- Home
- Knowledge Base
- References
References
Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species
Fulton S, Horn CC, Zhang C (2024) Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species. Physiol Behav 114474. doi: 10.1016/j.physbeh.2024.114474 PMID: 38272107
Objective: Characterize the ligand exenatide conjugated to saporin as a tool to ablate GLP1 receptor-expressing cells from human, mice, and shrews, a small animal model capable of emesis (vomiting).
Summary: Nausea is a distressing sensation that is a common side effect of many medications. Nausea and emesis are among the top adverse side effects of glucagon-like peptide-1 (GLP1) receptor (GLP1R) agonists-based medications to treat type 2 diabetes and obesity. The area postrema is a brain structure that mediates nausea effects. The authors provide characterization of Ex4-SAP (GLP-1-SAP) to specifically ablate GLP1R-expressing HEK293T cells in vitro and in area postrema neurons in mice and house musk shrews in vivo.
Usage: C57BL-6J mice were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 200 ng/ul, in a total of 400 nl at a rate of 2 nl/second. Musk shrews were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 500 ng/ul, in a total of 200 nl at a rate of 2 nl/second.
Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-Streptavidin-SAP (Cat. #IT-27B)
Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment
Janes TA, Cardani S, Saini JK, Pagliardini S (2024) Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) e14093. doi: 10.1111/apha.14093 PMID: 38258900
Objective: Examine the use of progestins and synthetic progestins in the stimulation of breathing, especially after chemoreflexive impairment.
Summary: Central CO2 chemoreflex is important for respiratory control. The retrotrapezoid nucleus is involved in CO2 chemosensitivity where its removal or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Progesterone stimulates restful breathing and CO2 chemoreflexes. The authors investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could help in the recovery of respiratory chemoreflexes following lesion of the retrotrapezoid nucleus via a SP-SAP.
Usage: Rats were injected with 26-43.3 ng/ul of SP-SAP (IT-11) or 46.7 ng/ul of Blank-SAP (IT-21), with 150 nl per injection.
Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)
Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs
Zhao Q, Zong H, Zhu P, Su C, Tang W, Chen Z, Jin S (2024) Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs. Exp Hematol Oncol 13(1):6. doi: 10.1186/s40164-024-00474-x PMID: 38254219
Summary: Cancer immunotherapy has become a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy. Cancer stem cells (CSCs) have the capabilities of self-renewal and differentiation and are also resistant to the traditional therapies of radiotherapy and chemotherapy. The authors review strategies for targeting colorectal CSCs, where one method described uses a biotinylated antibody against EpCAM (clone 3-171) conjugated to saporin via Streptavidin-ZAP (IT-27).
Related Products: Streptavidin-ZAP (Cat. #IT-27)
See Also:
A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats
Masmudi-Martín M, López-Aranda MF, Navarro-Lobato I, Khan ZU (2024) A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats. Eur J Neurosci doi: 10.1111/ejn.16243 PMID: 38238909
Objective: Provide evidence that the frontal association cortex and not the Perirhinal cortex is essential for object recognition memory (ORM) of objects with complex features.
Summary: The Perirhinal cortex is a brain area that has been seen as being crucial for ORM. However, the authors challenge that thought by using an ORM enhancer named RGS14414. Used as a tool, expression of it in rat brain frontal association cortex induced the formation of long-term complex ORM whereas the expression of the enhancer in Perirhinal cortex didn’t illicit the same effect. The authors also showed that expression of the enhancer in Perirhinal cortex instead caused formation of ORM of objects with only simple features. Furthermore, the selective elimination of frontal association cortex neurons via OX7-SAP (IT-02) completely removed the formation of complex ORM.
Usage: OX7-SAP (IT-02) was injected into the frontal association cortex of rats at a dose of 0.2 ug in 1 ul.
Related Products: OX7-SAP (Cat. #IT-02)
Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells
Gong S, Qiu J, Thayumanavan S (2023) Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells. J Am Chem Soc doi: 10.1021/jacs.3c09334 PMID: 38147631
Objective: To describe a simple self-assembly strategy for generating artificial immune complexes.
Summary: The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages while ensuring stability during delivery.
Usage: Cytotoxicity assay to measure cell death with targeted saporin.
Related Products: Saporin (Cat. #PR-01)
Intracellular protein delivery: Approaches, challenges, and clinical applications
Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers doi: 10.34133/bmef.0035
Objective: To review progress made towards achieving cytosolic delivery of recombinant proteins and possible strategies to enable proteins to cross cell membranes.
Summary: Drug delivery researchers have worked to deliver saporin into tumor cells in the hopes of producing potent next-generation cancer therapeutics. Cationic, anionic, and zwitterionic versions of poly(β-amino ester) have been developed for delivery of saporin. Chemically-modified saporin can be encapsulated by cationic LNPs for in vivo tumor inhibition. Saporin has been used as a model cargo protein for in vivo delivery via fluoropolymer nanoparticles for successful tumor growth inhibition.
Related Products: Saporin (Cat. #PR-01)
See Also:
Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens
Loftén A, Adermark L, Ericson M, Söderpalm B (2023) Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens. Addict Biol 28(12):e13349. doi: 10.1111/adb.13349 PMID: 38017639
Objective: The aim of this study was to explore the role of glycine receptors (GlyRs) on cholinergic interneurons (CIN) in sustaining extracellular dopamine levels and in ethanol-induced dopamine release.
Summary: Alcohol use disorder is one of the major psychiatric disorders worldwide. Ethanol reward is one of the many factors contributing to the disorder. The rewarding and reinforcing properties of ethanol have been linked to activation of the mesolimbic dopamine system, an effect that involves glycine receptors (GlyRs) in the nucleus accumbens. The study suggests that CIN are not important for GlyR-mediated regulation of basal dopamine output, but that CIN ablation blunts the ethanol-induced dopamine release by reducing the release of GlyR agonists.
Usage: CIN were ablated by Anti-ChAT-SAP administered locally in the nucleus accumbens of male Wistar rats. Rabbit-IgG-SAP was used as a control. Microinfusion was performed unilaterally into the nAc at a concentration of 0.5 ug/ul at 0.05 ul/min for 10 min for a total of 0.5 ul.
Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)
Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease
Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2023) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther doi: 10.1111/cns.14446 PMID: 37721421
Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).
Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.
Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents
Kubeil M, Suzuki Y, Casulli MA, Kamal R, Hashimoto T, Bachmann M, Hayashita T, Stephan H (2023) Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents. Adv Healthc Mater e2301404. doi: 10.1002/adhm.202301404 PMID: 37717209
Summary: This review provides a brief overview of current developments of nanogels in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. The authors described one development using saporin. Mimicking the function of molecular chaperones, Kawasaki et al. created magnetic in vivo protein transport nanogels with encapsulated iron oxide nanoparticles. The nanogels also contained saporin, which was rapidly released by an exchange reaction with serum protein. The evaluation using an oral cancer model revealed a reduction in tumor volume and suppression of tumor regrowth, with no change in body weight.
Related Products: Saporin (Cat. #PR-01)
See Also:
- Kawasaki R et al. (2021) Magnetically navigated protein transduction in vivo using iron oxide-nanogel chaperone hybrid. Adv Healthc Mater 10(9):e2001988. doi: 10.1002/adhm.202001988 PMID: 33694289
Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review)
Thongchot S, Aksonnam K, Thuwajit P, Yenchitsomanus PT, Thuwajit C (2023) Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review). Int J Mol Med 52(3):81. doi: 10.3892/ijmm.2023.5284 PMID: 37477132
Objective: The authors review the mechanisms through which the multiple functions of NCL can participate in the progression of cancer. In addition, the studies that define the utility of NCL‑dependent anticancer therapies are summarized, with specific focus being paid to cancer immunotherapeutic approaches.
Summary: NCL is a multifunctional protein abundantly distributed in the nucleus, cytoplasm and cell membrane. It influences carcinogenesis, and the proliferation, survival and metastasis of cancer cells, leading to cancer progression. The overexpression of nucleolin (NCL) in a number of types of cancer provides an attractive antigen target for the development of novel anticancer immunotherapeutic treatments.
Usage: The mice were treated with 0.5 mg/kg body weight of SAP-N6L via intraperitoneal injection.
See Also:
Emerging non-viral vectors for gene delivery
Wang C, Pan C, Yong H, Wang F, Bo T, Zhao Y, Ma B, He W, Li M (2023) Emerging non-viral vectors for gene delivery. J Nanobiotechnology 21(1):272. doi: 10.1186/s12951-023-02044-5 PMID: 37592351
Summary: This review describes the fastest-growing and efficient non-viral gene delivery vectors that include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). One group designed and synthesized HPAEs with positive and negative charges to deliver saporin. Another group performed cell experiments that demonstrated that a boronic acid-grafted dendrimer vector had good delivery ability for saporin.
Related Products: Saporin (Cat. #PR-01)
Novel approaches towards cancer-directed immune checkpoint inhibition
Ploeg E (2023) Novel approaches towards cancer-directed immune checkpoint inhibition. Univ Groningen Thesis. doi: 10.33612/diss.737906343
Objective: To evaluate a novel bispecific antibody, bsAb CD73xEGFR, that inhibits the immunosuppressive enzyme CD73 on cancer cells in an EGFR-directed manner.
Summary: The researchers constructed a bispecific antibody, bsAb CD73xEGFR, that binds to both CD73 and EGFR on cancer cells. In preclinical studies, they found that bsAb CD73xEGFR was more effective than the monospecific anti-CD73 antibody oleclumab at reducing tumor growth and enhancing anti-tumor immune responses, likely due to its ability to direct CD73 inhibition specifically to cancer cells overexpressing EGFR.
Usage: Cancer cells were incubated with bsAb CD73xEGFR (1 μg/ml) (or controls) in the presence of Fab-ZAP human (Cat. #IT-51). Apoptotic cancer cell death was evaluated after 24 h by flow cytometry using Annexin-V/PI staining.
Related Products: Fab-ZAP human (Cat. #IT-51)
Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases
Jin X, Yang GY (2023) Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases. Prog Lipid Res 101241. doi: 10.1016/j.plipres.2023.101241 PMID: 37524133
Objective: The authors review the tumor-related biological functions of GSLs and recent progress in using GSLs and related enzymes to diagnose and treat tumor diseases.
Summary: Glycosphingolipids (GSLs) are glycolipids present on the surface of living cell membranes. Specific GSLs and related enzymes are abnormally expressed in many cancer diseases and affect the malignant characteristics of tumors. The regulatory roles of GSLs in signaling pathways suggest that they are involved in tumor pathogenesis. GSLs have therefore been widely studied as diagnostic markers of cancer diseases and important targets of immunotherapy.
Usage: The stage-specific embryonic antigen-4 (SSEA4) mAb, MC-813-70, was mixed with Mab-ZAP at a molar ratio of approximately 3:1 with the complex used at nanomolar concentrations on MDA-MB-231 cells, a triple negative breast cancer cell known to express SSEA-4. The conjugate was able to reduce tumor viability in vitro.
Related Products: Mab-ZAP (Cat. #IT-04)
See Also:
Autonomic nerve and its modulation approaches for heart failure
Zhang H, Zhu Y, Chen S, Deng K, Zheng M, Zeng Z, Wang Q, Cai H, Lu Z (2023) Autonomic nerve and its modulation approaches for heart failure. Brain & Heart doi: 10.36922/bh.0913
Objective: Authors review neural modulation approaches that can assist in the management of heart failure.
Summary: The autonomic nervous system governs the heart’s neurological regulation through opposing functions of its sympathetic and parasympathetic components. Potential treatments for heart failure include inhibiting the sympathetic nerve’s overactivity and restoring parasympathetic activity in the heart. CTB-SAP was used to ablate cardiac sympathetic neurons via retrograde transport on stellate ganglion neurons.
Usage: CTB-SAP was injected into the right superior vervical ganglion of adult male Sprague-Dawley rats (50 ug/rat).
Related Products: CTB-SAP (Cat. #IT-14)
See Also:
Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation
Canarutto D, Omer Javed A, Pedrazzani G, Ferrari S, Naldini L (2023) Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation. Br Med Bull ldad017. doi: 10.1093/bmb/ldad017 PMID: 37460391
Objective: The authors review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.
Summary: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient’s. Ex vivo HSC gene therapy (HSC GT) is a form of HSCT in which HSCs are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow niche, which is required for the engraftment of infused cells. One approach reviewed by the authors involves Anti-CD45-SAP. The conjugate was shown to clear the white blood cell compartment. Administration into mice prior to HSCT resulted in comparable haematopoietic reconstitution as total body irradiation, with less side effects (Palchaudhuri R. et al, 2016) and faster T-cell repopulation likely due to sparing radio damage to the thymic stroma (Schiroli G et al., 2017).
Related Products: Anti-CD45.2-SAP (Cat. #IT-91)
See Also:
- Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
- Schiroli G et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9(411):eaan0820, 2017.
The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression
Kfoury YS, Ji F, Jain E, Mazzola MC, Schiroli G, Papazian A, Mercier FE, Sykes DB, Kiem A, Randolph MA, Abdel-Wahab OI, Calvi LM, Sadreyev R, Scadden DT (2023) The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression. Blood Adv bloodadvances.2022008268. doi: 10.1182/bloodadvances.2022008268 PMID: 37450380
Objective: Evaluate mesenchymal cell molecular features searching for modifications that could impact Myelodysplastic syndrome (MDS) and offer potential therapeutics.
Summary: MDS is a heterogenous group of diseases affecting hematopoietic stem cells and are curable only by stem cell transplantation. Animal models of MDS indicate that changes in specific mesenchymal progenitor subsets in the BM can induce or select for abnormal hematopoietic cells. The authors identified that osteopontin (SPP1) is overexpressed in human bone marrow mesenchymal cells. SPP1 expression in comparable mesenchymal stromal cell populations plays protective roles in disease progression in an MDS mouse model.
Usage: Streptavidin-ZAP was combined with biotinylated CD117 (cKit) Ab in a 1:1 molar ratio. Mice were dosed with the conjugate at 3 mg/kg. The authors used the antibody-drug conjugate as a conditioning strategy that spares the non-hematopoietic microenvironment in the BM from genotoxic injury. This approach has been shown to deplete host hematopoietic stem cells with minimal toxicity effectively.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Cannabinoids: Emerging sleep modulator
Low ZXB, Lee XR, Soga T, Goh BH, Alex D, Kumari Y (2023) Cannabinoids: Emerging sleep modulator. Biomed Pharmacother 165:115102. doi: 10.1016/j.biopha.2023.115102 PMID: 37406510
Objective: To review the modulation of sleep by cannabinoids and the endocannabinoid system.
Summary: This review article discusses the role of cannabinoids, including endocannabinoids like anandamide and phytocannabinoids like THC and CBD, in regulating the sleep-wake cycle. The authors review evidence that cannabinoids act on areas of the brain involved in promoting sleep, like the ventrolateral preoptic nucleus, and inhibit wake-promoting areas, like the locus coeruleus.
Related Products: Orexin-B-SAP (Cat. #IT-20)
The gut-brain axis mediates bacterial driven modulation of reward signaling
Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023
Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.
Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.
Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Intracellular delivery of therapeutic proteins. New advancements and future directions
Porello I, Cellesi F (2023) Intracellular delivery of therapeutic proteins. New advancements and future directions. Front Bioeng Biotechnol 11:1211798. doi: 10.3389/fbioe.2023.1211798 PMID: 37304137
Objective: To provide a brief overview of the current methods for intracellular protein delivery to mammalian cells.
Summary: The field of intracellular protein delivery is still a relatively young area of research and further advancements in this field will require the integration of chemistry, materials science, formulation science, nanomedicine, and biomedical engineering.
Usage: Saporin was referenced as a molecule with the advantage of being able to block the synthesis of proteins in cells.
Related Products: Saporin (Cat. #PR-01)
Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss
Keilholz A, Homan C, Schroeder A, Osman K, Smith C, Pathak I, Streeter K, Ozden I, Ma L, Lever T, Nichols N (2023) Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss. American Physiology Summit 2023 Meeting Abstracts 38(S1)
Objective: Examine if upper airway function/coordination can be improved in lower motor neuron (LMN) degeneration by tongue exercise-induced axis plasticity.
Summary: Tongue muscle weakness in patients with motor neuron diseases suggests a potential role for therapeutic exercise but lacks evidence due to lack of an appropriate model. Data suggests that tongue exercise in CTB-SAP rats results in enhanced XII motor plasticity and mitigates structural airway changes. In conclusion, tongue exercise appears to cause XII-tongue axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration.
Usage: The authors developed a novel rodent model using intralingual injections of CTB-SAP to induce targeted loss of XII motor neurons and motor output.
Related Products: CTB-SAP (Cat. #IT-14)