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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)
Direct cytosolic delivery of proteins and CRISPR-Cas9 genome editing by gemini amphiphiles via non-endocytic translocation pathways
Le Z, Pan Q, He A, Liu H, Shi Y, Liu L, Liu Z, Ping Y, Chen Y (2023) Direct cytosolic delivery of proteins and CRISPR-Cas9 genome editing by gemini amphiphiles via non-endocytic translocation pathways. ACS Cent Sci 9(7):1313-1326. doi: 10.1021/acscentsci.3c00207 PMID: 37521791
Objective: Create a library composed of 150 gemini amphiphiles (GAs), a molecule with polar and nonpolar regions, to identify means to facilitate delivery of saporin across the cell membrane.
Summary: The gemini amphiphiles studied differ in the spacing of functional groups, hydrophobicity and sterics. A Cas9 ribonucleoprotein conjugated to saporin showed highest efficacy for internalization. HeLa cells were used to study the efffects of this found gemini-amphiphile conjugated to saporin.
Usage: A1I2-1R2C18 [a gemini ampiphile] conjugated to saporin and treated against HeLa cells at 0.0625, 0.125, 0.25, 0.5, 1μg/mL for 4 hours and then assessed for cell viability.
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)
The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses.
Singh SA, Vellapandian C (2023) The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses. Futur J Pharm Sci 9:33. doi: 10.1186/s43094-023-00478-0
Objective: Identify and analyze the extract of the plant Luffa cylindrica for bioactive and biochemical properties, particularly as it relates to bioactivity in neurological diseases.
Summary: Luffa cylindrica contains a total of 80 compounds that were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for activity in receptors responsible for causing oxidative stress-associated Alzheimer’s disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 μg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of −46.1 kcal/mol showing promising drug for Alzheimer’s disease. The study reports the presence of a promising, bioactive compound (perlolyrine) with promisng applications in vivo, oxidative stress-related Alzheimer’s disease.
Related Products: Saporin (Cat. #PR-01)
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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.
Which type of RIP is saporin?
Q: I read on your website that, “There are two types of RIPs: type I, which are much less cytotoxic due to the lack of the B chain and type II, which are distinguished from type I RIPs by the presence of the B chain and their ability to enter cells on their own.”
In the IT-27 Streptavidin-ZAP product, which type of saporin is there? Is it both type I and type II because the saporin is purified from the plant, or is it one specific type only in the product.
A: All saporin molecules are Type I ribosome-inactivating proteins. We only use saporin. An example of a Type II RIP is ricin, which can enter a cell on its own and has been used throughout history as a method of assassination.
Streptavidin-ZAP is streptavidin attached to saporin. On its own it has no way to get inside a cell. By mixing Streptavidin-ZAP with a biotinylated molecule that is recognized on the cell surface, the resulting conjugate is able to bind and internalize saporin into a cell. Once inside saporin inactivates the ribosomes which causes cell death.
Analysis of the sequence preference of saporin by deep sequencing
Hauf S, Rotrattanadumrong R, Yokobayashi Y (2022) Analysis of the sequence preference of saporin by deep sequencing. ACS Chem Biol 17(9):2619-2630. doi: 10.1021/acschembio.3c00733 PMID: 35969718
Objective: To study sequence-specific depurination of oligo nucleotides caused by saporin.
Summary: Data shows the sequence preference of saporin for different substrates and show that the GAGA motif is not efficiently targeted by this protein, neither in RNA nor in DNA. Instead, a preference of saporin for certain hairpin DNAs was observed.
Usage: Depurination activity of Saporin on DNA and RNA substrates (500 fmol [17nM] of saporin, while 5 pmol [167nM] of saporin was required for the RNA substrate). Nonspecific DNA:Adenosine Glycosidase Activity (150nM saporin)
Related Products: Saporin (Cat. #PR-01)
From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?
Ardini M, Vago R, Fabbrini MS, Ippoliti R (2022) From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?. Toxins (Basel) 14(9):579. doi: 10.3390/toxins14090579 PMID: 36136517
Objective: To give an overview describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.
Summary: “Suicide gene” therapy (SGT), consists of the selective delivery of genes coding for toxic proteins, into target cancer cells. This new and promising approach may overcome some of the issues related to the use of chemical agents (chemotherapy) such as as specificity, high dosages with accompanying side effects, and chemoresistance induction.
From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?
Ardini M, Vago R, Fabbrini MS, Ippoliti R (2022) From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?. Toxins (Basel) 14(9):579. doi: 10.3390/toxins14090579 PMID: 36136517
Objective: To give an overview describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.
Summary: “Suicide gene” therapy (SGT), consists of the selective delivery of genes coding for toxic proteins, into target cancer cells. This new and promising approach may overcome some of the issues related to the use of chemical agents (chemotherapy) such as as specificity, high dosages with accompanying side effects, and chemoresistance induction.
Self-assembling nanocarriers from engineered proteins: Design, functionalization, and application for drug delivery
Li Y, Champion JA (2022) Self-assembling nanocarriers from engineered proteins: Design, functionalization, and application for drug delivery. Adv Drug Deliv Rev 189:114462. doi: 10.1016/j.addr.2022.114462 PMID: 35934126
Objective: Review recent advances in protein nano-carriers that are from ground-up design recombinant proteins.
Summary: Nanocarriers with a size range of 10-200 nm have emerged as platforms with significant potential for efficient drug delivery via a wide variety of administration routes. To develop nanocarriers for drug delivery, the following functionalities should be achieved. Nanocarriers encapsulate drugs with high loading efficiency and maintain stability in vivo to protect drugs from degradation and prolonged in vivo circulation in blood or residence time in other tissues help improve the fraction of drug-loaded nanocarriers that reach the target site or cells. The Design functionalization, and therapeutic application of protein nanocarriers will be reviewed.
Usage: Saporin is used as the molecular cargo for Protein-Glycan Nanocarriers.
Related Products: Saporin (Cat. #PR-01)