References

Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215

Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).

Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.

Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Nie Y, Liang J, Sun J, Li J, Zhai X, Zhao P (2023) Orexin A alleviates LPS-induced acute lung injury by inhibiting macrophage activation through JNK-mediated autophagy. Int Immunopharmacol 124(Pt B):111018. doi: 10.1016/j.intimp.2023.111018 PMID: 37801969

Objective: To investigate the crosstalk between the central nervous system and immune response through the inflammatory response caused by lung injury.

Summary: By modeling acute respiratory distress in mice, the role of orexin-A and orexin-B was investigated through their inflammatory response. Orexin neurons were eliminated through lesions with Orexin-B-SAP (IT-20). Inflammatory cell infiltration and pro-inflammatory cytokines generation were aggravated after orexin neurons were ablated.

Usage: Mice were injected in the bilateral hypothalamus with 1 μL of Orexin-B-SAP (0.36 μg/μL) using a permanent stainless steel internal cannula connected at a speed of 16.5 ng/23 nl/second.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. 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)

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

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:

• Dhez AC et al. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin. J Cell Physiol 233(5):4091-4105, 2018.

Marquez J (2023) PTGFRN as a target for antibody-drug conjugate (ADC) development in mesothelioma and medulloblastoma. Univ Maryland Baltimore Thesis.

Objective: To investigate the role of Prostaglandin F2 Receptor Negative (PTGFRN) regulator in cancer progression and develop an antibody-drug conjugate (ADC) targeting PTGFRN for the treatment of mesothelioma and pediatric medulloblastoma.

Summary: This dissertation explores the expression and function of PTGFRN in mesothelioma and pediatric medulloblastoma, identifying its association with aggressive cancer phenotypes. The study further develops a potent ADC using a PTGFRN-specific monoclonal antibody conjugated to the cytotoxic compound Duocarmycin, demonstrating significant anti-cancer efficacy in both in vitro and in vivo models .

Usage: Both a custom direct conjugate and Fab-ZAP Mouse (IT-48) were used (up to 10 nM) on transfected HEK-293A cells.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Custom Conjugates

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)

Miles AJ, Drew ED, Wallace BA (2023) DichroIDP: a method for analyses of intrinsically disordered proteins using circular dichroism spectroscopy. Commun Biol 6(1):823. doi: 10.1038/s42003-023-05178-2 PMID: 37553525

Objective: To use DichroIDP software to analyze secondary structures of proteins containing disordered structures via circular dichroism spectroscopy.

Summary: Globular proteins have specific shapes and mainly contain standard secondary structures. In contrast, intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) have flexible chains with limited persistent secondary structures.

Usage: Saporin is used to study secondary and tertiary protein structure

Related Products: Saporin (Cat. #PR-01)

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)