RPEP-04833 · 2020In mice lacking the adiponectin gene (Adipoq-/- knockouts), MOTS-c levels in blood and muscle were significantly lower than normal. This directly links adiponectin to MOTS-c production.
In muscle cells (C2C12 myotubes), adiponectin treatment increased MOTS-c gene expression. The researchers traced the signaling chain: adiponectin activates APPL1, which activates SIRT1, which activates PGC-1alpha, which drives MOTS-c production. Blocking any step in this chain (with inhibitors or siRNA) stopped the MOTS-c increase.
In mice on a high-fat diet, both exercise and injected adiponectin or MOTS-c raised MOTS-c levels in blood and muscle. This was accompanied by improved insulin sensitivity, suggesting MOTS-c is a key mediator of adiponectin's metabolic benefits.
Overexpressing SIRT1 amplified the adiponectin effect on MOTS-c, while blocking PGC-1alpha eliminated it. This establishes the APPL1-SIRT1-PGC-1alpha pathway as the mechanism.
Guo, Qi; Chang, Bo; Yu, Qiong-Li; Xu, Si-Tong; Yi, Xue-Jie; Cao, Shi-Cheng · Animal Study (Mice) + In Vitro
RPEP-04834 · 2020The researchers used a technique called hierarchical imprinting to create synthetic polymers with binding pockets shaped to grab the FLAG peptide tag (DYKDDDDK). They tested two different silane coatings to orient the template peptide correctly during manufacturing.
The version made with AETAZS silane performed significantly better: 87.4% recovery of the FLAG tag versus only 4.1% non-specific binding. The AEAPMS version recovered 73.4% but had much higher non-specific binding at 23.2%.
Computational modeling revealed why orientation matters. When the template peptide is properly anchored, the imprinted cavities form more precise shapes that better match the target.
Gómez-Arribas, Lidia N; Darder, María Del Mar; García, Nuria; Rodriguez, Yoel; Urraca, Javier L; Moreno-Bondi, María C · In Vitro (Materials Science)
RPEP-04835 · 2020The ghrelin receptor (GHSR) has unusually high constitutive activity, meaning it sends hunger and metabolic signals even when ghrelin is not present. An inverse agonist does not just block the receptor; it actively reduces this baseline signaling.
The researchers developed a series of compounds based on the 1,2,4-triazole chemical scaffold. By varying substituents at positions 3, 4, and 5, they created highly potent and selective GHSR inverse agonists. These compounds stabilize a specific inactive conformation of the receptor, effectively silencing its constant output.
In living systems, one of the most promising compounds affected insulin secretion in isolated rat pancreatic islets and counteracted ghrelin's appetite-stimulating effects in mice. This demonstrates both metabolic and appetite-related activity in vivo.
Haj Salah, Khoubaib Ben; Maingot, Mathieu; Blayo, Anne-Laure; M'Kadmi, Céline; Damian, Marjorie; Mary, Sophie; Cantel, Sonia; Neasta, Jérémie; Oiry, Catherine; Péraldi-Roux, Sylvie; Fernandez, Gimena; Romero, Guadalupe García; Perello, Mario; Marie, Jacky; Banères, Jean-Louis; Fehrentz, Jean-Alain; Denoyelle, Séverine · Medicinal Chemistry + Animal Study
RPEP-04836 · 2020The core problem: cell-penetrating peptides (CPPs) have positive charges that can interfere with the function of attached cargo peptides inside cells. Direct conjugation often does not work reliably.
The solution: an 8-unit PNA sequence conjugated to octa-arginine CPP (PNA1-CPP) paired with a complementary PNA attached to an autophagy-inducing peptide (PNA2-AIP). The two PNA strands hybridized, forming a stable 1:1 complex that kept the functional peptide connected to the CPP during delivery.
Once inside cells, at least some of the PNA1-CPP/PNA2-AIP complexes dissociated, releasing the functional AIP from the positively charged CPP. The released PNA2-AIP induced significantly more autophagy than AIP directly conjugated to CPP (CPP-AIP). The PNA hybrid system also caused minimal cell death.
Hakata, Yoshiyuki; Ishikawa, Suzuka; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki · In Vitro (Proof Of Concept)
RPEP-04838 · 2020Exenatide significantly attenuated resting forearm blood flow (FBF) at 3 hours after the meal (P = 0.003) and showed a trend at 6 hours (P = 0.056) compared to placebo. This means exenatide blunted the vasodilation (blood vessel widening) that normally happens after eating.
Exenatide also had beneficial metabolic effects: it prevented the post-meal glucose spike (glucose actually decreased at 2 hours while it rose with placebo and saxagliptin) and abated the transient triglyceride increase. Only the exenatide group did not show a significant insulin surge.
No differences were found in peak forearm blood flow, plasma nitrotyrosine (an oxidative stress marker), or plasma 8-iso-prostaglandin F2alpha between groups. Free fatty acids declined in all groups but less markedly with exenatide.
The researchers concluded the vascular effects were primarily endothelium-independent, meaning exenatide altered blood flow through mechanisms other than the vessel lining's nitric oxide system.
Hamidi, Vala; Riggs, Kayla; Zhu, Liang; Bermudez Saint Andre, Karla; Westby, Christian; Coverdale, Sara; Dursteler, Amy; Wang, Hongyu; Miller Iii, Charles; Taegtmeyer, Heinrich; Gutierrez, Absalon D · Randomized Controlled Crossover Trial
RPEP-04839 · 2020The protocol addresses a technical challenge in ADC development: hydrophobic drug-loaded peptides tend to precipitate out of solution during standard peptide mapping, making them invisible to mass spectrometry.
The improved method includes modifications to sample preparation that keep hydrophobic drug-loaded peptides dissolved, enables better chromatographic separation so these peptides are not lost, and uses diagnostic fragmentation ions from the drug payload to unambiguously identify conjugation sites in the LC-MS/MS data.
This allows researchers to map exactly which amino acids on the antibody have drugs attached, which is critical for understanding ADC potency and safety.
Han, Linjie; Zhao, Yanqun; Zhang, Qunying · Methods Paper
RPEP-04840 · 2020The cost-of-control analysis compared oral semaglutide 14 mg against six injectable GLP-1 receptor agonists for type 2 diabetes. The calculation divides annual drug cost by the proportion of patients reaching HbA1c targets.
For the HbA1c ≤6.5% target, costs per patient achieving control: injectable semaglutide 1 mg was cheapest at $15,430, followed by oral semaglutide 14 mg at $17,383. All others (dulaglutide, exenatide once-weekly and twice-daily, liraglutide, lixisenatide) cost more per controlled patient.
For HbA1c <7.0%: injectable semaglutide 1 mg led at $12,627, followed by oral semaglutide at $13,493. The pattern was consistent.
Oral semaglutide was likely cost-effective versus all comparators except injectable semaglutide. This matters because some patients strongly prefer pills over injections.
Hansen, B B; Nuhoho, S; Ali, S N; Dang-Tan, T; Valentine, W J; Malkin, S J P; Hunt, B · Cost Effectiveness Analysis
RPEP-04841 · 2020Despite identical fat content (45 grams, about 60% of meal calories), the four dairy products produced different hormonal and appetite responses.
Cheese stood out: it triggered higher plasma pancreatic polypeptide (PP) than butter or whipped cream (measured as incremental area under the curve over 6 hours). Cheese also produced higher cholecystokinin (CCK) than whipped cream.
Whipped cream produced the most appetite at 4 hours (compared to cheese and sour cream) and at 6 hours (compared to cheese and butter). This means cheese was the most satiating dairy product, and whipped cream was the least.
No significant meal effects were found for hunger ratings, satiety ratings, plasma PYY (peptide YY), or plasma ghrelin. The differences were specific to PP, CCK, and appetite VAS scores.
Hansson, Patrik; Holven, Kirsten B; Øyri, Linn K L; Brekke, Hilde K; Gjevestad, Gyrd O; Rehfeld, Jens F; Raza, Ghulam S; Herzig, Karl-Heinz; Ulven, Stine M · Randomized Controlled Crossover Trial
RPEP-04842 · 2020Seven beta-defensin genes (BD1a-b, BD2-4, BD5a-b) were characterized in Atlantic salmon, with BD1b and BD5 also newly identified in rainbow trout. Genomic analysis across salmonids revealed up to seven BD genes per species, organized into five subfamilies.
The evolutionary picture was clear: BD1-2 and BD4-5 exist in primitive bony fish, but advanced bony fish lost one chromosomal region and retained only BD1 and/or BD5. BD3 is found only in salmonids, making it a lineage-specific innovation. Fish beta-defensins have a unique three-exon gene structure different from mammalian defensins.
Expression patterns were unexpected. Traditional immune organs (head kidney, spleen) showed low-level expression. Instead, at least one BD gene was highly expressed in mucosal tissues, heart, blood, and liver. This suggests these peptides serve as frontline defenders at body surfaces and in circulation.
Harte, Anna; Tian, Guangming; Xu, Qiaoqing; Secombes, Christopher John; Wang, Tiehui · Genomics/Expression Analysis
RPEP-04844 · 2020Itch severity in bullous pemphigoid correlates with eosinophils, substance P, neurokinin 1 receptor, IL-31 signaling, IL-13, periostin, and basophils, while mast cells and TRPV1 were not significantly correlated.
Hashimoto, Takashi; Kursewicz, Christina Dorothy; Fayne, Rachel Alison; Nanda, Sonali; Shah, Serena Maya; Nattkemper, Leigh; Yokozeki, Hiroo; Yosipovitch, Gil · Observational (Cross Sectional)
RPEP-04845 · 2020A PLAC1-derived peptide epitope (PLAC131-50) stimulates promiscuous helper T cell responses that kill PLAC1-positive HNSCC cells in an HLA-DR-restricted manner, with reactive T cells detected in patient blood.
Hayashi, Ryusuke; Nagato, Toshihiro; Kumai, Takumi; Ohara, Kenzo; Ohara, Mizuho; Ohkuri, Takayuki; Hirata-Nozaki, Yui; Harabuchi, Shohei; Kosaka, Akemi; Nagata, Marino; Yajima, Yuki; Yasuda, Syunsuke; Oikawa, Kensuke; Kono, Michihisa; Kishibe, Kan; Takahara, Miki; Katada, Akihiro; Hayashi, Tatsuya; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya · Preclinical Immunology
RPEP-04846 · 2020Inflammation reduced TIMP3 expression in nucleus pulposus (NP) cells, the cells at the center of spinal discs. When TIMP3 was boosted using an adenovirus delivery system, several things happened:
Angiogenesis was suppressed: endothelial cell migration and tube formation (both measures of blood vessel growth) were inhibited. This happened without changing VEGF levels, a common angiogenesis driver.
The mechanism involved TACE (TNF-alpha converting enzyme). TIMP3 reduced TACE expression, which blocked TACE-mediated activation of TNF-alpha, a key inflammatory molecule.
Substance P expression was reduced in the NP tissue, as confirmed by immunohistochemical staining of intervertebral discs. Since Substance P transmits pain signals from nerve endings growing into damaged discs, reducing it could directly decrease pain perception.
The blood vessel and nerve ingrowth into damaged discs is believed to be a major cause of discogenic pain. TIMP3 appears to block both.
He, Mingwei; Pang, Jinlei; Sun, Haiyan; Zheng, Guanrong; Lin, Yan; Ge, Weipeng · In Vitro + Animal Model
RPEP-04847 · 2020Biotin deficiency at 0.012 mg/kg diet caused a cascade of immune impairments across the head kidney, spleen, and skin of grass carp:
Antimicrobial peptides were reduced: LEAP-2A, LEAP-2B, hepcidin, beta-defensin-1, and mucin 2 all had lower mRNA levels. These peptides form the first line of defense against bacterial invasion.
Innate immune function declined: lysozyme activity, acid phosphatase activity, complement C3 and C4, and immunoglobulin M all decreased.
Inflammation went up: pro-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-12p40, IL-15, IL-17D, TNF-alpha, IFN-gamma2) increased through NF-kB signaling. Anti-inflammatory cytokines (IL-4/13A, IL-10, IL-11, TGF-beta1) decreased through impaired TOR signaling.
Optimal biotin levels for growth, lesion prevention, and immune function ranged from 0.210 to 0.245 mg/kg diet.
He, Peng; Jiang, Wei-Dan; Liu, Xiang-An; Feng, Lin; Wu, Pei; Liu, Yang; Jiang, Jun; Tan, Bei-Ping; Yang, Qi-Hui; Kuang, Sheng-Yao; Tang, Ling; Zhou, Xiao-Qiu · Controlled Feeding Trial + Bacterial Challenge
RPEP-04848 · 2020The researchers created peptide dendrimer variants carrying fluorescent labels in their core. These labeled versions maintained the same siRNA transfection efficiency, pH-dependent aggregation, siRNA binding, and secondary structures as unlabeled dendrimers.
FRET (fluorescence resonance energy transfer) experiments revealed the delivery mechanism in detail: at pH 7.4 (normal cellular pH), dendrimers and siRNA are tightly packed together in nanoparticles. At pH 5.0 (endosomal pH), the complex loosens and dendrimers are released into solution.
At this acidic pH, the dendrimers destabilize endosomal membranes, enabling escape into the cytoplasm where siRNA can silence target genes.
Colocalization studies showed dendrimers and siRNA stay together throughout the uptake process, separating only after reaching acidic endosomes. This pH-triggered release mechanism is what makes the system effective.
Heitz, Marc; Zamolo, Susanna; Javor, Sacha; Reymond, Jean-Louis · In Vitro (Mechanistic)
RPEP-04849 · 2020A systematic computational screen of the SARS-CoV-2 proteome identified 310 sequences with cell-penetrating peptide (CPP) characteristics. These SCV2-CPPs spanned regions involved in replication, protein-nucleotide interaction, protein-protein interaction, and complex stabilization.
Safety and practicality analysis: 94.3% were predicted non-toxic. 38% were neither antigenic nor allergenic, important for therapeutic use. 36.7% resisted all four major protease families, meaning they could survive in biological fluids.
Structural analysis: about one-third had sufficient helix or sheet structure for efficient cellular uptake. Among helical CPPs, 44.3% were predicted lipid-binding, important for membrane interaction.
The top candidates for drug delivery were SCV2-CPP118, 119, 122, and 129, all from NSP12 (RNA-dependent RNA polymerase). Cysteine-rich CPPs from the helicase (NSP13) could potentially form cyclic structures in endosomes for better release.
Beyond delivery: 59.6% had predicted antibacterial activity, 29.6% antiviral, 32.3% antifungal, 63.6% immunomodulatory, and 21.9% anticancer properties.
Hemmati, Shiva; Behzadipour, Yasaman; Haddad, Mahdi · Computational/Bioinformatics
RPEP-04850 · 2020Three FDA-approved CGRP antagonists and four more in clinical development demonstrate consistent efficacy in reducing migraine attacks with favorable safety profiles.
Henson, Brianna; Hollingsworth, Hanna; Nevois, Erika; Herndon, Chris · Review
RPEP-04851 · 2020Weight loss produced the expected hormonal changes: leptin (the fullness hormone) decreased overall (P = 0.020 for area under curve and mean level). Ghrelin (the hunger hormone) increased. Both hormones' daily rhythms were modified to more closely resemble those of normal-weight individuals.
The amount of variability in leptin and ghrelin daily rhythms correlated with diet effectiveness (P < 0.001 for both). People whose hormone rhythms changed more also lost more weight.
The disconnect: despite these hormonal improvements, subjective appetite sensations (hunger, fullness, desire to eat) barely changed. Patients still felt approximately the same hunger after losing weight as before.
This confirms that in obesity, the hormonal signals (leptin and ghrelin) cannot properly reach or influence the brain centers that control conscious hunger and satiety. Weight loss partially restores the hormones but does not fix the broken communication.
Hernández Morante, Juan José; Díaz Soler, Inmaculada; Muñoz, Joaquín S Galindo; Sánchez, Horacio Pérez; Barberá Ortega, Mª Del Carmen; Martínez, Carlos Manuel; Morillas Ruiz, Juana Mª · Interventional (Diet Study With Controls)
RPEP-04852 · 2020The study overturned a previous assumption. DNA was thought to be the key NET component driving inflammation in psoriasis. Instead, RNA is the critical molecule.
NET-associated RNA (naRNA), when complexed with LL-37, triggered both cytokine release and new NET formation by neutrophils through TLR8 (human) and TLR13 (mouse) receptors. This happened independently of the canonical NET component DNA.
The self-amplifying mechanism: activated neutrophils release NETs containing RNA. That RNA binds LL-37 (abundant in psoriatic skin). The complex activates more neutrophils to release more NETs with more RNA. Each cycle amplifies the inflammation.
Transferring NETs from activated neutrophils to naive (unstimulated) neutrophils triggered additional NET release, directly demonstrating the self-propagating nature of the cycle.
RNA was abundant in NETs and in psoriatic skin but not in healthy skin. This positions naRNA as a physiologically relevant NET component and a driver of chronic psoriatic inflammation.
Herster, Franziska; Bittner, Zsofia; Archer, Nathan K; Dickhöfer, Sabine; Eisel, David; Eigenbrod, Tatjana; Knorpp, Thomas; Schneiderhan-Marra, Nicole; Löffler, Markus W; Kalbacher, Hubert; Vierbuchen, Tim; Heine, Holger; Miller, Lloyd S; Hartl, Dominik; Freund, Lukas; Schäkel, Knut; Heister, Martin; Ghoreschi, Kamran; Weber, Alexander N R · Mechanistic (In Vitro + In Vivo)
RPEP-04853 · 2020The standard assumption in peptide drug design is that stapling peptides into a helix in solution (the unbound state) makes them better drugs because they are pre-organized for binding. This study challenges that assumption.
Stapled peptides derived from HIF-1alpha were indeed more potent inhibitors of the HIF-1alpha/p300 protein-protein interaction. But circular dichroism (CD) spectroscopy showed they were not significantly more helical than unstapled versions when free in solution.
Molecular dynamics simulations and CD difference spectra revealed the real mechanism: stapling helped the peptides adopt the bioactive alpha-helical conformation specifically when bound to p300. The staple does not lock the helix beforehand; it enables better helix formation at the moment of binding.
This finding shifts the design paradigm: optimizing for bound-state helicity, not free-state helicity, is what matters for stapled peptide inhibitors.
Hetherington, Kristina; Hegedus, Zsofia; Edwards, Thomas A; Sessions, Richard B; Nelson, Adam; Wilson, Andrew J · Biophysical/Computational
RPEP-04854 · 2020The review synthesizes preclinical and clinical evidence for cardiovascular effects of GLP-1 receptor agonists (GLP-1RAs):
GLP-1 receptors are abundantly present in heart tissue, providing a direct mechanism for cardiac effects. Stimulating these receptors affects multiple cardiovascular parameters.
Heart rate increases slightly with GLP-1RAs, typically 2-4 beats per minute. Blood pressure decreases modestly. Both effects are consistent across drugs in the class.
Lipid profiles improve: reductions in postprandial triglycerides and total cholesterol. Inflammatory markers decrease, which may contribute to reduced atherosclerosis progression.
Microvascular function improves in human mechanistic studies, potentially protecting small blood vessels in the heart, kidneys, and other organs.
These individual effects, taken together, likely explain the reduced rates of heart attacks, strokes, and cardiovascular death seen in landmark trials like LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide).
Heuvelman, Valerie D; Van Raalte, Daniël H; Smits, Mark M · Review
RPEP-04855 · 2020Neutrophils kill M. tuberculosis through antimicrobial peptides (alpha-defensins/HNPs), cytokine signaling, and neutrophil extracellular traps, but their excessive activation causes pathological inflammation and tissue damage.
Hilda, J Nancy; Das, Sulochana; Tripathy, Srikanth P; Hanna, Luke Elizabeth · Review
RPEP-04856 · 2020The rationally designed peptide 'Stripe' was modified using two helix-stabilization strategies: Aib (2-aminoisobutyric acid) incorporation and side-chain stapling.
The Aib-containing variant was dramatically potent: MIC of 3.125 micromolar against gram-positive S. aureus and an astonishing 1.56 micromolar against a multi-drug resistant Pseudomonas aeruginosa (MDRP) strain. For context, many AMPs require 10-100 micromolar to achieve similar effects.
Safety margin was exceptional: no significant hemolytic activity up to 100+ micromolar, meaning the therapeutic window was at least 64-fold (1.56 vs 100 micromolar).
Electrophysiology experiments explained the selectivity: the peptide formed stable pores in DOPE/DOPG bilayers (mimicking bacterial membranes, which are negatively charged) but not in DOPC bilayers (mimicking mammalian membranes, which are neutral). This charge-based selectivity is why the peptide kills bacteria but not human cells.
Hirano, Motoharu; Saito, Chihiro; Goto, Chihiro; Yokoo, Hidetomo; Kawano, Ryuji; Misawa, Takashi; Demizu, Yosuke · In Vitro (Peptide Design + Microbiology)
RPEP-04858 · 2020Candidalysin, the first cytolytic peptide toxin identified in a human fungal pathogen, triggered release of multiple key immune molecules from epithelial cells:
Alarmins (danger signals) and antimicrobial peptides with known anti-Candida activity were released in response to candidalysin. The specific molecules were not all named in the abstract but include key innate immune effectors.
The signaling mechanism was novel: extracellular ATP released during candidalysin-mediated cell damage activated EGFR (epidermal growth factor receptor) and MAPK (mitogen-activated protein kinase) signaling cascades. These pathways then drove the downstream antimicrobial peptide and cytokine response.
This is important because it identifies the exact fungal factor responsible for triggering innate immune defense at mucosal surfaces during oral Candida infection.
Ho, Jemima; Wickramasinghe, Don N; Nikou, Spyridoula-Angeliki; Hube, Bernhard; Richardson, Jonathan P; Naglik, Julian R · In Vitro (Infection Model)
RPEP-04859 · 2020Two different autism spectrum disorder (ASD) mouse models were used. One was created by prenatal valproic acid exposure (environmental cause), the other by the Nl3R451C genetic mutation (genetic cause). Both had impaired social memory, the ability to distinguish familiar from novel mice.
Selectively expressing hM3Dq (an activating DREADD receptor) in oxytocin receptor-positive (OXTR+) neurons in the lateral septum (LS) allowed researchers to activate these specific neurons with a chemical trigger.
In the valproic acid model, activation restored social memory in the three-chamber social test. In the Nl3R451C model, social memory was restored in a single-field test. Both represent core ASD symptoms.
The OXTR+ neurons in the LS project to the CA1 region of the hippocampus, suggesting social memory depends on an oxytocin-responsive circuit from the lateral septum to the hippocampus. This identifies a specific neural pathway that could explain how intranasal oxytocin therapy improves social symptoms in ASD patients.
Horiai, Machi; Otsuka, Ayano; Hidema, Shizu; Hiraoka, Yuichi; Hayashi, Ryotaro; Miyazaki, Shinji; Furuse, Tamio; Mizukami, Hiroaki; Teruyama, Ryoichi; Tamura, Masaru; Bito, Haruhiko; Maejima, Yuko; Shimomura, Kenju; Nishimori, Katsuhiko · Animal Study (Mice, Neuroscience)
RPEP-04860 · 2020Anamorelin and HM01 are synthetic ghrelin receptor (GHSR-1a) agonists with clinical potential for appetite stimulation. In cellular assays, they showed biased signaling, activating some downstream pathways (calcium mobilization, IP-one) but differing from ghrelin in internalization and beta-arrestin recruitment patterns.
In rodent feeding studies, both drugs increased food intake, confirming appetite-stimulating effects. However, in reward paradigms (tests measuring motivation to work for food or pleasurable substances), both drugs paradoxically reduced reward-seeking behavior.
Brain c-Fos immunostaining (a marker of neuron activation) revealed divergent activation of central reward circuitry compared to what would be expected from natural ghrelin.
The key insight: biased signaling matters. These drugs activate the ghrelin receptor differently than natural ghrelin, leading to different behavioral outcomes. For future ghrelin-based therapies, understanding exactly which signaling pathways a drug activates, and whether it reaches reward areas of the brain, will determine success or failure.
Howick, Ken; Chruscicka, Barbara; Felice, Daniela; Ramirez, Valerie T; van Leuven, Lucas; Pietra, Claudio; Cryan, John F; Griffin, Brendan T; Schellekens, Harriët · In Vitro + Animal Study (Rodents)
RPEP-04861 · 2020BPC-157 produced concentration-dependent vasodilation in isolated rat aorta. The effect was primarily endothelium-dependent: removing the vessel lining nearly eliminated the relaxation, confirming the endothelium is where BPC-157 acts.
The signaling pathway was mapped step by step:
1. BPC-157 activates Src kinase (phosphorylation increased)
2. Activated Src phosphorylates Caveolin-1 (Cav-1)
3. Phosphorylated Cav-1 releases its inhibitory binding to eNOS
4. Free eNOS produces nitric oxide (NO)
5. NO relaxes the smooth muscle in the vessel wall
Co-immunoprecipitation confirmed that BPC-157 reduces the binding between Cav-1 and eNOS, freeing eNOS to work.
Blocking experiments confirmed each step: Src inhibitor abolished the cascade. L-NAME (NO synthase blocker) and hemoglobin (NO scavenger) both prevented vasodilation. Intracellular NO was directly detected using DAF-FM DA fluorescent labeling.
BPC-157 also promoted migration of vascular endothelial cells, consistent with its known angiogenic properties.
Hsieh, Ming-Jer; Lee, Cheng-Hung; Chueh, Ho-Yen; Chang, Gwo-Jyh; Huang, Hsiu-Yun; Lin, Yuling; Pang, Jong-Hwei S · In Vitro (Vascular Physiology)
RPEP-04862 · 2020The study analyzed 6 cancer-testis antigens (CTAs) and 95 common cancer mutations for their ability to produce peptides that bind HLA class I molecules in two populations.
For CTAs, the overall epitope prediction difference between white and East Asian populations was small. There was a linear relationship between peptide length and epitope occurrence, meaning longer fragments produced more potential targets.
For mutation-derived neoantigens (from missense mutations), population differences were larger, reflecting different HLA allele distributions.
The most striking finding: mutations with the highest incidence in cancer patients had the lowest predicted epitope occurrence. Conversely, rare mutations had the most immune-visible peptides. This inverse relationship suggests immunosurveillance: the immune system kills tumors with easily detectable mutations, so only mutations that evade immunity become common.
Frameshift/indel mutations fell between CTAs and point mutations in the peptide length-epitope relationship.
Hu, Wei; He, Meifang; Li, Liangping · Computational Immunology
RPEP-04863 · 2020Two probiotic strains (Lactobacillus rhamnosus GG and Bifidobacterium longum spp. infantis S12) produced a dual effect when administered to intestinal epithelial cells (SW480) before Pseudomonas aeruginosa infection:
hBD-2 was enhanced: probiotic pretreatment increased both mRNA expression and secreted protein of this antimicrobial peptide, strengthening the direct antimicrobial defense.
IL-8 was suppressed: the inflammatory chemokine IL-8 was reduced, meaning less inflammatory immune cell recruitment and less tissue damage.
The mechanism: probiotics enhanced P. aeruginosa-induced membranous NOD1 protein expression and Akt activation. When Akt or NOD1 were knocked down with siRNA, the probiotic effects on IL-8 and hBD-2 were both reversed. This confirms NOD1 and Akt are the regulatory nodes.
This reciprocal regulation (more antimicrobial defense, less inflammation) is the ideal immune response: kill the pathogen without destroying the tissue.
Huang, Fu-Chen; Lu, Yi-Ting; Liao, Yu-Hsuan · In Vitro (Infection Model)
RPEP-04864 · 2020Complete Freund's adjuvant (CFA) injection created inflammatory pain in rats, causing both mechanical allodynia (pain from normally non-painful touch) and heat hyperalgesia (increased heat sensitivity). Thymosin alpha-1 (Ta1) reduced both types of pain.
Ta1 lowered CFA-induced inflammatory mediators in the spinal cord: IFN-gamma, TNF-alpha, and brain-derived neurotrophic factor (BDNF) were all suppressed.
The Wnt3a/beta-catenin pathway, which was activated in the spinal cord after CFA injection in parallel with pain hypersensitivity, was reversed by Ta1 treatment. This pathway is increasingly recognized as a driver of chronic pain through its role in spinal cord neuroinflammation.
The combination of anti-inflammatory and Wnt pathway modulation provides a dual mechanism for Ta1's pain-reducing effects.
Huang, Jiahua; Jiang, Huaqing; Pan, Meijun; Jiang, Yanjun; Xie, Lijin · Animal Study (Rats)
RPEP-04865 · 2020Two copies of the pbd-2 gene linked by a T2A sequence were inserted into the porcine Rosa26 locus (a safe harbor site) using CRISPR/Cas9. The neomycin resistance marker was removed by cell-penetrating Cre recombinase with 48.3% efficiency, creating marker-free cells.
Cloned piglets were produced via somatic cell nuclear transfer. PCR and Southern blot confirmed correct gene insertion. Immunohistochemistry and immunofluorescence showed significantly higher PBD-2 protein across different tissues of transgenic piglets compared to wild-type littermates.
Functional testing was critical: cell culture supernatants from transgenic pig ear fibroblasts killed bacteria significantly more effectively than wild-type controls, confirming the extra PBD-2 is biologically active.
Huang, Jing; Wang, Antian; Huang, Chao; Sun, Yufan; Song, Bingxiao; Zhou, Rui; Li, Lu · Genetic Engineering (Proof Of Concept)
RPEP-04866 · 2020Peptidoglycan from probiotic L. rhamnosus MLGA produced a dose-dependent increase in avian beta-defensin 9 (AvBD9) mRNA in multiple immune cell types (PBMCs, splenocytes, thymocytes, hepatocytes) and in chicken embryo intestinal explants (jejunum, ileum, cecum).
Functional validation: lysates from peptidoglycan-treated PBMCs and splenocytes showed increased ability to inhibit Salmonella Enteritidis growth, confirming the induced defensin was biologically active.
Critically, this defensin induction occurred without activating pro-inflammatory cytokines IL-1beta, IL-8, and IL-12p40. When peptidoglycan was digested with lysozyme, the hydrolysate actually suppressed these inflammatory cytokines.
In contrast, peptidoglycan from pathogenic S. aureus reduced AvBD9 expression in PBMCs and splenocytes, showing pathogen-derived vs probiotic-derived cell wall material has opposite effects on defensin production.
Huang, Juan; Li, Junhui; Li, Qiufen; Li, Lin; Zhu, Nianhua; Xiong, Xiaowen; Li, Guanhong · In Vitro / Ex Vivo
RPEP-04867 · 2020pVACtools provides an end-to-end pipeline for personalized cancer vaccine design with several key modules:
pVACseq predicts neoantigens from point mutations, insertions, deletions, and gene fusions. It supports an ensemble of MHC binding prediction algorithms for both Class I and Class II, making predictions more robust than single-algorithm approaches.
Prioritization integrates multiple data types: mutant allele expression level (is the mutation actually producing protein?), binding affinity to the patient's HLA types, and whether the mutation is clonal (present in all tumor cells) or subclonal.
pVACviz provides a web-based graphical interface for clinical teams to review, interpret, and select candidates.
pVACvector optimizes peptide ordering to minimize junctional epitopes (unintended immune targets created where peptides join) in DNA vector vaccines.
Additional modules assess synthetic long peptide vaccine candidates for manufacturability factors like solubility and synthesis feasibility.
Hundal, Jasreet; Kiwala, Susanna; McMichael, Joshua; Miller, Christopher A; Xia, Huiming; Wollam, Alexander T; Liu, Connor J; Zhao, Sidi; Feng, Yang-Yang; Graubert, Aaron P; Wollam, Amber Z; Neichin, Jonas; Neveau, Megan; Walker, Jason; Gillanders, William E; Mardis, Elaine R; Griffith, Obi L; Griffith, Malachi · Software/Methods
RPEP-04868 · 2020Prior cardiovascular outcome trials showed semaglutide reduced MACE (major adverse cardiovascular events: CV death, non-fatal stroke, non-fatal MI) in high-risk patients. This post hoc analysis asked: does the benefit extend to lower-risk patients?
A cardiovascular risk prediction model was developed from LEADER trial data and validated on the semaglutide dataset (area under the curve: 0.77, indicating good predictive performance).
Key finding: semaglutide reduced both relative and absolute risk of MACE versus comparators across the entire continuum of cardiovascular risk. The relative risk reduction tended to be largest in patients with low CV risk scores. The absolute risk reduction was largest for intermediate to high risk scores (because these patients had more events to prevent).
Previous data: SUSTAIN-6 showed HR 0.74 [0.58-0.95] for injectable semaglutide vs placebo. PIONEER 6 showed HR 0.79 [0.57-1.11] for oral semaglutide vs placebo. This analysis extends those findings across the risk spectrum.
Similar patterns were seen for individual MACE components and when only placebo comparator data were included.
Husain, Mansoor; Bain, Stephen C; Holst, Anders Gaarsdal; Mark, Thomas; Rasmussen, Søren; Lingvay, Ildiko · Post Hoc Analysis Of Phase 3 Clinical Trials
RPEP-04869 · 2020Combining individual patient-level data from SUSTAIN 6 (injectable semaglutide) and PIONEER 6 (oral semaglutide) versus placebo:
Overall MACE: HR 0.76 (95% CI 0.62-0.92), a 24% reduction. This was statistically significant.
Individual components: non-fatal stroke showed the strongest effect at HR 0.65 (95% CI 0.43-0.97), a 35% reduction. CV death and non-fatal MI showed numerical reductions but individual confidence intervals were wider.
Heart failure hospitalization: HR 1.03 (95% CI 0.75-1.40), no benefit. Notably, patients with prior heart failure also showed no MACE benefit (interaction P = 0.046).
Subgroup analyses: consistent MACE reduction in patients with and without established CV disease or chronic kidney disease, and in patients with and without prior MI or stroke (all interaction P > 0.05 except HF).
In the combined glycemic efficacy trials (where comparators included active drugs, not just placebo), MACE HR was 0.85 (95% CI 0.55-1.33).
Husain, Mansoor; Bain, Stephen C; Jeppesen, Ole K; Lingvay, Ildiko; Sørrig, Rasmus; Treppendahl, Marianne B; Vilsbøll, Tina · Pooled Post Hoc Analysis Of Cardiovascular Outcome Trials
RPEP-04870 · 2020A computationally designed cyclopeptide successfully inhibits the TNFα-TNFR1 protein-protein interaction, validated by NMR structural analysis and biological activity assays.
Idress, Mohannad; Milne, Bruce F; Thompson, Gary S; Trembleau, Laurent; Jaspars, Marcel; Houssen, Wael E · Computational Design + In Vitro Validation
RPEP-04871 · 2020The study tested exenatide across three levels of evidence:
In frataxin-deficient mice, exenatide improved glucose handling through enhanced insulin content and secretion. More importantly, it induced frataxin protein and iron-sulfur cluster-containing proteins in both pancreatic beta cells and brain tissue. It was also protective to sensory neurons in dorsal root ganglia, the neurons that die in Friedreich ataxia.
In patient-derived induced pluripotent stem cells (iPSCs) differentiated into beta cells and sensory neurons, GLP-1 analogs induced frataxin expression, reduced oxidative stress, and improved mitochondrial function.
In a pilot human trial, Friedreich ataxia patients treated with exenatide for 5 weeks showed modest frataxin induction in platelets. While modest, this is the first demonstration that a GLP-1 drug can increase frataxin in actual patients.
The mechanism involves GLP-1 receptor (incretin receptor) activation, identifying this receptor as a new therapeutic target for Friedreich ataxia.
Igoillo-Esteve, Mariana; Oliveira, Ana F; Cosentino, Cristina; Fantuzzi, Federica; Demarez, Céline; Toivonen, Sanna; Hu, Amélie; Chintawar, Satyan; Lopes, Miguel; Pachera, Nathalie; Cai, Ying; Abdulkarim, Baroj; Rai, Myriam; Marselli, Lorella; Marchetti, Piero; Tariq, Mohammad; Jonas, Jean-Christophe; Boscolo, Marina; Pandolfo, Massimo; Eizirik, Décio L; Cnop, Miriam · Translational (Mouse + IPSC + Pilot Human Trial)
RPEP-04872 · 2020Two series of hybrid gamma/gamma-peptides (gamma-CC and gamma-CT) were designed using a chiral cyclobutane amino acid alternating with proline derivatives. Key findings:
Selectivity: both peptide series showed no cytotoxicity to human HeLa cells and only moderate uptake by these cells. In contrast, both 14-mer versions were microbicidal against Leishmania at concentrations above 25 micromolar, with significant intracellular accumulation in the parasite.
Drug delivery: when conjugated to fluorescent doxorubicin (Dox), the peptides showed toxicity to Leishmania above 1 micromolar, while free Dox at the same concentration was not toxic. Intracellular accumulation was 2.5 times higher than with a Dox-TAT conjugate (TAT being the standard cell-penetrating peptide).
Structural insight: computational calculations showed the drug-peptide conjugates fold to bury the Dox moiety inside a cavity while exposing positively charged groups to solvent. This improves Dox solubility and membrane translocation.
Illa, Ona; Olivares, José-Antonio; Gaztelumendi, Nerea; Martínez-Castro, Laura; Ospina, Jimena; Abengozar, María-Ángeles; Sciortino, Giuseppe; Maréchal, Jean-Didier; Nogués, Carme; Royo, Míriam; Rivas, Luis; Ortuño, Rosa M · In Vitro (Peptide Design + Parasitology)
RPEP-04873 · 2020The parent peptide LfcinB(20-30)2 is a dimeric version of a bovine lactoferricin fragment. Researchers systematically replaced the Met-26 residue with amino acids of varying polarity.
Key finding: hydrophobic substitutions dramatically enhanced cancer cell killing. IC50 values reached as low as 6 micromolar against both HTB-132 and MCF-7 breast cancer cell lines. Less hydrophobic or polar substitutions were less effective.
Selectivity: the modified peptides showed significantly lower cytotoxicity to MCF-12 non-tumorigenic breast cells, demonstrating cancer-cell selectivity.
Speed: the cytotoxic effect was remarkably fast, appearing within just 90 minutes and persisting for up to 48 hours.
Mechanism: flow cytometry confirmed death through apoptosis (programmed cell death), not necrosis. The cell membrane remained intact, ruling out a simple membrane-lytic mechanism. Intrinsic apoptotic pathway markers were detected.
This suggests these peptides trigger an internal death program in cancer cells rather than just punching holes in membranes.
Insuasty-Cepeda, Diego Sebastián; Barragán-Cárdenas, Andrea Carolina; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E; Fierro-Medina, Ricardo; García-Castañeda, Javier Eduardo; Rivera-Monroy, Zuly Jenny · In Vitro (Peptide Design + Cancer Biology)
RPEP-04874 · 2020The review covers multiple GLP-1 receptor agonists and their non-glycemic benefits:
Cardiovascular events: semaglutide and liraglutide demonstrated significant reduction in MACE with similar cardiovascular mortality rates. GLP-1RA use was associated with reduced cardiovascular and all-cause mortality versus placebo.
Safety: no increased risk of pancreatitis or thyroid cancer compared to placebo, addressing two common safety concerns.
Blood pressure and weight: exenatide and liraglutide decreased blood pressure values and body weight, and improved dyslipidemia.
Vascular biology: liraglutide specifically improved blood circulation by increasing nitric oxide levels and inhibiting adhesion molecules and procoagulant factors, both in lab experiments and clinical settings.
Cardiac remodeling: liraglutide showed beneficial effects on cardiac remodeling after heart attack in animal models, though more large trials were needed.
Guideline impact: international guidelines now recommend GLP-1RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line in metformin-intolerant patients.
Iorga, Roua Anamaria; Bacalbasa, Nicolae; Carsote, Mara; Bratu, Ovidiu Gabriel; Stanescu, Ana Maria Alexandra; Bungau, Simona; Pantis, Carmen; Diaconu, Camelia Cristina · Review
RPEP-04875 · 2020All variants had identical amino acid composition (same letters, different order), yet behaved very differently:
A6G: RGD at this position disrupted beta-sheet formation, preventing proper self-assembly.
A10G and A14G: both formed assembled nanofibers and produced hydrogels with higher viscoelasticities. Both showed substantial cell adhesion, performing as effective extracellular matrix mimics.
Other variants: significantly reduced cell adhesion despite containing the same RGD sequence.
The key insight is that the higher-order supramolecular structure strongly influences RGD functionality. Simply having the RGD sequence is not enough; it must be positioned where it does not disrupt self-assembly and where it is properly displayed on the nanofiber surface for integrins to access.
Ishida, Atsuya; Oshikawa, Mio; Ajioka, Itsuki; Muraoka, Takahiro · Biomaterials (In Vitro)
RPEP-04876 · 2020Genomic analysis of 99 Japanese quail revealed substantial diversity in the avian beta-defensin (AvBD) gene region:
Nine CjAvBD1 and 8 CjAvBD12 alleles were detected, combining into 10 haplotypes (3 were strain-specific). Next-generation sequencing of 7 homozygous haplotypes revealed 12 to 16 CjAvBD genes per haplotype.
All 7 haplotypes shared 11 common loci (CjAvBD1, -2, -4, -5, -8, -9, -10, -11, -12, -13, -14) but lacked CjAvBD3 and -7 found in chickens. Up to 5 copy number variants of CjAvBD101 (the AvBD6 ortholog) were found among haplotypes.
Functionally significant mutations were detected in CjAvBD4, -13, -14, and -101: amino acid substitutions that change the net charge of the defensin protein. Since defensin antimicrobial activity depends on positive charge for membrane interaction, these mutations could directly affect pathogen killing ability.
The quail AvBD region is uniquely organized compared to chicken, turkey, and bobwhite quail, suggesting rapid evolution of innate immune genes in galliform birds.
Ishige, Taichiro; Hara, Hiromi; Hirano, Takashi; Kono, Tomohiro; Hanzawa, Kei · Genomics
RPEP-04877 · 2020Exenatide is a peptide drug given by injection because it is destroyed in the gut and cannot cross the intestinal wall. Hydrophobic ion pairing (HIP) makes peptides lipophilic by pairing them with surfactant counterions.
Two surfactant types were tested: cationic THA (tetraheptylammonium bromide) and anionic DOC (sodium docusate). Both formed stable complexes with exenatide.
Exenatide-THA was more lipophilic (log D of 2.29 in simulated intestinal fluid vs 1.2 for exenatide-DOC). When loaded into lipid nanocarriers (41% Capmul MCM, 15% Captex 355, 40% Cremophor RH, 4% propylene glycol), the THA formulation showed:
- 10-fold enhancement in intestinal apparent membrane permeability vs free exenatide
- 28.0% ± 5.2% relative oral bioavailability in healthy rats
The DOC formulation achieved 3-fold permeability enhancement and 16.3% ± 6.6% bioavailability.
Neither formulation caused significant hemolytic activity at 0.25% concentration, indicating safety for oral use.
Ismail, Ruba; Phan, Thi Nhu Quynh; Laffleur, Flavia; Csóka, Ildikó; Bernkop-Schnürch, Andreas · Pharmaceutical Formulation + Animal Pharmacokinetics
RPEP-04878 · 2020Both Substance P (SP) and the neurokinin-1 receptor (NK-1R) were expressed in all thyroid tissue, normal and cancerous. But the pattern differed significantly:
In healthy thyroid: SP was found in follicular cell nuclei and colloid. NK-1R was in follicular cell cytoplasm and stroma.
In thyroid cancer: SP expanded to follicular cell cytoplasm (not just nucleus), stroma, and colloid. NK-1R appeared in colloid (not present in normal tissue).
Using the Allred scoring system (a semi-quantitative measure of protein expression), both SP and NK-1R had higher total scores in cancer compared to normal thyroid. SP in nuclei, cytoplasm, and stroma was more intense/abundant in cancer. NK-1R in cytoplasm and colloid was higher in cancer.
Interestingly, SP in colloid was actually lower in cancer than in normal thyroid, and NK-1R in stroma was higher in normal tissue than cancer.
All four thyroid cancer types (papillary, follicular, medullary, anaplastic) and metastases showed the elevated pattern.
Isorna, Inmaculada; Esteban, Francisco; Solanellas, Juan; Coveñas, Rafael; Muñoz, Miguel · Immunohistochemistry (Observational)
RPEP-04879 · 2020The K10H16 fusion peptide delivers functional enzymes to intracellular lysosomes via electrostatic complexation, restoring normal cell growth in lysosomal storage disease cells.
Iwasaki, Takashi; Murakami, Nodoka; Kawano, Tsuyoshi · In Vitro (Proof Of Concept)
RPEP-04880 · 2020This is the first demonstration that protein-peptide coassembly can induce gelation in a non-gelator peptide. The key findings:
A dipeptide that forms aggregates but not gels when alone was transformed into a fiber-forming hydrogel when proteins were added. The protein-peptide interactions converted aggregate-like structures into ordered fibrillar nanostructures.
The interactions were purely non-covalent (electrostatic, hydrophobic, hydrogen bonding). Biolayer interferometry and molecular docking confirmed dissociation constants and binding energies consistent with non-specific protein-peptide interactions.
Tunability: different proteins had different binding affinities to the peptide, producing gels with different mechanical and structural properties at the same peptide concentration. Simply changing the protein type or concentration tuned the gel.
Enzyme entrapment: an enzyme protein was successfully trapped within the gel network during coassembly without losing catalytic activity. This creates a scaffold that can both provide structural support and perform chemical reactions.
Jain, Rashmi; Pal, Vijay Kumar; Roy, Sangita · Biomaterials (Proof Of Concept)
RPEP-04881 · 2020The review synthesizes evidence for multiple cardioprotective mechanisms of oxytocin:
Direct cardiac protection: oxytocin reduces infarct size and improves functional recovery in ischemia-reperfusion models. When given at the onset of reperfusion, it enhances cardiomyocyte viability by activating PI3K and Akt phosphorylation.
Nitric oxide pathway: oxytocin stimulates local release of atrial natriuretic peptide (ANP) in the heart, which generates cGMP and nitric oxide synthesis. This vasodilatory and cytoprotective cascade is a key mechanism.
Anti-inflammatory: oxytocin reduces expression of pro-inflammatory cytokines and decreases immune cell infiltration into damaged heart tissue.
Regeneration: oxytocin stimulates differentiation of stem cells into cardiomyocyte lineages and promotes generation of endothelial and smooth muscle cells, supporting angiogenesis (new blood vessel growth).
Metabolic protection: oxytocin increases glucose uptake by cardiomyocytes, reduces hypertrophy, decreases oxidative stress, and protects mitochondria.
Signaling pathways: RISK (reperfusion injury salvage kinase) and STAT (signal transducer and activator of transcription) cardioprotective pathways are both involved.
Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta · Review
RPEP-04882 · 2020This massive real-world study compared outcomes across multiple diabetes drug combinations:
Worst performer: metformin plus sulfonylurea (SU) had the highest risk of cardiovascular events and death. Metformin plus basal insulin had the highest severe hypoglycemia risk.
Best cardiovascular protection: regimens including a GLP-1 receptor agonist had the lowest MACE risk.
Best overall: metformin + SGLT2 inhibitor + GLP-1 had the lowest risk for all three endpoints (cardiovascular events, severe hypoglycemia, and all-cause mortality).
Key clinical insight: adding GLP-1 to metformin + basal insulin reduced all three endpoints compared to metformin + insulin alone, especially severe hypoglycemia. This suggests GLP-1 agonists should be considered before or alongside insulin.
The results do not support sulfonylurea as the second-line treatment choice, a finding that aligns with evolving guidelines moving away from SU.
Jensen, Morten Hasselstrøm; Kjolby, Mads; Hejlesen, Ole; Jakobsen, Poul Erik; Vestergaard, Peter · Population Based Cohort Study
RPEP-04883 · 2020After ischemia/reperfusion injury in rats, Substance P (5 nmol/kg injection) had specific effects on the right atrium (RA):
SP promoted expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 only in the RA, not in other heart chambers. These are markers of cardiac progenitor cells (CPCs) and stem cell pluripotency.
In ex vivo RA explant outgrowths, NK1R-expressing c-Kit+/Nkx2.5+/GATA4+ CPCs migrated approximately 2-fold more from SP-treated RA tissue compared to untreated I/R tissue.
SP treatment promoted CPC proliferation, migration, cardiosphere formation (3D cell clusters indicating stemness), and differentiation into cardiomyocytes.
All effects were blocked by the NK1R antagonist RP67580, confirming the SP/NK1R pathway is required. The SP/NK1R system acts as a key mediator of CPC expansion in the RA within 24 hours after ischemia/reperfusion.
This identifies the right atrium as a specific niche for SP-responsive cardiac stem cells.
Jeong, Yun-Mi; Cheng, Xian Wu; Lee, Kyung Hye; Lee, Sora; Cho, Haneul; Kim, Weon · Animal Study (Rats)
RPEP-04884 · 2020The team created a multi-part nanocomplex that co-delivers a melanoma antigen peptide (Trp2) and a toll-like receptor 7 agonist (R837) to dendritic cells. Both ingredients dissolve poorly in water, which has made combined delivery difficult until now.
They used a sugar-coated cyclodextrin shell to carry R837 and target mannose receptors on dendritic cells. A fusion peptide combined Trp2 with a cell-penetrating sequence (TAT) to help it get inside cells. Sodium alginate wrapped everything together and added its own immune-boosting effect.
The nanocomplex improved cellular uptake and significantly increased the release of Th1 cytokines, which are signals linked to anti-tumor immunity.
Ji, Zhonghua; Tan, Zeng; Li, Min; Tao, Jin; Guan, Enshuang; Du, Junrong; Hu, Ying · In Vitro
RPEP-04886 · 2020Glycomacropeptide (GMP) given by mouth significantly increased filaggrin, beta-defensin 2, and cathelicidin expression in damaged skin. These are proteins critical for maintaining the skin barrier and fighting off infections.
GMP also strongly reduced epidermal thickening and IFN-gamma expression in damaged skin. This means it calmed the inflammatory response driving the eczema-like condition.
On the microbiome side, GMP prevented Staphylococcus aureus colonization of the skin, which is a major trigger for eczema flares. In the gut, GMP boosted Bifidobacterium levels and increased short-chain fatty acids (acetic acid and butyric acid), especially when given before eczema was induced.
Jiménez, Mariela; Muñoz, Fabiola C; Cervantes-García, Daniel; Cervantes, Maritza M; Hernández-Mercado, Alicia; Barrón-García, Berenice; Moreno Hernández-Duque, José L; Rodríguez-Carlos, Adrián; Rivas-Santiago, Bruno; Salinas, Eva · Animal Study