Ly-1 and Ly-II. Flt3 is a marker indicative of early differentiation found on MPP cells and was targeted for elimination via an antibody to Flt3 combined with Streptavidin-ZAP. This cell depletion provided evidence for the lack of self-renewal of Ly-1 and Ly-II cells in a transplantation setting and suggests that they need to be continuously replenished by upstream HSPCs.
Usage: Biotinylated anti-CD135 (clone A2F10) was combined with Streptavidin-ZAP at a 1:1 molar ratio, diluted in PBS to 0.2 mg/ml and injected into mice at 3 mg/kg.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities
Donertas-Ayaz B, Caudle RM (2023) Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities. Neurobiol Pain 13:100124. doi: 10.1016/j.ynpai.2023.100124 PMID: 36974102
Objective: To summarize the knowledge about the involvement of noradrenaline in acute and chronic trigeminal pain conditions and how the activity of the locus coeruleus (LC) noradrenergic neurons changes in response to acute and chronic pain conditions and how these changes might be involved in pain-related comorbidities including anxiety, depression, and sleep disturbance.
Summary: LC inhibition of nociceptive transmission in acute pain and in longterm neuropathic pain increases the tonic activity of LC-NA neurons. These changes may contribute to impaired descending pain modulation and pain-related comorbidities such as depression, anxiety, and sleep disorders.
Usage: Elimination of NA neurons via injection of anti-dopamine β-hydroxylase-saporin (Anti-DBH-SAP) into the lateral ventricle and trigeminal brainstem nuclei three weeks after infraorbital nerve injury attenuated mechanical allodynia
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory.
Zaichenko MI, Philenko P, Sidorina V, Grigoryan GA (2023) Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory. Biochemistry Moscow 88:526-538. doi: 10.1134/S0006297923040089 PMID: 37080938
Objective: Goal of the work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide- induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures.
Summary: Chronic stress, depression, and other neuropsychiatric disorders have been often associated with inflammation processes and activity of the brain immune system. In order to investigate association of neuroinflammation with such disorders the model of proinflammatory bacterial lipopolysaccharide intoxication was used. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze and caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Hprt and Ywhaz genes were selected for use as molecular biology reference genes based on the analysis of the rat hippocampus transcriptome from the work done by Dobryakova, Y.V. et. al (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Non-genotoxic restoration of the hematolymphoid system in fanconi anemia
Chan YY, Ho PY, Swartzrock L, Rayburn M, Nofal R, Thongthip S, Weinberg KI, Czechowicz A (2023) Non-genotoxic restoration of the hematolymphoid system in fanconi anemia. Transplant Cell Ther 29(3):164.e1-164.e9. doi: 10.1016/j.jtct.2022.08.015 PMID: 35995393
Objective: Evaluate the efficacy of different CD117 mAb agents and immunosuppression on hematopoietic stem cell (HSC) depletion, and their ability to safely establish therapeutic donor hematopoiesis post-HSCT in Fancomi Anemia (FA) disease models.
Summary: Patients with FA are particularly sensitive to genotoxic agents in the treatment of blood and immune diseases. By targeting the disease through use of a CD117 antibody conjugate to an antagonist agent, some of the sensitivities of Fancomi anemia can be circumvented compared to traditional therapeutics. The results demonstrated the efficacy of several different non-genotoxic monoclonal antibody-based conditioning strategies in Fancomi anemia.
Usage: Biotinylated CD117 mAb mixed with Streptavidin-ZAP (Anti-CD117-SAP) and was administered on Day 0. Anti-CD117-SAP was diluted with sterile PBS and administered at 1.5 mg/kg via i.v. injection.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)
Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia
Myers B, Islam S, Gleber Netto FO, Debnath KC, Srivastava S, Xie T, Akhter S, Adebayo AA, Miller J, Lothumalia S, Sathiskumar HN, Amit M (2023) Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia. Cancer Neuroscience Symposium
Objective: Explore the hypothesis that modulation of cholinergic (CHAT+) and nociceptive (CGRP+) neurons correlate with improved dysphagia.
Summary: Oropharyngeal squamous cell carcinoma is one of the most common types of head and neck cancer. Treatment for OPSCC includes surgery, radiation therapy, chemotherapy, or a combination of therapies. Despite advances in treatment, dysphagia (difficulty swallowing) is still a major burden for patients with OPSCC. The study established a novel murine OPSCC model to explore the role of nerves in dysphagia with cholinergic (CHAT) and nociceptive (CGRP) neurons playing an important role in swallowing outcomes. Targeting CHAT and CGRP could be a novel strategy for OPSCC patients with dysphagia.
Usage: 500 ng of Anti-ChAT-SAP was injected into the trigeminal ganglion in mice.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)
Streptavidin-saporin: Converting biotinylated materials into targeted toxins
Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2023) Streptavidin-saporin: Converting biotinylated materials into targeted toxins. Toxins 15(3):181. doi: 10.3390/toxins15030181 PMID: 36977072
Summary: This manuscript describes the myriad of ways Streptavidin-ZAP is used and how this technology supports the scientific process of ‘Molecular Surgery’ and progress in research and drug development. Insights from publications and research performed using Streptavidin-ZAP and its impact on academia and industry for research and drug development are presented.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Development of a new minimally invasive phototherapy for lung cancer using antibody-toxin conjugate
Sonokawa T, Obi N, Usuda J, Sudo Y, Hamakubo T (2023) Development of a new minimally invasive phototherapy for lung cancer using antibody-toxin conjugate. Thorac Cancer 14(7):645-653. doi: 10.1111/1759-7714.14776 PMID: 36655546
Objective: Using a photo-sensitizer and red light to release Cetuximab-saporin to target cancer.
Summary: Photodynamic therapy is a non-invasive cancer treatment using a photo-sensitizer and laser irradiation to control the delivery of the chemotherapy agent. Streptavidin-ZAP mixed with biotinylated Cetuximab and a photo-sensitizer (mono-L-aspartyl chlorin e6) is used as an anti-cancer immunotoxin. In vitro analysis demonstrated that the novel photodynamic therapy method enhanced the cytotoxicity of Cetuximabe-SAP.
Usage: Streptavidin-ZAP (IT-27) mixed with biotinylated Cetuximab was used in vitro in A431, A549, and MCF7 cells.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
