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Gravitostat: A homeostatic regulator of body weight
Zlatkovic J (2025) Gravitostat: A homeostatic regulator of body weight. Univ of Gothenburg Thesis.
Objective: To focus on elucidating central and peripheral physiological mechanisms behind load-induced body weight reduction.
Summary: The main findings in this thesis include the identification of a group of neurons activated by increased load in the medial Nucleus of Solitary Tract (mNTS) and the dorsal horn (DH) of the Lumbar Spine (LS) in mice.
Usage: Stereotaxic brain delivery of neurotoxin saporin conjugated with anti-dopamine-B-hydroxylase antibodies (5 ng, Anti-DBH-SAP, IT-03) was used as a method of targeted ablation of noradrenergic (NE) neurons in the Nucleus of the Solitary Tract in the brainstem.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells
Rahhal N, Rentzsch M, Seiser S, Freystätter C, Elbe-Bürger A, Rademacher C (2025) Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells. Nanoscale 17(7):4038-4046. doi: 10.1039/d4nr03638g PMID: 39775685
Summary: Saporin was used as a model protein to showcase the potential of delivering intact proteins to Langerhans cells. Authors observed specific killing of cells expressing langerin in vitro, and in primary Langerhans cells isolated from mouse and human skin ex vivo with minimal off target effects.
Related Products: Saporin (Cat. #PR-01)
Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing
Zhao Z, Zhang H, Li W, Wang Y, Wang Y, Yang H, Yin L, Liu X (2025) Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing. J Mater Chem B 13(6):1991-2002. doi: 10.1039/d4tb02009j PMID: 39760520
Objective: To develop an efficient strategy via cationic alpha-helical polypeptide-mediated anionic proprotein delivery.
Summary: The protein was reversibly modified with adenosine triphosphateviadynamic covalent chemistry to prepare an anionic proprotein (A-protein) with abundant phosphate groups. A guanidyl-decorated a-helical polypeptide (LPP) was employed not only to encapsulate A-protein through electrostatic attraction and hydrogen bonding, forming stable nanocomplexes, but also to enhance cell membrane penetration due to its rigid alpha-helical conformation. Consequently, this strategy mediated the effective delivery of various proteins with different isoelectric points and molecular weights, including a-chymotrypsin, bovine serum albumin, ribonuclease A, cytochromeC, saporin, horseradish peroxidase, b-galactosidase, and anti-phospho-Akt, into cancer cells.
Usage: Cytosolic delivery: Saporin, was employed to evaluate LPP-mediated cytosolic delivery and its cancer cell-killing efficacy. The LPP/A-saporin nocomplexes (NCs) caused significant toxicity, with an IC50 value of 0.4ug/mL. In vivo antitumor efficiency of LPP/A-saporin NCs: LPP/A-saporin NCs were administrated by intratumoral injection in HeLa xenograft tumor-bearing mice and their antitumor efficacy was evaluated. When the tumor volume reached B50 mm3, the mice were randomly divided into three groups (6 mice per group) and intratumorally injected with PBS, free saporin, or LPP/A-saporin NCs at 0.1 mg saporin per kg on days 0 and 2.
Related Products: Saporin (Cat. #PR-01)
CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb
Nakano T, Okita K, Okazaki S, Yoshimoto S, Masuko S, Yagi H, Kato K, Tomioka Y, Imai K, Hamada Y, Masuko K, Shimada-Takaura K, Nagai N, Saya H, Arai T, Ishiwata T, Masuko T (2025) CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb. FEBS Open Bio 15(5):867-884. doi: 10.1002/2211-5463.13963 PMID: 39757718
Objective: To analyze pancreatic ductal adenocarcinomas (PDAC) using novel rat mAbs against membrane proteins in conjunction with flow cytometry and immunohistochemistry
Summary: Internalization of membrane proteins by mAbs and growth inhibition by toxin-linked mAbs were demonstrated in many PDAC cell lines, and mAbs against S1PR1, ASCT2, HER3 and CD44v inhibited the growth of xenografted MIA PaCa-2PDAC cells. Furthermore, CD44v-high PDAC showed high mRNA expression of HER1–3, MET and CD44v, and was correlated with poor prognosis. Taken together, the results suggest that CD44v, S1PR1, HER3, MET and the above-mentioned cancer-associated amino acid transporters might be promising targets for the diagnosis and treatment of PDAC.
Usage: Growth inhibition by rat mAbs against PDAC cell lines with secondary antibodies conjugated to saporin (PR-01). Rat mAb solution (4 ug/mL), a PDAC cell suspension and Saporin-conjugated goat anti-rat IgG pAb (Rat-ZAP, IT-26 at 4 ug/mL) were added to each well of 96-well plates.
Related Products: Saporin (Cat. #PR-01), Rat-ZAP (Cat. #IT-26)
Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain
Dogrul BN, Dogrul BN, Machado Kopruszinski C, Dolatyari Eslami M, Watanabe M, Luo S, Moreira de Souza LH, Vizin RL, Yue X, Palmiter RD, Navratilova E, Porreca F (2025) Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain. Pain 166(1):153-159. doi: 10.1097/j.pain.0000000000003360 PMID: 39058958
Objective: To determine whether rostral ventromedial medulla (RVM) mu opioid receptor (MOR)–expressing neurons are required for the expression and maintenance of established neuropathic pain.
Summary: Using chemogenetic silencing of MOR-expressing neurons, the study showed that inhibition of RVM-MOR cells reversibly reduces tactile allodynia and the affective component of neuropathic pain, demonstrating that descending facilitation from these neurons sustains chronic pain. The authors reference earlier findings using Dermorphin-SAP to confirm that complete ablation of MOR-expressing RVM neurons prevents neuropathic pain development without affecting acute surgical pain.
Usage: Dermorphin-SAP (IT-12) was referenced from prior studies as a method for selective ablation of MOR-expressing RVM neurons that prevented mechanical allodynia following spinal nerve ligation.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
See Also:
Itaconate facilitates viral infection via alkylating GDI2 and retaining Rab GTPase on the membrane
Yin S, Tao Y, Li T, Li C, Cui Y, Zhang Y, Yin S, Zhao L, Hu P, Cui L, Wu Y, He Y, Yu S, Chen J, Lu S, Qiu G, Song M, Hou Q, Qian C, Zou Z, Xu S, Yu Y (2024) Itaconate facilitates viral infection via alkylating GDI2 and retaining Rab GTPase on the membrane. Signal Transduct Target Ther 9(1):371. doi: 10.1038/s41392-024-02077-8 PMID: 39730330
Objective: To demonstrate that the IRG1-itaconate axis facilitates the infections of vesicular stomatitis virus (VSV) and influenza A virus (IAV) in macrophages and epithelial cells via Rab GTPases redistribution.
Summary: The study reveals that neutrophils-derived itaconate facilitates viral infection via redistribution of Rab GTPases, suggesting potential targets for antiviral therapy.
Usage: Immunofluorescence: cells were fixed in PBS solution containing 4% formaldehyde, permeabilized with 0.2% saporin (PR-01) along with a mixture of 5% BSA and 10% FCS
Related Products: Saporin (Cat. #PR-01)
Recent insights into the pathophysiology of narcolepsy type 1
Vringer M, Zhou J, Gool JK, Bijlenga D, Lammers GJ, Fronczek R, Schinkelshoek MS (2024) Recent insights into the pathophysiology of narcolepsy type 1. Sleep Med Rev 78:101993. doi: 10.1016/j.smrv.2024.101993 PMID: 39241492
Objective: To focus on recent insights into Narcolepsy type 1 (NT1) pathophysiology, discussing structural and functional changes, immune system involvement, genetic findings, and future perspectives for the pathophysiology and treatment options.
Summary: Narcolepsy type 1 (NT1) is one of the central disorders of the hypersomnolence and results from hypocretin (Hcrt, also nown as orexin) deficiency in the brain. The development of HcrtR2-specific or dual HcrtR1 and HcrtR2 agonists, has shown promising results in pre-clinical and clinical trials. These agonists can potentially become the first drugs to directly target the Hcrt system and replace the shortage of Hcrt in NT1.
Usage: Hcrt-2 conjugated to the ribosome-inactivating toxic protein saporin (Orexin-SAP, Cat #IT-20) eliminated up to 90% of Hcrt neurons but also caused significant loss of neighboring neuronal cells, such as Melanin-concentrating hormone (MCH) neurons.
Related Products: Orexin-B-SAP (Cat. #IT-20)
Impaired basal forebrain cholinergic neuron gdnf signaling contributes to perioperative sleep deprivation–induced chronicity of postsurgical pain in mice through regulating cholinergic neuronal activity, apoptosis, and autophagy
Wang D, Wei SN, Zhang L, Lang ZC, Wang SN, Cheng B, Lu Y, Wang X, Wang W, Li FS, Zhang H (2024) Impaired basal forebrain cholinergic neuron gdnf signaling contributes to perioperative sleep deprivation–induced chronicity of postsurgical pain in mice through regulating cholinergic neuronal activity, apoptosis, and autophagy. CNS Nerusci Ther 30(12):e70147. doi: 10.1111/cns.70147 PMID: 39639706
Objective: This study investigated the roles of lateral basal forebrain glial cell line–derived neurotrophic factor (GDNF). The authors researched GDNF and the associated signaling and cholinergic neuron activity, apoptosis, and autophagy dysfunction in sleep deprivation–induced increased risk of chronic postsurgical pain (CPSP) in mice.
Summary: Perioperative sleep deprivation promotes chronicity of postsurgical pain possibly through decreasing basal forebrain GDNF signaling and causing cholinergic neuronal apoptosis and autophagy dysfunction.
Usage: To ablate the basal forebrain cholinergic neurons, 0.4μg/μL of mu p75-SAP (IT-16) in 0.6μL phosphate-buffered saline was used 3 weeks before the Skin/Muscle Incision and Retraction modeling.
Related Products: mu p75-SAP (Cat. #IT-16)
Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats
Lewis RD, Keilholz AN, Smith CL, Burd EA, Nichols NL (2024) Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats. Front Physiol 15:1488951. doi: 10.3389/fphys.2024.1488951 PMID: 39703667
Objective: To study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited.
Summary: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats, and that astrocytes were increased and exhibited reactive morphology in the phrenic motor nucleus of CTB-SAP rats. This work suggests that TNFR1 could be used as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease.
Usage: Intrapleural injection of CTB-SAP (25μg dissolved in PBS) to target respiratory motor neurons.
Related Products: CTB-SAP (Cat. #IT-14)
Medial septal cholinergic neurotransmission is essential for social memory in mice
Shivakumar AB, Mehak SF, Gupta A, Gangadharan G (2024) Medial septal cholinergic neurotransmission is essential for social memory in mice. Prog Neuropsychopharmacol Biol Psychiatry 136:111207. doi: 10.1016/j.pnpbp.2024.111207 PMID: 39615870
Objective: To identify the physiological link between medial septal dependent cholinergic theta oscillations in the hippocampus and social memory behavior.
Summary: Selective ablation of cholinergic neurons in the medial septum (MS) impaired social memory in mice, while their sociability and social novelty remained intact. Additionally, these mice showed an attenuation of cholinergic theta oscillations (3–7Hz) in the hippocampal dorsal CA2 (dCA2) region. Furthermore, enhancing dCA2 theta oscillations by elevating cholinergic signaling using acetylcholinesterase inhibitor rescued social memory deficit. Together, these results indicate that 1) medial septal cholinergic neurons are essential for modulating social memory and 2) cholinergic hippocampal theta oscillations contribute to social memory processes.
Usage: Ablation of cholinergic neurons in the MS using mu-p75-SAP (IT-16, 0.2μg/0.5μl).
Related Products: mu p75-SAP (Cat. #IT-16)
